Pseudomonas cremoricolorata Strain ND07 Produces N-acyl Homoserine Lactones as Quorum Sensing Molecules

PubMed Central

Yunos, Nina Yusrina Muhamad; Tan, Wen-Si; Koh, Chong-Lek; Sam, Choon-Kook; Mohamad, Nur Izzati; Tan, Pui-Wan; Adrian, Tan-Guan-Sheng; Yin, Wai-Fong; Chan, Kok-Gan

2014-01-01

Quorum sensing (QS) is a bacterial cell-to-cell communication system controlling QS-mediated genes which is synchronized with the population density. The regulation of specific gene activity is dependent on the signaling molecules produced, namely N-acyl homoserine lactones (AHLs). We report here the identification and characterization of AHLs produced by bacterial strain ND07 isolated from a Malaysian fresh water sample. Molecular identification showed that strain ND07 is clustered closely to Pseudomonas cremoricolorata. Spent culture supernatant extract of P. cremoricolorata strain ND07 activated the AHL biosensor Chromobacterium violaceum CV026. Using high resolution triple quadrupole liquid chromatography-mass spectrometry, it was confirmed that P. cremoricolorata strain ND07 produced N-octanoyl-l-homoserine lactone (C8-HSL) and N-decanoyl-l-homoserine lactone (C10-HSL). To the best of our knowledge, this is the first documentation on the production of C10-HSL in P. cremoricolorata strain ND07. PMID:24984061

Identification, synthesis and regulatory function of the N-acylated homoserine lactone signals produced by Pseudomonas chlororaphis HT66.

PubMed

Peng, Huasong; Ouyang, Yi; Bilal, Muhammad; Wang, Wei; Hu, Hongbo; Zhang, Xuehong

2018-01-22

Pseudomonas chlororaphis HT66 isolated from the rice rhizosphere is an important plant growth-promoting rhizobacteria that produce phenazine-1-carboxamide (PCN) in high yield. Phenazine production is regulated by a quorum sensing (QS) system that involves the N-acylated homoserine lactones (AHLs)-a prevalent type of QS molecule. Three QS signals were detected by thin layer chromatography (TLC) and high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS), which identified to be N-(3-hydroxy hexanoyl)-L-homoserine lactone (3-OH-C6-HSL), N-(3-hydroxy octanoyl)-L-homoserine lactone (3-OH-C8-HSL) and N-(3-hydroxy decanoyl)-L-homoserine lactone (3-OH-C10-HSL). The signal types and methods of synthesis were different from that in other phenazine-producing Pseudomonas strains. By non-scar deletion and heterologous expression techniques, the biosynthesis of the AHL-signals was confirmed to be only catalyzed by PhzI, while other AHLs synthases i.e., CsaI and HdtS were not involved in strain HT66. In comparison to wild-type HT66, PCN production was 2.3-folds improved by over-expression of phzI, however, phzI or phzR mutant did not produce PCN. The cell growth of HT66∆phzI mutant was significantly decreased, and the biofilm formation in phzI or phzR inactivated strains of HT66 decreased to various extents. In conclusion, the results demonstrate that PhzI-PhzR system plays a critical role in numerous biological processes including phenazine production.

Treatment of MDR1 Mutant Dogs with Macrocyclic Lactones

PubMed Central

Geyer, Joachim; Janko, Christina

2012-01-01

P-glycoprotein, encoded by the multidrug resistance gene MDR1, is an ATP-driven drug efflux pump which is highly expressed at the blood-brain barrier of vertebrates. Drug efflux of macrocyclic lactones by P-glycoprotein is highly relevant for the therapeutic safety of macrocyclic lactones, as thereby GABA-gated chloride channels, which are confined to the central nervous system in vertebrates, are protected from high drug concentrations that otherwise would induce neurological toxicity. A 4-bp deletion mutation exists in the MDR1 gene of many dog breeds such as the Collie and the Australian Shepherd, which results in the expression of a non-functional P-glycoprotein and is associated with multiple drug sensitivity. Accordingly, dogs with homozygous MDR1 mutation are in general prone to neurotoxicity by macrocyclic lactones due to their increased brain penetration. Nevertheless, treatment of these dogs with macrocyclic lactones does not inevitably result in neurological symptoms, since, the safety of treatment highly depends on the treatment indication, dosage, route of application, and the individual compound used as outlined in this review. Whereas all available macrocyclic lactones can safely be administered to MDR1 mutant dogs at doses usually used for heartworm prevention, these dogs will experience neurological toxicity following a high dose regimen which is common for mange treatment in dogs. Here, we review and discuss the neurotoxicological potential of different macrocyclic lactones as well as their treatment options in MDR1 mutant dogs. PMID:22039792

Acyl-Homoserine Lactone Production in Nitrifying Bacteria of the Genera Nitrosospira, Nitrobacter, and Nitrospira Identified via a Survey of Putative Quorum-Sensing Genes.

PubMed

Mellbye, Brett L; Spieck, Eva; Bottomley, Peter J; Sayavedra-Soto, Luis A

2017-11-15

The genomes of many bacteria that participate in nitrogen cycling through the process of nitrification contain putative genes associated with acyl-homoserine lactone (AHL) quorum sensing (QS). AHL QS or bacterial cell-cell signaling is a method of bacterial communication and gene regulation and may be involved in nitrogen oxide fluxes or other important phenotypes in nitrifying bacteria. Here, we carried out a broad survey of AHL production in nitrifying bacteria in three steps. First, we analyzed the evolutionary history of AHL synthase and AHL receptor homologs in sequenced genomes and metagenomes of nitrifying bacteria to identify AHL synthase homologs in ammonia-oxidizing bacteria (AOB) of the genus Nitrosospira and nitrite-oxidizing bacteria (NOB) of the genera Nitrococcus , Nitrobacter , and Nitrospira Next, we screened cultures of both AOB and NOB with uncharacterized AHL synthase genes and AHL synthase-negative nitrifiers by a bioassay. Our results suggest that an AHL synthase gene is required for, but does not guarantee, cell density-dependent AHL production under the conditions tested. Finally, we utilized mass spectrometry to identify the AHLs produced by the AOB Nitrosospira multiformis and Nitrosospira briensis and the NOB Nitrobacter vulgaris and Nitrospira moscoviensis as N -decanoyl-l-homoserine lactone (C 10 -HSL), N -3-hydroxy-tetradecanoyl-l-homoserine lactone (3-OH-C 14 -HSL), a monounsaturated AHL (C 10:1 -HSL), and N -octanoyl-l-homoserine lactone (C 8 -HSL), respectively. Our survey expands the list of AHL-producing nitrifiers to include a representative of Nitrospira lineage II and suggests that AHL production is widespread in nitrifying bacteria. IMPORTANCE Nitrification, the aerobic oxidation of ammonia to nitrate via nitrite by nitrifying microorganisms, plays an important role in environmental nitrogen cycling from agricultural fertilization to wastewater treatment. The genomes of many nitrifying bacteria contain genes associated with

Beckmann rearrangement within the ring C of oleanolic acid lactone: Synthesis, structural study and reaction mechanism analysis

NASA Astrophysics Data System (ADS)

Froelich, Anna; Bednarczyk-Cwynar, Barbara; Zaprutko, Lucjusz; Gzella, Andrzej

2017-05-01

Synthesis, spectral and X-ray analysis of three compounds, i.e. 3β-acetoxy-12-hydroxyimino-18β-oleanan-28,13β-olide (substrate) and 3β-acetoxy-12-nitrile-12,13-seco-15(14 → 13)-abeoolean-14(27)-en-28,13β-olide and 3β-acetoxy-12-oxo-12a-aza-C-homoolean-13(18)-en-28-oic acid (Beckmann rearrangement reaction products) are described. Structural analysis revealed that the oxime group in the ring C in substrate molecule had an E-configuration. The nitrile product with retained lactone group was a result of major transformations within rings C and D of oleanane skeleton. In lactam product free carboxyl group and a double bond in ring D instead of lactone system were formed in Beckmann rearrangement reaction.

Acyl-homoserine lactones produced by Pantoea sp. isolated from the "maize white spot" foliar disease.

PubMed

Pomini, Armando M; Paccola-Meirelles, Luzia D; Marsaioli, Anita J

2007-02-21

The "maize white spot" foliar disease is a problem of increasing importance to Brazilian maize crops. A bacterium isolated from water-soaked lesions from infected maize leaves was pathogenic in biological assays in vivo. It was identified as a Gram-negative, nonsporulating, facultative anaerobic bacterium, belonging to the genus Pantoea. Chemical study of the extracts from bacterial cultivation media allowed the identification of (S)-(-)-N-butanoyl-homoserine lactone and trace amounts of N-hexanoyl-homoserine lactone, widely recognized quorum-sensing signaling substances employed in cell-to-cell communication systems. The absolute configuration of natural (S)-(-)-N-butanoyl-homoserine lactone was determined by gas chromatography-flame ionization detection with a chiral stationary phase and by comparison of circular dichroism spectroscopic data with enantiopure synthetic substances. Biological evaluations with reporter Agrobacterium tumefaciens NTL4(pZLR4) were carried out with synthetic and natural products and also with extracts from maize leaves contaminated with the isolated bacterium, as well as from healthy leaves.

Insights into the Biosynthesis of 12-Membered Resorcylic Acid Lactones from Heterologous Production in Saccharomyces cerevisiae

PubMed Central

2015-01-01

The phytotoxic fungal polyketides lasiodiplodin and resorcylide inhibit human blood coagulation factor XIIIa, mineralocorticoid receptors, and prostaglandin biosynthesis. These secondary metabolites belong to the 12-membered resorcylic acid lactone (RAL12) subclass of the benzenediol lactone (BDL) family. Identification of genomic loci for the biosynthesis of lasiodiplodin from Lasiodiplodia theobromae and resorcylide from Acremonium zeae revealed collaborating iterative polyketide synthase (iPKS) pairs whose efficient heterologous expression in Saccharomyces cerevisiae provided a convenient access to the RAL12 scaffolds desmethyl-lasiodiplodin and trans-resorcylide, respectively. Lasiodiplodin production was reconstituted in the heterologous host by co-expressing an O-methyltransferase also encoded in the lasiodiplodin cluster, while a glutathione-S-transferase was found not to be necessary for heterologous production. Clarification of the biogenesis of known resorcylide congeners in the heterologous host helped to disentangle the roles that biosynthetic irregularities and chemical interconversions play in generating chemical diversity. Observation of 14-membered RAL homologues during in vivo heterologous biosynthesis of RAL12 metabolites revealed “stuttering” by fungal iPKSs. The close global and domain-level sequence similarities of the orthologous BDL synthases across different structural subclasses implicate repeated horizontal gene transfers and/or cluster losses in different fungal lineages. The absence of straightforward correlations between enzyme sequences and product structural features (the size of the macrocycle, the conformation of the exocyclic methyl group, or the extent of reduction by the hrPKS) suggest that BDL structural variety is the result of a select few mutations in key active site cavity positions. PMID:24597618

Production of Acylated Homoserine Lactones by Psychrotrophic Members of the Enterobacteriaceae Isolated from Foods

PubMed Central

Gram, Lone; Christensen, Allan Beck; Ravn, Lars; Molin, Søren; Givskov, Michael

1999-01-01

Bacteria are able to communicate and gene regulation can be mediated through the production of acylated homoserine lactone (AHL) signal molecules. These signals play important roles in several pathogenic and symbiotic bacteria. The following study was undertaken to investigate whether AHLs are produced by bacteria found in food at temperatures and NaCl conditions commercially used for food preservation and storage. A minimum of 116 of 154 psychrotrophic Enterobacteriaceae strains isolated from cold-smoked salmon or vacuum-packed chilled meat produced AHLs. Analysis by thin-layer chromatography indicated that N-3-oxo-hexanoyl homoserine lactone was the major AHL of several of the strains isolated from cold-smoked salmon and meat. AHL-positive strains cultured at 5°C in medium supplemented with 4% NaCl produced detectable amounts of AHL(s) at cell densities of 106 CFU/ml. AHLs were detected in cold-smoked salmon inoculated with strains of Enterobacteriaceae stored at 5°C under an N2 atmosphere when mean cell densities increased to 106 CFU/g and above. Similarly, AHLs were detected in uninoculated samples of commercially produced cold-smoked salmon when the level of indigenous Enterobacteriaceae reached 106 CFU/g. This level of Enterobacteriaceae is often found in lightly preserved foods, and AHL-mediated gene regulation may play a role in bacteria associated with food spoilage or food toxicity. PMID:10427034

Profile of Citrobacter freundii ST2, a Multi-acyl-homoserine Lactone Producer Associated with Marine Dinoflagellates.

PubMed

Huang, Xinqi; Gao, Yan; Ma, Zhiping; Lin, Guanghui; Cai, Zhonghua; Zhou, Jin

2017-01-01

Marine algae provide a unique niche termed the phycosphere for microorganism inhabitation. The phycosphere environment is an important niche for mutualistic and competitive interactions between algae and bacteria. Quorum sensing (QS) serves as a gene regulatory system in the microbial biosphere that allows bacteria to sense the population density with signaling molecules, such as acyl-homoserine lactone (AHL), and adapt their physiological activities to their surroundings. Understanding the QS system is important to elucidate the interactions between algal-associated microbial communities in the phycosphere condition. In this study, we isolated an epidermal bacterium (ST2) from the marine dinoflagellate Scrippsiella trochoidea and evaluated its AHL production profile. Strain ST2 was classified as a member of the genus Citrobacter closely related to Citrobacter freundii by 16S rRNA gene sequence analysis. Thin-layer chromatography revealed that C. freundii ST2 secreted three active AHL compounds into the culture supernatant. Specific compounds, such as N-butyryl-L-homoserine lactone (C4-AHL), N-octanoyl-DL-homoserine lactone (C8-AHL), and N-decanoyl-DL-homoserine lactone (C10-AHL), were identified by high-resolution tandem mass spectrometry. Carbon metabolic profiling with Biolog EcoPlate™ indicated that C. freundii ST2 was widely used as a carbon source and preferred carbohydrates, amino acids, and carboxylic acids as carbon substrates. Our results demonstrated that C. freundii ST2 is a multi-AHL producer that participates in the phycosphere carbon cycle.

Concurrent treatment with a macrocyclic lactone and benzimidazole provides season long performance advantages in grazing cattle harboring macrocyclic lactone resistant nematodes.

PubMed

Edmonds, M D; Vatta, A F; Marchiondo, A A; Vanimisetti, H B; Edmonds, J D

2018-03-15

control) was not statistically different from the concurrent therapy with conventional anthelmintics. The results indicate that concurrent treatment with a conventional macrocyclic lactone and benzimidazole may provide production benefits early in the grazing period that continue throughout the entire period for cattle harboring macrocyclic lactone resistant nematodes. By using two different anthelmintic classes together, macrocyclic lactone resistant parasites were effectively controlled early in the period. Furthermore, the use of an effective conventional anthelmintic treatment regimen without an extended period of drug release may help to promote refugia and decrease the further selection for anthelmintic resistant parasites. Copyright © 2018 Elsevier B.V. All rights reserved.

Verbalactone, a new macrocyclic dimer lactone from the roots of Verbascum undulatum with antibacterial activity.

PubMed

Magiatis, P; Spanakis, D; Mitaku, S; Tsitsa, E; Mentis, A; Harvala, C

2001-08-01

A novel macrocyclic dimer lactone, named verbalactone, was isolated from the roots of Verbascum undulatum and exhibited interesting antibacterial activity. It is the first time that 1,7-dioxacyclododecane is reported as the ring system of a natural product. The structure and the absolute stereochemistry of the new compound were determined by spectral methods and chemical correlation.

The molecular structure and catalytic mechanism of a quorum-quenching N-acyl-L-homoserine lactone hydrolase

PubMed Central

Kim, Myung Hee; Choi, Won-Chan; Kang, Hye Ok; Lee, Jong Suk; Kang, Beom Sik; Kim, Kyung-Jin; Derewenda, Zygmunt S.; Oh, Tae-Kwang; Lee, Choong Hwan; Lee, Jung-Kee

2005-01-01

In many Gram-negative bacteria, including a number of pathogens such as Pseudomonas aeruginosa and Erwinia carotovora, virulence factor production and biofilm formation are linked to the quorum-sensing systems that use diffusible N-acyl-l-homoserine lactones (AHLs) as intercellular messenger molecules. A number of organisms also contain genes coding for lactonases that hydrolyze AHLs into inactive products, thereby blocking the quorum-sensing systems. Consequently, these enzymes attract intense interest for the development of antiinfection therapies. However, the catalytic mechanism of AHL-lactonase is poorly understood and subject to controversy. We here report a 2.0-Å resolution structure of the AHL-lactonase from Bacillus thuringiensis and a 1.7-Å crystal structure of its complex with l-homoserine lactone. Despite limited sequence similarity, the enzyme shows remarkable structural similarities to glyoxalase II and RNase Z proteins, members of the metallo-β-lactamase superfamily. We present experimental evidence that AHL-lactonase is a metalloenzyme containing two zinc ions involved in catalysis, and we propose a catalytic mechanism for bacterial metallo-AHL-lactonases. PMID:16314577

Fragrance material review on 16-hydroxy-7-hexadecenoic acid lactone.

PubMed

McGinty, D; Letizia, C S; Api, A M

2011-12-01

A toxicologic and dermatologic review of 16-hydroxy-7-hexadecenoic acid lactone when used as a fragrance ingredient is presented. 16-Hydroxy-7-hexadecenoic acid lactone is a member of the fragrance structural group macrocyclic lactone and lactide derivatives. The fragrance ingredient described herein is one of 12 structurally diverse C14, C15 and C16 compounds that include (1) saturated mono-and (2) saturated di-ester lactones and (3) unsaturated lactones. For the latter, the double bond is not adjacent to (in conjugation with) the ester group. This review contains a detailed summary of all available toxicology and dermatology papers that are related to 16-hydroxy-7-hexadecenoic acid lactone and is not intended as a stand-alone document. Available data were evaluated, then summarized, and include physical properties data. A safety assessment of the entire macrocyclic lactone and lactide derivatives will be published simultaneously with this document. Please refer to Belsito et al., 2011 for an overall assessment of the safe use of this material and all macrocyclic lactone and lactide derivatives in fragrances. Belsito, D., Bickers, D., Bruze, M., Calow, P., Dagli, M., Fryer, A.D., Greim, H., Hanifin, J.H., Miyachi, Y., Saurat, J.H., Sipes, I.G., 2011. A toxicologic and dermatologic assessment of macrocylic lactones and lactide derivatives when used as fragrance ingredients. Copyright © 2011. Published by Elsevier Ltd.

Pantoea sp. Isolated from Tropical Fresh Water Exhibiting N-Acyl Homoserine Lactone Production

PubMed Central

Tan, Wen-Si; Tan, Pui-Wan; Adrian, Tan-Guan-Sheng; Yin, Wai-Fong; Chan, Kok-Gan

2014-01-01

N-Acyl homoserine lactone (AHL) serves as signaling molecule for quorum sensing (QS) in Gram-negative bacteria to regulate various physiological activities including pathogenicity. With the aim of isolating freshwater-borne bacteria that can cause outbreak of disease in plants and portrayed QS properties, environmental water sampling was conducted. Here we report the preliminary screening of AHL production using Chromobacterium violaceum CV026 and Escherichia coli [pSB401] as AHL biosensors. The 16S rDNA gene sequence of isolate M009 showed the highest sequence similarity to Pantoea stewartii S9-116, which is a plant pathogen. The isolated Pantoea sp. was confirmed to produce N-3-oxohexanoyl-L-HSL (3-oxo-C6-HSL) through analysis of high resolution mass tandem mass spectrometry. PMID:25197715

New sources and antifungal activity of sesquiterpene lactones.

PubMed

Barrero, A F; Oltra, J E; Alvarez, M; Raslan, D S; Saúde, D A; Akssira, M

2000-02-01

In the search for new sources of sesquiterpene lactones, six Centaurea species have been analyzed. The activity against the fungus Cunninghamella echinulata of (+)-cnicin (1) and (+)-salonitenolide (2), isolated from the Centaurea plants, as well as that of (+)-costunolide (3), (-)-dehydrocostuslactone (4), (-)-lychnopholide (5) and (-)-eremantholide C (6), has been evaluated. Compounds 3 and 4 showed noticeable EC50 values, whilst more polar lactones were inactive. These results suggest that a relatively low polarity is one of the molecular requirements for the antifungal activity of sesquiterpene lactones.

Characteristics of N-Acylhomoserine Lactones Produced by Hafnia alvei H4 Isolated from Spoiled Instant Sea Cucumber

PubMed Central

Hou, Hong-Man; Zhu, Yao-Lei; Wang, Jia-Ying; Jiang, Feng; Qu, Wen-Yan; Zhang, Gong-Liang; Hao, Hong-Shun

2017-01-01

This study aimed to identify N-acylhomoserine lactone (AHL) produced by Hafnia alvei H4, which was isolated from spoiled instant sea cucumber, and to investigate the effect of AHLs on biofilm formation. Two biosensor strains, Chromobacterium violaceum CV026 and Agrobacterium tumefaciens KYC55, were used to detect the quorum sensing (QS) activity of H. alvei H4 and to confirm the existence of AHL-mediated QS system. Thin layer chromatography (TLC) and high resolution triple quadrupole liquid chromatography/mass spectrometry (LC/MS) analysis of the AHLs extracted from the culture supernatant of H. alvei H4 revealed the existence of at least three AHLs: N-hexanoyl-l-homoserine lactone (C6-HSL), N-(3-oxo-octanoyl)-l-homoserine lactone (3-oxo-C8-HSL), and N-butyryl-l-homoserine lactone (C4-HSL). This is the first report of the production of C4-HSL by H. alvei. In order to determine the relationship between the production of AHL by H. alvei H4 and bacterial growth, the β-galactosidase assay was employed to monitor AHL activity during a 48-h growth phase. AHLs production reached a maximum level of 134.6 Miller unites at late log phase (after 18 h) and then decreased to a stable level of about 100 Miller unites. AHL production and bacterial growth displayed a similar trend, suggesting that growth of H. alvei H4 might be regulated by QS. The effect of AHLs on biofilm formation of H. alvei H4 was investigated by adding exogenous AHLs (C4-HSL, C6-HSL and 3-oxo-C8-HSL) to H. alvei H4 culture. Biofilm formation was significantly promoted (p < 0.05) by 5 and 10 µM C6-HSL, inhibited (p < 0.05) by C4-HSL (5 and 10 µM) and 5 µM 3-oxo-C8-HSL, suggesting that QS may have a regulatory role in the biofilm formation of H. alvei H4. PMID:28379194

Sesquiterpene lactones of Vernonia - influence of glaucolide-A on the growth rate and survival of Lepidopterous larvae.

PubMed

Jones, Samuel B; Burnett, William C; Coile, Nancy C; Mabry, Tom J; Betkouski, M F

1979-01-01

Sesquiterpene lactone glaucolide-A from Vernonia, incorporated in the rearing diets of five species of Lepidoptera, significantly reduced the rate of growth of larvae of the southern armyworm, Spodoptera eridania; fall armyworm, S. frugiperda; and yellowstriped armyworm, S. ornithogalli. Quantitative feeding tests demonstrated that decreased feeding levels and reduced growth resulted from ingestion of a sesquiterpene lactone. Ingestion of glaucolide-A increased the number of days to pupation in four of the species. In the southern armyworm, it significantly reduced pupal weight. Glaucolide-A decidedly reduced percentage of survival of southern and fall armyworms. Yellow woollybear, Diacrisia virginica, and cabbage looper, Trichoplusia ni, larvae were essentially uneffected by the ingestion of the sesquiterpene lactone. Sesquiterpene lactones adversely affect growth rate and survival of certain insects that feed upon plants containing them. They apparently function as defensive products, screening out a portion of the potential herbivores.

Two new aliphatic lactones from the fruits of Coriandrum sativum L.

PubMed Central

2012-01-01

Background The present paper describes the isolation and characterization of two new aliphatic δ-lactones along with three glycerides and n-nonadecanyl cetoleate from the fruits of Coriandrum sativum L. (Apiaceae). The structures of all the isolated phytoconstituents have been established on the basis of spectral data analysis and chemical reactions. Results Phytochemical investigation of the methanolic extract of C. sativum L. (Apiaceae) fruits resulted in the isolation of two new aliphatic δ-lactones characterized as 2α-n-heptatriacont-(Z)-3-en-1,5-olide (1) (coriander lactone) and 2α-n-tetracont-(Z,Z)-3,26-dien-18α-ol-1,5-olide (2) (hydroxy coriander lactone) together with glyceryl-1,2-dioctadec-9,12-dienoate-3-octadec-9-enoate (3); glyceryl-1,2,3-trioctadecanoate (4); n-nonadecanyl-n-docos-11-enoate (5) and oleiyl glucoside (6). Conclusions Phytochemical investigation of the methanolic extract of C. sativum gave coriander lactone and hydroxy coriander lactone as the new phytoconstituents. PMID:22800677

Potato plants genetically modified to produce N-acylhomoserine lactones increase susceptibility to soft rot erwiniae.

PubMed

Toth, I K; Newton, J A; Hyman, L J; Lees, A K; Daykin, M; Ortori, C; Williams, P; Fray, R G

2004-08-01

Many gram-negative bacteria employ N-acylhomoserine lactones (AHL) to regulate diverse physiological processes in concert with cell population density (quorum sensing [QS]). In the plant pathogen Erwinia carotovora, the AHL synthesized via the carI/expI genes are responsible for regulating the production of secreted plant cell wall-degrading exoenzymes and the antibiotic carbapen-3-em carboxylic acid. We have previously shown that targeting the product of an AHL synthase gene (yenI) from Yersinia enterocolitica to the chloroplasts of transgenic tobacco plants caused the synthesis in planta of the cognate AHL signaling molecules N-(3-oxohexanoyl)-L-homoserine lactone (3-oxo-C6-HSL) and N-hexanoylhomoserine lactone (C6-HSL), which in turn, were able to complement a carI-QS mutant. In the present study, we demonstrate that transgenic potato plants containing the yenI gene are also able to express AHL and that the presence and level of these AHL in the plant increases susceptibility to infection by E. carotovora. Susceptibility is further affected by both the bacterial level and the plant tissue under investigation.

Statin Lactonization by Uridine 5'-Diphospho-glucuronosyltransferases (UGTs).

PubMed

Schirris, Tom J J; Ritschel, Tina; Bilos, Albert; Smeitink, Jan A M; Russel, Frans G M

2015-11-02

Statins are cholesterol-lowering drugs that have proven to be effective in lowering the risk of major cardiovascular events. Although well tolerated, statin-induced myopathies are the most common side effects. Compared to their pharmacologically active acid form, statin lactones are more potent inducers of toxicity. They can be formed by glucuronidation mediated by uridine 5'-diphospho-glucuronosyltransferases (UGTs), but a systematic characterization of subtype specificity and kinetics of lactonization is lacking. Here, we demonstrate for six clinically relevant statins that only UGT1A1, 1A3, and 2B7 contribute significantly to their lactonization. UGT1A3 appeared to have the highest lactonization capacity with marked differences in statin conversion rates: pitavastatin ≫ atorvastatin > cerivastatin > lovastatin > rosuvastatin (simvastatin not converted). Using in silico modeling we could identify a probable statin interaction region in the UGT binding pocket. Polymorphisms in these regions of UGT1A1, 1A3, and 2B7 may be a contributing factor in statin-induced myopathies, which could be used in personalization of statin therapy with improved safety.

Systemic and cerebral exposure to and pharmacokinetics of flavonols and terpene lactones after dosing standardized Ginkgo biloba leaf extracts to rats via different routes of administration

PubMed Central

Chen, Feng; Li, Li; Xu, Fang; Sun, Yan; Du, Feifei; Ma, Xutao; Zhong, Chenchun; Li, Xiuxue; Wang, Fengqing; Zhang, Nating; Li, Chuan

2013-01-01

BACKGROUND AND PURPOSE Flavonols and terpene lactones are putatively responsible for the properties of Ginkgo biloba leaf extracts that relate to prevention and treatment of cardiovascular disease and cerebral insufficiency. Here, we characterized rat systemic and cerebral exposure to these ginkgo compounds after dosing, as well as the compounds’ pharmacokinetics. EXPERIMENTAL APPROACH Rats received single or multiple doses of ShuXueNing injection (prepared from GBE50 for intravenous administration) or GBE50 (a standardized extract of G. biloba leaves for oral administration). Brain delivery of the ginkgo compounds was assessed with microdialysis. Various rat samples were analysed using liquid chromatography/mass spectrometry. KEY RESULTS Slow terminal elimination features of the flavonols counterbalanced the influence of poor oral bioavailability on their systemic exposure levels, which also resulted in significant accumulation of the compounds in plasma during the subchronic treatment with ShuXueNing injection and GBE50. Unlike the flavonols, the terpene lactones had poor enterohepatic circulation due to their rapid renal excretion and unknown metabolism. The flavonol glycosides occurred as major forms in plasma after dosing with ShuXueNing injection, while the flavonol aglycone conjugates were predominant in plasma after dosing with GBE50. Cerebral exposure was negligible for the flavonols and low for the terpene lactones. CONCLUSION AND IMPLICATIONS Unlike the significant systemic exposure levels, the levels of cerebral exposure to the flavonols and terpene lactones are low. The elimination kinetic differences between the two classes of ginkgo compounds influence their relative systemic exposure levels. The information gained is relevant to linking ginkgo administration to the medicinal effects. PMID:23808355

Chemoselective synthesis of sialic acid 1,7-lactones.

PubMed

Allevi, Pietro; Rota, Paola; Scaringi, Raffaella; Colombo, Raffaele; Anastasia, Mario

2010-08-20

The chemoselective synthesis of the 1,7-lactones of N-acetylneuraminic acid, N-glycolylneuraminic acid, and 3-deoxy-d-glycero-d-galacto-nononic acid is accomplished in two steps: a simple treatment of the corresponding free sialic acid with benzyloxycarbonyl chloride and a successive hydrogenolysis of the formed 2-benzyloxycarbonyl 1,7-lactone. The instability of the 1,7-lactones to protic solvents has been also evidenced together with the rationalization of the mechanism of their formation under acylation conditions. The results permit to dispose of authentic 1,7-sialolactones to be used as reference standards and of a procedure useful for the preparation of their isotopologues to be used as inner standards in improved analytical procedures for the gas liquid chromatography-mass spectrometry (GLC-MS) analysis of 1,7-sialolactones in biological media.

Herbicidal and Fungicidal Activities of Lactones in Kava (Piper methysticum).

PubMed

Xuan, T D; Elzaawely, A A; Fukuta, M; Tawata, S

2006-02-08

This is the first report showing that kava lactones are plant and plant fungus growth inhibitors. Aqueous extract of kava roots showed high allelopathic potential and strongly suppressed germination and growth of lettuce, radish, barnyardgrass, and monochoria. Nine kava lactones were detected using GC-MS including desmethoxyyagonin, kavain, 7,8-dihydrokavain, hydroxykavain, yagonin, 5,6,7,8-tetrahydroxyyagonin, methysticin, dihydromethysticin, and 11-hydroxy-12-methoxydihydrokavain. Quantities of desmethoxyyagonin, kavain, 7,8-dihydrokavain, yagonin, methysticin, and dihydromethysticin detected were 4.3, 6.9, 18.6, 5.7, 1.4, and 5.4 mg/g of dry weight, respectively. These six major lactones in kava roots showed great herbicidal and antifungal activities. Growth of lettuce and barnyardgrass were significantly inhibited at 1-10 ppm, and four plant fungi including Colletotrichum gloeosporides, Fusarium solani, Fusarium oxysporum, and Trichoderma viride were significantly inhibited at 10-50 ppm. The biological activities of kava lactones were characterized by different double-bond linkage patterns in positions 5,6 and 7,8. The findings of this study suggest that kava lactones may be useful for the development of bioactive herbicides and fungicides.

Relationship between Menthiafolic Acid and Wine Lactone in Wine.

PubMed

Giaccio, Joanne; Curtin, Chris D; Sefton, Mark A; Taylor, Dennis K

2015-09-23

Menthiafolic acid (6-hydroxy-2,6-dimethylocta-2,7-dienoic acid, 2a) was quantified by GC-MS in 28 white wines, 4 Shiraz wines, and for the first time in 6 white grape juice samples. Menthiafolic acid was detected in all but one of the wine samples at concentrations ranging from 26 to 342 μg/L and in the juice samples from 16 to 236 μg/L. Various model fermentation experiments showed that some menthiafolic acid in wine could be generated from the grape-derived menthiafolic acid glucose ester (2b) during alcoholic and malolactic fermentation. Samples containing high concentrations of menthiafolic acid were also analyzed by enantioselective GC-MS and were shown to contain this compound in predominantly the (S)-configuration. Enantioselective analysis of wine lactone (1) in one of these samples, a four-year-old Chardonnay wine showed, for the first time, the presence of the 3R,3aR,7aS isomer of wine lactone (1b), which is the enantiomer of the form previously reported as the sole isomer present in young wine samples. The weakly odorous 3R,3aR,7aS 1b form comprised 69% of the total wine lactone in the sample. On the basis of the enantioselectivity of the hydrolytic conversion of menthiafolic acid to wine lactone at pH 3.0 determined previously and the relative proportions of (R)- and (S)-menthiafolic acid in the Chardonnay wine, the predicted ratio of wine lactone enantiomers that would be formed from hydrolysis at ambient temperature of the menthiafolic acid present in this wine was close to the ratio measured, which was consistent with menthiafolic acid being the major or sole precursor to wine lactone in this sample.

Unravelling the genome of long chain N-acylhomoserine lactone-producing Acinetobacter sp. strain GG2 and identification of its quorum sensing synthase gene

PubMed Central

How, Kah Yan; Hong, Kar-Wai; Sam, Choon-Kook; Koh, Chong-Lek; Yin, Wai-Fong; Chan, Kok-Gan

2015-01-01

Myriad proteobacteria use N-acyl homoserine lactone (AHL) molecules as quorum sensing (QS) signals to regulate different physiological functions, including virulence, antibiotic production, and biofilm formation. Many of these proteobacteria possess LuxI/LuxR system as the QS mechanism. Recently, we reported the 3.89 Mb genome of Acinetobacter sp. strain GG2. In this work, the genome of this long chain AHL-producing bacterium was unravelled which led to the molecular characterization of luxI homologue, designated as aciI. This 552 bp gene was cloned and overexpressed in Escherichia coli BL21(DE3). The purified protein was ∼20.5 kDa and is highly similar to several autoinducer proteins of LuxI family among Acinetobacter species. To verify the AHL synthesis activity of this protein, high-resolution liquid chromatography–mass spectrometry analysis revealed the production of 3-oxo-dodecanoyl-homoserine lactone and 3-hydroxy-dodecanoyl-homoserine lactone from induced E. coli harboring the recombinant AciI. Our data show for the first time, the cloning and characterization of the luxI homologue from Acinetobacter sp. strain GG2, and confirmation of its AHLs production. These data are of great significance as the annotated genome of strain GG2 has provided a valuable insight in the study of autoinducer molecules and its roles in QS mechanism of the bacterium. PMID:25926817

Structure determination of 3-O-caffeoyl-epi-gamma-quinide, an orphan bitter lactone in roasted coffee.

PubMed

Frank, Oliver; Blumberg, Simone; Krümpel, Gudrun; Hofmann, Thomas

2008-10-22

Recent investigations on the bitterness of coffee as well as 5- O-caffeoyl quinic acid roasting mixtures indicated the existence of another, yet unknown, bitter lactone besides the previously identified bitter compounds 5- O-caffeoyl- muco-gamma-quinide, 3- O-caffeoyl-gamma-quinide, 4- O-caffeoyl- muco-gamma-quinide, 5- O-caffeoyl- epi-delta-quinide, and 4- O-caffeoyl-gamma-quinide. In the present study, this orphan bitter lactone was isolated from the reaction products generated by dry heating of 5- O-caffeoylquinic acid model, and its structure was determined as the previously unreported 3- O-caffeoyl- epi-gamma-quinide by means of liquid chromatography-mass spectrometry (LC-MS) and one-/two-dimensional NMR experiments. The occurrence of this bitter lactone, exhibiting a low bitter recognition threshold of 58 micromol/L, in coffee beverages could be confirmed by LC-MS/MS (negative electrospray ionization) operating in the multiple reaction monitoring mode.

Sesquiterpene lactone stereochemistry influences herbivore resistance and plant fitness in the field.

PubMed

Ahern, Jeffrey R; Whitney, Kenneth D

2014-03-01

Stereochemical variation is widely known to influence the bioactivity of compounds in the context of pharmacology and pesticide science, but our understanding of its importance in mediating plant-herbivore interactions is limited, particularly in field settings. Similarly, sesquiterpene lactones are a broadly distributed class of putative defensive compounds, but little is known about their activities in the field. Natural variation in sesquiterpene lactones of the common cocklebur, Xanthium strumarium (Asteraceae), was used in conjunction with a series of common garden experiments to examine relationships between stereochemical variation, herbivore damage and plant fitness. The stereochemistry of sesquiterpene lactone ring junctions helped to explain variation in plant herbivore resistance. Plants producing cis-fused sesquiterpene lactones experienced significantly higher damage than plants producing trans-fused sesquiterpene lactones. Experiments manipulating herbivore damage above and below ambient levels found that herbivore damage was negatively correlated with plant fitness. This pattern translated into significant fitness differences between chemotypes under ambient levels of herbivore attack, but not when attack was experimentally reduced via pesticide. To our knowledge, this work represents only the second study to examine sesquiterpene lactones as defensive compounds in the field, the first to document herbivore-mediated natural selection on sesquiterpene lactone variation and the first to investigate the ecological significance of the stereochemistry of the lactone ring junction. The results indicate that subtle differences in stereochemistry may be a major determinant of the protective role of secondary metabolites and thus of plant fitness. As stereochemical variation is widespread in many groups of secondary metabolites, these findings suggest the possibility of dynamic evolutionary histories within the Asteraceae and other plant families showing

Systemic and cerebral exposure to and pharmacokinetics of flavonols and terpene lactones after dosing standardized Ginkgo biloba leaf extracts to rats via different routes of administration.

PubMed

Chen, Feng; Li, Li; Xu, Fang; Sun, Yan; Du, Feifei; Ma, Xutao; Zhong, Chenchun; Li, Xiuxue; Wang, Fengqing; Zhang, Nating; Li, Chuan

2013-09-01

Flavonols and terpene lactones are putatively responsible for the properties of Ginkgo biloba leaf extracts that relate to prevention and treatment of cardiovascular disease and cerebral insufficiency. Here, we characterized rat systemic and cerebral exposure to these ginkgo compounds after dosing, as well as the compounds' pharmacokinetics. Rats received single or multiple doses of ShuXueNing injection (prepared from GBE50 for intravenous administration) or GBE50 (a standardized extract of G. biloba leaves for oral administration). Brain delivery of the ginkgo compounds was assessed with microdialysis. Various rat samples were analysed using liquid chromatography/mass spectrometry. Slow terminal elimination features of the flavonols counterbalanced the influence of poor oral bioavailability on their systemic exposure levels, which also resulted in significant accumulation of the compounds in plasma during the subchronic treatment with ShuXueNing injection and GBE50. Unlike the flavonols, the terpene lactones had poor enterohepatic circulation due to their rapid renal excretion and unknown metabolism. The flavonol glycosides occurred as major forms in plasma after dosing with ShuXueNing injection, while the flavonol aglycone conjugates were predominant in plasma after dosing with GBE50. Cerebral exposure was negligible for the flavonols and low for the terpene lactones. Unlike the significant systemic exposure levels, the levels of cerebral exposure to the flavonols and terpene lactones are low. The elimination kinetic differences between the two classes of ginkgo compounds influence their relative systemic exposure levels. The information gained is relevant to linking ginkgo administration to the medicinal effects. © 2013 The Authors. British Journal of Pharmacology published by John Wiley &. Sons Ltd on behalf of The British Pharmacological Society.

Sesquiterpene lactones from Centaurea tweediei.

PubMed

Fortuna, A M.; de Riscala, E C.; Catalan, C A.N.; Gedris, T E.; Herz, W

2001-10-01

Aerial parts of Centaurea tweediei from Argentina afforded as the main constituent the sesquiterpene lactone onopordopicrin and minor amounts of a new heliangolide, a new guaianolide, a new eudesmanolide, a new eudesmane acid and the lignans arctigenin and matairesinol.

A New Mechanism for β‐Lactamases: Class D Enzymes Degrade 1β‐Methyl Carbapenems through Lactone Formation

PubMed Central

Lohans, Christopher T.; van Groesen, Emma; Kumar, Kiran; Tooke, Catherine L.; Spencer, James; Paton, Robert S.; Brem, Jürgen

2018-01-01

Abstract β‐Lactamases threaten the clinical use of carbapenems, which are considered antibiotics of last resort. The classical mechanism of serine carbapenemase catalysis proceeds through hydrolysis of an acyl‐enzyme intermediate. We show that class D β‐lactamases also degrade clinically used 1β‐methyl‐substituted carbapenems through the unprecedented formation of a carbapenem‐derived β‐lactone. β‐Lactone formation results from nucleophilic attack of the carbapenem hydroxyethyl side chain on the ester carbonyl of the acyl‐enzyme intermediate. The carbapenem‐derived lactone products inhibit both serine β‐lactamases (particularly class D) and metallo‐β‐lactamases. These results define a new mechanism for the class D carbapenemases, in which a hydrolytic water molecule is not required. PMID:29236332

Sesquiterpene lactone stereochemistry influences herbivore resistance and plant fitness in the field

PubMed Central

Ahern, Jeffrey R.; Whitney, Kenneth D.

2014-01-01

Background and Aims Stereochemical variation is widely known to influence the bioactivity of compounds in the context of pharmacology and pesticide science, but our understanding of its importance in mediating plant–herbivore interactions is limited, particularly in field settings. Similarly, sesquiterpene lactones are a broadly distributed class of putative defensive compounds, but little is known about their activities in the field. Methods Natural variation in sesquiterpene lactones of the common cocklebur, Xanthium strumarium (Asteraceae), was used in conjunction with a series of common garden experiments to examine relationships between stereochemical variation, herbivore damage and plant fitness. Key Results The stereochemistry of sesquiterpene lactone ring junctions helped to explain variation in plant herbivore resistance. Plants producing cis-fused sesquiterpene lactones experienced significantly higher damage than plants producing trans-fused sesquiterpene lactones. Experiments manipulating herbivore damage above and below ambient levels found that herbivore damage was negatively correlated with plant fitness. This pattern translated into significant fitness differences between chemotypes under ambient levels of herbivore attack, but not when attack was experimentally reduced via pesticide. Conclusions To our knowledge, this work represents only the second study to examine sesquiterpene lactones as defensive compounds in the field, the first to document herbivore-mediated natural selection on sesquiterpene lactone variation and the first to investigate the ecological significance of the stereochemistry of the lactone ring junction. The results indicate that subtle differences in stereochemistry may be a major determinant of the protective role of secondary metabolites and thus of plant fitness. As stereochemical variation is widespread in many groups of secondary metabolites, these findings suggest the possibility of dynamic evolutionary histories

Sesquiterpene Lactones from Artemisia Genus: Biological Activities and Methods of Analysis

PubMed Central

Miron, Anca; Corciova, Andreia

2015-01-01

Sesquiterpene lactones are a large group of natural compounds, found primarily in plants of Asteraceae family, with over 5000 structures reported to date. Within this family, genus Artemisia is very well represented, having approximately 500 species characterized by the presence of eudesmanolides and guaianolides, especially highly oxygenated ones, and rarely of germacranolides. Sesquiterpene lactones exhibit a wide range of biological activities, such as antitumor, anti-inflammatory, analgesic, antiulcer, antibacterial, antifungal, antiviral, antiparasitic, and insect deterrent. Many of the biological activities are attributed to the α-methylene-γ-lactone group in their molecule which reacts through a Michael-addition with free sulfhydryl or amino groups in proteins and alkylates them. Due to the fact that most sesquiterpene lactones are thermolabile, less volatile compounds, they present no specific chromophores in the molecule and are sensitive to acidic and basic mediums, and their identification and quantification represent a difficult task for the analyst. Another problematic aspect is represented by the complexity of vegetal samples, which may contain compounds that can interfere with the analysis. Therefore, this paper proposes an overview of the methods used for the identification and quantification of sesquiterpene lactones found in Artemisia genus, as well as the optimal conditions for their extraction and separation. PMID:26495156

Ketopantoyl lactone reductase is a conjugated polyketone reductase.

PubMed

Hata, H; Shimizu, S; Hattori, S; Yamada, H

1989-03-01

Ketopantoyl lactone reductase (EC 1.1.1.168) of Saccharomyces cerevisiae was found to catalyze the reduction of a variety of natural and unnatural conjugated polyketone compounds and quinones, such as isatin, ninhydrin, camphorquinone and beta-naphthoquinone in the presence of NADPH. 5-Bromoisatin is the best substrate for the enzyme (Km = 3.1 mM; Vmax = 650 mumol/min/mg). The enzyme is inhibited by quercetin, and several polyketones. These results suggest that ketopantoyl lactone reductase is a carbonyl reductase which specifically catalyzes the reduction of conjugated polyketones.

Antimalarial activity of sesquiterpene lactones from Vernonia cinerea.

PubMed

Chea, Aun; Hout, Sotheara; Long, Christophe; Marcourt, Laurence; Faure, Robert; Azas, Nadine; Elias, Riad

2006-10-01

Two new sesquiterpene lactones, vernolides C and D as well as six known ones were isolated from the dichloromethane fraction of an aqueous extract from Vernonia cinerea. Their structures were elucidated by spectroscopic methods. Among the known sesquiterpene lactones, three of them were described in this plant for the first time. In vitro antiplasmodial evaluation showed that the three major compounds 1, 7 and 8 were active against chloroquine resistant Plasmodium falciparum strain (W2) with IC(50) 3.9, 3.7 and 3.5 microM, respectively.

Chemical and Biological Investigation of Olive Mill Waste Water - OMWW Secoiridoid Lactones.

PubMed

Vougogiannopoulou, Konstantina; Angelopoulou, Maria T; Pratsinis, Harris; Grougnet, Raphaël; Halabalaki, Maria; Kletsas, Dimitris; Deguin, Brigitte; Skaltsounis, Leandros A

2015-08-01

Olive mill waste water is the major byproduct of the olive oil industry containing a range of compounds related to Olea europaea and olive oil constituents. Olive mill waste water comprises an important environmental problem in olive oil producing countries, but it is also a valuable material for the isolation of high added value compounds. In this study, an attempt to investigate the secoiridoid content of olive mill waste water is described with the aid of ultrahigh-performance liquid chromatography-electrospray ionization (±)-high-resolution mass spectrometry and centrifugal partition chromatography methods. In total, seven secoiridoid lactones were isolated, four of which are new natural products. This is the first time that a conjugate of hydroxytyrosol and a secoiridoid lactone has been isolated from olive mill waste water and structurally characterized. Furthermore, the range of isolated compounds allowed for the proposal of a hypothesis for the biotransformation of olive secoiridoids during the production of olive mill waste water. Finally, the ability of the representative compounds to reduce the intracellular reactive oxygen species was assessed with the dichlorofluorescein assay in conjunction with the known antioxidant agent hydroxytyrosol. Georg Thieme Verlag KG Stuttgart · New York.

Cascade Synthesis of Five-Membered Lactones using Biomass-Derived Sugars as Carbon Nucleophiles.

PubMed

Yamaguchi, Sho; Matsuo, Takeaki; Motokura, Ken; Miyaji, Akimitsu; Baba, Toshihide

2016-06-06

We report the cascade synthesis of five-membered lactones from a biomass-derived triose sugar, 1,3-dihydroxyacetone, and various aldehydes. This achievement provides a new synthetic strategy to generate a wide range of valuable compounds from a single biomass-derived sugar. Among several examined Lewis acid catalysts, homogeneous tin chloride catalysts exhibited the best performance to form carbon-carbon bonds. The scope and limitations of the synthesis of five-membered lactones using aldehyde compounds are investigated. The cascade reaction led to high product selectivity as well as diastereoselectivity, and the mechanism leading to the diastereoselectivity was discussed based on isomerization experiments and density functional theory (DFT) calculations. The present results are expected to support new approaches for the efficient utilization of biomass-derived sugars. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

New sesquiterpene lactones from Ambrosia cumanensis Kunth.

PubMed

Jimenez-Usuga, Nora Del Socorro; Malafronte, Nicola; Cotugno, Roberta; De Leo, Marinella; Osorio, Edison; De Tommasi, Nunziatina

2016-09-01

Eleven sesquiterpene lactones, including three new natural products (1-3), were isolated from the n-butanolic extract of Ambrosia cumanensis Kunth. aerial parts. The structure of all isolated compounds was elucidated by 1D- and 2D-NMR, and MS analyses. All compounds were tested for their antiproliferative activity on HeLa, Jurkat, and U937 cell lines. Compound 3, 2,3-dehydropsilostachyn C, showed cytotoxic activity with different potency in all cell lines. By means of flow cytometric studies, compound 3 was demonstrated to induce in Jurkat cells a G2/M cell cycle block, while in U937 elicited both cytostatic and cytotoxic responses. Copyright © 2016 Elsevier B.V. All rights reserved.

Fundamental role of the fostriecin unsaturated lactone and implications for selective protein phosphatase inhibition.

PubMed

Buck, Suzanne B; Hardouin, Christophe; Ichikawa, Satoshi; Soenen, Danielle R; Gauss, C-M; Hwang, Inkyu; Swingle, Mark R; Bonness, Kathy M; Honkanen, Richard E; Boger, Dale L

2003-12-24

Key derivatives and analogues of fostriecin were prepared and examined that revealed a fundamental role for the unsaturated lactone and confirmed the essential nature of the phosphate monoester. Thus, an identical 200-fold reduction in protein phosphatase 2A (PP2A) inhibition is observed with either the saturated lactone (7) or with an analogue that lacks the entire lactone (15). This 200-fold increase in PP2A inhibition attributable to the unsaturated lactone potentially may be due to reversible C269 alkylation within the PP beta12-beta13 active site loop accounting for PP2A/4 potency and selectivity.

Identification of crypto- and neochlorogenic lactones as potent xanthine oxidase inhibitors in roasted coffee beans.

PubMed

Honda, Sari; Miura, Yukari; Masuda, Akiko; Masuda, Toshiya

2014-01-01

Xanthine oxidase (XO) inhibitory activity has been found in boiling water extracts from roasted coffee beans. Therefore, assay-guided purification of the extracts was performed using size-exclusion column chromatography, and subsequently with reversed phase HPLC to afford lactone derivatives of chlorogenic acids. Among the tested lactones, crypto- and neochlorogenic lactones showed potent XO inhibitory activities compared with three major chlorogenic acids found in coffee beans. These XO inhibitory lactones may ameliorate gout and hyperuricemia in humans who drink coffee.

Dehydrocostus lactone is exuded from sunflower roots and stimulates germination of the root parasite Orobanche cumana.

PubMed

Joel, Daniel M; Chaudhuri, Swapan K; Plakhine, Dina; Ziadna, Hammam; Steffens, John C

2011-05-01

The germination of the obligate root parasites of the Orobanchaceae depends on the perception of chemical stimuli from host roots. Several compounds, collectively termed strigolactones, stimulate the germination of the various Orobanche species, but do not significantly elicit germination of Orobanche cumana, a specific parasite of sunflower. Phosphate starvation markedly decreased the stimulatory activity of sunflower root exudates toward O. cumana, and fluridone - an inhibitor of the carotenoid biosynthesis pathway - did not inhibit the production of the germination stimulant in both shoots and roots of young sunflower plants, indicating that the stimulant is not a strigolactone. We identified the natural germination stimulant from sunflower root exudates by bioassay-driven purification. Its chemical structure was elucidated as the guaianolide sesquiterpene lactone dehydrocostus lactone (DCL). Low DCL concentrations effectively stimulate the germination of O. cumana seeds but not of Phelipanche aegyptiaca (syn. Orobanche aegyptiaca). DCL and other sesquiterpene lactones were found in various plant organs, but were previously not known to be exuded to the rhizosphere where they can interact with other organisms. Copyright © 2011 Elsevier Ltd. All rights reserved.

Divergent synthesis and chemical reactivity of bicyclic lactone fragments of complex rearranged spongian diterpenes.

PubMed

Schnermann, Martin J; Beaudry, Christopher M; Genung, Nathan E; Canham, Stephen M; Untiedt, Nicholas L; Karanikolas, Breanne D W; Sütterlin, Christine; Overman, Larry E

2011-11-02

The synthesis and direct comparison of the chemical reactivity of the two highly oxidized bicyclic lactone fragments found in rearranged spongian diterpenes (8-substituted 6-acetoxy-2,7-dioxabicyclo[3.2.1]octan-3-one and 6-substituted 7-acetoxy-2,8-dioxabicyclo[3.3.0]octan-3-one) are reported. Details of the first synthesis of the 6-acetoxy-2,7-dioxabicyclo[3.2.1]octan-3-one ring system, including an examination of several possibilities for the key bridging cyclization reaction, are described. In addition, the first synthesis of 7-acetoxy-2,8-dioxabicyclo[3.3.0]octanones containing quaternary carbon substituents at C6 is disclosed. Aspects of the chemical reactivity and Golgi-modifying properties of these bicyclic lactone analogs of rearranged spongian diterpenes are also reported. Under both acidic and basic conditions, 8-substituted 2,7-dioxabicyclo[3.2.1]octanones are converted to 6-substituted-2,8-dioxabicyclo[3.3.0]octanones. Moreover, these dioxabicyclic lactones react with primary amines and lysine side chains of lysozyme to form substituted pyrroles, a conjugation that could be responsible for the unique biological properties of these compounds. These studies demonstrate that acetoxylation adjacent to the lactone carbonyl group, in either the bridged or fused series, is required to produce fragmented Golgi membranes in the pericentriolar region that is characteristic of macfarlandin E.

Sesquiterpene lactones from Taraxacum obovatum.

PubMed

Michalska, Klaudia; Kisiel, Wanda

2003-02-01

Two new guaianolide glucosides, deacetylmatricarin 8-O-beta-glucopyranoside and 11beta-hydroxyleukodin 11-O-beta-glucopyranoside, were isolated from roots of Taraxacum obovatum, along with four known sesquiterpene lactones, deacetylmatricarin, sonchuside A, taraxinic acid beta-glucopyranosyl ester and its 11beta,13-dihydro derivative. Their structures were established by spectral methods.

Investigation of N-acyl homoserine lactone (AHL) molecule production in Gram-negative bacteria isolated from cooling tower water and biofilm samples.

PubMed

Haslan, Ezgi; Kimiran-Erdem, Ayten

2013-09-01

In this study, 99 Gram-negative rod bacteria were isolated from cooling tower water, and biofilm samples were examined for cell-to-cell signaling systems, N-acyl homoserine lactone (AHL) signal molecule types, and biofilm formation capacity. Four of 39 (10 %) strains isolated from water samples and 14 of 60 (23 %) strains isolated from biofilm samples were found to be producing a variety of AHL signal molecules. It was determined that the AHL signal molecule production ability and the biofilm formation capacity of sessile bacteria is higher than planktonic bacteria, and there was a statistically significant difference between the AHL signal molecule production of these two groups (p < 0.05). In addition, it was found that bacteria belonging to the same species isolated from cooling tower water and biofilm samples produced different types of AHL signal molecules and that there were different types of AHL signal molecules in an AHL extract of bacteria. In the present study, it was observed that different isolates of the same strains did not produce the same AHLs or did not produce AHL molecules, and bacteria known as AHL producers did not produce AHL. These findings suggest that detection of signal molecules in bacteria isolated from cooling towers may contribute to prevention of biofilm formation, elimination of communication among bacteria in water systems, and blockage of quorum-sensing controlled virulence of these bacteria.

Biosynthesis of Costunolide, Dihydrocostunolide, and Leucodin. Demonstration of Cytochrome P450-Catalyzed Formation of the Lactone Ring Present in Sesquiterpene Lactones of Chicory

PubMed Central

de Kraker, Jan-Willem; Franssen, Maurice C.R.; Joerink, Maaike; de Groot, Aede; Bouwmeester, Harro J.

2002-01-01

Chicory (Cichorium intybus) is known to contain guaianolides, eudesmanolides, and germacranolides. These sesquiterpene lactones are postulated to originate from a common germacranolide, namely (+)-costunolide. Whereas a pathway for the formation of germacra-1(10),4,11(13)-trien-12-oic acid from farnesyl diphosphate had previously been established, we now report the isolation of an enzyme activity from chicory roots that converts the germacrene acid into (+)-costunolide. This (+)-costunolide synthase catalyzes the last step in the formation of the lactone ring present in sesquiterpene lactones and is dependent on NADPH and molecular oxygen. Incubation of the germacrene acid in the presence of 18O2 resulted in the incorporation of one atom of 18O into (+)-costunolide. The label was situated at the ring oxygen atom. Hence, formation of the lactone ring most likely occurs via C6-hydroxylation of the germacrene acid and subsequent attack of this hydroxyl group at the C12-atom of the carboxyl group. Blue light-reversible CO inhibition and experiments with cytochrome P450 inhibitors demonstrated that the (+)-costunolide synthase is a cytochrome P450 enzyme. In addition, enzymatic conversion of (+)-costunolide into 11(S),13-dihydrocostunolide and leucodin, a guaianolide, was detected. The first-mentioned reaction involves an enoate reductase, whereas the formation of leucodin from (+)-costunolide probably involves more than one enzyme, including a cytochrome P450 enzyme. PMID:12011356

Biosynthesis of costunolide, dihydrocostunolide, and leucodin. Demonstration of cytochrome p450-catalyzed formation of the lactone ring present in sesquiterpene lactones of chicory.

PubMed

de Kraker, Jan-Willem; Franssen, Maurice C R; Joerink, Maaike; de Groot, Aede; Bouwmeester, Harro J

2002-05-01

Chicory (Cichorium intybus) is known to contain guaianolides, eudesmanolides, and germacranolides. These sesquiterpene lactones are postulated to originate from a common germacranolide, namely (+)-costunolide. Whereas a pathway for the formation of germacra-1(10),4,11(13)-trien-12-oic acid from farnesyl diphosphate had previously been established, we now report the isolation of an enzyme activity from chicory roots that converts the germacrene acid into (+)-costunolide. This (+)-costunolide synthase catalyzes the last step in the formation of the lactone ring present in sesquiterpene lactones and is dependent on NADPH and molecular oxygen. Incubation of the germacrene acid in the presence of 18O2 resulted in the incorporation of one atom of 18O into (+)-costunolide. The label was situated at the ring oxygen atom. Hence, formation of the lactone ring most likely occurs via C6-hydroxylation of the germacrene acid and subsequent attack of this hydroxyl group at the C12-atom of the carboxyl group. Blue light-reversible CO inhibition and experiments with cytochrome P450 inhibitors demonstrated that the (+)-costunolide synthase is a cytochrome P450 enzyme. In addition, enzymatic conversion of (+)-costunolide into 11(S),13-dihydrocostunolide and leucodin, a guaianolide, was detected. The first-mentioned reaction involves an enoate reductase, whereas the formation of leucodin from (+)-costunolide probably involves more than one enzyme, including a cytochrome P450 enzyme.

Enantiodifferentiation of whisky and cognac lactones using gas chromatography with different cyclodextrin chiral stationary phases.

PubMed

Schmarr, Hans-Georg; Mathes, Maximilian; Wall, Kristina; Metzner, Frank; Fraefel, Marius

2017-09-22

The chiral lactone 5-butyl-4-methyloxolan-2-one or 5-butyl-4-methyldihydro-2(3H)-furanone, often named whisky lactone, is found in oak wood, then contributing to the appreciated flavor of beverages stored in such wooden barrels. Its next higher homologue is named cognac lactone (5-pentyl-4-methyloxolan-2-one or 5-pentyl-4-methyldihydro-2(3H)-furanone), however is much less known, probably due to its minor concentration level. In order to study the direct enantioseparation of both lactones by gas chromatography on chiral stationary phases, individual enantiomers, particularly for cognac lactone were made available. This was achieved by baker's yeast reduction of synthesized ethyl 3-methyl-4-oxononanoate or, after hydrolysis, of the corresponding 4-ketoacid, that gave access to individual enantiomers of cognac lactone. Good enantioseparation was achieved for both whisky and cognac lactone with high values for the chiral resolution with 6-O-tert. butyl dimethylsilyl-2,3-dialkylated or 6-O-tert. butyl dimethylsilyl-2,3-diacylated cyclodextrin derivatives as chiral selectors. The influence of the nature and position of derivatization of the cyclodextrin moiety revealed a strong impact on the chiral recognition mechanism, as the investigated alkylated derivatives heptakis-(2,6-di-O-iso-pentyl-3-O-allyl)-β-cyclodextrin and octakis-(2,3-di-O-pentyl-6-O-methyl)-γ-cyclodextrin did not provide any or only minor chiral selectivity for the two lactones. Copyright © 2017 Elsevier B.V. All rights reserved.

Strong inhibitory effect of furanoses and sugar lactones on beta-galactosidase Escherichia coli.

PubMed

Huber, R E; Brockbank, R L

1987-03-24

Various sugars and their lactones were tested for their inhibition of beta-galactosidase (Escherichia coli). L-Ribose, which in the furanose form has a hydroxyl configuration similar to that of D-galactose at positions equivalent to the 3- and 4-positions of D-galactose, was a very strong inhibitor, and D-lyxose, which in the furanose form also resembles D-galactose, was a much better inhibitor than expected. Structural comparisons prelude the pyranose forms of these sugars from being significant contributors to the inhibition, and inhibition at different temperatures (at which there are different furanose concentrations) strongly supported the conclusion that the furanose form is inhibitory. Studies with sugar derivatives that can only be in the furanose form also supported the conclusion. This is the first report of the inhibitory effect of furanose on beta-galactosidase. Lactones were also inhibitory. Every lactone tested was much more inhibitory than was its parent sugar. D-Galactonolactone was especially good. Experiments indicated that it was D-galactono-1,5-lactone rather than D-galactono-1,4-lactone which was inhibitory. Inhibition of beta-galactosidases from mammalian sources by lactones has been reported previously, but this is the first report of the effect of beta-galactosidase from E. coli. Since furanoses in the envelope form are analogous (in some ways) to half-chair or sofa conformations and since lactones with six-membered rings probably have half-chair or sofa conformations, the results indicate that beta-galactosidase probably destabilizes its substrate into a planar conformation of some type and that the galactose in the transition state may, therefore, also be quite planar.(ABSTRACT TRUNCATED AT 250 WORDS)

A grapevine cytochrome P450 generates the precursor of wine lactone, a key odorant in wine.

PubMed

Ilc, Tina; Halter, David; Miesch, Laurence; Lauvoisard, Florian; Kriegshauser, Lucie; Ilg, Andrea; Baltenweck, Raymonde; Hugueney, Philippe; Werck-Reichhart, Danièle; Duchêne, Eric; Navrot, Nicolas

2017-01-01

Monoterpenes are important constituents of the aromas of food and beverages, including wine. Among monoterpenes in wines, wine lactone has the most potent odor. It was proposed to form via acid-catalyzed cyclization of (E)-8-carboxylinalool during wine maturation. It only reaches very low concentrations in wine but its extremely low odor detection threshold makes it an important aroma compound. Using LC-MS/MS, we show here that the (E)-8-carboxylinalool content in wines correlates with their wine lactone content and estimate the kinetic constant for the very slow formation of wine lactone from (E)-8-carboxylinalool. We show that (E)-8-carboxylinalool is accumulated as a glycoside in grape (Vitis vinifera) berries and that one of the cytochrome P450 enzymes most highly expressed in maturing berries, CYP76F14, efficiently oxidizes linalool to (E)-8-carboxylinalool. Our analysis of (E)-8-carboxylinalool in Riesling × Gewurztraminer grapevine progeny established that the CYP76F14 gene co-locates with a quantitative trait locus for (E)-8-carboxylinalool content in grape berries. Our data support the role of CYP76F14 as the major (E)-8-carboxylinalool synthase in grape berries and the role of (E)-8-carboxylinalool as a precursor to wine lactone in wine, providing new insights into wine and grape aroma metabolism, and new methods for food and aroma research and production. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

Ketopantoyl-lactone reductase from Candida parapsilosis: purification and characterization as a conjugated polyketone reductase.

PubMed

Hata, H; Shimizu, S; Hattori, S; Yamada, H

1989-02-24

Ketopantoyl-lactone reductase (2-dehydropantoyl-lactone reductase, EC 1.1.1.168) was purified and crystallized from cells of Candida parapsilosis IFO 0708. The enzyme was found to be homogeneous on ultracentrifugation, high-performance gel-permeation liquid chromatography and SDS-polyacrylamide gel electrophoresis. The relative molecular mass of the native and SDS-treated enzyme is approximately 40,000. The isoelectric point of the enzyme is 6.3. The enzyme was found to catalyze specifically the reduction of a variety of natural and unnatural polyketones and quinones other than ketopantoyl lactone in the presence of NADPH. Isatin and 5-methylisatin are rapidly reduced by the enzyme, the Km and Vmax values for isatin being 14 microM and 306 mumol/min per mg protein, respectively. Ketopantoyl lactone is also a good substrate (Km = 333 microM and Vmax = 481 mumol/min per mg protein). Reverse reaction was not detected with pantoyl lactone and NADP+. The enzyme is inhibited by quercetin, several polyketones and SH-reagents. 3,4-Dihydroxy-3-cyclobutene-1,2-dione, cyclohexenediol-1,2,3,4-tetraone and parabanic acid are uncompetitive inhibitors for the enzyme, the Ki values being 1.4, 0.2 and 3140 microM, respectively, with isatin as substrate. Comparison of the enzyme with the conjugated polyketone reductase of Mucor ambiguus (S. Shimizu, H. Hattori, H. Hata and H. Yamada (1988) Eur. J. Biochem. 174, 37-44) and ketopantoyl-lactone reductase of Saccharomyces cerevisiae suggested that ketopantoyl-lactone reductase is a kind of conjugated polyketone reductase.

Membrane-Surface Anchoring of Charged Diacylglycerol-Lactones Correlates with Biological Activities | Center for Cancer Research

Cancer.gov

The inside cover picture shows the molecular structure of a DAG lactone derivative on top of the inner leaflet of a DMPC bilayer. The confocal microscopy image illustrates DAG-lactone-stimulated membrane localization of PKCδ-ECFP in living cells, while the space-filling model shows the surface of the C1B domain of PKCδ, the target of the lactone.

Structural and Sensory Characterization of Novel Sesquiterpene Lactones from Iceberg Lettuce.

PubMed

Mai, Franziska; Glomb, Marcus A

2016-01-13

Lactuca sativa var. capitate (iceberg lettuce) is a delicious vegetable and popular for its mild taste. Nevertheless, iceberg lettuce is a source of bitter substances, such as the sesquiterpene lactones. Chemical investigations on the n-butanol extract led to the isolation of three novel sesquiterpene lactones. All compounds were isolated by multilayer countercurrent chromatography followed by preparative high-performance liquid chromatography. The structures were verified by means of spectroscopic methods, including NMR and mass spectrometry techniques. For the first time 11ß,13-dihydrolactucin-8-O-sulfate (jaquinelin-8-O-sulfate) was structurally elucidated and identified in plants. In addition, the sesquiterpene lactones cichorioside B and 8-deacetylmatricarin-8-O-sulfate were identified as novel ingredients of iceberg lettuce. Further flowering plants in the daisy family Asteraceae were examined for the above three compounds. At least one of the compounds was identified in nine plants. The comparison between the lettuce butt end and the leaves of five types of the Cichorieae tribe showed an accumulation of the compounds in the butt end. Further experiments addressed the impact of sesquiterpene lactones on color formation and bitter taste.

Variability of sesquiterpene lactones in Neurolaena lobata of different origin.

PubMed

Passreiter, C M; Aldana, B E

1998-06-01

Leaves of Neurolaena lobata (L.) R. Br. originating from Guatemala, were analyzed using HPLC for their qualitative and quantitative sesquiterpene lactone contents. Significant differences in the individual amounts of neurolenins and furanoheliangolides were found between four natural populations. When plants were cultivated on proving fields at two different localities in Guatemala, their sesquiterpene lactone patterns matched the natural population, but differed quantitatively. The meaning of these differences for the use of N. lobata in traditional medicine and its cultivation is discussed.

Detecting and characterizing N-acyl-homoserine lactone signal molecules by thin-layer chromatography

PubMed Central

Shaw, Paul D.; Ping, Gao; Daly, Sean L.; Cha, Chung; Cronan, John E.; Rinehart, Kenneth L.; Farrand, Stephen K.

1997-01-01

Many Gram-negative bacteria regulate gene expression in response to their population size by sensing the level of acyl-homoserine lactone signal molecules which they produce and liberate to the environment. We have developed an assay for these signals that couples separation by thin-layer chromatography with detection using Agrobacterium tumefaciens harboring lacZ fused to a gene that is regulated by autoinduction. With the exception of N-butanoyl-l-homoserine lactone, the reporter detected acyl-homoserine lactones with 3-oxo-, 3-hydroxy-, and 3-unsubstituted side chains of all lengths tested. The intensity of the response was proportional to the amount of the signal molecule chromatographed. Each of the 3-oxo- and the 3-unsubstituted derivatives migrated with a unique mobility. Using the assay, we showed that some bacteria produce as many as five detectable signal molecules. Structures could be assigned tentatively on the basis of mobility and spot shape. The dominant species produced by Pseudomonas syringae pv. tabaci chromatographed with the properties of N-(3-oxohexanoyl)-l-homoserine lactone, a structure that was confirmed by mass spectrometry. An isolate of Pseudomonas fluorescens produced five detectable species, three of which had novel chromatographic properties. These were identified as the 3-hydroxy- forms of N-hexanoyl-, N-octanoyl-, and N-decanoyl-l-homoserine lactone. The assay can be used to screen cultures of bacteria for acyl-homoserine lactones, for quantifying the amounts of these molecules produced, and as an analytical and preparative aid in determining the structures of these signal molecules. PMID:9177164

Heliolactone, a non-sesquiterpene lactone germination stimulant for root parasitic weeds from sunflower.

PubMed

Ueno, Kotomi; Furumoto, Toshio; Umeda, Shuhei; Mizutani, Masaharu; Takikawa, Hirosato; Batchvarova, Rossitza; Sugimoto, Yukihiro

2014-12-01

Root exudates of sunflower (Helianthus annuus L.) line 2607A induced germination of seeds of root parasitic weeds Striga hermonthica, Orobanche cumana, Orobanche minor, Orobanche crenata, and Phelipanche aegyptiaca. Bioassay-guided purification led to the isolation of a germination stimulant designated as heliolactone. FT-MS analysis indicated a molecular formula of C20H24O6. Detailed NMR spectroscopic studies established a methylfuranone group, a common structural component of strigolactones connected to a methyl ester of a C14 carboxylic acid via an enol ether bridge. The cyclohexenone ring is identical to that of 3-oxo-α-ionol and the other part of the molecule corresponds to an oxidized carlactone at C-19. It is a carlactone-type molecule and functions as a germination stimulant for seeds of root parasitic weeds. Heliolactone induced seed germination of the above mentioned root parasitic weeds, while dehydrocostus lactone and costunolide, sesquiterpene lactones isolated from sunflower root exudates, were effective only on O. cumana and O. minor. Heliolactone production in aquacultures increased when sunflower seedlings were grown hydroponically in tap water and decreased on supplementation of the culture with either phosphorus or nitrogen. Costunolide, on the other hand, was detected at a higher concentration in well-nourished medium as opposed to nutrient-deficient media, thus suggesting a contrasting contribution of heliolactone and the sesquiterpene lactone to the germination of O. cumana under different soil fertility levels. Copyright © 2014 Elsevier Ltd. All rights reserved.

Developmental and Environmental Effects on Sesquiterpene Lactones in Cultivated Arnica montana L.

PubMed

Todorova, Milka; Trendafilova, Antoaneta; Vitkova, Antonina; Petrova, Maria; Zayova, Ely; Antonova, Daniela

2016-08-01

The amount of sesquiterpene lactones and the lactone profile of Arnica montana L. in flowering and seed formation stages in vitro and in vivo propagated from seeds of German, Ukrainian, and Austrian origin and grown in two experimental fields were studied. It was found that in vitro propagated 2-year plants in full flowering stage accumulated higher amount of lactones in comparison to in vivo propagated 3-year plants and to the seed formation stage, respectively. Helenalins predominated in in vivo propagated 2-year or in vitro propagated 3-year plants. 2-Methylbutyrate (2MeBu) was the principal ester in the samples with prevalence of helenalins, while isobutyrate (iBu) was the major one in the samples with predominance of 11,13-dihydrohelenalins. The results revealed that the environmental conditions on Vitosha Mt. are more suitable for cultivation of A. montana giving higher content of lactones. © 2016 Wiley-VHCA AG, Zürich.

Sesquiterpene lactones from neurolaena oaxacana

PubMed

Passreiter; Sandoval-Ramirez; Wright

1999-08-01

Twelve sesquiterpene lactones, two new (1 and 2) and 10 known neurolenin-type germacranolides and furanoheliangolides (3-12) were isolated from Neurolaena oaxacana, and their structures were elucidated by NMR and GC-MS analysis. The chemotaxonomic importance of these findings is discussed. As N. lobata is used against dysenteries, neurolenin B (4) and a mixture of the neurolenins C (5) and D (6) were tested against Entamoeba histolytica and Giardia intestinalis.

Titanocene(III) chloride mediated radical-induced addition to Baylis-Hillman adducts: synthesis of (E)- and (Z)-trisubstituted alkenes and alpha-methylene/arylidene delta-lactones.

PubMed

Mandal, Samir K; Paira, Moumita; Roy, Subhas C

2008-05-16

Baylis-Hillman adduct underwent smooth radical-induced condensation with activated bromo compounds and epoxides using titanocene(III) chloride (Cp2TiCl) as the radical generator. The reactions of activated bromo compounds with 3-acetoxy-2-methylene alkanoates provided (E)-alkenes exclusively, whereas similar reactions with 3-acetoxy-2-methylenealkanenitriles led to (Z)-alkenes as the major product. The reactions of epoxides with Baylis-Hillman adduct furnished alpha-methylene/arylidene-delta-lactones in good yield via addition followed by in situ lactonization.

Lipase-catalyzed ring-opening polymerization of lactones to polyesters and its mechanistic aspects.

PubMed

Namekawa, S; Suda, S; Uyama, H; Kobayashi, S

1999-01-01

Lipase catalysis induced a ring-opening polymerization of lactones with different ring-sizes. Small-size (four-membered) and medium-size lactones (six- and seven-membered) as well as macrolides (12-, 13-, 16-, and 17-membered) were subjected to lipase-catalyzed polymerization. The polymerization behaviors depended primarily on the lipase origin and the monomer structure. The macrolides showing much lower anionic polymerizability were enzymatically polymerized faster than epsilon-caprolactone. The granular immobilized lipase derived from Candida antartica showed extremely efficient catalysis in the polymerization of epsilon-caprolactone. Single-step terminal functionalization of the polyester was achieved by initiator and terminator methods. The enzymatic polymerizability of lactones was quantitatively evaluated by Michaelis-Menten kinetics.

Macrocyclic lactones: A versatile source for omega radiohalogenated fatty acid analogs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dougan, A.H.; Lyster, D.M.; Robertson, K.A.

For each omega halogenated fatty acid there exists a potential omega hydroxy fatty acid and the corresponding macrocyclic lactone. The authors have utilized such lactones as starting materials for omega /sup 123/I fatty acid analogs intended for myocardial imaging. Macrocyclic musk lactones are industrially available; 120 analogs are described in the literature. The preparation requires saponification, tosylation, and radio-iodide substitution. Iodo-fatty acids are readily separated from tosylate fatty acids on TLC. While providing a secure source of 16-iodo-hexadecanoic acid and 17-iodo-heptadecanoic acid, the scheme allows ready access to a large number of untried fatty acid analogs. Examples presented are 16-iodo-hexadecanoicmore » acid, 16-iodo-7-hexadecanoic acid, 16-iodo-12-oxa-hexadecanoic acid, 15-iodo-pentadecanoic acid, and 15-iodo-12-keto-pentadecanoic acid. Metabolic studies are in progress in mice and dogs to assess the utility of these analogs for myocardial imaging.« less

Biosynthesis of Jasmine Lactone in Tea ( Camellia sinensis) Leaves and Its Formation in Response to Multiple Stresses.

PubMed

Zeng, Lanting; Zhou, Ying; Fu, Xiumin; Liao, Yinyin; Yuan, Yunfei; Jia, Yongxia; Dong, Fang; Yang, Ziyin

2018-04-18

Jasmine lactone has a potent odor that contributes to the fruity, sweet floral aroma of tea ( Camellia sinensis). Our previous study demonstrated that jasmine lactone was mostly accumulated at the turnover stage of the oolong tea manufacturing process. This study investigates the previously unknown mechanism of formation of jasmine lactone in tea leaves exposed to multiple stresses occurring during the growth and manufacturing processes. Both continuous mechanical damage and the dual stress of low temperature and mechanical damage enhanced jasmine lactone accumulation in tea leaves. In addition, only one pathway, via hydroperoxy fatty acids from unsaturated fatty acid, including linoleic acid and α-linolenic acid, under the action of lipoxygenases (LOXs), especially CsLOX1, was significantly affected by these stresses. This is the first evidence of the mechanism of jasmine lactone formation in tea leaves and is a characteristic example of plant volatile formation in response to dual stress.

Transgenic plants producing the bacterial pheromone N-acyl-homoserine lactone exhibit enhanced resistance to the bacterial phytopathogen Erwinia carotovora.

PubMed

Mäe, A; Montesano, M; Koiv, V; Palva, E T

2001-09-01

Bacterial pheromones, mainly different homoserine lactones, are central to a number of bacterial signaling processes, including those involved in plant pathogenicity. We previously demonstrated that N-oxoacyl-homoserine lactone (OHL) is essential for quorum sensing in the soft-rot phytopathogen Erwinia carotovora. In this pathogen, OHL controls the coordinate activation of genes encoding the main virulence determinants, extracellular plant cell wall degrading enzymes (PCWDEs), in a cell density-dependent manner. We suggest that E. carotovora employ quorum sensing to avoid the premature production of PCWDEs and subsequent activation of plant defense responses. To test whether modulating this sensory system would affect the outcome of a plant-pathogen interaction, we generated transgenic tobacco, producing OHL. This was accomplished by ectopic expression in tobacco of the E. carotovora gene expI, which is responsible for OHL biosynthesis. We show that expI-positive transgenic tobacco lines produced the active pheromone and partially complemented the avirulent phenotype of expI mutants. The OHL-producing tobacco lines exhibited enhanced resistance to infection by wild-type E. carotovora. The results were confirmed by exogenous addition of OHL to wild-type plants, which also resulted in increased resistance to E. carotovora.

Lettuce Costunolide Synthase (CYP71BL2) and Its Homolog (CYP71BL1) from Sunflower Catalyze Distinct Regio- and Stereoselective Hydroxylations in Sesquiterpene Lactone Metabolism*

PubMed Central

Ikezawa, Nobuhiro; Göpfert, Jens Christian; Nguyen, Don Trinh; Kim, Soo-Un; O'Maille, Paul E.; Spring, Otmar; Ro, Dae-Kyun

2011-01-01

Sesquiterpene lactones (STLs) are terpenoid natural products possessing the γ-lactone, well known for their diverse biological and medicinal activities. The occurrence of STLs is sporadic in nature, but most STLs have been isolated from plants in the Asteraceae family. Despite the implication of the γ-lactone group in many reported bioactivities of STLs, the biosynthetic origins of the γ-lactone ring remains elusive. Germacrene A acid (GAA) has been suggested as a central precursor of diverse STLs. The regioselective (C6 or C8) and stereoselective (α or β) hydroxylation on a carbon of GAA adjacent to its carboxylic acid at C12 is responsible for the γ-lactone formation. Here, we report two cytochrome P450 monooxygenases (P450s) capable of catalyzing 6α- and 8β-hydroxylation of GAA from lettuce and sunflower, respectively. To identify these P450s, sunflower trichomes were isolated to generate a trichome-specific transcript library, from which 10 P450 clones were retrieved. Expression of these clones in a yeast strain metabolically engineered to synthesize substrate GAA identified a P450 catalyzing 8β-hydroxylation of GAA, but the STL was not formed by spontaneous lactonization. Subsequently, we identified the closest homolog of the GAA 8β-hydroxylase from lettuce and discovered 6α-hydroxylation of GAA by the recombinant enzyme. The resulting 6α-hydroxy-GAA spontaneously undergoes a lactonization to yield the simplest form of STL, costunolide. Furthermore, we demonstrate the milligram per liter scale de novo synthesis of costunolide using the lettuce P450 in an engineered yeast strain, an important advance that will enable exploitation of STLs. Evolution and homology models of these two P450s are discussed. PMID:21515683

Studies on the sesquiterpene lactones from Laurus novocanariensis lead to the clarification of the structures of 1-epi-tatridin B and its epimer tatridin B.

PubMed

Fraga, Braulio M; Terrero, David; Cabrera, Inmaculada; Reina, Matías

2018-06-01

The germacranolide 1-epi-tatridin B has been isolated from the aerial parts of Laurus novocanariensis. We have observed that the identification of this lactone and its epimer tetradin B in the scientific literature is confusing and contradictory. We have therefore studied this issue clarifying errors and contributing to the structural elucidation of other related products. Moreover, we have isolated from this plant a lactone with an 1,5-ether bridge, previously obtained from Austrolabium candidum. We have now named it austroliolide, reassigned its 13 C NMR spectrum and compared its structure with that of badgerin. In addition, we have also isolated from L. novocanariensis the known germacranolides artemorin, costunolide, tatridin A, tulirinol and verlotorin, the eudesmanolides β-cyclopyrethrosin, 1β-hydroxy-arbusculin A, magnoliaolide and reynosin, and the guaianolide dehydrocostus lactone. Copyright © 2018 Elsevier Ltd. All rights reserved.

Janthinocins A, B and C, novel peptide lactone antibiotics produced by Janthinobacterium lividum. II. Structure elucidation.

PubMed

Johnson, J H; Tymiak, A A; Bolgar, M S

1990-08-01

The structures of janthinocins A, B and C, three novel macrocyclic peptide lactone antibiotics isolated from fermentations of Janthinobacterium lividum, were determined. The janthinocins are of particular interest because they contain three amino acid residues that have not previously been reported in natural products: Each contains erythro-beta-hydroxy-D-leucine while janthinocins A and B also contain beta-hydroxytryptophan and beta-ketotryptophan, respectively.

Diastereocontrolled Electrophilic Fluorinations of 2-Deoxyribonolactone: Syntheses of All Corresponding 2-Deoxy-2-fluoro-lactones and 2’-Deoxy-2’-fluoro-NAD+s

PubMed Central

Cen, Yana; Sauve, Anthony A.

2009-01-01

Methods to construct 2’-deoxy-2’-fluoro-nucleosides have undergone limited improvement in the last twenty years in spite of substantially increased value of these compounds as pharmaceuticals and as tools for studying biological processes. We herein describe a consolidated approach to synthesize precursors to these commercially and scientifically valuable compounds via diastereocontrolled fluorination of the readily available precursor 2-deoxy-d-ribonolactone. With employment of appropriate sterically bulky silyl protecting groups at 3 and 5 positions, controlled electrophilic fluorination of the Li-ribonolactone enolate by N-fluorodibenezenesulfonamide yielded the corresponding 2-deoxy-2-fluoro-arabino-lactone in high isolated yield (72 %). The protected 2-deoxy-2, 2-difluoro-ribonolactone was obtained similarly in high yield from a second round of electrophilic fluorination (2 steps, 51% from protected ribonolactone starting material). Accomplishment of the difficult ribo-fluorination of the lactone was achieved by the directive effects of a diastereoselectively installed α-trimethylsilyl group. Electrophilic fluorination of a protected 2-deoxy-2-trimethylsilyl-arabino-lactone via enolate generation provided the protected 2-deoxy-2-fluoro-ribo-lactone as the exclusive fluorinated product. The reaction also yielded the starting material, the desilylated protected 2-deoxy-ribonolactone, which was recycled to provide a 38% chemical yield of the fluorinated product (versus initial protected ribonolactone) after consecutive silylation and fluorination cycles. Using our fluorinated sugar precursors we prepared the 2’-fluoro-arabino-, 2’-fluoro-ribo- and 2’,2’-difluoro-nicotinamide adenine dinucleotides (NAD+) of potential biological interest. These syntheses provide the most consolidated and efficient methods for production of sugar precursors of 2’-deoxy-2’-fluoronucleosides and have the advantage of utilizing an air-stable electrophilic fluorinating

Antibacterial and cytotoxic activities of the sesquiterpene lactones cnicin and onopordopicrin.

PubMed

Bach, Sandra M; Fortuna, Mario A; Attarian, Rodgoun; de Trimarco, Juliana T; Catalán, César A N; Av-Gay, Yossef; Bach, Horacio

2011-02-01

The antimicrobial and cytotoxic activities of chloroform extracts from the weeds Centaurea tweediei and C. diffusa, and the main sesquiterpene lactones isolated from these species, onopordopicrin and cnicin, respectively, were assayed. Results show that the chloroform extracts from both Centaurea species possess antibacterial activities against a panel of Gram-positive and Gram-negative bacteria. Remarkable antibacterial activity against methicillin-resistant Staphylococcus aureus was also measured. Both the extracts and the purified sesquiterpene lactones show high cytotoxicity against human-derived macrophages. Despite this cytotoxicity, C. diffusa chloroform extract and cnicin are attractive candidates for evaluation as antibiotics in topical preparations against skin-associated pathogens.

Penicimenolides A-F, Resorcylic Acid Lactones from Penicillium sp., isolated from the Rhizosphere Soil of Panax notoginseng.

PubMed

An, Ya-Nan; Zhang, Xue; Zhang, Tian-Yuan; Zhang, Meng-Yue; Qian-Zhang; Deng, Xiao-Yu; Zhao, Feng; Zhu, Ling-Juan; Wang, Guan; Zhang, Jie; Zhang, Yi-Xuan; Liu, Bo; Yao, Xin-Sheng

2016-06-08

Five new 12-membered resorcylic acid lactone derivatives, penicimenolides A-E (1-5), one new ring-opened resorcylic acid lactone derivative penicimenolide F (6), and six known biogenetically related derivatives (7-12) were isolated from the culture broth of a strain of Penicillium sp. (NO. SYP-F-7919), a fungus obtained from the rhizosphere soil of Panax notoginseng collected from the Yunnan province of China. Their structures were elucidated by extensive NMR analyses, a modified Mosher's method, chemical derivatization and single crystal X-ray diffraction analysis. Compounds 2-4 exhibited potent cytotoxicity against the U937 and MCF-7 tumour cell lines and showed moderate cytotoxic activity against the SH-SY5Y and SW480 tumour cell lines. The substitution of an acetyloxy or 2-hydroxypropionyloxy group at C-7 significantly increased the cytotoxic activity of the resorcylic acid lactone derivatives. Subsequently, the possible mechanism of compound 2 against MCF-7 cells was preliminarily investigated by in silico analysis and experimental validation, indicating compound 2 may act as a potential MEK/ERK inhibitor. Moreover, proteomics analysis was performed to explore compound 2-regulated concrete mechanism underlying MEK/ERK pathway, which is still need further study in the future. In addition, compounds 2-4 and 7 exhibited a significant inhibitory effect on NO production induced by LPS.

The Fe(III) and Ga(III) coordination chemistry of 3-(1-hydroxymethylidene) and 3-(1-hydroxydecylidene)-5-(2-hydroxyethyl)pyrrolidine-2,4-dione: Novel tetramic acid degradation products of homoserine lactone bacterial quorum sensing molecules

PubMed Central

Romano, Ariel A.; Hahn, Tobias; Davis, Nicole; Lowery, Colin A.; Struss, Anjali K.; Janda, Kim D.; Böttger, Lars H.; Matzanke, Berthold F.; Carrano, Carl J.

2011-01-01

Bacteria use small diffusible molecules to exchange information in a process called quorum sensing (QS). An important class of quorum sensing molecules used by Gram-negative bacteria is the family of N-acylhomoserine lactones (HSL). It was recently discovered that a degradation product of the QS molecule 3-oxo-C12-homoserine lactone, the tetramic acid 3-(1-hydroxydecylidene)-5-(2-hydroxyethyl)pyrrolidine-2,4-dione, is a potent antibacterial agent, thus implying roles for QS outside of simply communication. Because these tetramic acids also appear to bind iron with appreciable affinity it was suggested that metal binding might contribute to their biological activity. Here, using a variety of spectroscopic tools, we describe the coordination chemistry of both the methylidene and decylidene tetramic acid derivatives with Fe(III) and Ga(III) and discuss the potential biological significance of such metal binding. PMID:22178671

Effect of different types of sesquiterpene lactones on the maturation of Rhinella arenarum oocytes.

PubMed

Sánchez-Toranzo, G; Zapata-Martínez, J; Catalán, C; Bühler, M I

2015-06-01

The sesquiterpene lactones (STLs) are a large class of plant secondary metabolites that are generally found in the Asteraceae family and that have high diversity with respect to chemical structure as well as biological activity. STLs have been classified into different groups, such as guaianolides, germacranolides, and melampolides etc., based on their carboxylic skeleton. In amphibians, fully grown ovarian oocytes are arrested at the beginning of meiosis I. Under the stimulus of progesterone, this meiotic arrest is released and meiosis progresses to metaphase II, a process known as oocyte maturation. The purpose of this work was to determine whether sesquiterpene lactones from the germacranolide and melampolide groups act as inhibitor agents on the meiosis of amphibian oocytes in vitro. Results for germacranolides indicated that the addition of deoxyelephantopins caused a high degree of inhibition and that minimolide showed a moderate inhibitory effect, whereas glaucolide A was inactive. Furthermore, the addition of melampolides (uvedalin, enhydrin, polymatin A and polymatin B) showed inhibitory effects. For enhydrin and uvedalin, inhibitory effects were observed at the higher concentrations assayed. The results of this study suggest that the inhibitory activity of the tested sesquiterpene lactones on the meiosis of Rhinella arenarum oocytes is not dependent on the group to which they belong, i.e. not on the carboxylic skeleton, but probably due to the arrangement and type of function groups present in the molecules. All assayed lactones in the germacranolide group showed low toxicity. In contrast, important differences in toxicity were observed for lactones from the melampolide group: enhydrin and uvedalin showed low toxicity, but polymatin A and B were highly toxic.

Capillary zone electrophorsis for the analysis of naturally occurring 2-hydroxycitric acids and their lactones.

PubMed

Abhijith, B L; Mohan, Moolya; Joseph, David; Haleema, Simimole; Aboul-Enein, Hassan Y; Ibnusaud, Ibrahim

2017-08-01

A simple capillary zone electrophoresis method with direct ultraviolet detection has been developed for the analysis of naturally occurring diastereomeric 2-hydroxycitric acid lactones. Using 50 mM sodium phosphate buffer of pH 7, a baseline resolution R s > 3.0 was observed for all organic acids selected for the present study. This method was employed for the quantitative determination of title acids present in the plant sources namely Garcinia cambogia fruit rinds and Hibiscus sabdariffa calyx. Conversion of 2-hydroxycitric acids to their lactones on heating the above plant sources is deliberated. The Hydrolysis of hydroxycitric acid lactones in aqueous solution is reported for the first time. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Strategies for the control of Rhipicephalus microplus ticks in a world of conventional acaricide and macrocyclic lactone resistance.

PubMed

Rodriguez-Vivas, Roger I; Jonsson, Nicholas N; Bhushan, Chandra

2018-01-01

Infestations with the cattle tick, Rhipicephalus microplus, constitute the most important ectoparasite problem for cattle production in tropical and subtropical regions worldwide, resulting in major economic losses. The control of R. microplus is mostly based on the use of conventional acaricides and macrocyclic lactones. However, the intensive use of such compounds has resulted in tick populations that exhibit resistance to all major acaricide chemical classes. Consequently, there is a need for the development of alternative approaches, possibly including the use of animal husbandry practices, synergized pesticides, rotation of acaricides, pesticide mixture formulations, manual removal of ticks, selection for host resistance, nutritional management, release of sterile male hybrids, environmental management, plant species that are unfavourable to ticks, pasture management, plant extracts, essential oils and vaccination. Integrated tick management consists of the systematic combination of at least two control technologies aiming to reduce selection pressure in favour of acaricide-resistant individuals, while maintaining adequate levels of animal production. The purpose of this paper is to present a current review on conventional acaricide and macrocyclic lactone resistance for better understanding and control of resistant ticks with particular emphasis on R. microplus on cattle.

Neocosmospora sp.-derived resorcylic acid lactones with in vitro binding capacity for human opioid and cannabinoid receptors

USDA-ARS?s Scientific Manuscript database

Bioassay-guided fractionation of a fungus Neocosmospora sp. (UM-031509) resulted in the isolation of three new resorcyclic acid lactones, neocosmosin A (2), neocosmosin B (3) and neocosmosin C (4). Three known resorcylic acid lactones, monocillin IV (1), monocillin II (5) and monorden (6) were also ...

A Sinorhizobium meliloti-specific N-acyl homoserine lactone quorum-sensing signal increases nodule numbers in Medicago truncatula independent of autoregulation.

PubMed

Veliz-Vallejos, Debora F; van Noorden, Giel E; Yuan, Mengqi; Mathesius, Ulrike

2014-01-01

N-acyl homoserine lactones (AHLs) act as quorum sensing signals that regulate cell-density dependent behaviors in many gram-negative bacteria, in particular those important for plant-microbe interactions. AHLs can also be recognized by plants, and this may influence their interactions with bacteria. Here we tested whether the exposure to AHLs affects the nodule-forming symbiosis between legume hosts and rhizobia. We treated roots of the model legume, Medicago truncatula, with a range of AHLs either from its specific symbiont, Sinorhizobium meliloti, or from the potential pathogens, Pseudomonas aeruginosa and Agrobacterium vitis. We found increased numbers of nodules formed on root systems treated with the S. meliloti-specific AHL, 3-oxo-C14-homoserine lactone, at a concentration of 1 μM, while the other AHLs did not result in significant changes to nodule numbers. We did not find any evidence for altered nodule invasion by the rhizobia. Quantification of flavonoids that could act as nod gene inducers in S. meliloti did not show any correlation with increased nodule numbers. The effects of AHLs were specific for an increase in nodule numbers, but not lateral root numbers or root length. Increased nodule numbers following 3-oxo-C14-homoserine lactone treatment were under control of autoregulation of nodulation and were still observed in the autoregulation mutant, sunn4 (super numeric nodules4). However, increases in nodule numbers by 3-oxo-C14-homoserine lactone were not found in the ethylene-insensitive sickle mutant. A comparison between M. truncatula with M. sativa (alfalfa) and Trifolium repens (white clover) showed that the observed effects of AHLs on nodule numbers were specific to M. truncatula, despite M. sativa nodulating with the same symbiont. We conclude that plant perception of the S. meliloti-specific 3-oxo-C14-homoserine lactone influences nodule numbers in M. truncatula via an ethylene-dependent, but autoregulation-independent mechanism.

Natural synergism of acid and lactone type mixed sophorolipids in interfacial activities and cytotoxicities.

PubMed

Hirata, Yoshihiko; Ryu, Mizuyuki; Igarashi, Keisuke; Nagatsuka, Asami; Furuta, Taro; Kanaya, Shigenori; Sugiura, Masaki

2009-01-01

Sophorolipids (SLs) naturally produced from Candida bombicola are a mixture of lactonic (SL-lactone) and acidic (SL-acid) sophorosides of 17-L-hydroxydecanoic acid with an SL-lactone:SL-acid ratio of 72:28. SLs are biodegradable low-foaming surfactants with high detergency and hardness-tolerance properties. To analyze the effect of the SL-lactone:SL-acid ratio on these properties, SL-LXs containing X% SL-lactone, in which X varied from 0 to 100, were prepared and their interfacial activities and cytotoxicities examined. The minimum surface tension values for all SLs examined were comparable. The critical micelle concentration (CMC) was 680 mg/L for SL-L0 and 62-110 mg/L for the other SLs. Interestingly, natural SL (SL-L72) had the lowest surface tension and CMC among all of the SLs examined. The foaming ability and stability of the SLs were dependent on the SL-L content. SL-L0 and L17 had higher foaming values than the other SLs examined in 0-ppm hardness water. These values greatly reduced and became constant when the SL-L content increased over 55%. The detergencies of all of the SLs examined were comparable, except for those of SL-L0 and SL-L100, which were slightly lower than those of the other SLs. These results suggest that natural synergism between SLs creates a better balance for many interfacial activities. The cytotoxicity of SL-L72 was higher than that of SL-L0, but was comparable to that of surfactin, which is commercially available for cosmetic use. The low cytotoxicities and high interfacial properties of SLs increase their usefulness as biocompatible surface active agents for many applications.

Mode of Action of the Sesquiterpene Lactones Psilostachyin and Psilostachyin C on Trypanosoma cruzi

PubMed Central

Papademetrio, Daniela; Batlle, Alcira; Martino, Virginia S.; Frank, Fernanda M.; Lombardo, María E.

2016-01-01

Trypanosoma cruzi is the causative agent of Chagas’ disease, which is a major endemic disease in Latin America and is recognized by the WHO as one of the 17 neglected tropical diseases in the world. Psilostachyin and psilostachyin C, two sesquiterpene lactones isolated from Ambrosia spp., have been demonstrated to have trypanocidal activity. Considering both the potential therapeutic targets present in the parasite, and the several mechanisms of action proposed for sesquiterpene lactones, the aim of this work was to characterize the mode of action of psilostachyin and psilostachyin C on Trypanosoma cruzi and to identify the possible targets for these molecules. Psilostachyin and psilostachyin C were isolated from Ambrosia tenuifolia and Ambrosia scabra, respectively. Interaction of sesquiterpene lactones with hemin, the induction of oxidative stress, the inhibition of cruzipain and trypanothione reductase and their ability to inhibit sterol biosynthesis were evaluated. The induction of cell death by apoptosis was also evaluated by analyzing phosphatidylserine exposure detected using annexin-V/propidium iodide, decreased mitochondrial membrane potential, assessed with Rhodamine 123 and nuclear DNA fragmentation evaluated by the TUNEL assay. Both STLs were capable of interacting with hemin. Psilostachyin increased about 5 times the generation of reactive oxygen species in Trypanosoma cruzi after a 4h treatment, unlike psilostachyin C which induced an increase in reactive oxygen species levels of only 1.5 times. Only psilostachyin C was able to inhibit the biosynthesis of ergosterol, causing an accumulation of squalene. Both sesquiterpene lactones induced parasite death by apoptosis. Upon evaluating the combination of both compounds, and additive trypanocidal effect was observed. Despite their structural similarity, both sesquiterpene lactones exerted their anti-T. cruzi activity through interaction with different targets. Psilostachyin accomplished its

Aromatase inhibition by synthetic lactones and flavonoids in human placental microsomes and breast fibroblasts - A comparative study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meeuwen, J.A. van; Nijmeijer, S.; Mutarapat, T.

2008-05-01

Interference of exogenous chemicals with the aromatase enzyme can be useful as a tool to identify chemicals that could act either chemopreventive for hormone-dependent cancer or adverse endocrine disruptive. Aromatase is the key enzyme in the biosynthesis of steroids, as it converts androgens to estrogens. Certain flavonoids, plant derived chemicals, are known catalytic aromatase inhibitors. Various systems are in use to test aromatase inhibitory properties of compounds. Commonly used are microsomes derived from ovary or placental tissue characterized by high aromatase activity. To a lesser extent whole cell systems are used and specifically cell systems that are potential target tissuemore » in breast cancer development. In this study aromatase inhibitory properties of fadrozole, 8-prenylnaringenin and a synthetic lactone (TM-7) were determined in human placental microsomes and in human primary breast fibroblasts. In addition, apigenin, chrysin, naringenin and two synthetic lactones (TM-8 and TM-9) were tested in human microsomes only. Comparison of the aromatase inhibitory potencies of these compounds between the two test systems showed that the measurement of aromatase inhibition in human placental microsomes is a good predictor of aromatase inhibition in human breast fibroblasts.« less

The algicidal activity of Aeromonas sp. strain GLY-2107 against bloom-forming Microcystis aeruginosa is regulated by N-acyl homoserine lactone-mediated quorum sensing.

PubMed

Guo, Xingliang; Liu, Xianglong; Wu, Lishuang; Pan, Jianliang; Yang, Hong

2016-11-01

Cyanobacterial blooms have disrupted the efficient utilization of freshwater worldwide. A new freshwater bacterial strain with strong algicidal activity, GLY-2107, was isolated from Lake Taihu and identified as Aeromonas sp. It produced two algicidal compounds: 2107-A (3-benzyl-piperazine-2,5-dione) and 2107-B (3-methylindole). Both compounds exhibited potent algicidal activities against Microcystis aeruginosa, the dominant bloom-forming cyanobacterium in Lake Taihu. The EC 50 values (concentration for 50% maximal effect) of 3-benzyl-piperazine-2,5-dione and 3-methylindole were 4.72 and 1.10 μg ml -1 respectively. Based on a thin-layer chromatography biosensor assay and ultra-performance liquid chromatography-coupled high resolution-tandem mass spectrometry (UPLC-HRMS/MS), the N-acyl homoserine lactone (AHL) profile of strain GLY-2107 was identified as two short side-chain AHLs: N-butyryl-homoserine lactone (C4-HSL) and N-hexanoyl-homoserine lactone (C6-HSL). The production of the two algicidal compounds was controlled by AHL-mediated quorum sensing (QS), and C4-HSL was the key QS signal for the algicidal activity of the strain GLY-2107. Moreover, 3-methylindole was found to be positively regulated by C4-HSL-mediated QS, whereas 3-benzyl-piperazine-2,5-dione might be negatively controlled by C4-HSL-mediated QS. This study suggests that a QS-regulated algicidal system may have potential use for the development of a novel control strategy for harmful cyanobacterial blooms. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

15-Hydroxygermacranolides as Sources of Structural Diversity: Synthesis of Sesquiterpene Lactones by Cyclization and Rearrangement Reactions. Experimental and DFT Study.

PubMed

Álvarez-Calero, José María; Ruiz, Enrique; López-Pérez, José Luis; Jaraíz, Martín; Rubio, José E; Jorge, Zacarías D; Suárez, Margarita; Massanet, Guillermo M

2018-05-18

A study on the electrophile-induced rearrangement of two 15-hydroxygermacranolides, salonitenolide and artemisiifolin, was carried out. These compounds underwent electrophilic intramolecular cyclizations or acid-mediated rearrangements to give sesquiterpene lactones with different skeletons such as eudesmanolides, guaianolides, amorphanolides, or other germacranolides. The cyclization that gives guaianolides can be considered a biomimetic route to this type of sesquiterpene lactones. The use of acetone as a solvent changes the reactivity of the two starting germacranolides to the acid catalysts, with a 4,15-diol acetonide being the main product obtained. The δ-amorphenolide obtained by intramolecular cyclization of this acetonide is a valuable intermediate for accessing the antimalarials artemisinin and its derivatives. Mechanistic proposals for the transformations are raised, and to provide support them, quantum chemical calculations [DFT B3LYP/6-31+G(d,p) level] were undertaken.

Quantitative analysis of sesquiterpene lactones in extract of Arnica montana L. by 1H NMR spectroscopy.

PubMed

Staneva, Jordanka; Denkova, Pavletta; Todorova, Milka; Evstatieva, Ljuba

2011-01-05

(1)H NMR spectroscopy was used as a method for quantitative analysis of sesquiterpene lactones present in a crude lactone fraction isolated from Arnica montana. Eight main components - tigloyl-, methacryloyl-, isobutyryl- and 2-methylbutyryl-esters of helenalin (H) and 11α,13-dihydrohelenalin (DH) were identified in the studied sample. The method allows the determination of the total amount of sesquiterpene lactones and the quantity of both type helenalin and 11α,13-dihydrohelenalin esters separately. Furthermore, 6-O-tigloylhelenalin (HT, 1), 6-O-methacryloylhelenalin (HM, 2), 6-O-tigloyl-11α,13-dihydrohelenalin (DHT, 5), and 6-O-methacryloyl-11α,13-dihydrohelenalin (DHM, 6) were quantified as individual components. Copyright © 2010 Elsevier B.V. All rights reserved.

[Preparation of hydrophilic matrix sustained release tablets of total lactones from Andrographis paniculata and study on its in vitro release mechanism].

PubMed

Xu, Fang-Fang; Shi, Wei; Zhang, Hui; Guo, Qing-Ming; Wang Zhen-Zhong; Bi, Yu-An; Wang, Zhi-Min; Xiao, Wei

2015-01-01

In this study, hydrophilic matrix sustained release tablets of total lactones from Andrographis paniculata were prepared and the in vitro release behavior were also evaluated. The optimal prescription was achieved by studying the main factor of the type and amount of hydroxypropyl methylcellulose (HPMC) using single factor test and evaluating through cumulative release of three lactones. No burst drug release from the obtained matrix tablets was observed. Drug release sustained to 14 h. The release mechanism of three lactones from A. paniculata was accessed by zero-order, first-order, Higuchi and Peppas equation. The release behavior of total lactones from A. paniculata was better agreed with Higuchi model and the drug release from the tablets was controlled by degradation of the matrix. The preparation of hydrophilic matrix sustained release tablets of total lactones from A. paniculata with good performance of drug release was simple.

Two lactones in the androconial scent of the lycaenid butterfly Celastrina argiolus ladonides

NASA Astrophysics Data System (ADS)

Ômura, Hisashi; Yakumaru, Kazuhisa; Honda, Keiichi; Itoh, Takao

2013-04-01

Male adult butterflies of many species have characteristic odors originating from the disseminating organs known as androconia. Despite the fact that androconia exist in several species, there have been few investigations on adult scents from the lycaenid species. Celastrina argiolus ladonides (Lycaenidae) is a common species in Eurasia. We have reported that male adults of this species emit a faint odor, and the major components causing this odor have been newly found in the Insecta. By using field-caught individuals, we determined the chemical nature and location of this odor in the butterfly. Gas chromatography-mass spectrometry (GC-MS) analyses revealed that two lactone compounds, lavender lactone and δ-decalactone, are present in the extracts of males but absent in those of the females. On an average, approximately 50 ng of each compound was found per male. Chiral GC analyses performed using enantiomerically pure standards revealed that the natural lavender lactone was a mixture of two enantiomers with an R/ S ratio of 32:68, whereas the natural δ-decalactone contained only the R-enantiomer. When the analyses were conducted using different parts—forewings, hindwings, and body—of three males, the lactones were more abundantly found on the forewings and hindwings than on the body. Microscopic observation of the wings demonstrated that battledore scales known as androconia are scattered on the upper surface of both the wings of C. argiolus ladonides males. These results indicate that the specialized scales on the wings of males serve as scent-disseminating organs.

How do the macrocyclic lactones kill filarial nematode larvae?

PubMed

Wolstenholme, Adrian J; Maclean, Mary J; Coates, Ruby; McCoy, Ciaran J; Reaves, Barbara J

2016-09-01

The macrocyclic lactones (MLs) are one of the few classes of drug used in the control of the human filarial infections, onchocerciasis and lymphatic filariasis, and the only one used to prevent heartworm disease in dogs and cats. Despite their importance in preventing filarial diseases, the way in which the MLs work against these parasites is unclear. In vitro measurements of nematode motility have revealed a large discrepancy between the maximum plasma concentrations achieved after drug administration and the amounts required to paralyze worms. Recent evidence has shed new light on the likely functions of the ML target, glutamate-gated chloride channels, in filarial nematodes and supports the hypothesis that the rapid clearance of microfilariae that follows treatment involves the host immune system.

A Solvent-Free Baeyer-Villiger Lactonization for the Undergraduate Organic Laboratory: Synthesis of Gamma-T-Butyl-Epsilon-Caprolactone

ERIC Educational Resources Information Center

Esteb, John J.; Hohman, Nathan J.; Schlamandinger, Diana E.; Wilson, Anne M.

2005-01-01

The solvent-free or solid-state reaction systems like the Baeyer-Villiger rearrangement have become popular in the synthetic organic community and viable option for undergraduate laboratory series to reduce waste and cost and simplify reaction process. The reaction is an efficient method to transform ketones to esters and lactones.

N-acyl homoserine lactone binding to the CarR receptor determines quorum-sensing specificity in Erwinia.

PubMed

Welch, M; Todd, D E; Whitehead, N A; McGowan, S J; Bycroft, B W; Salmond, G P

2000-02-15

Quorum sensing via an N-acyl homoserine lactone (HSL) pheromone controls the biosynthesis of a carbapenem antibiotic in Erwinia carotovora. Transcription of the carbapenem biosynthetic genes is dependent on the LuxR-type activator protein, CarR. Equilibrium binding of a range of HSL molecules, which are thought to activate CarR to bind to its DNA target sequence, was examined using fluorescence quenching, DNA bandshift analysis, limited proteolysis and reporter gene assays. CarR bound the most physiologically relevant ligand, N-(3-oxohexanoyl)-L-homoserine lactone, with a stoichiometry of two molecules of ligand per dimer of protein and a dissociation constant of 1.8 microM, in good agreement with the concentration of HSL required to activate carbapenem production in vivo. In the presence of HSL, CarR formed a very high molecular weight complex with its target DNA, indicating that the ligand causes the protein to multimerize. Chemical cross-linking analysis supported this interpretation. Our data show that the ability of a given HSL to facilitate CarR binding to its target DNA sequence is directly proportional to the affinity of the HSL for the protein.

N-acyl-homoserine lactones-producing bacteria protect plants against plant and human pathogens.

PubMed

Hernández-Reyes, Casandra; Schenk, Sebastian T; Neumann, Christina; Kogel, Karl-Heinz; Schikora, Adam

2014-11-01

The implementation of beneficial microorganisms for plant protection has a long history. Many rhizobia bacteria are able to influence the immune system of host plants by inducing resistance towards pathogenic microorganisms. In this report, we present a translational approach in which we demonstrate the resistance-inducing effect of Ensifer meliloti (Sinorhizobium meliloti) on crop plants that have a significant impact on the worldwide economy and on human nutrition. Ensifer meliloti is usually associated with root nodulation in legumes and nitrogen fixation. Here, we suggest that the ability of S. meliloti to induce resistance depends on the production of the quorum-sensing molecule, oxo-C14-HSL. The capacity to enhanced resistance provides a possibility to the use these beneficial bacteria in agriculture. Using the Arabidopsis-Salmonella model, we also demonstrate that the application of N-acyl-homoserine lactones-producing bacteria could be a successful strategy to prevent plant-originated infections with human pathogens. © 2014 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

Acyl-homoserine lactone quorum sensing: from evolution to application.

PubMed

Schuster, Martin; Sexton, D Joseph; Diggle, Stephen P; Greenberg, E Peter

2013-01-01

Quorum sensing (QS) is a widespread process in bacteria that employs autoinducing chemical signals to coordinate diverse, often cooperative activities such as bioluminescence, biofilm formation, and exoenzyme secretion. Signaling via acyl-homoserine lactones is the paradigm for QS in Proteobacteria and is particularly well understood in the opportunistic pathogen Pseudomonas aeruginosa. Despite thirty years of mechanistic research, empirical studies have only recently addressed the benefits of QS and provided support for the traditional assumptions regarding its social nature and its role in optimizing cell-density-dependent group behaviors. QS-controlled public-goods production has served to investigate principles that explain the evolution and stability of cooperation, including kin selection, pleiotropic constraints, and metabolic prudence. With respect to medical application, appreciating social dynamics is pertinent to understanding the efficacy of QS-inhibiting drugs and the evolution of resistance. Future work will provide additional insight into the foundational assumptions of QS and relate laboratory discoveries to natural ecosystems.

A validated Fourier transform infrared spectroscopy method for quantification of total lactones in Inula racemosa and Andrographis paniculata.

PubMed

Shivali, Garg; Praful, Lahorkar; Vijay, Gadgil

2012-01-01

Fourier transform infrared (FT-IR) spectroscopy is a technique widely used for detection and quantification of various chemical moieties. This paper describes the use of the FT-IR spectroscopy technique for the quantification of total lactones present in Inula racemosa and Andrographis paniculata. To validate the FT-IR spectroscopy method for quantification of total lactones in I. racemosa and A. paniculata. Dried and powdered I. racemosa roots and A. paniculata plant were extracted with ethanol and dried to remove ethanol completely. The ethanol extract was analysed in a KBr pellet by FT-IR spectroscopy. The FT-IR spectroscopy method was validated and compared with a known spectrophotometric method for quantification of lactones in A. paniculata. By FT-IR spectroscopy, the amount of total lactones was found to be 2.12 ± 0.47% (n = 3) in I. racemosa and 8.65 ± 0.51% (n = 3) in A. paniculata. The method showed comparable results with a known spectrophotometric method used for quantification of such lactones: 8.42 ± 0.36% (n = 3) in A. paniculata. Limits of detection and quantification for isoallantolactone were 1 µg and 10 µg respectively; for andrographolide they were 1.5 µg and 15 µg respectively. Recoveries were over 98%, with good intra- and interday repeatability: RSD ≤ 2%. The FT-IR spectroscopy method proved linear, accurate, precise and specific, with low limits of detection and quantification, for estimation of total lactones, and is less tedious than the UV spectrophotometric method for the compounds tested. This validated FT-IR spectroscopy method is readily applicable for the quality control of I. racemosa and A. paniculata. Copyright © 2011 John Wiley & Sons, Ltd.

Sesquiterpene lactones from Gynoxys verrucosa and their anti-MRSA activity.

PubMed

Ordóñez, Paola E; Quave, Cassandra L; Reynolds, William F; Varughese, Kottayil I; Berry, Brian; Breen, Philip J; Malagón, Omar; Smeltzer, Mark S; Compadre, Cesar M

2011-09-02

Because of its virulence and antibiotic resistance, Staphylococcus aureus is a more formidable pathogen now than at any time since the pre-antibiotic era. In an effort to identify and develop novel antimicrobial agents with activity against this pathogen, we have examined Gynoxys verrucosa Wedd (Asteraceae), an herb used in traditional medicine in southern Ecuador for the treatment and healing of wounds. The sesquiterpene lactones leucodine (1) and dehydroleucodine (2) were extracted and purified from the aerial parts of Gynoxys verrucosa, and their structure was elucidated by spectroscopic methods and single-crystal X-ray analysis. The in vitro anti-microbial activity of Gynoxys verrucosa extracts and its purified constituents was determined against six clinical isolates including Staphylococcus aureus and Staphylococcus epidermidis strains with different drug-resistance profiles, using the microtiter broth method. Compound 1 has very low activity, while compound 2 has moderate activity with MIC(50)s between 49 and 195 μg/mL. The extract of Gynoxys verrucosa has weak activity with MIC(50)s between 908 and 3290 μg/mL. We are reporting the full assignment of the (1)H NMR and (13)C NMR of both compounds, and the crystal structure of compound 2, for the first time. Moreover, the fact that compound 2 has antimicrobial activity and compound 1 does not, demonstrates that the exocyclic conjugated methylene in the lactone ring is essential for the antimicrobial activity of these sesquiterpene lactones. However, the weak activity observed for the plant extracts, does not explain the use of Gynoxys verrucosa in traditional medicine for the treatment of wounds and skin infections. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Sesquiterpene Lactones from Gynoxys verrucosa and their Anti-MRSA Activity

PubMed Central

Ordóñez, Paola E.; Quave, Cassandra L.; Reynolds, William F.; Varughese, Kottayil I.; Berry, Brian; Breen, Philip J.; Malagón, Omar; Smeltzer, Mark S.; Compadre, Cesar M.

2011-01-01

Ethnopharmacological relevance Because of its virulence and antibiotic resistance, Staphylococcus aureus is a more formidable pathogen now than at any time since the pre-antibiotic era. In an effort to identify and develop novel antimicrobial agents with activity against this pathogen, we have examined Gynoxys verrucosa Wedd (Asteraceae), an herb used in traditional medicine in southern Ecuador for the treatment and healing of wounds. Materials and Methods The sesquiterpene lactones leucodine (1) and dehydroleucodine (2) were extracted and purified from the aerial parts of G. verrucosa, and their structure was elucidated by spectroscopic methods and single-crystal X-ray analysis. The in vitro anti-microbial activity of G. verrucosa extracts and its purified constituents was determined against six clinical isolates including S. aureus and Staphylococcus epidermidis strains with different drug-resistance profiles, using the microtiter broth method. Results Compound 1 has very low activity, while compound 2 has moderate activity with MIC50s between 49 and195 μg/mL. The extract of G. verrucosa has weak activity with MIC50s between 908 and 3290 μg/mL. Conclusions We are reporting the full assignment of the 1H-NMR and 13C-NMR of both compounds, and the crystal structure of compound 2, for the first time. Moreover, the fact that compound 2 has antimicrobial activity and compound 1 does not, demonstrates that the exocyclic conjugated methylene in the lactone ring is essential for the antimicrobial activity of these sesquiterpene lactones. However, the weak activity observed for the plants extracts, does not explain the use of G. verrucosa in traditional medicine for the treatment of wounds and skin infections. PMID:21782013

Patch testing with thin-layer chromatograms of chamomile tea in patients allergic to sesquiterpene lactones.

PubMed

Lundh, Kerstin; Gruvberger, Birgitta; Möller, Halvor; Persson, Lena; Hindsén, Monica; Zimerson, Erik; Svensson, Ake; Bruze, Magnus

2007-10-01

Patients with contact allergy to sesquiterpene lactones (SLs) are usually hypersensitive to Asteraceae plant products such as herbal teas. The objective of this study was to show sensitizers in chamomile tea by patch testing with thin-layer chromatograms. Tea made from German chamomile was separated by thin-layer chromatography. Strips of the thin-layer chromatograms were used for patch testing SL-positive patients. 15 (43%) of 35 patients tested positively to 1 or more spots on the thin-layer chromatogram, with many individual reaction patterns. Patch testing with thin-layer chromatograms of German chamomile tea showed the presence of several allergens.

Biosynthesis of Germacrene A Carboxylic Acid in Chicory Roots. Demonstration of a Cytochrome P450 (+)-Germacrene A Hydroxylase and NADP+-Dependent Sesquiterpenoid Dehydrogenase(s) Involved in Sesquiterpene Lactone Biosynthesis

PubMed Central

de Kraker, Jan-Willem; Franssen, Maurice C. R.; Dalm, Marcella C. F.; de Groot, Aede; Bouwmeester, Harro J.

2001-01-01

Sprouts of chicory (Cichorium intybus), a vegetable grown in the dark, have a slightly bitter taste associated with the presence of guaianolides, eudesmanolides, and germacranolides. The committed step in the biosynthesis of these compounds is catalyzed by a (+)-germacrene A synthase. Formation of the lactone ring is the postulated next step in biosynthesis of the germacrene-derived sesquiterpene lactones. The present study confirms this hypothesis by isolation of enzyme activities from chicory roots that introduce a carboxylic acid function in the germacrene A isopropenyl side chain, which is necessary for lactone ring formation. (+)-Germacrene A is hydroxylated to germacra-1(10),4,11(13)-trien-12-ol by a cytochrome P450 enzyme, and is subsequently oxidized to germacra-1(10),4,11(13)-trien-12-oic acid by NADP+-dependent dehydrogenase(s). Both oxidized germacrenes were detected as their Cope-rearrangement products elema-1,3,11(13)-trien-12-ol and elema-1,3,11(13)-trien-12-oic acid, respectively. The cyclization products of germacra-1(10),4,11(13)-trien-12-ol, i.e. costol, were also observed. The (+)-germacrene A hydroxylase is inhibited by carbon monoxide (blue-light reversible), has an optimum pH at 8.0, and hydroxylates β-elemene with a modest degree of enantioselectivity. PMID:11299372

Fungal strains as catalysts for the biotransformation of halolactones by hydrolytic dehalogenation with the dimethylcyclohexane system.

PubMed

Grabarczyk, Małgorzata

2012-08-14

Bicyclic chloro-, bromo- and iodo-γ-lactones with dimethylcyclohexane rings were used as substrates for bioconversion by several fungal strains (Fusarium, Botrytis and Beauveria). Most of the selected microorganisms transformed these lactones by hydrolytic dehalogenation into the new compound cis-2-hydroxy-4,6-dimethyl-9-oxabicyclo[4.3.0]- nonan-8-one, mainly the (-)-isomer. When iodo-γ-lactone was used as the substrate, two products were observed: a hydroxy-γ-lactone and an unsaturated lactone. The structures of all substrates and products were established on the basis of their spectral data. The mechanism of dehalogenation of three halolactones was also studied.

SELECTIVE HYDROGENATION OF ANHYDRIDES TO LACTONES UNDER SUPERCRITICAL CARBON DIOXIDE MEDIUM

EPA Science Inventory

Selective Hydrogenation of Anhydrides to Lactones Under Supercritical Carbon Dioxide Medium

Endalkachew Sahle-Demessie Unnikrishnan R Pillai
U.S. EPA , 26 W. Martin Luther King Dr. Cincinnati, OH 45268 Phone: 513-569-7739
Fax: 513-569-7677
Abstract:
Hydrogenat...

Two new diterpenoid lactones isolated from Andrographis paniculata.

PubMed

Wang, Gui-Yang; Wen, Ting; Liu, Fei-Fei; Tian, Hai-Yan; Chun-Lin, Fan; Huang, Xiao-Jun; Ye, Wen-Cai; Wang, Ying

2017-06-01

In the present study, two new diterpenoid lactones, 3-deoxy-andrographoside (1) and 14-deoxy-15-methoxy-andrographolide (2), were isolated from the aerial parts of Andrographis paniculata. Their structures were elucidated by combination of NMR, MS, and chemical methods. The configurations of 1 and 2 were established based on the analysis of ROESY data and single crystal X-ray diffraction experiment. Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

[Determination of terpene lactones in Ginkgo biloba leaves in different ages by UPLC-TQ-MS].

PubMed

Yao, Xin; Zhou, Gui-Sheng; Tang, Yu-Ping; Qian, Ye-Fei; Shang, Er-Xin; Su, Shu-Lan; Qian, Da-Wei; Duan, Jin-Ao

2013-02-01

To establish an ultra-high performance liquid chromatography coupled with triple quadrupole mass (UPLC-TQ-MS) for determination of four terpene lactones. Chromatographic separation was carried out on a ACQUITY UPLC BEH C18 column (2.1 mm x 100 mm, 1.7 microm) with isocratic elution of 70% methanol at a flow rate of 0.4 mL x min(-1), the column temperature was set at 30 degrees C; Waters Xevo TQ worked in multiple reaction monitoring mode. All calibration curves were linear (r > 0.990 3) over the tested ranges. The average recoveries ranged from 98.83% to 103.9% with RSD value below 3.0%. The contents of total terpene lactones in Ginkgo biloba leaves were significantly different in different ages. The contents in the leaves of young ginkgo tree were higher than that in old tree. The method was simple and fast with high precision, sensitivity and repeatability, which can be used for qualitative and quantitative analysis of terpene lactones in G. biloba leaves.

Nonbioluminescent strains of Photobacterium phosphoreum produce the cell-to-cell communication signal N-(3-Hydroxyoctanoyl)homoserine lactone.

PubMed

Flodgaard, L R; Dalgaard, P; Andersen, J B; Nielsen, K F; Givskov, M; Gram, L

2005-04-01

Bioluminescence is a common phenotype in marine bacteria, such as Vibrio and Photobacterium species, and can be quorum regulated by N-acylated homoserine lactones (AHLs). We extracted a molecule that induced a bacterial AHL monitor (Agrobacterium tumefaciens NT1 [pZLR4]) from packed cod fillets, which spoil due to growth of Photobacterium phosphoreum. Interestingly, AHLs were produced by 13 nonbioluminescent strains of P. phosphoreum isolated from the product. Of 177 strains of P. phosphoreum (including 18 isolates from this study), none of 74 bioluminescent strains elicited a reaction in the AHL monitor, whereas 48 of 103 nonbioluminescent strains did produce AHLs. AHLs were also detected in Aeromonas spp., but not in Shewanella strains. Thin-layer chromatographic profiles of cod extracts and P. phosphoreum culture supernatants identified a molecule similar in relative mobility (Rf value) and shape to N-(3-hydroxyoctanoyl)homoserine lactone, and the presence of this molecule in culture supernatants from a nonbioluminescent strain of P. phosphoreum was confirmed by high-performance liquid chromatography-positive electrospray high-resolution mass spectrometry. Bioluminescence (in a non-AHL-producing strain of P. phosphoreum) was strongly up-regulated during growth, whereas AHL production in a nonbioluminescent strain of P. phosphoreum appeared constitutive. AHLs apparently did not influence bioluminescence, as the addition of neither synthetic AHLs nor supernatants delayed or reduced this phenotype in luminescent strains of P. phosphoreum. The phenotypes of nonbioluminescent P. phosphoreum strains regulated by AHLs remains to be elucidated.

Involvement of the dehydroleucodine alpha-methylene-gamma-lactone function in GVBD inhibition in Bufo arenarum oocytes.

PubMed

Sánchez Toranzo, G; López, L A; Martínez, J Zapata; Bühler, M C Gramajo; Bühler, M I

2010-02-01

Dehydroleucodine (DhL), a sesquiterpenic lactone, was isolated and purified from aerial parts of Artemisia douglasiana Besser, a medicinal herb used in Argentina. DhL is an alpha-methylene butyro-gamma-lactone ring connected to a seven-membered ring fused to an exocyclic alpha,beta-unsaturated cyclopentenone ring. It has been previously shown that DhL selectively induces a dose-dependent transient arrest in G2 of both meristematic cells and vascular smooth muscle cells. Treatment with DhL induces an inhibition of spontaneous and progesterone-induced maturation in a dose-dependent manner in Bufo arenarum fully grown oocytes arrested at G2, at the beginning of meiosis I. However, the nature of the mechanisms involved in the process is still unknown. The aim of this work was to analyse whether DhL's alpha-methylene-gamma-lactone function is responsible for the inhibition effect on meiosis reinitiation of Bufo arenarum oocytes as well as some of the transduction pathways that could be involved in this effect using a derivative of DhL inactivated for alpha-methylenelactone, the 11,13-dihydro-dehydroleucodine (2H-DhL). The use of 2H-DhL in the maturation promoting factor (MPF) amplification experiments by injection of both cytoplasm with active MPF and of germinal vesicle content showed results similar to the ones obtained with DhL, suggesting that the hydrogenated derivative would act in a similar way to DhL. Pretreatment with DhL or 2H-DhL did not affect the percentage of germinal vesicle breakdown (GVBD) induced by H89, a protein kinase A (PKA) inhibitor, which suggests that these lactones would act on another step of the signalling pathway that induces MPF activation. The fact that both DhL and 2H-Dhl inhibit GVBD induced by okadaic acid microinjection suggests that they could act on the activity of the Myt1 kinase. This idea is supported by the experiments of injection of GV contents in which an inhibitory effect of these lactones on GVBD was also observed. Our

Dehalogenation Activity of Selected Fungi Toward δ-Iodo-γ-Lactone Derived from trans,trans-Farnesol.

PubMed

Gliszczyńska, Anna; Gładkowski, Witold; Świtalska, Marta; Wietrzyk, Joanna; Szumny, Antoni; Gębarowska, Elżbieta; Wawrzeńczyk, Czesław

2016-04-01

Time-course of biotransformation of racemic trans-4-((E)-4',8'-dimethylnona-3',7'-dien-1-yl)-5-iodomethyl-4-methyldihydrofuran-2-one (1) in fungal and yeast cultures was investigated. In these conditions, the substrate 1 was enantioselectively dehalogenated yielding 4-((E)-4',8'-dimethylnona-3',7'-dien-1-yl)-4-methyl-5-methylenedihydrofuran-2-one (2) and its structure was established based on the spectroscopic data. The most effective biocatalyst used was Didymosphaeria igniaria, which catalyzed the process with highest rate and enantioselectivity (ee of product = 76%). The antiproliferative activity of δ-iodo-γ-lactone 1, product of its biotransformation 2, and starting substrate (farnesol) were evaluated toward two cancer cell lines: A549 (human lung adenocarcinoma) and HL-60 (human promyelocytic leukemia). © 2016 Verlag Helvetica Chimica Acta AG, Zürich.

Determination of Lactones in Wines by Headspace Solid-Phase Microextraction and Gas Chromatography Coupled with Mass Spectrometry

PubMed Central

Pérez-Olivero, S. J.; Pérez-Pont, M. L.; Conde, J. E.; Pérez-Trujillo, J. P.

2014-01-01

Application of headspace solid-phase microextraction (HS-SPME) coupled with high-resolution gas chromatographic (HRGC) analysis was studied for determining lactones in wines. Six different SPME fibers were tested, and the influence of different factors such as temperature and time of desorption, ionic strength, time of extraction, content of sugar, ethanol, tannins and anthocyanins, and pH and influence of SO2 were studied. The proposed HS-SPME-GC method is an appropriate technique for the quantitative analysis of γ-butyrolactone, γ-hexalactone, trans-whiskey lactone, γ-octalactone, cis-whiskey lactone, γ-nonalactone, γ-decalactone, δ-decalactone, and γ-undecalactone in wines. Method reproducibility and repeatability ranged between 0.6 and 5.2% for all compounds. Detection limit for γ-butyrolactone was 0.17 mg/L and a few μg/L for the rest of the compounds. The optimized method has been applied to several wine samples. PMID:24782943

Free radical-scavenging delta-lactones from Boletus calopus.

PubMed

Kim, Jin-Woo; Yoo, Ick-Dong; Kim, Won-Gon

2006-12-01

The methanol extracts from the fruiting body of the mushroom Boletus calopus showed free radical-scavenging activity. Bioactivity-guided fractionation of the methanol extracts led to a new hydroxylated calopin named calopin B, along with the known delta-lactones calopin and cyclocalopin A. The structure of the new calopin analogue was elucidated by spectroscopic methods. All compounds showed potent free radical-scavenging activity against superoxide, DPPH, and ABTS radicals with IC (50) values of 1.2 - 5.4 microg/mL.

Isolation and characterization of 9-lipoxygenase and epoxide hydrolase 2 genes: Insight into lactone biosynthesis in mango fruit (Mangifera indica L.).

PubMed

Deshpande, Ashish B; Chidley, Hemangi G; Oak, Pranjali S; Pujari, Keshav H; Giri, Ashok P; Gupta, Vidya S

2017-06-01

Uniqueness and diversity of mango flavour across various cultivars are well known. Among various flavour metabolites lactones form an important class of aroma volatiles in certain mango varieties due to their ripening specific appearance and lower odour detection threshold. In spite of their biological and biochemical importance, lactone biosynthetic pathway in plants remains elusive. Present study encompasses quantitative real-time analysis of 9-lipoxygenase (Mi9LOX), epoxide hydrolase 2 (MiEH2), peroxygenase, hydroperoxide lyase and acyl-CoA-oxidase genes during various developmental and ripening stages in fruit of Alphonso, Pairi and Kent cultivars with high, low and no lactone content and explains their variable lactone content. Study also covers isolation, recombinant protein characterization and transient over-expression of Mi9LOX and MiEH2 genes in mango fruits. Recombinant Mi9LOX utilized linoleic and linolenic acids, while MiEH2 utilized aromatic and fatty acid epoxides as their respective substrates depicting their role in fatty acid metabolism. Significant increase in concentration of δ-valerolactone and δ-decalactone upon Mi9LOX over-expression and that of δ-valerolactone, γ-hexalactone and δ-hexalactone upon MiEH2 over-expression further suggested probable involvement of these genes in lactone biosynthesis in mango. Copyright © 2017 Elsevier Ltd. All rights reserved.

Presence of acyl-homoserine lactones in 57 members of the Vibrionaceae family

PubMed Central

Purohit, AA; Johansen, J A; Hansen, H; Leiros, H-KS; Kashulin, A; Karlsen, C; Smalås, A; Haugen, P; Willassen, NP

2013-01-01

Aims The aim of this study was to use a sensitive method to screen and quantify 57 Vibrionaceae strains for the production of acyl-homoserine lactones (AHLs) and map the resulting AHL profiles onto a host phylogeny. Methods and Results We used a high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS) protocol to measure AHLs in spent media after bacterial growth. First, the presence/absence of AHLs (qualitative analysis) was measured to choose internal standard for subsequent quantitative AHL measurements. We screened 57 strains from three genera (Aliivibrio,Photobacterium and Vibrio) of the same family (i.e. Vibrionaceae). Our results show that about half of the isolates produced multiple AHLs, typically at 25–5000 nmol l−1. Conclusions This work shows that production of AHL quorum sensing signals is found widespread among Vibrionaceae bacteria and that closely related strains typically produce similar AHL profiles. Significance and Impact of the Study The AHL detection protocol presented in this study can be applied to a broad range of bacterial samples and may contribute to a wider mapping of AHL production in bacteria, for example, in clinically relevant strains. PMID:23725044

Exogenous Supply of Pantoyl Lactone to Excised Leaves Increases their Pantothenate Levels

PubMed Central

RATHINASABAPATHI, BALA; RAMAN, SURESH BABU

2005-01-01

• Background and Aims All plants synthesize pantothenate but its synthesis and regulation are not well understood. The aim of this work is to study the effect of exogenous supply of precursor compounds on pantothenate levels in leaves. • Methods Precursor compounds were supplied in solution to excised leaves and the pantothenate content was measured using a microbial method. • Key Results Pantothenate levels in excised leaves of Limonium latifolium, tomato (Lycopersicon esculentum), bean (Phaseolus vulgaris) and grapefruit (Citrus × paradisi) were examined following an exogenous supply of the precursor compounds pantoyl lactone or β-alanine. Significantly higher levels of extractable pantothenate were found when pantoyl lactone was supplied, but not when β-alanine was supplied despite a measurable uptake of β-alanine into the leaf. • Conclusions The results suggested that the pantoate supply may be rate-limiting or regulating pantothenate synthesis in leaves. PMID:15767268

Assessment of sesquiterpene lactones isolated from Mikania plants species for their potential efficacy against Trypanosoma cruzi and Leishmania sp.

PubMed Central

Bivona, Augusto E.; Sánchez Alberti, Andrés; Giberti, Gustavo; Malchiodi, Emilio L.; Martino, Virginia S.; Catalan, Cesar A.; Alonso, María Rosario; Cazorla, Silvia I.

2017-01-01

Four sesquiterpene lactones, mikanolide, deoxymikanolide, dihydromikanolide and scandenolide, were isolated by a bioassay-guided fractionation of Mikania variifolia and Mikania micrantha dichloromethane extracts. Mikanolide and deoxymikanolide were the major compounds in both extracts (2.2% and 0.4% for Mikania variifolia and 21.0% and 6.4% for Mikania micrantha respectively, calculated on extract dry weight). Mikanolide, deoxymikanolide and dihydromikanolide were active against Trypanosoma cruzi epimastigotes (50% inhibitory concentrations of 0.7, 0.08 and 2.5 μg/mL, for each compound respectively). These sesquiterpene lactones were also active against the bloodstream trypomastigotes (50% inhibitory concentrations for each compound were 2.1, 1.5 and 0.3 μg/mL, respectively) and against amastigotes (50% inhibitory concentrations for each compound were 4.5, 6.3 and 8.5 μg/mL, respectively). By contrast, scandenolide was not active on Trypanosoma cruzi. Besides, mikanolide and deoxymikanolide were also active on Leishmania braziliensis promastigotes (50% inhibitory concentrations of 5.1 and 11.5 μg/mL, respectively). The four sesquiterpene lactones were tested for their cytotoxicity on THP 1 cells. Deoxymikanolide presented the highest selectivity index for trypomastigotes (SI = 54) and amastigotes (SI = 12.5). In an in vivo model of Trypanosoma cruzi infection, deoxymikanolide was able to decrease the parasitemia and the weight loss associated to the acute phase of the parasite infection. More importantly, while 100% of control mice died by day 22 after receiving a lethal T. cruzi infection, 70% of deoxymikanolide-treated mice survived. We also observed that this compound increased TNF-α and IL-12 production by macrophages, which could contribute to control T. cruzi infection. PMID:28945741

Pharmacological insight into the anti-inflammatory activity of sesquiterpene lactones from Neurolaena lobata (L.) R.Br. ex Cass.

PubMed

McKinnon, R; Binder, M; Zupkó, I; Afonyushkin, T; Lajter, I; Vasas, A; de Martin, R; Unger, C; Dolznig, H; Diaz, R; Frisch, R; Passreiter, C M; Krupitza, G; Hohmann, J; Kopp, B; Bochkov, V N

2014-10-15

Neurolaena lobata is a Caribbean medicinal plant used for the treatment of several conditions including inflammation. Recent data regarding potent anti-inflammatory activity of the plant and isolated sesquiterpene lactones raised our interest in further pharmacological studies. The present work aimed at providing a mechanistic insight into the anti-inflammatory activity of N. lobata and eight isolated sesquiterpene lactones, as well as a structure-activity relationship and in vivo anti-inflammatory data. The effect of the extract and its compounds on the generation of pro-inflammatory proteins was assessed in vitro in endothelial and monocytic cells by enzyme-linked immunosorbent assay. Their potential to modulate the expression of inflammatory genes was further studied at the mRNA level. In vivo anti-inflammatory activity of the chemically characterized extract was evaluated using carrageenan-induced paw edema model in rats. The compounds and extract inhibited LPS- and TNF-α-induced upregulation of the pro-inflammatory molecules E-selectin and interleukin-8 in HUVECtert and THP-1 cells. LPS-induced elevation of mRNA encoding for E-selectin and interleukin-8 was also suppressed. Furthermore, the extract inhibited the development of acute inflammation in rats. Sesquiterpene lactones from N. lobata interfered with the induction of inflammatory cell adhesion molecules and chemokines in cells stimulated with bacterial products and cytokines. Structure-activity analysis revealed the importance of the double bond at C-4-C-5 and C-2-C-3 and the acetyl group at C-9 for the anti-inflammatory activity. The effect was confirmed in vivo, which raises further interest in the therapeutic potential of the compounds for the treatment of inflammatory diseases. Copyright © 2014 Elsevier GmbH. All rights reserved.

Organocatalytic asymmetric anti-selective Michael reactions of aldehydes and the sequential reduction/lactonization/Pauson-Khand reaction for the enantioselective synthesis of highly functionalized hydropentalenes.

PubMed

Hong, Bor-Cherng; Dange, Nitin S; Yen, Po-Jen; Lee, Gene-Hsiang; Liao, Ju-Hsiou

2012-10-19

A new method has been developed for the enantioselective synthesis of highly functionalized hydropentalenes bearing up to four stereogenic centers with high stereoselectivity (up to 99% ee). This process combines an enantioselective organocatalytic anti-selective Michael addition with a highly efficient one-pot reduction/lactonization/Pauson-Khand reaction sequence. The structures and absolute configurations of the products were confirmed by X-ray analysis.

Volvalerelactones A and B, two new sesquiterpenoid lactones with an unprecedented skeleton from Valeriana officinalis var. latifolia.

PubMed

Wang, Peng-Cheng; Ran, Xin-Hui; Luo, Huai-Rong; Hu, Jiang-Miao; Chen, Rui; Ma, Qing-Yun; Dai, Hao-Fu; Liu, Yu-Qing; Xie, Ming-Jin; Zhou, Jun; Zhao, You-Xing

2011-06-17

Volvalerelactones A and B (1 and 2), two new sesquiterpenoid lactones with an unprecedented 3/7/6 tricyclic ring system, were isolated from the roots of Valeriana officinalis var. latifolia. Their structures and relative configurations were elucidated by spectroscopic data and single-crystal X-ray diffraction crystallography, and the absolute configuration was assigned by computational methods. The possible biosynthetic pathways of 1 and 2 were also proposed. © 2011 American Chemical Society

Metabolite profiling of sesquiterpene lactones from Lactuca species. Major latex components are novel oxalate and sulfate conjugates of lactucin and its derivatives.

PubMed

Sessa, R A; Bennett, M H; Lewis, M J; Mansfield, J W; Beale, M H

2000-09-01

Wounding leaves or stems of Lactuca species releases a milky latex onto the plant surface. We have examined the constituents of latex from Lactuca sativa (lettuce) cv. Diana. The major components were shown to be novel 15-oxalyl and 8-sulfate conjugates of the guaianolide sesquiterpene lactones, lactucin, deoxylactucin, and lactucopicrin. The oxalates were unstable, reverting to the parent sesquiterpene lactone on hydrolysis. Oxalyl derivatives have been reported rarely from natural sources. The sulfates were stable and are the first reported sesquiterpene sulfates from plants. Unusual tannins based on 4-hydroxyphenylacetyl conjugates of glucose were also identified. Significant qualitative and quantitative variation was found in sesquiterpene lactone profiles in different lettuce varieties and in other Lactuca spp. The proportions of each conjugate in latex also changed depending on the stage of plant development. A similar profile was found in chicory, in which oxalyl conjugates were identified, but the 8-sulfate conjugates were notably absent. The presence of the constitutive sesquiterpene lactones was not correlated with resistance to pathogens but may have a significant bearing on the molecular basis of the bitter taste of lettuce and related species. The induced sesquiterpene lactone phytoalexin, lettucenin A, was found in the Lactuca spp. but not in chicory.

Dendocarbin A: a sesquiterpene lactone from Drimys winteri.

PubMed

Paz Robles, Cristian; Burgos, Viviana; Suarez, Sebastián; Baggio, Ricardo

2014-11-01

The natural compound dendocarbin A, C15H22O3, is a sesquiterpene lactone isolated for the first time from Drimys winteri for var chilensis. The compound crystallizes in the orthorhombic space group P2₁2₁2₁ and its X-ray crystal structure confirmed the S/R character of the chiral centres at C-5/C-10 and C-9/C-11, respectively. The α-OH group at C-11 was found to be involved in intermolecular hydrogen bonding, defining chains along the <100> 2₁ screw axis.

Potent anti-inflammatory activity of sesquiterpene lactones from Neurolaena lobata (L.) R. Br. ex Cass., a Q'eqchi' Maya traditional medicine.

PubMed

Walshe-Roussel, Brendan; Choueiri, Christine; Saleem, Ammar; Asim, Muhammd; Caal, Federico; Cal, Victor; Rojas, Marco Otarola; Pesek, Todd; Durst, Tony; Arnason, John Thor

2013-08-01

The widespread use of Neurolaena lobata (L.) R. Br. ex Cass. by Q'eqchi' Maya and indigenous healers throughout the Caribbean for inflammatory conditions prompted the study of the anti-inflammatory activity of this traditional medicine. The objectives of this study were to conduct a detailed ethnobotanical investigation of the uses of N. lobata by the Q'eqchi' Maya of Belize for a variety of inflammatory symptoms and to evaluate the in vitro anti-inflammatory activity of leaf extract and isolated sesquiterpene lactones. The crude 80% EtOH extract of N. lobata leaves administered at 100 μg/mL reduced LPS-stimulated TNF-α production in THP-1 monocytes by 72% relative to the stimulated vehicle control. Isolated sesquiterpene lactones, neurolenins B, C+D, lobatin B and 9α-hydroxy-8β-isovalerianyloxy-calyculatolide were more active (IC50=0.17-2.32 μM) than the positive control parthenolide (IC50=4.79 μM). The results provide a pharmacological and phytochemical basis for the traditional use of this leaf for inflammatory conditions. Copyright © 2013 Elsevier Ltd. All rights reserved.

Complete Genome Sequence of Pseudomonas chlororaphis subsp. aurantiaca Reveals a Triplicate Quorum-Sensing Mechanism for Regulation of Phenazine Production

PubMed Central

Morohoshi, Tomohiro; Yamaguchi, Takahito; Xie, Xiaonan; Wang, Wen-zhao; Takeuchi, Kasumi; Someya, Nobutaka

2017-01-01

Pseudomonas chlororaphis subsp. aurantiaca StFRB508 regulates phenazine production through N-acyl-l-homoserine lactone (AHL)-mediated quorum sensing. Two sets of AHL-synthase and AHL-receptor genes, phzI/phzR and aurI/aurR, have been identified from the incomplete draft genome of StFRB508. In the present study, the complete genome of StFRB508, comprising a single chromosome of 6,997,933 bp, was sequenced. The complete genome sequence revealed the presence of a third quorum-sensing gene set, designated as csaI/csaR. An LC-MS/MS analysis revealed that StFRB508 produced six types of AHLs, with the most important AHL being N-(3-hydroxyhexanoyl)-l-homoserine lactone (3-OH-C6-HSL). PhzI mainly catalyzed the biosynthesis of 3-OH-C6-HSL, while AurI and CsaI catalyzed that of N-hexanoyl-l-homoserine lactone and N-(3-oxohexanoyl)-l-homoserine lactone, respectively. A mutation in phzI decreased phenazine production, whereas that in aurI or csaI did not. A phzI aurI csaI triple mutant (508ΔPACI) did not produce phenazine. Phenazine production by 508ΔPACI was stimulated by exogenous AHLs and 3-OH-C6-HSL exerted the strongest effects on phenazine production at the lowest concentration tested (0.1 μM). The plant protection efficacy of 508ΔPACI against an oomycete pathogen was lower than that of wild-type StFRB508. These results demonstrate that the triplicate quorum-sensing system plays an important role in phenazine production by and the biocontrol activity of StFRB508. PMID:28239068

Variecolactol: A New Sesterterpene Lactone from the Sclerotia of Aspergillus auricomus (Guegen) Saito

USDA-ARS?s Scientific Manuscript database

Variecolactol (1), a new sesterterpene lactone related to variecolin (2), has been isolated from the organic extracts of Aspergillus auricomus. Structure determination of this compound was achieved primarily through HMQC, HMBC, and NOESY experiments. The known compounds dihydropenicillic acid (3) ...

Diversity-oriented combinatorial biosynthesis of benzenediol lactone scaffolds by subunit shuffling of fungal polyketide synthases.

PubMed

Xu, Yuquan; Zhou, Tong; Zhang, Shuwei; Espinosa-Artiles, Patricia; Wang, Luoyi; Zhang, Wei; Lin, Min; Gunatilaka, A A Leslie; Zhan, Jixun; Molnár, István

2014-08-26

Combinatorial biosynthesis aspires to exploit the promiscuity of microbial anabolic pathways to engineer the synthesis of new chemical entities. Fungal benzenediol lactone (BDL) polyketides are important pharmacophores with wide-ranging bioactivities, including heat shock response and immune system modulatory effects. Their biosynthesis on a pair of sequentially acting iterative polyketide synthases (iPKSs) offers a test case for the modularization of secondary metabolic pathways into "build-couple-pair" combinatorial synthetic schemes. Expression of random pairs of iPKS subunits from four BDL model systems in a yeast heterologous host created a diverse library of BDL congeners, including a polyketide with an unnatural skeleton and heat shock response-inducing activity. Pairwise heterocombinations of the iPKS subunits also helped to illuminate the innate, idiosyncratic programming of these enzymes. Even in combinatorial contexts, these biosynthetic programs remained largely unchanged, so that the iPKSs built their cognate biosynthons, coupled these building blocks into chimeric polyketide intermediates, and catalyzed intramolecular pairing to release macrocycles or α-pyrones. However, some heterocombinations also provoked stuttering, i.e., the relaxation of iPKSs chain length control to assemble larger homologous products. The success of such a plug and play approach to biosynthesize novel chemical diversity bodes well for bioprospecting unnatural polyketides for drug discovery.

Anti-inflammatory sesquiterpene lactones from the flower of Vernonia cinerea.

PubMed

Youn, Ui Joung; Park, Eun-Jung; Kondratyuk, Tamara P; Simmons, Charles J; Borris, Robert P; Tanamatayarat, Patcharawan; Wongwiwatthananukit, Supakit; Toyama, Onoomar; Songsak, Thanapat; Pezzuto, John M; Chang, Leng Chee

2012-09-01

Bioassay-guided fractionation of the hexane extract from the flowers of Vernonia cinerea (Asteraceae) led to the isolation of a new sesquiterpene lactone, 8α-hydroxyhirsutinolide (2), and a new naturally occurring derivative, 8α-hydroxyl-1-O-methylhirsutinolide (3), along with seven known compounds (1 and 4-9). The structures of the new compounds were determined by 1D and 2D NMR experiments and by comparison with the structure of compound 1, whose relative stereochemistry was determined by X-ray analysis. The isolated compounds were evaluated for their cancer chemopreventive potential based on their ability to inhibit nitric oxide (NO) production and tumor necrosis factor alpha (TNF-α)-induced NF-κB activity. Compounds 1, 2, 4, 5, and 9 inhibited TNF-α-induced NF-κB activity with IC(50) values of 3.1, 1.9, 0.6, 5.2, and 1.6 μM, respectively; compounds 4 and 6-9 exhibited significant NO inhibitory activity with IC(50) values of 2.0, 1.5, 1.2, 2.7, and 2.4 μM, respectively. Published by Elsevier Ltd.

Binding modes of phosphotriesterase-like lactonase complexed with δ-nonanoic lactone and paraoxon using molecular dynamics simulations.

PubMed

Guan, Shanshan; Zhao, Li; Jin, Hanyong; Shan, Ning; Han, Weiwei; Wang, Song; Shan, Yaming

2017-02-01

Phosphotriesterase-like lactonases (PLLs) have received much attention because of their physical and chemical properties. They may have widespread applications in various fields. For example, they show potential for quorum-sensing signaling pathways and organophosphorus (OP) detoxification in agricultural science. However, the mechanism by which PLLs hydrolyze, which involves OP compounds and lactones and a variety of distinct catalytic efficiencies, has only rarely been explored. In the present study, molecular dynamics (MD) simulations were performed to characterize and contrast the structural dynamics of DrPLL, a member of the PLL superfamily in Deinococcus radiodurans, bound to two substrates, δ-nonanoic lactone and paraoxon. It has been observed that there is a 16-fold increase in the catalytic efficiency of the two mutant strains of DrPLL (F26G/C72I) vs. the wild-type enzyme toward the hydrolysis of paraoxon, but an explanation for this behavior is currently lacking. The analysis of the molecular trajectories of DrPLL bound to δ-nonanoic lactone indicated that lactone-induced conformational changes take place in loop 8, which is near the active site. Binding to paraoxon may lead to conformational displacement of loop 1 residues, which could lead to the deformation of the active site and so trigger the entry of the paraoxon into the active site. The efficiency of the F26G/C72I mutant was increased by decreasing the displacement of loop 1 residues and increasing the flexibility of loop 8 residues. These results provide a molecular-level explanation for the experimental behavior.

Novel anticancer alkene lactone from Persea americana.

PubMed

Falodun, Abiodun; Engel, Nadja; Kragl, Udo; Nebe, Barbara; Langer, Peter

2013-06-01

Persea americana Mill (Lauraceae) root bark is used in ethnomedicine for a variety of diseases including cancer. To isolate and characterize the chemical constituent in P. americana, and also to determine the anticancer property of a new alkene lactone from the root bark of P. americana. The MCF-7 cells were treated with different concentrations of the pure compound for 48 h. The percentage of cells in the various phases, online monitoring of metabolic changes and integrin receptor expression determined by flow cytometry. One novel alkene lactone (4-hydroxy-5-methylene-3-undecyclidenedihydrofuran-2 (3H)-one) (1) was isolated and characterized using 1D-NMR, 2D-NMR, infrared, UV and MS. At a concentration of 10 µg/mL, significant reduction of proliferation of MCF-7 was induced while MCF-12 A cell was significantly stimulated by 10 µg/mL. The IC50 value for MCF-7 cells is 20.48 µg/mL. Lower concentration of 1 harbor no significant effect on either MCF-7 or MCF-12A. The apoptotic rates of MCF-7 cells were increased significantly. At the final concentration 10 µg/mL, up to 80% of all breast cancer cells were dead. On the non-tumorigenic cell line MCF-12A, the same concentrations (1 and 10 µg/mL) of compound 1 caused significant enhanced apoptotic rates. A total of 1 µg/mL of 1 caused a decrease of α4-, α6-, β1- and β3-integrin expression. The compound caused a stimulatory effect on non-tumorigenic MCF-12A cells with respect to cell adhesion while tumorigenic MCF-7 cells detached continuously. This is the first report on the anticancer effects of this class of compound.

New macrocyclic lactones with acaricidal and nematocidal activities from a genetically engineered strain Streptomyces bingchenggensis BCJ60.

PubMed

Li, Jian-Song; Zhang, Hui; Zhang, Shao-Yong; Wang, Hai-Yan; Zhang, Ji; Chen, An-Liang; Wang, Ji-Dong; Xiang, Wen-Sheng

2017-04-01

Two new macrocyclic lactones, 4,25-diethyl-4,25-demethyl-milbemycin β 3 (1) and 27-formaldehyde-milbemycin β 14 (2), were isolated from a genetically engineered strain Streptomyces bingchenggensis BCJ60. Their structures were determined on the basis of spectroscopic analysis, including 1D and 2D NMR techniques as well as ESI-MS and comparison with data from the literature. The acaricidal and nematocidal capacities of compounds 1 and 2 were evaluated against Tetranychus cinnabarinus and Bursaphelenchus xylophilus, respectively. The results showed that the two new macrocyclic lactones 1 and 2 possessed potent acaricidal and nematocidal activities.

Development of Acid Functional Groups and Lactones During the Thermal Degradation of Wood and Wood Components

USGS Publications Warehouse

Rutherford, David W.; Wershaw, Robert L.; Reeves, James B.

2008-01-01

Black carbon (pyrogenic materials including chars) in soils has been recognized as a substantial portion of soil organic matter, and has been shown to play a vital role in nutrient cycling; however, little is known concerning the properties of this material. Previous studies have largely been concerned with the creation of high-surface-area materials for use as sorbents. These materials have been manufactured at high temperature and have often been activated. Chars occurring in the environment can be formed over a wide range of temperature. Because it is extremely difficult to isolate black carbon once it has been incorporated in soils, chars produced in the laboratory under controlled conditions can be used to investigate the range of properties possible for natural chars. This report shows that charring conditions (temperature and time) have substantial impact on the acid functional group and lactone content of chars. Low temperatures (250?C) and long charring times (greater than 72 hours) produce chars with the highest acid functional group and lactone content. The charring of cellulose appears to be responsible for the creation of the acid functional group and lactones. The significance of this study is that low-temperature chars can have acid functional group contents comparable to humic materials (as high as 8.8 milliequivalents per gram). Acid functional group and lactone content decreases as charring temperature increases. The variation in formation conditions expected under natural fire conditions will result in a wide range of sorption properties for natural chars which are an important component of soil organic matter. By controlling the temperature and duration of charring, it is possible to tailor the sorption properties of chars, which may be used as soil amendments.

Oocydin A, a chlorinated macrocyclic lactone with potent anti-oomycete activity from Serratia marcescens.

PubMed

Srobel, G; Li, J Y; Sugawara, F; Koshino, H; Harper, J; Hess, W M

1999-12-01

A unique chlorinated macrocyclic lactone, termed oocydin A, was isolated from a strain of Serratia marcescens growing as an epiphyte on Rhyncholacis pedicillata, an aquatic plant native to the Carrao river of the Venezuelan-Guyanan region of South America. The lactone has a molecular mass of 470 Da, and contains one atom of chlorine, a carboxyl group and a tetrahydrofuran ring internal to a larger macrocyclic ring. MICs of approximately 0.03 microg ml(-1) were noted for oocydin A against such phytopathogenic oomycetes as Pythium ultimum, Phytophthora parasitica, Phytophthora cinnamomi and Phytophthora citrophora. With regard to the true fungi, oocydin A had either minimal or no effect against certain Fungi Imperfecti (including several pathogens of humans), two ascomycetes and a basidiomycete. Oocydin A may have potential as an antimycotic in agricultural applications and especially for crop protection.

Chemoenzymatic Synthesis of an Enantiomerically Pure Lactone: A Three-Step Synthesis for Undergraduate Organic Chemistry Laboratory

NASA Astrophysics Data System (ADS)

McClure, Cynthia K.; Chenault, H. Keith

1996-05-01

A three-step laboratory sequence for the undergraduate organic laboratory is described. This series of experiments requires a student to use the product from one reaction as the starting material for a subsequent reaction, and thus the affords the student a "real world" experience of multistep synthesis. Thermal extrusion of sulfur dioxide from sulfolene is used to generate 1,3-butadiene in situ for a Diels-Alder cyclization with maleic anhydride. The anhydride is then reduced to the diol with lithium aluminum hydride. Oxidation of the diol to the chiral lactone is catalyzed by horse-liver alcohol dehydrogenase. This enzymatic oxidation illustrates in situ cofactor regeneration and allows students to measure simple enzyme kinetics.

Safety and clinical efficacy of tenvermectin, a novel antiparasitic 16-membered macrocyclic lactone antibiotics.

PubMed

Fei, Chenzhong; She, Rufeng; Li, Guiyu; Zhang, Lifang; Fan, Wushun; Xia, Suhan; Xue, Feiqun

2018-05-30

Tenvermectin (TVM) is a novel 16-membered macrocyclic lactone antibiotics, which contains component TVM A and TVM B. However there is not any report on safety and clinical efficacy of TVM for developing as a potential drug. In order to understand the part of safety and clinical efficacy of TVM, we conducted the acute toxicity test, the standard bacterial reverse mutation (Ames) test and the clinical deworming test. In the acute toxicity studies, TVM, TVM A and ivermectin (IVM) were administrated once by oral gavage to mice and rats. Results showed that the oral LD 50 values of TVM, TVM A and IVM in mice were 74.41, 106.95 and 53.06 mg/kg respectively. The oral LD 50 values of TVM and TVM A in rats were determined to be 164.22 and 749.34 mg/kg respectively. TVM and IVM are moderately toxic substances, meanwhile the TVM A belongs to low toxic compounds, implying that the acute toxicity is highly related to the length of side chain of TVM at position C25. In the Ames test, results showed that TVM did not induce mutagenicity in Salmonella typhimurium TA97a, TA98, TA100, TA102 and TA1535 with and without metabolic activation system, speculating that the mutagenicity is probably not related to the side chain at position C25 of 16-membered macrocyclic lactone antibiotics. In the efficacy trail of TVM against swine nematodes, growing pigs natural infection of Ascaris suum and Trichuris suis were treated with a single subcutaneous injection 0.3 mg/kg b.w.. Results showed that TVM and IVM had excellent effect in expelling Ascaris suum, and TVM had potential efficacy against Trichuris suis, however IVM had no effect on Trichuris suis. This study suggests that the side chain of TVM at position C25 may have important biological functions, which is one of the key sites of the studies on structure-activity relationship of 16-membered macrocyclic lactone compounds. TVM is a new compound exhibited some advantages worthy of developing. Copyright © 2018 Elsevier B.V. All

Hepatocurative potential of sesquiterpene lactones of Taraxacum officinale on carbon tetrachloride induced liver toxicity in mice.

PubMed

Mahesh, A; Jeyachandran, R; Cindrella, L; Thangadurai, D; Veerapur, V P; Muralidhara Rao, D

2010-06-01

The hepatocurative potential of ethanolic extract (ETO) and sesquiterpene lactones enriched fraction (SL) of Taraxacum officinale roots was evaluated against carbon tetrachloride (CCl 4 ) induced hepatotoxicity in mice. The diagnostic markers such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bilirubin contents were significantly elevated, whereas significant reduction in the level of reduced glutathione (GSH) and enhanced hepatic lipid peroxidation, liver weight and liver protein were observed in CCl 4 induced hepatotoxicity in mice. Post-treatment with ETO and SL significantly protected the hepatotoxicity as evident from the lower levels of hepatic enzyme markers, such as serum transaminase (ALT, AST), ALP and total bilirubin. Further, significant reduction in the liver weight and liver protein in drug-treated hepatotoxic mice and also reduced oxidative stress by increasing reduced glutathione content and decreasing lipid peroxidation level has been noticed. The histopathological evaluation of the liver also revealed that ETO and SL reduced the incidence of liver lesions induced by CCl 4 . The results indicate that sesquiterpene lactones have a protective effect against acute hepatotoxicity induced by the administration of CCl 4 in mice. Furthermore, observed activity of SL may be due to the synergistic action of two sesquiterpene lactones identified from enriched ethyl acetate fraction by HPLC method.

The Systematic Investigation of the Quorum Sensing System of the Biocontrol Strain Pseudomonas chlororaphis subsp. aurantiaca PB-St2 Unveils aurI to Be a Biosynthetic Origin for 3-Oxo-Homoserine Lactones

PubMed Central

Bauer, Judith S.; Hauck, Nils; Christof, Lisa; Mehnaz, Samina; Gust, Bertolt; Gross, Harald

2016-01-01

The shoot endophytic biocontrol strain Pseudomonas chlororaphis subsp. aurantiaca PB-St2 produces a wide range of exoproducts, including enzymes and antibiotics. The production of exoproducts is commonly tightly regulated. In order to get a deeper insight into the regulatory network of PB-St2, the strain was systematically investigated regarding its quorum sensing systems, both on the genetic and metabolic level. The genome analysis of PB-St2 revealed the presence of four putative acyl homoserine lactone (AHL) biosynthesis genes: phzI, csaI, aurI, and hdtS. LC-MS/MS analyses of the crude supernatant extracts demonstrated that PB-St2 produces eight AHLs. In addition, the concentration of all AHL derivatives was quantified time-resolved in parallel over a period of 42 h during the growth of P. aurantiaca PB-St2, resulting in production curves, which showed differences regarding the maximum levels of the AHLs (14.6 nM– 1.75 μM) and the production period. Cloning and heterologous overexpression of all identified AHL synthase genes in Escherichia coli proved the functionality of the resulting synthases PhzI, CsaI, and AurI. A clear AHL production pattern was assigned to each of these three AHL synthases, while the HdtS synthase did not lead to any AHL production. Furthermore, the heterologous expression study demonstrated unequivocally and for the first time that AurI directs the synthesis of two 3-oxo-AHLs. PMID:27861617

Short communication: Macrocyclic lactone residues in butter from Brazilian markets.

PubMed

Macedo, Fabio; Marsico, Eliane Teixeira; Conte-Júnior, Carlos Adam; de Almeida Furtado, Leonardo; Brasil, Taila Figueredo; Pereira Netto, Annibal Duarte

2015-06-01

Macrocyclic lactones (ML) are commonly used in drug formulations for the treatment of parasites in cattle. In Brazil, except for drugs (or formulations) with long-term (half-life) effects, ML are registered for use in bovines. Indiscriminate use of ML may result in the presence of residues in milk and dairy products due to their lipophilic properties and thermal stability. This study applied a method of liquid chromatography with fluorimetric detection, recently developed and validated for the determination of residues of abamectin, doramectin, ivermectin, and moxidectin in butter. The method was applied to 38 samples of commercial butter purchased in the metropolitan area of Rio de Janeiro, Brazil, between June and September 2013, analyzed in triplicate. Ivermectin was detected in 89.5% of the samples, with concentrations between 0.3 and 119.4 µg/kg; 76.3% of the samples contained doramectin (0.6 to 64.7 µg/kg) and 55.2% contained abamectin (0.7 to 4.5 µg/kg). Most butter samples (76.3%) contained residues of more than 1 ML; however, no residues of moxidectin were detected. The results showed a high incidence of the presence of avermectins in butter samples. Butter is not included in the Brazilian National Plan for Control of Residues and Contaminants in Animal Products. As ML residues concentrate in lipophilic compounds, butter and other fatty dairy products should be screened for the presence of ML residues. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Evaluation of anti-quorum-sensing activity of edible plants and fruits through inhibition of the N-acyl-homoserine lactone system in Chromobacterium violaceum and Pseudomonas aeruginosa.

PubMed

Musthafa, K Syed; Ravi, A Veera; Annapoorani, A; Packiavathy, I Sybiya Vasantha; Pandian, S Karutha

2010-01-01

To find out an alternative strategy to antibiotic usage against bacterial infection. The purpose of this study is to describe the quorum-sensing (QS) inhibitory activity of edible plants and fruits against N-acyl-homoserine lactone (AHL)-mediated violacein production in Chromobacterium violaceum and virulence factor expression in Pseudomonas aeruginosa PAO1. Aqueous extracts of Ananas comosus (Bromeliaceae), Musa paradiciaca (Musaceae), Manilkara zapota (Sapotaceae) and Ocimum sanctum (Lamiaceae) were prepared and anti-QS activity of each extract was tested against AHL-mediated phenotypic expressions of C. violaceum and PAO1. Most of these extracts showed significant reduction in AHL-mediated violacein production in C. violaceum as well as pyocyanin pigment, staphylolytic protease, elastase production and biofilm formation in PAO1. However, these extracts were not inhibitory to bacterial growth, revealing that the QS inhibition by the extracts is not related to static or killing effects on the bacteria. The present study identified the anti-QS activity of A. comosus, M. paradiciaca, M. zapota and O. sanctum. An AHL-inactivating compound from these plant sources can be used as an alternative to antibiotic compounds to prevent AHL-mediated bacterial infection in higher organisms. Copyright © 2010 S. Karger AG, Basel.

Regulation of acylated homoserine lactones (AHLs) in beef by spice marination.

PubMed

Gopu, Venkadesaperumal; Shetty, Prathapkumar Halady

2016-06-01

Quorum sensing (QS) is a signaling mechanism used by bacteria to communicate each other through the release of auto-inducing signaling molecules. Despite the fact that bacteria regulate its phenotypes by QS mechanism, their potential role in meat spoilage is not yet elucidated. In the current study, beef samples were analyzed for its microbial association and for the presence of N-acyl-homoserine-lactone (AHLs) throughout the storage experiments. Isolates were screened for AHLs production and selected spices were screened for their quorum sensing inhibitory (QSI) activity. In addition, effect of spices on AHLs production of Y. enterocolitica was quantified through high performance thin layer chromatography (HP-TLC). Outcome showed that microbial association of beef mainly consists of lactic acid bacteria (LAB) and Enterobacteriaceae. Samples stored at both aerobic and modified atmospheric packaging (MAP) exhibited higher counts whereas; marinated samples stored at MAP exhibited the lowest. It was found that out of 35 isolates Y. enterocolitica induced reporter strain CV026 and its cell-free supernatant contained 26.36 nM/100 ml of AHLs when compared to standard. Among the tested spices, C. cyminum exhibited pronounced results by significantly reducing the AHLs concentration up to 47.75 %. Findings revealed the presence of quorum molecules (AHLs) in beef meat throughout the spoilage process and spices can acts as quorum quenchers to influence the spoilage rate by reducing AHLs production.

Conformationally Constrained Analogues of Diacylglycerol. 29. Cells Sort Diacylglycerol-Lactone Chemical Zip Codes to Produce Diverse and Selective Biological Activities

PubMed Central

Duan, Dehui; Sigano, Dina M.; Kelley, James A.; Lai, Christopher C.; Lewin, Nancy E.; Kedei, Noemi; Peach, Megan L.; Lee, Jeewoo; Abeyweera, Thushara P.; Rotenberg, Susan A.; Kim, Hee; Kim, Young Ho; Kazzouli, Saïd El; Chung, Jae-Uk; Young, Howard A.; Young, Matthew R.; Baker, Alyson; Colburn, Nancy H.; Haimovitz-Friedman, Adriana; Truman, Jean-Philip; Parrish, Damon A.; Deschamps, Jeffrey R.; Perry, Nicholas A.; Surawski, Robert J.; Blumberg, Peter M.; Marquez, Victor E.

2008-01-01

Diacylglycerol-lactone (DAG-lactone) libraries generated by a solid-phase approach using IRORI technology produced a variety of unique biological activities. Subtle differences in chemical diversity in two areas of the molecule, the combination of which generates what we have termed “chemical zip codes”, are able to transform a relatively small chemical space into a larger universe of biological activities, as membrane-containing organelles within the cell appear to be able to decode these “chemical zip codes”. It is postulated that after binding to protein kinase C (PKC) isozymes or other non-kinase target proteins that contain diacylglycerol responsive, membrane interacting domains (C1 domains), the resulting complexes are directed to diverse intracellular sites where different sets of substrates are accessed. Multiple cellular bioassays show that DAG-lactones, which bind in vitro to PKCα to varying degrees, expand their biological repertoire into a larger domain, eliciting distinct cellular responses. PMID:18698758

Identification of N-acyl homoserine lactones produced by Gluconacetobacter diazotrophicus PAL5 cultured in complex and synthetic media.

PubMed

Nieto-Peñalver, Carlos G; Bertini, Elisa V; de Figueroa, Lucía I C

2012-07-01

The endophytic diazotrophic Gluconacetobacter diazotrophicus PAL5 was originally isolated from sugarcane (Saccharum officinarum). The biological nitrogen fixation, phytohormones secretion, solubilization of mineral nutrients and phytopathogen antagonism allow its classification as a plant growth-promoting bacterium. The recent genomic sequence of PAL5 unveiled the presence of a quorum sensing (QS) system. QS are regulatory mechanisms that, through the production of signal molecules or autoinducers, permit a microbial population the regulation of the physiology in a coordinated manner. The most studied autoinducers in gram-negative bacteria are the N-acyl homoserine lactones (AHLs). The usage of biosensor strains evidenced the presence of AHL-like molecules in cultures of G. diazotrophicus PAL5 grown in complex and synthetic media. Analysis of AHLs performed by LC-APCI-MS permitted the identification of eight different signal molecules, including C6-, C8-, C10-, C12- and C14-HSL. Mass spectra confirmed that this diazotrophic strain also synthesizes autoinducers with carbonyl substitutions in the acyl chain. No differences in the profile of AHLs could be determined under both culture conditions. However, although the level of short-chain AHLs was not affected, a decrease of 30% in the production of long-chain AHLs could be measured in synthetic medium.

Ultra-high-pressure liquid chromatography-tandem mass spectrometry for the analysis of six resorcylic acid lactones in bovine milk.

PubMed

Xia, Xi; Li, Xiaowei; Ding, Shuangyang; Zhang, Suxia; Jiang, Haiyang; Li, Jiancheng; Shen, Jianzhong

2009-03-20

This work reports a rapid, reliable and sensitive multi-residue method for the simultaneous determination of six resorcylic acid lactones in bovine milk by ultra-high-pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The resorcylic acid lactones were extracted, purified, and concentrated from milk samples in one step using a solid-phase extraction (SPE) cartridge that contained a polymeric mixed-mode anion-exchange sorbent. The analysis was performed on a Waters Acquity BEH C(18) column utilizing a gradient elution profile. Each LC run was completed in 3.5 min. The analytes were detected by multiple reaction monitoring (MRM) using electrospray ionization (ESI) negative mode. Mean recoveries from fortified samples ranged from 92.6% to 112.5%, with relative standard deviations lower than 11.4%. Using 5 mL bovine milk, the limits of detection and quantification for resorcylic acid lactones were in the ranges of 0.01-0.05 and 0.05-0.2 microg/L, respectively. The application of this newly developed method was demonstrated by analyzing bovine milk samples from markets.

Dehydroleucodine, a Sesquiterpene Lactone from Gynoxys verrucosa, Demonstrates Cytotoxic Activity against Human Leukemia Cells.

PubMed

Ordóñez, Paola E; Sharma, Krishan K; Bystrom, Laura M; Alas, Maria A; Enriquez, Raul G; Malagón, Omar; Jones, Darin E; Guzman, Monica L; Compadre, Cesar M

2016-04-22

The sesquiterpene lactones dehydroleucodine (1) and leucodine (2) were isolated from Gynoxys verrucosa, a species used in traditional medicine in southern Ecuador. The activity of these compounds was determined against eight acute myeloid leukemia (AML) cell lines and compared with their activity against normal peripheral blood mononuclear cells. Compound 1 showed cytotoxic activity against the tested cell lines, with LD50 values between 5.0 and 18.9 μM. Compound 2 was inactive against all of the tested cell lines, demonstrating that the exocyclic methylene in the lactone ring is required for cytotoxic activity. Importantly, compound 1 induced less toxicity to normal blood cells than to AML cell lines and was active against human AML cell samples from five patients, with an average LD50 of 9.4 μM. Mechanistic assays suggest that compound 1 has a similar mechanism of action to parthenolide (3). Although these compounds have significant structural differences, their lipophilic surface signatures show striking similarities.

Pinostrobin and Cajanus lactone isolated from Cajanus cajan (L.) leaves inhibits TNF-α and IL-1β production: in vitro and in vivo experimentation.

PubMed

Patel, Neeraj K; Bhutani, Kamlesh K

2014-06-15

The tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) inhibitory activities of Cajanus cajan (leaves) crude methanolic extract, its fractions and its phytochemical constituents were evaluated in lipopolysaccharide (LPS) stimulated RAW 264.7 and J774A.1 cells. Phytochemical investigation of the active ethyl acetate (CCE) and n-butanol (CCB) fractions of C. cajan L. leaves yielded 14 compounds. It was observed that both pinostrobin (9) and cajanus lactone (4) were found to be most active in inhibiting TNF-α (IC50<22 μM) and IL-1β (IC50<40 μM) whereas compounds 2, 3, 5-8, 10 and 14 showed moderate and mild effects (IC50=35.50-81.22 μM for TNF-α and 38.23-89.10 μM for IL-1β) in both the cell lines. Furthermore, at dose of 20mg/kg, both pinostrobin (9) and cajanus lactone (4) were found to reduce LPS-induced TNF-α levels by 48.6% and 55.0% respectively and IL-1β levels by 53.1% and 41.8% respectively in Sprague Dawley (SD) rats. These findings suggest that C. cajan L. leaves can be developed as an effective herbal remedy for the treatment and prevention of inflammation or associated ailments. Copyright © 2014 Elsevier GmbH. All rights reserved.

A comparison of the product formation induced by ultrasonic waves and gamma-rays in aqueous D-glucose solution.

PubMed

Heusinger, H

1987-08-01

The oxidation products obtained in aerated, aqueous alpha-D-glucose solutions after irradiation with ultrasonic waves and gamma-rays were compared. Separation and identification were performed by gas chromatography/mass spectrometry and three methods for the derivatization of the products were used: (1) trimethylsilylation of the OH groups; (2) methoximation of the carbonyl groups followed by trimethylsilylation of the OH groups; (3) reduction of the carbonyl and carboxyl groups to alcohols by sodium borodeuteride, followed by trimethylsilylation of the OH groups. When using ultrasound and gamma-irradiation identical products were observed: D-glucono-1,4-lactone, D-glucono-1,5-lactone, D-arabino-hexos-2-ulose, D-ribo-hexos-3-ulose, D-xylo-hexos-4-ulose, D-xylo-hexos-5-ulose, D-glucohexodialdose and arabino-1,4-lactone. From the results it was concluded that in ultrasound and gamma-irradiation the same primary species and consecutive reactions are involved in product formation.

Characterisation of two quorum sensing systems in the endophytic Serratia plymuthica strain G3: differential control of motility and biofilm formation according to life-style.

PubMed

Liu, Xiaoguang; Jia, Jinli; Popat, Roman; Ortori, Catherine A; Li, Jun; Diggle, Stephen P; Gao, Kexiang; Cámara, Miguel

2011-02-01

N-acylhomoserine lactone (AHL)-based quorum sensing (QS) systems have been described in many plant-associated Gram-negative bacteria to control certain beneficial phenotypic traits, such as production of biocontrol factors and plant growth promotion. However, the role of AHL-mediated signalling in the endophytic strains of plant-associated Serratia is still poorly understood. An endophytic Serratia sp. G3 with biocontrol potential and high levels of AHL signal production was isolated from the stems of wheat and the role of QS in this isolate was determined. Strain G3 classified as Serratia plymuthica based on 16S rRNA was subjected to phylogenetic analysis. Using primers to conserved sequences of luxIR homologues from the Serratia genus, splIR and spsIR from the chromosome of strain G3 were cloned and sequenced. AHL profiles from strain G3 and Escherichia coli DH5α expressing splI or spsI from recombinant plasmids were identified by liquid chromatography-tandem mass spectrometry. This revealed that the most abundant AHL signals produced by SplI in E. coli were N-3-oxo-hexanoylhomoserine lactone (3-oxo-C6-HSL), N-3-oxo-heptanoylhomoserine lactone (3-oxo-C7-HSL), N-3-hydroxy-hexanoylhomoserine lactone (3-hydroxy-C6-HSL), N-hexanoylhomoserine lactone (C6-HSL), and N-heptanoyl homoserine lactone (C7-HSL); whereas SpsI was primarily responsible for the synthesis of N-butyrylhomoserine lactone (C4-HSL) and N-pentanoylhomoserine lactone (C5-HSL). Furthermore, a quorum quenching analysis by heterologous expression of the Bacillus A24 AiiA lactonase in strain G3 enabled the identification of the AHL-regulated biocontrol-related traits. Depletion of AHLs with this lactonase resulted in altered adhesion and biofilm formation using a microtiter plate assay and flow cells coupled with confocal laser scanning microscopy respectively. This was different from the closely related S. plymuthica strains HRO-C48 and RVH1, where biofilm formation for both strains is AHL

Characterisation of two quorum sensing systems in the endophytic Serratia plymuthica strain G3: differential control of motility and biofilm formation according to life-style

PubMed Central

2011-01-01

Background N-acylhomoserine lactone (AHL)-based quorum sensing (QS) systems have been described in many plant-associated Gram-negative bacteria to control certain beneficial phenotypic traits, such as production of biocontrol factors and plant growth promotion. However, the role of AHL-mediated signalling in the endophytic strains of plant-associated Serratia is still poorly understood. An endophytic Serratia sp. G3 with biocontrol potential and high levels of AHL signal production was isolated from the stems of wheat and the role of QS in this isolate was determined. Results Strain G3 classified as Serratia plymuthica based on 16S rRNA was subjected to phylogenetic analysis. Using primers to conserved sequences of luxIR homologues from the Serratia genus, splIR and spsIR from the chromosome of strain G3 were cloned and sequenced. AHL profiles from strain G3 and Escherichia coli DH5α expressing splI or spsI from recombinant plasmids were identified by liquid chromatography-tandem mass spectrometry. This revealed that the most abundant AHL signals produced by SplI in E. coli were N-3-oxo-hexanoylhomoserine lactone (3-oxo-C6-HSL), N-3-oxo-heptanoylhomoserine lactone (3-oxo-C7-HSL), N-3-hydroxy-hexanoylhomoserine lactone (3-hydroxy-C6-HSL), N-hexanoylhomoserine lactone (C6-HSL), and N-heptanoyl homoserine lactone (C7-HSL); whereas SpsI was primarily responsible for the synthesis of N-butyrylhomoserine lactone (C4-HSL) and N-pentanoylhomoserine lactone (C5-HSL). Furthermore, a quorum quenching analysis by heterologous expression of the Bacillus A24 AiiA lactonase in strain G3 enabled the identification of the AHL-regulated biocontrol-related traits. Depletion of AHLs with this lactonase resulted in altered adhesion and biofilm formation using a microtiter plate assay and flow cells coupled with confocal laser scanning microscopy respectively. This was different from the closely related S. plymuthica strains HRO-C48 and RVH1, where biofilm formation for both strains is

Crystal Violet Lactone Salicylaldehyde Hydrazone Zn(II) Complex: a Reversible Photochromic Material both in Solution and in Solid Matrix

PubMed Central

Li, Kai; Li, Yuanyuan; Tao, Jing; Liu, Lu; Wang, Lili; Hou, Hongwei; Tong, Aijun

2015-01-01

Crystal violet lactone (CVL) is a classic halochromic dye which has been widely used as chromogenic reagent in thermochromic and piezochromic systems. In this work, a very first example of CVL-based reversible photochromic compound was developed, which showed distinct color change upon UV-visible light irradiation both in solution and in solid matrix. Moreover, metal complex of CVL salicylaldehyde hydrozone was facilely synthesized, exhibiting reversible photochromic properties with good fatigue resistance. It was served as promising solid material for photo-patterning. PMID:26412101

Sesquiterpene lactone mix as a diagnostic tool for Asteraceae allergic contact dermatitis: chemical explanation for its poor performance and Sesquiterpene lactone mix II as a proposed improvement.

PubMed

Jacob, Mathias; Brinkmann, Jürgen; Schmidt, Thomas J

2012-05-01

Two preparations are currently in use for the diagnosis of allergic contact dermatitis caused by Asteraceae: (i) Sesquiterpene lactone (SL) mix [three pure sesquiterpene lactones (STLs)], whose use has been questioned, owing to an insufficient rate of true-positive results; and (ii) Compositae mix, consisting of five Asteraceae extracts, which is problematic because of lack of standardization and questionable reproducibility. To analyse the reasons for the narrow sensitivity of SL mix from a chemoinformatic point of view, and to propose a solution by rational selection of alternative constituents for a new SL mix II covering a broader cohort of allergic patients. Structural and biological information on allergenic STLs was retrieved from databases and the literature, and molecular modelling and chemoinformatic computations were performed. An explanation for the insufficient hit rate of SL mix is that the three constituents possess extremely similar molecular structures/properties and do not represent well the structural diversity of allergenic STLs. STLs that are known as constituents of Compositae mix plants show much a wider diversity, which explains the higher positive rate. On the basis of their positions in chemical property space, a new collection of STLs that more evenly cover the overall structural diversity spectrum is proposed. SL mix II is likely to detect a larger number of patients sensitized to Asteraceae. © 2012 John Wiley & Sons A/S.

Complexation of sesquiterpene lactones with cyclodextrins: synthesis and effects on their activities on parasitic weeds.

PubMed

Cala, Antonio; Molinillo, José M G; Fernández-Aparicio, Mónica; Ayuso, Jesús; Álvarez, José A; Rubiales, Diego; Macías, Francisco A

2017-08-09

Allelochemicals are safer, more selective and more active alternatives than synthetic agrochemicals for weed control. However, the low solubility of these compounds in aqueous media limits their use as agrochemicals. Herein, we propose the application of α-, β- and γ-cyclodextrins to improve the physicochemical properties and biological activities of three sesquiterpene lactones: dehydrocostuslactone, costunolide and (-)-α-santonin. Complexation was achieved by kneading and coprecipitation methods. Aqueous solubility was increased in the range 100-4600% and the solubility-phase diagrams suggested that complex formation had been successful. The results of the PM3 semiempirical calculations were consistent with the experimental results. The activities on etiolated wheat coleoptiles, Standard Target Species and parasitic weeds were improved. Cyclodextrins preserved or enhanced the activity of the three sesquiterpene lactones. Free cyclodextrins did not show significant activity and therefore the enhancement in activity was due to complexation. These results are promising for applications in agrochemical design.

Staphylococcus intermedius produces a functional agr autoinducing peptide containing a cyclic lactone.

PubMed

Ji, Guangyong; Pei, Wuhong; Zhang, Linsheng; Qiu, Rongde; Lin, Jianqun; Benito, Yvonne; Lina, Gerard; Novick, Richard P

2005-05-01

The agr system is a global regulator of accessory functions in staphylococci, including genes encoding exoproteins involved in virulence. The agr locus contains a two-component signal transduction module that is activated by an autoinducing peptide (AIP) encoded within the agr locus and is conserved throughout the genus. The AIP has an unusual partially cyclic structure that is essential for function and that, in all but one case, involves an internal thiolactone bond between a conserved cysteine and the C-terminal carboxyl group. The exceptional case is a strain of Staphylococcus intermedius that has a serine in place of the conserved cysteine. We demonstrate here that the S. intermedius AIP is processed by the S. intermedius AgrB protein to generate a cyclic lactone, that it is an autoinducer as well as a cross-inhibitor, and that all of five other S. intermedius strains examined also produce serine-containing AIPs.

Sesquiterpene Lactone Composition and Cellular Nrf2 Induction of Taraxacum officinale Leaves and Roots and Taraxinic Acid β-d-Glucopyranosyl Ester.

PubMed

Esatbeyoglu, Tuba; Obermair, Betina; Dorn, Tabea; Siems, Karsten; Rimbach, Gerald; Birringer, Marc

2017-01-01

Taraxacum officinale, the common dandelion, is a plant of the Asteraceae family, which is used as a food and medical herb. Various secondary plant metabolites such as sesquiterpene lactones, triterpenoids, flavonoids, phenolic acids, coumarins, and steroids have been described to be present in T. officinale. Dandelion may exhibit various health benefits, including antioxidant, anti-inflammatory, and anticarcinogenic properties. We analyzed the leaves and roots of the common dandelion (T. officinale) using high-performance liquid chromatography/mass spectrometry to determine its sesquiterpene lactone composition. The main compound of the leaf extract taraxinic acid β-d-glucopyranosyl ester (1), a sesquiterpene lactone, was isolated and the structure elucidation was conducted by nuclear magnetic resonance spectrometry. The leaf extract and its main compound 1 activated the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) in human hepatocytes more significantly than the root extract. Furthermore, the leaf extract induced the Nrf2 target gene heme oxygenase 1. Overall, present data suggest that compound 1 may be one of the active principles of T. officinale.

Janthinocins A, B and C, novel peptide lactone antibiotics produced by Janthinobacterium lividum. I. Taxonomy, fermentation, isolation, physico-chemical and biological characterization.

PubMed

O'Sullivan, J; McCullough, J; Johnson, J H; Bonner, D P; Clark, J C; Dean, L; Trejo, W H

1990-08-01

Janthinocins A, B and C are novel antibacterial agents produced by Janthinobacterium lividum. They were isolated from fermentation broths and characterized by UV, IR, NMR and mass spectroscopy. They are cyclic decapeptide lactones with marked activity against aerobic and anaerobic Gram-positive bacteria and are 2 to 4 times more potent in vitro than vancomycin. Janthinocins A and B were also found to be effective in a Staphylococcus aureus systemic infection in mice.

Effect of oxidoreduction potential and of gas bubbling on rheological properties and microstructure of acid skim milk gels acidified with glucono-delta-lactone.

PubMed

Martin, F; Cayot, N; Marin, A; Journaux, L; Cayot, P; Gervais, P; Cachon, R

2009-12-01

Milk oxidoreduction potential was modified using gases during the production of a model dairy product and its effect on gel setting was studied. Acidification by glucono-delta-lactone was used to examine the physicochemistry of gelation and to avoid variations due to microorganisms sensitive to oxidoreduction potential. Four conditions of oxidoreduction potential were applied to milk: milk was gassed with air, nongassed, gassed with N(2), or gassed with N(2)H(2). The rheological properties and microstructure of these gels were determined using viscoelasticimetry, measurement of whey separation, and confocal laser scanning microscopy. It appeared that a reducing environment led to less-aggregated proteins within the matrix and consequently decreased whey separation significantly. The use of gas to modify oxidoreduction potential is a possible way to improve the quality of dairy products.

Concurrent and supercritical fluid chromatographic analysis of Terpene Lactones and ginkolic acids in Ginko biloba

USDA-ARS?s Scientific Manuscript database

Supercritical fluid chromatography was used to resolve and determine ginkgolic acids (GAs) and terpene lactones concurrently in ginkgo plant materials and commercial dietary supplements. Analysis of GAs (C13:0, C15:0, C15:1 and C17:1) was carried out by ESI (-) mass detection. The ESI (-) spectra of...

Antiplasmodial activities and cytotoxic effects of aqueous extracts and sesquiterpene lactones from Neurolaena lobata.

PubMed

François, G; Passreiter, C M; Woerdenbag, H J; Van Looveren, M

1996-04-01

Aqueous and lipophilic extracts of Neurolaena lobata (Asteraceae), obtained from Guatemala, were tested against Plasmodium falciparum in vitro. Moreover, sesquiterpene lactones, of the germacranolide and furanoheliangolide type, isolated from N. lobata, were shown to be active against P. falciparum in vitro. In addition to their antiplasmodial activity, their cytotoxic effects on human carcinoma cell lines were evaluated. Structure-activity relationships are discussed.

Effect of γ-lactones and γ-lactams compounds on Streptococcus mutans biofilms

PubMed Central

Sordi, Mariane Beatriz; Moreira, Thaís Altoé; Montero, Juan Felipe Dumes; Barbosa, Luis Cláudio; Benfatti, César Augusto Magalhães; Magini, Ricardo de Souza; Pimenta, Andréa de Lima

2018-01-01

Abstract Considering oral diseases, antibiofilm compounds can decrease the accumulation of pathogenic species such as Streptococcus mutans at micro-areas of teeth, dental restorations or implant-supported prostheses. Objective To assess the effect of thirteen different novel lactam-based compounds on the inhibition of S. mutans biofilm formation. Material and methods We synthesized compounds based on γ-lactones analogues from rubrolides by a mucochloric acid process and converted them into their corresponding γ-hydroxy-γ-lactams by a reaction with isobutylamine and propylamine. Compounds concentrations ranging from 0.17 up to 87.5 μg mL-1 were tested against S. mutans. We diluted the exponential cultures in TSB and incubated them (37°C) in the presence of different γ-lactones or γ-lactams dilutions. Afterwards, we measured the planktonic growth by optical density at 630 nm and therefore assessed the biofilm density by the crystal violet staining method. Results Twelve compounds were active against biofilm formation, showing no effect on bacterial viability. Only one compound was inactive against both planktonic and biofilm growth. The highest biofilm inhibition (inhibition rate above 60%) was obtained for two compounds while three other compounds revealed an inhibition rate above 40%. Conclusions Twelve of the thirteen compounds revealed effective inhibition of S. mutans biofilm formation, with eight of them showing a specific antibiofilm effect. PMID:29489934

Hypersensitive response and acyl‐homoserine lactone production of the fire blight antagonists Erwinia tasmaniensis and Erwinia billingiae

PubMed Central

Jakovljevic, Vladimir; Jock, Susanne; Du, Zhiqiang; Geider, Klaus

2008-01-01

Summary Fire blight caused by the Gram‐negative bacterium Erwinia amylovora can be controlled by antagonistic microorganisms. We characterized epiphytic bacteria isolated from healthy apple and pear trees in Australia, named Erwinia tasmaniensis, and the epiphytic bacterium Erwinia billingiae from England for physiological properties, interaction with plants and interference with growth of E. amylovora. They reduced symptom formation by the fire blight pathogen on immature pears and the colonization of apple flowers. In contrast to E. billingiae, E. tasmaniensis strains induced a hypersensitive response in tobacco leaves and synthesized levan in the presence of sucrose. With consensus primers deduced from lsc as well as hrpL, hrcC and hrcR of the hrp region of E. amylovora and of related bacteria, these genes were successfully amplified from E. tasmaniensis DNA and alignment of the encoded proteins to other Erwinia species supported a role for environmental fitness of the epiphytic bacterium. Unlike E. tasmaniensis, the epiphytic bacterium E. billingiae produced an acyl‐homoserine lactone for bacterial cell‐to‐cell communication. Their competition with the growth of E. amylovora may be involved in controlling fire blight. PMID:21261861

Influence of glucose concentrations on biofilm formation, motility, exoprotease production, and quorum sensing in Aeromonas hydrophila.

PubMed

Jahid, Iqbal Kabir; Lee, Na-Young; Kim, Anna; Ha, Sang-Do

2013-02-01

Aeromonas hydrophila recently has received increased attention because it is opportunistic and a primary human pathogen. A. hydrophila biofilm formation and its control are a major concern for food safety because biofilms are related to virulence. Therefore, we investigated biofilm formation, motility inhibition, quorum sensing, and exoprotease production of this opportunistic pathogen in response to various glucose concentrations from 0.05 to 2.5% (wt/vol). More than 0.05% glucose significantly impaired (P < 0.05) quorum sensing, biofilm formation, protease production, and swarming and swimming motility, whereas bacteria treated with 0.05% glucose had activity similar to that of the control (0% glucose). A stage shift biofilm assay revealed that the addition of glucose (2.5%) inhibited initial biofilm formation but not later stages. However, addition of quorum sensing molecules N-3-butanoyl-DL-homoserine lactone and N-3-hexanoyl homoserine lactone partially restored protease production, indicating that quorum sensing is controlled by glucose concentrations. Thus, glucose present in food or added as a preservative could regulate acyl-homoserine lactone quorum sensing molecules, which mediate biofilm formation and virulence in A. hydrophila.

A novel screen-printed mast cell-based electrochemical sensor for detecting spoilage bacterial quorum signaling molecules (N-acyl-homoserine-lactones) in freshwater fish.

PubMed

Jiang, Donglei; Liu, Yan; Jiang, Hui; Rao, Shengqi; Fang, Wu; Wu, Mangang; Yuan, Limin; Fang, Weiming

2018-04-15

A novel screen-printed cell-based electrochemical sensor was developed to assess bacterial quorum signaling molecules, N-acylhomoserine lactones (AHLs). Screen-printed carbon electrode (SPCE), which possesses excellent properties such as low-cost, disposable and energy-efficient, was modified with multi-walled carbon nanotubes (MWNTs) to improve electrochemical signals and enhance the sensitivity. Rat basophilic leukemia (RBL-2H3) mast cells encapsulated in alginate/graphene oxide (NaAgl/GO) hydrogel were immobilized on the MWNTs/SPCE to serve as recognition element. Electrochemical impedance spectroscopy (EIS) was employed to record the cell impedance signal as-influenced by Pseudomonas aeruginosa quorum-sensing molecule, N-3-oxododecanoyl homoserine lactone (3OC 12 -HSL). Experimental results show that 3OC 12 -HSL caused a significant decrease in cell viability in a dose dependent manner. The EIS value decreased with concentrations of 3OC 12 -HSL in the range of 0.1-1μM, and the detection limit for 3OC 12 -HSL was calculated to be 0.094μM. These results were confirmed via cell viability, SEM, TEM analysis. Next, the sensor was successfully applied to monitoring the production of AHLs by spoilage bacteria in three different freshwater fish juice samples which efficiently proved the practicability of this cell based method. Therefore, the proposed cell sensor may serve as an innovative and effective approach to the measurement of quorum signaling molecule and thus provides a new avenue for real-time monitoring the spoilage bacteria in freshwater fish production. Copyright © 2017 Elsevier B.V. All rights reserved.

Sesquiterpene Lactones from Cynara cornigera: Acetyl Cholinesterase Inhibition and In Silico Ligand Docking.

PubMed

Hegazy, Mohamed-Elamir F; Ibrahim, Abeer Y; Mohamed, Tarik A; Shahat, Abdelaaty A; El Halawany, Ali M; Abdel-Azim, Nahla S; Alsaid, Mansour S; Paré, Paul W

2016-01-01

Wild artichoke (Cynara cornigera), a thistle-like perennial belonging to the Asteraceae family, is native to the Mediterranean region, northwestern Africa, and the Canary Islands. While the pleasant, albeit bitter, taste of the leaves and flowers is attributed to the sesquiterpene lactones cynaropicrin and cynarin, a comprehensive phytochemical investigation still needs to be reported. In this study seven sesquiterpene lactones were isolated from an aqueous methanol plant extract, including a new halogenated metabolite (1), the naturally isolated compound sibthorpine (2), and five metabolites isolated for the first time from C. cornigera. Structures were established by spectroscopic methods, including HREIMS, (1 )H, (13 )C, DEPT, (1 )H-(1 )H COSY, HMQC, and HMBC-NMR experiments as well as by X-ray analysis. The isolated bioactive nutrients were analyzed for their antioxidant and metal chelating activity. Compound 1 exhibited a potent metal chelating activity as well as a high antioxidant capacity. Moreover, select compounds were effective as acetyl cholinesterase inhibitors presenting the possibility for such compounds to be examined for anti-neurodegenerative activity. A computational pharmacophore elucidation and docking study was performed to estimate the pharmacophoric features and binding conformation of isolated compounds in the acetyl cholinesterase active site. Georg Thieme Verlag KG Stuttgart · New York.

[Two new sesquiterpene lactones from the pericarp of Illicium macranthum].

PubMed

Ma, Hai-juan; Ma, Chang-hua; Huang, Jian-mei

2010-03-01

Silica gel column chromatography was used for the isolation and purification of the chemical constituents of the pericarp of Illicium macranthum. From dichloromethane-EtOAc (1:1) fraction and EtOAc fraction of the methanol extracts, eleven compounds were identified on the basis of chemical and spectral data. Two new compounds were elucidated to be 6-deoxyneomajucin (1) and 2-oxo-6-deoxyneomajucin (2), along with nine known compounds 6-deoxypseudoanisatin (3), pseudoanisatin (4), anisatin (5), pseudomajucin (6), protocatecheuic acid (7), shikimic acid (8), shikimic acid methylester (9), beta-sitosterol (10) and daucosterol (11). Compounds 1 and 2 are new majucin-type sesquiterpene lactones.

Polypropionate lactones of deoxysugars glycosides from slime mold Lycogala epidendrum.

PubMed

Rezanka, Tomás; Dvoráková, Radmila

2003-08-01

Two novel polypropionate lactone glycosides (1 and 2, i.e. lycogalinosides A and B) were isolated from the slime mold Lycogala epidendrum. Their structures, including the absolute configurations of the hydroxyl and methyls groups, were determined by means of extensive spectroscopic data such as mass, IR, UV, and 1D and 2D NMR spectra and chemical degradation followed by spectroscopic and chromatographic analysis. Compounds 1 and 2 are unique in structure containing a 2-deoxy-alpha-L-fucopyranosyl-(1-4)-6-deoxy-beta-D-gulopyranosyl unit and a beta-D-olivopyranosyl-(1-4)-beta-D-fucopyranosyl unit, respectively, and showed growth inhibitory activities against Gram-positive bacteria.

Growth Inhibitory, Bactericidal, and Morphostructural Effects of Dehydrocostus Lactone from Magnolia sieboldii Leaves on Antibiotic-Susceptible and -Resistant Strains of Helicobacter pylori

PubMed Central

Lee, Hyun-Kyung; Song, Ha Eun; Lee, Haeng-Byung; Kim, Cheol-Soo; Koketsu, Mamoru; Thi My Ngan, Luong; Ahn, Young-Joon

2014-01-01

Helicobacter pylori is associated with various diseases of the upper gastrointestinal tract, such as gastric inflammation and duodenal and gastric ulcers. The aim of the study was to assess anti-H. pylori effects of the sesquiterpene lactone dehydrocostus lactone (DCL) from Magnolia sieboldii leaves, compared to commercial pure DCL, two previously known sesquiterpene lactones (costunolide and parthenolide), (–)-epigallocatechin gallate, and four antibiotics. The antibacterial activity of natural DCL toward antibiotic-susceptible H. pylori ATCC 700392 and H. pylori ATCC 700824 strains (MIC, 4.9 and 4.4 mg/L) was similar to that of commercial DCL and was more effective than costunolide, parthenolide, and EGCG. The activity of DCL was slightly lower than that of metronidazole (MIC, 1.10 and 1.07 mg/L). The antibacterial activity of DCL was virtually identical toward susceptible and resistant strains, even though resistance to amoxicillin (MIC, 11.1 mg/L for PED 503G strain), clarithromycin (49.8 mg/L for PED 3582GA strain), metronidazole (21.6 mg/L for H. pylori ATCC 43504 strain; 71.1 mg/L for 221 strain), or tetracycline (14.2 mg/L for B strain) was observed. This finding indicates that DCL and the antibiotics do not share a common mode of action. The bactericidal activity of DCL toward H. pylori ATCC 43504 was not affected by pH values examined (4.0–7.0). DCL caused considerable conversion to coccoid form (94 versus 49% at 8 and 4 mg/L of DCL for 48 h). The Western blot analysis revealed that urease subunits (UreA and UreB) of H. pylori ATCC 43504 were not affected by 10 mM of DCL, whereas UreA monomer band completely disappeared at 0.1 mM of (–)-epigallocatechin gallate. Global efforts to reduce the level of antibiotics justify further studies on M. sieboldii leaf-derived materials containing DCL as potential antibacterial products or a lead molecule for the prevention or eradication of drug-resistant H. pylori. PMID:24747984

Violacein and biofilm production in Janthinobacterium lividum.

PubMed

Pantanella, F; Berlutti, F; Passariello, C; Sarli, S; Morea, C; Schippa, S

2007-04-01

To analyse the environmental stimuli modulating violacein and biofilm production in Janthinobacterium lividum. Violacein and biofilm production by J. lividum DSM1522(T) was assayed in different growth conditions. Our data suggest that violacein and biofilm production is controlled by the carbon source, being inhibited by glucose and enhanced by glycerol. J. lividum produced violacein also in the presence of different sub-inhibitory concentrations of ampicillin. As opposite, the production of N-acylhomoserine lactone(s), quorum sensing regulators was shown to be positively regulated by glucose. Moreover, violacein-producing cultures of J. lividum showed higher CFU counts than violacein-nonproducing ones. Taken together, our results suggest that violacein and biofilm production could be regulated by a common metabolic pathway and that violacein as well as biofilm could represent a response to environmental stresses and a key factor in the survival mechanisms of J. lividum. Although several recent studies disclosed a number of interesting biological properties of violacein, few data are reported on the physiologic function of violacein in J. lividum. This paper adds new information on the complex mechanisms allowing and regulating bacterial life in hostile environments.

Vitamin B12[c-lactone], a biologically inactive corrinoid compound, occurs in cultured and dried lion's mane mushroom (Hericium erinaceus) fruiting bodies.

PubMed

Teng, Fei; Bito, Tomohiro; Takenaka, Shigeo; Yabuta, Yukinori; Watanabe, Fumio

2014-02-19

This study determined the vitamin B12 content of the edible medicinal mushroom Hericium erinaceus, lion's mane mushroom fruiting body, using a microbiological assay based on Lactobacillus delbrueckii ATCC 7830. Trace levels (0.04-0.36 μg/100 g dry weight) of vitamin B12 were found in most of the dried mushroom samples, and two samples contained slightly higher levels (0.56 and 1.04 μg/100 g dry weight, respectively) of vitamin B12. We purified the corrinoid compounds from the extracts of dried lion's mane mushroom fruiting bodies using an immunoaffinity column and identified them as vitamin B12 or vitamin B12[c-lactone] (or both) based on LC/ESI-MS/MS chromatograms. This is the first report on an unnatural corrinoid, vitamin B12[c-lactone], occurring in foods. Vitamin B12[c-lactone] was simple to produce during incubation of authentic vitamin B12 and chloramine-T, an antimicrobial agent, at varying pH values (3.0-7.0) and was completely inactive in the vitamin B12-dependent bacteria that are generally used in vitamin B12 bioassays.

Molecular identification of tuliposide B-converting enzyme: a lactone-forming carboxylesterase from the pollen of tulip.

PubMed

Nomura, Taiji; Murase, Tatsunori; Ogita, Shinjiro; Kato, Yasuo

2015-07-01

6-Tuliposides A (PosA) and B (PosB), which are the major secondary metabolites in tulip (Tulipa gesneriana), are enzymatically converted to the antimicrobial lactonized aglycons, tulipalins A (PaA) and B (PaB), respectively. We recently identified a PosA-converting enzyme (TCEA) as the first reported member of the lactone-forming carboxylesterases. Herein, we describe the identification of another lactone-forming carboxylesterase, PosB-converting enzyme (TCEB), which preferentially reacts with PosB to give PaB. This enzyme was isolated from tulip pollen, which showed high PosB-converting activity. Purified TCEB exhibited greater activity towards PosB than PosA, which was contrary to that of the TCEA. Novel cDNA (TgTCEB1) encoding the TCEB was isolated from tulip pollen. TgTCEB1 belonged to the carboxylesterase family and was approximately 50% identical to the TgTCEA polypeptides. Functional characterization of the recombinant enzyme verified that TgTCEB1 catalyzed the conversion of PosB to PaB with an activity comparable with the native TCEB. RT-qPCR analysis of each part of plant revealed that TgTCEB1 transcripts were limited almost exclusively to the pollen. Furthermore, the immunostaining of the anther cross-section using anti-TgTCEB1 polyclonal antibody verified that TgTCEB1 was specifically expressed in the pollen grains, but not in the anther cells. N-terminal transit peptide of TgTCEB1 was shown to function as plastid-targeted signal. Taken together, these results indicate that mature TgTCEB1 is specifically localized in plastids of pollen grains. Interestingly, PosB, the substrate of TgTCEB1, accumulated on the pollen surface, but not in the intracellular spaces of pollen grains. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

N-Acyl-Homoserine Lactone Primes Plants for Cell Wall Reinforcement and Induces Resistance to Bacterial Pathogens via the Salicylic Acid/Oxylipin Pathway[C][W][OPEN

PubMed Central

Schenk, Sebastian T.; Hernández-Reyes, Casandra; Samans, Birgit; Stein, Elke; Neumann, Christina; Schikora, Marek; Reichelt, Michael; Mithöfer, Axel; Becker, Annette; Kogel, Karl-Heinz; Schikora, Adam

2014-01-01

The ability of plants to monitor their surroundings, for instance the perception of bacteria, is of crucial importance. The perception of microorganism-derived molecules and their effector proteins is the best understood of these monitoring processes. In addition, plants perceive bacterial quorum sensing (QS) molecules used for cell-to-cell communication between bacteria. Here, we propose a mechanism for how N-acyl-homoserine lactones (AHLs), a group of QS molecules, influence host defense and fortify resistance in Arabidopsis thaliana against bacterial pathogens. N-3-oxo-tetradecanoyl-l-homoserine lactone (oxo-C14-HSL) primed plants for enhanced callose deposition, accumulation of phenolic compounds, and lignification of cell walls. Moreover, increased levels of oxylipins and salicylic acid favored closure of stomata in response to Pseudomonas syringae infection. The AHL-induced resistance seems to differ from the systemic acquired and the induced systemic resistances, providing new insight into inter-kingdom communication. Consistent with the observation that short-chain AHLs, unlike oxo-C14-HSL, promote plant growth, treatments with C6-HSL, oxo-C10-HSL, or oxo-C14-HSL resulted in different transcriptional profiles in Arabidopsis. Understanding the priming induced by bacterial QS molecules augments our knowledge of plant reactions to bacteria and suggests strategies for using beneficial bacteria in plant protection. PMID:24963057

Experimental verification, and domain definition, of structural alerts for protein binding: epoxides, lactones, nitroso, nitros, aldehydes and ketones.

PubMed

Nelms, M D; Cronin, M T D; Schultz, T W; Enoch, S J

2013-01-01

This study outlines how a combination of in chemico and Tetrahymena pyriformis data can be used to define the applicability domain of selected structural alerts within the profilers of the OECD QSAR Toolbox. Thirty-three chemicals were profiled using the OECD and OASIS profilers, enabling the applicability domain of six structural alerts to be defined, the alerts being: epoxides, lactones, nitrosos, nitros, aldehydes and ketones. Analysis of the experimental data showed the applicability domains for the epoxide, nitroso, aldehyde and ketone structural alerts to be well defined. In contrast, the data showed the applicability domains for the lactone and nitro structural alerts needed modifying. The accurate definition of the applicability domain for structural alerts within in silico profilers is important due to their use in the chemical category in predictive and regulatory toxicology. This study highlights the importance of utilizing multiple profilers in category formation.

Antimicrobial activity and inactivation mechanism of lactonic and free acid sophorolipids against Escherichia coli O157:H7

USDA-ARS?s Scientific Manuscript database

In this study, we synthesized sophorolipids (SLs) from glucose and either palmitic, stearic or oleic acid via fermentation using the osmophilic yeast Starmerella bombicola, purified and separated the SLs into lactonic and free-acid forms and assessed their antimicrobial efficacy against 5 strains of...

A probable aculeacin A acylase from the Ralstonia solanacearum GMI1000 is N-acyl-homoserine lactone acylase with quorum-quenching activity

PubMed Central

2009-01-01

Background The infection and virulence functions of diverse plant and animal pathogens that possess quorum sensing systems are regulated by N-acylhomoserine lactones (AHLs) acting as signal molecules. AHL-acylase is a quorum quenching enzyme and degrades AHLs by removing the fatty acid side chain from the homoserine lactone ring of AHLs. This blocks AHL accumulation and pathogenic phenotypes in quorum sensing bacteria. Results An aac gene of undemonstrated function from Ralstonia solanacearum GMI1000 was cloned, expressed in Escherichia coli; it inactivated four AHLs that were tested. The sequence of the 795 amino acid polypeptide was considerably similar to the AHL-acylase from Ralstonia sp. XJ12B with 83% identity match and shared 39% identity with an aculeacin A acylase precursor from the gram-positive actinomycete Actinoplanes utahensis. Aculeacin A is a neutral lipopeptide antibiotic and an antifungal drug. An electrospray ionisation mass spectrometry (ESI-MS) analysis verified that Aac hydrolysed the amide bond of AHL, releasing homoserine lactone and the corresponding fatty acids. However, ESI-MS analysis demonstrated that the Aac could not catalyze the hydrolysis of the palmitoyl moiety of the aculeacin A. Moreover, the results of MIC test of aculeacin A suggest that Aac could not deacylate aculeacin A. The specificity of Aac for AHLs showed a greater preference for long acyl chains than for short acyl chains. Heterologous expression of the aac gene in Chromobacterium violaceum CV026 effectively inhibited violacein and chitinase activity, both of which were regulated by the quorum-sensing mechanism. These results indicated that Aac could control AHL-dependent pathogenicity. Conclusion This is the first study to find an AHL-acylase in a phytopathogen. Our data provide direct evidence that the functioning of the aac gene (NP520668) of R. solanacearum GMI1000 is via AHL-acylase and not via aculeacin A acylase. Since Aac is a therapeutic potential quorum

Preparative isolation and purification of three sesquiterpenoid lactones from Eupatorium lindleyanum DC. by high-speed counter-current chromatography.

PubMed

Yan, Guilong; Ji, Lilian; Luo, Yuming; Hu, Yonghong

2012-07-27

A high-speed counter-current chromatography (HSCCC) method was established for the preparative separation of three sesquiterpenoid lactones from Eupatorium lindleyanum DC. The two-phase solvent system composed of n-hexane-ethyl acetate-methanol-water (1:4:2:3, v/v/v/v) was selected. From 540 mg of the n-butanol fraction of Eupatorium lindleyanum DC., 10.8 mg of 3β-hydroxy-8β-[4'-hydroxytigloyloxy]-costunolide, 17.9 mg of eupalinolide A and 19.3 mg of eupalinolide B were obtained in a one-step HSCCC separation, with purities of 91.8%, 97.9% and 97.1%, respectively, as determined by HPLC. Their structures were further identified by ESI-MS and ¹H-NMR.

Five new lactone derivatives from the stems of Dendrobium nobile.

PubMed

Zhou, Xue-Ming; Zheng, Cai-Juan; Wu, Jia-Ting; Chen, Guang-Ying; Chen, Jun; Sun, Chong-Ge

2016-12-01

Five new lactone derivatives decumbic acids A and B (1 and 2), (-)-decumbic acid (3a), (-)- and (+)-dendrolactone (4a and 4b) together with four known compounds (3b and 5-7) were isolated from the stems of Dendrobium nobile. Their structures were elucidated using comprehensive spectroscopic methods. Compounds 3a and 3b, 4a and 4b were isolated as two pair of enantiomers by chiral HPLC. The absolute configurations of 1, 2, 3a, 4a and 4b were determined by optical rotation and X-ray crystallographic analysis. The inhibitory activities of all compounds against nine phytopathogenic fungi and three cancer cell lines were evaluated. Copyright © 2016 Elsevier B.V. All rights reserved.

Hydrodeoxygenation of the angelica lactone dimer, a cellulose-based feedstock: simple, high-yield synthesis of branched C7 -C10 gasoline-like hydrocarbons.

PubMed

Mascal, Mark; Dutta, Saikat; Gandarias, Inaki

2014-02-10

Dehydration of biomass-derived levulinic acid under solid acid catalysis and treatment of the resulting angelica lactone with catalytic K2 CO3 produces the angelica lactone dimer in excellent yield. This dimer serves as a novel feedstock for hydrodeoxygenation, which proceeds under relatively mild conditions with a combination of oxophilic metal and noble metal catalysts to yield branched C7 -C10 hydrocarbons in the gasoline volatility range. Considering that levulinic acid is available in >80 % conversion from raw biomass, a field-to-tank yield of drop-in, cellulosic gasoline of >60 % is possible. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

New spiral γ-lactone enantiomers from the plant endophytic fungus Pestalotiopsis foedan.

PubMed

Yang, Xiao-Long; Li, Zhuang-Zhuang

2013-02-11

(-)-(4S, 8S)-Foedanolide (1a) and (+)-(4R, 8R)-foedanolide (1b), a pair of new spiro-γ-lactone enantiomers, were isolated from the fermentation broth of the plant endophytic fungus Pestalotiopsis foedan by HPLC using a chiral column, achieving over 7% ee. Their structures and absolute configurations were determined on the basis of extensive analysis of NMR spectra combined with computational methods via calculation of the electronic circular dichroism (ECD) and optical rotation (OR). Compounds 1a and 1b showed moderate activities against HeLa, A-549, U-251, HepG2 and MCF-7 tumor cell lines.

Two novel sesquiterpene lactones, cytotoxic vernolide-A and -B, from Vernonia cinerea.

PubMed

Kuo, Yao-Haur; Kuo, Yu-Jen; Yu, Ang-Su; Wu, Ming-Der; Ong, Chi-Wi; Yang Kuo, Li-Ming; Huang, Jo-Ti; Chen, Chieh-Fu; Li, Shyh-Yuan

2003-04-01

Bioassay-directed fractionation of an ethanolic extract of stems of Vernonia cinerea has resulted in the isolation of two novel sesquiterpene lactones, vernolide-A and -B. Their structures were elucidated on the basis of spectroscopic analysis. Biological evaluation showed that vernolide-A demonstrated potent cytotoxicity against human KB, DLD-1, NCI-661, and Hela tumor cell lines (ED(50)=0.02, 0.05, 0.53, 0.04 microg/ml for KB, DLD-1, NCI-661, and Hela, respectively); vernolide-B had marginal cytoxicity (ED(50)=3.78, 5.88, 6.42 microg/ml for KB, NCI-661, and Hela, respectively).

Rubrolides as model for the development of new lactones and their aza analogs as potential photosynthesis inhibitors.

PubMed

Pereira, Ulisses A; Barbosa, Luiz C A; Demuner, Antônio J; Silva, Antônio A; Bertazzini, Michele; Forlani, Giuseppe

2015-07-01

Natural phytotoxins and their synthetic analogs are a potential source of new bioactive compounds for agriculture. Analogs of rubrolides, a class of γ-alkylidene-γ-lactones isolated from different ascidians, have been shown to interfere with the photosynthetic electron-transport chain, yet their activity needs to be improved. With this aim, ten 5-aryl-6-benzyl-4-bromopyridazin-3(2H)-ones were prepared in yields ranging from 44 to 88% by reaction of their correspondent γ-alkylidene-γ-lactones with NH2 NH2 . The structures of these rubrolide analogs were determined by (1) H- and (13) C-NMR, 2D-NMR (COSY and HETCOR), NOE difference, and MS techniques. These compounds were evaluated for their abilities of interfering with the light-driven reduction of ferricyanide by isolated spinach chloroplasts. Lactones with electron-withdrawing substituents in the para-position of the benzylidene ring were the most effective inhibitors. Characterization of the activity of 11b/11b' suggested a mechanism based on the interaction with the plastoquinone binding site of photosystem II. Addition of several compounds to the culture medium of a cyanobacterial model strain was found to inhibit algal growth. However, the relative effectiveness was not consistent with their activity in vitro, suggesting the occurrence of multiple targets and/or detoxyfication mechanisms. Indeed, the compounds showed differential effects on the heterotrophic growth of some crop species, Cucumis sativus and Sorghum bicolor. Pyridazin-3(2H)-ones 12e, 12i, and 12j, which have been found poorly active against the photosynthetic electron transport, were the most effective in inhibiting the growth of some weeds, Ipomoea grandifolia and Brachiaria decumbens, under greenhouse conditions. Copyright © 2015 Verlag Helvetica Chimica Acta AG, Zürich.

Phytotoxic properties of cnicin, a sesquiterpene lactone fromcentaurea maculosa (spotted knapweed).

PubMed

Kelsey, R G; Locken, L J

1987-01-01

Water and solvent extracts from the aerial tissues ofCentaurea maculosa, spotted knapweed, inhibited the root growth of lettuce. Column chromatography and lettuce bioassay of a chloroform extract led to the isolation of cnicin, a sesquiterpene lactone. Pure cnicin was bioassayed at 0, 1, 2, 4, 6, 8, and 10 mg/5 ml water with lettuce, created wheatgrass, bluebunch wheatgrass, rough fescue, western larch, lodgepole pine, and spotted knapweed. Germination was inhibited at one or more concentrations for all species except lodgepole pine and spotted knapweed. Growth, particularly of the roots, was retarded between 1 and 4 mg of cnicin. Lettuce, bluebunch wheatgrass, and spotted knapweed were inhibited significantly at all concentrations tested.

C-type natriuretic peptide modulates quorum sensing molecule and toxin production in Pseudomonas aeruginosa

PubMed Central

Blier, Anne-Sophie; Veron, Wilfried; Bazire, Alexis; Gerault, Eloïse; Taupin, Laure; Vieillard, Julien; Rehel, Karine; Dufour, Alain; Le Derf, Franck; Orange, Nicole; Hulen, Christian; Feuilloley, Marc G. J.

2011-01-01

Pseudomonas aeruginosa coordinates its virulence expression and establishment in the host in response to modification of its environment. During the infectious process, bacteria are exposed to and can detect eukaryotic products including hormones. It has been shown that P. aeruginosa is sensitive to natriuretic peptides, a family of eukaryotic hormones, through a cyclic nucleotide-dependent sensor system that modulates its cytotoxicity. We observed that pre-treatment of P. aeruginosa PAO1 with C-type natriuretic peptide (CNP) increases the capacity of the bacteria to kill Caenorhabditis elegans through diffusive toxin production. In contrast, brain natriuretic peptide (BNP) did not affect the capacity of the bacteria to kill C. elegans. The bacterial production of hydrogen cyanide (HCN) was enhanced by both BNP and CNP whereas the production of phenazine pyocyanin was strongly inhibited by CNP. The amount of 2-heptyl-4-quinolone (HHQ), a precursor to 2-heptyl-3-hydroxyl-4-quinolone (Pseudomonas quinolone signal; PQS), decreased after CNP treatment. The quantity of 2-nonyl-4-quinolone (HNQ), another quinolone which is synthesized from HHQ, was also reduced after CNP treatment. Conversely, both BNP and CNP significantly enhanced bacterial production of acylhomoserine lactone (AHL) [e.g. 3-oxo-dodecanoyl-homoserine lactone (3OC12-HSL) and butanoylhomoserine lactone (C4-HSL)]. These results correlate with an induction of lasI transcription 1 h after bacterial exposure to BNP or CNP. Concurrently, pre-treatment of P. aeruginosa PAO1 with either BNP or CNP enhanced PAO1 exotoxin A production, via a higher toxA mRNA level. At the same time, CNP led to elevated amounts of algC mRNA, indicating that algC is involved in C. elegans killing. Finally, we observed that in PAO1, Vfr protein is essential to the pro-virulent effect of CNP whereas the regulator PtxR supports only a part of the CNP pro-virulent activity. Taken together, these data reinforce the hypothesis that during

Photodynamic characterization of amino acid conjugated 15(1)-hydroxypurpurin-7-lactone for cancer treatment.

PubMed

Lim, Siang Hui; Yam, Mun Li; Lam, May Lynn; Kamarulzaman, Fadzly Azhar; Samat, Norazwana; Kiew, Lik Voon; Chung, Lip Yong; Lee, Hong Boon

2014-09-02

This study aims to improve the photodynamic properties and biological effectiveness of 15(1)-hydroxypurpurin-7-lactone dimethyl ester (G2), a semisynthetic photosensitizer, for the PDT treatment of cancer. The strategy we undertook was by conjugating G2 with aspartic acid and lysine amino acid moieties. The photophysical properties, singlet oxygen generation, distribution coefficiency (Log D in octanol/PBS pH 7.4), and photostability of these analogues and their in vitro bioactivities such as cellular uptake, intracellular localization, and photoinduced cytotoxicity were evaluated. In addition, selected analogues were also investigated for their PDT-induced vasculature occlusion in the chick chorioallantoic membrane model and for their antitumor efficacies in Balb/C mice bearing 4T1 mouse mammary tumor. From the study, conjugation with aspartic acid improved the aqueous solubility of G2 without affecting its photophysical characteristics. G2-Asp showed similar in vitro and in vivo antitumor efficacies compared to the parent compound. Given the hydrophilic nature of G2-Asp, the photosensitizer is a pharmaceutically advantageous candidate as it can be formulated easily for systemic administration and has reduced risk of aggregation in vascular system.

The structure of Pseudomonas P51 Cl-muconate lactonizing enzyme: Co-evolution of structure and dynamics with the dehalogenation function

PubMed Central

Kajander, Tommi; Lehtiö, Lari; Schlömann, Michael; Goldman, Adrian

2003-01-01

Bacterial muconate lactonizing enzymes (MLEs) catalyze the conversion of cis,cis-muconate as a part of the β-ketoadipate pathway, and some MLEs are also able to dehalogenate chlorinated muconates (Cl-MLEs). The basis for the Cl-MLEs dehalogenating activity is still unclear. To further elucidate the differences between MLEs and Cl-MLEs, we have solved the structure of Pseudomonas P51 Cl-MLE at 1.95 Å resolution. Comparison of Pseudomonas MLE and Cl-MLE structures reveals the presence of a large cavity in the Cl-MLEs. The cavity may be related to conformational changes on substrate binding in Cl-MLEs, at Gly52. Site-directed mutagenesis on Pseudomonas MLE core positions to the equivalent Cl-MLE residues showed that the variant Thr52Gly was rather inactive, whereas the Thr52Gly-Phe103Ser variant had regained part of the activity. These residues form a hydrogen bond in the Cl-MLEs. The Cl-MLE structure, as a result of the Thr-to-Gly change, is more flexible than MLE: As a mobile loop closes over the active site, a conformational change at Gly52 is observed in Cl-MLEs. The loose packing and structural motions in Cl-MLE may be required for the rotation of the lactone ring in the active site necessary for the dehalogenating activity of Cl-MLEs. Furthermore, we also suggest that differences in the active site mobile loop sequence between MLEs and Cl-MLEs result in lower active site polarity in Cl-MLEs, possibly affecting catalysis. These changes could result in slower product release from Cl-MLEs and make it a better enzyme for dehalogenation of substrate. PMID:12930985

Simultaneous quantitative determination of 11 sesquiterpene lactones in Jerusalem artichoke (Helianthus tuberosus L.) leaves by ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry.

PubMed

Yuan, Xiaoyan; Yang, Qianxu

2017-04-01

A method of ultra high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry was developed for the simultaneous quantification of 11 sesquiterpene lactones in 11 Jerusalem artichoke leaf samples harvested in a number of areas at different periods. The optimal chromatographic conditions were achieved on a ZORBAX Eclipse Plus C 18 column (3.0 × 150 mm, 1.8 μm) with linear gradient elution of methanol and water in 8 min. Quantitative analysis was carried out under selective ion monitoring mode. All of the sesquiterpene lactones showed good linearity (R 2 ≥ 0.9949), repeatability (relative standard deviations < 4.66%), and intra- and interday precisions (relative standard deviations < 4.52%) with an accuracy of 95.24-104.84%. The recoveries measured at three concentration levels varied from 95.07 to 104.87% with relative standard deviations less than 4.9%. The limit of detection and limit of quantitation for this method were 0.89-5.05 and 1.12-44.33 ng/mL, respectively. The results showed that the contents of sesquiterpene lactones varied significantly in the Jerusalem artichoke leaf samples from different areas. Among them, the content of sesquiterpene lactones in the sample collected from Dalian, Liaoning province was the highest and the early flowering period was considered to be the optimal harvest time. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Weak and Saturable Protein–Surfactant Interactions in the Denaturation of Apo-α-Lactalbumin by Acidic and Lactonic Sophorolipid

PubMed Central

Andersen, Kell K.; Vad, Brian S.; Roelants, Sophie; van Bogaert, Inge N. A.; Otzen, Daniel E.

2016-01-01

Biosurfactants are of growing interest as sustainable alternatives to fossil-fuel-derived chemical surfactants, particularly for the detergent industry. To realize this potential, it is necessary to understand how they affect proteins which they may encounter in their applications. However, knowledge of such interactions is limited. Here, we present a study of the interactions between the model protein apo-α-lactalbumin (apo-aLA) and the biosurfactant sophorolipid (SL) produced by the yeast Starmerella bombicola. SL occurs both as an acidic and a lactonic form; the lactonic form (lactSL) is sparingly soluble and has a lower critical micelle concentration (cmc) than the acidic form [non-acetylated acidic sophorolipid (acidSL)]. We show that acidSL affects apo-aLA in a similar way to the related glycolipid biosurfactant rhamnolipid (RL), with the important difference that RL is also active below the cmc in contrast to acidSL. Using isothermal titration calorimetry data, we show that acidSL has weak and saturable interactions with apo-aLA at low concentrations; due to the relatively low cmc of acidSL (which means that the monomer concentration is limited to ca. 0–1 mM SL), it is only possible to observe interactions with monomeric acidSL at high apo-aLA concentrations. However, the denaturation kinetics of apo-aLA in the presence of acidSL are consistent with a collaboration between monomeric and micellar surfactant species, similar to RL and non-ionic or zwitterionic surfactants. Inclusion of diacetylated lactonic sophorolipid (lactSL) as mixed micelles with acidSL lowers the cmc and this effectively reduces the rate of unfolding, emphasizing that SL like other biosurfactants is a gentle anionic surfactant. Our data highlight the potential of these biosurfactants for future use in the detergent and pharmaceutical industry. PMID:27877155

Uptake, degradation and chiral discrimination of N-acyl-D/L-homoserine lactones by barley (Hordeum vulgare) and yam bean (Pachyrhizus erosus) plants.

PubMed

Götz, Christine; Fekete, Agnes; Gebefuegi, Istvan; Forczek, Sándor T; Fuksová, Kvetoslava; Li, Xiaojing; Englmann, Matthias; Gryndler, Milan; Hartmann, Anton; Matucha, Miroslav; Schmitt-Kopplin, Philippe; Schröder, Peter

2007-11-01

Bacterial intraspecies and interspecies communication in the rhizosphere is mediated by diffusible signal molecules. Many Gram-negative bacteria use N-acyl-homoserine lactones (AHLs) as autoinducers in the quorum sensing response. While bacterial signalling is well described, the fate of AHLs in contact with plants is much less known. Thus, adsorption, uptake and translocation of N-hexanoyl- (C6-HSL), N-octanoyl- (C8-HSL) and N-decanoyl-homoserine lactone (C10-HSL) were studied in axenic systems with barley (Hordeum vulgare L.) and the legume yam bean (Pachyrhizus erosus (L.) Urban) as model plants using ultra-performance liquid chromatography (UPLC), Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) and tritium-labelled AHLs. Decreases in AHL concentration due to abiotic adsorption or degradation were tolerable under the experimental conditions. The presence of plants enhanced AHL decline in media depending on the compounds' lipophilicity, whereby the legume caused stronger AHL decrease than barley. All tested AHLs were traceable in root extracts of both plants. While all AHLs except C10-HSL were detectable in barley shoots, only C6-HSL was found in shoots of yam bean. Furthermore, tritium-labelled AHLs were used to determine short-term uptake kinetics. Chiral separation by GC-MS revealed that both plants discriminated D-AHL stereoisomers to different extents. These results indicate substantial differences in uptake and degradation of different AHLs in the plants tested.

Trypanocidal and Leishmanicidal Activities of Sesquiterpene Lactones from Ambrosia tenuifolia Sprengel (Asteraceae) ▿

PubMed Central

Sülsen, Valeria P.; Frank, Fernanda M.; Cazorla, Silvia I.; Anesini, Claudia A.; Malchiodi, Emilio L.; Freixa, Blanca; Vila, Roser; Muschietti, Liliana V.; Martino, Virginia S.

2008-01-01

Bioassay-guided fractionation of the organic extract of Ambrosia tenuifolia Sprengel (Asteraceae) led to the isolation of two bioactive sesquiterpene lactones with significant trypanocidal and leishmanicidal activities. By spectroscopic methods (1H- and 13C-nuclear magnetic resonance, distortionless enhancement by polarization transfer, correlated spectroscopy, heteronuclear multiple-quantum coherence, electron impact-mass spectrometry, and infrared spectroscopy), these compounds were identified as psilostachyin and peruvin. Both compounds showed a marked in vitro trypanocidal activity against Trypanosoma cruzi epimastigotes with 50% inhibitory concentration (IC50) values of less than 2 μg/ml. Psilostachyin exerted a significant in vitro activity against the trypomastigote forms of T. cruzi (IC50, 0.76 μg/ml) and was selected for in vivo testing. Psilostachyin-treated mice had a survival of 100% and lower parasitemia values than control mice. Both compounds were also tested on Leishmania sp. promastigotes: psilostachyin (IC50, 0.12 μg/ml) and peruvin (IC50, 0.39 μg/ml) exerted significant leishmanicidal activities. This is the first time that the trypanocidal and leishmanicidal activities of these compounds have been reported. The selectivity index (SI) was employed to evaluate the cytotoxic effect of lactones on T lymphocytes. Although the SIs of both compounds were high for T. cruzi epimastigotes, psilostachyin was more selective against trypomastigotes (SI, 33.8) while peruvin showed no specificity for this parasite. Both compounds presented high selectivity for Leishmania spp. The results shown herein suggest that psilostachyin and peruvin could be considered potential candidates for the development of new antiprotozoal agents against Chagas' disease and leishmaniasis. PMID:18443111

Changes in the Salmonella enterica Enteritidis phenotypes in presence of acyl homoserine lactone quorum sensing signals.

PubMed

Campos-Galvão, Maria Emilene Martino; Ribon, Andrea Oliveira Barros; Araújo, Elza Fernandes; Vanetti, Maria Cristina Dantas

2016-05-01

Quorum sensing is used by bacteria to coordinate gene expression in response to population density and involves the production, detection and response to extracellular signaling molecules known as autoinducers (AIs). Salmonella does not synthesize the AI-1, acyl homoserine lactone (AHL) common to gram-negative bacteria; however, it has a receptor for AI-1, the SdiA protein. The effect of SdiA in modulating phenotypes of Salmonella has not been elucidated. In this report, we provide evidence that the AIs-1 affect Salmonella enterica serovar Enteritidis behavior by enhancing the biofilm formation and expression of virulence genes under anaerobic conditions. Biofilm formation by Salmonella was detected by the crystal violet method and by scanning electron microscopy. The presence of AHLs, particularly C12-HSL, increased biofilm formation and promoted expression of biofilm formation genes (lpfA, fimF, fliF, glgC) and virulence genes (hilA, invA, invF). Our results demonstrated that AHLs produced by other organisms played an important role in virulence phenotypes of Salmonella Enteritidis. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Inhibitory role of acyl homoserine lactones in hemolytic activity and viability of Streptococcus pyogenes M6 S165

PubMed Central

Saroj, Sunil D.; Holmer, Linda; Berengueras, Júlia M.; Jonsson, Ann-Beth

2017-01-01

Streptococcus pyogenes an adapted human pathogen asymptomatically colonizes the nasopharynx, among other polymicrobial communities. However, information on the events leading to the colonization and expression of virulence markers subject to interspecies and host-bacteria interactions are limited. The interference of acyl homoserine lactones (AHLs) with the hemolytic activity and viability of S. pyogenes M6 S165 was examined. AHLs, with fatty acid side chains ≥12 carbon atoms, inhibited hemolytic activity by downregulating the expression of the sag operon involved in the production of streptolysin S. Inhibitory AHLs upregulated the expression of transcriptional regulator LuxR. Electrophoretic mobility shift assays revealed the interaction of LuxR with the region upstream of sagA. AHL-mediated bactericidal activity observed at higher concentrations (mM range) was an energy-dependent process, constrained by the requirement of glucose and iron. Ferrichrome transporter FtsABCD facilitated transport of AHLs across the streptococcal membrane. The study demonstrates a previously unreported role for AHLs in S. pyogenes virulence. PMID:28303956

Inhibitory role of acyl homoserine lactones in hemolytic activity and viability of Streptococcus pyogenes M6 S165.

PubMed

Saroj, Sunil D; Holmer, Linda; Berengueras, Júlia M; Jonsson, Ann-Beth

2017-03-17

Streptococcus pyogenes an adapted human pathogen asymptomatically colonizes the nasopharynx, among other polymicrobial communities. However, information on the events leading to the colonization and expression of virulence markers subject to interspecies and host-bacteria interactions are limited. The interference of acyl homoserine lactones (AHLs) with the hemolytic activity and viability of S. pyogenes M6 S165 was examined. AHLs, with fatty acid side chains ≥12 carbon atoms, inhibited hemolytic activity by downregulating the expression of the sag operon involved in the production of streptolysin S. Inhibitory AHLs upregulated the expression of transcriptional regulator LuxR. Electrophoretic mobility shift assays revealed the interaction of LuxR with the region upstream of sagA. AHL-mediated bactericidal activity observed at higher concentrations (mM range) was an energy-dependent process, constrained by the requirement of glucose and iron. Ferrichrome transporter FtsABCD facilitated transport of AHLs across the streptococcal membrane. The study demonstrates a previously unreported role for AHLs in S. pyogenes virulence.

Visible-Light-Promoted Metal-Free Aerobic Oxidation of Primary Amines to Acids and Lactones.

PubMed

Cheng, Xiaokai; Yang, Bo; Hu, Xingen; Xu, Qing; Lu, Zhan

2016-12-05

A unique metal-free aerobic oxidation of primary amines via visible light photocatalytic double carbon-carbon bonds cleavage and multi carbon-hydrogen bonds oxidation was observed. Aerobic oxidation of primary amines could be controlled to afford acids by using dioxane with 18 W CFL, and lactones by using DMF with 8 W green LEDs, respectively. A plausible mechanism was proposed based on control experiments. This observation showed direct evidences for the fragmentation in the aerobic oxidation of aliphatic primary amines. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Authentication of pineapple (Ananas comosus [L.] Merr.) fruit maturity stages by quantitative analysis of γ- and δ-lactones using headspace solid-phase microextraction and chirospecific gas chromatography-selected ion monitoring mass spectrometry (HS-SPME-GC-SIM-MS).

PubMed

Steingass, Christof B; Langen, Johannes; Carle, Reinhold; Schmarr, Hans-Georg

2015-02-01

Headspace solid phase microextraction and chirospecific gas chromatography-mass spectrometry in selected ion monitoring mode (HS-SPME-GC-SIM-MS) allowed quantitative determination of δ-lactones (δ-C8, δ-C10) and γ-lactones (γ-C6, γ-C8, γ-C10). A stable isotope dilution assay (SIDA) with d7-γ-decalactone as internal standard was used for quantitative analysis of pineapple lactones that was performed at three progressing post-harvest stages of fully ripe air-freighted and green-ripe sea-freighted fruits, covering the relevant shelf-life of the fruits. Fresh pineapples harvested at full maturity were characterised by γ-C6 of high enantiomeric purity remaining stable during the whole post-harvest period. In contrast, the enantiomeric purity of γ-C6 significantly decreased during post-harvest storage of sea-freighted pineapples. The biogenetical background and the potential of chirospecific analysis of lactones for authentication and quality evaluation of fresh pineapple fruits are discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Two cytotoxic sesquiterpene lactones from the leaves of Xanthium strumarium and their in vitro inhibitory activity on farnesyltransferase.

PubMed

Kim, Young Sup; Kim, Jeoung Seob; Park, Sung-Hee; Choi, Sang-Un; Lee, Chong Ock; Kim, Seong-Kie; Kim, Young-Kyoon; Kim, Sung Hoon; Ryu, Shi Yong

2003-04-01

Two xanthanolide sesquiterpene lactones, 8- epi-xanthatin (1) and 8- epi-xanthatin epoxide (2), isolated from the leaves of Xanthium strumarium (Compositae), demonstrated a significant inhibition on the proliferation of cultured human tumor cells, i. e., A549 (non-small cell lung), SK-OV-3 (ovary), SK-MEL-2 (melanoma), XF498 (central nervous system) and HCT-15 (colon) in vitro. They were also found to inhibit the farnesylation process of human lamin-B by farnesyltransferase (FTase), in a dose-dependent manner in vitro (IC 50 value was calculated as 64 and 58 microM, respectively). Due to the relatively high concentrations of 1 and 2 required to obtain an FTase inhibition as compared with those necessary for a cytotoxic effect on tumor cells, it remains unclear whether a relationship between these two activities exists.

SYNTHESIS OF ALPHA-AMINO GAMMA-LACTONE VIA A NOVEL TANDEM THREE-COMPONENT REACTION OF ALKENES, GLYOXYLATES AND AMINES. (R822668)

EPA Science Inventory

Abstract

-Amino -lactones were generated by an InCl₃...

Lethal and sub-lethal effects of select macrocyclic lactones insecticides on forager worker honey bees under laboratory experimental conditions.

PubMed

Abdu-Allah, Gamal A M; Pittendrigh, Barry R

2018-01-01

Selective insecticide application is one important strategy for more precisely targeting harmful insects while avoiding or mitigating collateral damage to beneficial insects like honey bees. Recently, macrocyclic lactone-class insecticides have been introduced into the market place as selective bio-insecticides for controlling many arthropod pests, but how to target this selectivity only to harmful insects has yet to be achieved. In this study, the authors investigated the acute toxicity of fourmacrocyclic lactone insecticides (commercialized as abamectin, emamectin benzoate, spinetoram, and spinosad) both topically and through feeding studies with adult forager honey bees. Results indicated emamectin benzoate as topically 133.3, 750.0, and 38.3-fold and orally 3.3, 7.6, and 31.7-fold more toxic, respectively than abamectin, spinetoram and spinosad. Using Hazard Quotients for estimates of field toxicity, abamectin was measured as the safest insecticide both topically and orally for honey bees. Moreover, a significant reduction of sugar solution consumption by treatment group honey bees for orally applied emamectin benzoate and spinetoram suggests that these insecticides may have repellent properties.

Growth inhibition of Candida species by Wickerhamomyces anomalus mycocin and a lactone compound of Aureobasidium pullulans.

PubMed

Tay, Sun-Tee; Lim, Su-Lin; Tan, Hui-Wee

2014-11-08

The increasing resistance of Candida yeasts towards antifungal compounds and the limited choice of therapeutic drugs have spurred great interest amongst the scientific community to search for alternative anti-Candida compounds. Mycocins and fungal metabolites have been reported to have the potential for treatment of fungal infections. In this study, the growth inhibition of Candida species by a mycocin produced by Wickerhamomyces anomalus and a lactone compound from Aureobasidium pullulans were investigated. Mycocin was purified from the culture supernatant of an environmental isolate of W. anomalus using Sephadex G-75 gel filtration column chromatography. The mycocin preparation was subjected to SDS-PAGE analysis followed by MALDI TOF/TOF mass spectrometry analysis. The thermal and temperature stability of the mycocin were determined. The glucanase activity of the mycocin was investigated by substrate staining of the mycocin with 4-methyl-umbelliferyl-ß-D-glucoside (MUG). Gas chromatography mass spectrometry (GCMS) analysis was used to identify anti-Candida metabolite in the culture supernatant of an environmental isolate of Aureobasidium pullulans. The inhibitory effects of the anti-Candida compound against planktonic and biofilm cultures of various Candida species were determined using broth microdilution and biofilm quantitation methods. A mycocin active against Candida mesorugosa but not C. albicans, C. parapsilosis and C. krusei was isolated from the culture supernatant of W. anomalus in this study. The mycocin, identified as exo-ß-1,3 glucanase by MALDI TOF/TOF mass spectrometry, was stable at pH 3-6 and temperature ranging from 4-37°C. The glucanase activity of the mycocin was confirmed by substrate staining with MUG. 5-hydroxy-2-decenoic acid lactone (HDCL) was identified from the culture supernatant of A. pullulans. Using a commercial source of HDCL, the planktonic and biofilm MICs of HDCL against various Candida species were determined in this study

Global and Phylogenetic Distribution of Quorum Sensing Signals, Acyl Homoserine Lactones, in the Family of Vibrionaceae

PubMed Central

Barker Rasmussen, Bastian; Fog Nielsen, Kristian; Machado, Henrique; Melchiorsen, Jette; Gram, Lone; Sonnenschein, Eva C.

2014-01-01

Bacterial quorum sensing (QS) and the corresponding signals, acyl homoserine lactones (AHLs), were first described for a luminescent Vibrio species. Since then, detailed knowledge has been gained on the functional level of QS; however, the abundance of AHLs in the family of Vibrionaceae in the environment has remained unclear. Three hundred and one Vibrionaceae strains were collected on a global research cruise and the prevalence and profile of AHL signals in this global collection were determined. AHLs were detected in 32 of the 301 strains using Agrobacterium tumefaciens and Chromobacterium violaceum reporter strains. Ethyl acetate extracts of the cultures were analysed by ultra-high performance liquid chromatography-high resolution mass spectrometry (MS) with automated tandem MS confirmation for AHLs. N-(3-hydroxy-hexanoyl) (OH-C6) and N-(3-hydroxy-decanoyl) (OH-C10) homoserine lactones were the most common AHLs found in 17 and 12 strains, respectively. Several strains produced a diversity of different AHLs, including N-heptanoyl (C7) HL. AHL-producing Vibrionaceae were found in polar, temperate and tropical waters. The AHL profiles correlated with strain phylogeny based on gene sequence homology, however not with geographical location. In conclusion, a wide range of AHL signals are produced by a number of clades in the Vibrionaceae family and these results will allow future investigations of inter- and intra-species interactions within this cosmopolitan family of marine bacteria. PMID:25419995

7-epi-griffonilide, a new lactone from Bauhinia pentandra: complete 1H and 13C chemical shift assignments.

PubMed

Almeida, Macia C S DE; Souza, Luciana G S; Ferreira, Daniele A; Pinto, Francisco C L; Oliveira, Débora R DE; Santiago, Gilvandete M P; Monte, Francisco J Q; Braz-Filho, Raimundo; Lemos, Telma L G DE

2017-01-01

A new lactone, 7-epi-griffonilide (1), and six known compounds, 2, 3a - 3c, 4a and 4b, were isolated from the leaves of Bauhinia pentandra (Fabaceae). The structures elucidation of 1 and 2 were based on detailed 2D NMR techniques and spectral comparison with related compounds, leading to complete assignment of the 1H and 13C NMR spectra.

P-glycoprotein, but not Multidrug Resistance Protein 4, Plays a Role in the Systemic Clearance of Irinotecan and SN-38 in Mice

PubMed Central

Tagen, Michael; Zhuang, Yanli; Zhang, Fan; Harstead, K. Elaine; Shen, Jun; Schaiquevich, Paula; Fraga, Charles H.; Panetta, John C.; Waters, Christopher M.; Stewart, Clinton F.

2015-01-01

The ATP-binding cassette transporters P-glycoprotein (ABCB1, MDR1) and multidrug resistance protein 4 (MRP4) efflux irinotecan and its active metabolite SN-38 in vitro, and thus may contribute to system clearance of these compounds. Mdr1a/b−/−, Mrp4−/−, and wild-type mice were administered 20 or 40 mg/kg irinotecan, and plasma samples were collected for 6 hours. Irinotecan and SN-38 lactone and carboxylate were quantitated and data were analyzed with nonlinear mixed-effects modeling. Mdr1a/b genotype was a significant covariate for the clearance of both irinotecan lactone and SN-38 lactone. Exposures to irinotecan lactone and SN-38 lactone after a 40 mg/kg dose were 1.6-fold higher in Mdr1a/b−/− mice compared to wild-type mice. Plasma concentrations of irinotecan lactone, irinotecan carboxylate, and SN-38 lactone in Mrp4−/− mice were similar to the wild-type controls. These results suggest that P-gp plays a role in irinotecan and SN-38 elimination, but Mrp4 does not affect irinotecan or SN-38 plasma pharmacokinetics. PMID:20583968

Targeting N-acyl-homoserine-lactones to mitigate membrane biofouling based on quorum sensing using a biofouling reducer.

PubMed

Siddiqui, Muhammad Faisal; Sakinah, Mimi; Singh, Lakhveer; Zularisam, A W

2012-10-31

Exploring novel biological anti-quorum sensing (QS) agents to control membrane biofouling is of great worth in order to allow sustainable performance of membrane bioreactors (MBRs) for wastewater treatment. In recent studies, QS inhibitors have provided evidence of alternative route to control membrane biofouling. This study investigated the role of Piper betle extract (PBE) as an anti-QS agent to mitigate membrane biofouling. Results demonstrated the occurrence of the N-acyl-homoserine-lactone (AHL) autoinducers (AIs), correlate QS activity and membrane biofouling mitigation. The AIs production in bioreactor was confirmed using an indicator strain Agrobacterium tumefaciens (NTL4) harboring plasmid pZLR4. Moreover, three different AHLs were found in biocake using thin layer chromatographic analysis. An increase in extracellular polymeric substances (EPS) and transmembrane pressure (TMP) was observed with AHL activity of the biocake during continuous MBR operation, which shows that membrane biofouling was in close relationship with QS activity. PBE was verified to mitigate membrane biofouling via inhibiting AIs production. SEM analysis further confirmed the effect of PBE on EPS and biofilm formation. These results exhibited that PBE could be a novel agent to target AIs for mitigation of membrane biofouling. Further work can be carried out to purify the active compound of Piper betle extract to target the QS to mitigate membrane biofouling. Copyright © 2012 Elsevier B.V. All rights reserved.

Preliminary study on an innovative, simple mast cell-based electrochemical method for detecting foodborne pathogenic bacterial quorum signaling molecules (N-acyl-homoserine-lactones).

PubMed

Jiang, Donglei; Feng, Dongdong; Jiang, Hui; Yuan, Limin; Yongqi, Yin; Xu, Xin; Fang, Weiming

2017-04-15

This paper reports the a novel and simple mast cell-based electrochemical method for detecting of bacterial quorum signaling molecules, N-acylhomoserine lactones (AHLs), which can be utilized to preliminarily evaluate the toxicity of food-borne pathogenic bacteria. Rat basophilic leukemia (RBL-2H3) mast cells encapsulated in alginate/graphene oxide hydrogel were immobilized on a gold electrode, while mast cells as recognition elements were cultured in a 3D cell culture system. Electrochemical impedance spectroscopy (EIS) was utilized to record the cell impedance signal as-influenced by Pseudomonas aeruginosa quorum-sensing molecule, N-3-oxododecanoyl homoserine lactone (3OC 12 -HSL). The results indicated that cellular activities such as cell viability, apoptosis, intracellular calcium, and degranulation were markedly influenced by the AHLs. Importantly, the exposure of 3OC 12 -HSL to mast cells induced a marked decrease in the electrochemical impedance signal in a dose-dependent manner. The detection limit for 3OC 12 -HSL was 0.034μM with a linear range of 0.1-1μM. These results were confirmed via conventional cell assay and transmission electron microscope (TEM) analysis. Altogether, the proposed method appears to be an innovative and effective approach to the quantitative measurement of Gram-negative bacterial quorum signaling molecules; to this effect, it also may serve as a primary evaluation of the cytotoxicity of food-borne pathogens. Copyright © 2016 Elsevier B.V. All rights reserved.

Loss of mitochondrial transmembrane potential and caspase-9 activation during apoptosis induced by the novel styryl-lactone goniothalamin in HL-60 leukemia cells.

PubMed

Inayat-Hussain, S H; Annuar, B O; Din, L B; Ali, A M; Ross, D

2003-08-01

Styryl-lactones such as goniothalamin represent a new class of compounds with potential anti-cancer properties. In this study, we investigated the mechanisms of goniothalamin (GTN), a plant styryl-lactone induced apoptosis in human promyelocytic leukemia HL-60 cells. This plant extract resulted in apoptosis in HL-60 cells as assessed by the externalisation of phosphatidylserine. Using the mitochondrial membrane dye (DIOC(6)) in conjunction with flow cytometry, we found that GTN treated HL-60 cells demonstrated a loss of mitochondrial transmembrane potential (Deltapsi(m)). Further immunoblotting on these cells showed activation of initiator caspase-9 and the executioner caspases-3 and -7. Pretreatment with the pharmacological caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp fluoromethyl ketone (Z-VAD.FMK) abrogated apoptosis as assessed by all of the apoptotic features in this study. In summary, our results demonstrate that goniothalamin-induced apoptosis occurs via the mitochondrial pathway in a caspase dependent manner.

Replacement of the lactone moiety on podophyllotoxin and steganacin analogues with a 1,5-disubstituted 1,2,3-triazole via ruthenium-catalyzed click chemistry.

PubMed

Imperio, Daniela; Pirali, Tracey; Galli, Ubaldina; Pagliai, Francesca; Cafici, Laura; Canonico, Pier Luigi; Sorba, Giovanni; Genazzani, Armando A; Tron, Gian Cesare

2007-11-01

Steganacin and podophyllotoxin are two naturally occurring lignans first isolated from plant sources, which share the capability to disrupt tubulin assembly. Although not strictly essential for its activity, the lactone ring on both structures represents Achilles' heel, as it is a potential site of metabolic degradation and epimerization on its C2 carbon brings about a significant loss in potency. In the present manuscript, we have used the ruthenium-catalyzed [3+2] azide-alkyne cycloaddition, a click-chemistry reaction, to replace the lactone ring with a 1,5-disubstituted triazole in few synthetic steps. The compounds were cytotoxic, although to a lesser degree compared to podophyllotoxin, while retaining antitubulin activity. The present structures might therefore represent a good platform for the fast generation of metabolically stable compounds with few stereogenic centers that might be of value from a medicinal chemistry point of view.

Paraoxonase 2 modulates a proapoptotic function in LS174T cells in response to quorum sensing molecule N-(3-oxododecanoyl)-L-homoserine lactone

PubMed Central

Tao, Shiyu; Luo, Yanwen; Bin He; Liu, Jie; Qian, Xi; Ni, Yingdong; Zhao, Ruqian

2016-01-01

A mucus layer coats the gastrointestinal tract and serves as the first line of intestinal defense against infection. N-acyl-homoserine lactone (AHL) quorum-sensing molecules produced by gram-negative bacteria in the gut can influence the homeostasis of intestinal epithelium. In this study, we investigated the effects of two representative long- and short-chain AHLs, N-3-(oxododecanoyl)-homoserine lactone (C12-HSL) and N-butyryl homoserine lactone (C4-HSL), on cell viability and mucus secretion in LS174T cells. C12-HSL but not C4-HSL significantly decreased cell viability by inducing mitochondrial dysfunction and activating cell apoptosis which led to a decrease in mucin expression. Pretreatment with lipid raft disruptor (Methyl-β-cyclodextrin, MβCD) and oxidative stress inhibitor (N-acetyl-L-cysteine, NAC) slightly rescued the viability of cells damaged by C12-HSL exposure, while the paraoxonase 2 (PON2) inhibitor (Triazolo[4,3-a]quinolone, TQ416) significantly affected recovering cells viability and mucin secretion. When LS174T cells were treated with C12-HSL and TQ416 simultaneously, TQ416 showed the maximal positive effect on cells viability. However, if cells were first treated with C12-HSL for 40 mins, and then TQ46 was added, the TQ416 had no effect on cell viability. These results suggest that the C12-HSL-acid process acts at an early step to activate apoptosis as part of C12-HSL’s effect on intestinal mucus barrier function. PMID:27364593

A Method for the Simultaneous Determination of Chlorogenic Acid and Sesquiterpene Lactone Content in Industrial Chicory Root Foodstuffs

PubMed Central

Hance, Philippe; Fertin, Anne; Voedts, Najia; Duhal, Nathalie; Goossens, Jean-François; Hilbert, Jean-Louis

2014-01-01

A method for the simultaneous determination of free chlorogenic acids (CGA) and sesquiterpene lactones (STL) in chicory root and its dried (flour) and roasted (grain) forms is described. The method uses one extraction and one analysis for all chicory root products. Various solvents with low to high polarity, such as methanol, chloroform, or n-hexane, were tested alone, in combination in different proportions or with acidified or neutral aqueous solvent. The water/chloroform/methanol (30/30/40, v/v/v) mixture generated the best extraction yield, 21% higher than alcohol mixtures. The profiling of CGA and STL content was performed through a conventional HPLC-DAD method using a PFP core shell column in a fast single run. Good retention time and area repeatability (RDD mean % 0.46 and 5.6, resp.) and linearity (R 2 ≥ 0.96) were obtained. The STL and chlorogenic acids levels determined were 254.7 and 100.2 μg/g of dry matter in the root, 792.5 and 1,547 μg/g in flour, and 160.4 and 822.5 μg/g in the roasted grains, respectively. With an average recovery of 106% and precision of 90%, this method is rapid, reproducible, and straightforward way to quantify the chlorogenic acids and STL in chicory raw material and end products. PMID:25548785

Formal [4+2] cycloaddition of di-tert-butyl 2-ethoxycyclobutane-1,1-dicarboxylate with ketones or aldehydes and tandem lactonization.

PubMed

Okado, Ryohei; Nowaki, Aya; Matsuo, Jun-Ichi; Ishibashi, Hiroyuki

2012-01-01

A catalytic amount of tin(IV) chloride catalyzed formal [4+2] cycloaddition reaction of di-tert-butyl 2-ethoxycyclobutane-1,1-carboxylate with ketones or aldehydes to give diethyl 6-ethoxydihydro-2H-pyran-3,3(4H)-dicarboxylates, whereas two equivalents of trimethylsilyl triflate promoted tandem [4+2] cycloaddition and lactonization to afford 3-oxo-2,6-dioxabicyclo[2.2.2]octane-4-carboxylate esters.

Biochar and microbial signaling: production conditions determine effects on microbial communication.

PubMed

Masiello, Caroline A; Chen, Ye; Gao, Xiaodong; Liu, Shirley; Cheng, Hsiao-Ying; Bennett, Matthew R; Rudgers, Jennifer A; Wagner, Daniel S; Zygourakis, Kyriacos; Silberg, Jonathan J

2013-10-15

Charcoal has a long soil residence time, which has resulted in its production and use as a carbon sequestration technique (biochar). A range of biological effects can be triggered by soil biochar that can positively and negatively influence carbon storage, such as changing the decomposition rate of organic matter and altering plant biomass production. Sorption of cellular signals has been hypothesized to underlie some of these effects, but it remains unknown whether the binding of biochemical signals occurs, and if so, on time scales relevant to microbial growth and communication. We examined biochar sorption of N-3-oxo-dodecanoyl-L-homoserine lactone, an acyl-homoserine lactone (AHL) intercellular signaling molecule used by many gram-negative soil microbes to regulate gene expression. We show that wood biochars disrupt communication within a growing multicellular system that is made up of sender cells that synthesize AHL and receiver cells that express green fluorescent protein in response to an AHL signal. However, biochar inhibition of AHL-mediated cell-cell communication varied, with the biochar prepared at 700 °C (surface area of 301 m(2)/g) inhibiting cellular communication 10-fold more than an equivalent mass of biochar prepared at 300 °C (surface area of 3 m(2)/g). These findings provide the first direct evidence that biochars elicit a range of effects on gene expression dependent on intercellular signaling, implicating the method of biochar preparation as a parameter that could be tuned to regulate microbial-dependent soil processes, like nitrogen fixation and pest attack of root crops.

Biochar and microbial signaling: production conditions determine effects on microbial communication

PubMed Central

Masiello, Caroline A.; Chen, Ye; Gao, Xiaodong; Liu, Shirley; Cheng, Hsiao-Ying; Bennett, Matthew R.; Rudgers, Jennifer A.; Wagner, Daniel S.; Zygourakis, Kyriacos; Silberg, Jonathan J.

2013-01-01

Charcoal has a long soil residence time, which has resulted in its production and use as a carbon sequestration technique (biochar). A range of biological effects can be triggered by soil biochar that can positively and negatively influence carbon storage, such as changing the decomposition rate of organic matter and altering plant biomass production. Sorption of cellular signals has been hypothesized to underlie some of these effects, but it remains unknown whether the binding of biochemical signals occurs, and if so, on time scales relevant to microbial growth and communication. We examined biochar sorption of N-3-oxo-dodecanoyl-L-homoserine lactone, an acyl-homoserine lactone (AHL) intercellular signaling molecule used by many gram-negative soil microbes to regulate gene expression. We show that wood biochars disrupt communication within a growing multicellular system that is made up of sender cells that synthesize AHL and receiver cells that express green fluorescent protein in response to an AHL signal. However, biochar inhibition of AHL-mediated cell-cell communication varied, with the biochar prepared at 700°C (surface area of 301 m2/g) inhibiting cellular communication 10-fold more than an equivalent mass of biochar prepared at 300°C (surface area of 3 m2/g). These findings provide the first direct evidence that biochars elicit a range of effects on gene expression dependent on intercellular signaling, implicating the method of biochar preparation as a parameter that could be tuned to regulate microbial-dependent soil processes, like nitrogen fixation and pest attack of root crops. PMID:24066613

Pharmacokinetics of the prototype and hydrolyzed carboxylic forms of ginkgolides A, B, and K administered as a ginkgo diterpene lactones meglumine injection in beagle dogs.

PubMed

Wang, Shu-Yao; A, Ji-Ye; Fei, Fei; Geng, Jian-Liang; Peng, Ying; Ouyang, Bing-Chen; Wang, Pei; Jin, Xiao-Liang; Zhao, Yu-Qing; Wang, Jian-Kun; Geng, Ting; Li, Yan-Jing; Huang, Wen-Zhe; Wang, Zhen-Zhong; Xiao, Wei; Wang, Guang-Ji

2017-10-01

Ginkgo diterpene lactones meglumine injection (GDLI) is a commercially available product used for neuroprotection. However, the pharmacokinetic properties of the prototypes and hydrolyzed carboxylic forms of the primary components in GDLI, i.e., ginkgolide A (GA), ginkgolide B (GB), and ginkgolide K (GK), have never been fully evaluated in beagle dogs. In this work, a simple, sensitive, and reliable method based on ultra-fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) was developed, and the prototypes and total amounts of GA, GB, and GK were determined in beagle dog plasma. The plasma concentrations of the hydrolyzed carboxylic forms were calculated by subtracting the prototype concentrations from the total lactone concentrations. For the first time, the pharmacokinetics of GA, GB, and GK were fully assessed in three forms, i.e., the prototypes, the hydrolyzed carboxylic forms, and the total amounts, after intravenous administration of GDLI in beagle dogs. It was shown that ginkgolides primarily existed in the hydrolyzed form in plasma, and the ratio of hydrolysates to prototype forms of GA and GB decreased gradually to a homeostatic ratio. All of the three forms of the three ginkgolides showed linear exposure of AUC to the dosages. GA, GB, and GK showed a constant half-life approximately 2.7, 3.4, and 1.2 h, respectively, which were consistent for the forms at three dose levels (0.3, 1.0, and 3.0 mg·kg -1 ) and after a consecutive injection of GDLI for 7 days (1.0 mg·kg -1 ). Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

(+)-Methyl 3β-acet­oxy-13-carb­oxy-19-hy­droxy-11-oxo-C-norolean-18-en-30-oate γ-lactone

PubMed Central

Gaware, Rawindra; Czollner, Laszlo; Jordis, Ulrich; Mereiter, Kurt

2010-01-01

The title compound, C33H46O7, is an unusual oxydation product of the therapeutic agent glycyrrhetinic acid that has, in comparison to the latter, a distinctly altered triterpene structure with one five- and four six-membered carbocycles complemented by a γ-lactone ring with a spiro-junction and a ring double bond. The junction between the five-membered ring C, a cyclo­penta­none ring, and the six-membered ring D, previously in question, was found to be cis, confirming earlier structure assignments based solely on chemical transformations. In the solid state, the compound exhibits five intra- and four inter­molecular C—H⋯O inter­actions with H⋯O distances less than or equal to 2.70 Å and C—H⋯O greater than 100°. PMID:21587575

Regulation of Long-Chain N-Acyl-Homoserine Lactones in Agrobacterium vitis

PubMed Central

Hao, Guixia; Burr, Thomas J.

2006-01-01

Homologs of quorum-sensing luxR and luxI regulatory genes, avsR and avsI, were identified in Agrobacterium vitis strain F2/5. Compared to other LuxI proteins from related species, the deduced AvsI shows the greatest identity to SinI (71%) from Sinorhizobium meliloti Rm1021. AvsR possesses characteristic autoinducer binding and helix-turn-helix DNA binding domains and shares a high level of identity with SinR (38%) from Rm1021. Site-directed mutagenesis of avsR and avsI was performed, and both genes are essential for hypersensitive-like response (HR) and necrosis. Two hypothetical proteins (ORF1 and ORF2) that are positioned downstream of avsR-avsI are also essential for the phenotypes. Profiles of N-acyl-homoserine lactones (AHLs) isolated from the wild type and mutants revealed that disruption of avsI, ORF1, or ORF2 abolished the production of long-chain AHLs. Disruption of avsR reduces long-chain AHLs. Expression of a cloned avsI gene in A. tumefaciens strain NT1 resulted in synthesis of long-chain AHLs. The necrosis and HR phenotypes of the avsI and avsR mutants were fully complemented with cloned avsI. The addition of synthetic AHLs (C16:1 and 3-O-C16:1) complemented grape necrosis in the avsR, avsI, ORF1, and ORF2 mutants. It was determined by reverse transcriptase PCR that the expression level of avsI is regulated by avsR but not by aviR or avhR, two other luxR homologs which were previously shown to be associated with induction of a tobacco hypersensitive response and grape necrosis. We further verified that avsR regulates avsI by measuring the expression of an avsI::lacZ fusion construct. PMID:16513747

Acyl-homoserine-lactone autoinducer (AHL) in the gastrointestinal tract of feedlot cattle and correlation to season, E. coli 0157:H7 prevalence and diet

USDA-ARS?s Scientific Manuscript database

Acyl-homoserine-lactone autoinducer (AHL) produced by non-enterohemorrhagic E. coli (EHEC) species in cattle appears to be required for EHEC colonization of the gastro¬intestinal tract (GIT). The objectives of the current research were to examine the effect of season, diet, EHEC shedding, and locat...

Quorum Sensing Activity of Serratia fonticola Strain RB-25 Isolated from an Ex-landfill Site

PubMed Central

Ee, Robson; Lim, Yan-Lue; Tee, Kok-Keng; Yin, Wai-Fong; Chan, Kok-Gan

2014-01-01

Quorum sensing is a unique bacterial communication system which permits bacteria to synchronize their behaviour in accordance with the population density. The operation of this communication network involves the use of diffusible autoinducer molecules, termed N-acylhomoserine lactones (AHLs). Serratia spp. are well known for their use of quorum sensing to regulate the expression of various genes. In this study, we aimed to characterized the AHL production of a bacterium designated as strain RB-25 isolated from a former domestic waste landfill site. It was identified as Serratia fonticola using matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry analysis and this was confirmed by 16S ribosomal DNA sequencing. High resolution triple quadrupole liquid chromatography-mass spectrometry analysis of S. fonticola strain RB-25 spent culture supernatant indicated the existence of three AHLs namely: N-butyryl-L-homoserine lactone (C4-HSL), N-hexanoyl-L-homoserine lactone (C6-HSL) and N-(3-oxohexanoyl) homoserine-lactone (3-oxo-C6 HSL). This is the first report of the production of these AHLs in S. fonticola. PMID:24625739

Biosynthetic studies on the botcinolide skeleton: new hydroxylated lactones from Botrytis cinerea.

PubMed

Reino, José L; Durán-Patrón, Rosa M; Daoubi, Mourad; Collado, Isidro G; Hernández-Galán, Rosario

2006-01-20

[reaction: see text] The biosynthetic origin of the botcinolide skeleton was investigated by means of feeding 13C- and 2H-labeled precursors to Botrytis cinerea. Three new compounds, two homobotcinolide derivatives, 3-O-acetylhomobotcinolide (5) and 8-methylhomobotcinolide (6), and a new 11-membered lactone (7), were isolated. Their structures were elucidated on the basis of spectroscopic data, including one-bond and long-range 1H-13C correlations. The relative stereochemistries were determined by combined analyses of NOE data and 1H-1H coupling constants. According to the results of feeding experiments with 13C- and 2H-labeled acetate and l-S-methylmethionine, 5 is an acetate-derived polyketide whose methyl groups originate from l-S-methylmethionine. This is a rare example of the incorporation of a methyl from methionine into a supposed C3 starter unit of the polyketide synthesis.

Macrocyclic lactones in the treatment and control of parasitism in small companion animals.

PubMed

Nolan, Thomas J; Lok, James B

2012-05-01

Macrocyclic lactones (MLs) have many anti-parasitic applications in small companion animal medicine. They were first developed as chemoprophylactics against heartworm (Dirofilaria immitis) infection to be applied monthly for retroactive killing of third- and fourth-stage larvae. ML-containing products formulated for oral (ivermectin, milbemycin oxime), topical (selamectin, moxidectin) or injectable sustained release (moxidectin, ivermectin) are approved for heartworm prevention in dogs or cats. Clearance of microfilariae and gradual or "soft" killing of adult heartworms constitute increasingly prevalent extra-label uses of MLs against D. immitis. Some commercial ML formulations contain sufficient levels of active ingredient (milbemycin oxime, selamectin, moxidectin) to support additional label claims against gastrointestinal nematode parasites such as hookworms (Ancylostoma spp.) and ascarid round worms (Toxocara spp. and Toxascaris leonina). Beyond these approved applications, safe, extra-label uses of MLs against nematodes parasitizing the urinary tract, such as Capillaria spp., and parasites of the tissues, such as Dipetalonema reconditum, Dirofilaria repens, Thelazia spp. and Spirocerca lupi, in dogs and cats as well as exotic pets have been reported. MLs as a group have intrinsic insecticidal and acaricidal activity, and topical or otic formulations of certain compounds (selamectin, moxidectin, milbemycin oxime or ivermectin) are approved for treatment and control of fleas, certain ixodid ticks, sarcoptiform and demodectic mange mites and psoroptiform ear mites. Extra-label applications of MLs against ectoparasites include notoedric mange mites, dermanyssids such as Ornythonussus bacoti, numerous species of fur mite (e.g. Cheyletiella spp. and Lynxacarus) and trombiculids ("chiggers") in cats, dogs and nontraditional or exotic pets.

The Nonartemisinin Sesquiterpene Lactones Parthenin and Parthenolide Block Plasmodium falciparum Sexual Stage Transmission

PubMed Central

Balaich, Jared N.; Mathias, Derrick K.; Torto, Baldwyn; Jackson, Bryan T.; Tao, Dingyin; Ebrahimi, Babak; Tarimo, Brian B.; Cheseto, Xavier; Foster, Woodbridge A.

2016-01-01

Parthenin and parthenolide are natural products that are closely related in structure to artemisinin, which is also a sesquiterpene lactone (SQL) and one of the most important antimalarial drugs available. Parthenin, like artemisinin, has an effect on Plasmodium blood stage development. We extended the evaluation of parthenin as a potential therapeutic for the transmissible stages of Plasmodium falciparum as it transitions between human and mosquito, with the aim of gaining potential mechanistic insight into the inhibitory activity of this compound. We posited that if parthenin targets different biological pathways in the parasite, this in turn could pave the way for the development of druggable compounds that could prevent the spread of artemisinin-resistant parasites. We examined parthenin's effect on male gamete activation and the ookinete-to-oocyst transition in the mosquito as well as on stage V gametocytes that are present in peripheral blood. Parthenin arrested parasite development for each of the stages tested. The broad inhibitory properties of parthenin on the evaluated parasite stages may suggest different mechanisms of action between parthenin and artemisinin. Parthenin's cytotoxicity notwithstanding, its demonstrated activity in this study suggests that structurally related SQLs with a better safety profile deserve further exploration. We used our battery of assays to test parthenolide, which has a more compelling safety profile. Parthenolide demonstrated activity nearly identical to that of parthenin against P. falciparum, highlighting its potential as a possible transmission-blocking drug scaffold. We discuss the context of the evidence with respect to the next steps toward expanding the current antimalarial arsenal. PMID:26787692

The Nonartemisinin Sesquiterpene Lactones Parthenin and Parthenolide Block Plasmodium falciparum Sexual Stage Transmission.

PubMed

Balaich, Jared N; Mathias, Derrick K; Torto, Baldwyn; Jackson, Bryan T; Tao, Dingyin; Ebrahimi, Babak; Tarimo, Brian B; Cheseto, Xavier; Foster, Woodbridge A; Dinglasan, Rhoel R

2016-04-01

Parthenin and parthenolide are natural products that are closely related in structure to artemisinin, which is also a sesquiterpene lactone (SQL) and one of the most important antimalarial drugs available. Parthenin, like artemisinin, has an effect onPlasmodiumblood stage development. We extended the evaluation of parthenin as a potential therapeutic for the transmissible stages ofPlasmodium falciparumas it transitions between human and mosquito, with the aim of gaining potential mechanistic insight into the inhibitory activity of this compound. We posited that if parthenin targets different biological pathways in the parasite, this in turn could pave the way for the development of druggable compounds that could prevent the spread of artemisinin-resistant parasites. We examined parthenin's effect on male gamete activation and the ookinete-to-oocyst transition in the mosquito as well as on stage V gametocytes that are present in peripheral blood. Parthenin arrested parasite development for each of the stages tested. The broad inhibitory properties of parthenin on the evaluated parasite stages may suggest different mechanisms of action between parthenin and artemisinin. Parthenin's cytotoxicity notwithstanding, its demonstrated activity in this study suggests that structurally related SQLs with a better safety profile deserve further exploration. We used our battery of assays to test parthenolide, which has a more compelling safety profile. Parthenolide demonstrated activity nearly identical to that of parthenin againstP. falciparum, highlighting its potential as a possible transmission-blocking drug scaffold. We discuss the context of the evidence with respect to the next steps toward expanding the current antimalarial arsenal. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Biomass pre-treatment for co-production of high-concentration C5- and C6-carbohydrates and their derivatives

DOEpatents

Dumesic, James A.; Martin Alonso, David; Luterbacher, Jeremy Scott

2016-06-07

Described is a method of processing biomass to separate it into a liquid fraction enriched in solubilized C5-sugar-containing oligomers and C-5 sugar monomers and a solid fraction enriched in substantially insoluble cellulose and C6-sugar-containing oligomers. The method includes the steps of reacting biomass with a solvent system comprising water, at least one lactone, or at least one furan, or at least one cyclic ether, and at least one acid, for a time and at a temperature to yield the liquid and solid fractions. The liquid and solid fractions may then be separated. Gamma-valeroloactone is a preferred lactone for use in the solvent system. Tetrahydrofuran is a preferred furan species for use in the solvent system.

In vitro antiplasmodial and cytotoxic activities of sesquiterpene lactones from Vernonia fimbrillifera Less. (Asteraceae).

PubMed

Bordignon, Annélise; Frédérich, Michel; Ledoux, Allison; Campos, Pierre-Eric; Clerc, Patricia; Hermann, Thomas; Quetin-Leclercq, Joëlle; Cieckiewicz, Ewa

2018-06-01

Due to the in vitro antiplasmodial activity of leaf extracts from Vernonia fimbrillifera Less. (Asteraceae), a bioactivity-guided fractionation was carried out. Three sesquiterpene lactones were isolated, namely 8-(4'-hydroxymethacrylate)-dehydromelitensin (1), onopordopicrin (2) and 8α-[4'-hydroxymethacryloyloxy]-4-epi-sonchucarpolide (3). Their structures were elucidated by spectroscopic methods (1D and 2D NMR and MS analyses) and by comparison with published data. The isolated compounds exhibited antiplasmodial activity with IC 50 values ≤ 5 μg/mL. Cytotoxicity of the compounds against a human cancer cell line (HeLa) and a mouse lung epithelial cell line (MLE12) was assessed to determine selectivity. Compound 3 displayed promising selective antiplasmodial activity (SI > 10).

Diverse profiles of N-acyl-homoserine lactones in biofilm forming strains of Cronobacter sakazakii.

PubMed

Singh, Niharika; Patil, Amrita; Prabhune, Asmita A; Raghav, Mamta; Goel, Gunjan

2017-04-03

The present study investigates the role of quorum sensing (QS) molecules expressed by C. sakazakii in biofilm formation and extracellular polysaccharide expression. The QS signaling was detected using Chromobacterium violaceum 026 and Agrobacterium tumefaciens NTL4(pZLR4) based bioassay. Long chain N-acyl-homoserine lactones (AHLs) with C6- C18 chain length were identified using High Performance Liquid Chromatography and Liquid Chromatography-High Resolution Mass Spectrometry. A higher Specific Biofilm Formation (SBF) index (p < 0.05) with the presence of genes associated with cellulose biosynthesis (bcsA, bcsC and bcsG) was observed in the strains. AHLs and their mechanisms can serve as novel targets for developing technologies to eradicate and prevent biofilm formation by C. sakazakii.

A novel lactone-forming carboxylesterase: molecular identification of a tuliposide A-converting enzyme in tulip.

PubMed

Nomura, Taiji; Ogita, Shinjiro; Kato, Yasuo

2012-06-01

Tuliposides, the glucose esters of 4-hydroxy-2-methylenebutanoate and 3,4-dihydroxy-2-methylenebutanoate, are major secondary metabolites in tulip (Tulipa gesneriana). Their lactonized aglycons, tulipalins, function as defensive chemicals due to their biological activities. We recently found that tuliposide-converting enzyme (TCE) purified from tulip bulbs catalyzed the conversion of tuliposides to tulipalins, but the possibility of the presence of several TCE isozymes was raised: TCE in tissues other than bulbs is different from bulb TCE. Here, to prove this hypothesis, TCE was purified from petals, which have the second highest TCE activity after bulbs. The purified enzyme, like the bulb enzyme, preferentially accepted tuliposides as substrates, with 6-tuliposide A the best substrate, which allowed naming the enzyme tuliposide A-converting enzyme (TCEA), but specific activity and molecular mass differed between the petal and bulb enzymes. After peptide sequencing, a novel cDNA (TgTCEA) encoding petal TCEA was isolated, and the functional characterization of the recombinant enzyme verified that TgTCEA catalyzes the conversion of 6-tuliposide A to tulipalin A. TgTCEA was transcribed in all tulip tissues but not in bulbs, indicating the presence of a bulb-specific TgTCEA, as suggested by the distinct enzymatic characters between the petal and bulb enzymes. Plastidial localization of TgTCEA enzyme was revealed, which allowed proposing a cytological mechanism of TgTCE-mediated tulipalin formation in the tulip defensive strategy. Site-directed mutagenesis of TgTCEA suggested that the oxyanion hole and catalytic triad characteristic of typical carboxylesterases are essential for the catalytic process of TgTCEA enzyme. To our knowledge, TgTCEA is the first identified member of the lactone-forming carboxylesterases, specifically catalyzing intramolecular transesterification.

Root production method system

Treesearch

Wayne Lovelace

2002-01-01

The RPM system (Root Production Method) is a multistep production system of container tree production that places primary emphasis on the root system because the root system ultimately determines the tree's survival and performance in its outplanted environment. This particular container production system has been developed to facilitate volume production, in a...

Rapid Acyl-Homoserine Lactone Quorum Signal Biodegradation in Diverse Soils†

PubMed Central

Wang, Ya-Juan; Leadbetter, Jared Renton

2005-01-01

Signal degradation impacts all communications. Although acyl-homoserine lactone (acyl-HSL) quorum-sensing signals are known to be degraded by defined laboratory cultures, little is known about their stability in nature. Here, we show that acyl-HSLs are biodegraded in soils sampled from diverse U.S. sites and by termite hindgut contents. When amended to samples at physiologically relevant concentrations, 14C-labeled acyl-HSLs were mineralized to 14CO2 rapidly and, at most sites examined, without lag. A lag-free turf soil activity was characterized in further detail. Heating or irradiation of the soil prior to the addition of radiolabel abolished mineralization, whereas protein synthesis inhibitors did not. Mineralization exhibited an apparent Km of 1.5 μM acyl-HSL, ca. 1,000-fold lower than that reported for a purified acyl-HSL lactonase. Under optimal conditions, acyl-HSL degradation proceeded at a rate of 13.4 nmol · h−1 · g of fresh weight soil−1. Bioassays established that the final extent of signal inactivation was greater than for its full conversion to CO2 but that the two processes were well coupled kinetically. A most probable number of 4.6 × 105 cells · g of turf soil−1 degraded physiologically relevant amounts of hexanoyl-[1-14C]HSL to 14CO2. It would take chemical lactonolysis months to match the level of signal decay achieved in days by the observed biological activity. Rapid decay might serve either to quiet signal cross talk that might otherwise occur between spatially separated microbial aggregates or as a full system reset. Depending on the context, biological signal decay might either promote or complicate cellular communications and the accuracy of population density-based controls on gene expression in species-rich ecosystems. PMID:15746331

Cellular effects of bacterial N-3-Oxo-dodecanoyl-L-Homoserine lactone on the sponge Suberites domuncula (Olivi, 1792): insights into an intimate inter-kingdom dialogue.

PubMed

Gardères, Johan; Henry, Joël; Bernay, Benoit; Ritter, Andrès; Zatylny-Gaudin, Céline; Wiens, Matthias; Müller, Werner E G; Le Pennec, Gaël

2014-01-01

Sponges and bacteria have lived together in complex consortia for 700 million years. As filter feeders, sponges prey on bacteria. Nevertheless, some bacteria are associated with sponges in symbiotic relationships. To enable this association, sponges and bacteria are likely to have developed molecular communication systems. These may include molecules such as N-acyl-L-homoserine lactones, produced by Gram-negative bacteria also within sponges. In this study, we examined the role of N-3-oxododecanoyl-L-homoserine lactone (3-oxo-C12-HSL) on the expression of immune and apoptotic genes of the host sponge Suberites domuncula. This molecule seemed to inhibit the sponge innate immune system through a decrease of the expression of genes coding for proteins sensing the bacterial membrane: a Toll-Like Receptor and a Toll-like Receptor Associated Factor 6 and for an anti-bacterial perforin-like molecule. The expression of the pro-apoptotic caspase-like 3/7 gene decreased as well, whereas the level of mRNA of anti-apoptotic genes Bcl-2 Homolog Proteins did not change. Then, we demonstrated the differential expression of proteins in presence of this 3-oxo-C12-HSL using 3D sponge cell cultures. Proteins involved in the first steps of the endocytosis process were highlighted using the 2D electrophoresis protein separation and the MALDI-TOF/TOF protein characterization: α and β subunits of the lysosomal ATPase, a cognin, cofilins-related proteins and cytoskeleton proteins actin, α tubulin and α actinin. The genetic expression of some of these proteins was subsequently followed. We propose that the 3-oxo-C12-HSL may participate in the tolerance of the sponge apoptotic and immune systems towards the presence of bacteria. Besides, the sponge may sense the 3-oxo-C12-HSL as a molecular evidence of the bacterial presence and/or density in order to regulate the populations of symbiotic bacteria in the sponge. This study is the first report of a bacterial secreted molecule acting on

Bioactive sesquiterpene lactones and other compounds isolated from Vernonia cinerea

PubMed Central

Youn, Ui Joung; Miklossy, Gabriella; Chai, Xingyun; Wongwiwatthananukit, Supakit; Toyama, Onoomar; Songsak, Thanapat; Turkson, James; Chang, Leng Chee

2014-01-01

Four new sesquiterpene lactones, 8α-(2′Z-tigloyloxy)-hirsutinolide (1), 8α-(2′Z-tigloyloxy)-hirsutinolide-13-O-acetate (2), 8α-(4-hydroxytigloyloxy)-hirsutinolide (3), and 8α-hydroxy-13-O-tigloyl-hirsutinolide (4), along with seven known derivatives (5–11), three norisoprenoids (12–14), a flavonoid (15), and a linoleic acid derivative (16), were isolated from the chloroform partition of a methanol extract from the combined leaves and stems of Vernonia cinerea. Their structures were established by 1D and 2D NMR, UV, and MS analyses. Compounds 1–16 were evaluated for their inhibitory effects against the viability of U251MG glioblastoma and MDA-MB-231 breast cancer cells that harbour aberrantly-active STAT3, compared to normal NIH3T3 mouse fibroblasts that show no evidence of activated STAT3. Among the isolates, compounds 2 and 7 inhibited the aberrant STAT3 activity in glioblastoma or breast cancer cells. Further, compounds 7 and 8 inhibited viability of all three cell lines, compounds 2, 4, and 9 predominantly inhibited the viability of the U251MG glioblastoma cell line. PMID:24370662

Bioactive sesquiterpene lactones and other compounds isolated from Vernonia cinerea.

PubMed

Youn, Ui Joung; Miklossy, Gabriella; Chai, Xingyun; Wongwiwatthananukit, Supakit; Toyama, Onoomar; Songsak, Thanapat; Turkson, James; Chang, Leng Chee

2014-03-01

Four new sesquiterpene lactones, 8α-(2'Z-tigloyloxy)-hirsutinolide (1), 8α-(2'Z-tigloyloxy)-hirsutinolide-13-O-acetate (2), 8α-(4-hydroxytigloyloxy)-hirsutinolide (3), and 8α-hydroxy-13-O-tigloyl-hirsutinolide (4), along with seven known derivatives (5-11), three norisoprenoids (12-14), a flavonoid (15), and a linoleic acid derivative (16), were isolated from the chloroform partition of a methanol extract from the combined leaves and stems of Vernonia cinerea. Their structures were established by 1D and 2D NMR, UV, and MS analyses. Compounds 1-16 were evaluated for their inhibitory effects against the viability of U251MG glioblastoma and MDA-MB-231 breast cancer cells that harbour aberrantly-active STAT3, compared to normal NIH3T3 mouse fibroblasts that show no evidence of activated STAT3. Among the isolates, compounds 2 and 7 inhibited the aberrant STAT3 activity in glioblastoma or breast cancer cells. Further, compounds 7 and 8 inhibited viability of all three cell lines, compounds 2, 4, and 9 predominantly inhibited the viability of the U251MG glioblastoma cell line. Copyright © 2014 Elsevier B.V. All rights reserved.

[Activation of the bioluminescence of the sensor Escherichia coli strains used for detecting N-acyl-homoserine lactones in the presence of nitrofurans and NO generators].

PubMed

Zaĭtseva, Iu V; Granik, V G; Belik, A S; Koksharova, O A; Khmel', I A

2010-01-01

Nitrofurans (nitrofurazone, nitrofurantoin, furazidin, nifuroxazide), and nitric oxide generators (sodium nitroprusside and isosorbide mononitrate) in subinhibitory concentrations were shown to significantly increase the bioluminescence of the sensor Escherichia coli strains used for detecting N-acyl-homoserine lactones, signaling molecules of Quorum Sensing (QS) regulatory systems. The highest activation of bioluminescence (up to 250-400 fold) was observed in the presence of nitrofurazone on E. coli DH5alpha biosensors containing lux-reporter plasmids pSB401 or pSB536. However, this activation was not specifically associated with the functioning of QS systems. We suggest that the effect observed results from a direct action of nitrofurans and NO donors on the process of bioluminescence. The data indicate the necessity of using the biosensors that make it possible to detect specific effects of substances tested on QS regulation.

Sesquiterpene lactone dermatitis in the young: is atopy a risk factor?

PubMed

Paulsen, Evy; Otkjaer, Aksel; Andersen, Klaus E

2008-07-01

Screening for Compositae contact allergy has documented fairly high prevalence in adults, and recent studies indicate that the allergy may be more common in children than previously believed. However, detailed information on sensitization in this age group is sparse. The objective of this study was to present another 2 cases in children and review the literature. Screening with sesquiterpene lactone (SL) mix has shown prevalence of 0.5% and 1.8% in 2 studies, while screening with 2 different Compositae mixes detected 4.2% and 2.6% positives among children and adolescents. All individual case reports describe sensitization in atopic children, and the largest screening study showed a prevalence of Compositae mix sensitization that was significantly higher in children with atopic dermatitis compared with non-atopics. Compositae sensitization should be considered in children with a family or personal history of atopy, summer-related, or -exacerbated dermatitis of any kind, and a history of plant exposure. Screening with SL mix is recommended but should be supplemented with plant extracts based on exposure history. Compositae weeds, especially dandelions, seem to be important sensitizers in children.

[Anti-aging action of the total lactones of ginkgo on aging mice].

PubMed

Dong, Liu-yi; Fan, Li; Li, Gui-fang; Guo, Yan; Pan, Jian; Chen, Zhi-wu

2004-03-01

To investigate the effects of total lactones of ginkgo on aging by using D-galactose induced aging mice and natural aging mice. By using D-galactose induced aging mice, to detect the LF content in heart and liver, the Hyp content in liver, the MAO, GSH-Px activities and the NO content in cerebrum. The apoptosis of cerebral cell was determined by terminal deoxy-nucleotidyl transforase-mediated dUTP-digoxigenin nick end-labeling (Tunel) in natural aging mice. TLG was shown to increase the GSH-Px activities, reduce the NO content and decrease the MAO activity in cerebrum. Meanwhile, TLG was found to reduce the LF content in liver and heart and raise the Hyp content in liver. TLG was shown to inhibit apoptosis of cerebral cell and decrease the number of apoptotic cells in the brain. TLG possesses effect on antiaging via attenuating lipid peroxidation and NO and apoptosis of cerebral cells.

Banana production systems: identification of alternative systems for more sustainable production.

PubMed

Bellamy, Angelina Sanderson

2013-04-01

Large-scale, monoculture production systems dependent on synthetic fertilizers and pesticides, increase yields, but are costly and have deleterious impacts on human health and the environment. This research investigates variations in banana production practices in Costa Rica, to identify alternative systems that combine high productivity and profitability, with reduced reliance on agrochemicals. Farm workers were observed during daily production activities; 39 banana producers and 8 extension workers/researchers were interviewed; and a review of field experiments conducted by the National Banana Corporation between 1997 and 2002 was made. Correspondence analysis showed that there is no structured variation in large-scale banana producers' practices, but two other banana production systems were identified: a small-scale organic system and a small-scale conventional coffee-banana intercropped system. Field-scale research may reveal ways that these practices can be scaled up to achieve a productive and profitable system producing high-quality export bananas with fewer or no pesticides.

Anti-inflammatory sesquiterpene lactones from Onopordum illyricum L. (Asteraceae), an Italian medicinal plant.

PubMed

Formisano, Carmen; Sanna, Cinzia; Ballero, Mauro; Chianese, Giuseppina; Sirignano, Carmina; Rigano, Daniela; Millán, Estrella; Muñoz, Eduardo; Taglialatela-Scafati, Orazio

2017-01-01

Onopordum illyricum L. is a medicinal plant used in the Mediterranean area as antipyretic for the treatment of respiratory and urinary inflammations and to treat skin ulcers. Repeated chromatographic purification of O. illyricum aerial parts led to the isolation of six known sesquiterpenes, which were evaluated for the inhibition of the pro-inflammatory transcription factors NF-κB and STAT3 and for the activation of the transcription factor Nrf2, which regulates the cellular antioxidant response. Structure-activity relationships were interpreted by the NMR-based cysteamine assay. The sesquiterpene lactone vernomelitensin significantly inhibited NF-κB and STAT3, showing also a significant Nrf2 activation. Accordingly, the cysteamine assay selected vernomelitensin as the most reactive of the isolated sesquiterpenes, identifying the α,β-unsaturated aldehyde moiety as responsible for the higher (re)activity. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparative Characterization of Total Flavonol Glycosides and Terpene Lactones at Different Ages, from Different Cultivation Sources and Genders of Ginkgo biloba Leaves

PubMed Central

Yao, Xin; Shang, Erxin; Zhou, Guisheng; Tang, Yuping; Guo, Sheng; Su, Shulan; Jin, Chun; Qian, Dawei; Qin, Yong; Duan, Jin-Ao

2012-01-01

The extract from Ginkgo biloba leaves has become a very popular plant medicine and herbal supplement for its potential benefit in alleviating symptoms associated with peripheral vascular disease, dementia, asthma and tinnitus. Most research on G. biloba leaves focus on the leaves collected in July and August from four to seven year-old trees, however a large number of leaves from fruit cultivars (trees older than 10 years) are ignored and become obsolete after fruit harvest season (November). In this paper, we expand the tree age range (from one to 300 years) and first comparatively analyze the total flavonol glycosides and terpene lactones at different ages, from different cultivation sources and genders of G. biloba leaves collected in November by using the validated HPLC-ELSD and HPLC-PDA methods. The results show that the contents of total terpene lactones and flavonol glycosides in the leaves of young ginkgo trees are higher than those in old trees, and they are higher in male trees than in female trees. Geographical factors appear to have a significant influence on the contents as well. These results will provide a good basis for the comprehensive utilization of G. biloba leaves, especially the leaves from fruit cultivars. PMID:22949862

Parthenolide, a sesquiterpene lactone, expresses multiple anti-cancer and anti-inflammatory activities.

PubMed

Mathema, Vivek Bhakta; Koh, Young-Sang; Thakuri, Balkrishna Chand; Sillanpää, Mika

2012-04-01

Parthenolide, a naturally occurring sesquiterpene lactone derived from feverfew (Tanacetum parthenium), exhibits exceptional anti-cancer and anti-inflammatory properties, making it a prominent candidate for further studies and drug development. In this review, we briefly investigate molecular events and cell-specific activities of this chemical in relation to cytochrome c, nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB), signal transduction and activation of transcription (STAT), reactive oxygen species (ROS), TCP, HDACs, microtubules, and inflammasomes. This paper reports that parthenolide shows strong NF-κB- and STAT-inhibition-mediated transcriptional suppression of pro-apoptotic genes. This compound acts both at the transcriptional level and by direct inhibition of associated kinases (IKK-β). Similarly, this review discusses parthenolide-induced ROS-mediated apoptosis of tumor cells via the intrinsic apoptotic signaling pathway. The unique ability of this compound to not harm normal cells but at the same time induce sensitization to extrinsic as well as intrinsic apoptosis signaling in cancer cells provides an important, novel therapeutic strategy for treatment of cancer and inflammation-related disorders.

N-(3-oxododecanoyl)-l-homoserine lactone modulates mitochondrial function and suppresses proliferation in intestinal goblet cells.

PubMed

Tao, Shiyu; Niu, Liqiong; Cai, Liuping; Geng, Yali; Hua, Canfeng; Ni, Yingdong; Zhao, Ruqian

2018-05-15

The quorum-sensing molecule N‑(3‑oxododecanoyl)‑l‑homoserine lactone (C12-HSL), produced by the Gram negative human pathogenic bacterium Pseudomonas aeruginosa, modulates mammalian cell behavior. Our previous findings suggested that C12-HSL rapidly decreases viability and induces apoptosis in LS174T goblet cells. In this study, the effects of 100 μM C12-HSL on mitochondrial function and cell proliferation in LS174T cells treated for 4 h were evaluated by real-time PCR, enzyme-linked immunosorbent assay (ELISA) and flow cytometry. The results showed that the activities of mitochondrial respiratory chain complexes IV and V were significantly increased (P < 0.05) in LS174T cells after C12-HSL treatment, with elevated intracellular ATP generation (P < 0.05). Flow cytometry analysis revealed significantly increased intracellular Ca 2+ levels (P < 0.05), as well as disrupted mitochondrial activity and cell cycle arrest upon C12-HSL treatment. Apoptosis and cell proliferation related genes showed markedly altered expression levels (P < 0.05) in LS174T cells after C12-HSL treatment. Moreover, the paraoxonase 2 (PON2) inhibitor TQ416 (1 μM) remarkably reversed the above C12-HSL associated effects in LS174T cells. These findings indicated that C12-HSL alters mitochondrial energy production and function, and inhibits cell proliferation in LS174T cells, with PON2 involvement. Copyright © 2018 Elsevier Inc. All rights reserved.

A Novel Lactone-Forming Carboxylesterase: Molecular Identification of a Tuliposide A-Converting Enzyme in Tulip1[W

PubMed Central

Nomura, Taiji; Ogita, Shinjiro; Kato, Yasuo

2012-01-01

Tuliposides, the glucose esters of 4-hydroxy-2-methylenebutanoate and 3,4-dihydroxy-2-methylenebutanoate, are major secondary metabolites in tulip (Tulipa gesneriana). Their lactonized aglycons, tulipalins, function as defensive chemicals due to their biological activities. We recently found that tuliposide-converting enzyme (TCE) purified from tulip bulbs catalyzed the conversion of tuliposides to tulipalins, but the possibility of the presence of several TCE isozymes was raised: TCE in tissues other than bulbs is different from bulb TCE. Here, to prove this hypothesis, TCE was purified from petals, which have the second highest TCE activity after bulbs. The purified enzyme, like the bulb enzyme, preferentially accepted tuliposides as substrates, with 6-tuliposide A the best substrate, which allowed naming the enzyme tuliposide A-converting enzyme (TCEA), but specific activity and molecular mass differed between the petal and bulb enzymes. After peptide sequencing, a novel cDNA (TgTCEA) encoding petal TCEA was isolated, and the functional characterization of the recombinant enzyme verified that TgTCEA catalyzes the conversion of 6-tuliposide A to tulipalin A. TgTCEA was transcribed in all tulip tissues but not in bulbs, indicating the presence of a bulb-specific TgTCEA, as suggested by the distinct enzymatic characters between the petal and bulb enzymes. Plastidial localization of TgTCEA enzyme was revealed, which allowed proposing a cytological mechanism of TgTCE-mediated tulipalin formation in the tulip defensive strategy. Site-directed mutagenesis of TgTCEA suggested that the oxyanion hole and catalytic triad characteristic of typical carboxylesterases are essential for the catalytic process of TgTCEA enzyme. To our knowledge, TgTCEA is the first identified member of the lactone-forming carboxylesterases, specifically catalyzing intramolecular transesterification. PMID:22474185

Self-organizing maps of molecular descriptors for sesquiterpene lactones and their application to the chemotaxonomy of the Asteraceae family.

PubMed

Scotti, Marcus T; Emerenciano, Vicente; Ferreira, Marcelo J P; Scotti, Luciana; Stefani, Ricardo; da Silva, Marcelo S; Mendonça Junior, Francisco Jaime B

2012-04-20

The Asteraceae, one of the largest families among angiosperms, is chemically characterised by the production of sesquiterpene lactones (SLs). A total of 1,111 SLs, which were extracted from 658 species, 161 genera, 63 subtribes and 15 tribes of Asteraceae, were represented and registered in two dimensions in the SISTEMATX, an in-house software system, and were associated with their botanical sources. The respective 11 block of descriptors: Constitutional, Functional groups, BCUT, Atom-centred, 2D autocorrelations, Topological, Geometrical, RDF, 3D-MoRSE, GETAWAY and WHIM were used as input data to separate the botanical occurrences through self-organising maps. Maps that were generated with each descriptor divided the Asteraceae tribes, with total index values between 66.7% and 83.6%. The analysis of the results shows evident similarities among the Heliantheae, Helenieae and Eupatorieae tribes as well as between the Anthemideae and Inuleae tribes. Those observations are in agreement with systematic classifications that were proposed by Bremer, which use mainly morphological and molecular data, therefore chemical markers partially corroborate with these classifications. The results demonstrate that the atom-centred and RDF descriptors can be used as a tool for taxonomic classification in low hierarchical levels, such as tribes. Descriptors obtained through fragments or by the two-dimensional representation of the SL structures were sufficient to obtain significant results, and better results were not achieved by using descriptors derived from three-dimensional representations of SLs. Such models based on physico-chemical properties can project new design SLs, similar structures from literature or even unreported structures in two-dimensional chemical space. Therefore, the generated SOMs can predict the most probable tribe where a biologically active molecule can be found according Bremer classification.

Non-critically phase-matched second harmonic generation and third order nonlinearity in organic crystal glucuronic acid γ-lactone

NASA Astrophysics Data System (ADS)

Saripalli, Ravi Kiran; Katturi, Naga Krishnakanth; Soma, Venugopal Rao; Bhat, H. L.; Elizabeth, Suja

2017-12-01

The linear, second order, and third order nonlinear optical properties of glucuronic acid γ-lactone single crystals were investigated. The optic axes and principal dielectric axes were identified through optical conoscopy and the principal refractive indices were obtained using the Brewster's angle method. Conic sections were observed which is perceived to be due to spontaneous non-collinear phase matching. The direction of collinear phase matching was determined and the deff evaluated in this direction was 0.71 pm/V. Open and closed aperture Z-scan measurements with femtosecond pulses revealed high third order nonlinearity in the form of self-defocusing, two-photon absorption, as well as saturable absorption.

Method to convert biomass to 5-(hydroxymethyl)-furfural (HMF) and furfural using lactones, furans, and pyrans as solvents

DOEpatents

Dumesic, James A.; Ribeiro Gallo, Jean Marcel; Alonso, David

2014-07-08

Described is a process to produce hydroxymethyl furfural (HMF) from biomass-derived sugars. The process includes the steps of reacting a C5 and/or C6 sugar-containing reactant derived from biomass in a monophasic or biphasic reaction solution comprising water and a co-solvent. The co-solvent can be beta-, gamma-, and/or delta-lactones derived from biomass, tetrahydrofuran (THF) derived from biomass, and/or methyltetrahydrofuran (MTHF) derived from biomass. The reaction takes place in the presence of an acid catalyst and a dehydration catalyst for a time and under conditions such that at least a portion of glucose or fructose present in the reactant is converted to HMF.

Development of a dry, stable and inhalable acyl-homoserine-lactone-acylase powder formulation for the treatment of pulmonary Pseudomonas aeruginosa infections.

PubMed

Wahjudi, Mariana; Murugappan, Senthil; van Merkerk, Ronald; Eissens, Anko C; Visser, Marinella R; Hinrichs, Wouter L J; Quax, Wim J

2013-03-12

In the lungs of cystic fibrosis (CF) patients, Pseudomonas aeruginosa commonly causes chronic infections. It has been shown that the P. aeruginosa quorum sensing (QS) system controls the expression of virulence factors during invasion and infection to host cells. PvdQ is an acyl-homoserine lactone (AHL) acylase able to degrade the signal molecule of P. aeruginosa QS. The role of PvdQ in inhibiting the QS and its successive virulence determinants has been established in in vitro as well as in in vivo, the latter in a Caenorabdhitis elegans model. For the treatment of pulmonary P. aeruginosa infections, we propose that PvdQ can be best administered directly to the lungs of the patients as a dry powder because this is expected to give specific advantages in delivery as compared to nebulizing. Therefore in this study we investigated the production of a PvdQ powder by spray-freeze drying using mannitol, trehalose and inulin as excipient. The activity of PvdQ in the powder was determined immediately after production and after subsequent storage during 4 weeks at 20°C and 55°C. We found that the enzymatic activity of PvdQ is fully maintained during spray-freeze drying using mannitol, trehalose or inulin as excipient. However, mannitol was not able to stabilize the protein during storage, while PvdQ incorporated in trehalose or inulin was fully stabilized even during storage at 55°C for at least 4 weeks. The poor stabilizing capacities of mannitol during storage could be related to its crystalline nature while the excellent stabilizing capacities of trehalose and inulin during storage could be related to their amorphous nature. The trehalose and inulin-based particles consisted of porous spheres with a volume average aerodynamical diameter of ∼1.8 μm implying that they are suitable for pulmonary delivery. This is the first study in which an AHL-degrading enzyme is processed into spray-freeze-dried powder suitable for inhalation. Copyright © 2013 Elsevier B.V. All

Safety assessment of aqueous extract from leaf Smallanthus sonchifolius and its main active lactone, enhydrin.

PubMed

Barcellona, Carolina Serra; Cabrera, Wilfredo Marcelino; Honoré, Stella Maris; Mercado, María Inés; Sánchez, Sara Serafina; Genta, Susana Beatriz

2012-11-21

Leaves of Smallanthus sonchifolius (Poepp. & Endl.) H. Robinson (yacon) have been used since pre-Columbian times in the Andean region to prepare medicinal herbal tea with beneficial health properties. However, there are still disagreements about the safe use. This work was carried out to evaluate the toxicity profile of both, 10% decoction of yacon leaves and their major active lactone, enhydrin. In vitro cytotoxicity assays were performed with Hep-G2, COS1, CHO-K1 and Vero cell lines using a test of metabolic competence based upon assessment of mitochondrial performance. In vivo toxicity study was performed in adult Wistar rats. In the acute oral toxicity each group of rats was orally given a single dose of 10% decoction or enhydrin. General condition, behavior and mortality were recorded for up to 14 days post treatment. In subchronic toxicity studies, both products were given orally for 90 days to rats. Body weight and food intakes were observed weekly. Hematological, clinical chemistry parameters and organ weight were determined in all animals at the end of the experimental period. Cell viability decreased in a concentration dependent fashion when cells were incubated with 2-200 μg of 10% decoction and 0.015-7.5 μg of enhydrin. In acute study in rats, there were no deaths or signs of toxicity observed after oral administration of single doses of 10% decoction or enhydrin at any dose level up to the highest dose tested (14.0 g/kg and 0.32 g/kg, respectively). In subchronic studies in rats, both products administered orally for 90 days at daily doses of 0.07, 0.14 and 0.28 g 10% decoction/kg and 0.4, 0.8 and 8.0 mg enhydrin/kg, did not caused haematological, biochemical and histological alterations. The results presented in this paper lead us to the conclusion that the use of 10% decoction and enhydrin is safe in rat at doses in which it is demonstrated the hypoglycaemic effect. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Structure-Function Analysis of Peptide Signaling in the Clostridium perfringens Agr-Like Quorum Sensing System

PubMed Central

Ma, Menglin; Li, Jihong

2015-01-01

ABSTRACT The accessory growth regulator (Agr)-like quorum sensing (QS) system of Clostridium perfringens controls the production of many toxins, including beta toxin (CPB). We previously showed (J. E. Vidal, M. Ma, J. Saputo, J. Garcia, F. A. Uzal, and B. A. McClane, Mol Microbiol 83:179–194, 2012, http://dx.doi.org/10.1111/j.1365-2958.2011.07925.x) that an 8-amino-acid, AgrD-derived peptide named 8-R upregulates CPB production by this QS system. The current study synthesized a series of small signaling peptides corresponding to sequences within the C. perfringens AgrD polypeptide to investigate the C. perfringens autoinducing peptide (AIP) structure-function relationship. When both linear and cyclic ring forms of these peptides were added to agrB null mutants of type B strain CN1795 or type C strain CN3685, the 5-amino-acid peptides, whether in a linear or ring (thiolactone or lactone) form, induced better signaling (more CPB production) than peptide 8-R for both C. perfringens strains. The 5-mer thiolactone ring peptide induced faster signaling than the 5-mer linear peptide. Strain-related variations in sensing these peptides were detected, with CN3685 sensing the synthetic peptides more strongly than CN1795. Consistent with those synthetic peptide results, Transwell coculture experiments showed that CN3685 exquisitely senses native AIP signals from other isolates (types A, B, C, and D), while CN1795 barely senses even its own AIP. Finally, a C. perfringens AgrD sequence-based peptide with a 6-amino-acid thiolactone ring interfered with CPB production by several C. perfringens strains, suggesting potential therapeutic applications. These results indicate that AIP signaling sensitivity and responsiveness vary among C. perfringens strains and suggest C. perfringens prefers a 5-mer AIP to initiate Agr signaling. IMPORTANCE Clostridium perfringens possesses an Agr-like quorum sensing (QS) system that regulates virulence, sporulation, and toxin production. The

Sesquiterpene lactones in Arnica montana: helenalin and dihydrohelenalin chemotypes in Spain.

PubMed

Perry, Nigel B; Burgess, Elaine J; Rodríguez Guitián, Manuel A; Romero Franco, Rosa; López Mosquera, Elvira; Smallfield, Bruce M; Joyce, Nigel I; Littlejohn, Roger P

2009-05-01

An analytical RPLC method for sesquiterpene lactones in Arnica montana has been extended to include quantitative analyses of dihydrohelenalin esters. LC-ESI-MS-MS distinguished the isomeric helenalin and dihydrohelenalin esters. The dihydrohelenalin esters have lower response factors for UV detection than do helenalin esters, which must be taken into account for quantitative analyses. Analyses of flowers from 16 different wild populations of A. montana in Spain showed differing proportions of helenalin and dihydrohelenalin esters. For the first time a chemotype with high levels of helenalin esters (total helenalins 5.2-10.3 mg/g dry weight) is reported in Spanish A. montana. These samples were from heath lands at high altitude (1330-1460 m), whereas samples from meadows and peat bogs at lower altitudes were the expected chemotype with high levels of dihydrohelenalin esters (total dihydrohelenalins 10.9-18.2 mg/g). The phenolic compounds, both flavonoid glycosides and caffeoylquinic acids, in Spanish A. montana are reported for the first time. The levels of several of these compounds differed significantly between samples from heath lands and samples from peat bogs or meadows, with the heath land samples being most similar to central European A. montana in their phenolic composition. Copyright Georg Thieme Verlag KG Stuttgart. New York.

N-acyl homoserine lactone-degrading microbial enrichment cultures isolated from Penaeus vannamei shrimp gut and their probiotic properties in Brachionus plicatilis cultures.

PubMed

Tinh, Nguyen Thi Ngoc; Asanka Gunasekara, R A Y S; Boon, Nico; Dierckens, Kristof; Sorgeloos, Patrick; Bossier, Peter

2007-10-01

Three bacterial enrichment cultures (ECs) were isolated from the digestive tract of Pacific white shrimp Penaeus vannamei, by growing the shrimp microbial communities in a mixture of N-acyl homoserine lactone (AHL) molecules. The ECs, characterized by denaturing gradient gel electrophoresis analysis and subsequent rRNA sequencing, degraded AHL molecules in the degradation assays. Apparently, the resting cells of the ECs also degraded one of the three types of quorum-sensing signal molecules produced by Vibrio harveyi in vitro [i.e. harveyi autoinducer 1 (HAI-1)]. The most efficient AHL-degrading ECs, EC5, was tested in Brachionus experiments. EC5 degraded the V. harveyi HAI-1 autoinducer in vivo, neutralizing the negative effect of V. harveyi autoinducer 2 (AI-2) mutant, in which only the HAI-1- and CAI-1-mediated components of the quorum-sensing system are functional on the growth of Brachionus. This suggests that EC5 interferes with HAI-1-regulated metabolism in V. harveyi. These AHL-degrading ECs need to be tested in other aquatic systems for their probiotic properties, preferably in combination with specific AI-2-degrading bacteria.

AiiA, an enzyme that inactivates the acylhomoserine lactone quorum-sensing signal and attenuates the virulence of Erwinia carotovora

PubMed Central

Dong, Yi-Hu; Xu, Jin-Ling; Li, Xian-Zhen; Zhang, Lian-Hui

2000-01-01

N-acylhomoserine lactones, known as autoinducers (AIs), are widely conserved signal molecules present in quorum-sensing systems of many Gram-negative bacteria. AIs are involved in the regulation of diverse biological functions, including expression of pathogenic genes in the plant pathogens Pseudomonas solanacearum, several Erwinia species, and the human pathogen Pseudomonas aeruginosa. A bacterial isolate, Bacillus sp. 240B1, is capable of enzymatic inactivation of AIs. The gene (aiiA) for AI inactivation from Bacillus sp. 240B1 has been cloned and shown to encode a protein of 250 amino acids. Sequence alignment indicates that AiiA contains a “HXHXDH” zinc-binding motif that is conserved in several groups of metallohydrolases. Site-directed mutagenesis showed that conserved aspartate and most histidine residues are required for AiiA activity. Expression of aiiA in transformed Erwinia carotovora strain SCG1 significantly reduces the release of AI, decreases extracellular pectolytic enzyme activities, and attenuates pathogenicity on potato, eggplant, Chinese cabbage, carrot, celery, cauliflower, and tobacco. Our results indicate that the AI-inactivation approach represents a promising strategy for prevention of diseases in which virulence is regulated by AIs. PMID:10716724

Disintegration of collagen fibrils by Glucono-δ-lactone: An implied lead for disintegration of fibrosis.

PubMed

Jayamani, Jayaraman; Ravikanth Reddy, R; Madhan, Balaraman; Shanmugam, Ganesh

2018-02-01

Excess accumulation of collagen (fibrosis) undergoes self-aggregation, which leads to fibrillar collagen, on the extracellular matrix is the hallmark of a number of diseases such as keloids, hypertrophic scars, and systemic scleroderma. Direct inhibition or disintegration of collagen fibrils by small molecules offer a therapeutic approach to prevent or treat the diseases related to fibrosis. Herein, the anti-fibrotic property of Glucono-δ-lactone (GdL), known as acidifier, on the fibrillation and its disintegration of collagen was investigated. As collagen fibrillation is pH dependent, the pH modulation property of GdL is attractive to inhibit self-association of collagen. Optical density and microscopic data indicate that GdL elicits concentration-dependent fibril inhibition and also disintegrates pre-formed collagen fibrils. The simultaneous pH analysis showed that the modulation(lowering) of pH by GdL is the primary cause for its anti-fibrotic activity. The intact triple helical structure of collagen upon treatment of GdL suggests that collagen fibril disintegration can be achieved without affecting the native structure of collagen which is essential for any anti-fibrotic agents. Saturation transfer difference (STD) NMR result reveals that GdL is in proximity to collagen. The present results thus suggest that GdL provides a lead to design novel anti-fibrotic agents for the pathologies related to collagen deposition. Copyright © 2017 Elsevier B.V. All rights reserved.

A Review on the Toxicity and Non-Target Effects of Macrocyclic Lactones in Terrestrial and Aquatic Environments

PubMed Central

Lumaret, Jean-Pierre; Errouissi, Faiek; Floate, Kevin; Römbke, Jörg; Wardhaugh, Keith

2012-01-01

The avermectins, milbemycins and spinosyns are collectively referred to as macrocyclic lactones (MLs) which comprise several classes of chemicals derived from cultures of soil micro-organisms. These compounds are extensively and increasingly used in veterinary medicine and agriculture. Due to their potential effects on non-target organisms, large amounts of information on their impact in the environment has been compiled in recent years, mainly caused by legal requirements related to their marketing authorization or registration. The main objective of this paper is to critically review the present knowledge about the acute and chronic ecotoxicological effects of MLs on organisms, mainly invertebrates, in the terrestrial and aquatic environment. Detailed information is presented on the mode-of-action as well as the ecotoxicity of the most important compounds representing the three groups of MLs. This information, based on more than 360 references, is mainly provided in nine tables, presenting the effects of abamectin, ivermectin, eprinomectin, doramectin, emamectin, moxidectin, and spinosad on individual species of terrestrial and aquatic invertebrates as well as plants and algae. Since dung dwelling organisms are particularly important non-targets, as they are exposed via dung from treated animals over their whole life-cycle, the information on the effects of MLs on dung communities is compiled in an additional table. The results of this review clearly demonstrate that regarding environmental impacts many macrocyclic lactones are substances of high concern particularly with larval instars of invertebrates. Recent studies have also shown that susceptibility varies with life cycle stage and impacts can be mitigated by using MLs when these stages are not present. However information on the environmental impact of the MLs is scattered across a wide range of specialised scientific journals with research focusing mainly on ivermectin and to a lesser extent on abamectin

D-Saccharic acid 1,4-lactone protects diabetic rat kidney by ameliorating hyperglycemia-mediated oxidative stress and renal inflammatory cytokines via NF-κB and PKC signaling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bhattacharya, Semantee; Manna, Prasenjit; Gachhui, Ratan

2013-02-15

Increasing evidence suggests that oxidative stress is involved in the pathogenesis of diabetic nephropathy (DN) and this can be attenuated by antioxidants. D-Saccharic acid 1,4-lactone (DSL) is known for its detoxifying and antioxidant properties. Our early investigation showed that DSL can ameliorate alloxan (ALX) induced diabetes mellitus and oxidative stress in rats by inhibiting pancreatic β-cell apoptosis. In the present study we, therefore, investigated the protective role of DSL against renal injury in ALX induced diabetic rats. ALX exposure (at a dose of 120 mg/kg body weight, i. p., once) elevated the blood glucose level, serum markers related to renalmore » injury, the production of reactive oxygen species (ROS), and disturbed the intra-cellular antioxidant machineries. Oral administration of DSL (80 mg/kg body weight) restored all these alterations close to normal. In addition, DSL could also normalize the aldose reductase activity which was found to increase in the diabetic rats. Investigating the mechanism of its protective activity, we observed the activation of different isoforms of PKC along with the accumulation of matrix proteins like collagen and fibronectin. The diabetic rats also showed nuclear translocation of NF-κB and increase in the concentration of inflammatory cytokines in the renal tissue. The activation of mitochondria dependent apoptotic pathway was observed in the diabetic rat kidneys. However, treatment of diabetic rats with DSL counteracted all these changes. These findings, for the first time, demonstrated that DSL could ameliorate renal dysfunction in diabetic rats by suppressing the oxidative stress related signalling pathways. - Highlights: ► Sustained hyperglycemia and oxidative stress lead to diabetic renal injury. ► D-saccharic acid 1,4-lactone prevents renal damage in alloxan-induced diabetes. ► It restores intra-cellular antioxidant machineries and kidney apoptosis. ► DSL reduces hyperglycemia-mediated oxidative

Yomogin, an inhibitor of nitric oxide production in LPS-activated macrophages.

PubMed

Ryu, J H; Lee, H J; Jeong, Y S; Ryu, S Y; Han, Y N

1998-08-01

In activated macrophages the inducible form of nitric oxide synthase (i-NOS) generates high amounts of toxic mediator, nitric oxide (NO) which contributes to the circulatory failure associated with septic shock. A sesquiterpene lactone compound (yomogin) isolated from medicinal plant Artemisia princeps Pampan inhibited the production of NO in LPS-activated RAW 264.7 cells by suppressing i-NOS enzyme expression. Thus, yomogin may be a useful candidate for the development of new drugs to treat endotoxemia and inflammation accompanied by the overproduction of NO.

Production of rosamicin derivatives in Micromonospora rosaria by introduction of D-mycinose biosynthetic gene with PhiC31-derived integration vector pSET152.

PubMed

Anzai, Yojiro; Iizaka, Yohei; Li, Wei; Idemoto, Naoki; Tsukada, Shu-ichi; Koike, Kazuo; Kinoshita, Kenji; Kato, Fumio

2009-08-01

Some of the polyketide-derived bioactive compounds contain sugars attached to the aglycone core, and these sugars often impart specific biological activity to the molecule or enhance this activity. Mycinamicin II, a 16-member macrolide antibiotic produced by Micromonospora griseorubida A11725, contains a branched lactone and two different deoxyhexose sugars, D-desosamine and D-mycinose, at the C-5 and C-21 positions, respectively. The D-mycinose biosynthesis genes, mycCI, mycCII, mycD, mycE, mycF, mydH, and mydI, present in the M. griseorubida A11725 chromosome were introduced into pSET152 under the regulation of the promoter of the apramycin-resistance gene aac(3)IV. The resulting plasmid pSETmycinose was introduced into Micromonospora rosaria IFO13697 cells, which produce the 16-membered macrolide antibiotic rosamicin containing a branched lactone and D-desosamine at the C-5 position. Although the M. rosaria TPMA0001 transconjugant exhibited low rosamicin productivity, two new compounds, IZI and IZII, were detected in the ethylacetate extract from the culture broth. IZI was identified as a mycinosyl rosamicin derivative, 23-O-mycinosyl-20-deoxo-20-dihydro-12,13-deepoxyrosamicin (MW 741), which has previously been synthesized by a bioconversion technique. This is the first report on production of mycinosyl rosamicin-derivatives by a engineered biosynthesis approach. The integration site PhiC31attB was identified on M. rosaria IFO13697 chromosome, and the site lay within an ORF coding a pirin homolog protein. The pSETmycinose could be useful for stimulating the production of "unnatural" natural mycinosyl compounds by various actinomycete strains using the bacteriophage PhiC31 att/int system.

Two drimane lactones, valdiviolide and 11-epivaldiviolide, in the form of a 1:1 cocrystal obtained from Drimys winteri extracts.

PubMed

Paz Robles, Cristian; Mercado, Darío; Suarez, Sebastián; Baggio, Ricardo

2014-12-01

A cocrystal, C15H22O3·C15H22O3, (I), obtained from Drimys winteri, is composed of two isomeric drimane sesquiterpene lactones, namely valdiviolide, (Ia), and 11-epivaldiviolide, (Ib), neither of which has been reported in the crystal form. Both diastereoisomers present three chiral centres at sites 5, 10 and 11, with an SSR sequence in (Ia) and an SSS sequence in (Ib). O-H···O hydrogen bonds bind molecules into chains running along [120] and the chains are in turn linked by π-π stacking interactions to define planar weakly interacting arrays parallel to (001).

Variation of sesquiterpene lactone contents in different Arnica montana populations: influence of ecological parameters.

PubMed

Seemann, Andreas; Wallner, Teresa; Poschlod, Peter; Heilmann, Jörg

2010-05-01

In ten grassland or heathland sites along a geographic (north to south) and climatic gradient in Germany, flowerheads of Arnica montana were collected, and the total content of sesquiterpene lactones (SLs) as well as the content of the detected single compounds were determined. The ratios of helenalin (H)- and corresponding 11 alpha,13-dihydrohelenalin(DH)-type compounds were calculated. All habitats were characterised concerning the climatic and soil conditions, and the values obtained were correlated with SL contents according to univariate statistical analyses. All populations showed very similar and constant ratios of helenalin ( 1)/11 alpha,13-dihydrohelenalin ( 2) at around 1.5-2/1 irrespective of different ecological parameters. The ratio of helenalin/11 alpha,13-dihydrohelenalin esters was several fold higher in all samples, but it was nearly identical in every habitat among each other, except for the helenalin/11 alpha,13-dihydrohelenalin 2-methylbutyrate pair ( 5/ 11), which showed a constantly twofold higher H/DH ratio. However, the 6- O-isovalerylhelenalin content ( 6) showed highly significant correlations to climatic factors. Georg Thieme Verlag KG Stuttgart New York.

N-(3-oxo-acyl) homoserine lactone inhibits tumor growth independent of Bcl-2 proteins.

PubMed

Zhao, Guoping; Neely, Aaron M; Schwarzer, Christian; Lu, Huayi; Whitt, Aaron G; Stivers, Nicole S; Burlison, Joseph A; White, Carl; Machen, Terry E; Li, Chi

2016-02-02

Pseudomonas aeruginosa produces N-(3-oxododecanoyl)-homoserine lactone (C12) as a quorum-sensing molecule for bacterial communication. C12 has also been reported to induce apoptosis in various types of tumor cells. However, the detailed molecular mechanism of C12-triggerred tumor cell apoptosis is still unclear. In addition, it is completely unknown whether C12 possesses any potential therapeutic effects in vivo. Our data indicate that, unlike most apoptotic inducers, C12 evokes a novel form of apoptosis in tumor cells through inducing mitochondrial membrane permeabilization independent of both pro- and anti-apoptotic Bcl-2 proteins. Importantly, C12 inhibits tumor growth in animals regardless of either pro- or anti-apoptotic Bcl-2 proteins. Furthermore, opposite to conventional chemotherapeutics, C12 requires paraoxonase 2 (PON2) to exert its cytotoxicity on tumor cells in vitro and its inhibitory effects on tumor growth in vivo. Overall, our results demonstrate that C12 inhibits tumor growth independent of both pro- and anti-apoptotic Bcl-2 proteins, and through inducing unique apoptotic signaling mediated by PON2 in tumor cells.

N-(3-oxo-acyl) homoserine lactone inhibits tumor growth independent of Bcl-2 proteins

PubMed Central

Zhao, Guoping; Neely, Aaron M.; Schwarzer, Christian; Lu, Huayi; Whitt, Aaron G.; Stivers, Nicole S.; Burlison, Joseph A.; White, Carl; Machen, Terry E.; Li, Chi

2016-01-01

Pseudomonas aeruginosa produces N-(3-oxododecanoyl)-homoserine lactone (C12) as a quorum-sensing molecule for bacterial communication. C12 has also been reported to induce apoptosis in various types of tumor cells. However, the detailed molecular mechanism of C12-triggerred tumor cell apoptosis is still unclear. In addition, it is completely unknown whether C12 possesses any potential therapeutic effects in vivo. Our data indicate that, unlike most apoptotic inducers, C12 evokes a novel form of apoptosis in tumor cells through inducing mitochondrial membrane permeabilization independent of both pro- and anti-apoptotic Bcl-2 proteins. Importantly, C12 inhibits tumor growth in animals regardless of either pro- or anti-apoptotic Bcl-2 proteins. Furthermore, opposite to conventional chemotherapeutics, C12 requires paraoxonase 2 (PON2) to exert its cytotoxicity on tumor cells in vitro and its inhibitory effects on tumor growth in vivo. Overall, our results demonstrate that C12 inhibits tumor growth independent of both pro- and anti-apoptotic Bcl-2 proteins, and through inducing unique apoptotic signaling mediated by PON2 in tumor cells. PMID:26758417

Quantification of Sesquiterpene Lactones in Asteraceae Plant Extracts: Evaluation of their Allergenic Potential

PubMed Central

Salapovic, Helena; Geier, Johannes; Reznicek, Gottfried

2013-01-01

Sesquiterpene lactones (SLs), mainly those with an activated exocyclic methylene group, are important allergens in Asteraceae (Compositae) plants. As a screening tool, the Compositae mix, consisting of five Asteraceae plant extracts with allergenic potential (feverfew, tansy, arnica, yarrow, and German chamomile) is part of several national patch test baseline series. However, the SL content of the Compositae mix may vary due to the source material. Therefore, a simple spectrophotometric method for the quantitative measurement of SLs with the α-methylene-γ-butyrolactone moiety was developed, giving the percentage of allergenic compounds in plant extracts. The method has been validated and five Asteraceae extracts, namely feverfew (Tanacetum parthenium L.), tansy (Tanacetum vulgare L.), arnica (Arnica montana L.), yarrow (Achillea millefolium L.), and German chamomile (Chamomilla recutita L. Rauschert) that have been used in routine patch test screening were evaluated. A good correlation could be found between the results obtained using the proposed spectrophotometric method and the corresponding clinical results. Thus, the introduced method is a valuable tool for evaluating the allergenic potential and for the simple and efficient quality control of plant extracts with allergenic potential. PMID:24106675

Production and Isomeric Distribution of Xanthylium Cation Pigments and Their Precursors in Wine-like Conditions: Impact of Cu(II), Fe(II), Fe(III), Mn(II), Zn(II), and Al(III).

PubMed

Guo, Anque; Kontoudakis, Nikolaos; Scollary, Geoffrey R; Clark, Andrew C

2017-03-22

This study establishes the influence of Cu(II), Fe(II), Fe(III), Zn(II), Al(III), and Mn(II) on the oxidative production of xanthylium cations from (+)-catechin and either tartaric acid or glyoxylic acid in model wine systems. The reaction was studied at 25 °C using UHPLC and LC-HRMS for the analysis of phenolic products and their isomeric distribution. In addition to the expected products, a colorless product, tentatively assigned as a lactone, was detected for the first time. The results show the importance of Fe ions and a synergistic influence of Mn(II) in degrading tartaric acid to glyoxylic acid, whereas the other metal ions had minimal activity in this mechanistic step. Fe(II) and Fe(III) were shown to mediate the (+)-catechin-glyoxylic acid addition reaction, a role previously attributed to only Cu(II). Importantly, the study demonstrates that C-8 addition products of (+)-catechin are promoted by Cu(II), whereas C-6 addition products are promoted by Fe ions.

Effects of natural and chemically synthesized furanones on quorum sensing in Chromobacterium violaceum

PubMed Central

Martinelli, Daniel; Grossmann, Gilles; Séquin, Urs; Brandl, Helmut; Bachofen, Reinhard

2004-01-01

Background Cell to cell signaling systems in Gram-negative bacteria rely on small diffusible molecules such as the N-acylhomoserine lactones (AHL). These compounds are involved in the production of antibiotics, exoenzymes, virulence factors and biofilm formation. They belong to the class of furanone derivatives which are frequently found in nature as pheromones, flavor compounds or secondary metabolites. To obtain more information on the relation between molecular structure and quorum sensing, we tested a variety of natural and chemically synthesized furanones for their ability to interfere with the quorum sensing mechanism using a quantitative bioassay with Chromobacterium violaceum CV026 for antagonistic and agonistic action. We were looking at the following questions: 1. Do these compounds affect growth? 2) Do these compounds activate the quorum sensing system of C. violaceum CV026? 3) Do these compounds inhibit violacein formation induced by the addition of the natural inducer N-hexanoylhomoserine lactone (HHL)? 4) Do these compounds enhance violacein formation in presence of HHL? Results The naturally produced N-acylhomoserine lactones showed a strong non-linear concentration dependent influence on violacein production in C. violaceum with a maximum at 3.7*10-8 M with HHL. Apart from the N-acylhomoserine lactones only one furanone (emoxyfurane) was found to simulate N-acylhomoserine lactone activity and induce violacein formation. The most effective substances acting negatively both on growth and quorum sensing were analogs and intermediates in synthesis of the butenolides from Streptomyces antibioticus. Conclusion As the regulation of many bacterial processes is governed by quorum sensing systems, the finding of natural and synthetic furanones acting as agonists or antagonists suggests an interesting tool to control and handle detrimental AHL induced effects. Some effects are due to general toxicity; others are explained by a competitive interaction for Lux

Enhanced cytostatic activity of the sesquiterpene lactone eupatoriopicrin by glutathione depletion.

PubMed Central

Woerdenbag, H. J.; Lemstra, W.; Malingré, T. M.; Konings, A. W.

1989-01-01

Eupatoriopicrin (EUP), a sesquiterpene lactone from Eupatorium cannabinum L., possesses cytostatic activity. This was demonstrated for FIO 26 cells in vitro with the aid of a clonogenic assay and in vivo by tumour growth delay in FIO 26 and Lewis lung tumour-bearing mice. In vitro the IC50 for 1 h exposure to EUP was 1.5 microgram ml-1 (4.1 nmol ml-1). This concentration depleted about 25% of its cellular GSH concentration. Pretreatment of FIO 26 cells with BSO, resulting in greater than 99%. GSH depletion, enhanced the cytotoxic effect of EUP. The dose-enhancement factor at the level of 10% cell survival was 2.3. Growth inhibition of the Lewis lung carcinoma and the FIO 26 fibrosarcoma, solidly growing in C57Bl mice, was found after i.v. injection of 20 or 40 mg kg-1 EUP, at a tumour volume of about 500 microliters. Pretreatment with BSO at a dose of 4 mmol kg-1 i.p., 6 h before EUP administration, resulted in a significantly stronger growth delay of both tumours compared with EUP only. At the time of EUP treatment, cellular GSH in the tumours was reduced by BSO treatment to about 60%. It is concluded that EUP possesses antitumour activity in vivo and that chemosensitisation of EUP may be accomplished by pretreatment with BSO, indicating that endogenous GSH protects against the cytostatic action of EUP. PMID:2757925

Savinin, a lignan from Pterocarpus santalinus inhibits tumor necrosis factor-alpha production and T cell proliferation.

PubMed

Cho, J Y; Park, J; Kim, P S; Yoo, E S; Baik, K U; Park, M H

2001-02-01

Two lignans were isolated from the heartwood of Pterocarpus santalinus by activity-guided fractionation and investigated for their biological properties and molecular mechanism of action. On the basis of their spectroscopic data, these compounds were identified as savinin (1) and calocedrin (2), dibenzyl butyrolactone-type lignan compounds having an alpha-arylidene gamma-lactone structure. These lignans significantly inhibited tumor necrosis factor (TNF)-a production in lipopolysaccharide (LPS)-stimulated RAW264.7 cells, and T cell proliferation elicited by concanavalin (Con A), without displaying cytotoxicity. The molecular inhibitory mechanism of compound 1 was confirmed to be mediated by the non-polar butyrolactone ring, according to a structure-relationship study with structurally related and unrelated compounds, such as arctigenin (a dibenzyl butyrolactone type lignan), eudesmin (a furofuran type lignan), isolariciresinol (a dibenzylbutane type lignan), and cynaropicrin (a sesquiterpene lactone). The results suggest that savinin may act as an active principle in the reported biological activities of P. santalinus, such as antiinflammatory effect, by mediation of the butyrolactone ring as a valuable pharmacophore.

Automated plant, production management system

NASA Astrophysics Data System (ADS)

Aksenova, V. I.; Belov, V. I.

1984-12-01

The development of a complex of tasks for the operational management of production (OUP) within the framework of an automated system for production management (ASUP) shows that it is impossible to have effective computations without reliable initial information. The influence of many factors involving the production and economic activity of the entire enterprise upon the plan and course of production are considered. It is suggested that an adequate model should be available which covers all levels of the hierarchical system: workplace, section (bridgade), shop, enterprise, and the model should be incorporated into the technological sequence of performance and there should be provisions for an adequate man machine system.

pH-Dependent stability of azithromycin in aqueous solution and structure identification of two new degradation products.

PubMed

Saita, Maria Grazia; Aleo, Danilo; Melilli, Barbara; Mangiafico, Sergio; Cro, Melina; Sanfilippo, Claudia; Patti, Angela

2018-05-28

The degradation profile of azithromycin in buffered solutions was investigated using HPLC and found to be pH dependent in the range of 6.0-7.2. Desosaminylazitromycin, derived from hydrolytic loss of cladinose of the parent molecule, was the major degradation product at pH 6.0 but its amount progressively decreased moving toward pH 7.2. Two additional unreported degradation products were also observed and their structures were fully elucidated by MS- and NMR-spectroscopy to be associated with opening of the macrocyclic lactone ring. Copyright © 2018. Published by Elsevier B.V.

Ascorbic Acid Metabolism in Pea Seedlings. A Comparison of d-Glucosone, l-Sorbosone, and l-Galactono-1,4-Lactone as Ascorbate Precursors1

PubMed Central

Pallanca, Jane E.; Smirnoff, Nicholas

1999-01-01

l-Ascorbic acid (AsA) accumulates in pea (Pisum sativum L.) seedlings during germination, with the most rapid phase of accumulation coinciding with radicle emergence. Monodehydroascorbate reductase and dehydroascorbic acid reductase were active in the embryonic axes before AsA accumulation started, whereas AsA oxidase and AsA peroxidase activities increased in parallel with AsA. Excised embryonic axes were used to investigate the osone pathway of AsA biosynthesis, in which d-glucosone and l-sorbosone are the proposed intermediates. [U-14C]Glucosone was incorporated into AsA and inhibited the incorporation of [U-14C]glucose (Glc) into AsA. A higher d-glucosone concentration (5 mm) inhibited AsA accumulation. l-Sorbosone did not affect AsA pool size but caused a small inhibition in the incorporation of [U-14C]Glc into AsA. Oxidase and dehydrogenase activities capable of converting Glc or Glc-6-phosphate to glucosone were not detected in embryonic axis extracts. The osones are therefore unlikely to be physiological intermediates of AsA biosynthesis. l-Galactono-1,4-lactone, recently proposed as the AsA precursor (G.L. Wheeler, M.A. Jones, N. Smirnoff [1998] Nature 393: 365–369), was readily converted to AsA by pea embryonic axes. Although l-galactono-1,4-lactone did not inhibit [14C]Glc incorporation into AsA, this does not mean that it is not a precursor, because competition between endogenous and exogenous pools was minimized by its very small pool size and rapid metabolism. PMID:10364396

Localization of sesquiterpene lactone biosynthesis in cells of capitate glandular trichomes of Helianthus annuus (Asteraceae).

PubMed

Amrehn, Evelyn; Aschenbrenner, Anna-Katharina; Heller, Annerose; Spring, Otmar

2016-03-01

Capitate glandular trichomes (CGT) of sunflower, Helianthus annuus, synthesize bioactive sesquiterpene lactones (STLs) within a short period of only a few days during trichome development. In the current project, the subcellular localization of H. annuus germacrene A monooxygenase (HaGAO), a key enzyme of the STL biosynthesis in sunflower CGT, was investigated. A polyclonal antibody raised against this enzyme was used for immunolabelling. HaGAO was found in secretory and stalk cells of CGT. This correlated with the appearance of smooth endoplasmic reticulum in both cell types. Stalk cells and secretory cells differed in form, size and types of plastids, but both had structures necessary for secretion. No HaGAO-specific immunoreaction was found in sunflower leaf tissue outside of CGT or in developing CGT before the secretory phase had started. Our results indicated that not only secretory cells but also nearly all cells of the CGT were involved in the biosynthesis of STL and that this process was not linked to the presence or absence of a specific type of plastid.

N-(3-Oxo-acyl)-homoserine lactone induces apoptosis primarily through a mitochondrial pathway in fibroblasts.

PubMed

Neely, Aaron M; Zhao, Guoping; Schwarzer, Christian; Stivers, Nicole S; Whitt, Aaron G; Meng, Shuhan; Burlison, Joseph A; Machen, Terry E; Li, Chi

2018-01-01

N-(3-Oxododecanoyl)-l-homoserine lactone (C12) is produced by Pseudomonas aeruginosa to function as a quorum-sensing molecule for bacteria-bacteria communication. C12 is also known to influence many aspects of human host cell physiology, including induction of cell death. However, the signalling pathway(s) leading to C12-triggered cell death is (are) still not completely known. To clarify cell death signalling induced by C12, we examined mouse embryonic fibroblasts deficient in "initiator" caspases or "effector" caspases. Our data indicate that C12 selectively induces the mitochondria-dependent intrinsic apoptotic pathway by quickly triggering mitochondrial outer membrane permeabilisation. Importantly, the activities of C12 to permeabilise mitochondria are independent of activation of both "initiator" and "effector" caspases. Furthermore, C12 directly induces mitochondrial outer membrane permeabilisation in vitro. Overall, our study suggests a mitochondrial apoptotic signalling pathway triggered by C12, in which C12 or its metabolite(s) acts on mitochondria to permeabilise mitochondria, leading to activation of apoptosis. © 2017 John Wiley & Sons Ltd.

Non-contact evaluation of milk-based products using air-coupled ultrasound

NASA Astrophysics Data System (ADS)

Meyer, S.; Hindle, S. A.; Sandoz, J.-P.; Gan, T. H.; Hutchins, D. A.

2006-07-01

An air-coupled ultrasonic technique has been developed and used to detect physicochemical changes of liquid beverages within a glass container. This made use of two wide-bandwidth capacitive transducers, combined with pulse-compression techniques. The use of a glass container to house samples enabled visual inspection, helping to verify the results of some of the ultrasonic measurements. The non-contact pulse-compression system was used to evaluate agglomeration processes in milk-based products. It is shown that the amplitude of the signal varied with time after the samples had been treated with lactic acid, thus promoting sample destabilization. Non-contact imaging was also performed to follow destabilization of samples by scanning in various directions across the container. The obtained ultrasonic images were also compared to those from a digital camera. Coagulation with glucono-delta-lactone of skim milk poured into this container could be monitored within a precision of a pH of 0.15. This rapid, non-contact and non-destructive technique has shown itself to be a feasible method for investigating the quality of milk-based beverages, and possibly other food products.

Development of two step liquid-liquid extraction tandem UHPLC-MS/MS method for the simultaneous determination of Ginkgo flavonoids, terpene lactones and nimodipine in rat plasma: Application to the pharmacokinetic study of the combination of Ginkgo biloba dispersible tablets and Nimodipine tablets.

PubMed

Xiao, Jie; Wang, Tianyang; Li, Pei; Liu, Ran; Li, Qing; Bi, Kaishun

2016-08-15

A sensitive, reliable and accurate UHPLC-MS/MS method has been firstly established and validated for the simultaneous quantification of ginkgo flavonoids, terpene lactones and nimodipine in rat plasma after oral administration of Ginkgo biloba dispersible tablets, Nimodipine tablets and the combination of the both, respectively. The plasma samples were extracted by two step liquid-liquid extraction, nimodipine was extracted by hexane-ether (3:1, v/v) at the first step, after that ginkgo flavonoids and terpene lactones were extracted by ethyl acetate. Then the analytes were successfully separated by running gradient elution with the mobile phase consisting of 0.1% formic acid in water and methanol at a flow rate of 0.6mL/min. The detection of the analytes was performed on a UHPLC-MS/MS system with turbo ion spray source in the negative ion and multiple reaction monitoring (MRM) mode. The calibration curves for the determination of all the analytes showed good linearity (R(2)>0.99), and the lower limits of quantification were 0.50-4.00ng/mL. Intra-day and inter-day precisions were in the range of 3.6%-9.2% and 3.2%-13.1% for all the analytes. The mean extraction recoveries of the analytes were within 69.82%-103.5% and the matrix were within 82.8%-110.0%. The validated method had been successfully applied to compare the pharmacokinetic parameters of ginkgo flavonoids, terpene lactones and nimodipine in rat plasma after oral administration of Ginkgo biloba dispersible tablets, Nimodipine tablets with the combination of the both. There were no statistically significant differences on the pharmacokinetic behaviors of all the analytes between the combined and single administration groups. Results showed that the combination of the two agents may avoid dosage adjustments in clinic and the combination is more convenient as well as efficient on different pathogenesis of cerebral ischemia. Copyright © 2016 Elsevier B.V. All rights reserved.

NDSI products system based on Hadoop platform

NASA Astrophysics Data System (ADS)

Zhou, Yan; Jiang, He; Yang, Xiaoxia; Geng, Erhui

2015-12-01

Snow is solid state of water resources on earth, and plays an important role in human life. Satellite remote sensing is significant in snow extraction with the advantages of cyclical, macro, comprehensiveness, objectivity, timeliness. With the continuous development of remote sensing technology, remote sensing data access to the trend of multiple platforms, multiple sensors and multiple perspectives. At the same time, in view of the remote sensing data of compute-intensive applications demand increase gradually. However, current the producing system of remote sensing products is in a serial mode, and this kind of production system is used for professional remote sensing researchers mostly, and production systems achieving automatic or semi-automatic production are relatively less. Facing massive remote sensing data, the traditional serial mode producing system with its low efficiency has been difficult to meet the requirements of mass data timely and efficient processing. In order to effectively improve the production efficiency of NDSI products, meet the demand of large-scale remote sensing data processed timely and efficiently, this paper build NDSI products production system based on Hadoop platform, and the system mainly includes the remote sensing image management module, NDSI production module, and system service module. Main research contents and results including: (1)The remote sensing image management module: includes image import and image metadata management two parts. Import mass basis IRS images and NDSI product images (the system performing the production task output) into HDFS file system; At the same time, read the corresponding orbit ranks number, maximum/minimum longitude and latitude, product date, HDFS storage path, Hadoop task ID (NDSI products), and other metadata information, and then create thumbnails, and unique ID number for each record distribution, import it into base/product image metadata database. (2)NDSI production module: includes

N-Acyl Homoserine Lactone-Mediated Quorum Sensing with Special Reference to Use of Quorum Quenching Bacteria in Membrane Biofouling Control

PubMed Central

Paul, Diby

2014-01-01

Membrane biofouling remains a severe problem to be addressed in wastewater treatment systems affecting reactor performance and economy. The finding that many wastewater bacteria rely on N-acyl homoserine lactone-mediated quorum sensing to synchronize their activities essential for biofilm formations; the quenching bacterial quorum sensing suggests a promising approach for control of membrane biofouling. A variety of quorum quenching compounds of both synthetic and natural origin have been identified and found effective in inhibition of membrane biofouling with much less environmental impact than traditional antimicrobials. Work over the past few years has demonstrated that enzymatic quorum quenching mechanisms are widely conserved in several prokaryotic organisms and can be utilized as a potent tool for inhibition of membrane biofouling. Such naturally occurring bacterial quorum quenching mechanisms also play important roles in microbe-microbe interactions and have been used to develop sustainable nonantibiotic antifouling strategies. Advances in membrane fabrication and bacteria entrapment techniques have allowed the implication of such quorum quenching bacteria for better design of membrane bioreactor with improved antibiofouling efficacies. In view of this, the present paper is designed to review and discuss the recent developments in control of membrane biofouling with special emphasis on quorum quenching bacteria that are applied in membrane bioreactors. PMID:25147787

Acyl homoserine lactone changes the abundance of proteins and the levels of organic acids associated with stationary phase in Salmonella Enteritidis.

PubMed

de Almeida, Felipe Alves; Pimentel-Filho, Natan de Jesus; Carrijo, Lanna Clícia; Bento, Cláudia Braga Pereira; Baracat-Pereira, Maria Cristina; Pinto, Uelinton Manoel; de Oliveira, Leandro Licursi; Vanetti, Maria Cristina Dantas

2017-01-01

Quorum sensing (QS) is cell-cell communication mechanism mediated by signaling molecules known as autoinducers (AIs) that lead to differential gene expression. Salmonella is unable to synthesize the AI-1 acyl homoserine lactone (AHL), but is able to recognize AHLs produced by other microorganisms through SdiA protein. Our study aimed to evaluate the influence of AI-1 on the abundance of proteins and the levels of organic acids of Salmonella Enteritidis. The presence of N-dodecyl-homoserine lactone (C12-HSL) did not interfere on the growth or the total amount of extracted proteins of Salmonella. However, the abundance of the proteins PheT, HtpG, PtsI, Adi, TalB, PmgI (or GpmI), Eno, and PykF enhanced while the abundance of the proteins RplB, RplE, RpsB, Tsf, OmpA, OmpC, OmpD, and GapA decreased when Salmonella Enteritidis was anaerobically cultivated in the presence of C12-HSL. Additionally, the bacterium produced less succinic, lactic, and acetic acids in the presence of C12-HSL. However, the concentration of extracellular formic acid reached 20.46 mM after 24 h and was not detected when the growth was in the absence of AI-1. Considering the cultivation period for protein extraction, their abundance, process and function, as well as the levels of organic acids, we observed in cells cultivated in presence of C12-HSL a correlation with what is described in the literature as entry into the stationary phase of growth, mainly related to nitrogen and amino acid starvation and acid stress. Further studies are needed in order to determine the specific role of the differentially abundant proteins and extracellular organic acids secreted by Salmonella in the presence of quorum sensing signaling molecules. Copyright © 2016 Elsevier Ltd. All rights reserved.

Methylobacterium extorquens AM1 produces a novel type of acyl-homoserine lactone with a double unsaturated side chain under methylotrophic growth conditions.

PubMed

Nieto Penalver, Carlos G; Morin, Danièle; Cantet, Franck; Saurel, Olivier; Milon, Alain; Vorholt, Julia A

2006-01-23

Acyl-homoserine lactones (acyl-HSLs) have emerged as important regulatory molecules for many gram-negative bacteria. We have found that Methylobacterium extorquens AM1, a member of the pink-pigmented facultative methylotrophs commonly present on plant surfaces, produces several acyl-HSLs depending upon the carbon source. A novel HSL was discovered with a double unsaturated carbon chain (N-(tetradecenoyl)) (C14:2) and characterized by MS and proton NMR. This long-chain acyl-HSL is synthesized by MlaI that also directs synthesis of C14:1-HSL. The Alphaproteobacterium also produces N-hexanoyl-HSL (C6-HSL) and N-octanoyl-HSL (C8-HSL) via MsaI.

The presence and role of bacterial quorum sensing in activated sludge

PubMed Central

Chong, Grace; Kimyon, Onder; Rice, Scott A.; Kjelleberg, Staffan; Manefield, Mike

2012-01-01

Summary Activated sludge used for wastewater treatment globally is composed of a high‐density microbial community of great biotechnological significance. In this study the presence and purpose of quorum sensing via N‐acylated‐l‐homoserine lactones (AHLs) in activated sludge was explored. The presence of N‐heptanoyl‐l‐homoserine lactone in organic extracts of sludge was demonstrated along with activation of a LuxR‐based AHL monitor strain deployed in sludge, indicating AHL‐mediated gene expression is active in sludge flocculates but not in the bulk aqueous phase. Bacterial isolates from activated sludge were screened for AHL production and expression of phenotypes commonly but not exclusively regulated by AHL‐mediated gene transcription. N‐acylated‐l‐homoserine lactone and exoenzyme production were frequently observed among the isolates. N‐acylated‐l‐homoserine lactone addition to sludge upregulated chitinase activity and an AHL‐ and chitinase‐producing isolate closely related to Aeromonas hydrophila was shown to respond to AHL addition with upregulation of chitinase activity. N‐acylated‐l‐homoserine lactones produced by this strain were identified and genes ahyI/R and chiA, encoding AHL production and response and chitinase activity respectively, were sequenced. These experiments provide insight into the relationship between AHL‐mediated gene expression and exoenzyme activity in activated sludge and may ultimately create opportunities to improve sludge performance. PMID:22583685

Improving laser system productivity through production line integration

NASA Astrophysics Data System (ADS)

Belforte, David A.

1994-09-01

Thousands of laser systems are employed profitably in a variety of industrial applications. These installations have proved successful for economic and technical reasons. And, in certain applications: ceramic scribing, resistor trimming, sheet metal cutting, and air foil drilling, for example, have become the industry standard. Most of these installations are free standing or, at best, part of an off-line manufacturing cell. Examples of laser systems fully integrated into a production line, where the laser process is synchronized with up and down stream manufacturing operation, are rare. The laser has been under utilized in its potential contribution to production line productivity. Current development in laser beam delivery: multiplexing, beam splitting and other distributed energy concepts make the laser an attractive option for just-in-time manufacturing operations. The reasons for this apparent neglect of the laser's full potential are reviewed in this paper, and suggestions for improvement of this situation are offered. Examples of fully integrated laser systems and their successful implementation are described and a forecast of changes in the way lasers contribute to improved productivity and profitability will be made.

Skin penetration studies of Arnica preparations and of their sesquiterpene lactones.

PubMed

Wagner, Steffen; Suter, Andreas; Merfort, Irmgard

2004-10-01

Alcoholic preparations of Arnica montana are widely used for the topical treatment of various inflammatory diseases. Sesquiterpene lactones (SLs) are mainly responsible for their anti-inflammatory activity. Here we have studied the penetration kinetics of Arnica tinctures prepared from dried Arnica flowers originating from different chemotypes as well as of their respective dominating SLs, helenalin isobutyrate and 11alpha,13-dihydrohelenalin acetate. Some alcoholic preparations of fresh Arnica flowers and an Arnica fresh plant gel were also included in the study. We used the stripping method with adhesive tape and pig skin as a model and determined the quantity of SLs in the stripped layers of the stratum corneum (SC). Thus, we observed the penetration into and permeation through this uppermost part of the skin. Whereas isolated SLs permeate through the SC only in a very small amount, permeation of SLs was much higher when they were present in the tinctures. Furthermore, differences of permeation were observed between helenalin and dihydrohelenalin derivatives. Permeation through the SC could be determined for the tested Arnica preparations of fresh Arnica flowers with two preparations showing the best penetration behaviour of all the tested substances. Moreover, the effects of incubation time as well as of repeated applications were investigated with one preparation. Altogether, this study shows that a sufficient amount of SLs might permeate the skin barrier by using Arnica preparations to exert anti-inflammatory effects and that the topical use of plant preparations may be advantageous compared to the isolated compounds.

Structure investigation of maltacine B1a, B1b, B2a and B2b: cyclic peptide lactones of the maltacine complex from Bacillus subtilis.

PubMed

Hagelin, Gunnar

2005-04-01

A new complex of cyclic peptide lactone antibiotics from Bacillus subtilis, which we named maltacines, has recently been described. The structure elucidation of four of them is reported in this paper. The amino acid sequences and structures of the peptides were found by MSn of the ring-opened linear peptides that gave uninterrupted sequences of Bn and Y''n ions. The identities of three unknown residues in the sequences were solved by a combination of derivatization with phenyl isothiocyanate (PITC), high-resolution mass spectrometry and H/D exchange. The nature and position of the cyclic structure were revealed by a chemoselective ring opening with Na18OH and was found to be a lactone formed between a hydroxyl of residue number 4 and the C-terminal amino acid number 12. For verification of the structure of the B2+ ion, peptides with different combinations of P/Q and P/K at the N-terminus were synthesized. The structures of the four peptides were found to be as follows: B1a/B2a, cyclo-4,12(P-Q-Y-HNLeu-A-E-T-Y-Orn-103-Y-I-OH); and B1b/B2b, cyclo-4,12(P-Q-Y-HNLeu-A-E-T-Y-K-103-Y-I-OH). Copyright 2005 John Wiley & Sons, Ltd.

Sterile Product Packaging and Delivery Systems.

PubMed

Akers, Michael J

2015-01-01

Both conventional and more advanced product container and delivery systems are the focus of this brief article. Six different product container systems will be discussed, plus advances in primary packaging for special delivery systems and needle technology.

Shifting the paradigm in Dirofilaria immitis prevention: blocking transmission from mosquitoes to dogs using repellents/insecticides and macrocyclic lactone prevention as part of a multimodal approach.

PubMed

McCall, John W; Varloud, Marie; Hodgkins, Elizabeth; Mansour, Abdelmoneim; DiCosty, Utami; McCall, Scott; Carmichael, James; Carson, Ben; Carter, Justin

2017-11-09

This study assessed the influence of a topical ectoparasiticide (dinotefuran-permethrin-pyriproxyfen, DPP, Vectra® 3D, Ceva Animal Health) combined with a macrocyclic lactone (milbemycin oxime, MBO, Interceptor®, Virbac) on transmission of heartworm L3 from mosquitoes to dogs and subsequent development of worms in treated dogs exposed to infected mosquitoes. Thirty-two beagle dogs were allocated to four groups of eight: Group 1, untreated controls; Group 2, treated topically with DPP on Day 0; Group 3, treated orally with MBO on Day 51; and Group 4, treated with DPP on Day 0 and MBO on Day 51. Dogs were exposed under sedation for 1 h to Dirofilaria immitis (JYD-34)-infected Aedes aegypti on Days 21 and 28. At the end of each exposure, mosquitoes were classified as live, moribund, or dead and engorged or non-engorged. Live or moribund mosquitoes were incubated for daily survival assessment for 3 days. Mosquitoes were dissected before and after exposure to estimate the number of L3 transmitted to each dog. Dogs were necropsied 148 to 149 days postinfection. A total of 418 mosquitoes fed on the 16 dogs in Groups 1 and 3, while only 6 fed on the 16 DPP-treated dogs in Groups 2 and 4. Mosquito anti-feeding (repellency) effect in Groups 2 and 4 was 98.1 and 99.1%, respectively. The estimated numbers of L3 transmitted to controls, DPP-treated, MBO-treated and DPP + MBO-treated dogs were 76, 2, 78, and 1, respectively. No heartworms were detected in any of the DPP + MBO-treated dogs (100% efficacy), while 8 out of 8 were infected in the control group (range, 21-66 worms per dog), 8 out of 8 were infected in the MBO-treated group (58% efficacy), and 3 out of 8 were infected in the DPP-treated group (96% efficacy). DPP repelled and killed most mosquitoes that were capable of transmitting heartworm L3 to dogs. The "Double Defense" protocol of DPP + MBO had better efficacy for protecting dogs against heartworm transmission and infection than MBO alone. This added

Acyl-homoserine lactone-based quorum sensing and quorum quenching hold promise to determine the performance of biological wastewater treatments: An overview.

PubMed

Huang, Jinhui; Shi, Yahui; Zeng, Guangming; Gu, Yanling; Chen, Guiqiu; Shi, Lixiu; Hu, Yi; Tang, Bi; Zhou, Jianxin

2016-08-01

Quorum sensing (QS) is a communication process between cells, in which bacteria secrete and sense the specific chemicals, and regulate gene expression in response to population density. Quorum quenching (QQ) blocks QS system, and inhibits gene expression mediating bacterial behaviors. Given the extensive research of acyl-homoserine lactone (AHL) signals, existences and effects of AHL-based QS and QQ in biological wastewater treatments are being subject to high concern. This review summarizes AHL structure, synthesis mode, degradation mechanisms, analytical methods, environmental factors, AHL-based QS and QQ mechanisms. The existences and roles of AHL-based QS and QQ in biomembrane processes, activated sludge processes and membrane bioreactors are summarized and discussed, and corresponding exogenous regulation strategy by selective enhancement of AHL-based QS or QQ coexisting in biological wastewater treatments is suggested. Such strategies including the addition of AHL signals, AHL-producing bacteria as well as quorum quenching enzyme or bacteria can effectively improve wastewater treatment performance without killing or limiting bacterial survival and growth. This review will present the theoretical and practical cognition for bacterial AHL-based QS and QQ, suggest the feasibility of exogenous regulation strategies in biological wastewater treatments, and provide useful information to scientists and engineers who work in this field. Copyright © 2016 Elsevier Ltd. All rights reserved.

Partitioning in parallel processing of production systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oflazer, K.

1987-01-01

This thesis presents research on certain issues related to parallel processing of production systems. It first presents a parallel production system interpreter that has been implemented on a four-processor multiprocessor. This parallel interpreter is based on Forgy's OPS5 interpreter and exploits production-level parallelism in production systems. Runs on the multiprocessor system indicate that it is possible to obtain speed-up of around 1.7 in the match computation for certain production systems when productions are split into three sets that are processed in parallel. The next issue addressed is that of partitioning a set of rules to processors in a parallel interpretermore » with production-level parallelism, and the extent of additional improvement in performance. The partitioning problem is formulated and an algorithm for approximate solutions is presented. The thesis next presents a parallel processing scheme for OPS5 production systems that allows some redundancy in the match computation. This redundancy enables the processing of a production to be divided into units of medium granularity each of which can be processed in parallel. Subsequently, a parallel processor architecture for implementing the parallel processing algorithm is presented.« less

Biophotolysis systems for hydrogen production

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rao, K.K.; Adams, M.W.W.; Gisby, P.E.

1981-01-01

Model systems containing natural and synthetic catalysts were constructed for the production of H/sub 2/ from water using visible solar radiation as the energy source. The authors have investigated the use of aqueous systems with proflavine as the light activator and artificial electron donors for subsequent production of H/sub 2/ when coupled to electron mediators and hydrogenase (or Pt). The characteristics, relative merits and defects of these systems are discussed. 22 refs.

A Second Quorum-Sensing System Regulates Cell Surface Properties but Not Phenazine Antibiotic Production in Pseudomonas aureofaciens

PubMed Central

Zhang, Zhongge; Pierson, Leland S.

2001-01-01

The root-associated biological control bacterium Pseudomonas aureofaciens 30-84 produces a range of exoproducts, including protease and phenazines. Phenazine antibiotic biosynthesis by phzXYFABCD is regulated in part by the PhzR-PhzI quorum-sensing system. Mutants defective in phzR or phzI produce very low levels of phenazines but wild-type levels of exoprotease. In the present study, a second genomic region of strain 30-84 was identified that, when present in trans, increased β-galactosidase activity in a genomic phzB::lacZ reporter and partially restored phenazine production to a phzR mutant. Sequence analysis identified two adjacent genes, csaR and csaI, that encode members of the LuxR-LuxI family of regulatory proteins. No putative promoter region is present upstream of the csaI start codon and no lux box-like element was found in either the csaR promoter or the 30-bp intergenic region between csaR and csaI. Both the PhzR-PhzI and CsaR-CsaI systems are regulated by the GacS-GacA two-component regulatory system. In contrast to the multicopy effects of csaR and csaI in trans, a genomic csaR mutant (30-84R2) and a csaI mutant (30-84I2) did not exhibit altered phenazine production in vitro or in situ, indicating that the CsaR-CsaI system is not involved in phenazine regulation in strain 30-84. Both mutants also produced wild-type levels of protease. However, disruption of both csaI and phzI or both csaR and phzR eliminated both phenazine and protease production completely. Thus, the two quorum-sensing systems do not interact for phenazine regulation but do interact for protease regulation. Additionally, the CsaI N-acylhomoserine lactone (AHL) signal was not recognized by the phenazine AHL reporter 30-84I/Z but was recognized by the AHL reporters Chromobacterium violaceum CV026 and Agrobacterium tumefaciens A136(pCF240). Inactivation of csaR resulted in a smooth mucoid colony phenotype and formation of cell aggregates in broth, suggesting that CsaR is involved in

New sesquiterpene lactones from Arnica tincture prepared from fresh flowerheads of Arnica montana.

PubMed

Kos, Olha; Lindenmeyer, Maja T; Tubaro, Aurelia; Sosa, Silvio; Merfort, Irmgard

2005-11-01

Investigation of an ethanolic extract prepared from fresh Arnica montana flowers afforded three new 1,5- trans-guaianolides, of which 11alpha,13-dihydro-2-O-tigloylflorilenalin and the respective 2-O-isovaleryl derivative are reported for the first time. Additionally, three new and one known 2beta-ethoxy-2,3-dihydrohelenalin esters were isolated. GC/MS studies of the extract after a two year storage at 4 degrees C demonstrated that the latter were artefacts that had been formed by addition of ethanol to the cyclopentenone structure of helenalin. Formation of these adducts gave compounds possessing an inhibitory activity comparable to that of 11alpha,13-dihydrohelenalin derivatives in the NF-kappaB EMSA and the IL-8 ELISA in vitro assays as well as in the in vivo croton oil-induced mouse ear edema test for one adduct, namely 2beta-ethoxy-6-O-acetyl-2,3-dihydrohelenalin. As expected, 6-O-(2-methylbutyryl)- and 6-O-methacryloyl-helenalin exhibited a stronger activity in the NF-kappaB EMSA and IL-8 ELISA. Sesquiterpene lactones seem to be the most important NF-kappaB inhibiting compounds in the Arnica extract. Bioguided fractionation using the luciferase reporter gene assay resulted in the isolation of only moderately active compounds, such as 6-acetoxy-2,2-dimethylchroman-4-one and 10-acetoxy-8,9-epoxythymol isobutyrate.

Pesticide Product Information System (PPIS)

EPA Pesticide Factsheets

The Pesticide Product Information System contains information concerning all pesticide products registered in the United States. It includes registrant name and address, chemical ingredients, toxicity category, product names, distributor brand names, site/pest uses, pesticidal type, formulation code, and registration status.

Impact of phenolic compounds in the acyl homoserine lactone-mediated quorum sensing regulatory pathways.

PubMed

Hossain, Md Akil; Lee, Seung-Jin; Park, Na-Hye; Mechesso, Abraham Fikru; Birhanu, Biruk Tesfaye; Kang, JeongWoo; Reza, Md Ahsanur; Suh, Joo-Won; Park, Seung-Chun

2017-09-06

Quorum sensing (QS) is a cell density-dependent regulation of virulent bacterial gene expression by autoinducers that potentially pertains in the epidemic of bacterial virulence. This study was initially designed to evaluate the effect of 5 phenolic compounds in the modulation of QS and virulence factors of Chromobacterium violaceum and Pseudomonas aeruginosa, and to determine the mechanisms of their effects. Biosensor strains were used to assess antibacterial and anti-QS effect of these compounds. Only methyl gallate (MG) among these compounds demonstrated profound anti-QS effect in the preliminary study, and thus only MG was utilized further to evaluate the effects on the synthesis and activity of acyl homoserine lactone (AHL) in C. violaceum and on the modulation of biofilm, motility, proteolytic, elastase, pyocyanin, and rhamnolipid activity in P. aeruginosa. Finally, the effect of MG on the expression of QS-regulated genes of P. aeruginosa was verified. MG suppressed both the synthesis and activity of AHL in C. violaceum. It also restricted the biofilm formation and other QS-associated virulence factor of P. aeruginosa. MG concentration-dependently suppressed the expression of lasI/R, rhlI/R, and pqsA of P. aeruginosa and was non-toxic in in vitro study. This is the first report of the anti-QS mechanism of MG.

Matching Livestock Production Systems and Environment

NASA Astrophysics Data System (ADS)

Becchetti, T.; Stackhouse, J.; Snell, L.; Lile, D.; George, H.; Harper, J. M.; Larson, S.; Mashiri, F.; Doran, M.; Barry, S.

2015-12-01

Livestock production systems vary greatly over the world. Producers try to match the resources they have with the demands of production, this can vary by species, class of animal, number of animals, and production goals, etc. Using California's diversity in production systems as an example, we explored how livestock producers best utilize the forage and feed found in different ecosystems and available in different parts of the state. Livestock grazing, the predominant land use in California and in much of the world, makes efficient use of the natural vegetation produced without additional water (irrigation), minimal inputs such as fertilizer while often supporting a variety of conservation objectives including vegetation management, fire fuels management, and habitat and open space conservation. The numerous by-products produced by other sectors of California's agriculture as well as food industries, such as brewer's grain, cottonseeds, and almond hulls are utilized as a feed source for livestock. These by-products are not only an important feed source especially in drought years but are diverted from our waste stream when utilized by livestock. The concept of matching available resources to livestock needs throughout the world is often overlooked and production systems are often over simplified in projects conducting a life cycle analysis or developing carbon foot prints for livestock production systems. This paper provides details on the various production systems found in California, the ecosystem they have adapted to, and how the producers use science and ecological knowledge to match the biological requirements of the livestock and conservation objectives to feed and forage resources.

Synthesis of Gold Mediated Biocompatible Nanocomposite of Lactone Enriched Fraction from Sahadevi (Vernonia cinerea Lees): An Assessment of Antimalarial Potential.

PubMed

Jyotshna; Shanker, Karuna; Khare, Puja; Tiwari, Nimisha; Mohanty, Shilpa; Bawankule, Dnyaneshwar U; Pal, Anirban

2016-01-01

Metals reduction into submicro/nano size through bhasma preparations for therapeutic use is well established in ancient traditional system of Indian medicines i.e. Ayurveda. Recently, nanotechnology has drawn the attention of researchers to develeope various size and shape nanoparicles / composite for number of applications.In this article, we report the enrichment of lactone enriched fraction (LEF) by liquid-liquid portioning of Vernonia cinerea metabolic extract and sysnthesis of mediated nano-gold composite (LEF-AuNPs) in single step process. The morphological characteristic based on transmission electron microscope (TEM) image analysis showed that LEF-AuNPs were predominantly nanopolygons and nanobots in shapes ranging from 50-200 nm in size. Abundance of phytochemicals in both LEF and LEF-AuNPs was dissimilar. In LEF, montanol- a diterpenoid, while in LEF-AuNPs, neophytadiene- a phytanes was the major compound. HPLC profile of relatively polar compounds also varied drastically. In-vitro biocompatibility, cytotoxicity [MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) based assay] and storage stabilitiy of LEF-AuNPs were evaluated. The moderate ability of LEF-AuNPs to restrict parasitaemia, extended mean survival time of mice infected with Plasmodium berghei and lack of any evident toxicity provides new opportunities for the safe delivery and applications of such nanocomposites in malaria therapy.

CsrA Represses Translation of sdiA, Which Encodes the N-Acylhomoserine-l-Lactone Receptor of Escherichia coli, by Binding Exclusively within the Coding Region of sdiA mRNA ▿ †

PubMed Central

Yakhnin, Helen; Baker, Carol S.; Berezin, Igor; Evangelista, Michael A.; Rassin, Alisa; Romeo, Tony; Babitzke, Paul

2011-01-01

The RNA binding protein CsrA is the central component of a conserved global regulatory system that activates or represses gene expression posttranscriptionally. In every known example of CsrA-mediated translational control, CsrA binds to the 5′ untranslated region of target transcripts, thereby repressing translation initiation and/or altering the stability of the RNA. Furthermore, with few exceptions, repression by CsrA involves binding directly to the Shine-Dalgarno sequence and blocking ribosome binding. sdiA encodes the quorum-sensing receptor for N-acyl-l-homoserine lactone in Escherichia coli. Because sdiA indirectly stimulates transcription of csrB, which encodes a small RNA (sRNA) antagonist of CsrA, we further explored the relationship between sdiA and the Csr system. Primer extension analysis revealed four putative transcription start sites within 85 nucleotides of the sdiA initiation codon. Potential σ70-dependent promoters were identified for each of these primer extension products. In addition, two CsrA binding sites were predicted in the initially translated region of sdiA. Expression of chromosomally integrated sdiA′-′lacZ translational fusions containing the entire promoter and CsrA binding site regions indicates that CsrA represses sdiA expression. The results from gel shift and footprint studies demonstrate that tight binding of CsrA requires both of these sites. Furthermore, the results from toeprint and in vitro translation experiments indicate that CsrA represses translation of sdiA by directly competing with 30S ribosomal subunit binding. Thus, this represents the first example of CsrA preventing translation by interacting solely within the coding region of an mRNA target. PMID:21908661

Stereoselective Synthesis of Functionalized Bicyclic Scaffolds by Passerini 3-Center-2-Component Reactions of Cyclic Ketoacids.

PubMed

Cioc, Răzvan C; Estévez, Verónica; van der Niet, Daan J; Vande Velde, Christophe M L; Turrini, Nikolaus G; Hall, Mélanie; Faber, Kurt; Ruijter, Eelco; Orru, Romano V A

2017-03-03

We report the use of bifunctional starting materials (ketoacids) in a diastereoselective Passerini three-center-two-component reaction. Study of the reaction scope revealed the required structural features for stereoselectivity in the isocyanide addition. In this system, an interesting isomerization of the primary Passerini product - the α-carboxamido lactone - into an atypical product, an α-hydroxy imide, was found to occur under acidic conditions. Furthermore, enantioenriched Passerini products can be generated from an enantioenriched ketoacid obtained by chemoenzymatic synthesis.

Microbial Baeyer-Villiger oxidation of 5α-steroids using Beauveria bassiana. A stereochemical requirement for the 11α-hydroxylation and the lactonization pathway.

PubMed

Świzdor, Alina; Panek, Anna; Milecka-Tronina, Natalia

2014-04-01

Beauveria bassiana KCH 1065, as was recently demonstrated, is unusual amongst fungal biocatalysts in that it converts C19 3-oxo-4-ene and 3β-hydroxy-5-ene as well as 3β-hydroxy-5α-saturated steroids to 11α-hydroxy ring-D lactones. The Baeyer-Villiger monooxygenase (BVMO) of this strain is distinguished from other enzymes catalyzing BVO of steroidal ketones by the fact that it oxidizes solely substrates with 11α-hydroxyl group. The current study using a series of 5α-saturated steroids (androsterone, 3α-androstanediol and androstanedione) has highlighted that a small change of the steroid structure can result in significant differences of the metabolic fate. It was found that the 3α-stereochemistry of hydroxyl group restricted "normal" binding orientation of the substrate within 11α-hydroxylase and, as a result, androsterone and 3α-androstanediol were converted into a mixture of 7β-, 11α- and 7α-hydroxy derivatives. Hydroxylation of androstanedione occurred only at the 11α-position, indicating that the 3-oxo group limits the alternative binding orientation of the substrate within the hydroxylase. Only androstanedione and 3α-androstanediol were metabolized to hydroxylactones. The study uniquely demonstrated preference for oxidation of equatorial (11α-, 7β-) hydroxyketones by BVMO from B. bassiana. The time course experiments suggested that the activity of 17β-HSD is a factor determining the amount of produced ring-D lactones. The obtained 11α-hydroxylactones underwent further transformations (oxy-red reactions) at C-3. During conversion of androstanedione, a minor dehydrogenation pathway was observed with generation of 11α,17β-dihydroxy-5α-androst-1-en-3-one. The introduction of C1C2 double bond has been recorded in B. bassiana for the first time. Copyright © 2014 Elsevier Inc. All rights reserved.

Genome sequencing-assisted identification and the first functional validation of N-acyl-homoserine-lactone synthases from the Sphingomonadaceae family

PubMed Central

Gan, Han Ming; Dailey, Lucas K.; Halliday, Nigel; Williams, Paul; Hudson, André O.

2016-01-01

Background Members of the genus Novosphingobium have been isolated from a variety of environmental niches. Although genomics analyses have suggested the presence of genes associated with quorum sensing signal production e.g., the N-acyl-homoserine lactone (AHL) synthase (luxI) homologs in various Novosphingobium species, to date, no luxI homologs have been experimentally validated. Methods In this study, we report the draft genome of the N-(AHL)-producing bacterium Novosphingobium subterraneum DSM 12447 and validate the functions of predicted luxI homologs from the bacterium through inducible heterologous expression in Agrobacterium tumefaciens strain NTL4. We developed a two-dimensional thin layer chromatography bioassay and used LC-ESI MS/MS analyses to separate, detect and identify the AHL signals produced by the N. subterraneum DSM 12447 strain. Results Three predicted luxI homologs were annotated to the locus tags NJ75_2841 (NovINsub1), NJ75_2498 (NovINsub2), and NJ75_4146 (NovINsub3). Inducible heterologous expression of each luxI homologs followed by LC-ESI MS/MS and two-dimensional reverse phase thin layer chromatography bioassays followed by bioluminescent ccd camera imaging indicate that the three LuxI homologs are able to produce a variety of medium-length AHL compounds. New insights into the LuxI phylogeny was also gleemed as inferred by Bayesian inference. Discussion This study significantly adds to our current understanding of quorum sensing in the genus Novosphingobium and provide the framework for future characterization of the phylogenetically interesting LuxI homologs from members of the genus Novosphingobium and more generally the family Sphingomonadaceae. PMID:27635318

Fenugreek lactone attenuates palmitate-induced apoptosis and dysfunction in pancreatic β-cells

PubMed Central

Gong, Jing; Dong, Hui; Jiang, Shu-Jun; Wang, Ding-Kun; Fang, Ke; Yang, De-Sen; Zou, Xin; Xu, Li-Jun; Wang, Kai-Fu; Lu, Fu-Er

2015-01-01

AIM: To investigate the effect of fenugreek lactone (FL) on palmitate (PA)-induced apoptosis and dysfunction in insulin secretion in pancreatic NIT-1 β-cells. METHODS: Cells were cultured in the presence or absence of FL and PA (0.25 mmol/L) for 48 h. Then, lipid droplets in NIT-1 cells were observed by oil red O staining, and the intracellular triglyceride content was measured by colorimetric assay. The insulin content in the supernatant was determined using an insulin radio-immunoassay. Oxidative stress-associated parameters, including total superoxide dismutase, glutathione peroxidase and catalase activity and malondialdehyde levels in the suspensions were also examined. The expression of upstream regulators of oxidative stress, such as protein kinase C-α (PKC-α), phospho-PKC-α and P47phox, were determined by Western blot analysis and real-time PCR. In addition, apoptosis was evaluated in NIT-1 cells by flow cytometry assays and caspase-3 viability assays. RESULTS: Our results indicated that compared to the control group, PA induced an increase in lipid accumulation and apoptosis and a decrease in insulin secretion in NIT-1 cells. Oxidative stress in NIT-1 cells was activated after 48 h of exposure to PA. However, FL reversed the above changes. These effects were accompanied by the inhibition of PKC-α, phospho-PKC-α and P47phox expression and the activation of caspase-3. CONCLUSION: FL attenuates PA-induced apoptosis and insulin secretion dysfunction in NIT-1 pancreatic β-cells. The mechanism for this action may be associated with improvements in levels of oxidative stress. PMID:26730156

Influence of dispatching rules on average production lead time for multi-stage production systems.

PubMed

Hübl, Alexander; Jodlbauer, Herbert; Altendorfer, Klaus

2013-08-01

In this paper the influence of different dispatching rules on the average production lead time is investigated. Two theorems based on covariance between processing time and production lead time are formulated and proved theoretically. Theorem 1 links the average production lead time to the "processing time weighted production lead time" for the multi-stage production systems analytically. The influence of different dispatching rules on average lead time, which is well known from simulation and empirical studies, can be proved theoretically in Theorem 2 for a single stage production system. A simulation study is conducted to gain more insight into the influence of dispatching rules on average production lead time in a multi-stage production system. We find that the "processing time weighted average production lead time" for a multi-stage production system is not invariant of the applied dispatching rule and can be used as a dispatching rule independent indicator for single-stage production systems.

Determination of N-acylhomoserine lactones of Pseudomonas aeruginosa in clinical samples from dogs with otitis externa.

PubMed

Kušar, Darja; Šrimpf, Karin; Isaković, Petra; Kalšek, Lina; Hosseini, Javid; Zdovc, Irena; Kotnik, Tina; Vengušt, Modest; Tavčar-Kalcher, Gabrijela

2016-10-18

Bacterial intercellular communication, called quorum sensing, takes place via the production and collective response to signal molecules. In Gram-negative bacteria, like Pseudomonas aeruginosa, these signaling molecules are N-acylhomoserine lactones (AHLs). P. aeruginosa is a common cause of inflammation of the ear canal (otitis externa) in dogs. It employs quorum sensing to coordinate the expression of host tissue-damaging factors, which are largely responsible for its virulence. The treatment of P. aeruginosa-associated otitis is challenging due to a high intrinsic resistance of P. aeruginosa to several antibiotics. Attenuation of quorum sensing signals to inhibit bacterial virulence is a novel strategy for the treatment of resistant bacterial pathogens, including P. aeruginosa. Therefore, it is important to recognize and define quorum sensing signal molecules in clinical samples. To date, there are no reports on determination of AHLs in the veterinary clinical samples. The purpose of this study was to validate an analytical procedure for determination of the concentration of AHLs in the ear rinses from dogs with P. aeruginosa-associated otitis externa. Samples were obtained with rinsing the ear canals with physiological saline solution. For validation, samples from healthy dogs were spiked with none or different known amounts of the selected AHLs. With the validated procedure, AHLs were analyzed in the samples taken in weekly intervals from two dogs, receiving a standard treatment for P. aeruginosa-associated otitis externa. Validation proved that the procedure enables quantification of AHLs in non-clinical and clinical samples. In addition, a time dependent reduction of AHL concentration was detected for the treated dogs. Our results indicate that liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) is superior in detecting AHLs compared to other chromatographic techniques. This is the first report on determination of AHLs in the clinical

Cover crops in vegetable production systems

USDA-ARS?s Scientific Manuscript database

Current vegetable production systems require an intensive amount Current vegetable production systems require an intensive amount of work and inputs, and if not properly managed could have detrimental effects on soil and the environment. Practices such as intensive tillage, increased herbicide use, ...

N-hexanoyl-L-homoserine lactone-degrading Pseudomonas aeruginosa PsDAHP1 protects zebrafish against Vibrio parahaemolyticus infection.

PubMed

Vinoj, Gopalakrishnan; Jayakumar, Rengarajan; Chen, Jiann-Chu; Withyachumnarnkul, Boonsirm; Shanthi, Sathappan; Vaseeharan, Baskaralingam

2015-01-01

Four strains of N-hexanoyl-L-homoserine lactone (AHL)-degrading Pseudomonas spp., named PsDAHP1, PsDAHP2, PsDAHP3, and PsDAHP4 were isolated and identified from the intestine of Fenneropenaeus indicus. PsDAHP1 showed the highest AHL-degrading activity among the four isolates. PsDAHP1 inhibited biofilm-forming exopolysaccharide and altered cell surface hydrophobicity of virulent green fluorescent protein (GFP)-tagged Vibrio parahaemolyticus DAHV2 (GFP-VpDAHV2). Oral administration of PsDAHP1 significantly reduced zebrafish mortality caused by GFP-VpDAHV2 challenge, and inhibited colonisation of GFP-VpDAHV2 in the gills and intestine of zebrafish as evidence by confocal laser scanning microscope and selective plating. Furthermore, zebrafish receiving PsDAHP1-containing feed had increased phagocytic cells of its leucocytes, increased serum activities of superoxide dismutase and lysozyme. The results suggest that Pseudomonas aeruginosa PsDAHP1 could protect zebrafish from V. parahaemolyticus infection by inhibiting biofilm formation and enhancing defence mechanisms of the fish. Copyright © 2014 Elsevier Ltd. All rights reserved.

Highly enantioselective rhodium(I)-catalyzed carbonyl carboacylations initiated by C-C bond activation.

PubMed

Souillart, Laetitia; Cramer, Nicolai

2014-09-01

The lactone motif is ubiquitous in natural products and pharmaceuticals. The Tishchenko disproportionation of two aldehydes, a carbonyl hydroacylation, is an efficient and atom-economic access to lactones. However, these reaction types are limited to the transfer of a hydride to the accepting carbonyl group. The transfer of alkyl groups enabling the formation of CC bonds during the ester formation would be of significant interest. Reported herein is such asymmetric carbonyl carboacylation of aldehydes and ketones, thus affording complex bicyclic lactones in excellent enantioselectivities. The rhodium(I)-catalyzed transformation is induced by an enantiotopic CC bond activation of a cyclobutanone and the formed rhodacyclic intermediate reacts with aldehyde or ketone groups to give highly functionalized lactones. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A comparison of production system life cycle models

NASA Astrophysics Data System (ADS)

Attri, Rajesh; Grover, Sandeep

2012-09-01

Companies today need to keep up with the rapidly changing market conditions to stay competitive. The main issues in this paper are related to a company's market and its competitors. The prediction of market behavior is helpful for a manufacturing enterprise to build efficient production systems. However, these predictions are usually not reliable. A production system is required to adapt to changing markets, but such requirement entails higher cost. Hence, analyzing different life cycle models of the production system is necessary. In this paper, different life cycle models of the production system are compared to evaluate the distinctive features and the limitations of each model. Furthermore, the difference between product life cycle and production life cycle is summarized, and the effect of product life cycle on production life cycle is explained. Finally, a production system life cycle model, along with key activities to be performed in each stage, is proposed specifically for the manufacturing sector.

Conception of Self-Construction Production Scheduling System

NASA Astrophysics Data System (ADS)

Xue, Hai; Zhang, Xuerui; Shimizu, Yasuhiro; Fujimura, Shigeru

With the high speed innovation of information technology, many production scheduling systems have been developed. However, a lot of customization according to individual production environment is required, and then a large investment for development and maintenance is indispensable. Therefore now the direction to construct scheduling systems should be changed. The final objective of this research aims at developing a system which is built by it extracting the scheduling technique automatically through the daily production scheduling work, so that an investment will be reduced. This extraction mechanism should be applied for various production processes for the interoperability. Using the master information extracted by the system, production scheduling operators can be supported to accelerate the production scheduling work easily and accurately without any restriction of scheduling operations. By installing this extraction mechanism, it is easy to introduce scheduling system without a lot of expense for customization. In this paper, at first a model for expressing a scheduling problem is proposed. Then the guideline to extract the scheduling information and use the extracted information is shown and some applied functions are also proposed based on it.

Non-native acylated homoserine lactones reveal that LuxIR quorum sensing promotes symbiont stability

PubMed Central

Ho, Jessica S.; Geske, Grant D.; Blackwell, Helen E.; Ruby, Edward G.

2014-01-01

SUMMARY Quorum sensing, a group behavior coordinated by a diffusible pheromone signal and a cognate receptor, is typical of bacteria that form symbioses with plants and animals. LuxIR-type acyl homoserine-lactone (AHL) quorum sensing is common in Gram-negative proteobacteria, and many members of this group have additional quorum-sensing networks. The bioluminescent symbiont Vibrio fischeri encodes two AHL signal synthases: AinS and LuxI. AinS-dependent quorum sensing converges with LuxI-dependent quorum sensing at the LuxR regulatory element. Both AinS- and LuxI-mediated signaling are required for efficient and persistent colonization of the squid host, Euprymna scolopes. The basis of the mutualism is symbiont bioluminescence, which is regulated by both LuxI- and AinS-dependent quorum sensing, and is essential for maintaining a colonization of the host. Here, we used chemical and genetic approaches to probe the dynamics of LuxI- and AinS-mediated regulation of bioluminescence during symbiosis. We demonstrate that both native AHLs and non-native AHL analogs can be used to non-invasively and specifically modulate induction of symbiotic bioluminescence via LuxI-dependent quorum sensing. Our data suggest that the first day of colonization, during which symbiont bioluminescence is induced by LuxIR, is a critical period that determines the stability of the V. fischeri population once symbiosis is established. PMID:24191970

Wolbachia, doxycycline and macrocyclic lactones: New prospects in the treatment of canine heartworm disease.

PubMed

Kramer, L; Crosara, S; Gnudi, G; Genchi, M; Mangia, C; Viglietti, A; Quintavalla, C

2018-04-30

Melarsomine dihydrochloride (Immiticide®, Merial) is the only approved adulticidal drug for the treatment of canine heartworm disease (HWD). However, in cases where arsenical therapy is not possible or is contraindicated, a monthly heartworm preventive along with doxycycline for a 4-week period, which targets the bacterial endosymbiont Wolbachia, might be considered. There are published reports on the efficacy of ivermectin and doxycycline in both experimentally and naturally infected dogs, but no data on the use of other macrocyclic lactones (MLs) with a similar treatment regime. Preliminary results of studies in dogs show that a topical formulation of moxidectin, the only ML currently registered as a microfilaricide, is also adulticidal when combined with doxycycline. It is not yet known if the efficacy of these combination therapies is due to pharmacokinetic synergism. A recent study showed that serum levels of doxycycline in dogs treated with the combination protocol were not statistically different compared to dogs treated with doxycycline alone. However, lungs from dogs treated with the combination therapy showed a marked reduction in T regulatory cells, indicating that treatment efficacy may be due to a heightened immune response against the parasite. Further studies are necessary to evaluate the long-term clinical outcome of combination protocols and to establish the most efficient treatment for HWD in dogs. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Activity of the Rhodopseudomonas palustris p-coumaroyl-homoserine lactone-responsive transcription factor RpaR.

PubMed

Hirakawa, Hidetada; Oda, Yasuhiro; Phattarasukol, Somsak; Armour, Christopher D; Castle, John C; Raymond, Christopher K; Lappala, Colin R; Schaefer, Amy L; Harwood, Caroline S; Greenberg, E Peter

2011-05-01

The Rhodopseudomonas palustris transcriptional regulator RpaR responds to the RpaI-synthesized quorum-sensing signal p-coumaroyl-homoserine lactone (pC-HSL). Other characterized RpaR homologs respond to fatty acyl-HSLs. We show here that RpaR functions as a transcriptional activator, which binds directly to the rpaI promoter. We developed an RNAseq method that does not require a ribosome depletion step to define a set of transcripts regulated by pC-HSL and RpaR. The transcripts include several noncoding RNAs. A footprint analysis showed that purified His-tagged RpaR (His(6)-RpaR) binds to an inverted repeat element centered 48.5 bp upstream of the rpaI transcript start site, which we mapped by S1 nuclease protection and primer extension analyses. Although pC-HSL-RpaR bound to rpaI promoter DNA, it did not bind to the promoter regions of a number of RpaR-regulated genes not in the rpaI operon. This indicates that RpaR control of these other genes is indirect. Because the RNAseq analysis allowed us to track transcript strand specificity, we discovered that there is pC-HSL-RpaR-activated antisense transcription of rpaR. These data raise the possibility that this antisense RNA or other RpaR-activated noncoding RNAs mediate the indirect activation of genes in the RpaR-controlled regulon.

Atomic Force Microscopy Reveals a Morphological Differentiation of Chromobacterium violaceum Cells Associated with Biofilm Development and Directed by N-Hexanoyl-L-Homoserine Lactone

PubMed Central

Kamaeva, Anara A.; Vasilchenko, Alexey S.; Deryabin, Dmitry G.

2014-01-01

Chromobacterium violaceum abounds in soil and water ecosystems in tropical and subtropical regions and occasionally causes severe and often fatal human and animal infections. The quorum sensing (QS) system and biofilm formation are essential for C. violaceum's adaptability and pathogenicity, however, their interrelation is still unknown. C. violaceum's cell and biofilm morphology were examined by atomic force microscopy (AFM) in comparison with growth rates, QS-dependent violacein biosynthesis and biofilm biomass quantification. To evaluate QS regulation of these processes, the wild-type strain C. violaceum ATCC 31532 and its mini-Tn5 mutant C. violaceum NCTC 13274, cultivated with and without the QS autoinducer N-hexanoyl-L-homoserine lactone (C6-HSL), were used. We report for the first time the unusual morphological differentiation of C. violaceum cells, associated with biofilm development and directed by the QS autoinducer. AFM revealed numerous invaginations of the external cytoplasmic membrane of wild-type cells, which were repressed in the mutant strain and restored by exogenous C6-HSL. With increasing bacterial growth, polymer matrix extrusions formed in place of invaginations, whereas mutant cells were covered with a diffusely distributed extracellular substance. Thus, quorum sensing in C. violaceum involves a morphological differentiation that organises biofilm formation and leads to a highly differentiated matrix structure. PMID:25111599

Atomic force microscopy reveals a morphological differentiation of chromobacterium violaceum cells associated with biofilm development and directed by N-hexanoyl-L-homoserine lactone.

PubMed

Kamaeva, Anara A; Vasilchenko, Alexey S; Deryabin, Dmitry G

2014-01-01

Chromobacterium violaceum abounds in soil and water ecosystems in tropical and subtropical regions and occasionally causes severe and often fatal human and animal infections. The quorum sensing (QS) system and biofilm formation are essential for C. violaceum's adaptability and pathogenicity, however, their interrelation is still unknown. C. violaceum's cell and biofilm morphology were examined by atomic force microscopy (AFM) in comparison with growth rates, QS-dependent violacein biosynthesis and biofilm biomass quantification. To evaluate QS regulation of these processes, the wild-type strain C. violaceum ATCC 31532 and its mini-Tn5 mutant C. violaceum NCTC 13274, cultivated with and without the QS autoinducer N-hexanoyl-L-homoserine lactone (C6-HSL), were used. We report for the first time the unusual morphological differentiation of C. violaceum cells, associated with biofilm development and directed by the QS autoinducer. AFM revealed numerous invaginations of the external cytoplasmic membrane of wild-type cells, which were repressed in the mutant strain and restored by exogenous C6-HSL. With increasing bacterial growth, polymer matrix extrusions formed in place of invaginations, whereas mutant cells were covered with a diffusely distributed extracellular substance. Thus, quorum sensing in C. violaceum involves a morphological differentiation that organises biofilm formation and leads to a highly differentiated matrix structure.

Evolution of Enzymatic Activities in the Enolase Superfamily: Stereochemically Distinct Mechanisms in Two Families of cis,cis-Muconate Lactonizing Enzymes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sakai, A.; Fedorov, A; Fedorov, E

2009-01-01

The mechanistically diverse enolase superfamily is a paradigm for elucidating Nature's strategies for divergent evolution of enzyme function. Each of the different reactions catalyzed by members of the superfamily is initiated by abstraction of the a-proton of a carboxylate substrate that is coordinated to an essential Mg2+. The muconate lactonizing enzyme (MLE) from Pseudomonas putida, a member of a family that catalyzes the syn-cycloisomerization of cis,cis-muconate to (4S)-muconolactone in the e-ketoadipate pathway, has provided critical insights into the structural bases for evolution of function within the superfamily. A second, divergent family of homologous MLEs that catalyzes anti-cycloisomerization has been identified.more » Structures of members of both families liganded with the common (4S)-muconolactone product (syn, Pseudomonas fluorescens, gi 70731221; anti, Mycobacterium smegmatis, gi 118470554) document that the conserved Lys at the end of the second e-strand in the (e/a)7e-barrel domain serves as the acid catalyst in both reactions. The different stereochemical courses (syn and anti) result from different structural strategies for determining substrate specificity: although the distal carboxylate group of the cis,cis-muconate substrate attacks the same face of the proximal double bond, opposite faces of the resulting enolate anion intermediate are presented to the conserved Lys acid catalyst. The discovery of two families of homologous, but stereochemically distinct, MLEs likely provides an example of 'pseudoconvergent' evolution of the same function from different homologous progenitors within the enolase superfamily, in which different spatial arrangements of active site functional groups and substrate specificity determinants support catalysis of the same reaction.« less

Curiouser and Curiouser: The Macrocyclic Lactone, Abamectin, Is also a Potent Inhibitor of Pyrantel/Tribendimidine Nicotinic Acetylcholine Receptors of Gastro-Intestinal Worms

PubMed Central

Abongwa, Melanie; Buxton, Samuel K.; Robertson, Alan P.; Martin, Richard J.

2016-01-01

Nematode parasites may be controlled with drugs, but their regular application has given rise to concerns about the development of resistance. Drug combinations may be more effective than single drugs and delay the onset of resistance. A combination of the nicotinic antagonist, derquantel, and the macrocyclic lactone, abamectin, has been found to have synergistic anthelmintic effects against gastro-intestinal nematode parasites. We have observed in previous contraction and electrophysiological experiments that derquantel is a potent selective antagonist of nematode parasite muscle nicotinic receptors; and that abamectin is an inhibitor of the same nicotinic receptors. To explore these inhibitory effects further, we expressed muscle nicotinic receptors of the nodular worm, Oesophagostomum dentatum (Ode-UNC-29:Ode-UNC-63:Ode-UNC-38), in Xenopus oocytes under voltage-clamp and tested effects of abamectin on pyrantel and acetylcholine responses. The receptors were antagonized by 0.03 μM abamectin in a non-competitive manner (reduced Rmax, no change in EC50). This antagonism increased when abamectin was increased to 0.1 μM. However, when we increased the concentration of abamectin further to 0.3 μM, 1 μM or 10 μM, we found that the antagonism decreased and was less than with 0.1 μM abamectin. The bi-phasic effects of abamectin suggest that abamectin acts at two allosteric sites: one high affinity negative allosteric (NAM) site causing antagonism, and another lower affinity positive allosteric (PAM) site causing a reduction in antagonism. We also tested the effects of 0.1 μM derquantel alone and in combination with 0.3 μM abamectin. We found that derquantel on these receptors, like abamectin, acted as a non-competitive antagonist, and that the combination of derquantel and abamectin produced greater inhibition. These observations confirm the antagonistic effects of abamectin on nematode nicotinic receptors in addition to GluCl effects, and illustrate more complex

Measuring healthcare productivity - from unit to system level.

PubMed

Kämäräinen, Vesa Johannes; Peltokorpi, Antti; Torkki, Paulus; Tallbacka, Kaj

2016-04-18

Purpose - Healthcare productivity is a growing issue in most Western countries where healthcare expenditure is rapidly increasing. Therefore, accurate productivity metrics are essential to avoid sub-optimization within a healthcare system. The purpose of this paper is to focus on healthcare production system productivity measurement. Design/methodology/approach - Traditionally, healthcare productivity has been studied and measured independently at the unit, organization and system level. Suggesting that productivity measurement should be done in different levels, while simultaneously linking productivity measurement to incentives, this study presents the challenges of productivity measurement at the different levels. The study introduces different methods to measure productivity in healthcare. In addition, it provides background information on the methods used to measure productivity and the parameters used in these methods. A pilot investigation of productivity measurement is used to illustrate the challenges of measurement, to test the developed measures and to prove the practical information for managers. Findings - The study introduces different approaches and methods to measure productivity in healthcare. Practical implications - A pilot investigation of productivity measurement is used to illustrate the challenges of measurement, to test the developed measures and to prove the practical benefits for managers. Originality/value - The authors focus on the measurement of the whole healthcare production system and try to avoid sub-optimization. Additionally considering an individual patient approach, productivity measurement is examined at the unit level, the organizational level and the system level.

Animal production systems in the industrialised world.

PubMed

Sørensen, J T; Edwards, S; Noordhuizen, J; Gunnarsson, S

2006-08-01

The production of food from animal origin is relatively stable in the industrialised world. However, animal production systems are changing dramatically with respect to location, herd size and specialisation. Increased pressure from a critical public is moving animal-based production towards systems such as organic production and loose-housing systems which allow the animals to better express normal behaviour. The focus on food safety promotes systems with a high degree of biosecurity, often associated with an increase in herd size and self-containment. The globalisation of agricultural trade and increased competition also favours an increase in herd size and specialisation. These trends also lead to regions with livestock-dense areas, giving rise to environmental concerns. Therefore, good farming practice regulations and systems to provide a higher level of transparency, such as quality risk management programmes, are being developed.

GC-MS Profiling of Volatile Components in Different Fermentation Products of Cordyceps Sinensis Mycelia.

PubMed

Zhang, Hongyang; Li, Yahui; Mi, Jianing; Zhang, Min; Wang, Yuerong; Jiang, Zhihong; Hu, Ping

2017-10-24

The fermentation products of Cordyceps sinensis ( C. sinensis ) mycelia are sustainable substitutes for natural C. sinensis . However, the volatile compositions of the commercial products are still unclear. In this paper, we have developed a simultaneous distillation-extraction (SDE) and gas chromatography-mass spectrometry (GC-MS) method for the profiling of volatile components in five fermentation products. A total of 64, 39, 56, 52, and 44 components were identified in the essential oils of Jinshuibao capsule (JSBC), Bailing capsule (BLC), Zhiling capsule (ZLC), Ningxinbao capsule (NXBC), and Xinganbao capsule (XGBC), respectively. 5,6-Dihydro-6-pentyl-2H-pyran-2-one (massoia lactone) was first discovered as the dominant component in JSBC volatiles. Fatty acids including palmitic acid (C16:0) and linoleic acid (C18:2) were also found to be major volatile compositions of the fermentation products. The multivariate partial least squares-discriminant analysis (PLS-DA) showed a clear discrimination among the different commercial products as well as the counterfeits. This study may provide further chemical evidences for the quality evaluation of the fermentation products of C. sinensis mycelia.

Glucono-delta-lactone and citric acid as acidulants for lowering the heat resistance of Clostridium sporogenes PA 3679 in HTST working conditions.

PubMed

Silla Santos, M H; Torres Zarzo, J

1995-04-01

The heat resistance of Clostridium sporogenes PA 3679 spores has been studied to establish the influence of acidification with glucono-delta-lactone (GDL) and citric acid on the thermal resistance parameters (DT and z) of this microorganism and to compare their effect with phosphate buffer and natural asparagus as reference substrates. A reduction in DT values was observed in asparagus purée as the acidification level increased with both acidulants although this effect was more evident at the lower treatment temperatures studied (121-127 degrees C). Citric acid was more effective for reducing the heat resistance of spores than GDL at all of the temperatures. The reduction in pH diminished the value of the z parameter, although it was necessary to lower the pH to 4.5 to obtain a significant reduction.

Effect of Vertical Shoot-Positioned, Scott-Henry, Geneva Double-Curtain, Arch-Cane, and Parral Training Systems on the Volatile Composition of Albariño Wines.

PubMed

Vilanova, Mar; Genisheva, Zlatina; Tubio, Miguel; Álvarez, Katia; Lissarrague, Jose Ramón; Oliveira, José Maria

2017-09-08

Viticultural practices influence both grape and wine quality. The influence of training systems on volatile composition was investigated for Albariño wine from Rías Baixas AOC in Northwest Spain. The odoriferous contribution of the compounds to the wine aroma was also studied. Volatile compounds belonging to ten groups (alcohols, C₆-compounds, ethyl esters, acetates, terpenols, C 13 -norisoprenoids, volatile phenols, volatile fatty acids, lactones and carbonyl compounds) were determined in Albariño wines from different training systems, Vertical Shoot-Positioned (VSP), Scott-Henry (SH), Geneva Double-Curtain (GDC), Arch-Cane (AC), and Parral (P) during 2010 and 2011 vintages. Wines from GDC showed the highest total volatile composition with the highest concentrations of alcohols, ethyl esters, fatty acids, and lactones families. However, the highest levels of terpenes and C 13 -norisoprenoids were quantified in the SH system. A fruitier aroma was observed in Albariño wines from GDC when odor activity values were calculated.

Quorum sensing activity of Citrobacter amalonaticus L8A, a bacterium isolated from dental plaque.

PubMed

Goh, Share-Yuan; Khan, Saad Ahmed; Tee, Kok Keng; Abu Kasim, Noor Hayaty; Yin, Wai-Fong; Chan, Kok-Gan

2016-02-10

Cell-cell communication is also known as quorum sensing (QS) that happens in the bacterial cells with the aim to regulate their genes expression in response to increased cell density. In this study, a bacterium (L8A) isolated from dental plaque biofilm was identified as Citrobacter amalonaticus by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS). Its N-acylhomoserine-lactone (AHL) production was screened by using two types of AHL biosensors namely Chromobacterium violaceum CV026 and Escherichia coli [pSB401]. Citrobacter amalonaticus strain L8A was identified and confirmed producing numerous types of AHL namely N-butyryl-L-homoserine lactone (C4-HSL), N-hexanoyl-L-homoserine lactone (C6-HSL), N-octanoyl-L-homoserine lactone (C8-HSL) and N-hexadecanoyl-L-homoserine lactone (C16-HSL). We performed the whole genome sequence analysis of this oral isolate where its genome sequence reveals the presence of QS signal synthase gene and our work will pave the ways to study the function of the related QS genes in this bacterium.

Quorum sensing activity of Citrobacter amalonaticus L8A, a bacterium isolated from dental plaque

PubMed Central

Goh, Share-Yuan; Khan, Saad Ahmed; Tee, Kok Keng; Abu Kasim, Noor Hayaty; Yin, Wai-Fong; Chan, Kok-Gan

2016-01-01

Cell-cell communication is also known as quorum sensing (QS) that happens in the bacterial cells with the aim to regulate their genes expression in response to increased cell density. In this study, a bacterium (L8A) isolated from dental plaque biofilm was identified as Citrobacter amalonaticus by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS). Its N-acylhomoserine-lactone (AHL) production was screened by using two types of AHL biosensors namely Chromobacterium violaceum CV026 and Escherichia coli [pSB401]. Citrobacter amalonaticus strain L8A was identified and confirmed producing numerous types of AHL namely N-butyryl-L-homoserine lactone (C4-HSL), N-hexanoyl-L-homoserine lactone (C6-HSL), N-octanoyl-L-homoserine lactone (C8-HSL) and N-hexadecanoyl-L-homoserine lactone (C16-HSL). We performed the whole genome sequence analysis of this oral isolate where its genome sequence reveals the presence of QS signal synthase gene and our work will pave the ways to study the function of the related QS genes in this bacterium. PMID:26860259

Systems, methods and apparatus for developing and maintaining evolving systems with software product lines

NASA Technical Reports Server (NTRS)

Hinchey, Michael G. (Inventor); Rash, James L. (Inventor); Pena, Joaquin (Inventor)

2011-01-01

Systems, methods and apparatus are provided through which an evolutionary system is managed and viewed as a software product line. In some embodiments, the core architecture is a relatively unchanging part of the system, and each version of the system is viewed as a product from the product line. Each software product is generated from the core architecture with some agent-based additions. The result may be a multi-agent system software product line.

Biophotolysis systems for hydrogen production

NASA Astrophysics Data System (ADS)

Rao, K. K.; Adams, M. W. W.; Morris, P.; Hall, D. O.; Gisby, P. E.

Model systems containing natural and sythetic catalysts were constructed for the production of H2 from water using visible solar radiation as the energy source. Chloroplast membranes were used for light absorption and photodecomposition of water, ferredoxin, flavodoxin, cytochrome, viologen dyes, 'Jeevanu' particles or synthetic clusters containing Fe-Mo-S centers were used as electron transfer catalysts, and hydrogenase or PtO2 served as the proton activator. We have also investigated the use of aqueous systems with proflavine as the light activator and artificial electron donors for subsequent production of H2 when coupled to electron mediators and hydrogenase (or Pt). The characteristics, relative merits and defects of these systems are discussed.

Systems biology and livestock production.

PubMed

Headon, D

2013-12-01

The mapping of complete sets of genes, transcripts and proteins from many organisms has prompted the development of new '-omic' technologies for collecting and analysing very large amounts of data. Now that the tools to generate and interrogate such complete data sets are widely used, much of the focus of biological research has begun to turn towards understanding systems as a whole, rather than studying their components in isolation. This very broadly defined systems approach is being deployed across a range of problems and scales of organisation, including many aspects of the animal sciences. Here I review selected examples of this systems approach as applied to poultry and livestock production, product quality and welfare.

Withaferin-A, a steroidal lactone encapsulated mannose decorated liposomes ameliorates rheumatoid arthritis by intriguing the macrophage repolarization in adjuvant-induced arthritic rats.

PubMed

Sultana, Farhath; Neog, Manoj Kumar; Rasool, MahaboobKhan

2017-07-01

In order to develop a better therapeutic approach for the treatment of rheumatoid arthritis (RA), withaferin-A; a steroidal lactone incorporated with mannosylated liposomes (ML-WA) was administered to adjuvant induced arthritic rats in intent to target the synovial macrophages. The confocal microscopy studies showed a successful internalization of ML-WA in the primarily isolated synovial macrophages. Consequently, targeting synovial macrophages via ML-WA reduced the oxidative stress (ROS and NO), and paw edema, however, a progressive gain in the body weight was observed in AIA rats. ML-WA treatment upregulated the production of osteoprotegerin (OPG) and downregulated the release of receptor activator of nuclear factor-κB ligand (RANKL), favoring osteoclastogenesis negatively. Correspondingly, the ankle joints were found intact with no bone erosion and cartilage degradation in ML-WA treated AIA rats as evidenced by histopathological analysis. Also, synovial macrophage assessment showed that the concentration and the gene amplification of M1 macrophage mediated pro-inflammatory mediators (TNF-α, IL-1β, IL-6, MCP-1 and VEGF) were curtailed in ML-WA treated AIA rats. In contrast, anti-inflammatory cytokine (IL-10) was found abundantly released. Furthermore, the mRNA expression of the M1 surface marker (CD86) was found down regulated, whereas, M2 marker (CD163) was highly amplified in ML-WA treated synovial macrophages of arthritic rats. Cumulatively, our result signified that targeted delivery of ML-WA ameliorated the severity of inflammation and bone resorption in AIA rats via M1 to M2 macrophage repolarization. Copyright © 2017 Elsevier B.V. All rights reserved.

Material Processing Laser Systems In Production

NASA Astrophysics Data System (ADS)

Taeusch, David R.

1988-11-01

The laser processing system is now a respected, productive machine tool in the manufacturing industries. Systems in use today are proving their cost effectiveness and capabilities of processing quality parts. Several types of industrial lasers are described and their applications are discussed, with emphasis being placed on the production environment and methods of protection required for optical equipment against this normally hostile environment.

Energy and nutrient cycling in pig production systems

NASA Astrophysics Data System (ADS)

Lammers, Peter J.

United States pig production is centered in Iowa and is a major influence on the economic and ecological condition of that community. A pig production system includes buildings, equipment, production of feed ingredients, feed processing, and nutrient management. Although feed is the largest single input into a pig production system, nearly 30% of the non-solar energy use of a conventional--mechanically ventilated buildings with liquid manure handling--pig production system is associated with constructing and operating the pig facility. Using bedded hoop barns for gestating sows and grow-finish pigs reduces construction resource use and construction costs of pig production systems. The hoop based systems also requires approximately 40% less non-solar energy to operate as the conventional system although hoop barn-based systems may require more feed. The total non-solar energy input associated with one 136 kg pig produced in a conventional farrow-to-finish system in Iowa and fed a typical corn-soybean meal diet that includes synthetic lysine and exogenous phytase is 967.9 MJ. Consuming the non-solar energy results in emissions of 79.8 kg CO2 equivalents. Alternatively producing the same pig in a system using bedded hoop barns for gestating sows and grow-finish pigs requires 939.8 MJ/pig and results in emission of 70.2 kg CO2 equivalents, a reduction of 3 and 12% respectively. Hoop barn-based swine production systems can be managed to use similar or less resources than conventional confinement systems. As we strive to optimally allocate non-solar energy reserves and limited resources, support for examining and improving alternative systems is warranted.

Embedded systems engineering for products and services design.

PubMed

Ahram, Tareq Z; Karwowski, Waldemar; Soares, Marcelo M

2012-01-01

Systems engineering (SE) professionals strive to develop new techniques to enhance the value of contributions to multidisciplinary smart product design teams. Products and services designers challenge themselves to search beyond the traditional design concept of addressing the physical, social, and cognitive factors. This paper covers the application of embedded user-centered systems engineering design practices into work processes based on the ISO 13407 framework [20] to support smart systems and services design and development. As practitioners collaborate to investigate alternative smart product designs, they concentrate on creating valuable products which will enhance positive interaction. This paper capitalizes on the need to follow a user-centered SE approach to smart products design [4, 22]. Products and systems intelligence should embrace a positive approach to user-centered design while improving our understanding of usable value-adding, experience and extending our knowledge of what inspires others to design enjoyable services and products.

System for extracting protein from a fermentation product

DOEpatents

Lawton, Jr., John Warren; Bootsma, Jason Alan; Lewis, Stephen Michael

2016-04-26

A method of producing bioproducts from a feedstock in a system configured to produce ethanol and distillers grains from a fermentation product is disclosed. A system configured to process feedstock into a fermentation product and bioproducts including ethanol and meal is disclosed. A bioproduct produced from a fermentation product produced from a feedstock in a biorefining system is disclosed.

Basic characteristics and realization of production system control

NASA Astrophysics Data System (ADS)

Cheng, Shaopeng; Shell, Richard; Hall, Ernest L.

1992-11-01

This paper analyzes the issues involved in developing an intelligent production control system. It describes the basic characteristics of a production control system and an effective design methodology to realize the production control functions. Petri net, subsystem and hierarchical control concepts are applied to a computer integrated material handling system (MHS). Some communication and interface requirements of the MHS are also considered in this paper. The control system solution is illustrated with an actual MHS operation case which indicates that a truly flexible and integrated production system can be realized with a Petri net operation model and a hierarchical control structure. The significance of this work is related to the different operation testing and evaluation requirements encountered in manufacturing.

Entropy Production in Convective Hydrothermal Systems

NASA Astrophysics Data System (ADS)

Boersing, Nele; Wellmann, Florian; Niederau, Jan

2016-04-01

Exploring hydrothermal reservoirs requires reliable estimates of subsurface temperatures to delineate favorable locations of boreholes. It is therefore of fundamental and practical importance to understand the thermodynamic behavior of the system in order to predict its performance with numerical studies. To this end, the thermodynamic measure of entropy production is considered as a useful abstraction tool to characterize the convective state of a system since it accounts for dissipative heat processes and gives insight into the system's average behavior in a statistical sense. Solving the underlying conservation principles of a convective hydrothermal system is sensitive to initial conditions and boundary conditions which in turn are prone to uncertain knowledge in subsurface parameters. There exist multiple numerical solutions to the mathematical description of a convective system and the prediction becomes even more challenging as the vigor of convection increases. Thus, the variety of possible modes contained in such highly non-linear problems needs to be quantified. A synthetic study is carried out to simulate fluid flow and heat transfer in a finite porous layer heated from below. Various two-dimensional models are created such that their corresponding Rayleigh numbers lie in a range from the sub-critical linear to the supercritical non-linear regime, that is purely conductive to convection-dominated systems. Entropy production is found to describe the transient evolution of convective processes fairly well and can be used to identify thermodynamic equilibrium. Additionally, varying the aspect ratio for each Rayleigh number shows that the variety of realized convection modes increases with both larger aspect ratio and higher Rayleigh number. This phenomenon is also reflected by an enlarged spread of entropy production for the realized modes. Consequently, the Rayleigh number can be correlated to the magnitude of entropy production. In cases of moderate

New production systems at ISOLDE

NASA Astrophysics Data System (ADS)

Hagebø, E.; Hoff, P.; Jonsson, O. C.; Kugler, E.; Omtvedt, J. P.; Ravn, H. L.; Steffensen, K.

1992-08-01

New target systems for the ISOLDE on-line mass separator facility are presented. Targets of carbides, metal/graphite mixtures, foils of refractory metals, molten metals and oxides have been tested. Beams of high intensity of neutron-rich isotopes of a large number of elements are obtained from a uranium carbide target with a hot plasma-discharge ion source. A target of ZrO 2 has been shown to provide high intensity beams of neutron-deficient isotopes of Mn, Cu, Zn, Ga, Ge, As, Se, Br, Kr and Rb, while a SiC target with a hot plasma ion source gives intense beams of radioactive isotopes of a number of light elements. All these systems are rather chemically unselective. Chemically selective performance has been obtained for several systems, i.e.: the production of neutron-deficient Au from ( 3He, pχn) reactions on a Pt/graphite target with a hot plasma ion source; the production of neutron-deficient Lu and LuF + and Hf and HfF 3+ from a Ta-foil target with a hot plasma ion source under CF 4 addition; the production of neutron-deficient Sr as SrF + and Y as YF 2+ form a Nb-foil target with a W surface ionizer under CF 4 addition; the production of neutron-deficient Se as COSe + from a ZrO 2 target with a hot plasma ion source under O 2 addition; and the production of radioactive F from a SiC target with a hot plasma ion source operating in Al vapour.

Agent-based model of diffusion of N-acyl homoserine lactones in a multicellular environment of Pseudomonas aeruginosa and Candida albicans.

PubMed

Pérez-Rodríguez, Gael; Dias, Sónia; Pérez-Pérez, Martín; Fdez-Riverola, Florentino; Azevedo, Nuno F; Lourenço, Anália

2018-03-08

Experimental incapacity to track microbe-microbe interactions in structures like biofilms, and the complexity inherent to the mathematical modelling of those interactions, raises the need for feasible, alternative modelling approaches. This work proposes an agent-based representation of the diffusion of N-acyl homoserine lactones (AHL) in a multicellular environment formed by Pseudomonas aeruginosa and Candida albicans. Depending on the spatial location, C. albicans cells were variably exposed to AHLs, an observation that might help explain why phenotypic switching of individual cells in biofilms occurred at different time points. The simulation and algebraic results were similar for simpler scenarios, although some statistical differences could be observed (p < 0.05). The model was also successfully applied to a more complex scenario representing a small multicellular environment containing C. albicans and P. aeruginosa cells encased in a 3-D matrix. Further development of this model may help create a predictive tool to depict biofilm heterogeneity at the single-cell level.

Task Management in the New ATLAS Production System

NASA Astrophysics Data System (ADS)

De, K.; Golubkov, D.; Klimentov, A.; Potekhin, M.; Vaniachine, A.; Atlas Collaboration

2014-06-01

This document describes the design of the new Production System of the ATLAS experiment at the LHC [1]. The Production System is the top level workflow manager which translates physicists' needs for production level processing and analysis into actual workflows executed across over a hundred Grid sites used globally by ATLAS. As the production workload increased in volume and complexity in recent years (the ATLAS production tasks count is above one million, with each task containing hundreds or thousands of jobs) there is a need to upgrade the Production System to meet the challenging requirements of the next LHC run while minimizing the operating costs. In the new design, the main subsystems are the Database Engine for Tasks (DEFT) and the Job Execution and Definition Interface (JEDI). Based on users' requests, DEFT manages inter-dependent groups of tasks (Meta-Tasks) and generates corresponding data processing workflows. The JEDI component then dynamically translates the task definitions from DEFT into actual workload jobs executed in the PanDA Workload Management System [2]. We present the requirements, design parameters, basics of the object model and concrete solutions utilized in building the new Production System and its components.

Oxygen production System Models for Lunar ISRU

NASA Technical Reports Server (NTRS)

Santiago-Maldonado, Edgardo

2007-01-01

In-Situ Resource Utilization (ISRU) seeks to make human space exploration feasible; by using available resources from a planet or the moon to produce consumables, parts, and structures that otherwise would be brought from Earth. Producing these in situ reduces the mass of such that must be launched and doing so allows more payload mass' for each mission. The production of oxygen from lunar regolith, for life support and propellant, is one of the tasks being studied under ISRU. NASA is currently funding three processes that have shown technical merit for the production of oxygen from regolith: Molten Salt Electrolysis, Hydrogen Reduction of Ilmenite, and Carbothermal Reduction. The ISRU program is currently developing system models of, the , abovementioned processes to: (1) help NASA in the evaluation process to select the most cost-effective and efficient process for further prototype development, (2) identify key parameters, (3) optimize the oxygen production process, (4) provide estimates on energy and power requirements, mass and volume.of the system, oxygen production rate, mass of regolith required, mass of consumables, and other important parameters, and (5) integrate into the overall end-to-end ISRU system model, which could be integrated with mission architecture models. The oxygen production system model is divided into modules that represent unit operations (e.g., reactor, water electrolyzer, heat exchanger). Each module is modeled theoretically using Excel and Visual Basic for Applications (VBA), and will be validated using experimental data from on-going laboratory work. This modularity (plug-n-play) feature of each unit operation allows the use of the same model on different oxygen production systems simulations resulting in comparable results. In this presentation, preliminary results for mass, power, volume will be presented along with brief description of the oxygen production system model.

Camphor revisited: involvement of a unique monooxygenase in metabolism of 2-oxo-delta 3-4,5,5-trimethylcyclopentenylacetic acid by Pseudomonas putida.

PubMed Central

Ougham, H J; Taylor, D G; Trudgill, P W

1983-01-01

Previously, Pseudomonas putida was shown to degrade (+)-camphor, and cleavage of the first ring of the bicyclic structure involved two monooxygenases (a hydroxylase and a ring oxygen-inserting enzyme), a dehydrogenase, and spontaneous cleavage of an unstable oxygenation product (lactone). Cleavage of the second ring was not demonstrated but was assumed also to occur by ring oxygen insertion, since the predicted oxygenation product was extracted from whole-cell incubation systems. Our investigation established that metabolism of the first ring cleavage intermediate, 2-oxo-delta 3-4,5,5-trimethylcyclopentenylacetic acid, occurred through the sequential action of two inducible enzymes, a coenzyme A ester synthetase and an oxygenase. The oxygenase was purified to homogeneity and had a molecular weight of 106,000. This enzyme carried a single molecule of flavin adenine dinucleotide and consisted of two identical subunits. Iron was not present at a significant level. The oxygenase was specific for NADPH as the electron donor and absolutely specific for the coenzyme A ester of 2-oxo-delta 3-4,5,5-trimethylcyclopentenylacetic acid as the substrate. The reaction stoichiometry was compatible with this enzyme being a monooxygenase, and a mass spectral analysis of the methyl ester of the product confirmed the insertion of a single oxygen atom. The enzyme appeared to be analogous to, although distinct from. 2,5-diketocamphane 1,2-monooxygenase in catalyzing a "biological Baeyer-Villiger" reaction with the formation of a lactone. Structural analogy suggested that this lactone, like the first, was also unstable and susceptible to spontaneous ring opening, although this was not experimentally established. Images PMID:6848481

Camphor revisited: involvement of a unique monooxygenase in metabolism of 2-oxo-delta 3-4,5,5-trimethylcyclopentenylacetic acid by Pseudomonas putida.

PubMed

Ougham, H J; Taylor, D G; Trudgill, P W

1983-01-01

Previously, Pseudomonas putida was shown to degrade (+)-camphor, and cleavage of the first ring of the bicyclic structure involved two monooxygenases (a hydroxylase and a ring oxygen-inserting enzyme), a dehydrogenase, and spontaneous cleavage of an unstable oxygenation product (lactone). Cleavage of the second ring was not demonstrated but was assumed also to occur by ring oxygen insertion, since the predicted oxygenation product was extracted from whole-cell incubation systems. Our investigation established that metabolism of the first ring cleavage intermediate, 2-oxo-delta 3-4,5,5-trimethylcyclopentenylacetic acid, occurred through the sequential action of two inducible enzymes, a coenzyme A ester synthetase and an oxygenase. The oxygenase was purified to homogeneity and had a molecular weight of 106,000. This enzyme carried a single molecule of flavin adenine dinucleotide and consisted of two identical subunits. Iron was not present at a significant level. The oxygenase was specific for NADPH as the electron donor and absolutely specific for the coenzyme A ester of 2-oxo-delta 3-4,5,5-trimethylcyclopentenylacetic acid as the substrate. The reaction stoichiometry was compatible with this enzyme being a monooxygenase, and a mass spectral analysis of the methyl ester of the product confirmed the insertion of a single oxygen atom. The enzyme appeared to be analogous to, although distinct from. 2,5-diketocamphane 1,2-monooxygenase in catalyzing a "biological Baeyer-Villiger" reaction with the formation of a lactone. Structural analogy suggested that this lactone, like the first, was also unstable and susceptible to spontaneous ring opening, although this was not experimentally established.

Pollution monitoring system. [photographic laboratory by-products

NASA Technical Reports Server (NTRS)

Goodding, R. A.

1973-01-01

An investigation was undertaken to identify those photographic laboratory by-products which can produce harmful reactions if released untreated. After identification of these by-products, specific monitoring systems for each of the offending ions were investigated and recommendations for implementation are presented. Appropriate monitoring systems are discussed.

Germacranolide-type sesquiterpene lactones from Smallanthus sonchifolius with promising activity against Leishmania mexicana and Trypanosoma cruzi.

PubMed

Ulloa, Jerónimo L; Spina, Renata; Casasco, Agustina; Petray, Patricia B; Martino, Virginia; Sosa, Miguel A; Frank, Fernanda M; Muschietti, Liliana V

2017-11-13

Leishmaniasis and Chagas disease are life-threatening illnesses caused by the protozoan parasites Leishmania spp. and Trypanosoma cruzi, respectively. They are known as "neglected diseases" due to the lack of effective drug treatments and the scarcity of research work devoted to them. Therefore, the development of novel and effective drugs is an important and urgent need. Natural products are an important source of bioactive molecules for the development of new drugs. In this study, we evaluated the activity of enhydrin, uvedalin and polymatin B, three sesquiterpene lactones (STLs) isolated from Smallanthus sonchifolius, on Leishmania mexicana (MNYC/BZ/62/M) and Trypanosoma cruzi (Dm28c). In addition, the in vivo trypanocidal activity of enhydrin and uvedalin and the effects of these STLs on parasites' ultrastructure were evaluated. The inhibitory effect of the three STLs on the growth of L. mexicana amastigotes and promastigotes as well as T. cruzi epimastigotes was evaluated in vitro. The changes produced by the STLs on the ultrastructure of parasites were examined by transmission electron microscopy (TEM). Enhydrin and uvedalin were also studied in a murine model of acute T. cruzi infection (RA strain). Serum activities of the hepatic enzymes alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase were used as biochemical markers of hepatotoxicity. The three compounds exhibited leishmanicidal activity on both parasite forms with IC 50 values of 0.42-0.54 μg/ml for promastigotes and 0.85-1.64 μg/ml for intracellular amastigotes. Similar results were observed on T. cruzi epimastigotes (IC 50 0.35-0.60 μg/ml). The TEM evaluation showed marked ultrastructural alterations, such as an intense vacuolization and mitochondrial swelling in both L. mexicana promastigotes and T. cruzi epimastigotes exposed to the STLs. In the in vivo study, enhydrin and uvedalin displayed a significant decrease in circulating parasites (50-71%) and no signs of

Organic watermelon production systems

USDA-ARS?s Scientific Manuscript database

The increasing perception by consumers that organic food tastes better and is healthier continues to expand the demand for organically produced crops. Research investigating certified organic production requires a systems approach to determine the optimum combination of individual components to max...

Productivity changes in OECD healthcare systems: bias-corrected Malmquist productivity approach.

PubMed

Kim, Younhee; Oh, Dong-Hyun; Kang, Minah

2016-10-01

This study evaluates productivity changes in the healthcare systems of 30 Organization for Economic Co-operation and Development (OECD) countries over the 2002-2012 periods. The bootstrapped Malmquist approach is used to estimate bias-corrected indices of healthcare performance in productivity, efficiency and technology by modifying the original distance functions. Two inputs (health expenditure and school life expectancy) and two outputs (life expectancy at birth and infant mortality rate) are used to calculate productivity growth. There are no perceptible trends in productivity changes over the 2002-2012 periods, but positive productivity improvement has been noticed for most OECD countries. The result also informs considerable variations in annual productivity scores across the countries. Average annual productivity growth is evenly yielded by efficiency and technical changes, but both changes run somewhat differently across the years. The results of this study assert that policy reforms in OECD countries have improved productivity growth in healthcare systems over the past decade. Countries that lag behind in productivity growth should benchmark peer countries' practices to increase performance by prioritizing an achievable trajectory based on socioeconomic conditions. For example, relatively inefficient countries in this study indicate higher income inequality, corresponding to inequality and health outcomes studies. Although income inequality and globalization are not direct measures to estimate healthcare productivity in this study, these issues could be latent factors to explain cross-country healthcare productivity for future research. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Advances in ethanol production using immobilized cell systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Margaritis, A.; Merchant, F.J.A.

The application of immobilized cell systems for the production of ethanol has resulted in substantial improvements in the efficiency of the process when compared to the traditional free cell system. In this review, the various methods of cell immobilization employed in ethanol production systems have been described in detail. Their salient features, performance characteristics, advantages and limitations have been critically assessed. More recently, these immobilized cell systems have also been employed for the production of ethanol from non-conventional feedstocks such as Jerusalem artichoke extracts, cheese whey, cellulose, cellobiose and xylose. Ethanol production by immobilized yeast and bacterial cells has beenmore » attempted in various bioreactor types. Although most of these studies have been carried out using laboratory scale prototype bioreactors, it appears that only fluidized bed, horizontally packed bed bioreactors and tower fermenters may find application on scale-up. Several studies have indicated that upon immobilization, yeast cells performing ethanol fermentation exhibit more favourable physiological and metabolic properties. This, in addition to substantial improvements in ethanol productivities by immobilized cell systems, is indicative of the fact that future developments in the production of ethanol and alcoholic beverages will be directed towards the use of immobilized cell systems. 291 references.« less

Viewing hybrid systems as products of control systems and automata

NASA Technical Reports Server (NTRS)

Grossman, R. L.; Larson, R. G.

1992-01-01

The purpose of this note is to show how hybrid systems may be modeled as products of nonlinear control systems and finite state automata. By a hybrid system, we mean a network of consisting of continuous, nonlinear control system connected to discrete, finite state automata. Our point of view is that the automata switches between the control systems, and that this switching is a function of the discrete input symbols or letters that it receives. We show how a nonlinear control system may be viewed as a pair consisting of a bialgebra of operators coding the dynamics, and an algebra of observations coding the state space. We also show that a finite automata has a similar representation. A hybrid system is then modeled by taking suitable products of the bialgebras coding the dynamics and the observation algebras coding the state spaces.

Beneficial effects of bacteria-plant communication based on quorum sensing molecules of the N-acyl homoserine lactone group.

PubMed

Schikora, Adam; Schenk, Sebastian T; Hartmann, Anton

2016-04-01

Bacterial quorum sensing (QS) mechanisms play a crucial role in the proper performance and ecological fitness of bacterial populations. Many key physiological processes are regulated in a QS-dependent manner by auto-inducers, like the N-acyl homoserine lactones (AHLs) in numerous Gram-negative bacteria. In addition, also the interaction between bacteria and eukaryotic hosts can be regulated by AHLs. Those mechanisms gained much attention, because of the positive effects of different AHL molecules on plants. This positive impact ranges from growth promotion to induced resistance and is quite contrasting to the rather negative effects observed in the interactions between bacterial AHL molecules and animals. Only very recently, we began to understand the molecular mechanisms underpinning plant responses to AHL molecules. In this review, we gathered the latest information in this research field. The first part gives an overview of the bacterial aspects of quorum sensing. Later we focus on the impact of AHLs on plant growth and AHL-priming, as one of the most understood phenomena in respect to the inter-kingdom interactions based on AHL-quorum sensing molecules. Finally, we discuss the potential benefits of the understanding of bacteria-plant interaction for the future agricultural applications.

Solution and solid-state effects on NMR chemical shifts in sesquiterpene lactones: NMR, X-ray, and theoretical methods.

PubMed

Dračínský, Martin; Buděšínský, Miloš; Warżajtis, Beata; Rychlewska, Urszula

2012-01-12

Selected guaianolide type sesquiterpene lactones were studied combining solution and solid-state NMR spectroscopy with theoretical calculations of the chemical shifts in both environments and with the X-ray data. The experimental (1)H and (13)C chemical shifts in solution were successfully reproduced by theoretical calculations (with the GIAO method and DFT B3LYP 6-31++G**) after geometry optimization (DFT B3LYP 6-31 G**) in vacuum. The GIPAW method was used for calculations of solid-state (13)C chemical shifts. The studied cases involved two polymorphs of helenalin, two pseudopolymorphs of 6α-hydroxydihydro-aromaticin and two cases of multiple asymmetric units in crystals: one in which the symmetry-independent molecules were connected by a series of hydrogen bonds (geigerinin) and the other in which the symmetry-independent molecules, deprived of any specific intermolecular interactions, differed in the conformation of the side chain (badkhysin). Geometrically different molecules present in the crystal lattices could be easily distinguished in the solid-state NMR spectra. Moreover, the experimental differences in the (13)C chemical shifts corresponding to nuclei in different polymorphs or in geometrically different molecules were nicely reproduced with the GIPAW calculations.

Production Systems. Laboratory Activities.

ERIC Educational Resources Information Center

Gallaway, Ann, Ed.

This production systems guide provides teachers with learning activities for secondary students. Introductory materials include an instructional planning outline and worksheet, an outline of essential elements, domains and objectives, a course description, and a content outline. The guide contains 30 modules on the following topics: production…

Evaluation of pig production practices, constraints and opportunities for improvement in smallholder production systems in Kenya.

PubMed

Mbuthia, Jackson Mwenda; Rewe, Thomas Odiwuor; Kahi, Alexander Kigunzu

2015-02-01

This study evaluated pig production practices by smallholder farmers in two distinct production systems geared towards addressing their constraints and prospects for improvement. The production systems evaluated were semi-intensive and extensive and differed in remoteness, market access, resource availability and pig production intensity. Data were collected using structured questionnaires where a total of 102 pig farmers were interviewed. Qualitative and quantitative research methods were employed to define the socioeconomic characteristics of the production systems, understanding the different roles that pigs play, marketing systems and constraints to production. In both systems, regular cash income and insurance against emergencies were ranked as the main reasons for rearing pigs. Marketing of pigs was mainly driven by the type of production operation. Finances, feeds and housing were identified as the major constraints to production. The study provides important parameters and identifies constraints important for consideration in design of sustainable production improvement strategies. Feeding challenges can be improved through understanding the composition and proper utilization of local feed resources. Provision of adequate housing would improve the stocking rates and control mating.

Anomalous regioselective four-member multicomponent Biginelli reaction II: one-pot parallel synthesis of spiro heterobicyclic aliphatic rings.

PubMed

Byk, Gerardo; Kabha, Eihab

2004-01-01

In a previous preliminary study, we found that a cyclic five-member ring beta-keto ester (lactone) reacts with one molecule of urea and two of aldehyde to give a new family of spiro heterobicyclic aliphatic rings in good yields with no traces of the expected dihydropyrimidine (Biginelli) products. The reaction is driven by a regiospecific condensation of two molecules of aldehyde with urea and beta-keto-gamma-lactone to afford only products harboring substitutions exclusively in a syn configuration (Byk, G.; Gottlieb, H. E.; Herscovici, J.; Mirkin, F. J. Comb. Chem. 2000, 2, 732-735). In the present work ((a) Presented in part at ISCT Combitech, October 15, 2002, Israel, and Eurocombi-2, Copenhagen 2003 (oral and poster presentation). (b) Also in American Peptide Society Symposium, Boston, 2003 (poster presentation). (c) Abstract in Biopolymers 2003, 71 (3), 354-355), we report a large and exciting extension of this new reaction utilizing parallel organic synthesis arrays, as demonstrated by the use of chiral beta-keto-gamma-lactams, derived from natural amino acids, instead of tetronic acid (beta-keto-gamma-lactone) and the potential of the spirobicyclic products for generating "libraries from libraries". Interestingly, we note an unusual and important anisotropy effect induced by perpendicular interactions between rigid pi systems and different groups placed at the alpha position of the obtained spirobicyclic system. Stereo/regioselectivity of the aldehyde condensation is driven by the nature of the substitutions on the starting beta-keto-gamma-lactam. Aromatic aldehydes can be used as starting reagents with good yields; however, when aliphatic aldehydes are used, the desired products are obtained in poor yields, as observed in the classical Biginelli reaction. The possible reasons for these poor yields are addressed and clarify, to some extent, the complexity of the Biginelli multicomponent reaction mechanism and, in particular, the mechanism of the present

Skin penetration behaviour of sesquiterpene lactones from different Arnica preparations using a validated GC-MSD method.

PubMed

Wagner, Steffen; Merfort, Irmgard

2007-01-04

Preparations of Arnica montana L. are widely used for the topical treatment of inflammatory diseases. The anti-inflammatory activity is mainly attributed to their sesquiterpene lactones (SLs) from the helenalin and 11alpha,13-dihydrohelenalin type. To study the penetration kinetics of SLs in Arnica preparations, a stripping method with adhesive tape and pig skin as a model was used. For the determination of SLs in the stripped layers of the stratum corneum (SC), a gas chromatography/mass spectrometry method was developed and validated. Thereby the amount of helenalin derivatives was calculated as helenalin isobutyrate, and 11alpha,13-dihydrohelenalin derivatives as 11alpha,13-dihydrohelenalin methacrylate. This GC-MSD method is suitable also to determine low amounts of SLs in Arnica preparations. The penetration behaviour of one gel preparation and two ointment preparations was investigated. The SLs of all preparations show a comparable penetration in and a permeation through the stratum corneum, the uppermost part of the skin. Interestingly, the gel preparation showed a decrease of the penetration rate over 4h, whereas the penetration rate of ointments kept constant over time. Moreover, we could demonstrate that the totally penetrated amount of SLs only depends on the kind of the formulation and of the SLs-content in the formulation but not on the SLs composition or on the used extraction agent.

Linking environment-productivity trade-offs and correlated uncertainties: Greenhouse gas emissions and crop productivity in paddy rice production systems.

PubMed

Hayashi, Kiyotada; Nagumo, Yoshifumi; Domoto, Akiko

2016-11-15

In comparative life cycle assessments of agricultural production systems, analyses of both the trade-offs between environmental impacts and crop productivity and of the uncertainties specific to agriculture such as fluctuations in greenhouse gas (GHG) emissions and crop yields are crucial. However, these two issues are usually analyzed separately. In this paper, we present a framework to link trade-off and uncertainty analyses; correlated uncertainties are integrated into environment-productivity trade-off analyses. We compared three rice production systems in Japan: a system using a pelletized, nitrogen-concentrated organic fertilizer made from poultry manure using closed-air composting techniques (high-N system), a system using a conventional organic fertilizer made from poultry manure using open-air composting techniques (low-N system), and a system using a chemical compound fertilizer (conventional system). We focused on two important sources of uncertainties in paddy rice cultivation-methane emissions from paddy fields and crop yields. We found trade-offs between the conventional and high-N systems and the low-N system and the existence of positively correlated uncertainties in the conventional and high-N systems. We concluded that our framework is effective in recommending the high-N system compared with the low-N system, although the performance of the former is almost the same as the conventional system. Copyright © 2016 Elsevier B.V. All rights reserved.

Efficient catalytic system for the direct transformation of lignocellulosic biomass to furfural and 5-hydroxymethylfurfural.

PubMed

Zhang, Luxin; Xi, Guoyun; Zhang, Jiaxin; Yu, Hongbing; Wang, Xiaochang

2017-01-01

A feasible approach was developed for the co-production of 5-hydroxymethylfurfural (5-HMF) and furfural from corncob via a new porous polytriphenylamine-SO 3 H (SPTPA) solid acid catalyst in lactone solvents. XRD, SEM, XPS, N 2 adsorption-desorption, elemental analysis, TG-DTA, acid-base titration and FTIR spectroscopy techniques were used to characterize the catalyst. This study demonstrates and optimizes the catalytic performance of SPTPA and solvent selection. SPTPA was found to exhibit superior catalytic ability in γ-valerolactone (GVL). Under the optimum reaction conditions, simultaneously encouraging yields of furfural (73.9%) and 5-HMF (32.3%) were achieved at 448K. The main advantages of this process include reasonable yields of both 5-HMF and furfural in the same reaction system, practical simplicity for the raw biomass utilization, and the use of a safe and environmentally benign solvent. Copyright © 2016 Elsevier Ltd. All rights reserved.

Natural production of biological optical systems

NASA Astrophysics Data System (ADS)

Choi, Seung Ho; Kim, Young L.

2015-03-01

Synthesis and production in nature often provide ideas to design and fabricate advanced biomimetic photonic materials and structures, leading to excellent physical properties and enhanced performance. In addition, the recognition and utilization of natural or biological substances have been typical routes to develop biocompatible and biodegradable materials for medical applications. In this respect, biological lasers utilizing such biomaterials and biostructures have been received considerable attention, given a variety of implications and potentials for bioimaging, biosensing, implantation, and therapy. However, without relying on industrial facilities, eco-friendly massive production of such optical components or systems has not yet been investigated. We show examples of bioproduction of biological lasers using agriculture and fisheries. We anticipate that such approaches will open new possibilities for scalable eco-friendly `green' production of biological photonics components and systems.

Production costs and animal welfare for four stylized hog production systems.

PubMed

Seibert, Lacey; Norwood, F Bailey

2011-01-01

Nonhuman animal welfare is arguably the most contentious issue facing the hog industry. Animal advocacy groups influence the regulation of hog farms and induce some consumers to demand more humane pork products. Hog producers are understandably reluctant to improve animal well being unless the premium they extract exceeds the corresponding increase in cost. To better understand the relationship between animal welfare and production costs under different farm systems, this study investigates 4 stylized hog production systems. The results show that increasing animal welfare for all hogs in the United States will increase retail pork prices by a maximum of 2% for a small welfare increase and 5% for a large welfare increase. The cost of banning gestation crates measured by this study is lower than the consumer willingness-to-pay from other studies.

Influence of bacterial N-acyl-homoserine lactones on growth parameters, pigments, antioxidative capacities and the xenobiotic phase II detoxification enzymes in barley and yam bean.

PubMed

Götz-Rösch, Christine; Sieper, Tina; Fekete, Agnes; Schmitt-Kopplin, Philippe; Hartmann, Anton; Schröder, Peter

2015-01-01

Bacteria are able to communicate with each other and sense their environment in a population density dependent mechanism known as quorum sensing (QS). N-acyl-homoserine lactones (AHLs) are the QS signaling compounds of Gram-negative bacteria which are frequent colonizers of rhizospheres. While cross-kingdom signaling and AHL-dependent gene expression in plants has been confirmed, the responses of enzyme activities in the eukaryotic host upon AHLs are unknown. Since AHL are thought to be used as so-called plant boosters or strengthening agents, which might change their resistance toward radiation and/or xenobiotic stress, we have examined the plants' pigment status and their antioxidative and detoxifying capacities upon AHL treatment. Because the yield of a crop plant should not be negatively influenced, we have also checked for growth and root parameters. We investigated the influence of three different AHLs, namely N-hexanoyl- (C6-HSL), N-octanoyl- (C8-HSL), and N-decanoyl- homoserine lactone (C10-HSL) on two agricultural crop plants. The AHL-effects on Hordeum vulgare (L.) as an example of a monocotyledonous crop and on the tropical leguminous crop plant Pachyrhizus erosus (L.) were compared. While plant growth and pigment contents in both plants showed only small responses to the applied AHLs, AHL treatment triggered tissue- and compound-specific changes in the activity of important detoxification enzymes. The activity of dehydroascorbate reductase in barley shoots after C10-HSL treatment for instance increased up to 384% of control plant levels, whereas superoxide dismutase activity in barley roots was decreased down to 23% of control levels upon C6-HSL treatment. Other detoxification enzymes reacted similarly within this range, with interesting clusters of positive or negative answers toward AHL treatment. In general the changes on the enzyme level were more severe in barley than in yam bean which might be due to the different abilities of the plants to

Influence of bacterial N-acyl-homoserine lactones on growth parameters, pigments, antioxidative capacities and the xenobiotic phase II detoxification enzymes in barley and yam bean

PubMed Central

Götz-Rösch, Christine; Sieper, Tina; Fekete, Agnes; Schmitt-Kopplin, Philippe; Hartmann, Anton; Schröder, Peter

2015-01-01

Bacteria are able to communicate with each other and sense their environment in a population density dependent mechanism known as quorum sensing (QS). N-acyl-homoserine lactones (AHLs) are the QS signaling compounds of Gram-negative bacteria which are frequent colonizers of rhizospheres. While cross-kingdom signaling and AHL-dependent gene expression in plants has been confirmed, the responses of enzyme activities in the eukaryotic host upon AHLs are unknown. Since AHL are thought to be used as so-called plant boosters or strengthening agents, which might change their resistance toward radiation and/or xenobiotic stress, we have examined the plants’ pigment status and their antioxidative and detoxifying capacities upon AHL treatment. Because the yield of a crop plant should not be negatively influenced, we have also checked for growth and root parameters. We investigated the influence of three different AHLs, namely N-hexanoyl- (C6-HSL), N-octanoyl- (C8-HSL), and N-decanoyl- homoserine lactone (C10-HSL) on two agricultural crop plants. The AHL-effects on Hordeum vulgare (L.) as an example of a monocotyledonous crop and on the tropical leguminous crop plant Pachyrhizus erosus (L.) were compared. While plant growth and pigment contents in both plants showed only small responses to the applied AHLs, AHL treatment triggered tissue- and compound-specific changes in the activity of important detoxification enzymes. The activity of dehydroascorbate reductase in barley shoots after C10-HSL treatment for instance increased up to 384% of control plant levels, whereas superoxide dismutase activity in barley roots was decreased down to 23% of control levels upon C6-HSL treatment. Other detoxification enzymes reacted similarly within this range, with interesting clusters of positive or negative answers toward AHL treatment. In general the changes on the enzyme level were more severe in barley than in yam bean which might be due to the different abilities of the plants to

Creating Productive Roadways : Developing an Advanced Energy Production, Storage, and Distribution System

DOT National Transportation Integrated Search

2013-05-01

Renewable electric power production could reduce highway maintenance and operating costs and provide backup for critical systems during power outages. Using the public right-of-way and roadway infrastructure as a source for energy production, storage...

Production Management System for AMS Computing Centres

NASA Astrophysics Data System (ADS)

Choutko, V.; Demakov, O.; Egorov, A.; Eline, A.; Shan, B. S.; Shi, R.

2017-10-01

The Alpha Magnetic Spectrometer [1] (AMS) has collected over 95 billion cosmic ray events since it was installed on the International Space Station (ISS) on May 19, 2011. To cope with enormous flux of events, AMS uses 12 computing centers in Europe, Asia and North America, which have different hardware and software configurations. The centers are participating in data reconstruction, Monte-Carlo (MC) simulation [2]/Data and MC production/as well as in physics analysis. Data production management system has been developed to facilitate data and MC production tasks in AMS computing centers, including job acquiring, submitting, monitoring, transferring, and accounting. It was designed to be modularized, light-weighted, and easy-to-be-deployed. The system is based on Deterministic Finite Automaton [3] model, and implemented by script languages, Python and Perl, and the built-in sqlite3 database on Linux operating systems. Different batch management systems, file system storage, and transferring protocols are supported. The details of the integration with Open Science Grid are presented as well.

NF-κB p65 repression by the sesquiterpene lactone, Helenalin, contributes to the induction of autophagy cell death

PubMed Central

2012-01-01

Background Numerous studies have demonstrated that autophagy plays a vital role in maintaining cellular homeostasis. Interestingly, several anticancer agents were found to exert their anticancer effects by triggering autophagy. Emerging data suggest that autophagy represents a novel mechanism that can be exploited for therapeutic benefit. Pharmacologically active natural compounds such as those from marine, terrestrial plants and animals represent a promising resource for novel anticancer drugs. There are several prominent examples from the past proving the success of natural products and derivatives exhibiting anticancer activity. Helenalin, a sesquiterpene lactone has been demonstrated to have potent anti-inflammatory and antitumor activity. Albeit previous studies demonstrating helenalin’s multi modal action on cellular proliferative and apoptosis, the mechanisms underlying its action are largely unexplained. Methods To deduce the mechanistic action of helenalin, cancer cells were treated with the drug at various concentrations and time intervals. Using western blot, FACS analysis, overexpression and knockdown studies, cellular signaling pathways were interrogated focusing on apoptosis and autophagy markers. Results We show here that helenalin induces sub-G1 arrest, apoptosis, caspase cleavage and increases the levels of the autophagic markers. Suppression of caspase cleavage by the pan caspase inhibitor, Z-VAD-fmk, suppressed induction of LC3-B and Atg12 and reduced autophagic cell death, indicating caspase activity was essential for autophagic cell death induced by helenalin. Additionally, helenalin suppressed NF-κB p65 expression in a dose and time dependent manner. Exogenous overexpression of p65 was accompanied by reduced levels of cell death whereas siRNA mediated suppression led to augmented levels of caspase cleavage, autophagic cell death markers and increased cell death. Conclusions Taken together, these results show that helenalin mediated

Parallel machine architecture for production rule systems

DOEpatents

Allen, Jr., John D.; Butler, Philip L.

1989-01-01

A parallel processing system for production rule programs utilizes a host processor for storing production rule right hand sides (RHS) and a plurality of rule processors for storing left hand sides (LHS). The rule processors operate in parallel in the recognize phase of the system recognize -Act Cycle to match their respective LHS's against a stored list of working memory elements (WME) in order to find a self consistent set of WME's. The list of WME is dynamically varied during the Act phase of the system in which the host executes or fires rule RHS's for those rules for which a self-consistent set has been found by the rule processors. The host transmits instructions for creating or deleting working memory elements as dictated by the rule firings until the rule processors are unable to find any further self-consistent working memory element sets at which time the production rule system is halted.

Modernizing the Regulatory System for Biotechnology Products

EPA Pesticide Factsheets

This Web page describes the continuing effort to modernize the federal regulatory system for biotechnology products as well as clarify various roles of EPA, FDA and USDA in evaluating new biotechnology products.

Intra-species bacterial quorum sensing studied at single cell level in a double droplet trapping system.

PubMed

Bai, Yunpeng; Patil, Santoshkumar N; Bowden, Steven D; Poulter, Simon; Pan, Jie; Salmond, George P C; Welch, Martin; Huck, Wilhelm T S; Abell, Chris

2013-05-21

In this paper, we investigated the intra-species bacterial quorum sensing at the single cell level using a double droplet trapping system. Escherichia coli transformed to express the quorum sensing receptor protein, LasR, were encapsulated in microdroplets that were positioned adjacent to microdroplets containing the autoinducer, N-(3-oxododecanoyl)-L-homoserine lactone (OdDHL). Functional activation of the LasR protein by diffusion of the OdDHL across the droplet interface was measured by monitoring the expression of green fluorescent protein (GFP) from a LasR-dependent promoter. A threshold concentration of OdDHL was found to induce production of quorum-sensing associated GFP by E. coli. Additionally, we demonstrated that LasR-dependent activation of GFP expression was also initiated when the adjacent droplets contained single E. coli transformed with the OdDHL synthase gene, LasI, representing a simple quorum sensing circuit between two droplets.

Phytotoxic Effects and Phytochemical Fingerprinting of Hydrodistilled Oil, Enriched Fractions, and Isolated Compounds Obtained from Cryptocarya massoy (Oken) Kosterm. Bark.

PubMed

Rolli, Enrico; Marieschi, Matteo; Maietti, Silvia; Guerrini, Alessandra; Grandini, Alessandro; Sacchetti, Gianni; Bruni, Renato

2016-01-01

The hydrodistilled oil of Cryptocarya massoy bark was characterized by GC-FID and GC/MS analyses, allowing the identification of unusual C10 massoia lactone (3, 56.2%), C12 massoia lactone (4, 16.5%), benzyl benzoate (1, 12.7%), C8 massoia lactone (3.4%), δ-decalactone (5, 1.5%), and benzyl salicylate (2, 1.8%) as main constituents. The phytotoxic activities of the oil, three enriched fractions (lactone-rich, ester-rich, and sesquiterpene-rich), and four constituents (compounds 1, 2, 5, and δ-dodecalactone (6)) against Lycopersicon esculentum and Cucumis sativus seeds and seedlings were screened. At a concentration of 1000 μl/l, the essential oil and the massoia lactone-rich fraction caused a complete inhibition of the germination of both seeds, and, when applied on tomato plantlets, they induced an 85 and 100% dieback, respectively. These performances exceeded those of the well-known phytotoxic essential oils of Syzygium aromaticum and Cymbopogon citratus, already used in commercial products for the weed and pest management. The same substances were also evaluated against four phytopathogenic bacteria and ten phytopathogenic fungi, providing EC50 values against the most susceptible strains in the 100-500 μl/l range for the essential oil and in the 10-50 μl/l range for compound 6 and the lactone-rich fraction. The phytotoxic behavior was related mainly to massoia lactones and benzyl esters, while a greater amount of 6 may infer a good activity against some phytopathogenic fungi. Further investigations of these secondary metabolites are warranted, to evaluate their use as natural herbicides. Copyright © 2016 Verlag Helvetica Chimica Acta AG, Zürich.

LOGDIS (Logistics Data Integration System): Productivity evaluation report. [Logistics Data Integration System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schultz, E.E.; Abrahams, S.; Banks, W.W. Jr.

1987-08-26

This report presents the results of an end-user productivity study associated with the implementation of LOGDIS (Logistics Data Integration System), a prototype LLNL Gateway system. Its purpose is to provide AFLC decision-makers with data pertaining to estimates of any productivity changes that can be expected or realized by the use of advanced technology and applications software. The effort described in this report focuses on objective functional user productivity and performance changes which can be attributed directly and objectively to LOGDIS.

Production of 6-pentyl-α-pyrone by trichoderma harzianum in solid-state fermentation.

PubMed

de Souza Ramos, Aline; Fiaux, Sorele Batista; Leite, Selma Gomes Ferreira

2008-10-01

Many Trichoderma species are able to produce 6-pentyl-α-pyrone (6-PP), a lactone with coconut-like aroma. In the present work, several culture parameters were studied to enhance the production of 6-PP by Trichoderma harzianum 4040 in solid-state fermentation. Green coir powder added to a nutrient solution was used as support material for fermentation. A Plackett-Burman screening technique was applied, followed by a fractionary factorial design. The best culture conditions within the experimental domain studied were (100 g support)(-1): sucrose, 3 g; NaNO3, 0.24 g; (NH4)2SO4, 0.18 g; KH2PO4, 0.1 g; inoculum concentration, 2.2 × 10(6) spores; moisture level, 55%. The temperature established was 28°C. The fermentation under the selected conditions led to a 6-PP production six times higher (5.0 mg/g dry matter) than the initial one (0.8 mg/g dry matter) after seven days of cultivation.

Production of 6-pentyl-α-pyrone by trichoderma harzianum in solid-state fermentation

PubMed Central

de Souza Ramos, Aline; Fiaux, Sorele Batista; Leite, Selma Gomes Ferreira

2008-01-01

Many Trichoderma species are able to produce 6-pentyl-α-pyrone (6-PP), a lactone with coconut-like aroma. In the present work, several culture parameters were studied to enhance the production of 6-PP by Trichoderma harzianum 4040 in solid-state fermentation. Green coir powder added to a nutrient solution was used as support material for fermentation. A Plackett-Burman screening technique was applied, followed by a fractionary factorial design. The best culture conditions within the experimental domain studied were (100 g support)−1: sucrose, 3 g; NaNO3, 0.24 g; (NH4)2SO4, 0.18 g; KH2PO4, 0.1 g; inoculum concentration, 2.2 × 106 spores; moisture level, 55%. The temperature established was 28°C. The fermentation under the selected conditions led to a 6-PP production six times higher (5.0 mg/g dry matter) than the initial one (0.8 mg/g dry matter) after seven days of cultivation. PMID:24031295

New polyenic antibiotics active against gram-positive and gram-negative bacteria. VIII. Construction of synthetic medium for production of mono-chloro-congeners of enacyloxins.

PubMed

Watanabe, T; Sugiyama, T; Chino, K; Suzuki, T; Wakabayashi, S; Hayashi, H; Itami, R; Shima, J; Izaki, K

1992-04-01

New antibiotics enacyloxins (ENXs) are a family of non-lactonic polyene antibiotics produced by Frateuria sp. W-315. For the production of antibiotics, we had to employ two-step fermentations, the first is the production of spent medium of Neurospora crassa and the second is the production of antibiotics by Frateuria. To simplify the production of antibiotics, systematic analyses have been done on the spent medium, and factors which affect the production of antibiotics characterized. From the above results, we constructed a new medium for antibiotic production. Moreover, we could get a new antibiotic named enacyloxin IIIa (1), C33H48O11NCl (m/z 669). 1 was deduced to be one of the congeners of enacyloxins because it was similar to ENX IIa or ENX IVa both in biological and physico-chemical properties. Chlorine of 1 could be replaced by bromine, biosynthetically, and the resultant bromine-containing antibiotic also showed an antibacterial activity comparable to 1.

Sesquiterpene lactones from the methanol extracts of twenty-eight Hieracium species from the Balkan Peninsula and their chemosystematic significance.

PubMed

Milutinović, Violeta; Niketić, Marjan; Krunić, Aleksej; Nikolić, Dejan; Petković, Miloš; Ušjak, Ljuboš; Petrović, Silvana

2018-06-20

Four sesquiterpene lactones (SLs), including three undescribed proline-SL conjugates, the guaianolides calophyllamine A and 8-epiixerisamine A, and the eudesmanolide calophyllamine B, were isolated from the methanol extract of Hieracium calophyllum R. Uechtr. (Compositae) flowering heads. Another known guaianolide, crepiside E, was detected in Hieracium L. species for the first time. Their structures were elucidated using extensive 1D and 2D NMR spectroscopy in combination with HRMS. The isolated SLs were used as external standards for qualitative and quantitative LC-MS analysis of the dry methanol extracts of the flowering aerial parts of 28 Hieracium species from the Balkan Peninsula. Guaianolides were the dominant SLs in 27 species studied. The chemosystematic significance of detected SLs was evaluated using multivariate statistics (PCA, nMDS and UPGMA). Differentiation between the main groups was well supported. All four compounds significantly and equally contributed to the differences between the species. In addition, the eudesmanolide calophyllamine B could be a significant chemosystematic marker for H. sect. Villosa (Griseb.) Gremli s.l. and Glauciformia (Freyn) Zahn-Italica (Fr.) Av. Touv. Copyright © 2018 Elsevier Ltd. All rights reserved.

Antiplasmodial activity of sesquiterpene lactones and a sucrose ester from Vernonia guineensis Benth. (Asteraceae)

PubMed Central

Toyang, Ngeh J.; Krause, Michael A.; Fairhurst, Rick M.; Tane, Pierre; Bryant, Joseph; Verpoorte, Rob

2013-01-01

Ethnopharmacological relevance Aqueous preparations of Vernonia guineensis Benth. (Asteraceae) are used in Cameroonian folk medicine as a general stimulant and to treat various illnesses and conditions including malaria, bacterial infections and helminthic infestations. Materials and methods 10-g samples of the leaf and tuber powders of V. guineensis were extracted separately using dichloromethane, methanol and distilled water. The extracts were dried in vacuo and used in bioassays. These extracts and three compounds previously isolated from V. guineensis [vernopicrin (1), vernomelitensin (2) and pentaisovalerylsucrose (3)] were screened for antiplasmodial activity against chloroquine (CQ)-sensitive (Hb3) and CQ-resistant (Dd2) Plasmodium falciparum lines. Results Crude extracts and pure compounds from V. guineensis showed antiplasmodial activity against both Hb3 and Dd2. The IC50 values of extracts ranged from 1.64 – 27.2 μg/ml for Hb3 and 1.82 – 30.0 μg/ml for Dd2; those for compounds 1, 2 and 3 ranged from 0.47 – 1.62 μg/ml (1364 – 1774 nM) for Hb3 and 0.57 – 1.50 μg/ml (1644 – 2332 nM) for Dd2. None of the crude extracts or pure compounds was observed to exert toxic effects on the erythrocytes used to cultivate the P. falciparum lines. Conclusion In Cameroonian folk medicine, V. guineensis may be used to treat malaria in part due to the antiplasmodial activity of sesquiterpene lactones (1, 2), a sucrose ester (3) and perhaps other compounds present in crude plant extracts. Exploring the safety and antiplasmodial efficacy of these compounds in vivo requires further study. PMID:23542146

Transformation products and reaction kinetics of fragrances in advanced wastewater treatment with ozone.

PubMed

Janzen, Niklas; Dopp, Elke; Hesse, Julia; Richards, Jessica; Türk, Jochen; Bester, Kai

2011-11-01

The reaction of the fragrance compounds 4,6,6,7,8,8-hexamethyl-1,3,4,7-tetrahydrocyclopenta[g]isochromene (HHCB), 1-(3,5,5,6,8,8-hexamethyl-6,7-dihydronaphthalen-2-yl)ethanone (AHTN), 1-tert-butyl-3,5-dimethyl-2,4,6-trinitrobenzene (musk xylene/MX), 1-(4-tert-butyl-2,6-dimethyl-3,5-dinitrophenyl)ethanone (musk ketone/MK), and 1-(2,3,8,8-tetramethyl-1,3,4,5,6,7-hexahydronaphthalen-2-yl)ethanone (OTNE) with ozone in tap water as well as waste water treatment plant (WWTP) effluents is described. Several transformation products are characterized by means of gas chromatography coupled to mass spectrometry. One transformation product (HHCB-Lactone) was confirmed by means of a true standard. Musk xylene and musk ketone do not react with ozone under the conditions used in this study. AHTN and HHCB reacted slowly to a multitude of transformation products, while OTNE reacted quickly to several stable transformation products. The reaction constants and half lives are used to predict removal efficiencies for full scale reactors. Copyright © 2011 Elsevier Ltd. All rights reserved.

Desiderata for product labeling of medical expert systems.

PubMed

Geissbühler, A; Miller, R A

1997-12-01

The proliferation and increasing complexity of medical expert systems raise ethical and legal concerns about the ability of practitioners to protect their patients from defective or misused software. Appropriate product labeling of expert systems can help clinical users to understand software indications and limitations. Mechanisms of action and knowledge representation schema should be explained in layperson's terminology. User qualifications and resources available for acquiring the skills necessary to understand and critique the system output should be listed. The processes used for building and maintaining the system's knowledge base are key determinants of the product's quality, and should be carefully documented. To meet these desiderata, a printed label is insufficient. The authors suggest a new, more active, model of product labeling for medical expert systems that involves embedding 'knowledge of the knowledge base', creating user-specific data, and sharing global information using the Internet.

Expression systems for therapeutic glycoprotein production.

PubMed

Durocher, Yves; Butler, Michael

2009-12-01

There are slightly over 165 recombinant pharmaceuticals currently approved for human use. Another 500 protein candidates are in preclinical and clinical development, about 70% of these being glycosylated proteins. The need for expression systems allowing the efficient manufacturing of high quality glycoproteins is thus becoming imperative. Recent developments with CHO cells, the predominant mammalian expression system, have focused on either increasing cell specific productivity or prolonging the life span of cells in culture that translates to high integrated viable cell densities. These two factors have allowed volumetric productivities in excess of 5 g/L under conditions of controlled nutrient feeding. In addition to glycoengineering strategies, which are offering considerable advantage in producing proteins with enhanced therapeutic properties, several alternative expression systems are being developed for their manufacture, each with their advantages and limitations.

77 FR 46377 - Foreign-Trade Zone 37-Orange County, NY, Notification of Proposed Production Activity, Takasago...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-03

...-jasmone; citronellol-L; trepanol; menthol; musk; oxalide; perilla oil; cyclohexyl lactone; hotact VBE; santalex T; heliotropyl acetate; ambretone; menthol-L synthetic flakes; citral natural; citronellyl formate...

Development of Souvenir Production Transaction Processing System

NASA Astrophysics Data System (ADS)

Rumambi, H.; Kaparang, R.; Lintong, J.

2018-01-01

This research aims to design a souvenir production transaction processing system for the craftsmen in North Sulawesi. The craftsmen make very simple recordings about souvenir production transactions and use documents that are not in accordance with the generally accepted accounting practices. This research uses qualitative method. The data is collected through interviews, observations, documents and literatures studies. The research stages are conducted in preliminary studies, data collection, data analyzed and system design. The design of system is built from chart of account, accounting cycle and documents as input and get processed in accounting recording. The outputs are financial statements. The system design provides benefits for the craftsmen in assessing the financial performance and getting financing from bank.

Expert systems for automated maintenance of a Mars oxygen production system

NASA Technical Reports Server (NTRS)

Ash, Robert L.; Huang, Jen-Kuang; Ho, Ming-Tsang

1989-01-01

A prototype expert system was developed for maintaining autonomous operation of a Mars oxygen production system. Normal operation conditions and failure modes according to certain desired criteria are tested and identified. Several schemes for failure detection and isolation using forward chaining, backward chaining, knowledge-based and rule-based are devised to perform several housekeeping functions. These functions include self-health checkout, an emergency shut down program, fault detection and conventional control activities. An effort was made to derive the dynamic model of the system using Bond-Graph technique in order to develop the model-based failure detection and isolation scheme by estimation method. Finally, computer simulations and experimental results demonstrated the feasibility of the expert system and a preliminary reliability analysis for the oxygen production system is also provided.

30 CFR 250.804 - Production safety-system testing and records.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 2 2013-07-01 2013-07-01 false Production safety-system testing and records... Gas Production Safety Systems § 250.804 Production safety-system testing and records. (a) Inspection... devices operating at temperatures which could ignite a methane-air mixture shall not be used. All...

30 CFR 250.804 - Production safety-system testing and records.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 2 2012-07-01 2012-07-01 false Production safety-system testing and records... Gas Production Safety Systems § 250.804 Production safety-system testing and records. (a) Inspection... devices operating at temperatures which could ignite a methane-air mixture shall not be used. All...

30 CFR 250.804 - Production safety-system testing and records.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 2 2014-07-01 2014-07-01 false Production safety-system testing and records... Gas Production Safety Systems § 250.804 Production safety-system testing and records. (a) Inspection... devices operating at temperatures which could ignite a methane-air mixture shall not be used. All...

Systems Biology of Microbial Exopolysaccharides Production.

PubMed

Ates, Ozlem

2015-01-01

Exopolysaccharides (EPSs) produced by diverse group of microbial systems are rapidly emerging as new and industrially important biomaterials. Due to their unique and complex chemical structures and many interesting physicochemical and rheological properties with novel functionality, the microbial EPSs find wide range of commercial applications in various fields of the economy such as food, feed, packaging, chemical, textile, cosmetics and pharmaceutical industry, agriculture, and medicine. EPSs are mainly associated with high-value applications, and they have received considerable research attention over recent decades with their biocompatibility, biodegradability, and both environmental and human compatibility. However, only a few microbial EPSs have achieved to be used commercially due to their high production costs. The emerging need to overcome economic hurdles and the increasing significance of microbial EPSs in industrial and medical biotechnology call for the elucidation of the interrelations between metabolic pathways and EPS biosynthesis mechanism in order to control and hence enhance its microbial productivity. Moreover, a better understanding of biosynthesis mechanism is a significant issue for improvement of product quality and properties and also for the design of novel strains. Therefore, a systems-based approach constitutes an important step toward understanding the interplay between metabolism and EPS biosynthesis and further enhances its metabolic performance for industrial application. In this review, primarily the microbial EPSs, their biosynthesis mechanism, and important factors for their production will be discussed. After this brief introduction, recent literature on the application of omics technologies and systems biology tools for the improvement of production yields will be critically evaluated. Special focus will be given to EPSs with high market value such as xanthan, levan, pullulan, and dextran.

Systems Biology of Microbial Exopolysaccharides Production

PubMed Central

Ates, Ozlem

2015-01-01

Exopolysaccharides (EPSs) produced by diverse group of microbial systems are rapidly emerging as new and industrially important biomaterials. Due to their unique and complex chemical structures and many interesting physicochemical and rheological properties with novel functionality, the microbial EPSs find wide range of commercial applications in various fields of the economy such as food, feed, packaging, chemical, textile, cosmetics and pharmaceutical industry, agriculture, and medicine. EPSs are mainly associated with high-value applications, and they have received considerable research attention over recent decades with their biocompatibility, biodegradability, and both environmental and human compatibility. However, only a few microbial EPSs have achieved to be used commercially due to their high production costs. The emerging need to overcome economic hurdles and the increasing significance of microbial EPSs in industrial and medical biotechnology call for the elucidation of the interrelations between metabolic pathways and EPS biosynthesis mechanism in order to control and hence enhance its microbial productivity. Moreover, a better understanding of biosynthesis mechanism is a significant issue for improvement of product quality and properties and also for the design of novel strains. Therefore, a systems-based approach constitutes an important step toward understanding the interplay between metabolism and EPS biosynthesis and further enhances its metabolic performance for industrial application. In this review, primarily the microbial EPSs, their biosynthesis mechanism, and important factors for their production will be discussed. After this brief introduction, recent literature on the application of omics technologies and systems biology tools for the improvement of production yields will be critically evaluated. Special focus will be given to EPSs with high market value such as xanthan, levan, pullulan, and dextran. PMID:26734603

High-Sensitivity Monoclonal Antibodies Specific for Homoserine Lactones Protect Mice from Lethal Pseudomonas aeruginosa Infections

PubMed Central

Downham, Christina; Broadbent, Ian; Charlton, Keith; Porter, Andrew J.

2014-01-01

A number of bacteria, including pathogens like Pseudomonas aeruginosa, utilize homoserine lactones (HSLs) as quorum sensing (QS) signaling compounds and engage in cell-to-cell communication to coordinate their behavior. Blocking this bacterial communication may be an attractive strategy for infection control as QS takes a central role in P. aeruginosa biology. In this study, immunomodulation of HSL molecules by monoclonal antibodies (MAbs) was used as a novel approach to prevent P. aeruginosa infections and as tools to detect HSLs in bodily fluids as a possible first clue to an undiagnosed Gram-negative infection. Using sheep immunization and recombinant antibody technology, a panel of sheep-mouse chimeric MAbs were generated which recognized HSL compounds with high sensitivity (nanomolar range) and cross-reactivity. These MAbs retained their nanomolar sensitivity in complex matrices and were able to recognize HSLs in P. aeruginosa cultures grown in the presence of urine. In a nematode slow-killing assay, HSL MAbs significantly increased the survival of worms fed on the antibiotic-resistant strain PA058. The therapeutic benefit of these MAbs was further studied using a mouse model of Pseudomonas infection in which groups of mice treated with HSL-2 and HSL-4 MAbs survived, 7 days after pathogen challenge, in significantly greater numbers (83 and 67%, respectively) compared with the control groups. This body of work has provided early proof-of-concept data to demonstrate the potential of HSL-specific, monoclonal antibodies as theranostic clinical leads suitable for the diagnosis, prevention, and treatment of life-threatening bacterial infections. PMID:24185854

Whole genome sequencing enables the characterization of BurI, a LuxI homologue of Burkholderia cepacia strain GG4

PubMed Central

Hong, Kar Wai; Chan, Kok-Gan

2015-01-01

Quorum sensing is a mechanism for regulating proteobacterial gene expression in response to changes in cell population. In proteobacteria, N-acyl homoserine lactone (AHL) appears to be the most widely used signalling molecules in mediating, among others, the production of extracellular virulence factors for survival. In this work, the genome of B. cepacia strain GG4, a plasmid-free strain capable of AHL synthesis was explored. In silico analysis of the 6.6 Mb complete genome revealed the presence of a LuxI homologue which correspond to Type I quorum sensing. Here, we report the molecular cloning and characterization of this LuxI homologue, designated as BurI. This 609 bp gene was cloned and overexpressed in Escherichia coli BL21(DE3). The purified protein was approximately 25 kDa and is highly similar to several autoinducer proteins of the LuxI family among Burkholderia species. To verify the AHL synthesis activity of this protein, high resolution liquid chromatography-mass spectrometry analysis revealed the production of 3-oxo-hexanoylhomoserine lactone, N-octanoylhomoserine lactone and 3-hydroxy-octanoylhomoserine lactone from induced E. coli BL21 harboring the recombinant BurI. Our data show, for the first time, the cloning and characterization of the LuxI homologue from B. cepacia strain GG4 and confirmation of its AHL synthesis activity. PMID:26290785

Multiple products management system with sensors array in automated storage and retrieval systems

NASA Astrophysics Data System (ADS)

Vongbunyong, Supachai; Roengritronnachai, Perawat; Kongsanit, Savanut; Chanok-owat, Chawisa; Polchankajorn, Pongsakorn

2018-01-01

Automated Storage and Retrieval Systems (AS/RS) have now been widely used in a number of industries due to its capability to automatically manage the storage of products in effective ways. One of the key features of AS/RS is that each rack is not assigned for a specific product resulting in the benefit of space utilization and logistics related issues. In this research, sensor arrays are equipped at each rack in order to enhance this feature. As a result, various products can be identified and mixed in each rack, so that the space utilization efficiency can be increased. To prove the concept, a prototype system consisting of a Cartesian robot that manages the storage and retrieval of products with 9 variations based on size and color. The concept of Cyber-Physical System and self-awareness of the system are also implemented in this concept prototype.

Spirocyclic systems derived from pyroglutamic acid.

PubMed

Cowley, Andrew R; Hill, Thomas J; Kocis, Petr; Moloney, Mark G; Stevenson, Robert D; Thompson, Amber L

2011-10-21

The synthesis and likely conformational structure of rigid spirocyclic bislactams and lactam-lactones derived from pyroglutamic acid, and their suitability as lead structures for applications in drug development programmes using cheminformatic analysis, has been investgated.

Influence of cnicin, a sesquiterpene lactone ofCentaurea maculosa (Asteraceae), on specialist and generalist insect herbivores.

PubMed

Landau, I; Müller-Schärer, H; Ward, P I

1994-04-01

The sesquiterpene lactone cnicin was extracted fromCentaurea maculosa andCentaurea vallesiaca. We examined its effects on the ovipositional response and larval development of generalist and specialist insect herbivores associated withC. maculosa. For the oviposition trials, three plant species (C. maculosa, Achillea millefolium, andCichorium intybus), half of which were sprayed with 3% of cnicin, were exposed to the specialist mothsStenodes straminea, Agapeta zoegana, andPterolonche inspersa in field cages. All three species significantly preferredC. maculosa to other plants andP. inspersa significantly preferred cnicin-sprayed plants to untreated plants for oviposition. Tested over all species, cnicin significantly increased the number of eggs laid on a given plant. A larval diet test examined the toxicity of cnicin for larvae of the generalist noctuid mothSpodoptera littoralis. Cnicin concentrations of 3% and 6% were lethal and 1% and 0.5% seriously inhibited growth and development. The larvae of theC. maculosa specialistStenodes straminea survived at 6% cnicin, but none of the pupae hatched.Agapeta zoegana was able to survive at 1% and 3% cnicin. Both specialists had difficulties with the artificial diet, but weight increase and survival was not further reduced when cnicin was present compared with on the control diet. In conclusion, cnicin influenced host recognition by the specialist species, and larvae of the generalist did not survive on natural levels of cnicin. Growth and survival of the specialist were not influenced by cnicin but were considerably hampered on artificial diet.

Activity of the Rhodopseudomonas palustris p-Coumaroyl-Homoserine Lactone-Responsive Transcription Factor RpaR ▿ †

PubMed Central

Hirakawa, Hidetada; Oda, Yasuhiro; Phattarasukol, Somsak; Armour, Christopher D.; Castle, John C.; Raymond, Christopher K.; Lappala, Colin R.; Schaefer, Amy L.; Harwood, Caroline S.; Greenberg, E. Peter

2011-01-01

The Rhodopseudomonas palustris transcriptional regulator RpaR responds to the RpaI-synthesized quorum-sensing signal p-coumaroyl-homoserine lactone (pC-HSL). Other characterized RpaR homologs respond to fatty acyl-HSLs. We show here that RpaR functions as a transcriptional activator, which binds directly to the rpaI promoter. We developed an RNAseq method that does not require a ribosome depletion step to define a set of transcripts regulated by pC-HSL and RpaR. The transcripts include several noncoding RNAs. A footprint analysis showed that purified His-tagged RpaR (His6-RpaR) binds to an inverted repeat element centered 48.5 bp upstream of the rpaI transcript start site, which we mapped by S1 nuclease protection and primer extension analyses. Although pC-HSL-RpaR bound to rpaI promoter DNA, it did not bind to the promoter regions of a number of RpaR-regulated genes not in the rpaI operon. This indicates that RpaR control of these other genes is indirect. Because the RNAseq analysis allowed us to track transcript strand specificity, we discovered that there is pC-HSL-RpaR-activated antisense transcription of rpaR. These data raise the possibility that this antisense RNA or other RpaR-activated noncoding RNAs mediate the indirect activation of genes in the RpaR-controlled regulon. PMID:21378182

Determination of D-saccharic acid-1,4-lactone from brewed kombucha broth by high-performance capillary electrophoresis.

PubMed

Wang, Kan; Gan, Xuhua; Tang, Xinyun; Wang, Shuo; Tan, Huarong

2010-02-01

Kombucha is a health tonic. D-saccharic acid-1,4-lactone (DSL), a component of kombucha, inhibits the activity of glucuronidase, an enzyme indirectly related with cancers. To date, there is no efficient method to determine the content of DSL in kombucha samples. In this paper, we report a rapid and simple method for the separation and determination of DSL in kombucha samples, using the high-performance capillary electrophoresis (HPCE) method with diode array detection (DAD). With optimized conditions, DSL can be separated in a 50 cm length capillary at a separation voltage of 20 kV in 40 mmol/L borax buffer (pH 6.5) containing 30 mmol/L SDS and 15% methanol (v/v). Quantitative evaluation of DSL was determined by ultraviolet absorption at lambda=190 nm. The relationship between the peak areas and the DSL concentrations, in a specified working range with linear response, was determined by first-order polynomial regression over the range 50-1500 microg/mL with a detection limit of 17.5 microg/mL. Our method demonstrated excellent reproducibility and accuracy with relative standard deviations (RSD) of less than 5% DSL content (n=5). This is the first report to determine DSL by HPCE. We have successfully applied this method to determine DSL in kombucha samples in various fermented conditions. 2009 Elsevier B.V. All rights reserved.

Evolution of tsunami warning systems and products.

PubMed

Bernard, Eddie; Titov, Vasily

2015-10-28

Each year, about 60 000 people and $4 billion (US$) in assets are exposed to the global tsunami hazard. Accurate and reliable tsunami warning systems have been shown to provide a significant defence for this flooding hazard. However, the evolution of warning systems has been influenced by two processes: deadly tsunamis and available technology. In this paper, we explore the evolution of science and technology used in tsunami warning systems, the evolution of their products using warning technologies, and offer suggestions for a new generation of warning products, aimed at the flooding nature of the hazard, to reduce future tsunami impacts on society. We conclude that coastal communities would be well served by receiving three standardized, accurate, real-time tsunami warning products, namely (i) tsunami energy estimate, (ii) flooding maps and (iii) tsunami-induced harbour current maps to minimize the impact of tsunamis. Such information would arm communities with vital flooding guidance for evacuations and port operations. The advantage of global standardized flooding products delivered in a common format is efficiency and accuracy, which leads to effectiveness in promoting tsunami resilience at the community level. © 2015 The Authors.

Evolution of tsunami warning systems and products

PubMed Central

Bernard, Eddie; Titov, Vasily

2015-01-01

Each year, about 60 000 people and $4 billion (US$) in assets are exposed to the global tsunami hazard. Accurate and reliable tsunami warning systems have been shown to provide a significant defence for this flooding hazard. However, the evolution of warning systems has been influenced by two processes: deadly tsunamis and available technology. In this paper, we explore the evolution of science and technology used in tsunami warning systems, the evolution of their products using warning technologies, and offer suggestions for a new generation of warning products, aimed at the flooding nature of the hazard, to reduce future tsunami impacts on society. We conclude that coastal communities would be well served by receiving three standardized, accurate, real-time tsunami warning products, namely (i) tsunami energy estimate, (ii) flooding maps and (iii) tsunami-induced harbour current maps to minimize the impact of tsunamis. Such information would arm communities with vital flooding guidance for evacuations and port operations. The advantage of global standardized flooding products delivered in a common format is efficiency and accuracy, which leads to effectiveness in promoting tsunami resilience at the community level. PMID:26392620

Development and validation of a method for the determination of low-ppb levels of macrocyclic lactones in butter, using HPLC-fluorescence.

PubMed

Macedo, Fabio; Marsico, Eliane Teixeira; Conte-Júnior, Carlos Adam; de Resende, Michele Fabri; Brasil, Taila Figueiredo; Pereira Netto, Annibal Duarte

2015-07-15

An analytical method was developed and validated for the simultaneous determination of four macrocyclic lactones (ML) (abamectin, doramectin, ivermectin and moxidectin) in butter, using liquid chromatography with fluorescence detection. The method employed heated liquid-liquid extraction and a mixture of acetonitrile, ethyl acetate and water, with preconcentration and derivatization, to produce stable fluorescent derivatives. The chromatographic run time was <12.5 min, with excellent separation. The method validation followed international guidelines and employed fortified butter samples. The figures of merit obtained, e.g. recovery (72.4-106.5%), repeatability (8.8%), within-laboratory reproducibility (15.7%) and limits of quantification (0.09-0.16 μg kg(-1)) were satisfactory for the desired application. The application of the method to real samples showed that ML residues were present in six of the ten samples evaluated. The method proved to be simple, easy and appropriate for simultaneous determination of ML residues in butter. To our knowledge, this is the first method described for the evaluation of ML in butter. Copyright © 2015. Published by Elsevier Ltd.

Applications of Molecular Modeling to Transition State Energies and Conformations

DTIC Science & Technology

1992-05-08

reactivity trends for similar systems are known. Illuminati and Mandolini have done research on the lactone formation from w-bromoalkane-carboxylate...strikingly similar to that determined for Illuminati and Mandolini’s similar lactonization system (see Figure 20). The AE, for the 4- 69 membered ring...Brown, F.K.; Spellmeyer, D.C.; Metz, J.T.; Li, Y.; Loncharich, R.L. Science. 1986, 231, 1108-17. Illuminati , G.; Mandolini, L. Accts. of Chem. Res. 1981

Identification of the Quorum-Sensing Target DNA Sequence and N-Acyl Homoserine Lactone Responsiveness of the Brucella abortus virB promoter▿

PubMed Central

Arocena, Gastón M.; Sieira, Rodrigo; Comerci, Diego J.; Ugalde, Rodolfo A.

2010-01-01

VjbR is a LuxR-type quorum-sensing (QS) regulator that plays an essential role in the virulence of the intracellular facultative pathogen Brucella, the causative agent of brucellosis. It was previously described that VjbR regulates a diverse group of genes, including the virB operon. The latter codes for a type IV secretion system (T4SS) that is central for the pathogenesis of Brucella. Although the regulatory role of VjbR on the virB promoter (PvirB) was extensively studied by different groups, the VjbR-binding site had not been identified so far. Here, we identified the target DNA sequence of VjbR in PvirB by DNase I footprinting analyses. Surprisingly, we observed that VjbR specifically recognizes a sequence that is identical to a half-binding site of the QS-related regulator MrtR of Mesorhizobium tianshanense. As shown by DNase I footprinting and electrophoretic mobility shift assays, generation of a palindromic MrtR-like-binding site in PvirB increased both the affinity and the stability of the VjbR-DNA complex, which confirmed that the QS regulator of Brucella is highly related to that of M. tianshanense. The addition of N-dodecanoyl homoserine lactone dissociated VjbR from the promoter, which confirmed previous reports that indicated a negative effect of this signal on the VjbR-mediated activation of PvirB. Our results provide new molecular evidence for the structure of the virB promoter and reveal unusual features of the QS target DNA sequence of the main regulator of virulence in Brucella. PMID:20400542

Evaluation of a Stirling Solar Dynamic System for Lunar Oxygen Production

NASA Technical Reports Server (NTRS)

Colozza, Anthony J.; Wong, Wayne A.

2006-01-01

An evaluation of a solar concentrator-based system for producing oxygen from the lunar regolith was performed. The system utilizes a solar concentrator mirror to provide thermal energy for the oxygen production process as well as thermal energy to power a Stirling heat engine for the production of electricity. The electricity produced is utilized to operate the equipment needed in the oxygen production process. The oxygen production method utilized in the analysis was the hydrogen reduction of ilmenite. Utilizing this method of oxygen production a baseline system design was produced. This baseline system had an oxygen production rate of 0.6 kg/hr with a concentrator mirror size of 5 m. Variations were performed on the baseline design to show how changes in the system size and process rate effected the oxygen production rate.

Carbon footprint and ammonia emissions of California beef production systems.

PubMed

Stackhouse-Lawson, K R; Rotz, C A; Oltjen, J W; Mitloehner, F M

2012-12-01

Beef production is a recognized source of greenhouse gas (GHG) and ammonia (NH(3)) emissions; however, little information exists on the net emissions from beef production systems. A partial life cycle assessment (LCA) was conducted using the Integrated Farm System Model (IFSM) to estimate GHG and NH(3) emissions from representative beef production systems in California. The IFSM is a process-level farm model that simulates crop growth, feed production and use, animal growth, and the return of manure nutrients back to the land to predict the environmental impacts and economics of production systems. Ammonia emissions are determined by summing the emissions from animal housing facilities, manure storage, field applied manure, and direct deposits of manure on pasture and rangeland. All important sources and sinks of methane, nitrous oxide, and carbon dioxide are predicted from primary and secondary emission sources. Primary sources include enteric fermentation, manure, cropland used in feed production, and fuel combustion. Secondary emissions occur during the production of resources used on the farm, which include fuel, electricity, machinery, fertilizer, and purchased animals. The carbon footprint is the net exchange of all GHG in carbon dioxide equivalent (CO(2)e) units per kg of HCW produced. Simulated beef production systems included cow-calf, stocker, and feedlot phases for the traditional British beef breeds and calf ranch and feedlot phases for Holstein steers. An evaluation of differing production management strategies resulted in ammonia emissions ranging from 98 ± 13 to 141 ± 27 g/kg HCW and carbon footprints of 10.7 ± 1.4 to 22.6 ± 2.0 kg CO(2)e/kg HCW. Within the British beef production cycle, the cow-calf phase was responsible for 69 to 72% of total GHG emissions with 17 to 27% from feedlot sources. Holstein steers that entered the beef production system as a by-product of dairy production had the lowest carbon footprint because the emissions

Diversifying crop rotations with pulses enhances system productivity

PubMed Central

Gan, Yantai; Hamel, Chantal; O’Donovan, John T.; Cutforth, Herb; Zentner, Robert P.; Campbell, Con A.; Niu, Yining; Poppy, Lee

2015-01-01

Agriculture in rainfed dry areas is often challenged by inadequate water and nutrient supplies. Summerfallowing has been used to conserve rainwater and promote the release of nitrogen via the N mineralization of soil organic matter. However, summerfallowing leaves land without any crops planted for one entire growing season, creating lost production opportunity. Additionally, summerfallowing has serious environmental consequences. It is unknown whether alternative systems can be developed to retain the beneficial features of summerfallowing with little or no environmental impact. Here, we show that diversifying cropping systems with pulse crops can enhance soil water conservation, improve soil N availability, and increase system productivity. A 3-yr cropping sequence study, repeated for five cycles in Saskatchewan from 2005 to 2011, shows that both pulse- and summerfallow-based systems enhances soil N availability, but the pulse system employs biological fixation of atmospheric N2, whereas the summerfallow-system relies on ‘mining’ soil N with depleting soil organic matter. In a 3-yr cropping cycle, the pulse system increased total grain production by 35.5%, improved protein yield by 50.9%, and enhanced fertilizer-N use efficiency by 33.0% over the summerfallow system. Diversifying cropping systems with pulses can serve as an effective alternative to summerfallowing in rainfed dry areas. PMID:26424172

Multidisciplinary approach to successful implementation of production information system (PRISM)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shariff, M.R.; Gopalakrishnan, S.G.; Francis, N.

1995-12-31

A company wide corporate and regional production database supporting all production areas was envisaged critical to the current expansion within Petronas Carigali Sdn Bhd (PCSB). A multi disciplinary project team was thus formed to analyze the requirements prior to developing, testing, implementing and training users. PCSB has currently evolved into a mature E & P company on par with other E & P companies within the region. This expansion necessitates a common Production Information System for the efficient dissemination of vital Production Information for Production Surveillance, Reservoir Management, Reserve Assessment, Special Studies and Standardized Group-wide Reporting. This paper will discussmore » all the phases involved in the project which includes Systems Requirement Study, Data Migration, System Development, System Implementation and Post-Implementation Plan.« less

A detachable ester bond enables perfect Z-alkylations of olefins for the synthesis of tri- and tetrasubstituted alkenes.

PubMed

Nishikata, Takashi; Nakamura, Kimiaki; Inoue, Yuki; Ishikawa, Shingo

2015-06-25

2-Vinyl-substituted phenol and an alpha-bromoester undergo a tandem esterification-alkylation reaction in the presence of a Cu-amine catalyst system to produce benzene-fused lactone. Z-Alkylated styrene is obtained after hydrolysis of the lactone with perfect selectivity. The simple protocol developed in this work opens a new avenue in the multi-substitution chemistry of alkenes.

Pseudomonas aeruginosa biofilm-associated homoserine lactone C12 rapidly activates apoptosis in airway epithelia

PubMed Central

Schwarzer, Christian; Fu, Zhu; Patanwala, Maria; Hum, Lauren; Lopez-Guzman, Mirielle; Illek, Beate; Kong, Weidong; Lynch, Susan V.; Machen, Terry E.

2014-01-01

Pseudomonas aeruginosa (PA) forms biofilms in lungs of cystic fibrosis CF) patients, a process regulated by quorum sensing molecules including N-(3-oxododecanoyl)-L-homoserine lactone, C12. C12 (10–100 μM) rapidly triggered events commonly associated with the intrinsic apoptotic pathway in JME (CFΔF508CFTR, nasal surface) epithelial cells: depolarization of mitochondrial (mito) membrane potential (Δψmito) and release of cytochrome C (cytoC) from mitos into cytosol and activation of caspases 3/7, 8 and 9. C12 also had novel effects on the endoplasmic reticulum (release of both Ca2+ and ER-targeted GFP and oxidized contents into the cytosol). Effects began within 5 minutes and were complete in 1–2 hrs. C12 caused similar activation of caspases and release of cytoC from mitos in Calu-3 (wtCFTR, bronchial gland) cells, showing that C12-triggered responses occurred similarly in different airway epithelial types. C12 had nearly identical effects on three key aspects of the apoptosis response (caspase 3/7, depolarization of Δψmito and reduction of redox potential in the ER) in JME and CFTR-corrected JME cells (adenoviral expression), showing that CFTR was likely not an important regulator of C12-triggered apoptosis in airway epithelia. Exposure of airway cultures to biofilms from PAO1wt caused depolarization of Δψmito and increases in Cacyto like 10–50 μM C12. In contrast, biofilms from PAO1ΔlasI (C12 deficient) had no effect, suggesting that C12 from P. aeruginosa biofilms may contribute to accumulation of apoptotic cells that cannot be cleared from CF lungs. A model to explain the effects of C12 is proposed. PMID:22233488

Systems Thinking, Lean Production and Action Learning

ERIC Educational Resources Information Center

Seddon, John; Caulkin, Simon

2007-01-01

Systems thinking underpins "lean" management and is best understood through action-learning as the ideas are counter-intuitive. The Toyota Production System is just that--a system; the failure to appreciate that starting-place and the advocacy of "tools" leads many to fail to grasp what is, without doubt, a significant…

The role of the production scheduling system in rescheduling

NASA Astrophysics Data System (ADS)

Kalinowski, K.; Grabowik, C.; Kempa, W.; Paprocka, I.

2015-11-01

The paper presents the rescheduling problem in the context of cooperation between production scheduling system (PSS) and other units in an integrated manufacturing environment - decision makers and software systems. The main aim is to discuss the PSS functionality for maximizing automation of the rescheduling process, reducing the response time and improving the quality of generated solutions. PSSs operate in the meeting of tactical and operational level of planning and control, and play an important role in the production preparation and control. On the basis of information about orders, technology and production system state (e.g. resources availability) they prepare and/or update a detailed plan of production flow - a schedule. All necessary data for scheduling and rescheduling are usually collected in other systems both from organizational and technical production preparation, e.g. ERP, PLM, MES, CAPP or others, as well as they are entered directly by the decision- makers/operators. Data acquired in this way are often incomplete and inconsistent. Therefore the existing rescheduling software works according to interactive method - rather support but does not replace the human decision maker in tasks planning. When rescheduling, due to the limited amount of time to make a decision this interaction is particularly important. An additional problem arises in data acquisition, in the process of data exchanging between systems or in the identification of new data sources and their processing. Different approaches to rescheduling were characterized, including those solutions, where all these operations are carried out by an autonomous system and those in which scheduling is performed only upon request from the outside, for the newly created scheduling data representing the current state of the production system.

A simple assay for the simultaneous determination of rosuvastatin acid, rosuvastatin-5S-lactone, and N-desmethyl rosuvastatin in human plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS).

PubMed

Macwan, Joyce S; Ionita, Ileana A; Akhlaghi, Fatemeh

2012-01-01

A simple and sensitive assay was developed and validated for the simultaneous quantification of rosuvastatin acid (RST), rosuvastatin-5S-lactone (RST-LAC), and N-desmethyl rosuvastatin (DM-RST), in buffered human plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS). All the three analytes and the corresponding deuterium-labeled (d6) internal standards were extracted from 50 μL of buffered human plasma by protein precipitation. The analytes were chromatographically separated using a Zorbax-SB Phenyl column (2.1 mm × 100 mm, 3.5 μm). The mobile phase comprised of a gradient mixture of 0.1% v/v glacial acetic acid in 10% v/v methanol in water (solvent A) and 40% v/v methanol in acetonitrile (solvent B). The analytes were separated at baseline within 6.0 min using a flow rate of 0.35 mL/min. Mass spectrometry detection was carried out in positive electrospray ionization mode. The calibration curves for all three analytes were linear (R ≥ 0.9964, n = 3) over the concentration range of 0.1-100 ng/mL for RST and RST-LAC, and 0.5-100 ng/mL for DM-RST. Mean extraction recoveries ranged within 88.0-106%. Intra- and inter-run mean percent accuracy were within 91.8-111% and percent imprecision was ≤15%. Stability studies revealed that all the analytes were stable in matrix during bench-top (6 h on ice-water slurry), at the end of three successive freeze and thaw cycles and at -80°C for 1 month. The method was successfully applied in a clinical study to determine the concentrations of RST and the lactone metabolite over 12-h post-dose in patients who received a single dose of rosuvastatin.

Environmental impacts and sustainability of egg production systems.

PubMed

Xin, H; Gates, R S; Green, A R; Mitloehner, F M; Moore, P A; Wathes, C M

2011-01-01

As part of a systemic assessment toward social sustainability of egg production, we have reviewed current knowledge about the environmental impacts of egg production systems and identified topics requiring further research. Currently, we know that 1) high-rise cage houses generally have poorer air quality and emit more ammonia than manure belt (MB) cage houses; 2) manure removal frequency in MB houses greatly affects ammonia emissions; 3) emissions from manure storage are largely affected by storage conditions, including ventilation rate, manure moisture content, air temperature, and stacking profile; 4) more baseline data on air emissions from high-rise and MB houses are being collected in the United States to complement earlier measurements; 5) noncage houses generally have poorer air quality (ammonia and dust levels) than cage houses; 6) noncage houses tend to be colder during cold weather due to a lower stocking density than caged houses, leading to greater feed and fuel energy use; 7) hens in noncage houses are less efficient in resource (feed, energy, and land) utilization, leading to a greater carbon footprint; 8) excessive application of hen manure to cropland can lead to nutrient runoff to water bodies; 9) hen manure on open (free) range may be subject to runoff during rainfall, although quantitative data are lacking; 10) mitigation technologies exist to reduce generation and emission of noxious gases and dust; however, work is needed to evaluate their economic feasibility and optimize design; and 11) dietary modification shows promise for mitigating emissions. Further research is needed on 1) indoor air quality, barn emissions, thermal conditions, and energy use in alternative hen housing systems (1-story floor, aviary, and enriched cage systems), along with conventional housing systems under different production conditions; 2) environmental footprint for different US egg production systems through life cycle assessment; 3) practical means to mitigate air

Different approaches to overcome uncertainties of production systems

NASA Astrophysics Data System (ADS)

Azizi, Amir; Sorooshian, Shahryar

2015-05-01

This study presented a comprehensive review on the understanding of uncertainty and the current approaches that have been proposed to handle the uncertainties in the production systems. This paper classified proposed approaches into 11 groups. The paper studied 114 scholarly papers through various international journals. The paper added the latest findings to the body of knowledge to the current reservoir of understanding of the production uncertainties. Thus, the paper prepared the needs of researchers and practitioners for easy references in this area. This review also provided an excellent source to continue further studies on how to deal with the uncertainties of production system.

Targeting overall equipment efficiency for small medium enterprises with irregular production system

NASA Astrophysics Data System (ADS)

Prasetyawan, Y.; Suef, M.; Claudia, L.; Handayani, F. D.

2018-04-01

Overall Equipment Effectiveness (OEE) is widely used to measure the maturity of a production system. The company will be considered as World Class Manufacturing if it reaches more than 85% value, with near perfect value for availability, performance and quality factor. This assessment is usually taken on industries with regular production times named shift system. A typical 8 hours shift system is used in OEE measurement and performance monitoring. There are few Small to Medium Enterprise (SME) perform regular production times with shift systems, others using irregular production systems. The irregular production time in the SME production system is used because of demand fluctuations. This paper shows a quantitative analysis as a part of manufacturing system design to achieve a specific value of OEE for SME with irregular production systems, for individual businesses as well as collective business systems (some companies use the same production facilities for several processes). The results of experiments on several companies are presented, as a basis for determining the technical strategy of achieving OEE values.

Energy use in pig production: an examination of current Iowa systems.

PubMed

Lammers, P J; Kenealy, M D; Kliebenstein, J B; Harmon, J D; Helmers, M J; Honeyman, M S

2012-03-01

This paper compares energy use for different pig production systems in Iowa, a leader in US swine production. Pig production systems include not only the growth and performance of the pigs, but also the supporting infrastructure of pig production. This supporting infrastructure includes swine housing, facility management, feedstuff provision, swine diets, and manure management. Six different facility type × diet formulation × cropping sequence scenarios were modeled and compared. The baseline system examined produces 15,600 pigs annually using confinement facilities and a corn-soybean cropping sequence. Diet formulations for the baseline system were corn-soybean meal diets that included the synthetic AA l-lysine and exogenous phytase. The baseline system represents the majority of current US pork production in the Upper Midwest, where most US swine are produced. This system was found to require 744.6 MJ per 136-kg market pig. An alternative system that uses bedded hoop barns for grow-finish pigs and gestating sows would require 3% less (720.8 MJ) energy per 136-kg market pig. When swine production systems were assessed, diet type and feed ingredient processing were the major influences on energy use, accounting for 61 and 79% of total energy in conventional and hoop barn-based systems, respectively. Improving feed efficiency and better matching the diet formulation with the thermal environment and genetic potential are thus key aspects of reducing energy use by pig production, particularly in a hoop barn-based system. The most energy-intensive aspect of provisioning pig feed is the production of synthetic N for crop production; thus, effectively recycling manure nutrients to cropland is another important avenue for future research. Almost 25% of energy use by a conventional farrow-to-finish pig production system is attributable to operation of the swine buildings. Developing strategies to minimize energy use for heating and ventilation of swine buildings while

Operational System-Impact Products for the Space Situational Awareness Environmental Effects Fusion System (SEEFS)

NASA Astrophysics Data System (ADS)

Quigley, S.; Scro, K.

2006-12-01

The Space Vehicles Directorate of the Air Force Research Laboratory (AFRL/VSBX) and the Technology Applications Division of the Space and Missile Systems Center (SMC/WXT) have combined efforts under the Rapid Prototyping Center (RPC) to design, develop, test, implement, and validate numerical and graphical products for the Air Force Space Command (AFSPC) Space Situational Awareness Environmental Effects Fusion System (SEEFS). These products are generated to analyze, specify, and forecast the effects of the near-earth space environment on Department of Defense weapons, navigation, communications, and surveillance systems. Jointly developed projects that have been completed as prototypes and are undergoing development for real-time operations include a SEEFS architecture and database, five system-impact products, and a high-level decision aid product. This first round of SEEFS products includes Solar Radio Burst Effects (SoRBE) on radar and satellite communications, Radar Auroral Clutter (RAC), Scintillation Effects on radar and satellite communications (RadScint and SatScint), and Satellite Surface and Deep Charge/Discharge (Char/D). The SEEFS architecture and database enable modular use and execution of SEEFS products, and the high-level Decision Aid shows the combined effects of all SEEFS product output on a given asset and on multi-asset missions. This presentation provides a general overview of the SEEFS program, along with details of the first round of products expected to be operational for use in exercises and/or real-time operations in 2007-2008.

Cytotoxic sesquiterpene lactones from the leaves of Vernonia guineensis Benth. (Asteraceae)

PubMed Central

Toyang, Ngeh J.; Wabo, Hippolyte K.; Ateh, Eugene N.; Davis, Harry; Tane, Pierre; Sondengam, Luc B.; Bryant, Joseph; Verpoorte, Rob

2015-01-01

Ethnopharmacological relevance Vernonia guineensis Benth. (Asteraceae) preparations are used in folk medicine in Cameroon to treat a number of ailments, including prostate cancer and malaria, and is used as an anthelmintic, adaptogen and antidote. The aim of this study was to continue the validation of the activity of Vernonia guineensis Benth. extracts and isolated molecules against cancer cell lines following the previous isolation of an anti-prostate cancer sugar ester from the root extract. Materials and methods Acetone extracts of Vernonia guineensis Benth. leaves were tested for activity against 10 cancer cell lines (Breast—MDA-MB-231, Breast—MCF-7, Colon—HCT-116, Leukemia—HL-60, Lung—A549, Melanoma—A375, Ovarian—OVCAR3, Pancreas—Mia-paca, Prostate—PC-3 and Prostate—DU-145). The acetone extract was subjected to bioactivity guided fractionation. Anti-proliferation and clonogenic activity of the isolated compounds were tested. The WST-1 assay was used for the anti-proliferation activity, while the standard clonogenic test was used to determine the clonogenic activity. Results The acetone extract of Vernonia guineensis Benth. demonstrated in vitro activity ranging from IC50 4–26 mg/mL against the 10 cell lines. Activity guided fractionation of this extract yielded two sesquiterpene lactones, isolated for the first time from the genus Vernonia. The compounds were characterized using spectroscopic experiments, including a combination of 1D and 2D NMR data. Vernopicrin (1) and Vernomelitensin (2) demonstrated in vitro activity against human cancer cell lines with IC50 ranging from 0.35–2.04 μM (P < 0.05) and 0.13–1.5 μM (P < 0.05), respectively, between the most and least sensitive cell lines for each compound. Vernopicrin was most active against the human melanoma (A375) cell line and least active against the lung cancer (A549) cell line, while Vernomelitensin was also most active against the human melanoma (A375) cell line and least

Method and system for ethanol production

DOEpatents

Feder, H.M.; Chen, M.J.

1980-05-21

A transition metal carbonyl and a tertiary amine are employed as a homogeneous catalytic system in methanol or a less volatile solvent to react methanol with carbon monoxide and hydrogen gas producing ethanol and carbon dioxide. The gas contains a high carbon monoxide to hydrogen ratio as is present in a typical gasifier product. The reaction has potential for anhydrous ethanol production as carbon dioxide rather than water is produced. The only other significant by-product is methane. Selected transition metal carbonyls include those of iron, ruthenium and possibly manganese and osmium. Selected amines include trimethylamine, N-Methylpyrrolidine, 24-diazabicyclooctane, dimethyneopentylamine and 2-pryidinol.

Method and system for ethanol production

DOEpatents

Feder, Harold M.; Chen, Michael J.

1981-01-01

A transition metal carbonyl and a tertiary amine are employed as a homogeneous catalytic system in methanol or a less volatile solvent to react methanol with carbon monoxide and hydrogen gas producing ethanol and carbon dioxide. The gas contains a high carbon monoxide to hydrogen ratio as is present in a typical gasifier product. The reaction has potential for anhydrous ethanol production as carbon dioxide rather than water is produced. The only other significant by product is methane. Selected transition metal carbonyls include those of iron, ruthenium and possibly manganese and osmium. Selected amines include trimethylamine, N-Methylpyrrolidine, 24-diazabicyclooctane, dimethyneopentylamine and 2-pryidinol.

Continuous whole-system monitoring toward rapid understanding of production HPC applications and systems

DOE PAGES

Agelastos, Anthony; Allan, Benjamin; Brandt, Jim; ...

2016-05-18

A detailed understanding of HPC applications’ resource needs and their complex interactions with each other and HPC platform resources are critical to achieving scalability and performance. Such understanding has been difficult to achieve because typical application profiling tools do not capture the behaviors of codes under the potentially wide spectrum of actual production conditions and because typical monitoring tools do not capture system resource usage information with high enough fidelity to gain sufficient insight into application performance and demands. In this paper we present both system and application profiling results based on data obtained through synchronized system wide monitoring onmore » a production HPC cluster at Sandia National Laboratories (SNL). We demonstrate analytic and visualization techniques that we are using to characterize application and system resource usage under production conditions for better understanding of application resource needs. Furthermore, our goals are to improve application performance (through understanding application-to-resource mapping and system throughput) and to ensure that future system capabilities match their intended workloads.« less

Total synthesis of (+)-achalensolide based on the rh(i)-catalyzed allenic Pauson-Khand-type reaction.

PubMed

Hirose, Toshiyuki; Miyakoshi, Naoki; Mukai, Chisato

2008-02-01

The first total synthesis of (+)-achalensolide was achieved from a commercially available d-(-)-isoascorbic acid. The known epoxide, derived from d-(-)-isoascorbic acid, was converted into the allenyne, the Rh(I)-catalyzed Pauson-Khand-type reaction of which directly provided the bicyclo[5.3.0]decane system, a core framework of the title natural product. The construction of the gamma-lactone moiety and some chemical modifications resulted in the completion of the total synthesis of (+)-achalensolide.

Increasing radiographer productivity by an incentive point system.

PubMed

Williams, B; Chacko, P T

1982-01-01

Because of a very low technologist productivity in their Radiology Department, the authors describe a Productive Point System they developed and implemented to solve this personnel problem. After establishing the average time required to perform all exams, point credits (one point for every ten minutes utilized) were assigned to each exam performed, thereby determining an index of production. A Productive Index of 80% was considered realistic and was the equivalent of 192 points for a 40-hour work week. From 1975 to 1978 personal productivity increased from 79% to 113%. This resulted in an average yearly fiscal savings of over $20,000.00 for this three-year period. There was also a significant improvement in exam efficiency and quality, job attitude, personnel morale, and public relations. This program was highly successful because technologist acceptance and cooperation was complete, and this occurred mainly because the system supports the normal occupational goals and expectations of technologists.

Increasing radiographer productivity by an incentive point system.

PubMed

Williams, B; Chacko, P T

1983-01-01

Because of a very low technologist productivity in their Radiology Department, the authors describe a Productive Point System they developed and implemented to solve this personnel problem. After establishing the average time required to perform all exams, point credits (one point for every ten minutes utilized) were assigned to each exam performed, thereby determining an index of production. A Productive Index of 80% was considered realistic and was the equivalent of 192 points for a 40-hour work week. From 1975 to 1978 personal productivity increased from 79% to 113%. This resulted in an average yearly fiscal savings of over $20,000.00 for this three-year period. There was also a significant improvement in exam efficiency and quality, job attitude, personnel morale, and public relations. This program was highly successful because technologist acceptance and cooperation was complete, and this occurred mainly because the system supports the normal occupational goals and expectations of technologists.

Nutrient balances as indicators for sustainability of broiler production systems.

PubMed

Kratz, S; Halle, I; Rogasik, J; Schnug, E

2004-04-01

1. Flock balances of nitrogen, phosphorus, zinc and copper (N, P, Zn, Cu) were calculated in order to evaluate environmental effects of three different broiler production systems (intensive indoor, free range and organic). 2. Nutrient gain in birds per unit nutrient intake (retention) in intensive indoor production was higher than in free range and organic production. 3. Nutrient surplus relative to nutrient retention was higher in organic production than in free range and intensive indoor production. 4. The main reasons for differences in nutrient efficiency between intensive indoor, free range and organic production were duration of growth period, strain of broilers and feeding strategy. 5. The calculation of whole farm indicators (livestock density, N and P excretions per hectare of farmland) demonstrates how defining system boundaries affects the outcome of an evaluation: organic farms had the smallest livestock densities and the lowest N and P excretions per hectare of farmland. 6. In the efforts to reach a more holistic evaluation of agricultural production systems, the definition of adequate system boundaries must be discussed. In addition to nutrient balances, further indicators of sustainability, such as human and ecological toxicity, should be considered.

Exploring agricultural production systems and their fundamental components with system dynamics modeling

USDA-ARS?s Scientific Manuscript database

Agricultural production in the United States is undergoing marked changes due to rapid shifts in consumer demands, input costs, and concerns for food safety and environmental impact. Agricultural production systems are comprised of multidimensional components and drivers that interact in complex wa...

[Transgenic plants as medicine production systems].

PubMed

Okada, Y

1997-10-01

Transgenic plants are emerging as an important system for the expression of many recombinant proteins, especially those intended for therapeutic purpose. The production of foreign proteins in plants has several advantages. In terms of required equipment and cost, mass production in plants is far easier to achieve than techniques involving animal cells. Successful production of several proteins in plants, including human serum albumin, haemoglobin, monoclonal antibodies, viral antigens (vaccines), enkephalin, and trichosanthin, has been reported. Particularly, the demonstration that vaccine antigens can be produced in plants in their native, immunogenic forms opens exciting possibilities for the "bio-farming" of vaccines. If the antigens are orally active, food-based "edible vaccines" could allow economical production. In this review, I will discuss the progress that has been made by several groups in what is now an expanding area of medicine research that utilizes transgenic plants.

The lux autoinducer regulates the production of exoenzyme virulence determinants in Erwinia carotovora and Pseudomonas aeruginosa.

PubMed Central

Jones, S; Yu, B; Bainton, N J; Birdsall, M; Bycroft, B W; Chhabra, S R; Cox, A J; Golby, P; Reeves, P J; Stephens, S

1993-01-01

Erwinia carotovora and Pseudomonas aeruginosa secrete exoenzymes that contribute to the pathogenesis of plant and mammalian infections respectively. E.carotovora mutants defective in synthesis of the pectinase, cellulase and protease exoenzymes were isolated and classified into two groups. Group 2 mutants were found to be defective in the production of a small freely diffusible molecule, N-3-(oxohexanoyl)-L-homoserine, lactone (HSL), and were avirulent. Addition of exogenous HSL to these group 2 mutants restores synthesis of the exoenzymes and virulence in planta. Of the exoenzymes of P.aeruginosa the metalloprotease, elastase, is an established virulence determinant. Mutants of P.aeruginosa that are defective in elastase production have been isolated and were again found to fall into two groups. Analogous to the group 2 mutants of E.carotovora, group 2 mutants of P. aeruginosa are defective in the synthesis of HSL and exogenous HSL restores elastase production. HSL has now been linked to the control of bioluminescence in Vibrio fischeri, carbapenem antibiotic production of E.carotovora and the above exoenzyme virulence determinants. This information significantly enhances our understanding of the extent and nature of pheromone mediated gene expression control in prokaryotes. Images PMID:8508773

Optimal pattern distributions in Rete-based production systems

NASA Technical Reports Server (NTRS)

Scott, Stephen L.

1994-01-01

Since its introduction into the AI community in the early 1980's, the Rete algorithm has been widely used. This algorithm has formed the basis for many AI tools, including NASA's CLIPS. One drawback of Rete-based implementation, however, is that the network structures used internally by the Rete algorithm make it sensitive to the arrangement of individual patterns within rules. Thus while rules may be more or less arbitrarily placed within source files, the distribution of individual patterns within these rules can significantly affect the overall system performance. Some heuristics have been proposed to optimize pattern placement, however, these suggestions can be conflicting. This paper describes a systematic effort to measure the effect of pattern distribution on production system performance. An overview of the Rete algorithm is presented to provide context. A description of the methods used to explore the pattern ordering problem area are presented, using internal production system metrics such as the number of partial matches, and coarse-grained operating system data such as memory usage and time. The results of this study should be of interest to those developing and optimizing software for Rete-based production systems.

Double promoter expression systems for recombinant protein production by industrial microorganisms.

PubMed

Öztürk, Sibel; Ergün, Burcu Gündüz; Çalık, Pınar

2017-10-01

Using double promoter expression systems is a promising approach to increase heterologous protein production. In this review, current double promoter expression systems for the production of recombinant proteins (r-proteins) by industrially important bacteria, Bacillus subtilis and Escherichia coli; and yeasts, Saccharomyces cerevisiae and Pichia pastoris, are discussed by assessing their potentials and drawbacks. Double promoter expression systems need to be designed to maintain a higher specific product formation rate within the production domain. While bacterial double promoter systems have been constructed as chimeric tandem promoters, yeast dual promoter systems have been developed as separate expression cassettes. To increase production and productivity, the optimal transcriptional activity should be justified either by simultaneously satisfying the requirements of both promoters, or by consecutively stimulating the changeover from one to another in a biphasic process or via successive-iterations. Thus, considering the dynamics of a fermentation process, double promoters can be classified according to their operational mechanisms, as: i) consecutively operating double promoter systems, and ii) simultaneously operating double promoter systems. Among these metabolic design strategies, extending the expression period with two promoters activated under different conditions, or enhancing the transcriptional activity with two promoters activated under similar conditions within the production domain, can be applied independently from the host. Novel studies with new insights, which aim a rational systematic design and construction of dual promoter expression vectors with tailored transcriptional activity, will empower r-protein production with enhanced production and productivity. Finally, the current state-of-the-art review emphasizes the advantages of double promoter systems along with the necessity for discovering new promoters for the development of more

Development of Hybrid Product Breakdown Structure for NASA Ground Systems

NASA Technical Reports Server (NTRS)

Monaghan, Mark W.; Henry, Robert J.

2013-01-01

The Product Breakdown Structure is traditionally a method of identification of the products of a project in a tree structure. It is a tool used to assess, plan, document, and display the equipment requirements for a project. It is part of a product based planning technique, and attempts to break down all components of a project in as much detail as possible, so that nothing is overlooked. The PBS for ground systems at the Kennedy Space Center is being developed to encompass the traditional requirements including the alignment of facility, systems, and components to the organizational hierarchy. The Ground Operations Product Breakdown Structure is a hybrid in nature in that some aspects of a work breakdown structure will be incorporated and merged with the Architecture Concept of Operations, Master Subsystem List, customer interface, and assigned management responsibility. The Ground Operations Product Breakdown Structure needs to be able to identify the flexibility of support differing customers (internal and external) usage of ground support equipment within the Kennedy Space Center launch and processing complex. The development of the Product Breakdown Structure is an iterative activity Initially documenting the organization hierarchy structure and relationships. The Product Breakdown Structure identifies the linkage between the customer program requirements, allocation of system resources, development of design goals, and identification logistics products. As the Product Breakdown Structure progresses the incorporation of the results of requirement planning for the customer occurs identifying facility needs and systems. The mature Product Breakdown Structure is baselined with a hierarchical drawing, the Product Breakdown Structure database, and an associated document identifying the verification of the data through the life cycle of the program/product line. This paper will document, demonstrate, and identify key aspects of the life cycle of a Hybrid Product

Research on the ITOC based scheduling system for ship piping production

NASA Astrophysics Data System (ADS)

Li, Rui; Liu, Yu-Jun; Hamada, Kunihiro

2010-12-01

Manufacturing of ship piping systems is one of the major production activities in shipbuilding. The schedule of pipe production has an important impact on the master schedule of shipbuilding. In this research, the ITOC concept was introduced to solve the scheduling problems of a piping factory, and an intelligent scheduling system was developed. The system, in which a product model, an operation model, a factory model, and a knowledge database of piping production were integrated, automated the planning process and production scheduling. Details of the above points were discussed. Moreover, an application of the system in a piping factory, which achieved a higher level of performance as measured by tardiness, lead time, and inventory, was demonstrated.

The quorum-quenching lactonase from Geobacillus caldoxylosilyticus : purification, characterization, crystallization and crystallographic analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bergonzi, Celine; Schwab, Michael; Elias, Mikael

Lactonases are enzymes that are capable of hydrolyzing various lactones such as aliphatic lactones or acyl-homoserine lactones (AHLs), with the latter being used as chemical signaling molecules by numerous Gram-negative bacteria. Lactonases therefore have the ability to quench the chemical communication, also known as quorum sensing, of numerous bacteria, and in particular to inhibit behaviors that are regulated by this system, such as the expression of virulence factors or the production of biofilms. A novel representative from the metallo-β-lactamase superfamily, dubbed GcL, was isolated from the thermophilic bacteriumGeobacillus caldoxylosilyticus. Because of its thermophilic origin, GcL may constitute an interesting candidatemore » for the development of biocontrol agents. Here, we show that GcL is a thermostable enzyme with a half-life at 75°C of 152.5 ± 10 min. Remarkably, it is also shown that GcL is among the most active lactonases characterized to date, with catalytic efficiencies (k cat/K m) against AHLs of greater than 10 6 M $-$1 s $-$1. The structure of GcL is expected to shed light on the catalytic mechanism of the enzyme and the molecular determinants for the substrate specificity in this class of lactonases. Here, the expression, purification, characterization, crystallization and X-ray diffraction data collection to 1.6 Å resolution of GcL are reported.« less

Organic dairy production systems in Pennsylvania: a case study evaluation.

PubMed

Rotz, C A; Kamphuis, G H; Karsten, H D; Weaver, R D

2007-08-01

The current market demand and price for organic milk is encouraging dairy producers, particularly those on smaller farms, to consider organic production as a means for improving the economic viability of their operations. Organic production systems vary widely in scale, in practices, and across agroclimatic settings. Within this context, case studies of 4 actual organic dairy farms were used to characterize existing systems in Pennsylvania. Based on data from these farms, a whole-farm simulation model (Integrated Farm System Model) was used to compare 4 production systems representing organic grass, organic crop, conventional crop with grazing, and conventional confinement production. The performance of each of these systems was simulated over each year of 25 yr of central Pennsylvania weather data. Simulation results indicated that farm level accumulation of soil P and K may be a concern on organic farms that use poultry manure as a primary crop nutrient source, and that erosion and runoff loss of P may be of concern on organic farms producing annual crops because more tillage is required for weed control. Whole-farm budgets with prices that reflect recent conditions showed an economic advantage for organic over conventional production. A sensitivity analysis showed that this economic advantage depended on a higher milk price for producers of organic milk and was influenced by the difference in milk production maintained by herds using organic and conventional systems. Factors found to have little effect on the relative profitability of organic over conventional production included the differences between organic and conventional prices for seed, chemicals, forage, and animals and the overall costs or prices assumed for organic certification, machinery, pasture fencing, fuel, and labor. Thus, at the current organic milk price, relative to other prices, the case study organic production systems seem to provide an option for improving the economic viability of dairy

Vegetable Production System (Veggie)

NASA Technical Reports Server (NTRS)

Levine, Howard G.; Smith, Trent M.

2016-01-01

The Vegetable Production System (Veggie) was developed by Orbital Technologies Corp. to be a simple, easily stowed, and high growth volume yet low resource facility capable of producing fresh vegetables on the International Space Station (ISS). In addition to growing vegetables in space, Veggie can support a variety of experiments designed to determine how plants respond to microgravity, provide real-time psychological benefits for the crew, and conduct outreach activities. Currently, Veggie provides the largest volume available for plant growth on the ISS.

Theoretical and structural analysis of the active site of the transcriptional regulators LasR and TraR, using molecular docking methodology for identifying potential analogues of acyl homoserine lactones (AHLs) with anti-quorum sensing activity.

PubMed

Ahumedo, Maicol; Díaz, Antonio; Vivas-Reyes, Ricardo

2010-02-01

In the present study the homology of transcriptional receptors LuxR type were evaluated using as point of reference the receptors TraR and LasR of the bacterial types Agrobacterium tumefaciens and Pseudomonas aureginosa respectively. A series of alignments were performed in order to demonstrate that the active site of the protein is conserved in wide range of gram negative bacteria. Moreover, some docking calculations were carried out for analogs of the acyl homoserin lactones (AHLs) and regulatory proteins LasR and TraR, to understand the complex microenvironment in which the ligands are exposed. The molecular alignments show clearly that there are preserved motifs in the residues (Y53, Y61, W57, D70, W85 to TraR, Y56, Y64, W60, D73, W88 to LasR) analyzed, which may serve as site-specific targets for the development of potential antagonists. In this study was found that the anti-quorum sensing activity of the AHLs molecular analogs appears to depend on; the structure of the lactone ring and on appropriate combination of absolute and relative stereochemistry of the carbonyl (C=O) and amide (NH(2)) groups of the side chain of these AHLs molecular analogs, in combination with the interactions with the conserved amino acids (D73, W60, Y56, S129 to LasR and D70, W57, Y53 to TraR) of the LuxR type protein family. Copyright 2009 Elsevier Masson SAS. All rights reserved.

Characterization of the Biosynthetic Genes for 10,11-Dehydrocurvularin, a Heat Shock Response-Modulating Anticancer Fungal Polyketide from Aspergillus terreus

PubMed Central

Xu, Yuquan; Espinosa-Artiles, Patricia; Schubert, Vivien; Xu, Ya-ming; Zhang, Wei; Lin, Min; Gunatilaka, A. A. Leslie; Süssmuth, Roderich

2013-01-01

10,11-Dehydrocurvularin is a prevalent fungal phytotoxin with heat shock response and immune-modulatory activities. It features a dihydroxyphenylacetic acid lactone polyketide framework with structural similarities to resorcylic acid lactones like radicicol or zearalenone. A genomic locus was identified from the dehydrocurvularin producer strain Aspergillus terreus AH-02-30-F7 to reveal genes encoding a pair of iterative polyketide synthases (A. terreus CURS1 [AtCURS1] and AtCURS2) that are predicted to collaborate in the biosynthesis of 10,11-dehydrocurvularin. Additional genes in this locus encode putative proteins that may be involved in the export of the compound from the cell and in the transcriptional regulation of the cluster. 10,11-Dehydrocurvularin biosynthesis was reconstituted in Saccharomyces cerevisiae by heterologous expression of the polyketide synthases. Bioinformatic analysis of the highly reducing polyketide synthase AtCURS1 and the nonreducing polyketide synthase AtCURS2 highlights crucial biosynthetic programming differences compared to similar synthases involved in resorcylic acid lactone biosynthesis. These differences lead to the synthesis of a predicted tetraketide starter unit that forms part of the 12-membered lactone ring of dehydrocurvularin, as opposed to the penta- or hexaketide starters in the 14-membered rings of resorcylic acid lactones. Tetraketide N-acetylcysteamine thioester analogues of the starter unit were shown to support the biosynthesis of dehydrocurvularin and its analogues, with yeast expressing AtCURS2 alone. Differential programming of the product template domain of the nonreducing polyketide synthase AtCURS2 results in an aldol condensation with a different regiospecificity than that of resorcylic acid lactones, yielding the dihydroxyphenylacetic acid scaffold characterized by an S-type cyclization pattern atypical for fungal polyketides. PMID:23335766

Locally indistinguishable orthogonal product bases in arbitrary bipartite quantum system

PubMed Central

Xu, Guang-Bao; Yang, Ying-Hui; Wen, Qiao-Yan; Qin, Su-Juan; Gao, Fei

2016-01-01

As we know, unextendible product basis (UPB) is an incomplete basis whose members cannot be perfectly distinguished by local operations and classical communication. However, very little is known about those incomplete and locally indistinguishable product bases that are not UPBs. In this paper, we first construct a series of orthogonal product bases that are completable but not locally distinguishable in a general m ⊗ n (m ≥ 3 and n ≥ 3) quantum system. In particular, we give so far the smallest number of locally indistinguishable states of a completable orthogonal product basis in arbitrary quantum systems. Furthermore, we construct a series of small and locally indistinguishable orthogonal product bases in m ⊗ n (m ≥ 3 and n ≥ 3). All the results lead to a better understanding of the structures of locally indistinguishable product bases in arbitrary bipartite quantum system. PMID:27503634

Biogenic trypanocidal sesquiterpenes: lead compounds to design future trypanocidal drugs - a mini review

PubMed Central

2013-01-01

Human trypanosomiasis is a parasitic disease among poor people in Africa and Latin America. Therapy against African and American trypanosomiasis is based on a few drugs that often cause severe side-effects. Therefore, it is essential to develop drug discovery especially from natural origins. Sesquiterpenes, a diverse group of natural terpenoids, are found in essential oils of many plants and show a broad range of bioactivities. They act through multiple mechanisms in the chemotherapy of trypanosomiasis. Some of these active compounds contain hydroperoxides, aldehydes, alcohols, α,β-unsaturated γ-lactone and even halogenated moieties. Among the compounds reported, sesquiterpene lactones showed a potent anti-trypanosoma effect comparable with commercial trypanocidal drugs. Trypanocidal activity of sesquiterpene lactones mostly depends on the reaction between γ-lactone moieties and nucleophile groups of trypanithione, which is essential for Trypanosoma defense against the oxidative stresses. Elatol is a sesquiterpenoid from marine algae, with a different structure and considerable trypanocidal activity which could be an interesting candidate for further antiprotozoal investigations. To develop novel drugs with higher efficacy and lower toxicity from natural products, this review summarizes the more recent information on trypanocidal activities of various sesquiterpenes. PMID:23676125

In vitro meat production system: why and how?

PubMed

Sharma, Shruti; Thind, Sukhcharanjit Singh; Kaur, Amarjeet

2015-12-01

Due to the nutritional importance and the sustained popularity of meat as a foodstuff, the livestock production sector has been expanding incessantly. This exponential growth of livestock meat sector poses a gigantic challenge to the sustainability of food production system. A new technological breakthrough is being contemplated to develop a substitute for livestock meat. The idea is to grow meat in a culture in the lab and manipulate its composition selectively. This paper aims to discuss the concept of In Vitro Meat production system, articulate the underlying technology and analyse the context of its implications, as proposed by several scientists and stakeholders. The challenges facing this emerging technology have also been discussed.

Elements of oxygen production systems using Martian atmosphere

NASA Technical Reports Server (NTRS)

Ash, R. L.; Huang, J.-K.; Johnson, P. B.; Sivertson, W. E., Jr.

1986-01-01

Hardware elements have been studied in terms of their applicability to Mars oxygen production systems. Various aspects of the system design are discussed and areas requiring further research are identified. Initial work on system reliability is discussed and a methodology for applying expert system technology to the oxygen processor is described.

Design of systems for productivity and well being.

PubMed

Edwards, Kasper; Jensen, Per Langaa

2014-01-01

It has always been an ambition within the ergonomic profession to ensure that design or redesign of production systems consider both productivity and employee well being, but there are many approaches to how to achieve this. This paper identifies the basic issues to be addressed in light of some research activities at DTU, especially by persons responsible for facilitating design processes. Four main issues must be addressed: (1) determining the limits and scope of the system to be designed; (2) identifying stakeholders related to the system and their role in the system design; (3) handling the process' different types of knowledge; and (4) emphasizing that performance management systems, key performance indicators (KPIs), and leadership are also part of the system design and must be given attention. With the examples presented, we argue that knowledge does exist to help system design facilitators address these basic issues. Copyright © 2013. Published by Elsevier Ltd.

Insights into the Quorum Sensing Regulon of the Acidophilic Acidithiobacillus ferrooxidans Revealed by Transcriptomic in the Presence of an Acyl Homoserine Lactone Superagonist Analog

PubMed Central

Mamani, Sigde; Moinier, Danielle; Denis, Yann; Soulère, Laurent; Queneau, Yves; Talla, Emmanuel; Bonnefoy, Violaine; Guiliani, Nicolas

2016-01-01

While a functional quorum sensing system has been identified in the acidophilic chemolithoautotrophic Acidithiobacillus ferrooxidans ATCC 23270T and shown to modulate cell adhesion to solid substrates, nothing is known about the genes it regulates. To address the question of how quorum sensing controls biofilm formation in A. ferrooxidansT, the transcriptome of this organism in conditions in which quorum sensing response is stimulated by a synthetic superagonist AHL (N-acyl homoserine lactones) analog has been studied. First, the effect on biofilm formation of a synthetic AHL tetrazolic analog, tetrazole 9c, known for its agonistic QS activity, was assessed by fluorescence and electron microscopy. A fast adherence of A. ferrooxidansT cells on sulfur coupons was observed. Then, tetrazole 9c was used in DNA microarray experiments that allowed the identification of genes regulated by quorum sensing signaling, and more particularly, those involved in early biofilm formation. Interestingly, afeI gene, encoding the AHL synthase, but not the A. ferrooxidans quorum sensing transcriptional regulator AfeR encoding gene, was shown to be regulated by quorum sensing. Data indicated that quorum sensing network represents at least 4.5% (141 genes) of the ATCC 23270T genome of which 42.5% (60 genes) are related to biofilm formation. Finally, AfeR was shown to bind specifically to the regulatory region of the afeI gene at the level of the palindromic sequence predicted to be the AfeR binding site. Our results give new insights on the response of A. ferrooxidans to quorum sensing and on biofilm biogenesis. PMID:27683573

Insights into the Quorum Sensing Regulon of the Acidophilic Acidithiobacillus ferrooxidans Revealed by Transcriptomic in the Presence of an Acyl Homoserine Lactone Superagonist Analog.

PubMed

Mamani, Sigde; Moinier, Danielle; Denis, Yann; Soulère, Laurent; Queneau, Yves; Talla, Emmanuel; Bonnefoy, Violaine; Guiliani, Nicolas

2016-01-01

While a functional quorum sensing system has been identified in the acidophilic chemolithoautotrophic Acidithiobacillus ferrooxidans ATCC 23270(T) and shown to modulate cell adhesion to solid substrates, nothing is known about the genes it regulates. To address the question of how quorum sensing controls biofilm formation in A. ferrooxidans (T), the transcriptome of this organism in conditions in which quorum sensing response is stimulated by a synthetic superagonist AHL (N-acyl homoserine lactones) analog has been studied. First, the effect on biofilm formation of a synthetic AHL tetrazolic analog, tetrazole 9c, known for its agonistic QS activity, was assessed by fluorescence and electron microscopy. A fast adherence of A. ferrooxidans (T) cells on sulfur coupons was observed. Then, tetrazole 9c was used in DNA microarray experiments that allowed the identification of genes regulated by quorum sensing signaling, and more particularly, those involved in early biofilm formation. Interestingly, afeI gene, encoding the AHL synthase, but not the A. ferrooxidans quorum sensing transcriptional regulator AfeR encoding gene, was shown to be regulated by quorum sensing. Data indicated that quorum sensing network represents at least 4.5% (141 genes) of the ATCC 23270(T) genome of which 42.5% (60 genes) are related to biofilm formation. Finally, AfeR was shown to bind specifically to the regulatory region of the afeI gene at the level of the palindromic sequence predicted to be the AfeR binding site. Our results give new insights on the response of A. ferrooxidans to quorum sensing and on biofilm biogenesis.

Multiperiod planning tool for multisite pig production systems.

PubMed

Nadal-Roig, E; Plà, L M

2014-09-01

This paper presents a multiperiod planning tool for multisite pig production systems based on Linear Programming (LP). The aim of the model is to help pig managers of multisite systems in making short-term decisions (mainly related to pig transfers between farms and batch management in fattening units) and mid-term or long-term decisions (according to company targets and expansion strategy). The model skeleton follows the structure of a three-site system that can be adapted to any multisite system present in the modern pig industry. There are three basic phases, namely, piglet production, rearing pigs, and fattening. Each phase involves a different set of farms; therefore, transportation between farms and delivering of pigs to the abattoir are under consideration. The model maximizes the total gross margin calculated from the income of sales to the abattoir and the production costs over the time horizon considered. Production cost depends on each type of farm involved in the process. Parameters like number of farms per phase and distance, farm capacity, reproduction management policies, feeding and veterinary expenses, and transportation costs are taken into account. The model also provides a schedule of transfers between farms in terms of animals to be transported and number of trucks involved. The use of the model is illustrated with a case study based on a real instance of a company located in Catalonia (Spain).

Continuous hydroponic wheat production using a recirculating system

NASA Technical Reports Server (NTRS)

Mackowiak, C. L.; Owens, L. P.; Hinkle, C. R.; Prince, R. P.

1989-01-01

Continuous crop production, where plants of various ages are growing simultaneously in a single recirculating nutrient solution, is a possible alternative to batch production in a Controlled Ecological Life Support System. A study was conducted at John F. Kennedy Space Center where 8 trays (0.24 sq m per tray) of Triticum aestivum L. Yecora Rojo were grown simultaneously in a growth chamber at 23 C, 65 percent relative humidity, 1000 ppm CO2, continuous light, with a continuous flow, thin film nutrient delivery system. The same modified Hoagland nutrient solution was recirculated through the plant trays from an 80 L reservoir throughout the study. It was maintained by periodic addition of water and nutrients based on chemical analyses of the solution. The study was conducted for 216 days, during which 24 trays of wheat were consecutively planted (one every 9 days), 16 of which were grown to maturity and harvested. The remaining 8 trays were harvested on day 216. Grain yields averaged 520 g m(exp -2), and had an average edible biomass of 32 percent. Consecutive yields were unaffected by nutrient solution age. It was concluded that continual wheat production will work in this system over an extended period of time. Certain micronutrient deficiencies and toxicities posed problems and must be addressed in future continuous production systems.

Automatic milking systems, farm size, and milk production.

PubMed

Rotz, C A; Coiner, C U; Soder, K J

2003-12-01

Automatic milking systems (AMS) offer relief from the demanding routine of milking. Although many AMS are in use in Europe and a few are used in the United States, the potential benefit for American farms is uncertain. A farm-simulation model was used to determine the long-term, whole-farm effect of implementing AMS on farm sizes of 30 to 270 cows. Highest farm net return to management and unpaid factors was when AMS were used at maximal milking capacity. Adding stalls to increase milking frequency and possibly increase production generally did not improve net return. Compared with new traditional milking systems, the greatest potential economic benefit was a single-stall AMS on a farm size of 60 cows at a moderate milk production level (8600 kg/cow). On other farm sizes using single-stall type robotic units, losses in annual net return of 0 dollars to 300 dollars/cow were projected, with the greatest losses on larger farms and at high milk production (10,900 kg/cow). Systems with one robot serving multiple stalls provided a greater net return than single-stall systems, and this net return was competitive with traditional parlors for 50- to 130-cow farm sizes. The potential benefit of AMS was improved by 100 dollars/cow per year if the AMS increased production an additional 5%. A 20% reduction in initial equipment cost or doubling milking labor cost also improved annual net return of an AMS by up to 100 dollars/cow. Annual net return was reduced by 110 dollars/cow, though, if the economic life of the AMS was reduced by 3 yr for a more rapid depreciation than that normally used with traditional milking systems. Thus, under current assumptions, the economic return for an AMS was similar to that of new parlor systems on smaller farms when the milking capacity of the AMS was well matched to herd size and milk production level.

Environmental effect of constructed wetland as biofuel production system

NASA Astrophysics Data System (ADS)

Liu, Dong

2017-04-01

Being as a renewable energy, biofuel has attracted worldwide attention. Clean biofuel production is an effective way to mitigate global climate change and energy crisis. Biofuel may offer a promising alternative to fossil fuels, but serious concerns arise about the adverse greenhouse gas consequences from using nitrogen fertilizers. Waste-nitrogen recycling is an attractive idea. Here we advocate a win-win approach to biofuel production which takes advantage of excessive nitrogen in domestic wastewater treated via constructed wetland (CW) in China. This study will carry on environmental effect analysis of CW as a biomass generation system through field surveys and controllable simulated experiments. This study intends to evaluate net energy balance, net greenhouse effect potential and ecosystem service of CW as biomass generation system, and make comparation with traditional wastewater treatment plant and other biofuel production systems. This study can provide a innovation mode in order to solve the dilemma between energy crops competed crops on production land and excessive nitrogen fertilizer of our traditional energy plant production. Data both from our experimental CWs in China and other researches on comparable CWs worldwide showed that the biomass energy yield of CWs can reach 182.3 GJ ha-1 yr-1, which was two to eight times higher than current biofuel-production systems. Energy output from CW was ˜137% greater than energy input for biofuel production. If CWs are designed with specific goal of biofuel production, biofuel production can be greatly enhanced through the optimization of N supply, hydraulic structures, and species selection in CWs. Assuming that 2.0 Tg (1 Tg = 1012 g) waste nitrogen contained in domestic wastewater is treated by CWs, biofuel production can account for 1.2% of national gasoline consumption in China. The proportion would increase to 6.7% if extra nitrogen (9.5 Tg) from industrial wastewater and agricultural runoff was included

Approach to an Affordable and Productive Space Transportation System

NASA Technical Reports Server (NTRS)

McCleskey, Carey M.; Rhodes, Russel E.; Lepsch, Roger A.; Henderson, Edward M.; Robinson, John W.

2012-01-01

This paper describes an approach for creating space transportation architectures that are affordable, productive, and sustainable. The architectural scope includes both flight and ground system elements, and focuses on their compatibility to achieve a technical solution that is operationally productive, and also affordable throughout its life cycle. Previous papers by the authors and other members of the Space Propulsion Synergy Team (SPST) focused on space flight system engineering methods, along with operationally efficient propulsion system concepts and technologies. This paper follows up previous work by using a structured process to derive examples of conceptual architectures that integrate a number of advanced concepts and technologies. The examples are not intended to provide a near-term alternative architecture to displace current near-term design and development activity. Rather, the examples demonstrate an approach that promotes early investments in advanced system concept studies and trades (flight and ground), as well as in advanced technologies with the goal of enabling highly affordable, productive flight and ground space transportation systems.

National Strategy for Modernizing the Regulatory System for Biotechnology Products

EPA Pesticide Factsheets

This National Strategy for Modernizing the Regulatory System for Biotechnology Products sets forth a vision for ensuring that the federal regulatory system is prepared to efficiently assess the risks, if any, of the future products of biotechnology.

Production system with process quality control: modelling and application

NASA Astrophysics Data System (ADS)

Tsou, Jia-Chi

2010-07-01

Over the past decade, there has been a great deal of research dedicated to the study of quality and the economics of production. In this article, we develop a dynamic model which is based on the hypothesis of a traditional economic production quantity model. Taguchi's cost of poor quality is used to evaluate the cost of poor quality in the dynamic production system. A practical case from the automotive industry, which uses the Six-sigma DMAIC methodology, is discussed to verify the proposed model. This study shows that there is an optimal value of quality investment to make the production system reach a reasonable quality level and minimise the production cost. Based on our model, the management can adjust its investment in quality improvement to generate considerable financial return.

Characterization of indigenous chicken production systems in Rwanda.

PubMed

Mahoro, J; Muasya, T K; Mbuza, F; Habimana, R; Kahi, A K

2017-12-01

Characterization of indigenous chicken (IC) production systems in Rwanda was conducted from November 2015 to January 2016 with the aim of understanding socio-economic characteristics, management of IC, production parameters, feed resources, and constraints faced by farmers rearing IC. A survey involving 206 households was carried out in 5 districts with the highest populations of IC using structured questionnaires. Data were analyzed using SAS software. The results showed that the majority of respondents (62.4%) were males and 37.6% were females. The majority of respondents (83.6%) had formal education. All family members were involved in the chicken husbandry practices. However, women (78%) were highly responsible for IC management activities. The family size averaged 5 persons (ranging 2 to 13) per household. Land was privately owned by farmers (84%) with a mean holding of 0.87 ha per household. The production system was mainly extensive with minimum provision of supplementary feeds. Chickens were being housed in separate houses at night and mating was uncontrolled. Breeding and replacement stocks were mainly sourced from the hatching of eggs using broody hens (60.68% of respondents). There were no vaccination programs, and ecto- and endo-parasites control was done when need arose. Egg production, income generation, meat production, and production of breeding stock were the main reasons of keeping IC. The first 3 main challenges facing IC production were diseases outbreaks, lack of investment capital, and predators. Others challenges, such as feed shortage, thieves, fluctuation of market price, lack of information on poultry rearing, and lack of chicken houses, also were mentioned. The IC production constraints mentioned need urgent mitigation measures to sustain utilization of IC against the changing climatic and economic conditions. Therefore, individual, public institution, and non-governmental organization efforts are required to develop sustainable breeding

Guide for Transitioning Army Missile Systems From Development to Production.

DTIC Science & Technology

1981-07-01

cost reduction ideas. 3 e! M. atumtion0 !eM . One missile system currently In fall *"I* develoluft, MM9 bee foregone the traditional engineering... costs , delivery schedules and deployment dates. Because of these difficulties and a desire to improve the weapon systems acquisition process, the...tered during the transition of new missile systems into production include: 1. High production unit costs - Occasionally the number of systems to be

Livestock production systems in developing countries: status, drivers, trends.

PubMed

Steinfeld, H; Wassenaar, T; Jutzi, S

2006-08-01

This paper describes and assesses the current status of livestock production systems, the drivers of global livestock production, and the major trends in such production. The analysis covers the six major livestock species: cattle and buffaloes, goats and sheep, pigs and chickens. Global drivers of the livestock sector include economic growth and income, demographic and land use changes, dietary adjustments and technological change. The rate of change and direction of livestock development vary greatly among world regions, with Asia showing the most rapid growth and structural change. The paper also examines system dynamics, by analysing the ways livestock production has adjusted to external forces. A brief discussion of how these trends link to food safety concludes the paper.

Phylogenetically Novel LuxI/LuxR-Type Quorum Sensing Systems Isolated Using a Metagenomic Approach

PubMed Central

Nasuno, Eri; Fujita, Masaki J.; Nakatsu, Cindy H.; Kamagata, Yoichi; Hanada, Satoshi

2012-01-01

A great deal of research has been done to understand bacterial cell-to-cell signaling systems, but there is still a large gap in our current knowledge because the majority of microorganisms in natural environments do not have cultivated representatives. Metagenomics is one approach to identify novel quorum sensing (QS) systems from uncultured bacteria in environmental samples. In this study, fosmid metagenomic libraries were constructed from a forest soil and an activated sludge from a coke plant, and the target genes were detected using a green fluorescent protein (GFP)-based Escherichia coli biosensor strain whose fluorescence was screened by spectrophotometry. DNA sequence analysis revealed two pairs of new LuxI family N-acyl-l-homoserine lactone (AHL) synthases and LuxR family transcriptional regulators (clones N16 and N52, designated AubI/AubR and AusI/AusR, respectively). AubI and AusI each produced an identical AHL, N-dodecanoyl-l-homoserine lactone (C12-HSL), as determined by nuclear magnetic resonance (NMR) and mass spectrometry. Phylogenetic analysis based on amino acid sequences suggested that AusI/AusR was from an uncultured member of the Betaproteobacteria and AubI/AubR was very deeply branched from previously described LuxI/LuxR homologues in isolates of the Proteobacteria. The phylogenetic position of AubI/AubR indicates that they represent a QS system not acquired recently from the Proteobacteria by horizontal gene transfer but share a more ancient ancestry. We demonstrated that metagenomic screening is useful to provide further insight into the phylogenetic diversity of bacterial QS systems by describing two new LuxI/LuxR-type QS systems from uncultured bacteria. PMID:22983963

Consumer product safety: A systems problem

NASA Technical Reports Server (NTRS)

Clark, C. C.

1971-01-01

The manufacturer, tester, retailer, consumer, repairer disposer, trade and professional associations, national and international standards bodies, and governments in several roles are all involved in consumer product safety. A preliminary analysis, drawing on system safety techniques, is utilized to distinguish the inter-relations of these many groups and the responsibilities that they are or could take for product safety, including the slow accident hazards as well as the more commonly discussed fast accident hazards. The importance of interactive computer aided information flow among these groups is particularly stressed.

The Student Production System: A Study of Encoding Knowledge in Production Systems

DTIC Science & Technology

1975-10-01

i !. tttf n.- i n,-’. ir- tin n.-’ i nm pin nn’. »? oil ( I -1!»;. W4 M »nPIHflllClltWH II« !M,|.« M„N 1’, m firr... i I , Best Available Copy .. , :■-■.-■■ -;:■■■>■.-■’■;.!-’■■ .:--.-■... ■.r--,-.-,■-,-..M. . IVhrn Diftt* F.ntorrd) AD-A955 862 "ATION...90-Ü 1*^ W.a.| i ;<J Las„Li UUila, ’ i RiiPORT NUMUEH 4 T\\Tl.E (and Subtitle) i THE STUMT^ PRODUCTION SYSTEM A Study

Chemo-Enzymatic Synthesis of Chiral Epoxides Ethyl and Methyl (S)-3-(Oxiran-2-yl)propanoates from Renewable Levoglucosenone: An Access to Enantiopure (S)-Dairy Lactone.

PubMed

Peru, Aurélien A M; Flourat, Amandine L; Gunawan, Christian; Raverty, Warwick; Jevric, Martyn; Greatrex, Ben W; Allais, Florent

2016-07-29

Chiral epoxides-such as ethyl and methyl (S)-3-(oxiran-2-yl)propanoates ((S)-1a/1b)-are valuable precursors in many chemical syntheses. Until recently, these compounds were synthesized from glutamic acid in four steps (deamination, reduction, tosylation and epoxide formation) in low to moderate overall yield (20%-50%). Moreover, this procedure requires some harmful reagents such as sodium nitrite ((eco)toxic) and borane (carcinogen). Herein, starting from levoglucosenone (LGO), a biobased chiral compound obtained through the flash pyrolysis of acidified cellulose, we propose a safer and more sustainable chemo-enzymatic synthetic pathway involving lipase-mediated Baeyer-Villiger oxidation, palladium-catalyzed hydrogenation, tosylation and treatment with sodium ethoxide/methoxide as key steps. This route afforded ethyl and methyl (S)-3-(oxiran-2-yl)propanoates in 57% overall yield, respectively. To demonstrate the potentiality of this new synthetic pathway from LGO, the synthesis of high value-added (S)-dairy lactone was undertaken from these epoxides and provided the target in 37% overall yield from LGO.

Brazilian Citizens’ Opinions and Attitudes about Farm Animal Production Systems

PubMed Central

Yunes, Maria C.; von Keyserlingk, Marina A. G.; Hötzel, Maria J.

2017-01-01

Simple Summary The inclusion of societal input is needed for food animal production industries to retain their “social license to operate”. Little is known about the knowledge and attitudes of Brazilian citizens regarding food animal production systems. The aim of this study was to explore the beliefs and attitudes of Brazilians not associated with livestock production towards farm animal production systems. Overall, our participants expressed a preference for free-range, cage-free, and more “natural” production systems. They also expressed concerns with livestock production systems that limited the movement or expression of natural behaviours, particularly those that they associated with animal suffering or distress. They recognized farm animals as deserving respect and dignity beyond the provision of basic needs. Our findings indicate that Brazil’s current farm animal housing practices that are associated with restriction of movement may not align with societal expectations. Abstract The inclusion of societal input is needed for food animal production industries to retain their “social license to operate”; failure to engage with the public on this topic risks the long-term sustainability of these industries. The primary aim of this study was to explore the beliefs and attitudes of Brazilians citizens not associated with livestock production towards farm animal production. A related secondary aim was to identify the specific beliefs and attitudes towards systems that are associated with restriction of movement. Each participant was shown pictures representing two of five possible major food animal industries (laying hens, beef cattle, pregnant sows, lactating sows, and poultry meat). Participants were presented a six pages survey that included demographic questions plus two sets of two pictures and a series of questions pertaining to the pictures. Each set of pictures represented a particular industry where one picture represented a housing type that

Development of Product Availability Monitoring System In Production Unit In Automotive Component Industry

NASA Astrophysics Data System (ADS)

Hartono, Rachmad; Raharno, Sri; Yuwana Martawirya, Yatna; Arthaya, Bagus

2018-03-01

This paper described a methodology to monitor the availability of products in a production unit in the automotive component industry. Automotive components made are automotive components made through sheet metal working. Raw material coming into production unit in the form of pieces of plates that have a certain size. Raw materials that come stored in the warehouse. Data of raw each material in the warehouse are recorded and stored in a data base system. The material will then undergo several production processes in the production unit. When the material is taken from the warehouse, material data are also recorded and stored in a data base. The data recorded are the amount of material, material type, and date when the material is out of the warehouse. The material coming out of the warehouse is labeled with information related to the production processes that the material must pass. Material out of the warehouse is a product will be made. The products have been completed, are stored in the warehouse products. When the product is entered into the product warehouse, product data is also recorded by scanning the barcode contained on the label. By recording the condition of the product at each stage of production, we can know the availability of the product in a production unit in the form of a raw material, the product being processed and the finished product.

Structural characterization of electrochemically and in vitro biologically generated oxidation products of atorvastatin using UHPLC/MS/MS.

PubMed

Jirásko, Robert; Mikysek, Tomáš; Chagovets, Vitaliy; Vokřál, Ivan; Holčapek, Michal

2013-09-01

Ultrahigh-performance liquid chromatography coupled with high-mass-accuracy tandem mass spectrometry (UHPLC-MS-MS) has been used for elucidation of the structures of oxidation products of atorvastatin (AT), one of the most popular commercially available drugs. The purpose of the study was identification of AT metabolites in rat hepatocytes and comparison with electrochemically generated oxidation products. AT was incubated with rat hepatocytes for 24 h. Electrochemical oxidation of AT was performed by use of a three-electrode off-line system with a glassy carbon working electrode. Three supporting electrolytes (0.1 mol L(-1) H2SO4, 0.1 mol L(-1) HCl, and 0.1 mol L(-1) NaCl) were tested, and dependence on pH was also investigated. AT undergoes oxidation by a single irreversible process at approximately +1.0 V vs. Ag/AgCl electrode. The results obtained revealed a simple and relatively fast way of determining the type of oxidation and its position, on the basis of characteristic neutral losses (NLs) and fragment ions. Unfortunately, different products were obtained by electrochemical oxidation and biotransformation of AT. High-mass-accuracy measurement combined with different UHPLC-MS-MS scans, for example reconstructed ion-current chromatograms, constant neutral loss chromatograms, or exact mass filtering, enable rapid identification of drug-related compounds. β-Oxidation, aromatic hydroxylation of the phenylaminocarbonyl group, sulfation, AT lactone and glycol formation were observed in rat biotransformation samples. In contrast, a variety of oxidation reactions on the conjugated skeleton of isopropyl substituent of AT were identified as products of electrolysis.

Novel Hydrogen Production Systems Operative at Thermodynamic Extremes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gunsalus, Robert

2012-11-30

We have employed a suite of molecular, bioinformatics, and biochemical tools to interrogate the thermodynamically limiting steps of H{sub 2} production from fatty acids in syntrophic communities. We also developed a new microbial model system that generates high H{sub 2} concentrations (over 17% of the gas phase) with high H{sub 2} yields of over 3 moles H{sub 2} per mole glucose. Lastly, a systems-based study of biohydrogen production in model anaerobic consortia was performed to begin identifying key regulated steps as a precursor to modeling co-metabolism. The results of these studies significantly expand our ability to predict and model systemsmore » for H{sub 2} production in novel anaerobes that are currently very poorly documented or understood.« less

It Systems Supporting the Management of Production Capacity

NASA Astrophysics Data System (ADS)

Milewska, Elżbieta

2017-03-01

The paper presents the problem of manufacturing process flexibility in view of a company's material and information flow stream management. The author of the article has described the functions of a production process control system and presented the characteristics of production capacity intensive and extensive reserves. The MRP II/ERP, MES and APS class IT tools supporting the process of production planning, organization and control have also been discussed.

SuperB Simulation Production System

NASA Astrophysics Data System (ADS)

Tomassetti, L.; Bianchi, F.; Ciaschini, V.; Corvo, M.; Del Prete, D.; Di Simone, A.; Donvito, G.; Fella, A.; Franchini, P.; Giacomini, F.; Gianoli, A.; Longo, S.; Luitz, S.; Luppi, E.; Manzali, M.; Pardi, S.; Paolini, A.; Perez, A.; Rama, M.; Russo, G.; Santeramo, B.; Stroili, R.

2012-12-01

The SuperB asymmetric e+e- collider and detector to be built at the newly founded Nicola Cabibbo Lab will provide a uniquely sensitive probe of New Physics in the flavor sector of the Standard Model. Studying minute effects in the heavy quark and heavy lepton sectors requires a data sample of 75 ab-1 and a peak luminosity of 1036 cm-2 s-1. The SuperB Computing group is working on developing a simulation production framework capable to satisfy the experiment needs. It provides access to distributed resources in order to support both the detector design definition and its performance evaluation studies. During last year the framework has evolved from the point of view of job workflow, Grid services interfaces and technologies adoption. A complete code refactoring and sub-component language porting now permits the framework to sustain distributed production involving resources from two continents and Grid Flavors. In this paper we will report a complete description of the production system status of the art, its evolution and its integration with Grid services; in particular, we will focus on the utilization of new Grid component features as in LB and WMS version 3. Results from the last official SuperB production cycle will be reported.

Systems Biology of Recombinant Protein Production in Bacillus megaterium

NASA Astrophysics Data System (ADS)

Biedendieck, Rebekka; Bunk, Boyke; Fürch, Tobias; Franco-Lara, Ezequiel; Jahn, Martina; Jahn, Dieter

Over the last two decades the Gram-positive bacterium Bacillus megaterium was systematically developed to a useful alternative protein production host. Multiple vector systems for high yield intra- and extracellular protein production were constructed. Strong inducible promoters were combined with DNA sequences for optimised ribosome binding sites, various leader peptides for protein export and N- as well as C-terminal affinity tags for affinity chromatographic purification of the desired protein. High cell density cultivation and recombinant protein production were successfully tested. For further system biology based control and optimisation of the production process the genomes of two B. megaterium strains were completely elucidated, DNA arrays designed, proteome, fluxome and metabolome analyses performed and all data integrated using the bioinformatics platform MEGABAC. Now, solid theoretical and experimental bases for primary modeling attempts of the production process are available.

Chemical production processes and systems

DOEpatents

Holladay, Johnathan E.; Muzatko, Danielle S.; White, James F.; Zacher, Alan H.

2014-06-17

Hydrogenolysis systems are provided that can include a reactor housing an Ru-comprising hydrogenolysis catalyst and wherein the contents of the reactor is maintained at a neutral or acidic pH. Reactant reservoirs within the system can include a polyhydric alcohol compound and a base, wherein a weight ratio of the base to the compound is less than 0.05. Systems also include the product reservoir comprising a hydrogenolyzed polyhydric alcohol compound and salts of organic acids, and wherein the moles of base are substantially equivalent to the moles of salts or organic acids. Processes are provided that can include an Ru-comprising catalyst within a mixture having a neutral or acidic pH. A weight ratio of the base to the compound can be between 0.01 and 0.05 during exposing.

Chemical production processes and systems

DOEpatents

Holladay, Johnathan E; Muzatko, Danielle S; White, James F; Zacher, Alan H

2015-04-21

Hydrogenolysis systems are provided that can include a reactor housing an Ru-comprising hydrogenolysis catalyst and wherein the contents of the reactor is maintained at a neutral or acidic pH. Reactant reservoirs within the system can include a polyhydric alcohol compound and a base, wherein a weight ratio of the base to the compound is less than 0.05. Systems also include the product reservoir comprising a hydrogenolyzed polyhydric alcohol compound and salts of organic acids, and wherein the moles of base are substantially equivalent to the moles of salts or organic acids. Processes are provided that can include an Ru-comprising catalyst within a mixture having a neutral or acidic pH. A weight ratio of the base to the compound can be between 0.01 and 0.05 during exposing.

On-Board Hydrogen Gas Production System For Stirling Engines

DOEpatents

Johansson, Lennart N.

2004-06-29

A hydrogen production system for use in connection with Stirling engines. The production system generates hydrogen working gas and periodically supplies it to the Stirling engine as its working fluid in instances where loss of such working fluid occurs through usage through operation of the associated Stirling engine. The hydrogen gas may be generated by various techniques including electrolysis and stored by various means including the use of a metal hydride absorbing material. By controlling the temperature of the absorbing material, the stored hydrogen gas may be provided to the Stirling engine as needed. A hydrogen production system for use in connection with Stirling engines. The production system generates hydrogen working gas and periodically supplies it to the Stirling engine as its working fluid in instances where loss of such working fluid occurs through usage through operation of the associated Stirling engine. The hydrogen gas may be generated by various techniques including electrolysis and stored by various means including the use of a metal hydride absorbing material. By controlling the temperature of the absorbing material, the stored hydrogen gas may be provided to the Stirling engine as needed.

Development of an in vitro bioassay for measuring susceptibility to macrocyclic lactone anthelmintics in Dirofilaria immitis.

PubMed

Evans, Christopher C; Moorhead, Andrew R; Storey, Bobby E; Wolstenholme, Adrian J; Kaplan, Ray M

2013-12-01

For more than 20 years, anthelmintics of the macrocyclic lactone (ML) drug class have been widely and effectively used as preventives against the canine heartworm, Dirofilaria immitis. However, in recent years an increased number of lack of efficacy (LOE) cases are being reported, in which dogs develop mature heartworm infections despite receiving monthly prophylactic doses of ML drugs. While this situation is raising concerns that heartworms may be developing resistance to MLs, compelling evidence for this is still lacking. Resolution of this dilemma requires validated biological or molecular diagnostic assays, but, unfortunately, no such tests currently exist. To address this need, we developed and optimized a larval migration inhibition assay (LMIA) for use with D. immitis third-stage larvae. The LMIA was used to measure the in vitro dose-response of two ML drugs (ivermectin and eprinomectin) on a known ML-susceptible laboratory strain of D. immitis. A nonlinear regression model was fit to the dose-response data, from which IC50 values were calculated; the mean IC50 and 95% confidence interval for IVM was 4.56 μM (1.26-16.4 μM), greater than that for EPR at 2.02 μM (1.68-2.42 μM), and this difference was significant (p = 0.0428). The R (2) value for EPR assays (0.90) was also greater than that for IVM treatment (0.71). The consistency and reproducibility of the dose-response data obtained with this assay suggests that it may be a useful technique for investigating the relative susceptibilities to ML drugs in other D. immitis populations.

Productivity and technical efficiency of suckler beef production systems: trends for the period 1990 to 2012.

PubMed

Veysset, P; Lherm, M; Roulenc, M; Troquier, C; Bébin, D

2015-12-01

Over the past 23 years (1990 to 2012), French beef cattle farms have expanded in size and increased labour productivity by over 60%, chiefly, though not exclusively, through capital intensification (labour-capital substitution) and simplifying herd feeding practices (more concentrates used). The technical efficiency of beef sector production systems, as measured by the ratio of the volume value (in constant euros) of farm output excluding aids to volume of intermediate consumption, has fallen by nearly 20% while income per worker has held stable thanks to subsidies and the labour productivity gains made. This aggregate technical efficiency of beef cattle systems is positively correlated to feed self-sufficiency, which is in turn negatively correlated to farm and herd size. While volume of farm output per hectare of agricultural area has not changed, forage feed self-sufficiency decreased by 6 percentage points. The continual increase in farm size and labour productivity has come at a cost of lower production-system efficiency - a loss of technical efficiency that 20 years of genetic, technical, technological and knowledge-driven progress has barely managed to offset.

Resonance production in high energy collisions from small to big systems

NASA Astrophysics Data System (ADS)

Werner, K.; Knospe, A. G.; Markert, C.; Guiot, B.; Karpenko, Iu.; Pierog, T.; Sophys, G.; Stefaniak, M.; Bleicher, M.; Steinheimer, J.

2018-02-01

The aim of this paper is to understand resonance production (and more generally particle production) for different collision systems, namely proton-proton (pp), proton-nucleus (pA), and nucleus-nucleus (AA) scattering at the LHC. We will investigate in particular particle yields and ratios versus multiplicity, using the same multiplicity definition for the three different systems, in order to analyse in a compact way the evolution of particle production with the system size and the origin of a very different system size dependence of the different particles.

Research-to-operations (R2O) for the Space Environmental Effects Fusion System (SEEFS) system-impact products

NASA Astrophysics Data System (ADS)

Quigley, Stephen

The Space Vehicles Directorate of the Air Force Research Laboratory (AFRL/RVBX) and the Space Environment Branch of the Space and Missile Systems Center (SMC SLG/WMLE) have combined efforts to design, develop, test, implement, and validate numerical and graphical products for Air Force Space Command's (AFSPC) Space Environmental Effects Fusion System (SEEFS). These products are generated to analyze, specify, and forecast the effects of the near-earth space environment on Department of Defense weapons, navigation, communications, and surveillance systems. Jointly developed projects that have been completed as prototypes and are undergoing development for real-time operations include a SEEFS architecture and database, five system-impact products, and a high-level decision aid product. This first round of SEEFS products includes the Solar Radio Burst Effects (SoRBE) on radar and satellite communications, Radar Auroral Clutter (RAC), Scintillation Effects on radar and satellite communications (RadScint and SatScint), and Satellite Surface and Deep Charge/Discharge (Char/D) products. This presentation will provide overviews of the current system impact products, along with plans and potentials for future products expected for the SEEFS program. The overviews will include information on applicable research-to-operations (R2O) issues, to include input data coverage and quality control, output confidence levels, modeling standards, and validation efforts.

Effect of production system (barn and free range) and slaughter age on some production traits of guinea fowl.

PubMed

Yamak, U S; Sarica, M; Boz, M A; Ucar, A

2018-01-01

A total of 200 guinea fowl was reared in either barn or free-range systems and slaughtered at 14, 16, or 18 wk of age in order to determine the effects of production system on live weight, feed consumption, and some carcass and slaughter traits. Production system had a significant effect on live weight until 14 wk of age. Live weights were similar between free-range and indoor production systems at 16 (1,150 g vs. 1,152 g) and 18 (1,196 g vs. 1,203 g) wk of age. Guinea fowl reared in a free-range system consumed more feed (7,693 g vs. 6,983 g), and guinea fowl reared in a barn had better feed conversion ratio (5.80 vs. 6.43) (P < 0.05). Production system, gender, and slaughter age did not affect the dressing percentage. Guinea fowl reared in a free-range system had significantly less abdominal fat (P < 0.05). © 2017 Poultry Science Association Inc.

Methods and systems for chemoautotrophic production of organic compounds

DOEpatents

Fischer, Curt R.; Che, Austin J.; Shetty, Reshma P.; Kelly, Jason R.

2013-01-08

The present disclosure identifies pathways, mechanisms, systems and methods to confer chemoautotrophic production of carbon-based products of interest, such as sugars, alcohols, chemicals, amino acids, polymers, fatty acids and their derivatives, hydrocarbons, isoprenoids, and intermediates thereof, in organisms such that these organisms efficiently convert inorganic carbon to organic carbon-based products of interest using inorganic energy, such as formate, and in particular the use of organisms for the commercial production of various carbon-based products of interest.

Methods and systems for chemoautotrophic production of organic compounds

DOEpatents

Fischer, Curt R.; Che, Austin J.; Shetty, Reshma P.; Kelly, Jason R.

2018-02-27

The present disclosure identifies pathways, mechanisms, systems and methods to confer chemoautotrophic production of carbon-based products of interest, such as sugars, alcohols, chemicals, amino acids, polymers, fatty acids and their derivatives, hydrocarbons, isoprenoids, and intermediates thereof, in organisms such that these organisms efficiently convert inorganic carbon to organic carbon-based products of interest using inorganic energy, such as formate, and in particular the use of organisms for the commercial production of various carbon-based products of interest.

Carbon footprint of dairy production systems

USDA-ARS?s Scientific Manuscript database

Greenhouse gas (GHG) emissions and their potential impact on global warming has become an important national and international concern. Dairy production systems along with all other types of animal agriculture are recognized as a source of GHG. Although little information exists on the net GHG emiss...

From prototype to production system: lessons learned from the evolution of the SignOut System at Mount Sinai Medical Center.

PubMed

Kushniruk, Andre; Karson, Tom; Moore, Carlton; Kannry, Joseph

2003-01-01

Approaches to the development of information systems in large health care institutions range from prototyping to conventional development of large scale production systems. This paper discusses the development of the SignOut System at Mount Sinai Medical Center, which was designed in 1997 to capture vital resident information. Local need quickly outstripped proposed delays for building a production system and a prototype system quickly became a production system. By the end of 2002 the New SignOut System was built to create an integrated application that was a true production system. In this paper we discuss the design and implementation issues in moving from a prototype to a production system. The production system had a number of advantages, including increased organizational visibility, integration into enterprise resource planning and full time staff for support. However, the prototype allowed for more rapid design and subsequent changes, less training, and equal to or superior help desk support. It is argued that healthcare IT systems may need characteristics of both prototype and production system development to rapidly meet the changing and different needs of healthcare user populations.

Quantification of phenolic acids and their methylates, glucuronides, sulfates and lactones metabolites in human plasma by LC-MS/MS after oral ingestion of soluble coffee.

PubMed

Marmet, Cynthia; Actis-Goretta, Lucas; Renouf, Mathieu; Giuffrida, Francesca

2014-01-01

Chlorogenic acids and derivatives like phenolic acids are potentially bioactive phenolics, which are commonly found in many foods. Once absorbed, chlorogenic and phenolic acids are highly metabolized by the intestine and the liver, producing glucuronidated and/or sulphated compounds. These metabolites were analyzed in human plasma using a validated liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method. After protein precipitation, phenolic acids and their metabolites were extracted by using ethanol and chromatographic separation was achieved by reversed-phase using an Acquity UPLC BEH C18 column combined with a gradient elution system using 1% acetic acid aqueous solution and 1% acetic acid with 100% acetonitrile. The method was able to quantify 56 different compounds including 24 phenolic acids, 4 lactones, 15 sulfates and 13 glucuronides metabolites between 5 and 1000nM in plasma for most of them, except for m-dihydrocoumaric acid, 5-ferulloylquinic-glucuronide, 4-methoxycinnamic acid, 3-phenylpropionic acid, 3-(4-methoxyphenyl)propionic acid (25 to 1000nM) and p-dihydrocoumaric acid (50-1000nM). Values of repeatability and intermediate reproducibility were below 15% of deviation in general, and maximum 20% for the lowest concentrations. The validated method was successfully applied to quantify phenolic acids and their metabolites in plasma obtained after oral ingestion of soluble coffee. In conclusion, the developed and validated method is proved to be very sensitive, accurate and precise for the quantification of these possible dietary phenols. Copyright © 2013 Elsevier B.V. All rights reserved.

Container system for enabling commercial production of cryopreserved cell therapy products.

PubMed

Woods, Erik J; Bagchi, Aniruddha; Goebel, W Scott; Vilivalam, Vinod D; Vilivalam, Vinod D

2010-07-01

The expansion of cellular therapeutics will require large-scale manufacturing processes to expand and package cell products, which may not be feasible with current blood-banking bag technology. This study investigated the potential for freezing, storing and shipping cell therapy products using novel pharmaceutical-grade Crystal Zenith((R)) (CZ) plastic vials. CZ vials (0.5, 5 and 30 ml volume) with several closure systems were filled with mesenchymal stem cells and stored at either -85 or -196 degrees C for 6 months. Vials were tested for their ability to maintain cell viability, proliferative and differentiation capacity, as well as durability and integrity utilizing a 1-m drop test. As controls, 2 ml polypropylene vials were investigated under the same conditions. Post-thaw viability utilizing a dye exclusion assay was over 95% in all samples. Stored cells exhibited rapid recovery 2 h post-thaw and cultures were approximately 70% confluent within 5-7 days, consistent with nonfrozen controls and indicative of functional recovery. Doubling times were consistent over all vials. The doubling rate for cells from CZ vials were 2.14 + or - 0.83 days (1 week), 1.84 + or - 0.68 days (1 month) and 1.79 + or - 0.71 days (6 months), which were not significantly different compared with frozen and fresh controls. Cells recovered from the vials exhibited trilineage differentiation consistent with controls. As part of vial integrity via drop testing, no evidence of external damage was found on vial surfaces or on closure systems. Furthermore, the filled vials stored for 6 months were tested for container closure integrity. Vials removed from freezer conditions were transported to the test laboratory on dry ice and tested using pharmaceutical packaging tests, including dye ingress and microbial challenge. The results of all stoppered vials indicated container closure integrity with no failures. Pharmaceutical-grade plastic CZ vials, which are commercially used to package

Inactivation of gacS Does Not Affect the Competitiveness of Pseudomonas chlororaphis in the Arabidopsis thaliana Rhizosphere

PubMed Central

Schmidt-Eisenlohr, Heike; Gast, Astrid; Baron, Christian

2003-01-01

Quorum-sensing-controlled processes are considered to be important for the competitiveness of microorganisms in the rhizosphere. They affect cell-cell communication, biofilm formation, and antibiotic production, and the GacS-GacA two-component system plays a role as a key regulator. In spite of the importance of this system for the regulation of various processes, strains with a Gac− phenotype are readily recovered from natural habitats. To analyze the influence of quorum sensing and the influence of the production of the antibiotic phenazine-1-carboxamide on rhizosphere colonization by Pseudomonas chlororaphis, a gnotobiotic system based on Arabidopsis thaliana seedlings in soil was investigated. Transposon insertion mutants of P. chlororaphis isolate SPR044 carrying insertions in different genes required for the production of N-acyl-homoserine lactones and phenazine-1-carboxamide were generated. Analysis of solitary rhizosphere colonization revealed that after prolonged growth, the population of the wild type was significantly larger than that of the homoserine lactone-negative gacS mutant and that of a phenazine-1-carboxamide-overproducing strain. In cocultivation experiments, however, the population size of the gacS mutant was similar to that of the wild type after extended growth in the rhizosphere. A detailed analysis of growth kinetics was performed to explain this phenomenon. After cells grown to the stationary phase were transferred to fresh medium, the gacS mutant had a reduced lag phase, and production of the stationary-phase-specific sigma factor RpoS was strongly reduced. This may provide a relative competitive advantage in cocultures with other bacteria, because it permits faster reinitiation of growth after a change to nutrient-rich conditions. In addition, delayed entry into the stationary phase may allow more efficient nutrient utilization. Thus, GacS-GacA-regulated processes are not absolutely required for efficient rhizosphere colonization in

Productivity and nutrient cycling in bioenergy cropping systems

NASA Astrophysics Data System (ADS)

Heggenstaller, Andrew Howard

One of the greatest obstacles confronting large-scale biomass production for energy applications is the development of cropping systems that balance the need for increased productive capacity with the maintenance of other critical ecosystem functions including nutrient cycling and retention. To address questions of productivity and nutrient dynamics in bioenergy cropping systems, we conducted two sets of field experiments during 2005-2007, investigating annual and perennial cropping systems designed to generate biomass energy feedstocks. In the first experiment we evaluated productivity and crop and soil nutrient dynamics in three prototypical bioenergy double-crop systems, and in a conventionally managed sole-crop corn system. Double-cropping systems included fall-seeded forage triticale (x Triticosecale Wittmack), succeeded by one of three summer-adapted crops: corn (Zea mays L.), sorghum-sudangrass [Sorghum bicolor (L.) Moench], or sunn hemp (Crotalaria juncea L.). Total dry matter production was greater for triticale/corn and triticale/sorghum-sudangrass compared to sole-crop corn. Functional growth analysis revealed that photosynthetic duration was more important than photosynthetic efficiency in determining biomass productivity of sole-crop corn and double-crop triticale/corn, and that greater yield in the tiritcale/corn system was the outcome of photosynthesis occurring over an extended duration. Increased growth duration in double-crop systems was also associated with reductions in potentially leachable soil nitrogen relative to sole-crop corn. However, nutrient removal in harvested biomass was also greater in the double-crop systems, indicating that over the long-term, double-cropping would mandate increased fertilizer inputs. In a second experiment we assessed the effects of N fertilization on biomass and nutrient partitioning between aboveground and belowground crop components, and on carbon storage by four perennial, warm-season grasses: big bluestem

Carbon footprint and ammonia emissions of California beef production systems

USDA-ARS?s Scientific Manuscript database

Beef production is a recognized source of greenhouse gas (GHG) and ammonia (NH3) emissions; however, little information exists on the net emissions from beef production systems. A partial life cycle assessment (LCA) was conducted using the Integrated Farm System Model (IFSM) to estimate GHG and NH3 ...

Increasing Cropping System Diversity Balances Productivity, Profitability and Environmental Health

PubMed Central

Davis, Adam S.; Hill, Jason D.; Chase, Craig A.; Johanns, Ann M.; Liebman, Matt

2012-01-01

Balancing productivity, profitability, and environmental health is a key challenge for agricultural sustainability. Most crop production systems in the United States are characterized by low species and management diversity, high use of fossil energy and agrichemicals, and large negative impacts on the environment. We hypothesized that cropping system diversification would promote ecosystem services that would supplement, and eventually displace, synthetic external inputs used to maintain crop productivity. To test this, we conducted a field study from 2003–2011 in Iowa that included three contrasting systems varying in length of crop sequence and inputs. We compared a conventionally managed 2-yr rotation (maize-soybean) that received fertilizers and herbicides at rates comparable to those used on nearby farms with two more diverse cropping systems: a 3-yr rotation (maize-soybean-small grain + red clover) and a 4-yr rotation (maize-soybean-small grain + alfalfa-alfalfa) managed with lower synthetic N fertilizer and herbicide inputs and periodic applications of cattle manure. Grain yields, mass of harvested products, and profit in the more diverse systems were similar to, or greater than, those in the conventional system, despite reductions of agrichemical inputs. Weeds were suppressed effectively in all systems, but freshwater toxicity of the more diverse systems was two orders of magnitude lower than in the conventional system. Results of our study indicate that more diverse cropping systems can use small amounts of synthetic agrichemical inputs as powerful tools with which to tune, rather than drive, agroecosystem performance, while meeting or exceeding the performance of less diverse systems. PMID:23071739

Increasing cropping system diversity balances productivity, profitability and environmental health.

PubMed

Davis, Adam S; Hill, Jason D; Chase, Craig A; Johanns, Ann M; Liebman, Matt

2012-01-01

Balancing productivity, profitability, and environmental health is a key challenge for agricultural sustainability. Most crop production systems in the United States are characterized by low species and management diversity, high use of fossil energy and agrichemicals, and large negative impacts on the environment. We hypothesized that cropping system diversification would promote ecosystem services that would supplement, and eventually displace, synthetic external inputs used to maintain crop productivity. To test this, we conducted a field study from 2003-2011 in Iowa that included three contrasting systems varying in length of crop sequence and inputs. We compared a conventionally managed 2-yr rotation (maize-soybean) that received fertilizers and herbicides at rates comparable to those used on nearby farms with two more diverse cropping systems: a 3-yr rotation (maize-soybean-small grain + red clover) and a 4-yr rotation (maize-soybean-small grain + alfalfa-alfalfa) managed with lower synthetic N fertilizer and herbicide inputs and periodic applications of cattle manure. Grain yields, mass of harvested products, and profit in the more diverse systems were similar to, or greater than, those in the conventional system, despite reductions of agrichemical inputs. Weeds were suppressed effectively in all systems, but freshwater toxicity of the more diverse systems was two orders of magnitude lower than in the conventional system. Results of our study indicate that more diverse cropping systems can use small amounts of synthetic agrichemical inputs as powerful tools with which to tune, rather than drive, agroecosystem performance, while meeting or exceeding the performance of less diverse systems.