High-temperature gas chromatography-mass spectrometry for skin surface lipids profiling.

PubMed

Michael-Jubeli, Rime; Bleton, Jean; Baillet-Guffroy, Arlette

2011-01-01

Skin surface lipids (SSLs) arising from both sebaceous glands and skin removal form a complex lipid mixture composed of free fatty acids and neutral lipids. High-temperature gas chromatography coupled with electron impact or chemical ionization mass spectrometry was used to achieve a simple analytical protocol, without prior separation in classes and without prior cleavage of lipid molecules, in order to obtain simultaneously i) a qualitative characterization of the individual SSLs and ii) a quantitative evaluation of lipid classes. The method was first optimized with SSLs collected from the forehead of a volunteer. More than 200 compounds were identified in the same run. These compounds have been classified in five lipid classes: free fatty acids, hydrocarbons, waxes, sterols, and glycerides. The advantage to this method was it provided structural information on intact compounds, which is new for cholesteryl esters and glycerides, and to obtain detailed fingerprints of the major SSLs. These fingerprints were used to compare the SSL compositions from different body areas. The squalene/cholesterol ratio was used to determine the balance between sebaceous secretion and skin removal. This method could be of general interest in fields where complex lipid mixtures are involved.

Molecular diversity management strategies for building and enhancement of diverse and focused lead discovery compound screening collections.

PubMed

Schuffenhauer, A; Popov, M; Schopfer, U; Acklin, P; Stanek, J; Jacoby, E

2004-12-01

This publication describes processes for the selection of chemical compounds for the building of a high-throughput screening (HTS) collection for drug discovery, using the currently implemented process in the Discovery Technologies Unit of the Novartis Institute for Biomedical Research, Basel Switzerland as reference. More generally, the currently existing compound acquisition models and practices are discussed. Our informatics, chemistry and biology-driven compound selection consists of two steps: 1) The individual compounds are filtered and grouped into three priority classes on the basis of their individual structural properties. Substructure filters are used to eliminate or penalize compounds based on unwanted structural properties. The similarity of the structures to reference ligands of the main proven druggable target families is computed, and drug-similar compounds are prioritized for the following diversity analysis. 2) The compounds are compared to the archive compounds and a diversity analysis is performed. This is done separately for the prioritized, regular and penalized compounds with increasingly stringent dissimilarity criterion. The process includes collecting vendor catalogues and monitoring the availability of samples together with the selection and purchase decision points. The development of a corporate vendor catalogue database is described. In addition to the selection methods on a per single molecule basis, selection criteria for scaffold and combinatorial chemistry projects in collaboration with compound vendors are discussed.

The identification of trends in outgassing technology

NASA Technical Reports Server (NTRS)

Colony, J. A.

1980-01-01

A large amount of chemical analysis data involving identification of outgassing products from spacecraft, experiment modules, and support equipment accumulated at the Goddard Space Flight Center over the past ten years were reduced to a computer compatible format and subjected to a variety of relevant program operations. From these data a list of the most troublesome outgassing species were compiled and several useful and interesting materials' correlations were developed. The frequency of occurrence totals show that in aerospace program, di(2-ethyl hexyl) phthalate (DEHP) is the most often found individual species in outgassing samples and that esters are the leading generic class of compounds. The effectiveness of this data bank was demonstrated by the good correlations between materials and their outgassing products for solar panel bakeouts and cable bakeouts. However, trends in frequency of occurrence of many compounds were demonstrated where no correlation could be established. In the case of the class of compounds called aliphatic hydrocarbons, it is shown that the number of instances of significant outgassing due to these materials is increasing.

Polyfluoroalkyl compounds in the aquatic environment: a review of their occurrence and fate.

PubMed

Ahrens, Lutz

2011-01-01

The occurrence and fate of polyfluoroalkyl compounds (PFCs) in the aquatic environment has been recognized as one of the emerging issues in environmental chemistry. PFCs comprise a diverse group of chemicals that are widely used as processing additives during fluoropolymer production and as surfactants in consumer applications for over 50 years. PFCs are known to be persistent, bioaccumulative and have possible adverse effects on humans and wildlife. As a result, perfluorooctane sulfonate (PFOS) has been added to the persistent organic pollutants (POPs) list of the Stockholm Convention in May 2009. However, their homologues, neutral precursor compounds and new PFCs classes continue to be produced. In general, several PFCs from different classes have been detected ubiquitously in the aqueous environment while the concentrations usually range between pg and ng per litre for individual compounds. Sources of PFCs into the aqueous environment are both point sources (e.g., wastewater treatment plant effluents) and nonpoint sources (e.g., surface runoff). The detected congener composition in environmental samples depends on their physicochemical characteristics and may provide information to their sources and transport pathways. However, the dominant transport pathways of individual PFCs to remote regions have not been conclusively characterised to date. The objective of this article is to give an overview on existing knowledge of the occurrence, fate and processes of PFCs in the aquatic environment. Finally, this article identifies knowledge gaps, presents conclusions and recommendations for future work.

Molecular and Enantiomeric Analysis of Organic Compounds in Carbonaceous Meteorites

NASA Technical Reports Server (NTRS)

Cooper, George

2003-01-01

Carbonaceous meteorites are relatively enriched in carbon. Much of this carbon is in the form of soluble organic compounds. The Murchison and Murray meteorites are the best-characterized carbonaceous meteorites with respect to organic chemistry. Their content of organic compounds has led to an initial understanding of early solar system organic chemistry as well as what compounds may have played a role in the origin of life (Cronin and Chang, 1993). Reported compounds include: amino acids, amides, carboxylic acids, sulfonic acids, and polyols. This talk will focus on the molecular and enantiomeric analysis of individual meteoritic compounds: polyol acids; and a newly identified class of meteorite compounds, keto acids, i.e., acetoacetic acid, levulinic acid, etc. Keto acids (including pyruvic) are critically important in all contemporary organisms. They are key intermediates in metabolism and processes such as the citric acid cycle. Using gas chromatography-mass spectrometry we identified individual meteoritic keto acids after derivatization to one or more of the following forms: isopropyl ester (ISP), trimethyIsiIy1 (TMS), tert-butyldimethylsilyl (BDMS). Ongoing analyses will determine if, in addition to certain amino acids from Murchison (Cronin and Pizzarello, 1997), other potentially important prebiotic compounds also contain enantiomeric excesses, i.e., excesses that could have contributed to the current homochirality of life.

Anaerobic Degradation of Chloroaromatic Compounds in Aquatic Sediments under a Variety of Enrichment Conditions †

PubMed Central

Genthner, Barbara R. Sharak; Price, W. Allen; Pritchard, P. H.

1989-01-01

Anaerobic degradation of monochlorophenols and monochlorobenzoates in a variety of aquatic sediments was compared under four enrichment conditions. A broader range of compounds was degraded in enrichments inoculated with sediment exposed to industrial effluents. Degradation of chloroaromatic compounds was observed most often in methanogenic enrichments and in enrichments amended with 1 mM bromoethane sulfonic acid. Degradation was observed least often in enrichments with added nitrate or sulfate. The presence of 10 mM bromoethane sulfonic acid prevented or inhibited degradation of most compounds tested. Primary enrichments in which KNO3 was periodically replenished to maintain enrichment characteristics degraded chlorobenzoates, but not chlorophenols. In contrast, primary enrichments in which Na2SO4 was periodically replenished failed to degrade any chloroaromatic compounds. Upon transfer to fresh medium, none of the sulfate enrichments required the presence of Na2SO4 for degradation, while only two nitrate enrichments required the presence of KNO3 for degradation. As a class of compounds, chlorophenols were degraded more readily than chlorobenzoates. However, as individual compounds 3-chlorobenzoate, 2-chlorophenol, and 3-chlorophenol degradation was observed most often and with an equal frequency. Within the chlorophenol class, the relative order of degradability was ortho > meta > para, while that of chlorobenzoates was meta > ortho > para, In laboratory transfers, 2-chlorobenzoate, 3-chlorobenzoate, and 2-chlorophenol degradation was most easily maintained, while degradation of para-chlorinated compounds was very difficult to maintain. PMID:16347940

Effect of solvent on the extraction of phenolic compounds and antioxidant capacity of hazelnut kernel.

PubMed

Fanali, Chiara; Tripodo, Giusy; Russo, Marina; Della Posta, Susanna; Pasqualetti, Valentina; De Gara, Laura

2018-03-22

Hazelnut kernel phenolic compounds were recovered applying two different extraction approaches, namely ultrasound-assisted solid/liquid extraction (UA-SLE) and solid-phase extraction (SPE). Different solvents were tested evaluating total phenolic compounds and total flavonoids contents together to antioxidant activity. The optimum extraction conditions, in terms of the highest value of total phenolic compounds extracted together to other parameters like simplicity and cost were selected for method validation and individual phenolic compounds analysis. The UA-SLE protocol performed using 0.1 g of defatted sample and 15 mL of extraction solvent (1 mL methanol/1 mL water/8 mL methanol 0.1% formic acid/5 mL acetonitrile) was selected. The analysis of hazelnut kernel individual phenolic compounds was obtained by HPLC coupled with DAD and MS detections. Quantitative analysis was performed using a mixture of six phenolic compounds belonging to phenolic classes' representative of hazelnut. Then, the method was fully validated and the resulting RSD% values for retention time repeatability were below 1%. A good linearity was obtained giving R 2 no lower than 0.997.The accuracy of the extraction method was also assessed. Finally, the method was applied to the analysis of phenolic compounds in three different hazelnut kernel varieties observing a similar qualitative profile with differences in the quantity of detected compounds. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enantiomeric and Isotopic Analysis of Organic Compounds in Carbonaceous Meteorites

NASA Technical Reports Server (NTRS)

Cooper, George

2004-01-01

Carbonaceous meteorites are relatively enriched in soluble organic compounds. The Murchison and Murray meteorites contain numerous compounds of interest in the study of early solar system organic chemistry and organic compounds of potential importance for the origin of life. These include: amino acids, amides, carboxylic acids, and polyols. This talk will focus on the enantiomeric and isotopic analysis of individual meteoritic compounds - primarily polyol acids. The analyses will determine if, in addition to certain amino acids from Murchison, another potentially important class of prebiotic compounds also contains enantiomeric excesses, i.e., excesses that could have contributed to the current homochirality of life. Preliminary enantiomeric and isotopic (C- 13) measurements of Murchison glyceric acid show that it is indeed extraterrestrial. C-13 and D isotope analysis of meteoritic sugar alcohols (glycerol, threitol, ribitol, etc.) has shown that they are also indigenous to the meteorite.

Size-resolved ultrafine particle composition analysis 1. Atlanta

NASA Astrophysics Data System (ADS)

Rhoads, K. P.; Phares, D. J.; Wexler, A. S.; Johnston, M. V.

2003-04-01

During August 1999 as part of the Southern Oxidants Study Supersite Experiment, our group collected size-resolved measurements of the chemical composition of single ambient aerosol particles with a unique real-time laser desorption/ionization mass spectrometry technique. The rapid single-particle mass spectrometry instrument is capable of analyzing "ultrafine" particles with aerodynamic diameters ranging from 0.01 to 1.5 μm. Under the heaviest loading observed in Atlanta, particles were analyzed at a rate of roughly one per second in sizes ranging from 0.1 to 0.2 μm. Nearly 16,000 individual spectra were recorded over the course of the month during both daytime and nighttime sampling periods. Evaluation of the data indicates that the composition of the ultrafine (less than 100 nm) particles is dominated by carbon-containing compounds. Larger particles show varied compositions but typically appeared to have organic carbon characteristics mixed with an inorganic component (e.g., crustal materials, metals, etc.). During the experiment, 70 composition classes were identified. In this paper we report the average spectra and correlations with various meteorological parameters for all major compound classes and a number of minor ones. The major composition classes are identified from the primary peaks in their spectra as organic carbon (about 74% of the particles), potassium (8%), iron (3%), calcium (2%), nitrate (2%), elemental carbon (1.5%), and sodium (1%). Many of these compound classes appeared in repeatable size ranges and quadrants of the wind rose, indicating emission from specific sources.

Indoor air-assessment: Indoor concentrations of environmental carcinogens

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

Gold, K.W.; Naugle, D.F.; Berry, M.A.

1991-01-01

In the report, indoor concentration data are presented for the following general categories of air pollutants: radon-222, environmental tobacco smoke (ETS), asbestos, gas phase organic compounds, formaldehyde, polycyclic aromatic hydrocarbons (PAH), pesticides, and inorganic compounds. These pollutants are either known or suspect carcinogens (i.e., radon-222, asbestos) or more complex mixtures or classes of compounds which contain known or suspect carcinogens. Concentration data for individual carcinogenic compounds in complex mixtures are usually far from complete. The data presented for complex mixtures often include compounds which are not carcinogenic or for which data are insufficient to evaluate carcinogenicity. Their inclusion is justified,more » however, by the possibility that further work may show them to be carcinogens, cocarcinogens, initiators or promotors, or that they may be employed as markers (e.g., nicotine, acrolein) for the estimation of exposure to complex mixtures.« less

Characterization of exhaust emissions from diesel-powered passenger cars with particular reference to unregulated components

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

Lies, K.H.; Postulka, A.; Gring, H.

Besides regulated components VW's research program in the field of characterization of diesel emissions comprises a detailed analysis of the particulates and a comprehensive study of a number of unregulated gaseous compounds. The following chemical compounds and classes of compounds are measured: particulates, traces of metals, major elements, sulfates, sulfur dioxide, hydrogen sulfide, hydrogen cyanide, aldehydes, ammonia, phenols, individual hydrocarbons, and odor (DOAS). The test fleet of this investigation included a number of VW and Audi cars equipped with 4-, and 5-cylinder diesel engines (naturally aspirated and turbocharged). All measurements were performed on a chassis dynamometer in accordance with themore » specification of the known US-test-procedures: Federal Test Procedure, Sulfate Emission Test, Fuel Economy Test. For sampling , in principle, the dilution tunnel technique was used combined with an automatically working collection system. This micro-processor controlled system involves 13 individual sample lines, 8 for gaseous and 5 for particulate components.« less

Synthesis and in vitro activity of dicationic bis-benzimidazoles as a new class of anti-MRSA and anti-VRE agents.

PubMed

Hu, Laixing; Kully, Maureen L; Boykin, David W; Abood, Norman

2009-03-01

A new class of novel bis-benzimidazole diamidine compounds have been synthesized and evaluated for in vitro antibacterial activities, including drug-resistant bacterial strains. Anti-MRSA and anti-VRE activities of the most potent compound 1 were more active than Vancomycin. The mechanism of action for this class of compounds appears to be different from existing antibiotics. Bis-benzimidazole diamidine compounds have potential for further investigation as a new class of potent anti-MRSA and anti-VRE agents.

Individual organic compounds in water extracts from podzolic soils of the Komi Republic

NASA Astrophysics Data System (ADS)

Shamrikova, E. V.; Punegov, V. V.; Gruzdev, I. V.; Vanchikova, E. V.; Vetoshkina, A. A.

2012-10-01

The contents of organic compounds in water extracts from organic horizons of loamy soils with different water contents from the medium taiga zone of the Komi Republic were determined by gas-liquid chromatography and chromatography-mass spectrometry. The mass concentration of organic carbon in the extracts was in the range of 290-330 mg/dm3; the mass fraction of the carbon from the identified compounds was 0.5-1.9%. Hydrocarbons made up about 60% of the total identified compounds; acids and their derivatives composed less than 40%. Most of the acids (40-70%) were aliphatic hydroxy acids. The tendencies in the formation of different classes of organic compounds were revealed depending on the degree of the soil hydromorphism. The acid properties of the water-soluble compounds were studied by pK spectroscopy. Five groups of compounds containing acid groups with similar pKa values were revealed. The compounds containing groups with pKa < 4.0 were predominant. The increase in the surface wetting favored the formation of compounds with pKa 3.2-4.0 and 7.4-8.4.

Feasibility of Active Machine Learning for Multiclass Compound Classification.

PubMed

Lang, Tobias; Flachsenberg, Florian; von Luxburg, Ulrike; Rarey, Matthias

2016-01-25

A common task in the hit-to-lead process is classifying sets of compounds into multiple, usually structural classes, which build the groundwork for subsequent SAR studies. Machine learning techniques can be used to automate this process by learning classification models from training compounds of each class. Gathering class information for compounds can be cost-intensive as the required data needs to be provided by human experts or experiments. This paper studies whether active machine learning can be used to reduce the required number of training compounds. Active learning is a machine learning method which processes class label data in an iterative fashion. It has gained much attention in a broad range of application areas. In this paper, an active learning method for multiclass compound classification is proposed. This method selects informative training compounds so as to optimally support the learning progress. The combination with human feedback leads to a semiautomated interactive multiclass classification procedure. This method was investigated empirically on 15 compound classification tasks containing 86-2870 compounds in 3-38 classes. The empirical results show that active learning can solve these classification tasks using 10-80% of the data which would be necessary for standard learning techniques.

Discovery of novel inhibitors of the NorA multidrug transporter of Staphylococcus aureus.

PubMed

Brincat, Jean Pierre; Carosati, Emanuele; Sabatini, Stefano; Manfroni, Giuseppe; Fravolini, Arnaldo; Raygada, Jose L; Patel, Diixa; Kaatz, Glenn W; Cruciani, Gabriele

2011-01-13

Four novel inhibitors of the NorA efflux pump of Staphylococcus aureus, discovered through a virtual screening process, are reported. The four compounds belong to different chemical classes and were tested for their in vitro ability to block the efflux of a well-known NorA substrate, as well as for their ability to potentiate the effect of ciprofloxacin (CPX) on several strains of S. aureus, including a NorA overexpressing strain. Additionally, the MIC values of each of the compounds individually are reported. A structure-activity relationship study was also performed on these novel chemotypes, revealing three new compounds that are also potent NorA inhibitors. The virtual screening procedure employed FLAP, a new methodology based on GRID force field descriptors.

Embryotoxic and teratogenic effects of petroleum hydrocarbons in mallards (Anas platyrhynchos)

USGS Publications Warehouse

Hoffman, D.J.

1979-01-01

Egg surface applications of microliter quantities of crude and refined oils of high aromatic content are embryotoxic to mallards (Anas platyrhynchos) and other avian species; applications of aliphatic hydrocarbons have virtually no effect. Mallard eggs at 72 h of development were exposed to a mixture of aromatic hydrocarbons or to aromatic compounds representative to those present in crude oil to assess their toxicity. The class composition of the mixture was similar to that of South Louisiana crude oil, an American Petroleum Institute reference oil. Application of 20 microliter of the mixture reduced embryonic survival by nearly 70%. The temporal pattern of embryonic death was similar to that after exposure to South Louisiana crude oil. Embryonic growth was stunted, as reflected by weight, crown-rump length, and bill length, and there was a significant increase in the incidence of abnormal survivors. When individual classes of aromatic hydrocarbons were tested, tetracyclics caused some embryonic death at the concentrations in the mixture. When classes were tested in all possible combinations of two, no combination appeared to be as toxic as the entire mixture. Addition of the tetracyclic compound chrysene to the aromatic mixture considerably enhanced embryotoxicity, but could not completely account for the toxicity of the crude oil. The presence of additional unidentified polycyclic aromatic hydrocarbons as well as methylated derivatives of polycyclic aromatic compounds such as chrysene may further account for the embryotoxicity of the crude oil.

Retinoic Acid and Affective Disorders: The Evidence for an Association

PubMed Central

Bremner, J Douglas; Shearer, Kirsty; McCaffery, Peter

2011-01-01

Objective Isotretinoin (13-cis-retinoic acid, or 13-cis-RA) (Accutane), approved by the FDA for the treatment of acne, carries a black box warning related to the risk of depression, suicide, and psychosis. Retinoic acid (RA), the active form of vitamin A, regulates gene expression in the brain, and isotretinoin is its 13-cis isomer. Retinoids represent a group of compounds derived from vitamin A that perform a large variety of functions in many systems, in particular the CNS, and abnormal retinoid levels can have neurological effects. Although infrequent, proper recognition and treatment of psychiatric side effects in acne patients is critical given the risk of death and disability. This paper reviews the evidence for a relationship between isotretinoin, depression and suicidality. Data Sources Evidence examined includes: 1) case reports; 2) temporal association between onset of depression and exposure to the drug; 3) challenge-rechallenge cases; 4) class effect (other compounds in the same class, like vitamin A, having similar neuropsychiatric effects); 5) dose response; and 6) biologically plausible mechanisms. Study Selection All papers in the literature related to isotretinoin, depression and suicide were reviewed, as well as papers related to class effect, dose response, and biological plausibility. Data Extraction Information from individual articles in the literature was extracted. Data Synthesis The literature reviewed is consistent with an association between isotretinoin administration, depression and suicide in some individuals. Conclusions The relationship between isotretinoin and depression may have implications for a greater understanding of the neurobiology of affective disorders. PMID:21903028

Identification and Structure-Function Analysis of Subfamily Selective G Protein-Coupled Receptor Kinase Inhibitors

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

Homan, Kristoff T.; Larimore, Kelly M.; Elkins, Jonathan M.

2015-02-13

Selective inhibitors of individual subfamilies of G protein-coupled receptor kinases (GRKs) would serve as useful chemical probes as well as leads for therapeutic applications ranging from heart failure to Parkinson’s disease. To identify such inhibitors, differential scanning fluorimetry was used to screen a collection of known protein kinase inhibitors that could increase the melting points of the two most ubiquitously expressed GRKs: GRK2 and GRK5. Enzymatic assays on 14 of the most stabilizing hits revealed that three exhibit nanomolar potency of inhibition for individual GRKs, some of which exhibiting orders of magnitude selectivity. Most of the identified compounds can bemore » clustered into two chemical classes: indazole/dihydropyrimidine-containing compounds that are selective for GRK2 and pyrrolopyrimidine-containing compounds that potently inhibit GRK1 and GRK5 but with more modest selectivity. The two most potent inhibitors representing each class, GSK180736A and GSK2163632A, were cocrystallized with GRK2 and GRK1, and their atomic structures were determined to 2.6 and 1.85 Å spacings, respectively. GSK180736A, developed as a Rho-associated, coiled-coil-containing protein kinase inhibitor, binds to GRK2 in a manner analogous to that of paroxetine, whereas GSK2163632A, developed as an insulin-like growth factor 1 receptor inhibitor, occupies a novel region of the GRK active site cleft that could likely be exploited to achieve more selectivity. However, neither compound inhibits GRKs more potently than their initial targets. This data provides the foundation for future efforts to rationally design even more potent and selective GRK inhibitors.« less

Medicinal Uses, Phytochemistry, and Pharmacology of Origanum onites (L.): A Review.

PubMed

Tepe, Bektas; Cakir, Ahmet; Sihoglu Tepe, Arzuhan

2016-05-01

Origanum onites L., known as Turkish oregano, has great traditional, medicinal, preservative, and commercial importance. It is used for the treatment of several kinds of ailments, such as gastrointestinal disorders, diabetes, high cholesterol, leukemia, bronchitis, etc. In this review, traditional use, phytochemistry, and pharmacology of O. onites reported between 1988 and 2014 were discussed. This review was prepared based on literature survey on scientific journals and books from libraries and electronic sources, such as Web of Science, PubMed, Scopus, Google Scholar, etc. All databases were searched up to June 2014. Several different classes of terpenoids, triterpene acids, phenolic acids, hydroquinones, flavonoids, hydrocarbons, sterols, pigments, fatty acids, tocopherols, and inorganic compounds were detected mainly in the aerial parts of this plant. Pharmacological studies revealed that extracts obtained from several solvents and individual compounds exhibited antimicrobial, antiviral, antioxidant, insecticidal, anticancer, hepatoprotective, genotoxic, antidiabetic, cholinesterase inhibitory, anti-inflammatory, analgesic activities, etc. O. onites, in general, exhibited remarkable activity potential in almost all test systems. The results of toxicity studies indicated that O. onites did not show any significant toxicity and mutagenicity on Drosophila and Salmonella. Toxicity of the extracts/essential oils and also individual compounds should be evaluated on mammalian cells to ensure their safety. The bioactivity of individual compounds aside from terpenoids should also be assessed in detail. Additionally, mode of action for the bioactive compounds should be evaluated to understand the complex pharmacological effects of these phytochemicals. © 2016 Verlag Helvetica Chimica Acta AG, Zürich.

Organic chemistry of Murchison meteorite: Carbon isotopic fractionation

NASA Technical Reports Server (NTRS)

Yuen, G. U.; Blair, N. E.; Desmarais, D. J.; Cronin, J. R.; Chang, S.

1986-01-01

The carbon isotopic composition of individual organic compounds of meteoritic origin remains unknown, as most reported carbon isotopic ratios are for bulk carbon or solvent extractable fractions. The researchers managed to determine the carbon isotopic ratios for individual hydrocarbons and monocarboxylic acids isolated from a Murchison sample by a freeze-thaw-ultrasonication technique. The abundances of monocarboxylic acids and saturated hydrocarbons decreased with increasing carbon number and the acids are more abundant than the hydrocarbon with the same carbon number. For both classes of compounds, the C-13 to C-12 ratios decreased with increasing carbon number in a roughly parallel manner, and each carboxylic acid exhibits a higher isotopic number than the hydrocarbon containing the same number of carbon atoms. These trends are consistent with a kinetically controlled synthesis of higher homologues for lower ones.

Changes in heartwood chemistry of dead yellow-cedar trees that remain standing for 80 years or more in southeast Alaska.

Treesearch

Rick G. Kelsey; Paul E. Hennon; Manuela Huso; Joseph G. Karchesy

2005-01-01

We measured the concentrations of extractable bioactive compounds in heartwood of live yellow-cedar (Chamaecyparis noothtensis) trees and five classes of standing snags (1-5, averaging 4, 14,26,5 1, and 81 years since-death, respectively) to determine how the concentrations changed in the slowly deteriorating snags. Three individuals from each of...

Variation in the expression of ergot alkaloids between individual tillers of perennial ryegrass

NASA Astrophysics Data System (ADS)

Mace, Wade; Lunn, Kristy; Lloyd-West, Catherine

2014-11-01

Epichloë fungal endophytes of cool season grasses are well known to produce a range of alkaloids of benefit to the host. Some of these compounds are advantageous to agriculture due to qualities that promote pasture persistence (e.g. the loline class of alkaloids confer insect protection) while others are detrimental to the wellbeing of grazing livestock. The ergot alkaloids (e.g. ergovaline), produced in ryegrass and tall fescue associations, causes poor animal health in farming regions in many countries around the world and further study is required to improve our knowledge on this class of compounds. Here we present the application of a quantitative LC-MS/MS (liquid chromatography coupled to mass spectrometry) method measuring eight ergot alkaloids (chanoclavine, agroclavine, elymoclavine, lysergol, lysergic acid, ergine, lysergyl alanine, ergovaline) produced by endophyte infected grasses, to monitor levels in individual tillers from multiple plants of a single cultivar of perennial ryegrass (Lolium perenne cv. ‘Grasslands Samson’) infected with a common toxic endophyte strain (Epichloë festucae var. lolii). Monitoring the expression in individual tillers allows an estimation of the variability within a plant (between tillers) as well as between plants. The study showed that there is significant variation in the concentration of the ergot alkaloids between tillers of a single plant, at or exceeding the level of variation observed between individual plants of a population. This result emphasizes the fundamental importance of robust experimental design and sampling procedures when alkaloid expression assessment is required and these need to be rigorously tailored to the hypothesis being tested.

Natural product-inspired cascade synthesis yields modulators of centrosome integrity.

PubMed

Dückert, Heiko; Pries, Verena; Khedkar, Vivek; Menninger, Sascha; Bruss, Hanna; Bird, Alexander W; Maliga, Zoltan; Brockmeyer, Andreas; Janning, Petra; Hyman, Anthony; Grimme, Stefan; Schürmann, Markus; Preut, Hans; Hübel, Katja; Ziegler, Slava; Kumar, Kamal; Waldmann, Herbert

2011-12-25

In biology-oriented synthesis, the scaffolds of biologically relevant compound classes inspire the synthesis of focused compound collections enriched in bioactivity. This criterion is, in particular, met by the scaffolds of natural products selected in evolution. The synthesis of natural product-inspired compound collections calls for efficient reaction sequences that preferably combine multiple individual transformations in one operation. Here we report the development of a one-pot, twelve-step cascade reaction sequence that includes nine different reactions and two opposing kinds of organocatalysis. The cascade sequence proceeds within 10-30 min and transforms readily available substrates into complex indoloquinolizines that resemble the core tetracyclic scaffold of numerous polycyclic indole alkaloids. Biological investigation of a corresponding focused compound collection revealed modulators of centrosome integrity, termed centrocountins, which caused fragmented and supernumerary centrosomes, chromosome congression defects, multipolar mitotic spindles, acentrosomal spindle poles and multipolar cell division by targeting the centrosome-associated proteins nucleophosmin and Crm1.

Characterization of the antibiotic compound no. 70 produced by Streptomyces sp. IMV-70.

PubMed

Trenozhnikova, Lyudmila P; Khasenova, Almagul K; Balgimbaeva, Assya S; Fedorova, Galina B; Katrukha, Genrikh S; Tokareva, Nina L; Kwa, Boo H; Azizan, Azliyati

2012-01-01

We describe the actinomycete strain IMV-70 isolated from the soils of Kazakhstan, which produces potent antibiotics with high levels of antibacterial activity. After the research of its morphological, chemotaxonomic, and cultural characteristics, the strain with potential to be developed further as a novel class of antibiotics with chemotherapeutics potential was identified as Streptomyces sp. IMV-70. In the process of fermentation, the strain Streptomyces spp. IMV-70 produces the antibiotic no. 70, which was isolated from the culture broth by extraction with organic solvents. Antibiotic compound no. 70 was purified and separated into individual components by HPLC, TLC, and column chromatography methods. The main component of the compound is the antibiotic 70-A, which was found to be identical to the peptolide etamycin A. Two other antibiotics 70-B and 70-C have never been described and therefore are new antibiotics. The physical-chemical and biological characteristics of these preparations were described and further researched. Determination of the optimal growth conditions to cultivate actinomycete-producer strain IMV-70 and development of methods to isolate, purify, and accumulate preparations of the new antibiotic no. 70 enable us to research further the potential of this new class of antibiotics.

Characterization of the Antibiotic Compound No. 70 Produced by Streptomyces sp. IMV-70

PubMed Central

Trenozhnikova, Lyudmila P.; Khasenova, Almagul K.; Balgimbaeva, Assya S.; Fedorova, Galina B.; Katrukha, Genrikh S.; Tokareva, Nina L.; Kwa, Boo H.; Azizan, Azliyati

2012-01-01

We describe the actinomycete strain IMV-70 isolated from the soils of Kazakhstan, which produces potent antibiotics with high levels of antibacterial activity. After the research of its morphological, chemotaxonomic, and cultural characteristics, the strain with potential to be developed further as a novel class of antibiotics with chemotherapeutics potential was identified as Streptomyces sp. IMV-70. In the process of fermentation, the strain Streptomyces spp. IMV-70 produces the antibiotic no. 70, which was isolated from the culture broth by extraction with organic solvents. Antibiotic compound no. 70 was purified and separated into individual components by HPLC, TLC, and column chromatography methods. The main component of the compound is the antibiotic 70-A, which was found to be identical to the peptolide etamycin A. Two other antibiotics 70-B and 70-C have never been described and therefore are new antibiotics. The physical-chemical and biological characteristics of these preparations were described and further researched. Determination of the optimal growth conditions to cultivate actinomycete-producer strain IMV-70 and development of methods to isolate, purify, and accumulate preparations of the new antibiotic no. 70 enable us to research further the potential of this new class of antibiotics. PMID:22536145

Imidazopyridazine Inhibitors of Plasmodium falciparum Calcium-Dependent Protein Kinase 1 Also Target Cyclic GMP-Dependent Protein Kinase and Heat Shock Protein 90 To Kill the Parasite at Different Stages of Intracellular Development

PubMed Central

Moon, Robert W.; Whalley, David; Bowyer, Paul W.; Wallace, Claire; Rochani, Ankit; Nageshan, Rishi K.; Howell, Steven A.; Grainger, Munira; Jones, Hayley M.; Ansell, Keith H.; Chapman, Timothy M.; Taylor, Debra L.; Osborne, Simon A.; Baker, David A.; Tatu, Utpal

2015-01-01

Imidazopyridazine compounds are potent, ATP-competitive inhibitors of calcium-dependent protein kinase 1 (CDPK1) and of Plasmodium falciparum parasite growth in vitro. Here, we show that these compounds can be divided into two classes depending on the nature of the aromatic linker between the core and the R2 substituent group. Class 1 compounds have a pyrimidine linker and inhibit parasite growth at late schizogony, whereas class 2 compounds have a nonpyrimidine linker and inhibit growth in the trophozoite stage, indicating different modes of action for the two classes. The compounds also inhibited cyclic GMP (cGMP)-dependent protein kinase (PKG), and their potency against this enzyme was greatly reduced by substitution of the enzyme's gatekeeper residue at the ATP binding site. The effectiveness of the class 1 compounds against a parasite line expressing the modified PKG was also substantially reduced, suggesting that these compounds kill the parasite primarily through inhibition of PKG rather than CDPK1. HSP90 was identified as a binding partner of class 2 compounds, and a representative compound bound to the ATP binding site in the N-terminal domain of HSP90. Reducing the size of the gatekeeper residue of CDPK1 enabled inhibition of the enzyme by bumped kinase inhibitors; however, a parasite line expressing the modified enzyme showed no change in sensitivity to these compounds. Taken together, these findings suggest that CDPK1 may not be a suitable target for further inhibitor development and that the primary mechanism through which the imidazopyridazines kill parasites is by inhibition of PKG or HSP90. PMID:26711771

Imidazopyridazine Inhibitors of Plasmodium falciparum Calcium-Dependent Protein Kinase 1 Also Target Cyclic GMP-Dependent Protein Kinase and Heat Shock Protein 90 To Kill the Parasite at Different Stages of Intracellular Development.

PubMed

Green, Judith L; Moon, Robert W; Whalley, David; Bowyer, Paul W; Wallace, Claire; Rochani, Ankit; Nageshan, Rishi K; Howell, Steven A; Grainger, Munira; Jones, Hayley M; Ansell, Keith H; Chapman, Timothy M; Taylor, Debra L; Osborne, Simon A; Baker, David A; Tatu, Utpal; Holder, Anthony A

2015-12-28

Imidazopyridazine compounds are potent, ATP-competitive inhibitors of calcium-dependent protein kinase 1 (CDPK1) and of Plasmodium falciparum parasite growth in vitro. Here, we show that these compounds can be divided into two classes depending on the nature of the aromatic linker between the core and the R2 substituent group. Class 1 compounds have a pyrimidine linker and inhibit parasite growth at late schizogony, whereas class 2 compounds have a nonpyrimidine linker and inhibit growth in the trophozoite stage, indicating different modes of action for the two classes. The compounds also inhibited cyclic GMP (cGMP)-dependent protein kinase (PKG), and their potency against this enzyme was greatly reduced by substitution of the enzyme's gatekeeper residue at the ATP binding site. The effectiveness of the class 1 compounds against a parasite line expressing the modified PKG was also substantially reduced, suggesting that these compounds kill the parasite primarily through inhibition of PKG rather than CDPK1. HSP90 was identified as a binding partner of class 2 compounds, and a representative compound bound to the ATP binding site in the N-terminal domain of HSP90. Reducing the size of the gatekeeper residue of CDPK1 enabled inhibition of the enzyme by bumped kinase inhibitors; however, a parasite line expressing the modified enzyme showed no change in sensitivity to these compounds. Taken together, these findings suggest that CDPK1 may not be a suitable target for further inhibitor development and that the primary mechanism through which the imidazopyridazines kill parasites is by inhibition of PKG or HSP90. Copyright © 2016 Green et al.

Isotopic Measurements of Organic Sulfonates From The Murchison Meteorite

NASA Technical Reports Server (NTRS)

Cooper, G. W.; Chang, S.; DeVincenzi, Donald L. (Technical Monitor)

1995-01-01

Organic sulfonates and phosphonates have been extracted from the Murchison meteorite for stable isotope measurements. Preliminary stable isotope measurements of individual alkyl sulfonates, R-SO3H (R=C(sub n)H(sub 2n+l)), are shown. These compounds were found in aqueous extracts of Murchison. Both groups show trends similar to other homologous series of organic compounds indigenous to Murchison. Molecular abundances decrease with increasing carbon number, and all possible isomers at each carbon number (through C-4) are present. Carbon isotope measurements of the sulfonates show a decrease in the C-13/C-12 ratio with increasing carbon number. The overall objectives of this project are to obtain dime element carbon, hydrogen, and sulfur - intramolecular isotopic analyses of individual sulfonates, and isotopic measurement of carbon and hydrogen of the phosphonates as a group. The Murchison meteorite is the best characterized carbonaceous chondrite with respect to organic chemistry. The finding of organic sulfonates and phosphonates in Murchison is of interest because they are the first well-characterized series of sulfur and phosphorus containing organic compounds found in meteorites. Also, meteorites, comets, and interplanetary dust particles may have been involved in chemical evolution on the early Earth. Because of the critical role of organic phosphorus and sulfur in all living systems, it is particularly interesting to see examples of abiotic syntheses of these classes of compounds. The study of the isotopic composition of the sulfonates and phosphonates can yield insight into their possible interstellar origin as well as their mechanisms of synthesis in the early solar system. Previous isotopic analyses of other classes of organic compounds indigenous to meteorites, e.g., amino acids, carboxylic acids, and hydrocarbons indicate the possibility that interstellar molecules were incorporated into meteorite parent bodies. In these compounds the ratios of heavy to light isotopes of hydrogen (D/H), carbon (C-13/C-12), and nitrogen (N-15/N-14), are anomalous relative to bulk terrestrial and meteoritic values. In some cases, the D/H ratios approach those observed for molecules in interstellar clouds.

Expedited Selection of NMR Chiral Solvating Agents for Determination of Enantiopurity

PubMed Central

2016-01-01

The use of NMR chiral solvating agents (CSAs) for the analysis of enantiopurity has been known for decades, but has been supplanted in recent years by chromatographic enantioseparation technology. While chromatographic methods for the analysis of enantiopurity are now commonplace and easy to implement, there are still individual compounds and entire classes of analytes where enantioseparation can prove extremely difficult, notably, compounds that are chiral by virtue of very subtle differences such as isotopic substitution or small differences in alkyl chain length. NMR analysis using CSAs can often be useful for such problems, but the traditional approach to selection of an appropriate CSA and the development of an NMR-based analysis method often involves a trial-and-error approach that can be relatively slow and tedious. In this study we describe a high-throughput experimentation approach to the selection of NMR CSAs that employs automation-enabled screening of prepared libraries of CSAs in a systematic fashion. This approach affords excellent results for a standard set of enantioenriched compounds, providing a valuable comparative data set for the effectiveness of CSAs for different classes of compounds. In addition, the technique has been successfully applied to challenging pharmaceutical development problems that are not amenable to chromatographic solutions. Overall, this methodology provides a rapid and powerful approach for investigating enantiopurity that compliments and augments conventional chromatographic approaches. PMID:27280168

Nontargeted Screening of Halogenated Organic Compounds in Bottlenose Dolphins (Tursiops truncatus) from Rio de Janeiro, Brazil.

PubMed

Alonso, Mariana B; Maruya, Keith A; Dodder, Nathan G; Lailson-Brito, José; Azevedo, Alexandre; Santos-Neto, Elitieri; Torres, Joao P M; Malm, Olaf; Hoh, Eunha

2017-02-07

To catalog the diversity and abundance of halogenated organic compounds (HOCs) accumulating in high trophic marine species from the southwestern Atlantic Ocean, tissue from bottlenose dolphins (Tursiops truncatus) stranded or incidentally captured along the coast of Rio de Janeiro, Brazil, were analyzed by a nontargeted approach based on GC×GC/TOF-MS. A total of 158 individual HOCs from 32 different structural classes were detected in the blubber of 4 adult male T. truncatus. Nearly 90% of the detected compounds are not routinely monitored in the environment. DDT-related and mirex/dechlorane-related compounds were the most abundant classes of anthropogenic origin. Methoxy-brominated diphenyl ethers (MeO-BDEs) and chlorinated methyl- and dimethyl bipyrroles (MBPs and DMBPs) were the most abundant natural products. Reported for the first time in southwestern Atlantic cetaceans and in contrast to North American marine mammals, chlorinated MBPs and DMBPs were more abundant than their brominated and/or mixed halogenated counterparts. HOC profiles in coastal T. truncatus from Brazil and California revealed a distinct difference, with a higher abundance of MeO-BDEs, mirex/dechloranes and chlorinated bipyrroles in the Brazilian dolphins. Thirty-six percent of the detected HOCs had an unknown structure. These results suggest broad geographical differences in the patterns of bioaccumulative chemicals found in the marine environment and indicate the need to develop more complete catalogs of HOCs from various marine environments.

21 CFR 880.5440 - Intravascular administration set.

Code of Federal Regulations, 2012 CFR

2012-04-01

...) Classification. Class II (special controls). The special control for pharmacy compounding systems within this classification is the FDA guidance document entitled “Class II Special Controls Guidance Document: Pharmacy Compounding Systems; Final Guidance for Industry and FDA Reviewers.” Pharmacy compounding systems classified...

21 CFR 880.5440 - Intravascular administration set.

Code of Federal Regulations, 2011 CFR

2011-04-01

...) Classification. Class II (special controls). The special control for pharmacy compounding systems within this classification is the FDA guidance document entitled “Class II Special Controls Guidance Document: Pharmacy Compounding Systems; Final Guidance for Industry and FDA Reviewers.” Pharmacy compounding systems classified...

21 CFR 880.5440 - Intravascular administration set.

Code of Federal Regulations, 2013 CFR

2013-04-01

...) Classification. Class II (special controls). The special control for pharmacy compounding systems within this classification is the FDA guidance document entitled “Class II Special Controls Guidance Document: Pharmacy Compounding Systems; Final Guidance for Industry and FDA Reviewers.” Pharmacy compounding systems classified...

21 CFR 880.5440 - Intravascular administration set.

Code of Federal Regulations, 2014 CFR

2014-04-01

...) Classification. Class II (special controls). The special control for pharmacy compounding systems within this classification is the FDA guidance document entitled “Class II Special Controls Guidance Document: Pharmacy Compounding Systems; Final Guidance for Industry and FDA Reviewers.” Pharmacy compounding systems classified...

Effects of sodium-glucose cotransporter-2 inhibitors on cardiovascular disease, death and safety outcomes in type 2 diabetes - A systematic review.

PubMed

Rådholm, Karin; Wu, Jason Hy; Wong, Muh Geot; Foote, Celine; Fulcher, Gregory; Mahaffey, Kenneth W; Perkovic, Vlado; Neal, Bruce

2018-06-01

Sodium glucose co-transporter 2 (SGLT2) inhibitors appear to protect against increased risks of cardiovascular and kidney disease in patients with type 2 diabetes but also cause some harms. Whether effects are comparable across drug class or specific to individual compounds is unclear. This meta-analysis assessed the class and individual compound effects of SGLT2 inhibition versus control on cardiovascular events, death, kidney disease and safety outcomes in patients with type 2 diabetes. MEDLINE, EMBASE, the Cochrane Library and regulatory databases were systematically searched for data from randomized clinical trials that included reporting of cardiovascular events, deaths or safety outcomes. We used fixed effects models and inverse variance weighting to calculate relative risks with the 95% confidence intervals. The analyses included data from 82 trials, four overviews and six regulatory reports and there were 1,968 major cardiovascular events identified for analysis. Patients randomly assigned to SGLT2 had lower risks of major cardiovascular events (RR 0.85, 95%CI 0.77-0.93), heart failure (RR 0.67, 95%CI 0.55-0.80), all-cause death (RR 0.79, 95%CI 0.70-0.88) and serious decline in kidney function (RR 0.59, 0.49-0.71). Significant adverse effects were observed for genital infections (RR 3.06, 95%CI 2.73-4.43), volume depletion events (RR 1.24, 95%CI 1.07-1.43) and amputation (RR 1.44 95%CI 1.13-1.83). There was a high likelihood of differences in the associations of the individual compounds with cardiovascular death, hypoglycaemia and amputation (all I 2  > 80%) and a moderate likelihood of differences in the associations with non-fatal stroke, all-cause death, urinary tract infection and fracture (all I 2  > 30%). There are strong overall associations of SGLT2 inhibition with protection against major cardiovascular events, heart failure, serious decline in kidney function and all-cause death. SGLT2 inhibitors were also associated with infections, volume depletion effects and amputation. Some associations appear to differ between compounds. Copyright © 2018 Elsevier B.V. All rights reserved.

Previously unknown class of metalorganic compounds revealed in meteorites

PubMed Central

Ruf, Alexander; Kanawati, Basem; Hertkorn, Norbert; Yin, Qing-Zhu; Moritz, Franco; Harir, Mourad; Lucio, Marianna; Michalke, Bernhard; Wimpenny, Joshua; Shilobreeva, Svetlana; Bronsky, Basil; Saraykin, Vladimir; Gabelica, Zelimir; Gougeon, Régis D.; Quirico, Eric; Ralew, Stefan; Jakubowski, Tomasz; Haack, Henning; Gonsior, Michael; Jenniskens, Peter; Hinman, Nancy W.; Schmitt-Kopplin, Philippe

2017-01-01

The rich diversity and complexity of organic matter found in meteorites is rapidly expanding our knowledge and understanding of extreme environments from which the early solar system emerged and evolved. Here, we report the discovery of a hitherto unknown chemical class, dihydroxymagnesium carboxylates [(OH)2MgO2CR]−, in meteoritic soluble organic matter. High collision energies, which are required for fragmentation, suggest substantial thermal stability of these Mg-metalorganics (CHOMg compounds). This was corroborated by their higher abundance in thermally processed meteorites. CHOMg compounds were found to be present in a set of 61 meteorites of diverse petrological classes. The appearance of this CHOMg chemical class extends the previously investigated, diverse set of CHNOS molecules. A connection between the evolution of organic compounds and minerals is made, as Mg released from minerals gets trapped into organic compounds. These CHOMg metalorganic compounds and their relation to thermal processing in meteorites might shed new light on our understanding of carbon speciation at a molecular level in meteorite parent bodies. PMID:28242686

Mapping and quantifying isomer sets of hydrocarbons (≥ C12) in diesel exhaust, lubricating oil and diesel fuel samples using GC × GC-ToF-MS

NASA Astrophysics Data System (ADS)

Alam, Mohammed S.; Zeraati-Rezaei, Soheil; Liang, Zhirong; Stark, Christopher; Xu, Hongming; MacKenzie, A. Rob; Harrison, Roy M.

2018-05-01

Airborne particles and vapours, like many other environmental samples including water, soils and sediments, contain complex mixtures of hydrocarbons, often deriving from crude oil either before or after fractionation into fuels, lubricants and feedstocks. Comprehensive 2D gas chromatography time-of-flight mass spectrometry (GC × GC-ToF-MS), offers a very powerful technique that separates and identifies many compounds in complicated hydrocarbon mixtures. However, quantification and identification of individual constituents at high ionization energies would require hundreds of expensive (when available) standards for calibration. Although the precise chemical structure of hydrocarbons does matter for their environmental impact and fate, strong similarities can be expected for compounds having very similar chemical structures and carbon numbers. There is, therefore, a clear benefit in an analytical technique which is specific enough to separate different classes of compounds and to distinguish homologous series while avoiding the need to handle each isomer individually. Varying EI (electron impact) ionization mass spectrometry significantly enhances the identification of individual isomers and homologous compound groups, which we refer to as isomer sets. Advances are reported in mapping and quantifying isomer sets of hydrocarbons (≥ C12) in diesel fuel, lubricating oil and diesel exhaust emissions. By using this analysis we report mass closures of ca. 90 and 75 % for diesel fuel and lubricating oil, and identify 85 and 75 % of the total ion current for gas- and particulate-phase diesel exhaust emissions.

Evaluation of Volatile Species in Green Monopropellant Project

NASA Technical Reports Server (NTRS)

Greene, Benjamin

2015-01-01

NASA is interested in green monopropellants to replace hydrazine in reaction control systems (RCSs). Some current NASA programs require reduced vapor pressure and low toxicity monopropellant (green) and superior performance (specific impulse and density) formulations. Earlier vapor phase studies of a candidate green monopropellant at the NASA White Sands Test Facility (WSTF) showed the presence of a volatile species that warranted further investigation. The purpose of this study was to further characterize the volatile species and to evaluate it. The evaluation was with respect to whether the volatile species was an impurity or how it is formed, and to use that information to examine whether its presence as an impurity can be eliminated during formulation. The evaluation also considered whether formation of the volatile impurity could be prevented while not compromising the propellant. To reduce variables associated with evaluation of the propellant formulation as a whole, a precursor to one of the individual components in the propellant formulation was subjected to a NASA Standard 6001B Flammability, Off-gassing, and Compatibility Requirements and Test Procedures "Determination of Off-gassed Products (Test 7)". Testing took place in the NASA WSTF Molecular Desorption and Analysis Laboratory. One gram of the precursor was placed in a flask within a specimen container. After thermal conditioning for 72 +/- 1 h at 50 +/- 3 deg C (122 +/- 5 deg F), the atmosphere inside the specimen container was analyzed for off-gassed compounds by cryotrap gas chromatography-mass spectrometry (GC-MS) and fixed sample loop GC-flame ionization detection (GC-FID). The specimen container used was glass to minimize potential catalytic surfaces. The identification of compounds was difficult due to the complexity of the vapor phase concentrations and overlapping chromatographic peaks and mass spectra. However, eleven compounds were specifically identified and five compounds or classes of compounds were reported as unidentified. Quantitation of most of the compounds, including unidentified compounds, was as methane. Quantitating compounds or classes of compounds that were detected but for which specific calibration is not established as methane is in accordance with the Test 7 standard protocol. The thermal decomposition temperature of the precursor was significantly higher than the test temperature. Based on thermal decomposition temperature and on an examination of the structure and chemistry of the identified volatile species, the presence of the volatile species appears to be chemically reasonable with respect to the propellant formulation and is at this time attributed to impurities. Further examination of the overall propellant formulation process (including the individual components' synthesis processes) and process quality control (including purity of reagents and possible decomposition reactions) is indicated.

An atlas of histone deacetylase expression in breast cancer: fluorescence methodology for comparative semi-quantitative analysis

PubMed Central

Ververis, Katherine; Karagiannis, Tom C

2012-01-01

The histone deacetylase inhibitors, suberoylanilide hydroxamic acid (Vorinostat, Zolinza™) and depsipeptide (Romidepsin, Istodax™) have been approved by the US Food and Drug Administration for the treatment of refractory cutaneous T-cell lymphoma. Numerous histone deacetylase inhibitors are currently undergoing clinical trials, predominantly in combination with other cancer modalities, for the treatment of various haematological and solid malignancies. Most of the traditional compounds are known as broad-spectrum or pan-histone deacetylase inhibitors, possessing activity against a number of the 11 metal-dependent enzymes. One of the main questions in the field is whether class- or isoform-specific compounds would offer a therapeutic benefit compared to broad-spectrum inhibitors. Therefore, analysis of the relative expression of the different histone deacetylase enzymes in cancer cells and tissues is important to determine whether there are specific targets. We used a panel of antibodies directed against the 11 known mammalian histone deacetylases to determine expression levels in MCF7 breast cancer cells and in tissue representative of invasive ductal cell carcinoma and ductal carcinoma in situ. Firstly, we utilized a semi-quantitative method based on immunofluorescence staining to examine expression of the different histone deacetylases in MCF7 cells. Our findings indicate high expression levels of HDAC1, 3 and 6 in accordance with findings from others using RT-PCR and immunoblotting. Following validation of our approach we examined the expression of the different isoforms in representative control and breast cancer tissue. In general, our findings indicate higher expression of class I histone deacetylases compared to class II enzymes in breast cancer tissue. Analysis of individual cancer cells in the same tissue indicated marked heterogeneity in the expression of most class I enzymes indicating potential complications with the use of class- or isoform-specific compounds. Overall, our approach can be utilized to rapidly compare, in an unbiased semi-quantitative manner, the differential levels of expression of histone deacetylase enzymes in cells and tissues using widely available imaging software. It is anticipated that such analysis will become increasingly important as class- or isoform-specific histone deacetylase inhibitors become more readily available. PMID:22347520

An atlas of histone deacetylase expression in breast cancer: fluorescence methodology for comparative semi-quantitative analysis.

PubMed

Ververis, Katherine; Karagiannis, Tom C

2012-01-01

The histone deacetylase inhibitors, suberoylanilide hydroxamic acid (Vorinostat, Zolinza™) and depsipeptide (Romidepsin, Istodax™) have been approved by the US Food and Drug Administration for the treatment of refractory cutaneous T-cell lymphoma. Numerous histone deacetylase inhibitors are currently undergoing clinical trials, predominantly in combination with other cancer modalities, for the treatment of various haematological and solid malignancies. Most of the traditional compounds are known as broad-spectrum or pan-histone deacetylase inhibitors, possessing activity against a number of the 11 metal-dependent enzymes. One of the main questions in the field is whether class- or isoform-specific compounds would offer a therapeutic benefit compared to broad-spectrum inhibitors. Therefore, analysis of the relative expression of the different histone deacetylase enzymes in cancer cells and tissues is important to determine whether there are specific targets. We used a panel of antibodies directed against the 11 known mammalian histone deacetylases to determine expression levels in MCF7 breast cancer cells and in tissue representative of invasive ductal cell carcinoma and ductal carcinoma in situ. Firstly, we utilized a semi-quantitative method based on immunofluorescence staining to examine expression of the different histone deacetylases in MCF7 cells. Our findings indicate high expression levels of HDAC1, 3 and 6 in accordance with findings from others using RT-PCR and immunoblotting. Following validation of our approach we examined the expression of the different isoforms in representative control and breast cancer tissue. In general, our findings indicate higher expression of class I histone deacetylases compared to class II enzymes in breast cancer tissue. Analysis of individual cancer cells in the same tissue indicated marked heterogeneity in the expression of most class I enzymes indicating potential complications with the use of class- or isoform-specific compounds. Overall, our approach can be utilized to rapidly compare, in an unbiased semi-quantitative manner, the differential levels of expression of histone deacetylase enzymes in cells and tissues using widely available imaging software. It is anticipated that such analysis will become increasingly important as class- or isoform-specific histone deacetylase inhibitors become more readily available.

Crystallization tendency of active pharmaceutical ingredients following rapid solvent evaporation--classification and comparison with crystallization tendency from undercooled melts.

PubMed

Van Eerdenbrugh, Bernard; Baird, Jared A; Taylor, Lynne S

2010-09-01

In this study, the crystallization behavior of a variety of compounds was studied following rapid solvent evaporation using spin coating. Initial screening to determine model compound suitability was performed using a structurally diverse set of 51 compounds in three different solvent systems [dichloromethane (DCM), a 1:1 (w/w) dichloromethane/ethanol mixture (MIX), and ethanol (EtOH)]. Of this starting set of 153 drug-solvent combinations, 93 (40 compounds) were selected for further evaluation based on solubility, chemical solution stability, and processability criteria. These systems were spin coated and their crystallization was monitored using polarized light microscopy (7 days, dry conditions). The crystallization behavior of the samples could be classified as rapid (Class I: 39 cases), intermediate (Class II: 23 cases), or slow (Class III: 31 cases). The solvent system employed influenced the classification outcome for only four of the compounds. The various compounds showed very diverse crystallization behavior. Upon comparison of classification results with those of a previous study, where cooling from the melt was used as a preparation technique, a good similarity was found whereby 68% of the cases were identically classified. Multivariate analysis was performed using a set of relevant physicochemical compound characteristics. It was found that a number of these parameters tended to differ between the different classes. These could be further interpreted in terms of the nature of the crystallization process. Additional multivariate analysis on the separate classes of compounds indicated some potential in predicting the crystallization tendency of a given compound.

Robust Classification of Small-Molecule Mechanism of Action Using a Minimalist High-Content Microscopy Screen and Multidimensional Phenotypic Trajectory Analysis

PubMed Central

Twarog, Nathaniel R.; Low, Jonathan A.; Currier, Duane G.; Miller, Greg; Chen, Taosheng; Shelat, Anang A.

2016-01-01

Phenotypic screening through high-content automated microscopy is a powerful tool for evaluating the mechanism of action of candidate therapeutics. Despite more than a decade of development, however, high content assays have yielded mixed results, identifying robust phenotypes in only a small subset of compound classes. This has led to a combinatorial explosion of assay techniques, analyzing cellular phenotypes across dozens of assays with hundreds of measurements. Here, using a minimalist three-stain assay and only 23 basic cellular measurements, we developed an analytical approach that leverages informative dimensions extracted by linear discriminant analysis to evaluate similarity between the phenotypic trajectories of different compounds in response to a range of doses. This method enabled us to visualize biologically-interpretable phenotypic tracks populated by compounds of similar mechanism of action, cluster compounds according to phenotypic similarity, and classify novel compounds by comparing them to phenotypically active exemplars. Hierarchical clustering applied to 154 compounds from over a dozen different mechanistic classes demonstrated tight agreement with published compound mechanism classification. Using 11 phenotypically active mechanism classes, classification was performed on all 154 compounds: 78% were correctly identified as belonging to one of the 11 exemplar classes or to a different unspecified class, with accuracy increasing to 89% when less phenotypically active compounds were excluded. Importantly, several apparent clustering and classification failures, including rigosertib and 5-fluoro-2’-deoxycytidine, instead revealed more complex mechanisms or off-target effects verified by more recent publications. These results show that a simple, easily replicated, minimalist high-content assay can reveal subtle variations in the cellular phenotype induced by compounds and can correctly predict mechanism of action, as long as the appropriate analytical tools are used. PMID:26886014

Robust Classification of Small-Molecule Mechanism of Action Using a Minimalist High-Content Microscopy Screen and Multidimensional Phenotypic Trajectory Analysis.

PubMed

Twarog, Nathaniel R; Low, Jonathan A; Currier, Duane G; Miller, Greg; Chen, Taosheng; Shelat, Anang A

2016-01-01

Phenotypic screening through high-content automated microscopy is a powerful tool for evaluating the mechanism of action of candidate therapeutics. Despite more than a decade of development, however, high content assays have yielded mixed results, identifying robust phenotypes in only a small subset of compound classes. This has led to a combinatorial explosion of assay techniques, analyzing cellular phenotypes across dozens of assays with hundreds of measurements. Here, using a minimalist three-stain assay and only 23 basic cellular measurements, we developed an analytical approach that leverages informative dimensions extracted by linear discriminant analysis to evaluate similarity between the phenotypic trajectories of different compounds in response to a range of doses. This method enabled us to visualize biologically-interpretable phenotypic tracks populated by compounds of similar mechanism of action, cluster compounds according to phenotypic similarity, and classify novel compounds by comparing them to phenotypically active exemplars. Hierarchical clustering applied to 154 compounds from over a dozen different mechanistic classes demonstrated tight agreement with published compound mechanism classification. Using 11 phenotypically active mechanism classes, classification was performed on all 154 compounds: 78% were correctly identified as belonging to one of the 11 exemplar classes or to a different unspecified class, with accuracy increasing to 89% when less phenotypically active compounds were excluded. Importantly, several apparent clustering and classification failures, including rigosertib and 5-fluoro-2'-deoxycytidine, instead revealed more complex mechanisms or off-target effects verified by more recent publications. These results show that a simple, easily replicated, minimalist high-content assay can reveal subtle variations in the cellular phenotype induced by compounds and can correctly predict mechanism of action, as long as the appropriate analytical tools are used.

Clinical expression of patients with the D1152H CFTR mutation.

PubMed

Terlizzi, Vito; Carnovale, Vincenzo; Castaldo, Giuseppe; Castellani, Carlo; Cirilli, Natalia; Colombo, Carla; Corti, Fabiola; Cresta, Federico; D'Adda, Alice; Lucarelli, Marco; Lucidi, Vincenzina; Macchiaroli, Annamaria; Madarena, Elisa; Padoan, Rita; Quattrucci, Serena; Salvatore, Donatello; Zarrilli, Federica; Raia, Valeria

2015-07-01

Discordant results were reported on the clinical expression of subjects bearing the D1152H CFTR mutation, and also for the small number of cases reported so far. A retrospective review of clinical, genetic and biochemical data was performed from individuals homozygous or compound heterozygous for the D1152H mutation followed in 12 Italian cystic fibrosis (CF) centers. 89 subjects carrying at least D1152H on one allele were identified. 7 homozygous patients had very mild clinical expression. Over half of the 74 subjects compound heterozygous for D1152H and a I-II-III class mutation had borderline or pathological sweat test and respiratory or gastrointestinal symptoms; one third had pulmonary bacteria colonization and 10/74 cases had complications (i.e. diabetes, allergic bronchopulmonary aspergillosis, and hemoptysis). However, their clinical expression was less severe as compared to a group of CF patients homozygous for the F508del mutation. Finally, 8 subjects compound heterozygous for D1152H and a IV-V class mutation showed very mild disease. The natural history of subjects bearing the D1152H mutation is widely heterogeneous and is influenced by the mutation in trans. Copyright © 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Diverse Soil Carbon Dynamics Expressed at the Molecular Level

NASA Astrophysics Data System (ADS)

van der Voort, T. S.; Zell, C. I.; Hagedorn, F.; Feng, X.; McIntyre, C. P.; Haghipour, N.; Graf Pannatier, E.; Eglinton, T. I.

2017-12-01

The stability and potential vulnerability of soil organic matter (SOM) to global change remain incompletely understood due to the complex processes involved in its formation and turnover. Here we combine compound-specific radiocarbon analysis with fraction-specific and bulk-level radiocarbon measurements in order to further elucidate controls on SOM dynamics in a temperate and subalpine forested ecosystem. Radiocarbon contents of individual organic compounds isolated from the same soil interval generally exhibit greater variation than those among corresponding operationally defined fractions. Notably, markedly older ages of long-chain plant leaf wax lipids (n-alkanoic acids) imply that they reflect a highly stable carbon pool. Furthermore, marked 14C variations among shorter- and longer-chain n-alkanoic acid homologues suggest that they track different SOM pools. Extremes in SOM dynamics thus manifest themselves within a single compound class. This exploratory study highlights the potential of compound-specific radiocarbon analysis for understanding SOM dynamics in ecosystems potentially vulnerable to global change.

Unified model for the corneal permeability of related and diverse compounds with respect to their physicochemical properties.

PubMed

Yoshida, F; Topliss, J G

1996-08-01

Corneal permeability data taken from the literature were analyzed for possible quantitative relationships with physicochemical properties. Although a parabolic relationship was obtained with good correlation between lipophilicity, as expressed by the 1-octanol-water partition coefficients, log Poctanol (or the distribution coefficients, log D for ionizable compounds), and the permeability in individual analyses of compound classes such as beta-adrenoceptor blockers and steroids, the correlation was reduced when taken together. However, delta log P (i.e., log Poctanol-log Palkane) correlated inversely with the combined permeability data for beta-blockers and steroids and played a key role as a unifying variable. To a lesser extent, lipophilicity itself also contributes positively to corneal permeation. Even with the addition of miscellaneous compounds such as methanol and ibuprofen, the delta log P and lipophilicity terms were still significant. However, small molecules were likely to be underestimated, which is consistent with penetration via another pathway besides that governed by delta log P and lipophilicity.

Comparison of the phytochemical profiles of five native plant species in two different forest formations.

PubMed

Pilatti, D M; Fortes, A M T; Jorge, T C M; Boiago, N P

2018-06-14

The expression of chemical compounds by individual plants of the same species in different locations may be affected by abiotic factors resulting in differences in the production of allelopathic compounds. The objective of this study was to compare the phytochemical profiles of plant species from two different forest formations in the state of Paraná, Brazil. The forest formations were Seasonal Semideciduous Forest (SSF) and Lowland Ombrophilous Dense Forest (LODF), and the five study species were Jacaranda micrantha, Cecropia pachystachya, Mimosa bimucronata, Schinus terebinthifolius and Cedrela fissilis. Secondary metabolites were extracted by exhaustive extraction with methanol, and the crude extract was fractionated using column chromatography. The fractions were used to calculate the retention factor of the main compounds using thin layer chromatography and phytochemical tests. The classes of compounds identified were practically the same among the analyzed species, however, at different levels of concentration. The type of tannins found in S. terebinthifolius differed between the two forest formations.

A review of the volatiles from the healthy human body.

PubMed

de Lacy Costello, B; Amann, A; Al-Kateb, H; Flynn, C; Filipiak, W; Khalid, T; Osborne, D; Ratcliffe, N M

2014-03-01

A compendium of all the volatile organic compounds (VOCs) emanating from the human body (the volatolome) is for the first time reported. 1840 VOCs have been assigned from breath (872), saliva (359), blood (154), milk (256), skin secretions (532) urine (279), and faeces (381) in apparently healthy individuals. Compounds were assigned CAS registry numbers and named according to a common convention where possible. The compounds have been grouped into tables according to their chemical class or functionality to permit easy comparison. Some clear differences are observed, for instance, a lack of esters in urine with a high number in faeces. Careful use of the database is needed. The numbers may not be a true reflection of the actual VOCs present from each bodily excretion. The lack of a compound could be due to the techniques used or reflect the intensity of effort e.g. there are few publications on VOCs from blood compared to a large number on VOCs in breath. The large number of volatiles reported from skin is partly due to the methodologies used, e.g. collecting excretions on glass beads and then heating to desorb VOCs. All compounds have been included as reported (unless there was a clear discrepancy between name and chemical structure), but there may be some mistaken assignations arising from the original publications, particularly for isomers. It is the authors' intention that this database will not only be a useful database of VOCs listed in the literature, but will stimulate further study of VOCs from healthy individuals. Establishing a list of volatiles emanating from healthy individuals and increased understanding of VOC metabolic pathways is an important step for differentiating between diseases using VOCs.

Isolation and identification of molecular species of phosphatidylcholine and lysophosphatidylcholine from jojoba seed meal (Simmondsia chinensis).

PubMed

Léon, Fabian; Van Boven, Maurits; de Witte, Peter; Busson, Roger; Cokelaere, Marnix

2004-03-10

A mixture of lysophosphatidylcholine (LPC) and phosphatidylcholine (PC) has been isolated by column chromatography from a jojoba meal (Simmondsia chinensis) extract. The molecular species of both classes could be separated and isolated by C18 reversed phase HPLC. The two major compounds were identified by 1D and 2D (1)H and (13)C NMR, by MS, and by GC-MS as 1-oleoyl-3-lysophosphatidylcholine and 1,2-dioleoyl-3-phosphatidylcholine. Eight other molecular species of LPC and four other molecular species of PC could be assigned by comparison of the mass spectra of the isolated compounds with the spectra of the two major compounds. Complete characterization of the individual molecular species was achieved by GC and GC-MS analysis of the fatty acyl composition from the isolated compounds. The PC/LPC proportion in the phospholipid mixture from three different samples is 1.6 +/- 0.1. LPC is considered to be an important bioactive compound; the results of this study suggest further research for the evaluation of potential health benefits of jojoba meal phospholipids.

Is the full potential of the biopharmaceutics classification system reached?

PubMed

Bergström, Christel A S; Andersson, Sara B E; Fagerberg, Jonas H; Ragnarsson, Gert; Lindahl, Anders

2014-06-16

In this paper we analyse how the biopharmaceutics classification system (BCS) has been used to date. A survey of the literature resulted in a compilation of 242 compounds for which BCS classes were reported. Of these, 183 compounds had been reported to belong to one specific BCS class whereas 59 compounds had been assigned to multiple BCS classes in different papers. Interestingly, a majority of the BCS class 2 compounds had fraction absorbed (FA) values >85%, indicating that they were completely absorbed after oral administration. Solubility was computationally predicted at pH 6.8 for BCS class 2 compounds to explore the impact of the pH of the small intestine, where most of the absorption occurs, on the solubility. In addition, the solubilization capacity of lipid aggregates naturally present in the intestine was studied computationally and experimentally for a subset of 12 compounds. It was found that all acidic compounds with FA>85% were completely dissolved in the pH of the small intestine. Further, lipids at the concentration used in fasted state simulated intestinal fluid (FaSSIF) dissolved the complete dose given of the most lipophilic (logD6.5>3) compounds studied. Overall, biorelevant dissolution media (pure buffer of intestinal pH or FaSSIF) identified that for 20 of the 29 BCS class 2 compounds with FA>85% the complete dose given orally would be dissolved. These results indicate that a more relevant pH restriction for acids and/or dissolution medium with lipids present better forecast solubility-limited absorption in vivo than the presently used BCS solubility criterion. The analysis presented herein further strengthens the discussion on the requirement of more physiologically relevant dissolution media for the in vitro solubility classification performed to reach the full potential of the BCS. Copyright © 2013 Elsevier B.V. All rights reserved.

E-Mail Molecules—Individualizing the Large Lecture Class

NASA Astrophysics Data System (ADS)

Wamser, Carl C.

2003-11-01

All students in the organic chemistry class are assigned a unique set of nine molecules to report on as optional extra credit assignments. The molecules are taken from a list containing over 200 molecules on the class Web site; they represent an assortment of biologically relevant compounds, from acetaminophen to yohimbine. Once a week, students may submit information about one of the molecules for two points extra credit (where the course includes a total of over 600 points from traditional quizzes and exams). The information requested about the molecules varies slightly each term as student expertise grows, for example, molecular formula, hybridizations, functional groups, or number of stereocenters, but always includes biological relevance and sources of information. Initially students submitted data directly to the instructor by e-mail, but submissions now are handled by a Web-based course management system (WebCT). The goal is to give students individualized assignments that are relatively realistic in light of their future careers in health sciences. Nearly all of the students do some of the molecules, and many students do all of them. About 30 40% of the students who do the assignments regularly gain a grade benefit. Student responses to the exercise have been positive.

Triaryl Benzimidazoles as a New Class of Antibacterial Agents against Resistant Pathogenic Microorganisms.

PubMed

Picconi, Pietro; Hind, Charlotte; Jamshidi, Shirin; Nahar, Kazi; Clifford, Melanie; Wand, Matthew E; Sutton, J Mark; Rahman, Khondaker Miraz

2017-07-27

A new class of nontoxic triaryl benzimidazole compounds, derived from existing classes of DNA minor groove binders, were designed, synthesized, and evaluated for their antibacterial activity against multidrug resistant (MDR) Gram-positive and Gram-negative species. Molecular modeling experiments suggest that the newly synthesized class cannot be accommodated within the minor groove of DNA due to a change in the shape of the molecules. Compounds 8, 13, and 14 were found to be the most active of the series, with MICs in the range of 0.5-4 μg/mL against the MDR Staphylococci and Enterococci species. Compound 13 showed moderate activity against the MDR Gram-negative strains, with MICs in the range of 16-32 μg/mL. Active compounds showed a bactericidal mode of action, and a mechanistic study suggested the inhibition of bacterial gyrase as the mechanism of action (MOA) of this chemical class. The MOA was further supported by the molecular modeling study.

Influence of thermal hydrolysis-anaerobic digestion treatment of wastewater solids on concentrations of triclosan, triclocarban, and their transformation products in biosolids.

PubMed

Armstrong, Dana L; Rice, Clifford P; Ramirez, Mark; Torrents, Alba

2017-03-01

The growing concern worldwide regarding the presence of emerging contaminants in biosolids calls for a better understanding of how different treatment technologies at water resource recovery facilities (WRRFs) can influence concentrations prior to biosolids land application. This study focuses on the influence of solids treatment via the Cambi Thermal Hydrolysis Process™ in conjunction with anaerobic digestion (TH-AD) on concentrations of triclosan (TCS), triclocarban (TCC), and their transformation products in biosolids and sludges. Concentrations of the target analytes in biosolids from the TH-AD process (Class A), sludges from the individual TH-AD treatment steps, and limed biosolids (Class B) from the same WRRF were compared. TCC concentrations were significantly lower in Class A biosolids than those in the Class B product - a removal that occurred during thermal hydrolysis. Concentrations of TCS, methyl triclosan, and 2,4-dichlorophenol, conversely, increased during anaerobic digestion, leading to significantly higher concentrations of these compounds in Class A biosolids when compared to Class B biosolids. Implementation of the TH-AD process had mixed effect on contaminant concentrations. Copyright © 2016 Elsevier Ltd. All rights reserved.

URANIUM EXTRACTION PROCESS USING SYNERGISTIC REAGENTS

DOEpatents

Schmitt, J.M.; Blake, C.A. Jr.; Brown, K.B.; Coleman, C.F.

1958-11-01

Improved methods are presented for recovering uranium values from aqueous solutions by organic solvent extraction. The improvement lies in the use, in combination, of two classes of organic compounds so that their extracting properties are enhanced synergistically. The two classes of organic compounds are dialkylphosphoric acid and certain neutral organophosphorus compounds such as trialkylphosphates, trialkylphosphonates, trlalkylphosphinates and trialkylphosphine oxides.

Differences in Pop Levels between Conventional and Omega-3 Fatty Acid-Enriched Milk and Dairy Products

PubMed Central

Guerranti, Cristiana; Focardi, Silvano Ettore

2011-01-01

Conventional and omega-3 fatty acid-enriched milk and cheese were analyzed for persistent organic pollutants (POPs). Omega-3-enriched products are usually supplemented with fish oil which is potentially contaminated. All classes of the considered POPs (PCBs, DDT, HCB, PBDEs, and PCDD/Fs) were found in the samples, with average concentrations higher in omega-3-enriched products than in conventional ones. For PCBs, DDT, and HCB, differences were statistically significant and, therefore, cannot be ascribed to normal variability. With regard to all classes of compounds, the highest levels in individual samples were always found in omega-3 products, in line with the hypothesis that these foods are potentially more contaminated than conventional ones. PMID:23724286

A Dinitroaniline-Resistant Mutant of Eleusine indica Exhibits Cross-Resistance and Supersensitivity to Antimicrotubule Herbicides and Drugs 1

PubMed Central

Vaughn, Kevin C.; Marks, M. David; Weeks, Donald P.

1987-01-01

A dinitroaniline-resistant (R) biotype of Eleusine indica (L.) Gaertner. (goosegrass) is demonstrated to be cross-resistant to a structurally non-related herbicide, amiprophosmethyl, and supersensitive to two other classes of compounds which disrupt mitosis. These characteristics of the R biotype were discovered in a comparative test of the effects of 24 different antimitotic compounds on the R biotype and susceptible (S) wild-type Eleusine. The compounds tested could be classified into three groups based upon their effects on mitosis in root tips of the susceptible (S) biotype. Class I compounds induced effects like the well known mitotic disrupter colchicine: absence of cortical and spindle microtubules, mitosis arrested at prometaphase, and the formation of polymorphic nuclei after arrested mitosis. The R biotype was resistant to treatment with some class I inhibitors (all dinitroaniline herbicides and amiprophosmethyl) but not all (e.g. colchicine, podophyllotoxin, vinblastine, and pronamide). Roots of the R biotype, when treated with either dinitroaniline herbicides or amiprophosmethyl, exhibited no or only small increases in the mitotic index nor were the spindle and cortical microtubules affected. Compounds of class II (carbamate herbicides and griseofulvin) cause misorientation of microtubules which results in multinucleated cells. Compounds of class III (caffeine and structually related alkaloids) cause imcomplete cell walls to form at telophase. Each of these last two classes of compounds affected the R biotype more than the S biotype (supersensitivity). The cross-resistance and high levels of resistance of the R biotype of Eleusine to the dinitroaniline herbicides and the structurally distinct herbicide, amiprophosmethyl, indicate that a mechanism of resistance based upon metabolic modification, translocation, or compartmentation of the herbicides is probably not operative. Images Fig. 1 Fig. 2 Fig. 3 Fig. 5 Fig. 6 PMID:16665371

A Dinitroaniline-Resistant Mutant of Eleusine indica Exhibits Cross-Resistance and Supersensitivity to Antimicrotubule Herbicides and Drugs.

PubMed

Vaughn, K C; Marks, M D; Weeks, D P

1987-04-01

A dinitroaniline-resistant (R) biotype of Eleusine indica (L.) Gaertner. (goosegrass) is demonstrated to be cross-resistant to a structurally non-related herbicide, amiprophosmethyl, and supersensitive to two other classes of compounds which disrupt mitosis. These characteristics of the R biotype were discovered in a comparative test of the effects of 24 different antimitotic compounds on the R biotype and susceptible (S) wild-type Eleusine. The compounds tested could be classified into three groups based upon their effects on mitosis in root tips of the susceptible (S) biotype. Class I compounds induced effects like the well known mitotic disrupter colchicine: absence of cortical and spindle microtubules, mitosis arrested at prometaphase, and the formation of polymorphic nuclei after arrested mitosis. The R biotype was resistant to treatment with some class I inhibitors (all dinitroaniline herbicides and amiprophosmethyl) but not all (e.g. colchicine, podophyllotoxin, vinblastine, and pronamide). Roots of the R biotype, when treated with either dinitroaniline herbicides or amiprophosmethyl, exhibited no or only small increases in the mitotic index nor were the spindle and cortical microtubules affected. Compounds of class II (carbamate herbicides and griseofulvin) cause misorientation of microtubules which results in multinucleated cells. Compounds of class III (caffeine and structually related alkaloids) cause imcomplete cell walls to form at telophase. Each of these last two classes of compounds affected the R biotype more than the S biotype (supersensitivity). The cross-resistance and high levels of resistance of the R biotype of Eleusine to the dinitroaniline herbicides and the structurally distinct herbicide, amiprophosmethyl, indicate that a mechanism of resistance based upon metabolic modification, translocation, or compartmentation of the herbicides is probably not operative.

Establishing the pharmaceutical quality of Chinese herbal medicine: a provisional BCS classification.

PubMed

Fong, Sophia Y K; Liu, Mary; Wei, Hai; Löbenberg, Raimar; Kanfer, Isadore; Lee, Vincent H L; Amidon, Gordon L; Zuo, Zhong

2013-05-06

The Biopharmaceutical Classification System (BCS), which is a scientific approach to categorize active drug ingredient based on its solubility and intestinal permeability into one of the four classes, has been used to set the pharmaceutical quality standards for drug products in western society. However, it has received little attention in the area of Chinese herbal medicine (CHM). This is likely, in part, due to the presence of multiple active components as well as lack of standardization of CHM. In this report, we apply BCS classification to CHMs provisionally as a basis for establishing improved in vitro quality standards. Based on a top-200 drugs selling list in China, a total of 31 CHM products comprising 50 official active marker compounds (AMCs) were provisionally classified according to BCS. Information on AMC content and doses of these CHM products were retrieved from the Chinese Pharmacopoeia. BCS parameters including solubility and permeability of the AMCs were predicted in silico (ACD/Laboratories). A BCS classification of CHMs according to biopharmaceutical properties of their AMCs is demonstrated to be feasible in the current study and can be used to provide a minimum set of quality standards. Our provisional results showed that 44% of the included AMCs were classified as Class III (high solubility, low permeability), followed by Class II (26%), Class I (18%), and Class IV (12%). A similar trend was observed when CHMs were classified in accordance with the BCS class of AMCs. Most (45%) of the included CHMs were classified as Class III, followed by Class II (16%), Class I (10%), and Class IV (6%); whereas 23% of the CHMs were of mixed class due to the presence of multiple individual AMCs with different BCS classifications. Moreover, about 60% of the AMCs were classified as high-solubility compounds (Class I and Class III), suggesting an important role for an in vitro dissolution test in setting quality control standards ensuring consistent biopharmaceutical quality for the commercially available CHM products. That is, provisionally, more than half of the AMCs of the top-selling CHMs included in this study would be candidates for a bioequivalence (BE) biowaiver, based on WHO recommendations and EMEA guidelines. Thus a dissolution requirement on these AMCs would represent a significant advance in the pharmaceutical quality of CHM today.

Synthesis and Biological Evaluation of Ginsenoside Compound K Derivatives as a Novel Class of LXRα Activator.

PubMed

Huang, Yan; Liu, Hongmei; Zhang, Yingxian; Li, Jin; Wang, Chenping; Zhou, Li; Jia, Yi; Li, Xiaohui

2017-07-24

Compound K is one of the active metabolites of Panaxnotoginseng saponins, which could attenuate the formation of atherosclerosis in mice modelsvia activating LXRα. We synthesized and evaluated a series of ginsenoside compound K derivatives modified with short chain fatty acids. All of the structures of this class of ginsenoside compound K derivative exhibited comparable or better biological activity than ginsenoside compound K. Especially structure 1 exhibited the best potency (cholesteryl ester content: 41.51%; expression of ABCA1 mRNA: 319%) and low cytotoxicity.

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

Porta, Miquel; Facultat de Medicina, Universitat Autonoma de Barcelona; CIBER en Epidemiologia y Salud Publica

Background: The relationships between social factors and body concentrations of environmental chemical agents are unknown in many human populations. Some chemical compounds may play an etiopathogenic role in pancreatic cancer. Objective: To analyze the relationships between occupational social class and serum concentrations of seven selected organochlorine compounds (OCs) in exocrine pancreatic cancer: dichlorodiphenyltrichloroethane (p,p'-DDT), dichlorodiphenyldichloroethene (p,p'-DDE), 3 polychlorinated biphenyls (PCBs), hexachlorobenzene, and {beta}-hexachlorocyclohexane. Methods: Incident cases of exocrine pancreatic cancer were prospectively identified, and interviewed face-to-face during hospital admission (n=135). Serum concentrations of OCs were analyzed by high-resolution gas chromatography with electron-capture detection. Social class was classified according to occupation.more » Results: Multivariate-adjusted concentrations of all seven compounds were higher in occupational social classes IV-V (the less affluent) than in classes I-II; they were higher as well in class III than in classes I-II for four compounds. Concentrations of six OCs were higher in manual workers than in non-manual workers (p<0.05 for PCBs). Social class explained statistically between 3.7% and 5.7% of the variability in concentrations of PCBs, and 2% or less variability in the other OCs. Conclusions: Concentrations of most OCs were higher in the less affluent occupational social classes. In pancreatic cancer the putative causal role of these persistent organic pollutants may not be independent of social class. There is a need to integrate evidence on the contribution of different social processes and environmental chemical exposures to the etiology of pancreatic and other cancers.« less

Contextual control using a go/no-go procedure with compound abstract stimuli.

PubMed

Modenesi, Rafael Diego; Debert, Paula

2015-05-01

Contextual control has been described as (1) a five-term contingency, in which the contextual stimulus exerts conditional control over conditional discriminations, and (2) allowing one stimulus to be a member of different equivalence classes without merging them into one. Matching-to-sample is the most commonly employed procedure to produce and study contextual control. The present study evaluated whether the go/no-go procedure with compound stimuli produces equivalence classes that share stimuli. This procedure does not allow the identification of specific stimulus functions (e.g., contextual, conditional, or discriminative functions). If equivalence classes were established with this procedure, then only the latter part of the contextual control definition (2) would be met. Six undergraduate students participated in the present study. In the training phases, responses to AC, BD, and XY compounds with stimuli from the same classes were reinforced, and responses to AC, BD, and XY compounds with stimuli from different classes were not. In addition, responses to X1A1B1, X1A2B2, X2A1B2, and X2A2B1 compounds were reinforced and responses to the other combinations were not. During the tests, the participants had to respond to new combinations of stimuli compounds YCD to indicate the formation of four equivalence classes that share stimuli: X1A1B1Y1C1D1, X1A2B2Y1C2D2, X2A1B2Y2C1D2, and X2A2B1Y2C2D1. Four of the six participants showed the establishment of these classes. These results indicate that establishing contextual stimulus functions is unnecessary to produce equivalence classes that share stimuli. Therefore, these results are inconsistent with the first part of the definition of contextual control. © Society for the Experimental Analysis of Behavior.

Analytical methods in environmental effects-directed investigations of effluents.

PubMed

Hewitt, L Mark; Marvin, Chris H

2005-05-01

Effluent discharges are released into aquatic environments as complex mixtures for which there is commonly either no knowledge of the toxic components or a lack of understanding of how known toxicants interact with other effluent components. Effects-directed investigations consist of chemical extraction and iterative fractionation steps directed by a biological endpoint that is designed to permit the identification or characterization of the chemical classes or compounds in a complex mixture responsible for the observed biological activity. Our review of the literature on effects-directed analyses of effluents for non-mutagenic as well as mutagenic endpoints showed that common extraction and concentration methods have been used. Since the mid-1980s, the methods have evolved from the use of XAD resins to C18 solid-phase extraction (SPE). Blue cotton, blue rayon, and blue chitin have been used specifically for investigations of mutagenic activity where polycyclic compounds were involved or suspected. After isolation, subsequent fractionations have been accomplished using SPE or a high-pressure liquid chromatography (HPLC) system commonly fitted with a C18 reverse-phase column. Substances in active fractions are characterized by gas chromatography/mass spectrometry (GC-MS) and/or other spectrometric techniques for identification. LC-MS methods have been developed for difficult-to-analyze polar substances identified from effects-directed studies, but the potential for LC-MS to identify unknown polar compounds has yet to be fully realized. Salmonella-based assays (some miniaturized) have been coupled with fractionation methods for most studies aimed at identifying mutagenic fractions and chemical classes in mixtures. Effects-directed investigations of mutagens have focused mostly on drinking water and sewage, whereas extensive investigations of non-mutagenic effects have also included runoff, pesticides, and pulp mill effluents. The success of effects-directed investigations should be based on a realistic initial objective of each project. Identification of chemical classes associated with the measured biological endpoint is frequently achievable; however, confirmation of individual compounds is much more difficult and not always a necessary goal of effects-directed chemical analysis.

Development of "one-pot" method for multi-class compounds in porcine formula feed by multi-function impurity adsorption cleaning followed ultra-performance liquid chromatography-tandem mass spectrometry detection.

PubMed

Wang, Peilong; Wang, Xiao; Zhang, Wei; Su, Xiaoou

2014-02-01

A novel and efficient determination method for multi-class compounds including β-agonists, sedatives, nitro-imidazoles and aflatoxins in porcine formula feed based on a fast "one-pot" extraction/multifunction impurity adsorption (MFIA) clean-up procedure has been developed. 23 target analytes belonging to four different class compounds could be determined simultaneously in a single run. Conditions for "one-pot" extraction were studied in detail. Under the optimized conditions, the multi-class compounds in porcine formula feed samples were extracted and purified with methanol contained ammonia and absorbents by one step. The compounds in extracts were purified by using multi types of absorbent based on MFIA in one pot. The multi-walled carbon nanotubes were employed to improved clean-up efficiency. Shield BEH C18 column was used to separate 23 target analytes, followed by tandem mass spectrometry (MS/MS) detection using an electro-spray ionization source in positive mode. Recovery studies were done at three fortification levels. Overall average recoveries of target compounds in porcine formula feed at each levels were >51.6% based on matrix fortified calibration with coefficients of variation from 2.7% to 13.2% (n=6). The limit of determination (LOD) of these compounds in porcine formula feed sample matrix was <5.0 μg/kg. This method was successfully applied in screening and confirmation of target drugs in >30 porcine formula feed samples. It was demonstrated that the integration of the MFIA protocol with the MS/MS instrument could serve as a valuable strategy for rapid screening and reliable confirmatory analysis of multi-class compounds in real samples. Copyright © 2013 Elsevier B.V. All rights reserved.

A Connectionist Model of Stimulus Class Formation with a Yes/No Procedure and Compound Stimuli

ERIC Educational Resources Information Center

Tovar, Angel E.; Chavez, Alvaro Torres

2012-01-01

We analyzed stimulus class formation in a human study and in a connectionist model (CM) with a yes/no procedure, using compound stimuli. In the human study, the participants were six female undergraduate students; the CM was a feed-forward back-propagation network. Two 3-member stimulus classes were trained with a similar procedure in both the…

Molecular Diversity of Sea Spray Aerosol Particles: Impact of Ocean Biology on Particle Composition and Hygroscopicity

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

Cochran, Richard E.; Laskina, Olga; Trueblood, Jonathan V.

The impact of sea spray aerosol (SSA) on climate depends on the size and chemical composition of individual particles that make-up the total SSA ensemble. While the organic fraction of SSA has been characterized from a bulk perspective, there remains a lack of understanding as to the composition of individual particles within the SSA ensemble. To better understand the molecular components within SSA particles and how SSA composition changes with ocean biology, simultaneous measurements of seawater and SSA were made during a month-long mesocosm experiment performed in an ocean-atmosphere facility. Herein, we deconvolute the composition of freshly emitted SSA devoidmore » of anthropogenic and terrestrial influences by characterizing classes of organic compounds as well as specific molecules within individual SSA particles. Analysis of SSA particles show that the diversity of molecules within the organic fraction varies between two size fractions (submicron and supermicron) with contributions from fatty acids, monosaccharides, polysaccharides and siliceous material. Significant changes in the distribution of these compounds within individual particles are observed to coincide with the rise and fall of phytoplankton and bacterial populations within the seawater. Furthermore, water uptake is impacted as shown by hygroscopicity measurements of model systems composed of representative organic compounds. Thus, the how changes in the hygroscopic growth of SSA evolves with composition can be elucidated. Overall, this study provides an important connection between biological processes that control the composition of seawater and changes in single particle composition which will enhances our ability to predict the impact of SSA on climate.« less

Effect of pH, temperature, and moisture on the formation of volatile compounds in glycine/glucose model systems.

PubMed

Ames, J M; Guy, R C; Kipping, G J

2001-09-01

Mixtures of glycine, glucose, and starch were extrusion cooked using sodium hydroxide at 0, 3, and 6 g/L of extruder water feed, 18% moisture, and 120, 150, and 180 degrees C target die temperatures, giving extrudates with pH values of 5.6, 6.8, and 7.4. Freeze-dried equimolar solutions of glucose and glycine were heated either dry or after equilibration to approximately 13% moisture at 180 degrees C in a reaction-tube system designed to mimic the heating profile in an extruder. Volatile compounds were isolated onto Tenax and analyzed by gas chromatography-mass spectrometry. For the extrudates, total yields of volatiles increased with decreasing pH at 180 degrees C, reached a maximum at pH 6.8 at 150 degrees C, and increased with increasing pH at 120 degrees C. Amounts increased with temperature at all pH values. Pyrazines were the most abundant class for all sets of conditions (54-79% of total volatiles). Pyrroles, ketones, furans, oxazoles, and pyridines were also identified. Yields of volatiles from the reaction-tube samples increased by >60% in the moist system. Levels of individual classes also increased in the presence of moisture, except pyrazines, which decreased approximately 3.5-fold. Twenty-one of the compounds were common to the reaction-tube samples and the extrudates.

[Evaluation of the sanitary-and-epidemiological safety of flocculating agents used for portable water purification].

PubMed

Zholdakova, Z I; Sinitsyna, O O; Tul'skaia, E A

2006-01-01

Polyelectrolytes used in the practice of water supply to the population were comparatively hygienically studied, by using a complex of hazard indices and a new approach to sanitary-and-epidemiological evaluation of the safety of water-soluble polymers is substantiated. The anionic and cationic flocculating agents from different chemical classes, such as Superflok A-100, Fennopol A 321E, Fennopol K 221E, Praestol 2530 TR, VPK-402, Superflok C-577, Saipan, KF-91, Ecosol-401, a low molecular-weight sodium polyacrylate were tested as model compounds. Moreover, the information already available in the scientific literature on the toxicity of synthetic polyelectrolytes was analyzed. The generalized maximum permissible concentrations were substantiated for individual chemical classes of synthetic polyelectrolytes: polyacrylamides, polyamines, polydiallyldimethylammonium chloride.

Safe and targeted anticancer therapy for ovarian cancer using a novel class of curcumin analogs

PubMed Central

2013-01-01

A diagnosis of advanced ovarian cancer is the beginning of a long and arduous journey for a patient. Worldwide, approximately half of the individuals undergoing therapy for advanced cancer will succumb to the disease, or consequences of treatment. Well-known and widely-used chemotherapeutic agents such as cisplatin, paclitaxel, 5-fluorouracil, and doxorubicin are toxic to both cancer and non-cancerous cells, and have debilitating side effects Therefore, development of new targeted anticancer therapies that can selectively kill cancer cells while sparing the surrounding healthy tissues is essential to develop more effective therapies. We have developed a new class of synthetic curcumin analogs, diarylidenyl-piperidones (DAPs), which have higher anticancer activity and enhanced bio-absorption than curcumin. The DAP backbone structure exhibits cytotoxic (anticancer) activity, whereas the N-hydroxypyrroline (-NOH) moiety found on some variants functions as a cellular- or tissue-specific modulator (antioxidant) of cytotoxicity. The anticancer activity of the DAPs has been evaluated using a number of ovarian cancer cell lines, and the safety has been evaluated in a number of non-cancerous cell lines. Both variations of the DAP compounds showed similar levels of cell death in ovarian cancer cells, however the compounds with the -NOH modification were less toxic to non-cancerous cells. The selective cytotoxicity of the DAP–NOH compounds suggests that they will be useful as safe and effective anticancer agents. This article reviews some of the key findings of our work with the DAP compounds, and compares this to some of the targeted therapies currently used in ovarian cancer therapy. PMID:23663277

31P-edited diffusion-ordered 1H NMR spectroscopy for the spectral isolation and identification of organophosphorus compounds related to chemical weapons agents and their degradation products.

PubMed

Mayer, Brian P; Valdez, Carlos A; Hok, Saphon; Chinn, Sarah C; Hart, Bradley R

2012-12-04

Organophosphorus compounds represent a large class of molecules that include pesticides, flame-retardants, biologically relevant molecules, and chemical weapons agents (CWAs). The detection and identification of organophosphorus molecules, particularly in the cases of pesticides and CWAs, are paramount to the verification of international treaties by various organizations. To that end, novel analytical methodologies that can provide additional support to traditional analyses are important for unambiguous identification of these compounds. We have developed an NMR method that selectively edits for organophosphorus compounds via (31)P-(1)H heteronuclear single quantum correlation (HSQC) and provides an additional chromatographic-like separation based on self-diffusivities of the individual species via (1)H diffusion-ordered spectroscopy (DOSY): (1)H-(31)P HSQC-DOSY. The technique is first validated using the CWA VX (O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate) by traditional two-dimensional DOSY spectra. We then extend this technique to a complex mixture of VX degradation products and identify all the main phosphorus-containing byproducts generated after exposure to a zinc-cyclen organometallic homogeneous catalyst.

Phytochemical Characterization of an Adaptogenic Preparation from Rhodiola heterodonta

PubMed Central

Grace, Mary H.; Yousef, Gad G.; Kurmukov, Anvar G.; Raskin, Ilya; Lila, Mary Ann

2013-01-01

The phytochemical constituents of a biologically active, standardized, 80% ethanol extract of Rhodiola heterodonta were characterized. The extract was fractionated over a Sephadex LH-20 column to afford two main fractions representing two classes of secondary metabolites: phenylethanoids and proanthocyanidins. This fractionation facilitated the identification and quantification of individual compounds in the fractions and sub-fractions using HPLC, and LC-MS. The major compounds in the phenylethanoid fraction were heterodontoside, tyrosol methyl ether, salidroside, viridoside, mongrhoside, tyrosol, and the cyanogenic glucoside rhodiocyanoside A. These seven compounds comprised 17.4% of the EtOH extract. Proanthocyanidins ranged from oligomers to polymers based on epigallocatechin and gallate units. The main identified oligomeric compounds in the proanthocyanidin fraction were epigallocatechin gallate, epigallocatechin-epigallocatechin-3-O-gallate and 3-O-galloylepigallocatechin-epigallocatechin-3-O-gallate, which constituted 1.75% of the ethanol extract. Tyrosol methyl ether, mongrhoside, and the two proanthocyanidin dimers were reported for the first time from this species in this study. Intraperitoneal injection of the 80% ethanol extract increased survival time of mice under hypoxia by 192%, as an indication of adaptogenic activity. PMID:19768982

Combinatorial support vector machines approach for virtual screening of selective multi-target serotonin reuptake inhibitors from large compound libraries.

PubMed

Shi, Z; Ma, X H; Qin, C; Jia, J; Jiang, Y Y; Tan, C Y; Chen, Y Z

2012-02-01

Selective multi-target serotonin reuptake inhibitors enhance antidepressant efficacy. Their discovery can be facilitated by multiple methods, including in silico ones. In this study, we developed and tested an in silico method, combinatorial support vector machines (COMBI-SVMs), for virtual screening (VS) multi-target serotonin reuptake inhibitors of seven target pairs (serotonin transporter paired with noradrenaline transporter, H(3) receptor, 5-HT(1A) receptor, 5-HT(1B) receptor, 5-HT(2C) receptor, melanocortin 4 receptor and neurokinin 1 receptor respectively) from large compound libraries. COMBI-SVMs trained with 917-1951 individual target inhibitors correctly identified 22-83.3% (majority >31.1%) of the 6-216 dual inhibitors collected from literature as independent testing sets. COMBI-SVMs showed moderate to good target selectivity in misclassifying as dual inhibitors 2.2-29.8% (majority <15.4%) of the individual target inhibitors of the same target pair and 0.58-7.1% of the other 6 targets outside the target pair. COMBI-SVMs showed low dual inhibitor false hit rates (0.006-0.056%, 0.042-0.21%, 0.2-4%) in screening 17 million PubChem compounds, 168,000 MDDR compounds, and 7-8181 MDDR compounds similar to the dual inhibitors. Compared with similarity searching, k-NN and PNN methods, COMBI-SVM produced comparable dual inhibitor yields, similar target selectivity, and lower false hit rate in screening 168,000 MDDR compounds. The annotated classes of many COMBI-SVMs identified MDDR virtual hits correlate with the reported effects of their predicted targets. COMBI-SVM is potentially useful for searching selective multi-target agents without explicit knowledge of these agents. Copyright © 2011 Elsevier Inc. All rights reserved.

Analysis of volatile compounds in exhaled breath condensate in patients with severe pulmonary arterial hypertension.

PubMed

Mansoor, J K; Schelegle, Edward S; Davis, Cristina E; Walby, William F; Zhao, Weixiang; Aksenov, Alexander A; Pasamontes, Alberto; Figueroa, Jennifer; Allen, Roblee

2014-01-01

An important challenge to pulmonary arterial hypertension (PAH) diagnosis and treatment is early detection of occult pulmonary vascular pathology. Symptoms are frequently confused with other disease entities that lead to inappropriate interventions and allow for progression to advanced states of disease. There is a significant need to develop new markers for early disease detection and management of PAH. Exhaled breath condensate (EBC) samples were compared from 30 age-matched normal healthy individuals and 27 New York Heart Association functional class III and IV idiopathic pulmonary arterial hypertenion (IPAH) patients, a subgroup of PAH. Volatile organic compounds (VOC) in EBC samples were analyzed using gas chromatography/mass spectrometry (GC/MS). Individual peaks in GC profiles were identified in both groups and correlated with pulmonary hemodynamic and clinical endpoints in the IPAH group. Additionally, GC/MS data were analyzed using autoregression followed by partial least squares regression (AR/PLSR) analysis to discriminate between the IPAH and control groups. After correcting for medicaitons, there were 62 unique compounds in the control group, 32 unique compounds in the IPAH group, and 14 in-common compounds between groups. Peak-by-peak analysis of GC profiles of IPAH group EBC samples identified 6 compounds significantly correlated with pulmonary hemodynamic variables important in IPAH diagnosis. AR/PLSR analysis of GC/MS data resulted in a distinct and identifiable metabolic signature for IPAH patients. These findings indicate the utility of EBC VOC analysis to discriminate between severe IPAH and a healthy population; additionally, we identified potential novel biomarkers that correlated with IPAH pulmonary hemodynamic variables that may be important in screening for less severe forms IPAH.

Analysis of Volatile Compounds in Exhaled Breath Condensate in Patients with Severe Pulmonary Arterial Hypertension

PubMed Central

Mansoor, J. K.; Schelegle, Edward S.; Davis, Cristina E.; Walby, William F.; Zhao, Weixiang; Aksenov, Alexander A.; Pasamontes, Alberto; Figueroa, Jennifer; Allen, Roblee

2014-01-01

Background An important challenge to pulmonary arterial hypertension (PAH) diagnosis and treatment is early detection of occult pulmonary vascular pathology. Symptoms are frequently confused with other disease entities that lead to inappropriate interventions and allow for progression to advanced states of disease. There is a significant need to develop new markers for early disease detection and management of PAH. Methodolgy and Findings Exhaled breath condensate (EBC) samples were compared from 30 age-matched normal healthy individuals and 27 New York Heart Association functional class III and IV idiopathic pulmonary arterial hypertenion (IPAH) patients, a subgroup of PAH. Volatile organic compounds (VOC) in EBC samples were analyzed using gas chromatography/mass spectrometry (GC/MS). Individual peaks in GC profiles were identified in both groups and correlated with pulmonary hemodynamic and clinical endpoints in the IPAH group. Additionally, GC/MS data were analyzed using autoregression followed by partial least squares regression (AR/PLSR) analysis to discriminate between the IPAH and control groups. After correcting for medicaitons, there were 62 unique compounds in the control group, 32 unique compounds in the IPAH group, and 14 in-common compounds between groups. Peak-by-peak analysis of GC profiles of IPAH group EBC samples identified 6 compounds significantly correlated with pulmonary hemodynamic variables important in IPAH diagnosis. AR/PLSR analysis of GC/MS data resulted in a distinct and identifiable metabolic signature for IPAH patients. Conclusions These findings indicate the utility of EBC VOC analysis to discriminate between severe IPAH and a healthy population; additionally, we identified potential novel biomarkers that correlated with IPAH pulmonary hemodynamic variables that may be important in screening for less severe forms IPAH. PMID:24748102

Precursors to radiopharmaceutical agents for tissue imaging

DOEpatents

Srivastava, Prem C.; Knapp, Jr., Furn F.

1988-01-01

A class of radiolabeled compounds to be used in tissue imaging that exhibits rapid brain uptake, good brain:blood radioactivity ratios, and long retention times. The imaging agents are more specifically radioiodinated aromatic amines attached to dihydropyridine carriers, that exhibit heart as well as brain specificity. In addition to the radiolabeled compounds, classes of compounds are also described that are used as precursors and intermediates in the preparation of the imaging agents.

Better End-Cap Processing for Oxidation-Resistant Polyimides

NASA Technical Reports Server (NTRS)

Meador, Mary Ann B.; Frimer, Aryeh A.

2004-01-01

A class of end-cap compounds that increase the thermo-oxidative stab ility of polyimides of the polymerization of monomeric reactants (PM R) type has been extended. In addition, an improved processing proto col for this class of end-cap compounds has been invented.

Pain: Systematic Review of Pharmacy Compounding of Pain Medication.

PubMed

Shawaqfeh, Mohammad S; Harrington, Catherine

2018-01-01

There are limited resources available for pharmacists and doctors to reference proper compounded formulas for pain medications. The systematic review discussed within this article provides the foundation for a searchable database, allowing users to find various compounded formulations. It also provides data about the safety and efficacy of the preparations. Compounding information about several drug classes was reviewed. Those drug classes included, but were not limited to, opioids, non-steroidal anti-inflammatory drugs, central nervous system agents, and anesthetics, with evidence that of the various drugs that could be compounded for pain, anesthetics, non-steroidal anti-inflammatory drugs, and opioids ranked highest within the articles researched. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Is scaffold hopping a reliable indicator for the ability of computational methods to identify structurally diverse active compounds?

NASA Astrophysics Data System (ADS)

Dimova, Dilyana; Bajorath, Jürgen

2017-07-01

Computational scaffold hopping aims to identify core structure replacements in active compounds. To evaluate scaffold hopping potential from a principal point of view, regardless of the computational methods that are applied, a global analysis of conventional scaffolds in analog series from compound activity classes was carried out. The majority of analog series was found to contain multiple scaffolds, thus enabling the detection of intra-series scaffold hops among closely related compounds. More than 1000 activity classes were found to contain increasing proportions of multi-scaffold analog series. Thus, using such activity classes for scaffold hopping analysis is likely to overestimate the scaffold hopping (core structure replacement) potential of computational methods, due to an abundance of artificial scaffold hops that are possible within analog series.

Linopirdine. A depolarization-activated releaser of transmitters for treatment of dementia.

PubMed

Tam, S W; Zaczek, R

1995-01-01

Linopirdine (DuP 996, AVIVA), currently in Phase III clinical trial for the treatment of Alzheimer's disease, is a representative of a class of novel molecules which enhances the stimulus-evoked but not basal release of several neurotransmitters including ACh, DA, 5-HT and Glu. Linopiridine has been shown to enhance ACh release in the hippocampus in vivo. In addition, linopiridine produces a number of effects including EEG patterns of enhanced vigilance, induction of c-fos expression in cerebral cortex, reduction of the increase of cerebral glucose utilization induced by hypoxia, and improved performance in animal models of learning and memory. The specific action of linopiridine on depolarized neurons but not on basal release suggests that compounds of this class will enhance normal brain activity and not lead to a non-specific activation. Furthermore, the effect of linopiridine on multiple neurotransmitter systems that are deficient in Alzheimer's disease suggests that this class of agents may be more efficacious in the treatment of dementia than therapies aimed at individual neurotransmitters systems.

Multiple Classes of Environmental Chemicals are Associated ...

EPA Pesticide Factsheets

Biomonitoring of human tissues and fluids has shown that virtually all individuals, worldwide, carry a “body burden” of synthetic chemicals (Thornton et al. 2002; CDC 2009). Although the measurement of an environmental chemical in a person’s tissues or fluids is an indication of exposure, it does not by itself mean that the chemical or the exposure concentration is sufficient to cause a disease or an adverse effect. However, since humans are exposed to multiple chemicals, there may be a combination effect (e.g., additive, synergistic) on health risks associated with exposure even at low levels (Kortenkamp 2008). Further, biomonitoring studies show that humans carry a body burden of multiple classes of contaminants which are often not studied together. We used the 2003-2006 National Health and Nutrition Examination Survey to evaluate the relationship between alanine aminotransferase (ALT) and 53 environmental contaminants across six classes (metals; perfluorinated compounds [PFCs]; phthalates; phenols; coplanar and non-dioxin-like polychlorinated biphenyls [PCBs]) using a novel method.

QSAR modeling and chemical space analysis of antimalarial compounds

NASA Astrophysics Data System (ADS)

Sidorov, Pavel; Viira, Birgit; Davioud-Charvet, Elisabeth; Maran, Uko; Marcou, Gilles; Horvath, Dragos; Varnek, Alexandre

2017-05-01

Generative topographic mapping (GTM) has been used to visualize and analyze the chemical space of antimalarial compounds as well as to build predictive models linking structure of molecules with their antimalarial activity. For this, a database, including 3000 molecules tested in one or several of 17 anti- Plasmodium activity assessment protocols, has been compiled by assembling experimental data from in-house and ChEMBL databases. GTM classification models built on subsets corresponding to individual bioassays perform similarly to the earlier reported SVM models. Zones preferentially populated by active and inactive molecules, respectively, clearly emerge in the class landscapes supported by the GTM model. Their analysis resulted in identification of privileged structural motifs of potential antimalarial compounds. Projection of marketed antimalarial drugs on this map allowed us to delineate several areas in the chemical space corresponding to different mechanisms of antimalarial activity. This helped us to make a suggestion about the mode of action of the molecules populating these zones.

QSAR modeling and chemical space analysis of antimalarial compounds.

PubMed

Sidorov, Pavel; Viira, Birgit; Davioud-Charvet, Elisabeth; Maran, Uko; Marcou, Gilles; Horvath, Dragos; Varnek, Alexandre

2017-05-01

Generative topographic mapping (GTM) has been used to visualize and analyze the chemical space of antimalarial compounds as well as to build predictive models linking structure of molecules with their antimalarial activity. For this, a database, including ~3000 molecules tested in one or several of 17 anti-Plasmodium activity assessment protocols, has been compiled by assembling experimental data from in-house and ChEMBL databases. GTM classification models built on subsets corresponding to individual bioassays perform similarly to the earlier reported SVM models. Zones preferentially populated by active and inactive molecules, respectively, clearly emerge in the class landscapes supported by the GTM model. Their analysis resulted in identification of privileged structural motifs of potential antimalarial compounds. Projection of marketed antimalarial drugs on this map allowed us to delineate several areas in the chemical space corresponding to different mechanisms of antimalarial activity. This helped us to make a suggestion about the mode of action of the molecules populating these zones.

A diversity oriented synthesis of natural product inspired molecular libraries.

PubMed

Chauhan, Jyoti; Luthra, Tania; Gundla, Rambabu; Ferraro, Antonio; Holzgrabe, Ulrike; Sen, Subhabrata

2017-11-07

Natural products are the source of innumerable pharmaceutical drug candidates and also form an important aspect of herbal remedies. They are also a source of various bioactive compounds. Herein we have leveraged the structural attributes of several natural products in building a library of architecturally diverse chiral molecules by harnessing R-tryptophan as the chiral auxiliary. It is converted to its corresponding methyl ester 1 which in turn provided a bevy of 1-aryl-tetrahydro-β-carbolines 2a-d, which were then converted to chiral compounds via a diversity oriented synthetic strategy (DOS). In general, intermolecular and intramolecular ring rearrangements facilitated the formation of the final compounds. Four different classes of molecules with distinct architectures were generated, adding up to nearly twenty-two individual molecules. Phenotypic screening of a representative section of the library revealed two molecules that selectively inhibit MCF7 breast cancer cells with IC 50 of ∼5 μg mL -1 potency.

Heat generated by Er:YAG laser in the pulp chamber of teeth submitted to removal of dental tissue and composite resin

NASA Astrophysics Data System (ADS)

Zanin, Fatima; Brugnera, Aldo, Jr.; Pecora, Jesus D.; Pinheiro, Antonio; Spano, Julio; Barbin, Eduardo; Marchesan, Melissa A.

2004-05-01

The knowledge about and control of thermal energy produced by Er:YAG laser after irradiating hard dental tissues and compound resin is important because the pulp, like all vital biological tissue, has a certain capacity for supporting stimulus. The objective of this study was to analyze the thermal variation generated by Er:YAG laser (λ=2.94μm) during the preparation of a Class I cavity in the dental structure and in the removal of microhybrid Z100 (3M) compound resin. An evaluation was made of 30 maxillary human pre-molar teeth from the bank of the Endodontic Laboratory Center of Ribeirao Preto Dental School, Brasil. The sample was divided into 6 groups of 5 teeth each: Group 1, preparation of Class I cavity with Er:YAG laser (350mJ, 3Hz, 343 impulses, 120J, 113 seconds); Group 2, preparation of Class I cavity with Er:YAG laser (350mJ, 4Hz, 343 impulses, 120J, 81 seconds); Group 3, preparation of Class I cavity with Er:YAG laser (350mJ, 6Hz, 343 impulses, 120J, 58 seconds); Group 4, removal of compound resin from Class I preparation with Er:YAG laser (350mJ, 3Hz, 258 impulses, 90J, 85 seconds); Group 5, removal of compound resin from Class I preparation with Er:YAG laser (350mJ, 4Hz, 258 impulses, 90J, 67 seconds); Group 6, removal of compound resin from Class I preparation with Er:YAG laser (350mJ, 6Hz, 258 impulses, 42 seconds). The laser used was KaVo Key 2 (Biberach, Germany), λ=2,94μm, P=3 Watts, pulse duration of 250μs, with air-water cooling. The increase in temperature during dental preparation and the removal of the compound resin was evaluated by means of a Tektronix DMM916 Thermocouple (Consitec, Brasil). The results showed that the application of laser for the removal of the hard dental tissues and for the removal of compound resins with the pulse frequencies 3, 4 and 6 Hz did not generate heating greater than 3.1°C and remained within the histopathological limits permitted for pulp tissue (5.5°C) and there was a significant statistical difference between the heat generated by the application of laser in the removal of the hard dental tissues and in the removal of compound resins (p<0.01). The average increase in temperature of the compound resin component was greater than the tooth.

The Generation of Diazo Compounds in Continuous-Flow.

PubMed

Hock, Katharina J; Koenigs, Rene M

2018-03-25

Toxic, cancerogenic and explosive - these attributes are typically associated with diazo compounds. Nonetheless, diazo compounds are nowadays a highly demanded class of reagents for organic synthesis, yet the concerns with regards to safe and scalable transformations of these compounds are still exceptionally high. Lately, the research area of the continuous-flow synthesis of diazo compounds attracted significant interest and a whole variety of protocols for their "on-demand" preparation have been realized to date. This concept article focuses on the recent developments using continuous-flow technologies to access diazo compounds; thus minimizing risks and hazards when working with this particular class of compounds. In this article we discuss these concepts and highlight different pre-requisites to access and to perform downstream functionalization reaction. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

General Analytical Procedure for Determination of Acidity Parameters of Weak Acids and Bases

PubMed Central

Pilarski, Bogusław; Kaliszan, Roman; Wyrzykowski, Dariusz; Młodzianowski, Janusz; Balińska, Agata

2015-01-01

The paper presents a new convenient, inexpensive, and reagent-saving general methodology for the determination of pK a values for components of the mixture of diverse chemical classes weak organic acids and bases in water solution, without the need to separate individual analytes. The data obtained from simple pH-metric microtitrations are numerically processed into reliable pK a values for each component of the mixture. Excellent agreement has been obtained between the determined pK a values and the reference literature data for compounds studied. PMID:25692072

General analytical procedure for determination of acidity parameters of weak acids and bases.

PubMed

Pilarski, Bogusław; Kaliszan, Roman; Wyrzykowski, Dariusz; Młodzianowski, Janusz; Balińska, Agata

2015-01-01

The paper presents a new convenient, inexpensive, and reagent-saving general methodology for the determination of pK a values for components of the mixture of diverse chemical classes weak organic acids and bases in water solution, without the need to separate individual analytes. The data obtained from simple pH-metric microtitrations are numerically processed into reliable pK a values for each component of the mixture. Excellent agreement has been obtained between the determined pK a values and the reference literature data for compounds studied.

49 CFR 173.221 - Polymeric beads, expandable and Plastic molding compound.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 2 2011-10-01 2011-10-01 false Polymeric beads, expandable and Plastic molding... Than Class 1 and Class 7 § 173.221 Polymeric beads, expandable and Plastic molding compound. (a) Non-bulk shipments of Polymeric beads (or granules), expandable, evolving flammable vapor and Plastic...

49 CFR 173.221 - Polymeric beads, expandable and Plastic molding compound.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 2 2010-10-01 2010-10-01 false Polymeric beads, expandable and Plastic molding... Than Class 1 and Class 7 § 173.221 Polymeric beads, expandable and Plastic molding compound. (a) Non-bulk shipments of Polymeric beads (or granules), expandable, evolving flammable vapor and Plastic...

Understanding the tolerance of the industrial yeast Saccharomyces cerevisiae against a major class of toxic aldehyde compounds

USDA-ARS?s Scientific Manuscript database

Development of the next-generation biocatalyst is vital for fermentation-based industrial applications and a sustainable bio-based economy. Overcoming the major class of toxic compounds associated with lignocellulose-to-biofuels conversion is one of the significant challenges for new strain developm...

49 CFR 173.221 - Polymeric beads, expandable and Plastic molding compound.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 2 2012-10-01 2012-10-01 false Polymeric beads, expandable and Plastic molding... Than Class 1 and Class 7 § 173.221 Polymeric beads, expandable and Plastic molding compound. (a) Non-bulk shipments of Polymeric beads (or granules), expandable, evolving flammable vapor and Plastic...

49 CFR 173.221 - Polymeric beads, expandable and Plastic molding compound.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 2 2014-10-01 2014-10-01 false Polymeric beads, expandable and Plastic molding... Than Class 1 and Class 7 § 173.221 Polymeric beads, expandable and Plastic molding compound. (a) Non-bulk shipments of Polymeric beads (or granules), expandable evolving flammable vapor and Plastic...

49 CFR 173.221 - Polymeric beads, expandable and Plastic molding compound.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 2 2013-10-01 2013-10-01 false Polymeric beads, expandable and Plastic molding... Than Class 1 and Class 7 § 173.221 Polymeric beads, expandable and Plastic molding compound. (a) Non-bulk shipments of Polymeric beads (or granules), expandable evolving flammable vapor and Plastic...

A Screening Assay Based on Host-Pathogen Interaction Models Identifies a Set of Novel Antifungal Benzimidazole Derivatives▿

PubMed Central

Burger-Kentischer, Anke; Finkelmeier, Doris; Keller, Petra; Bauer, Jörg; Eickhoff, Holger; Kleymann, Gerald; Abu Rayyan, Walid; Singh, Anurag; Schröppel, Klaus; Lemuth, Karin; Wiesmüller, Karl-Heinz; Rupp, Steffen

2011-01-01

Fungal infections are a serious health problem in clinics, especially in the immune-compromised patient. Disease ranges from widespread superficial infections like vulvovaginal infections to life-threatening systemic candidiasis. Especially for systemic mycoses, only a limited arsenal of antifungals is available. The most commonly used classes of antifungal compounds used include azoles, polyenes, and echinocandins. Due to emerging resistance to standard therapy, significant side effects, and high costs for several antifungals, there is a medical need for new antifungals in the clinic and general practice. In order to expand the arsenal of compounds with antifungal activities, we screened a compound library including more than 35,000 individual compounds derived from organic synthesis as well as combinatorial compound collections representing mixtures of compounds for antimycotic activity. In total, more than 100,000 compounds were screened using a new type of activity-selectivity assay, analyzing both the antifungal activity and the compatibility with human cells at the same time. One promising hit, an (S)-2-aminoalkyl benzimidazole derivative, was developed among a series of lead compounds showing potent antifungal activity. (S)-2-(1-Aminoisobutyl)-1-(3-chlorobenzyl) benzimidazole showed the highest antifungal activity and the best compatibility with human cells in several cell culture models and against a number of clinical isolates of several species of pathogenic Candida yeasts. Transcriptional profiling indicates that the newly discovered compound is a potential inhibitor of the ergosterol pathway, in contrast to other benzimidazole derivatives, which target microtubules. PMID:21746957

Higher social class predicts increased unethical behavior.

PubMed

Piff, Paul K; Stancato, Daniel M; Côté, Stéphane; Mendoza-Denton, Rodolfo; Keltner, Dacher

2012-03-13

Seven studies using experimental and naturalistic methods reveal that upper-class individuals behave more unethically than lower-class individuals. In studies 1 and 2, upper-class individuals were more likely to break the law while driving, relative to lower-class individuals. In follow-up laboratory studies, upper-class individuals were more likely to exhibit unethical decision-making tendencies (study 3), take valued goods from others (study 4), lie in a negotiation (study 5), cheat to increase their chances of winning a prize (study 6), and endorse unethical behavior at work (study 7) than were lower-class individuals. Mediator and moderator data demonstrated that upper-class individuals' unethical tendencies are accounted for, in part, by their more favorable attitudes toward greed.

Acute bioassays and hazard evaluation of representative contaminants detected in Great Lakes fish

USGS Publications Warehouse

Passino, Dora R. May; Smith, Stephen B.

1987-01-01

We have provided a hazard ranking for 19 classes of compounds representing many of the nearly 500 organic compounds identified by gas chromatography-mass spectrometry in lake trout (Salvelinus namaycush) and walleye (Stizostedion vitreum vitreum) from the Great Lakes and Lake St. Clair. We initially made a provisional hazard ranking based on available published and unpublished information on aquatic toxicity, bioaccumulation, occurrence and sources. Acute toxicity tests with Daphnia pulex at 17A°C in reconstituted hard water were performed with 30 compounds representative of the 19 classes that were highest in the provisional ranking. The resulting toxicity data, along with information on the compounds' occurrence in Great Lakes fish and their sources, were ranked and weighted and then used in calculating the revised hazard ranking. The 10 most hazardous classes, in descending order, are as follows (values shown are mean 48-h EC50s, in μ/ml): arene halides (e.g., polychlorinated biphenyls, DDT), 0.0011; phthalate esters, 0.133; chlorinated camphenes (toxaphene), 0.0082; polyaromatic hydrocarbons (PAHs; e.g., dimethylnaphthalene) and reduced derivatives, 1.01; chlorinated fused polycyclics (e.g., trans-nonachlor), 0.022; nitrogen-containing compounds (e.g., O-methylhydroxyl-amine), 1.35; alkyl halides (e.g., (bromomethyl)cyclohexene), 10.1; cyclic alkanes (e.g., cyclododecane), 20.9; silicon-containing compounds (e.g., dimethyldiethoxy silane), 1.25; and heterocyclic nitrogen compounds (e.g., nicotine), 2.48. We recommend that chronic bioassays be conducted with fish and invertebrates to determine the sublethal effects of the following classes of compounds, for which few toxicity data are available: PAHs, heterocyclic nitrogen compounds, other nitrogen-containing compounds, alkyl halides, cyclic alkanes and silicon-containing compounds. Information from these types of studies will aid researchers in determining the possible causal role these contaminants play in the decline and reproductive impairment of Great Lakes fish.

Current and evolving approaches for improving the oral permeability of BCS Class III or analogous molecules.

PubMed

Dave, Vivek S; Gupta, Deepak; Yu, Monica; Nguyen, Phuong; Varghese Gupta, Sheeba

2017-02-01

The Biopharmaceutics Classification System (BCS) classifies pharmaceutical compounds based on their aqueous solubility and intestinal permeability. The BCS Class III compounds are hydrophilic molecules (high aqueous solubility) with low permeability across the biological membranes. While these compounds are pharmacologically effective, poor absorption due to low permeability becomes the rate-limiting step in achieving adequate bioavailability. Several approaches have been explored and utilized for improving the permeability profiles of these compounds. The approaches include traditional methods such as prodrugs, permeation enhancers, ion-pairing, etc., as well as relatively modern approaches such as nanoencapsulation and nanosizing. The most recent approaches include a combination/hybridization of one or more traditional approaches to improve drug permeability. While some of these approaches have been extremely successful, i.e. drug products utilizing the approach have progressed through the USFDA approval for marketing; others require further investigation to be applicable. This article discusses the commonly studied approaches for improving the permeability of BCS Class III compounds.

Social-class differences in self-concept clarity and their implications for well-being

PubMed Central

Na, Jinkyung; Chan, Micaela Y.; Lodi-Smith, Jennifer; Park, Denise C.

2017-01-01

A consistent/stable sense of the self is more valued in middle-class contexts than working-class contexts; hence we predicted that middle-class individuals would have higher SCC than working-class individuals. It is further expected that SCC would be more important to one’s well-being among middle-class individuals than among working-class individuals. Supporting these predictions, SCC was positively associated with higher social-class. Moreover, although SCC was associated with higher life satisfaction and better mental health, the association significantly attenuated among working-class individuals. In addition, SCC was not associated with physical health and its association with physical health did not interact with social class. PMID:27114215

Deposit formation in liquid fuels. II - The effect of selected compounds on the storage stability of Jet A turbine fuel

NASA Technical Reports Server (NTRS)

Worstell, J. H.; Daniel, S. R.

1981-01-01

The influence of substituted pyridines, pyrroles, indoles, and quinolines on the storage stability of conventional Jet A turbine fuel is evaluated. Significant increases in the amount of deposit formed in accelerated storage tests are found upon addition of these compounds at levels as low as one ppm nitrogen. While the effect is correlated with basicity of the nitrogen compound within a given compound class, the correlation does not hold between classes (pyridines, quinolines, etc.). Steric hindrance at the nitrogen atom greatly inhibits deposit promotion. The characteristics, but not the elemental composition, of deposits vary with the identity of the added nitrogen compound and with deposition temperature.

New insights into the parametrization of temperature and light responses of mono - and sesquiterpene emissions from Aleppo pine and rosemary

NASA Astrophysics Data System (ADS)

Staudt, M.; Bourgeois, I.; Al Halabi, R.; Song, W.; Williams, J.

2017-03-01

Phytogenic emission of large volatile organic compounds (VOCs) such as monoterpenes (MTs) and sesquiterpenes (SQTs) are key precursors to the formation and growth of atmospheric particles. However, controlled environment studies to elucidate emission responses to temperature and light are still sparse. In this study, the volatile contents and emission responses of Aleppo pine and Rosemary have been investigated. These two common Mediterranean species store semivolatiles inside (resin ducts) and outside (trichomes) their foliage tissues respectively. Both species emitted mainly MTs with basal emission rates of around 5 (Rosemary) and 10 (pine) μg g-1 h-1 and SQTs about one order of magnitude lower. In Aleppo pine, two volatile sources could be clearly distinguished: 1) de-novo synthesized emission of (E)-β-ocimene and linalool, which accounted for about 70% of the total VOC release, were not found in foliar VOC extracts and expressed light dependency (LD) and temperature responses typical for enzyme driven emissions; and 2) storage-derived emissions of various MTs and SQTs whose emissions increased exponentially with temperature, showed no light dependency and were all present in leaf extracts. In Rosemary, all emitted MTs and SQTs including many oxygenated compounds, showed responses typical for stored volatiles and were all found in leaf extracts. The emissions of individual volatiles or volatile classes could be well described with the commonly applied empirical algorithms developed for LD or non LD emissions. However, the shapes of the temperature responses, and hence the deduced coefficient values, were significantly different between oxygenated and non-oxygenated compounds. They also differed between the storage-derived emissions of the two plant species, for individual VOCs or VOC classes. We address the possible reasons for this variation in temperature responses and argue that they are mostly due to molecular interactions along the species specific leaf-internal diffusion paths including the build-up of transient VOC pools and degradation.

Detection and formation scenario of citric acid, pyruvic acid, and other possible metabolism precursors in carbonaceous meteorites

PubMed Central

Cooper, George; Reed, Chris; Nguyen, Dang; Carter, Malika; Wang, Yi

2011-01-01

Carbonaceous meteorites deliver a variety of organic compounds to Earth that may have played a role in the origin and/or evolution of biochemical pathways. Some apparently ancient and critical metabolic processes require several compounds, some of which are relatively labile such as keto acids. Therefore, a prebiotic setting for any such individual process would have required either a continuous distant source for the entire suite of intact precursor molecules and/or an energetic and compact local synthesis, particularly of the more fragile members. To date, compounds such as pyruvic acid, oxaloacetic acid, citric acid, isocitric acid, and α-ketoglutaric acid (all members of the citric acid cycle) have not been identified in extraterrestrial sources or, as a group, as part of a “one pot” suite of compounds synthesized under plausibly prebiotic conditions. We have identified these compounds and others in carbonaceous meteorites and/or as low temperature (laboratory) reaction products of pyruvic acid. In meteorites, we observe many as part of three newly reported classes of compounds: keto acids (pyruvic acid and homologs), hydroxy tricarboxylic acids (citric acid and homologs), and tricarboxylic acids. Laboratory syntheses using 13C-labeled reactants demonstrate that one compound alone, pyruvic acid, can produce several (nonenzymatic) members of the citric acid cycle including oxaloacetic acid. The isotopic composition of some of the meteoritic keto acids points to interstellar or presolar origins, indicating that such compounds might also exist in other planetary systems. PMID:21825143

Detection and formation scenario of citric acid, pyruvic acid, and other possible metabolism precursors in carbonaceous meteorites.

PubMed

Cooper, George; Reed, Chris; Nguyen, Dang; Carter, Malika; Wang, Yi

2011-08-23

Carbonaceous meteorites deliver a variety of organic compounds to Earth that may have played a role in the origin and/or evolution of biochemical pathways. Some apparently ancient and critical metabolic processes require several compounds, some of which are relatively labile such as keto acids. Therefore, a prebiotic setting for any such individual process would have required either a continuous distant source for the entire suite of intact precursor molecules and/or an energetic and compact local synthesis, particularly of the more fragile members. To date, compounds such as pyruvic acid, oxaloacetic acid, citric acid, isocitric acid, and α-ketoglutaric acid (all members of the citric acid cycle) have not been identified in extraterrestrial sources or, as a group, as part of a "one pot" suite of compounds synthesized under plausibly prebiotic conditions. We have identified these compounds and others in carbonaceous meteorites and/or as low temperature (laboratory) reaction products of pyruvic acid. In meteorites, we observe many as part of three newly reported classes of compounds: keto acids (pyruvic acid and homologs), hydroxy tricarboxylic acids (citric acid and homologs), and tricarboxylic acids. Laboratory syntheses using (13)C-labeled reactants demonstrate that one compound alone, pyruvic acid, can produce several (nonenzymatic) members of the citric acid cycle including oxaloacetic acid. The isotopic composition of some of the meteoritic keto acids points to interstellar or presolar origins, indicating that such compounds might also exist in other planetary systems.

Hydrothermal liquefaction oil and hydrotreated product from pine feedstock characterized by heteronuclear two-dimensional NMR spectroscopy and FT-ICR mass spectrometry

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

Sudasinghe, Nilusha; Cort, John R.; Hallen, Richard

2014-12-01

Hydrothermal liquefaction (HTL) crude oil and hydrotreated product from pine tree farm waste (forest product residual, FPR) have been analyzed by direct infusion electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI FT-ICR MS) in both positive- and negative-ionization modes and high-resolution twodimensional heteronuclear 1H-13C NMR spectroscopy. FT-ICR MS resolves thousands of compounds in complex oils and provides unparalleled compositional details for individual molecules for identification of compound class (heteroatom content), type (number of rings plus double bonds to carbon or double bond equivalents (DBE) and carbon number (degree of alkylation). Heteronuclear 1H-13C NMR spectroscopy provides one-bond and multiple-bondmore » correlations between pairs of 1H and 13C chemical shifts that are characteristic of different organic functional groups. Taken together this information provides a picture of the chemical composition of these oils. Pyrolysis crude oil product from pine wood was characterized for comparison. Generally, pyrolysis oil is comprised of a more diverse distribution of heteroatom classes with higher oxygen number relative to HTL oil as shown by both positive- and negative-ion ESI FT-ICR MS. A total of 300 N1, 594 O1 and 267 O2 compounds were observed as products of hydrotreatment. The relative abundance of N1O1, N1O2, N1O3, N2, N2O1, N2O2 and O3 compounds are reduced to different degrees after hydrotreatment and other higher heteroatom containing species (O4-O10, N1O4, N1O5 and N2O3) are completely removed by hydrotreatment.« less

Lay theories about social class buffer lower-class individuals against poor self-rated health and negative affect.

PubMed

Tan, Jacinth J X; Kraus, Michael W

2015-03-01

The economic conditions of one's life can profoundly and systematically influence health outcomes over the life course. Our present research demonstrates that rejecting the notion that social class categories are biologically determined-a nonessentialist belief-buffers lower-class individuals from poor self-rated health and negative affect, whereas conceiving of social class categories as rooted in biology-an essentialist belief-does not. In Study 1, lower-class individuals self-reported poorer health than upper-class individuals when they endorsed essentialist beliefs but showed no such difference when they rejected such beliefs. Exposure to essentialist theories of social class also led lower-class individuals to report greater feelings of negative self-conscious emotions (Studies 2 and 3), and perceive poorer health (Study 3) than upper-class individuals, whereas exposure to nonessentialist theories did not lead to such differences. Discussion considers how lay theories of social class potentially shape long-term trajectories of health and affect of lower-class individuals. © 2015 by the Society for Personality and Social Psychology, Inc.

NEW FRONTIERS IN DRUGGABILITY

PubMed Central

Kozakov, Dima; Hall, David R.; Napoleon, Raeanne L.; Yueh, Christine; Whitty, Adrian; Vajda, Sandor

2016-01-01

A powerful early approach to evaluating the druggability of proteins involved determining the hit rate in NMR-based screening of a library of small compounds. Here we show that a computational analog of this method, based on mapping proteins using small molecules as probes, can reliably reproduce druggability results from NMR-based screening, and can provide a more meaningful assessment in cases where the two approaches disagree. We apply the method to a large set of proteins. The results show that, because the method is based on the biophysics of binding rather than on empirical parameterization, meaningful information can be gained about classes of proteins and classes of compounds beyond those resembling validated targets and conventionally druglike ligands. In particular, the method identifies targets that, while not druggable by druglike compounds, may become druggable using compound classes such as macrocycles or other large molecules beyond the rule-of-five limit. PMID:26230724

Chemical Space Mapping and Structure-Activity Analysis of the ChEMBL Antiviral Compound Set.

PubMed

Klimenko, Kyrylo; Marcou, Gilles; Horvath, Dragos; Varnek, Alexandre

2016-08-22

Curation, standardization and data fusion of the antiviral information present in the ChEMBL public database led to the definition of a robust data set, providing an association of antiviral compounds to seven broadly defined antiviral activity classes. Generative topographic mapping (GTM) subjected to evolutionary tuning was then used to produce maps of the antiviral chemical space, providing an optimal separation of compound families associated with the different antiviral classes. The ability to pinpoint the specific spots occupied (responsibility patterns) on a map by various classes of antiviral compounds opened the way for a GTM-supported search for privileged structural motifs, typical for each antiviral class. The privileged locations of antiviral classes were analyzed in order to highlight underlying privileged common structural motifs. Unlike in classical medicinal chemistry, where privileged structures are, almost always, predefined scaffolds, privileged structural motif detection based on GTM responsibility patterns has the decisive advantage of being able to automatically capture the nature ("resolution detail"-scaffold, detailed substructure, pharmacophore pattern, etc.) of the relevant structural motifs. Responsibility patterns were found to represent underlying structural motifs of various natures-from very fuzzy (groups of various "interchangeable" similar scaffolds), to the classical scenario in medicinal chemistry (underlying motif actually being the scaffold), to very precisely defined motifs (specifically substituted scaffolds).

Metabolomics and Ionomics of Potato Tuber Reveals an Influence of Cultivar and Market Class on Human Nutrients and Bioactive Compounds

PubMed Central

Chaparro, Jacqueline M.; Holm, David G.; Broeckling, Corey D.; Prenni, Jessica E.; Heuberger, Adam L.

2018-01-01

Potato (Solanum tuberosum L.) is an important global food crop that contains phytochemicals with demonstrated effects on human health. Understanding sources of chemical variation of potato tuber can inform breeding for improved health attributes of the cooked food. Here, a comprehensive metabolomics (UPLC- and GC-MS) and ionomics (ICP-MS) analysis of raw and cooked potato tuber was performed on 60 unique potato genotypes that span 5 market classes including russet, red, yellow, chip, and specialty potatoes. The analyses detected 2,656 compounds that included known bioactives (43 compounds), nutrients (42), lipids (76), and 23 metals. Most nutrients and bioactives were partially degraded during cooking (44 out of 85; 52%), however genotypes with high quantities of bioactives remained highest in the cooked tuber. Chemical variation was influenced by genotype and market class. Specifically, ~53% of all detected compounds from cooked potato varied among market class and 40% varied by genotype. The most notable metabolite profiles were observed in yellow-flesh potato which had higher levels of carotenoids and specialty potatoes which had the higher levels of chlorogenic acid as compared to the other market classes. Variation in several molecules with known association to health was observed among market classes and included vitamins (e.g., pyridoxal, ~2-fold variation), bioactives (e.g., chlorogenic acid, ~40-fold variation), medicinals (e.g., kukoamines, ~6-fold variation), and minerals (e.g., calcium, iron, molybdenum, ~2-fold variation). Furthermore, more metabolite variation was observed within market class than among market class (e.g., α-tocopherol, ~1-fold variation among market class vs. ~3-fold variation within market class). Taken together, the analysis characterized significant metabolite and mineral variation in raw and cooked potato tuber, and support the potential to breed new cultivars for improved health traits. PMID:29876353

Compounds affecting cholesterol absorption

NASA Technical Reports Server (NTRS)

Koo, Sung I. (Inventor); Noh, Sang K. (Inventor); Hua, Duy H. (Inventor)

2004-01-01

A class of novel compounds is described for use in affecting lymphatic absorption of cholesterol. Compounds of particular interest are defined by Formula I: ##STR1## or a pharmaceutically acceptable salt thereof.

Incipient class II mixed valency in a plutonium solid-state compound

NASA Astrophysics Data System (ADS)

Cary, Samantha K.; Galley, Shane S.; Marsh, Matthew L.; Hobart, David L.; Baumbach, Ryan E.; Cross, Justin N.; Stritzinger, Jared T.; Polinski, Matthew J.; Maron, Laurent; Albrecht-Schmitt, Thomas E.

2017-09-01

Electron transfer in mixed-valent transition-metal complexes, clusters and materials is ubiquitous in both natural and synthetic systems. The degree to which intervalence charge transfer (IVCT) occurs, dependent on the degree of delocalization, places these within class II or III of the Robin-Day system. In contrast to the d-block, compounds of f-block elements typically exhibit class I behaviour (no IVCT) because of localization of the valence electrons and poor spatial overlap between metal and ligand orbitals. Here, we report experimental and computational evidence for delocalization of 5f electrons in the mixed-valent PuIII/PuIV solid-state compound, Pu3(DPA)5(H2O)2 (DPA = 2,6-pyridinedicarboxylate). The properties of this compound are benchmarked by the pure PuIII and PuIV dipicolinate complexes, [PuIII(DPA)(H2O)4]Br and PuIV(DPA)2(H2O)3·3H2O, as well as by a second mixed-valent compound, PuIII[PuIV(DPA)3H0.5]2, that falls into class I instead. Metal-to-ligand charge transfer is involved in both the formation of Pu3(DPA)5(H2O)2 and in the IVCT.

Social-class differences in self-concept clarity and their implications for well-being.

PubMed

Na, Jinkyung; Chan, Micaela Y; Lodi-Smith, Jennifer; Park, Denise C

2018-06-01

A consistent/stable sense of the self is more valued in middle-class contexts than working-class contexts; hence, we predicted that middle-class individuals would have higher self-concept clarity than working-class individuals. It is further expected that self-concept clarity would be more important to one's well-being among middle-class individuals than among working-class individuals. Supporting these predictions, self-concept clarity was positively associated with higher social class. Moreover, although self-concept clarity was associated with higher life satisfaction and better mental health, the association significantly attenuated among working-class individuals. In addition, self-concept clarity was not associated with physical health and its association with physical health did not interact with social class.

Higher social class predicts increased unethical behavior

PubMed Central

Piff, Paul K.; Stancato, Daniel M.; Côté, Stéphane; Mendoza-Denton, Rodolfo; Keltner, Dacher

2012-01-01

Seven studies using experimental and naturalistic methods reveal that upper-class individuals behave more unethically than lower-class individuals. In studies 1 and 2, upper-class individuals were more likely to break the law while driving, relative to lower-class individuals. In follow-up laboratory studies, upper-class individuals were more likely to exhibit unethical decision-making tendencies (study 3), take valued goods from others (study 4), lie in a negotiation (study 5), cheat to increase their chances of winning a prize (study 6), and endorse unethical behavior at work (study 7) than were lower-class individuals. Mediator and moderator data demonstrated that upper-class individuals’ unethical tendencies are accounted for, in part, by their more favorable attitudes toward greed. PMID:22371585

25 CFR 522.10 - Individually owned class II and class III gaming operations other than those operating on...

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 2 2010-04-01 2010-04-01 false Individually owned class II and class III gaming... GAMING COMMISSION, DEPARTMENT OF THE INTERIOR APPROVAL OF CLASS II AND CLASS III ORDINANCES AND RESOLUTIONS SUBMISSION OF GAMING ORDINANCE OR RESOLUTION § 522.10 Individually owned class II and class III...

Disability Prevalence According to a Class, Race, and Sex (CSR) Hypothesis.

PubMed

Siordia, Carlos

2015-09-01

Disability has been shown to be related in definite ways to social class. In modern industrial societies, disability is influenced by and has the potential to contribute to the production and reproduction of social inequality. However, markers of social stratification processes are sometimes ignored determinants of health. A Class, Race, Sex (CRS) hypothesis is presented to argue that a "low-education disadvantage"; "racial-minority disadvantage"; and "female disadvantage" will compound to affect the risks for being disable. In particular, the CRS hypothesis posits that class is more important than race and the latter more than sex when predicting presence or severity of disability. The cross-sectional study of community-dwelling adults between the ages of 45 and 64 uses data from the American Community Survey (ACS) Public Use Microdata Sample (PUMS) 2008-2012 file. By using 3,429,523 individuals-which weighted equal to 61,726,420-the results of the study suggest the CRS hypothesis applies to both Non-Latino-Blacks and Non-Latino-Whites. There is a "male disadvantage" exception for Non-Latino-Whites. Decreasing between-group differences in health may be achieved by making the age-health association at lower socioeconomic stratum similar to that of the upper socioeconomic strata.

Computational and experimental study of the interactions between ionic liquids and volatile organic compounds.

PubMed

Gao, Tingting; Andino, Jean M; Alvarez-Idaboy, J Raul

2010-09-07

Computational chemistry calculations were performed to investigate the interactions of ionic liquids with different classes of volatile organic compounds (VOCs), including alcohols, aldehydes, ketones, alkanes, alkenes, alkynes and aromatic compounds. At least one VOC was studied to represent each class. Initially, 1-butyl-3-methylimindazolium chloride (abbreviated as C(4)mimCl) was used as the test ionic liquid compound. Calculated interaction lengths between atoms in the ionic liquid and the VOC tested as well as thermodynamic data suggest that C(4)mimCl preferentially interacts with alcohols as compared to other classes of volatile organic compounds. The interactions of methanol with different kinds of ionic liquids, specifically 1-butyl-3-methylimidazolium bromine (C(4)mimBr) and 1-butyl-3-methylimidazolium tetrafluoroborate (C(4)mimBF(4)) were also studied. In comparing C(4)mimCl, C(4)mimBr, and C(4)mimBF(4), the computational results suggest that C(4)mimCl is more likely to interact with methanol. Laboratory experiments were performed to provide further evidence for the interaction between C(4)mimCl and different classes of VOCs. Fourier transform infrared spectroscopy was used to probe the ionic liquid surface before and after exposure to the VOCs that were tested. New spectral features were detected after exposure of C(4)mimCl to various alcohols. The new features are characteristic of the alcohols tested. No new IR features were detected after exposure of the C(4)mimCl to the aldehyde, ketone, alkane, alkene, alkyne or aromatic compounds studied. In addition, after exposing the C(4)mimCl to a multi-component mixture of various classes of compounds (including an alcohol), the only new peaks that were detected were characteristic of the alcohol that was tested. These experimental results demonstrated that C(4)mimCl is selective to alcohols, even in complex mixtures. The findings in this work provide information for future gas-phase alcohol sensor design.

Discovery of Rigidified α,β-Unsaturated Imines as New Resistance-breaking Insecticides for Malaria Vector Control.

PubMed

Arlt, Alexander; Böhnke, Niels; Horstmann, Sebastian; Vermeer, Arnoldus W P; Werner, Stefan; Velten, Robert

2016-10-01

During our continuous search for new resistance-breaking insecticides applicable to malaria vector control, a new class of α,β-unsaturated imines was identified by applying the principle of conformational rigidification as a powerful tool for compound optimisation. Herein we describe the successful synthesis of these compounds and their biological test results. Our lead compound 16 from this insecticidal class outperforms market standards, notably for the control of mosquito strains that exhibit either metabolic or target-site resistance to these established insecticides. In our model system for insecticide-treated mosquito nets the compound reveals long-lasting efficacy for up to several months.

Synchroton and Simulations Techniques Applied to Problems in Materials Science: Catalysts and Azul Maya Pigments

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

Chianelli, R.

2005-01-12

Development of synchrotron techniques for the determination of the structure of disordered, amorphous and surface materials has exploded over the past twenty years due to the increasing availability of high flux synchrotron radiation and the continuing development of increasingly powerful synchrotron techniques. These techniques are available to materials scientists who are not necessarily synchrotron scientists through interaction with effective user communities that exist at synchrotrons such as the Stanford Synchrotron Radiation Laboratory (SSRL). In this article we review the application of multiple synchrotron characterization techniques to two classes of materials defined as ''surface compounds.'' One class of surface compounds aremore » materials like MoS{sub 2-x}C{sub x} that are widely used petroleum catalysts used to improve the environmental properties of transportation fuels. These compounds may be viewed as ''sulfide supported carbides'' in their catalytically active states. The second class of ''surface compounds'' is the ''Maya Blue'' pigments that are based on technology created by the ancient Maya. These compounds are organic/inorganic ''surface complexes'' consisting of the dye indigo and palygorskite, a common clay. The identification of both surface compounds relies on the application of synchrotron techniques as described in this report.« less

Extraction, evolution, and sensory impact of phenolic compounds during red wine maceration.

PubMed

Casassa, L Federico; Harbertson, James F

2014-01-01

We review the extraction into wine and evolution of major phenolic classes of sensory relevance. We present a historical background to highlight that previously established aspects of phenolic extraction and retention into red wine are still subjects of much research. We argue that management of the maceration length is one of the most determining factors in defining the proportion and chemical fate of phenolic compounds in wine. The extraction of anthocyanins, flavonols, flavan-3-ols, and oligomeric and polymeric proanthocyanidins (PAs) is discussed in the context of their individual extraction patterns but also with regard to their interaction with other wine components. The same approach is followed to present the sensory implications of phenolic and phenolic-derived compounds in wine. Overall, we conclude that the chemical diversity of phenolic compounds in grapes is further enhanced as soon as vacuolar and pulp components are released upon crushing, adding a variety of new sensory dimensions to the already present chemical diversity. Polymeric pigments formed by the covalent reaction of anthocyanin and PAs are good candidates to explain some of the observed sensory changes in the color, taste, and mouthfeel attributes of red wines during maceration and aging.

Enantiomeric and Isotopic Analysis of Sugar Derivatives in Carbonaceous Meteorites

NASA Technical Reports Server (NTRS)

Cooper, George; Asiyo, Cynthia; Turk, Kendra; DeVincenzi, Donald (Technical Monitor)

2002-01-01

Several classes of organic compounds are found in carbonaceous meteorites including amino acids, carboxylic acids, hydroxy acids, purines, and pyrimidines. Such compounds are thought to have been delivered to the early Earth in asteroids and comets and may have played a role in the origin of life. Likewise, sugar derivatives are critical to all known lifeforms. Recent analyses of the Murchison and Murray carbonaceous meteorites revealed a diverse suite of such derivatives, i.e., sugar alcohols, and sugar acids. This presentation will focus primarily on the analysis of individual sugar acids - their enantiomeric and isotopic composition. Analysis of these compounds may reveal the nature of past (or present) meteoritic sugars themselves. For example, if parent sugars decomposed (by well-known mechanisms) to give the present acids, were their enantiomeric ratios preserved? Combined with other evidence, the enantiomeric composition of such compounds as glyceric acid and (especially) rare acids may help to answer such questions. C-13 and D isotope analysis of meteoritic sugar alcohols (glycerol, threitol, ribitol, etc.) as a group revealed that they were indigenous to the meteorite. Preliminary C-13 analysis of glyceric acid shows that it is also extraterrestrial.

The Sophora flavescens flavonoid compound trifolirhizin inhibits acetylcholine induced airway smooth muscle contraction.

PubMed

Yang, Nan; Liang, Banghao; Srivastava, Kamal; Zeng, Jia; Zhan, Jixun; Brown, LaVerne; Sampson, Hugh; Goldfarb, Joseph; Emala, Charles; Li, Xiu-Min

2013-11-01

Asthma is a serious health problem worldwide, particularly in industrialized countries. Despite a better understanding of the pathophysiology of asthma, there are still considerable gaps in knowledge as well as a need for classes of drugs. ASHMI™ (Anti-asthma Herbal Medicine Intervention) is an aqueous extract of Ganoderma lucidum (Fr.) P. Karst (Ling Zhi), Sophora flavescens Aiton (Ku Shen) and Glycyrrhiza uralensis Fisch. ex DC (Gan Cao). It prevents allergic asthma airway hyper-reactivity in mice and inhibits acetylcholine (ACh) induced airway smooth muscle (ASM) contraction in tracheal rings from allergic asthmatic mice. The purpose of this research was to identify individual herb(s) and their active compound(s) that inhibit ASM contraction. It was found that S. flavescens, but not G. lucidum or G. uralensis aqueous extracts, inhibited ASM contraction in tracheal rings from asthmatic mice. Bioassay-guided isolation and identification of flavonoid fractions/compound(s) via methylene chloride extraction, preparative HPLC fractionation, and LC-MS and NMR spectroscopic analyses showed that trifolirhizin is an active constituent that inhibits acetylcholine mediated ASM contraction or directly relaxes pre-contracted ASM independent of β2-adrenoceptors. Copyright © 2013 Elsevier Ltd. All rights reserved.

The Sophora Flavescens flavonoid compound trifolirhizin inhibits acetylcholine induced airway smooth muscle contraction

PubMed Central

Zeng, Jia; Zhan, Jixun; Brown, LaVerne; Sampson, Hugh; Goldfarb, Joseph; Emala, Charles; Li, Xiu-Min

2014-01-01

Asthma is a serious health problem worldwide, particularly in industrialized countries. Despite a better understanding of the pathophysiology of asthma, there are still considerable gaps in knowledge as well as a need for new classes of drugs. ASHMI™ (Anti-asthma Herbal Medicine Intervention) is an aqueous extract of Ganoderma lucidum (Fr.) P. Karst (Ling Zhi), Sophora flavescens Aiton (Ku Shen) and Glycyrrhiza uralensis Fisch. ex DC (Gan Cao). It prevents allergic asthma airway hyper-reactivity in mice and inhibits acetylcholine (ACh) induced airway smooth muscle (ASM) contraction in tracheal rings from allergic asthmatic mice. The purpose of this research was to identify individual herb(s) and their active compound(s) that inhibit ASM contraction. It was found that Sophora flavescens (S. flavescens), but not Ganoderma lucidum (G. lucidum) or Glycyrrhiza uralensis (G. uralensis) aqueous extracts, inhibited ASM contraction in tracheal rings from asthmatic mice. Bioassay-guided isolation and identification of flavonoid fractions/compound(s) via methylene chloride extraction, preparative HPLC fractionation, and LC-MS and NMR spectroscopic analyses showed that trifolirhizin is an active constituent that inhibits acetylcholine mediated ASM contraction or directly relaxes pre-contracted ASM independent of β2-adrenoceptors. PMID:23993294

OliveNet™: a comprehensive library of compounds from Olea europaea

PubMed Central

Bonvino, Natalie P; Liang, Julia; McCord, Elizabeth D; Zafiris, Elena; Benetti, Natalia; Ray, Nancy B; Hung, Andrew; Boskou, Dimitrios

2018-01-01

Abstract Accumulated epidemiological, clinical and experimental evidence has indicated the beneficial health effects of the Mediterranean diet, which is typified by the consumption of virgin olive oil (VOO) as a main source of dietary fat. At the cellular level, compounds derived from various olive (Olea europaea), matrices, have demonstrated potent antioxidant and anti-inflammatory effects, which are thought to account, at least in part, for their biological effects. Research efforts are expanding into the characterization of compounds derived from Olea europaea, however, the considerable diversity and complexity of the vast array of chemical compounds have made their precise identification and quantification challenging. As such, only a relatively small subset of olive-derived compounds has been explored for their biological activity and potential health effects to date. Although there is adequate information describing the identification or isolation of olive-derived compounds, these are not easily searchable, especially when attempting to acquire chemical or biological properties. Therefore, we have created the OliveNet™ database containing a comprehensive catalogue of compounds identified from matrices of the olive, including the fruit, leaf and VOO, as well as in the wastewater and pomace accrued during oil production. From a total of 752 compounds, chemical analysis was sufficient for 676 individual compounds, which have been included in the database. The database is curated and comprehensively referenced containing information for the 676 compounds, which are divided into 13 main classes and 47 subclasses. Importantly, with respect to current research trends, the database includes 222 olive phenolics, which are divided into 13 subclasses. To our knowledge, OliveNet™ is currently the only curated open access database with a comprehensive collection of compounds associated with Olea europaea. Database URL: https://www.mccordresearch.com.au PMID:29688352

Nature and prevalence of non-additive toxic effects in industrially relevant mixtures of organic chemicals.

PubMed

Parvez, Shahid; Venkataraman, Chandra; Mukherji, Suparna

2009-06-01

The concentration addition (CA) and the independent action (IA) models are widely used for predicting mixture toxicity based on its composition and individual component dose-response profiles. However, the prediction based on these models may be inaccurate due to interaction among mixture components. In this work, the nature and prevalence of non-additive effects were explored for binary, ternary and quaternary mixtures composed of hydrophobic organic compounds (HOCs). The toxicity of each individual component and mixture was determined using the Vibrio fischeri bioluminescence inhibition assay. For each combination of chemicals specified by the 2(n) factorial design, the percent deviation of the predicted toxic effect from the measured value was used to characterize mixtures as synergistic (positive deviation) and antagonistic (negative deviation). An arbitrary classification scheme was proposed based on the magnitude of deviation (d) as: additive (< or =10%, class-I) and moderately (10< d < or =30 %, class-II), highly (30< d < or =50%, class-III) and very highly (>50%, class-IV) antagonistic/synergistic. Naphthalene, n-butanol, o-xylene, catechol and p-cresol led to synergism in mixtures while 1, 2, 4-trimethylbenzene and 1, 3-dimethylnaphthalene contributed to antagonism. Most of the mixtures depicted additive or antagonistic effect. Synergism was prominent in some of the mixtures, such as, pulp and paper, textile dyes, and a mixture composed of polynuclear aromatic hydrocarbons. The organic chemical industry mixture depicted the highest abundance of antagonism and least synergism. Mixture toxicity was found to depend on partition coefficient, molecular connectivity index and relative concentration of the components.

The Potential Protective Effects of Phenolic Compounds against Low-density Lipoprotein Oxidation.

PubMed

Amarowicz, Ryszard; Pegg, Ronald B

2017-01-01

The exact mechanism(s) of atherosclerosis in humans remains elusive, but one theory hypothesizes that this deleterious process results from the oxidative modification of low-density lipoprotein (LDL). Research suggests that foods rich in dietary phenolic compounds with antioxidant activity can mitigate the extent of LDL oxidation in vivo. With regard to the different classes of flavonoids, there appears to be a structurefunction relationship between the various moieties/constituents attached to the flavonoids' three ring system and their impact at retarding LDL oxidation. This article summarizes the findings to date of both in vitro and in vivo studies using foods or phenolic extracts isolated from foodstuffs at inhibiting the incidence of LDL oxidation. Three bases: SCOPUS, Web Science, and PubMed were used for search. An often used method for the determination of antioxidant properties of natural phenolic compounds is the LDL oxidation assay. LDLs are isolated from human plasma and their oxidation is induced by Cu2+ ions or 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AAPH). The sample is incubated with a phenolic extract or individual/isolated phenolic compounds. LDL oxidation is then monitored by various chemical methods (e.g., measurement of the generation of conjugated dienes and trienes). This technique confirmed the antioxidant properties of several extracts as obtained from plant material (e.g., grapes, berries, orange, grapefruit, coffee, tea, chocolate, olives, nuts) as well as the individual phenolic compounds (e.g., luteolinidin, apigenidin, caffeic acid, chlorogenic acid, catechin, quercetin, rutin). Several studies in vivo confirmed protective effects of phenolic compounds against LDL oxidation. They covered the healthy subjects with hyperlipidaemia, overweight, obesity, metabolic syndrome, heavy smokers, patients receiving haemodialysis, patients with peripheral vascular disease, and subjects at high cardiovascular risk. The studies comprise individuals of all ages, and the number of participants in the different experiments varied widely. Properly designed double-blind, placebo-controlled randomised clinical trials offer stronger evidence as to the impact of dietary phenolics consumption at retarding LDL oxidation. More such clinical trials are needed to strengthen the hypothesis that foods rich in dietary phenolic compounds with antioxidant activity can mitigate the extent of LDL oxidation in vivo. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Differential cytokine modulation and T cell activation by two distinct classes of thalidomide analogues that are potent inhibitors of TNF-alpha.

PubMed

Corral, L G; Haslett, P A; Muller, G W; Chen, R; Wong, L M; Ocampo, C J; Patterson, R T; Stirling, D I; Kaplan, G

1999-07-01

TNF-alpha mediates both protective and detrimental manifestations of the host immune response. Our previous work has shown thalidomide to be a relatively selective inhibitor of TNF-alpha production in vivo and in vitro. Additionally, we have recently reported that thalidomide exerts a costimulatory effect on T cell responses. To develop thalidomide analogues with increased anti-TNF-alpha activity and reduced or absent toxicities, novel TNF-alpha inhibitors were designed and synthesized. When a selected group of these compounds was examined for their immunomodulatory activities, different patterns of cytokine modulation were revealed. The tested compounds segregated into two distinct classes: one class of compounds, shown to be potent phosphodiesterase 4 inhibitors, inhibited TNF-alpha production, increased IL-10 production by LPS-induced PBMC, and had little effect on T cell activation; the other class of compounds, similar to thalidomide, were not phosphodiesterase 4 inhibitors and markedly stimulated T cell proliferation and IL-2 and IFN-gamma production. These compounds inhibited TNF-alpha, IL-1beta, and IL-6 and greatly increased IL-10 production by LPS-induced PBMC. Similar to thalidomide, the effect of these agents on IL-12 production was dichotomous; IL-12 was inhibited when PBMC were stimulated with LPS but increased when cells were stimulated by cross-linking the TCR. The latter effect was associated with increased T cell CD40 ligand expression. The distinct immunomodulatory activities of these classes of thalidomide analogues may potentially allow them to be used in the clinic for the treatment of different immunopathological disorders.

Di-pentyl phthalate dosing during sexual differentiation disrupts fetal testis function and postnatal development of the male Sprague dawley rat with greater relative potency than other phthalates

EPA Science Inventory

Phthalate esters (PEs) constitute a large class of plasticizer compounds that are widely used for many consumer product applications. Ten or more members of the PE class of compounds have been shown to induce male fetal endocrine toxicity and postnatal reproductive malformations ...

Identification and hit-to-lead optimization of a novel class of CB1 antagonists.

PubMed

Letourneau, Jeffrey J; Jokiel, Patrick; Olson, John; Riviello, Christopher M; Ho, Koc-Kan; McAleer, Lihong; Yang, Jingchun; Swanson, Robert N; Baker, James; Cowley, Phillip; Edwards, Darren; Ward, Nick; Ohlmeyer, Michael H J; Webb, Maria L

2010-09-15

The discovery, synthesis and preliminary structure-activity relationships (SARs) of a novel class of CB1 antagonists is described. Initial optimization of benzimidazole-based screening hit 4 led to the identification of 'inverted' indole-based lead compound 18c with improved properties versus compound 4 including reduced AlogP, improved microsomal stability and improved aqueous solubility. Compound 18c demonstrates in vivo CB1 antagonist efficacy (CB1 agonist induced hypothermia model) and is orally bioavailable in rat. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

A Perturbation Based Decomposition of Compound-Evoked Potentials for Characterization of Nerve Fiber Size Distributions.

PubMed

Szlavik, Robert B

2016-02-01

The characterization of peripheral nerve fiber distributions, in terms of diameter or velocity, is of clinical significance because information associated with these distributions can be utilized in the differential diagnosis of peripheral neuropathies. Electro-diagnostic techniques can be applied to the investigation of peripheral neuropathies and can yield valuable diagnostic information while being minimally invasive. Nerve conduction velocity studies are single parameter tests that yield no detailed information regarding the characteristics of the population of nerve fibers that contribute to the compound-evoked potential. Decomposition of the compound-evoked potential, such that the velocity or diameter distribution of the contributing nerve fibers may be determined, is necessary if information regarding the population of contributing nerve fibers is to be ascertained from the electro-diagnostic study. In this work, a perturbation-based decomposition of compound-evoked potentials is proposed that facilitates determination of the fiber diameter distribution associated with the compound-evoked potential. The decomposition is based on representing the single fiber-evoked potential, associated with each diameter class, as being perturbed by contributions, of varying degree, from all the other diameter class single fiber-evoked potentials. The resultant estimator of the contributing nerve fiber diameter distribution is valid for relatively large separations in diameter classes. It is also useful in situations where the separation between diameter classes is small and the concomitant single fiber-evoked potentials are not orthogonal.

phzO, a Gene for Biosynthesis of 2-Hydroxylated Phenazine Compounds in Pseudomonas aureofaciens 30-84

PubMed Central

Delaney, Shannon M.; Mavrodi, Dmitri V.; Bonsall, Robert F.; Thomashow, Linda S.

2001-01-01

Certain strains of root-colonizing fluorescent Pseudomonas spp. produce phenazines, a class of antifungal metabolites that can provide protection against various soilborne root pathogens. Despite the fact that the phenazine biosynthetic locus is highly conserved among fluorescent Pseudomonas spp., individual strains differ in the range of phenazine compounds they produce. This study focuses on the ability of Pseudomonas aureofaciens 30-84 to produce 2-hydroxyphenazine-1-carboxylic acid (2-OH-PCA) and 2-hydroxyphenazine from the common phenazine metabolite phenazine-1-carboxylic acid (PCA). P. aureofaciens 30-84 contains a novel gene located downstream from the core phenazine operon that encodes a 55-kDa aromatic monooxygenase responsible for the hydroxylation of PCA to produce 2-OH-PCA. Knowledge of the genes responsible for phenazine product specificity could ultimately reveal ways to manipulate organisms to produce multiple phenazines or novel phenazines not previously described. PMID:11114932

Comprehensive Review of Applicable Supercritical Fluid Extraction Research

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

Harvey, Scott; Wright, Cherylyn W.; Wright, Bob W.

2001-09-10

This comprehensive supercritical fluid extraction (SFE) literature review is divided into three major sections. The first section describes the electronic literature search details including the abstract service used and the different topics searched. This section also contains an overview of the seven search topics that yielded relevant references along with a brief synopsis of the most significant literature citations. These seven groupings are (1) chemical warfare agents; (2) explosives; (3) hazardous chemicals; (4) poisons, toxins and mycotoxins; (5) toxic (lethal) chemical and toxicants; (6) pesticides in soil; and (7) pesticides from plant and animal tissues. The second section contains tablesmore » of each of these groupings. Each of the seven tables contains entries for individual literature citations listed along with the specific compounds or compound classes that are addressed. The third section refers to the abstracts used in the literature search.« less

Chemical constituents and bioactivities of the plants of genus Flemingia Roxb. et Ait. (Leguminosae).

PubMed

Li, Hua; Zhai, Fengyan; Liu, Zhongdong

2012-09-01

The genus Flemingia Roxb. et Ait. (Leguminosae) has been used for disease prevention and therapy in China since ancient times. So the material basis of the pharmacological activity in the genus Flemingia should be clear for how to use this kind of traditional Chinese medicines more reasonably in pharmacology. Therefore, this review gives an account of the current knowledge on the chemical constituents, biological activities and pharmacological properties of the plants of the genus. Several different classes of compounds were previously isolated, which the main groups are flavones, particularly prenylated flavones, and triterpenes accompanied with sterols, anthraquinones, and others. The names and structures of the chemical constituents are given in this review. In addition, the pharmacological effects of the extracts and individual compounds (mainly for flavones) derived from the genus plants have been found, including neuroprotection, anti-inflammation, anti-oxidation, cytotoxicity, hormone-like effects, antimicrobial activities, and so on.

Automatic classification of visual evoked potentials based on wavelet decomposition

NASA Astrophysics Data System (ADS)

Stasiakiewicz, Paweł; Dobrowolski, Andrzej P.; Tomczykiewicz, Kazimierz

2017-04-01

Diagnosis of part of the visual system, that is responsible for conducting compound action potential, is generally based on visual evoked potentials generated as a result of stimulation of the eye by external light source. The condition of patient's visual path is assessed by set of parameters that describe the time domain characteristic extremes called waves. The decision process is compound therefore diagnosis significantly depends on experience of a doctor. The authors developed a procedure - based on wavelet decomposition and linear discriminant analysis - that ensures automatic classification of visual evoked potentials. The algorithm enables to assign individual case to normal or pathological class. The proposed classifier has a 96,4% sensitivity at 10,4% probability of false alarm in a group of 220 cases and area under curve ROC equals to 0,96 which, from the medical point of view, is a very good result.

Nanowire Electron Scattering Spectroscopy

NASA Technical Reports Server (NTRS)

Hunt, Brian; Bronikowsky, Michael; Wong, Eric; VonAllmen, Paul; Oyafuso, Fablano

2009-01-01

Nanowire electron scattering spectroscopy (NESS) has been proposed as the basis of a class of ultra-small, ultralow-power sensors that could be used to detect and identify chemical compounds present in extremely small quantities. State-of-the-art nanowire chemical sensors have already been demonstrated to be capable of detecting a variety of compounds in femtomolar quantities. However, to date, chemically specific sensing of molecules using these sensors has required the use of chemically functionalized nanowires with receptors tailored to individual molecules of interest. While potentially effective, this functionalization requires labor-intensive treatment of many nanowires to sense a broad spectrum of molecules. In contrast, NESS would eliminate the need for chemical functionalization of nanowires and would enable the use of the same sensor to detect and identify multiple compounds. NESS is analogous to Raman spectroscopy, the main difference being that in NESS, one would utilize inelastic scattering of electrons instead of photons to determine molecular vibrational energy levels. More specifically, in NESS, one would exploit inelastic scattering of electrons by low-lying vibrational quantum states of molecules attached to a nanowire or nanotube.

Hit-to-Lead Optimization of a Novel Class of Potent, Broad-Spectrum Trypanosomacides.

PubMed

Russell, Stephanie; Rahmani, Raphaël; Jones, Amy J; Newson, Harriet L; Neilde, Kevin; Cotillo, Ignacio; Rahmani Khajouei, Marzieh; Ferrins, Lori; Qureishi, Sana; Nguyen, Nghi; Martinez-Martinez, Maria S; Weaver, Donald F; Kaiser, Marcel; Riley, Jennifer; Thomas, John; De Rycker, Manu; Read, Kevin D; Flematti, Gavin R; Ryan, Eileen; Tanghe, Scott; Rodriguez, Ana; Charman, Susan A; Kessler, Albane; Avery, Vicky M; Baell, Jonathan B; Piggott, Matthew J

2016-11-10

The parasitic trypanosomes Trypanosoma brucei and T. cruzi are responsible for significant human suffering in the form of human African trypanosomiasis (HAT) and Chagas disease. Drugs currently available to treat these neglected diseases leave much to be desired. Herein we report optimization of a novel class of N-(2-(2-phenylthiazol-4-yl)ethyl)amides, carbamates, and ureas, which rapidly, selectively, and potently kill both species of trypanosome. The mode of action of these compounds is unknown but does not involve CYP51 inhibition. They do, however, exhibit clear structure-activity relationships, consistent across both trypanosome species. Favorable physicochemical parameters place the best compounds in CNS drug-like chemical space but, as a class, they exhibit poor metabolic stability. One of the best compounds (64a) cleared all signs of T. cruzi infection in mice when CYP metabolism was inhibited, with sterile cure achieved in one mouse. This family of compounds thus shows significant promise for trypanosomiasis drug discovery.

ACUTE TOXICITY OF SELECTED ORGANIC COMPOUNDS TO FATHEAD MINNOWS

EPA Science Inventory

Static nonrenewal laboratory bioassays were conducted with 26 organic compounds commonly used by industry. The selected compounds represented the five following chemical classes: acids, alcohols, hydrocarbons, ketones and aldehydes, and phenols. Juvenile fathead minnows (Pimephal...

Ontology-based content analysis of US patent applications from 2001-2010.

PubMed

Weber, Lutz; Böhme, Timo; Irmer, Matthias

2013-01-01

Ontology-based semantic text analysis methods allow to automatically extract knowledge relationships and data from text documents. In this review, we have applied these technologies for the systematic analysis of pharmaceutical patents. Hierarchical concepts from the knowledge domains of chemical compounds, diseases and proteins were used to annotate full-text US patent applications that deal with pharmacological activities of chemical compounds and filed in the years 2001-2010. Compounds claimed in these applications have been classified into their respective compound classes to review the distribution of scaffold types or general compound classes such as natural products in a time-dependent manner. Similarly, the target proteins and claimed utility of the compounds have been classified and the most relevant were extracted. The method presented allows the discovery of the main areas of innovation as well as emerging fields of patenting activities - providing a broad statistical basis for competitor analysis and decision-making efforts.

From the Test Tube to the Treatment Room: Fundamentals of Boron-containing Compounds and their Relevance to Dermatology.

PubMed

Del Rosso, James Q; Plattner, Jacob J

2014-02-01

The development of new drug classes and novel molecules that are brought to the marketplace has been a formidable challenge, especially for dermatologic drugs. The relative absence of new classes of antimicrobial agents is also readily apparent. Several barriers account for slow drug development, including regulatory changes, added study requirements, commercial pressures to bring drugs to market quickly by developing new generations of established compounds, and the greater potential for failure and higher financial risk when researching new drug classes. In addition, the return on investment is usually much lower with dermatologic drugs as compared to the potential revenue from "blockbuster" drugs for cardiovascular or gastrointestinal disease, hypercholesterolemia, and mood disorders. Nevertheless, some researchers are investigating new therapeutic platforms, one of which is boron-containing compounds. Boron-containing compounds offer a wide variety of potential applications in dermatology due to their unique physical and chemical properties, with several in formal phases of development. Tavaborole, a benzoxaborole compound, has been submitted to the United States Food and Drug Administration for approval for treatment of onychomycosis. This article provides a thorough overview of the history of boron-based compounds in medicine, their scientific rationale, physiochemical and pharmacologic properties, and modes of actions including therapeutic targets. A section dedicated to boron-based compounds in development for treatment of various skin disorders is also included.

Class and compassion: socioeconomic factors predict responses to suffering.

PubMed

Stellar, Jennifer E; Manzo, Vida M; Kraus, Michael W; Keltner, Dacher

2012-06-01

Previous research indicates that lower-class individuals experience elevated negative emotions as compared with their upper-class counterparts. We examine how the environments of lower-class individuals can also promote greater compassionate responding-that is, concern for the suffering or well-being of others. In the present research, we investigate class-based differences in dispositional compassion and its activation in situations wherein others are suffering. Across studies, relative to their upper-class counterparts, lower-class individuals reported elevated dispositional compassion (Study 1), as well as greater self-reported compassion during a compassion-inducing video (Study 2) and for another person during a social interaction (Study 3). Lower-class individuals also exhibited heart rate deceleration-a physiological response associated with orienting to the social environment and engaging with others-during the compassion-inducing video (Study 2). We discuss a potential mechanism of class-based influences on compassion, whereby lower-class individuals' are more attuned to others' distress, relative to their upper-class counterparts.

Assessment of Multiple Solvents for Extraction and Direct GC-MS Determination of the Phytochemical Inventory of Sansevieria Extrafoliar Nectar Droplets.

PubMed

Gaylor, Michael O; Juntunen, Hope L; Hazelwood, Donna; Videau, Patrick

2018-04-01

Considerable effort has been devoted to analytical determinations of sugar and amino acid constituents of plant nectars, with the primary aim of understanding their ecological roles, yet few studies have reported more exhaustive organic compound inventories of plant nectars or extrafoliar nectars. This work evaluated the efficacy of four solvents (ethyl acetate, dichloromethane, toluene and hexane) to extract the greatest number of organic compound classes and unique compounds from extrafoliar nectar drops produced by Sansevieria spp. Aggregation of the results from each solvent revealed that 240 unique compounds were extracted in total, with 42.5% of those detected in multiple extracts. Aliphatic hydrocarbons dominated in all but the ethyl acetate extracts, with 44 unique aliphatic hydrocarbons detected in dichloromethane (DCM) extracts, followed by 41, 19 and 8 in hexane, toluene and ethyl acetate extracts, respectively. Hexane extracted the most unique compounds (79), followed by DCM (73), ethyl acetate (56) and toluene (32). Integrated total ion chromatographic peak areas of extracted compound classes were positively correlated with numbers of unique compounds detected within those classes. In addition to demonstrating that multi-solvent extraction with direct GC-MS detection is a suitable analytical approach for determining secondary nectar constituents, to the best of our knowledge, this study also represents: (i) the first attempt to inventory the secondary phytochemical constituents of Sansevieria spp. extrafoliar nectar secretions and (ii) the largest organic solvent extractable compound inventory reported for any plant matrix to date.

Anti-trypanosomal activities and structural chemical properties of selected compound classes.

PubMed

Ponte-Sucre, Alicia; Bruhn, Heike; Schirmeister, Tanja; Cecil, Alexander; Albert, Christian R; Buechold, Christian; Tischer, Maximilian; Schlesinger, Susanne; Goebel, Tim; Fuß, Antje; Mathein, Daniela; Merget, Benjamin; Sotriffer, Christoph A; Stich, August; Krohne, Georg; Engstler, Markus; Bringmann, Gerhard; Holzgrabe, Ulrike

2015-02-01

Potent compounds do not necessarily make the best drugs in the market. Consequently, with the aim to describe tools that may be fundamental for refining the screening of candidates for animal and preclinical studies and further development, molecules of different structural classes synthesized within the frame of a broad screening platform were evaluated for their trypanocidal activities, cytotoxicities against murine macrophages J774.1 and selectivity indices, as well as for their ligand efficiencies and structural chemical properties. To advance into their modes of action, we also describe the morphological and ultrastructural changes exerted by selected members of each compound class on the parasite Trypanosoma brucei. Our data suggest that the potential organelles targeted are either the flagellar pocket (compound 77, N-Arylpyridinium salt; 15, amino acid derivative with piperazine moieties), the endoplasmic reticulum membrane systems (37, bisquaternary bisnaphthalimide; 77, N-Arylpyridinium salt; 68, piperidine derivative), or mitochondria and kinetoplasts (88, N-Arylpyridinium salt; 68, piperidine derivative). Amino acid derivatives with fumaric acid and piperazine moieties (4, 15) weakly inhibiting cysteine proteases seem to preferentially target acidic compartments. Our results suggest that ligand efficiency indices may be helpful to learn about the relationship between potency and chemical characteristics of the compounds. Interestingly, the correlations found between the physico-chemical parameters of the selected compounds and those of commercial molecules that target specific organelles indicate that our rationale might be helpful to drive compound design toward high activities and acceptable pharmacokinetic properties for all compound families.

Outdoor passive air monitoring of semi volatile organic compounds (SVOCs): a critical evaluation of performance and limitations of polyurethane foam (PUF) disks.

PubMed

Bohlin, P; Audy, O; Škrdlíková, L; Kukučka, P; Přibylová, P; Prokeš, R; Vojta, Š; Klánová, J

2014-03-01

The most commonly used passive air sampler (PAS) (i.e. polyurethane foam (PUF) disk) is cheap, versatile, and capable of accumulating compounds present both in gas and particle phases. Its performance for particle associated compounds is however disputable. In this study, twelve sets of triplicate PUF-PAS were deployed outdoors for exposure periods of 1-12 weeks together with continuously operated active samplers, to characterize sampling efficiency and derive sampling rates (RS) for compounds belonging to 7 SVOC classes (including particle associated compounds). PUF-PAS efficiently and consistently sampled polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), polycyclic aromatic hydrocarbons (PAHs), and eight novel brominated flame retardant (nBFR) compounds. Low accuracy and lack of sensitivity was observed for most polychlorinated dibenzo-p-dioxins/furans PCDD/Fs and polybrominated diphenyl ethers (PBDEs) (under the conditions of this study), with the exception of some congeners which may be used as qualitative markers for their respective classes. Application of compound specific RS was found crucial for all compounds except PCBs. Sampling efficiency of the particle associated compounds was often low.

ION COMPOSITION ELUCIDATION (ICE): A HIGH ...

EPA Pesticide Factsheets

Unidentified Organic Compounds. For target analytes, standards are purchased, extraction and clean-up procedures are optimized, and mass spectra and retention times for the chromatographic separation are obtained for comparison to the target compounds in environmental sample extracts. This is an efficient approach and selective extraction and clean-up can decrease detection limits for the target compounds relative to analyzing a raw extract containing compounds that yield mass interferences. But selection of a class of compounds for study ignores many potentially toxic compounds. All compounds should be considered, because even trace amounts of compounds found to be endocrine disrupting chemicals might influence embryonic development. Before the toxicology of the hundreds of compounds found in sewage treatment effluents and water reservoirs can be studied alone and in mixtures, they must first be identified. A given compound might be one of the 3800 high production volume chemicals used commercially, a human or microorganism metabolite of such a compound, a photochemical degradation, hydrolysis, or thermal decomposition product, a chlorination or ozonolysis byproduct for drinking water samples, or a naturally occurring compound. Numerous researchers targeting assorted classes of analytes could easily overlook or be unable to identify many of these compounds. Most non-targeted compounds will not be in mass spectral libraries and can seldom be tentatively identifi

Metabolic profiling of Arabidopsis thaliana epidermal cells

PubMed Central

Ebert, Berit; Zöller, Daniela; Erban, Alexander; Fehrle, Ines; Hartmann, Jürgen; Niehl, Annette; Kopka, Joachim; Fisahn, Joachim

2010-01-01

Metabolic phenotyping at cellular resolution may be considered one of the challenges in current plant physiology. A method is described which enables the cell type-specific metabolic analysis of epidermal cell types in Arabidopsis thaliana pavement, basal, and trichome cells. To achieve the required high spatial resolution, single cell sampling using microcapillaries was combined with routine gas chromatography-time of flight-mass spectrometry (GC-TOF-MS) based metabolite profiling. The identification and relative quantification of 117 mostly primary metabolites has been demonstrated. The majority, namely 90 compounds, were accessible without analytical background correction. Analyses were performed using cell type-specific pools of 200 microsampled individual cells. Moreover, among these identified metabolites, 38 exhibited differential pool sizes in trichomes, basal or pavement cells. The application of an independent component analysis confirmed the cell type-specific metabolic phenotypes. Significant pool size changes between individual cells were detectable within several classes of metabolites, namely amino acids, fatty acids and alcohols, alkanes, lipids, N-compounds, organic acids and polyhydroxy acids, polyols, sugars, sugar conjugates and phenylpropanoids. It is demonstrated here that the combination of microsampling and GC-MS based metabolite profiling provides a method to investigate the cellular metabolism of fully differentiated plant cell types in vivo. PMID:20150518

Differentiation of antiinflammatory and antitumorigenic properties of stabilized enantiomers of thalidomide analogs

PubMed Central

Jacques, Vincent; Czarnik, Anthony W.; Judge, Thomas M.; Van der Ploeg, Lex H. T.; DeWitt, Sheila H.

2015-01-01

Therapeutics developed and sold as racemates can exhibit a limited therapeutic index because of side effects resulting from the undesired enantiomer (distomer) and/or its metabolites, which at times, forces researchers to abandon valuable scaffolds. Therefore, most chiral drugs are developed as single enantiomers. Unfortunately, the development of some chirally pure drug molecules is hampered by rapid in vivo racemization. The class of compounds known as immunomodulatory drugs derived from thalidomide is developed and sold as racemates because of racemization at the chiral center of the 3-aminoglutarimide moiety. Herein, we show that replacement of the exchangeable hydrogen at the chiral center with deuterium allows the stabilization and testing of individual enantiomers for two thalidomide analogs, including CC-122, a compound currently in human clinical trials for hematological cancers and solid tumors. Using “deuterium-enabled chiral switching” (DECS), in vitro antiinflammatory differences of up to 20-fold are observed between the deuterium-stabilized enantiomers. In vivo, the exposure is dramatically increased for each enantiomer while they retain similar pharmacokinetics. Furthermore, the single deuterated enantiomers related to CC-122 exhibit profoundly different in vivo responses in an NCI-H929 myeloma xenograft model. The (−)-deuterated enantiomer is antitumorigenic, whereas the (+)-deuterated enantiomer has little to no effect on tumor growth. The ability to stabilize and differentiate enantiomers by DECS opens up a vast window of opportunity to characterize the class effects of thalidomide analogs and improve on the therapeutic promise of other racemic compounds, including the development of safer therapeutics and the discovery of new mechanisms and clinical applications for existing therapeutics. PMID:25775521

Identification of the functional binding pocket for compounds targeting small-conductance Ca2+-activated potassium channels

PubMed Central

Zhang, Miao; Pascal, John M.; Schumann, Marcel; Armen, Roger S.; Zhang, Ji-fang

2012-01-01

Small- and intermediate-conductance Ca2+-activated potassium channels, activated by Ca2+-bound calmodulin, play an important role in regulating membrane excitability. These channels are also linked to clinical abnormalities. A tremendous amount of effort has been devoted to developing small molecule compounds targeting these channels. However, these compounds often suffer from low potency and lack of selectivity, hindering their potentials for clinical use. A key contributing factor is the lack of knowledge of the binding site(s) for these compounds. Here we demonstrate by X-ray crystallography that the binding pocket for the compounds of the 1-EBIO class is located at the calmodulin-channel interface. We show that, based on structure data and molecular docking, mutations of the channel can effectively change the potency of these compounds. Our results provide insight into the molecular nature of the binding pocket and its contribution to the potency and selectivity of the compounds of the 1-EBIO class. PMID:22929778

Identification of the functional binding pocket for compounds targeting small-conductance Ca²⁺-activated potassium channels.

PubMed

Zhang, Miao; Pascal, John M; Schumann, Marcel; Armen, Roger S; Zhang, Ji-Fang

2012-01-01

Small- and intermediate-conductance Ca(2+)-activated potassium channels, activated by Ca(2+)-bound calmodulin, have an important role in regulating membrane excitability. These channels are also linked to clinical abnormalities. A tremendous amount of effort has been devoted to developing small molecule compounds targeting these channels. However, these compounds often suffer from low potency and lack of selectivity, hindering their potential for clinical use. A key contributing factor is the lack of knowledge of the binding site(s) for these compounds. Here we demonstrate by X-ray crystallography that the binding pocket for the compounds of the 1-ethyl-2-benzimidazolinone (1-EBIO) class is located at the calmodulin-channel interface. We show that, based on structure data and molecular docking, mutations of the channel can effectively change the potency of these compounds. Our results provide insight into the molecular nature of the binding pocket and its contribution to the potency and selectivity of the compounds of the 1-EBIO class.

Antifungal, Anticancer and Aminopeptidase Inhibitory Potential of a Phenazine Compound Produced by Lactococcus BSN307.

PubMed

Varsha, Kontham Kulangara; Nishant, Gopalan; Sneha, Srambikal Mohandas; Shilpa, Ganesan; Devendra, Leena; Priya, Sulochana; Nampoothiri, Kesavan Madhavan

2016-12-01

A bioactive compound was purified from the culture medium of a new strain of Lactococcus BSN307 by solvent extraction followed by chromatographic techniques. This bioactive compound was identified to belong to phenazine class of compounds by MS, NMR and FTIR. The phenazine compound showed antifungal activity against Aspergillus niger , Penicillium chrysogenum as well as Fusarium oxysporum by disc diffusion assay in addition to antioxidant potential as demonstrated by DPPH scavenging assay. The compound demonstrated selective cytotoxicity against cancer cell lines HeLa and MCF-7 where IC 50 was achieved with 20 and 24 µg/mL respectively. At the same time no cytotoxicity was occurred in normal H9c2 cells. The bioactive found to be inhibitory to both leucine and proline aminopeptidases and thus revealed its potential as metalloenzyme inhibitor. This study, for the first time reports the production of phenazine class of compounds by lactic acid bacteria.

Consumer palatability scores and volatile beef flavor compounds of five USDA quality grades and four muscles.

PubMed

Legako, J F; Brooks, J C; O'Quinn, T G; Hagan, T D J; Polkinghorne, R; Farmer, L J; Miller, M F

2015-02-01

Proximate data, consumer palatability scores and volatile compounds were investigated for four beef muscles (Longissimus lumborum, Psoas major, Semimembranosus and Gluteus medius) and five USDA quality grades(Prime, Upper 2/3 Choice, Low Choice, Select, and Standard). Quality grade did not directly affect consumer scores or volatiles but interactions (P < 0.05) between muscle and grade were determined. Consumer scores and volatiles differed (P < 0.05) between muscles. Consumers scored Psoas major highest for tenderness, juiciness, flavor liking and overall liking, followed by Longissimus lumborum, Gluteus medius, and Semimembranosus (P < 0.05). Principal component analysis revealed clustering of compound classes, formed by related mechanisms. Volatile n-aldehydes were inversely related to percent fat. Increases in lipid oxidation compounds were associated with Gluteus medius and Semimembranosus, while greater quantities of sulfur-containing compounds were associated with Psoas major. Relationships between palatability scores and volatile compound classes suggest that differences in the pattern of volatile compounds may play a valuable role in explaining consumer liking.

Analysis of phenolic compounds in different parts of pomegranate (Punica granatum) fruit by HPLC-PDA-ESI/MS and evaluation of their antioxidant activity: application to different Italian varieties.

PubMed

Russo, Marina; Fanali, Chiara; Tripodo, Giusy; Dugo, Paola; Muleo, Rosario; Dugo, Laura; De Gara, Laura; Mondello, Luigi

2018-06-01

The analysis of pomegranate phenolic compounds belonging to different classes in different fruit parts was performed by high-performance liquid chromatography coupled with photodiode array and mass spectrometry detection. Two different separation methods were optimized for the analysis of anthocyanins and hydrolyzable tannins along with phenolic acids and flavonoids. Two C 18 columns, core-shell and fully porous particle stationary phases, were used. The parameters for separation of phenolic compounds were optimized considering chromatographic resolution and analysis time. Thirty-five phenolic compounds were found, and 28 of them were tentatively identified as belonging to four different phenolic compound classes; namely, anthocyanins, phenolic acids, hydrolyzable tannins, and flavonoids. Quantitative analysis was performed with a mixture of nine phenolic compounds belonging to phenolic compound classes representative of pomegranate. The method was then fully validated in terms of retention time precision, expressed as the relative standard deviation, limit of detection, limit of quantification, and linearity range. Phenolic compounds were analyzed directly in pomegranate juice, and after solvent extraction with a mixture of water and methanol with a small percentage of acid in peel and pulp samples. The accuracy of the extraction method was also assessed, and satisfactory values were obtained. Finally, the method was used to study identified analytes in pomegranate juice, peel, and pulp of six different Italian varieties and one international variety. Differences in phenolic compound profiles among the different pomegranate parts were observed. Pomegranate peel samples showed a high concentration of phenolic compounds, ellagitannins being the most abundant ones, with respect to pulp and juice samples for each variety. With the same samples, total phenols and antioxidant activity were evaluated through colorimetric assays, and the results were correlated among them.

Identifying Marine Copper-Binding Ligands in Seawater

NASA Astrophysics Data System (ADS)

Whitby, H.; Hollibaugh, J. T.; Maldonado, M. T.; Ouchi, S.; van den Berg, S. M.

2016-02-01

Complexation reactions are important because they affect the bioavailability of trace metals such as copper and iron. For example, organic complexation can determine whether copper is a limiting or a toxic micronutrient at natural levels. Copper competes with iron for complexing ligands, and when iron is limiting, copper can also substitute for iron in some metabolic pathways. The speciation of copper can be measured using complexing capacity titrations, which provide the concentration of individual ligand classes (L1, L2 etc.) and the complex stabilities (log K). Using methods recently developed in our laboratory, we show that the ligands within these classes can be measured independently of titrations, thus confirming the titration method and simultaneously identifying the ligands within each class. Thiols were identified as the L1 ligand class and humic compounds as the weaker L2 class in samples from coastal Georgia, USA, collected monthly from April to December. Log K values of the ligand complexes were consistent with values expected for thiols and humic substances. Recent results from culture studies and from samples collected along Line P, a coastal - oceanic transect in the HNLC region of the NE subarctic Pacific, will be presented in comparison to the estuarine results. This comparison will help to broaden our perspective on copper complexation and the ligands responsible, furthering our understanding of ligand sources and life cycles.

Promiscuous Actions of Small Molecule Inhibitors of the Protein Kinase D-Class IIa HDAC Axis in Striated Muscle

PubMed Central

Lemon, Douglas D.; Harrison, Brooke C.; Horn, Todd R.; Stratton, Matthew S.; Ferguson, Bradley S.; Wempe, Michael F.; McKinsey, Timothy A.

2015-01-01

PKD-mediated phosphorylation of class IIa HDACs frees the MEF2 transcription factor to activate genes that govern muscle differentiation and growth. Studies of the regulation and function of this signaling axis have involved MC1568 and Gö-6976, which are small molecule inhibitors of class IIa HDAC and PKD catalytic activity, respectively. We describe unanticipated effects of these compounds. MC1568 failed to inhibit class IIa HDAC catalytic activity in vitro, and exerted divergent effects on skeletal muscle differentiation compared to a bona fide inhibitor of these HDACs. In cardiomyocytes, Gö-6976 triggered calcium signaling and activated stress-inducible kinases. Based on these findings, caution is warranted when employing MC1568 and Gö-6976 as pharmacological tool compounds to assess functions of class IIa HDACs and PKD. PMID:25816750

Comparison and Enumeration of Chemical Graphs

PubMed Central

Akutsu, Tatsuya; Nagamochi, Hiroshi

2013-01-01

Chemical compounds are usually represented as graph structured data in computers. In this review article, we overview several graph classes relevant to chemical compounds and the computational complexities of several fundamental problems for these graph classes. In particular, we consider the following problems: determining whether two chemical graphs are identical, determining whether one input chemical graph is a part of the other input chemical graph, finding a maximum common part of two input graphs, finding a reaction atom mapping, enumerating possible chemical graphs, and enumerating stereoisomers. We also discuss the relationship between the fifth problem and kernel functions for chemical compounds. PMID:24688697

Detection of Stimulants and Narcotics by Liquid Chromatography-Tandem Mass Spectrometry and Gas Chromatography-Mass Spectrometry for Sports Doping Control.

PubMed

Ahrens, Brian D; Kucherova, Yulia; Butch, Anthony W

2016-01-01

Sports drug testing laboratories are required to detect several classes of compounds that are prohibited at all times, which include anabolic agents, peptide hormones, growth factors, beta-2 agonists, hormones and metabolic modulators, and diuretics/masking agents. Other classes of compounds such as stimulants, narcotics, cannabinoids, and glucocorticoids are also prohibited, but only when an athlete is in competition. A single class of compounds can contain a large number of prohibited substances and all of the compounds should be detected by the testing procedure. Since there are almost 70 stimulants on the prohibited list it can be a challenge to develop a single screening method that will optimally detect all the compounds. We describe a combined liquid chromatography-tandem mass spectrometry (LC-MS/MS) and gas chromatography-mass spectrometry (GC-MS) testing method for detection of all the stimulants and narcotics on the World Anti-Doping Agency prohibited list. Urine for LC-MS/MS testing does not require sample pretreatment and is a direct dilute and shoot method. Urine samples for the GC-MS method require a liquid-liquid extraction followed by derivatization with trifluoroacetic anhydride.

Effects of twenty-five compounds on four species of aquatic fungi (Saprolegniales) pathogenic to fish

USGS Publications Warehouse

Bailey, T.A.

1984-01-01

Four species of aquatic fungi (Achlya flagellata, A. racemosa, Saprolegnia hypogyna, and S. megasperma) were exposed to 25 chemicals representing seven classes of compounds for 15 and 60 min, in an effort to identify potential fungicidal agents for use in fish culture. The antifungal activity of each chemical was compared with that of malachite green, a reference compound with known fungicidal properties but not registered for fishery use. Six compounds which inhibited fungal growth on artificial media at concentrations of < 100 mg/l (listed in order of decreasing antifungal activity) were the cationics Du-terA? and copper oxychloride sulfate, the amine LesanA?, the amide BAS-389-O1F and the cationics CuprimyxinA? and RoccalA? II. Certain chemicals from these classes of compounds may have promise as aquatic fungicides.

The Effectiveness of learning materials based on multiple intelligence on the understanding of global warming

NASA Astrophysics Data System (ADS)

Liliawati, W.; Purwanto; Zulfikar, A.; Kamal, R. N.

2018-05-01

This study aims to examine the effectiveness of the use of teaching materials based on multiple intelligences on the understanding of high school students’ material on the theme of global warming. The research method used is static-group pretest-posttest design. Participants of the study were 60 high school students of XI class in one of the high schools in Bandung. Participants were divided into two classes of 30 students each for the experimental class and control class. The experimental class uses compound-based teaching materials while the experimental class does not use a compound intelligence-based teaching material. The instrument used is a test of understanding of the concept of global warming with multiple choices form amounted to 15 questions and 5 essay items. The test is given before and after it is applied to both classes. Data analysis using N-gain and effect size. The results obtained that the N-gain for both classes is in the medium category and the effectiveness of the use of teaching materials based on the results of effect-size test results obtained in the high category.

Detecting trace pesticides in real time using single particle aerosol mass spectrometry.

PubMed

Barker, Zachary; Venkatchalam, Veena; Martin, Audrey N; Farquar, George R; Frank, Matthias

2010-02-28

Pesticides are toxic substances and may cause unintentional harm if improperly used. The ubiquitous nature of pesticides, with frequent use in agriculture and the household, and the potential for harm that pesticides pose to non-target organisms such as wildlife, humans, and pets, demonstrate the need for rapid and effective detection and identification of these compounds. In this study, single particle aerosol mass spectrometry (SPAMS) was used to rapidly detect compounds from four classes of pesticides commonly used in agricultural and household applications. These include permethrin (pyrethroid class), malathion and dichlorvos (organophosphate class), imidacloprid (chloronicotinyl class), and carbaryl (carbamate class). Analytical standards of each compound were diluted and aerosolized using a nebulizer to create particles for analysis in the SPAMS instrument. The resultant dual-polarity time-of-flight mass spectra were then analyzed to identify the characteristic peaks of the compound in each sample. In addition, samples of commercial products containing pesticides, a commercial insecticide spray, containing permethrin, and a canine flea collar, containing carbaryl, were analyzed in their original form using SPAMS without any significant sample preparation. The characteristic mass spectral peaks of the active pesticides in these samples were identified using the mass spectra obtained earlier from the pesticide analytical standards. By successfully identifying pesticides in analytical standards and in commercial products, it is demonstrated herein that the SPAMS system may be capable of pesticide detection in numerous environmental and agricultural situations. Copyright 2010 Elsevier B.V. All rights reserved.

Perfluorinated Compounds: Emerging POPs with Potential Immunotoxicity

EPA Science Inventory

Perfluorinated compounds (PFCs) have been recognized as an important class of environmental contaminants commonly detected in blood samples of both wildlife and humans. These compounds have been in use for more than 60 years as surface treatment chemicals, polymerization aids, an...

Experimental Solubility Approach to Determine PDMS-Water Partition Constants and PDMS Activity Coefficients.

PubMed

Grant, Sharon; Schacht, Veronika J; Escher, Beate I; Hawker, Darryl W; Gaus, Caroline

2016-03-15

Freely dissolved aqueous concentration and chemical activity are important determinants of contaminant transport, fate, and toxic potential. Both parameters are commonly quantified using Solid Phase Micro-Extraction (SPME) based on a sorptive polymer such as polydimethylsiloxane (PDMS). This method requires the PDMS-water partition constants, KPDMSw, or activity coefficient to be known. For superhydrophobic contaminants (log KOW >6), application of existing methods to measure these parameters is challenging, and independent measures to validate KPDMSw values would be beneficial. We developed a simple, rapid method to directly measure PDMS solubilities of solid contaminants, SPDMS(S), which together with literature thermodynamic properties was then used to estimate KPDMSw and activity coefficients in PDMS. PDMS solubility for the test compounds (log KOW 7.2-8.3) ranged over 3 orders of magnitude (4.1-5700 μM), and was dependent on compound class. For polychlorinated biphenyls (PCBs) and polychlorinated dibenzo-p-dioxins (PCDDs), solubility-derived KPDMSw increased linearly with hydrophobicity, consistent with trends previously reported for less chlorinated congeners. In contrast, subcooled liquid PDMS solubilities, SPDMS(L), were approximately constant within a compound class. SPDMS(S) and KPDMSw can therefore be predicted for a compound class with reasonable robustness based solely on the class-specific SPDMS(L) and a particular congener's entropy of fusion, melting point, and aqueous solubility.

Combined effects of education level and perceived social class on self-rated health and life satisfaction: Results of Korean labor and income panel study wave 8-wave 15.

PubMed

Kim, Jae-Hyun; Yoo, Ki-Bong; Park, Eun-Cheol; Lee, Sang Gyu; Kim, Tae Hyun

2015-11-02

To examine the combined effects of education level and perceived social class on self-rated health and life satisfaction in South Korea. We used data drawn from the 8 to 15th wave of the Korean Labor and Income Panel Study (KLIPS). Using wave 8 at baseline, data included 11,175 individuals. We performed a longitudinal analysis at baseline estimating the prevalence of self-rated health and life satisfaction among individuals by education level (high, middle, and low education level) and perceived social class (high, middle, and low social class). For self-rated health, odds ratio (OR) of individuals with low education and low perceived social class was 0.604 times lower (95% CI: 0.555-0.656) and the OR of individuals with low education and middle perceived social class was 0.853 time lower (95% CI: 0.790-0.922) when compared to individuals with high education and high perceived social class. For life satisfaction, OR of individuals with low education and low perceived social class was 0.068 times lower (95% CI: 0.063-0.074) and the OR of individuals with middle education and middle perceived social class was 0.235 time lower (95% CI: 0.221-0.251) compared to individuals with high education and high perceived social class. This study shows that the combined effects of education level and perceived social class associated with self-rated health and life satisfaction. Our study suggests increasing education level and perceived social class. Additionally, it will be important to develop multi-dimensional measurement tools including education level and subjective social class.

Characterization of E 471 food emulsifiers by high-performance thin-layer chromatography-fluorescence detection.

PubMed

Oellig, Claudia; Brändle, Klara; Schwack, Wolfgang

2018-07-13

Mono- and diacylglycerol (MAG and DAG) emulsifiers, also known as food additive E 471, are widely used to adjust techno-functional properties in various foods. Besides MAGs and DAGs, E 471 emulsifiers additionally comprise different amounts of triacylglycerols (TAGs) and free fatty acids (FFAs). MAGs, DAGs, TAGs and FFAs are generally determined by high-performance liquid chromatography (HPLC) or gas chromatography (GC) coupled to mass selective detection, analyzing the individual representatives of the lipid classes. In this work we present a rapid and sensitive method for the determination of MAGs, DAGs, TAGs and FFAs in E 471 emulsifiers by high-performance thin-layer chromatography with fluorescence detection (HPTLC-FLD), including a response factor system for quantitation. Samples were simply dissolved and diluted with t-butyl methyl ether before a two-fold development was performed on primuline pre-impregnated LiChrospher silica gel plates with diethyl ether and n-pentane/n-hexane/diethyl ether (52:20:28, v/v/v) as the mobile phases to 18 and 75 mm, respectively. For quantitation, the plate was scanned in the fluorescence mode at UV 366/>400 nm, when the cumulative signal for each lipid class was used. Calibration was done with 1,2-distearin and amounts of lipid classes were calculated with response factors and expressed as monostearin, distearin, tristearin and stearic acid. Limits of detection and quantitation were 1 and 4 ng/zone, respectively, for 1,2-distearin. Thus, the HPTLC-FLD approach represents a simple, rapid and convenient screening alternative to HPLC and GC analysis of the individual compounds. Visual detection additionally enables an easy characterization and the direct comparison of emulsifiers through the lipid class pattern, when utilized as a fingerprint. Copyright © 2018 Elsevier B.V. All rights reserved.

Social class, contextualism, and empathic accuracy.

PubMed

Kraus, Michael W; Côté, Stéphane; Keltner, Dacher

2010-11-01

Recent research suggests that lower-class individuals favor explanations of personal and political outcomes that are oriented to features of the external environment. We extended this work by testing the hypothesis that, as a result, individuals of a lower social class are more empathically accurate in judging the emotions of other people. In three studies, lower-class individuals (compared with upper-class individuals) received higher scores on a test of empathic accuracy (Study 1), judged the emotions of an interaction partner more accurately (Study 2), and made more accurate inferences about emotion from static images of muscle movements in the eyes (Study 3). Moreover, the association between social class and empathic accuracy was explained by the tendency for lower-class individuals to explain social events in terms of features of the external environment. The implications of class-based patterns in empathic accuracy for well-being and relationship outcomes are discussed.

Multiscale Modelling of Relationships between Protein Classes and Drug Behavior Across all Diseases Using the CANDO Platform

PubMed Central

Samudrala, Ram

2015-01-01

We have examined the effect of eight different protein classes (channels, GPCRs, kinases, ligases, nuclear receptors, proteases, phosphatases, transporters) on the benchmarking performance of the CANDO drug discovery and repurposing platform (http://protinfo.org/cando). The first version of the CANDO platform utilizes a matrix of predicted interactions between 48278 proteins and 3733 human ingestible compounds (including FDA approved drugs and supplements) that map to 2030 indications/diseases using a hierarchical chem and bio-informatic fragment based docking with dynamics protocol (> one billion predicted interactions considered). The platform uses similarity of compound-proteome interaction signatures as indicative of similar functional behavior and benchmarking accuracy is calculated across 1439 indications/diseases with more than one approved drug. The CANDO platform yields a significant correlation (0.99, p-value < 0.0001) between the number of proteins considered and benchmarking accuracy obtained indicating the importance of multitargeting for drug discovery. Average benchmarking accuracies range from 6.2 % to 7.6 % for the eight classes when the top 10 ranked compounds are considered, in contrast to a range of 5.5 % to 11.7 % obtained for the comparison/control sets consisting of 10, 100, 1000, and 10000 single best performing proteins. These results are generally two orders of magnitude better than the average accuracy of 0.2% obtained when randomly generated (fully scrambled) matrices are used. Different indications perform well when different classes are used but the best accuracies (up to 11.7% for the top 10 ranked compounds) are achieved when a combination of classes are used containing the broadest distribution of protein folds. Our results illustrate the utility of the CANDO approach and the consideration of different protein classes for devising indication specific protocols for drug repurposing as well as drug discovery. PMID:25694071

Decision trees to characterise the roles of permeability and solubility on the prediction of oral absorption.

PubMed

Newby, Danielle; Freitas, Alex A; Ghafourian, Taravat

2015-01-27

Oral absorption of compounds depends on many physiological, physiochemical and formulation factors. Two important properties that govern oral absorption are in vitro permeability and solubility, which are commonly used as indicators of human intestinal absorption. Despite this, the nature and exact characteristics of the relationship between these parameters are not well understood. In this study a large dataset of human intestinal absorption was collated along with in vitro permeability, aqueous solubility, melting point, and maximum dose for the same compounds. The dataset allowed a permeability threshold to be established objectively to predict high or low intestinal absorption. Using this permeability threshold, classification decision trees incorporating a solubility-related parameter such as experimental or predicted solubility, or the melting point based absorption potential (MPbAP), along with structural molecular descriptors were developed and validated to predict oral absorption class. The decision trees were able to determine the individual roles of permeability and solubility in oral absorption process. Poorly permeable compounds with high solubility show low intestinal absorption, whereas poorly water soluble compounds with high or low permeability may have high intestinal absorption provided that they have certain molecular characteristics such as a small polar surface or specific topology. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Novel structural analogues of piperine as inhibitors of the NorA efflux pump of Staphylococcus aureus.

PubMed

Kumar, Ashwani; Khan, Inshad Ali; Koul, Surrinder; Koul, Jawahir Lal; Taneja, Subhash Chandra; Ali, Intzar; Ali, Furqan; Sharma, Sandeep; Mirza, Zahid Mehmood; Kumar, Manoj; Sangwan, Pyare Lal; Gupta, Pankaj; Thota, Niranjan; Qazi, Ghulam Nabi

2008-06-01

Evaluation of novel synthetic analogues of piperine as inhibitors of multidrug efflux pump NorA of Staphylococcus aureus. A library of piperine-derived compounds was evaluated for their potential to inhibit ethidium bromide efflux in NorA-overexpressing S. aureus SA 1199B. The active compounds were then individually combined with ciprofloxacin to study the potentiation of ciprofloxacin's activity. Based on the efflux inhibition assay, a library of 200 compounds was screened. Three piperine analogues, namely SK-20, SK-56 and SK-29, were found to be the most potent inhibitors of the NorA efflux pump. These inhibitors acted in a synergistic manner with ciprofloxacin, by substantially increasing its activity against both NorA-overexpressing and wild-type S. aureus isolates. These analogues were 2- to 4-fold more potent than piperine at a significantly lower minimal effective concentration. Furthermore, these inhibitors also significantly suppressed the in vitro emergence of ciprofloxacin-resistant S. aureus. A newly identified class of compounds derived from a natural amide, piperine, is more potent than the parent molecule in potentiating the activity of ciprofloxacin through the inhibition of the NorA efflux pump. These molecules may prove useful in augmenting the antibacterial activities of fluoroquinolones in a clinical setting.

Synthesis of Organic Matter of Prebiotic Chemistry at the Protoplanetary Disc

NASA Astrophysics Data System (ADS)

Snytnikov, Valeriy; Stoynovskaya, Olga; Rudina, Nina

We have carried out scanning electron microscopic examination of CM carbonaceous chondrites meteorites Migey, Murchison, Staroe Boriskino aged more than 4.56 billion years (about 50 million years from the beginning of the formation of the Solar system). Our study confirmed the conclusion of Rozanov, Hoover and other researchers about the presence of microfossils of bacterial origin in the matrix of all these meteorites. Since the time of the Solar system formation is 60 - 100 million years, the primary biocenosis emerged in the protoplanetary disc of the Solar system before meteorites or simultaneously with them. It means that prebiological processes and RNA world appeared even earlier in the circumsolar protoplanetary disc. Most likely, this appearance of prebiotic chemistry takes place nowday in massive and medium-massive discs of the observed young stellar objects (YSO) class 0 and I. The timescale of the transition from chemical to biological evolution took less than 50 million years for the Solar system. Further evolution of individual biocenosis in a protoplanetary disc associated with varying physico-chemical conditions during the formation of the Solar system bodies. Biocenosis on these bodies could remove or develop under the influence of many cosmic factors and geological processes in the case of Earth. To complete the primary biosphere formation in short evolution time - millions of years - requires highly efficient chemical syntheses. In industrial chemistry for the efficient synthesis of ammonia, hydrogen cyanide, methanol and other organic species, that are the precursors to obtain prebiotic compounds, catalytic reactors of high pressure are used. Thus (1) necessary amount of the proper catalyst in (2) high pressure areas of the disc can trigger these intense syntheses. The disc contains the solids with the size from nanoparticle to pebble. Iron and magnesium is catalytically active ingredient for such solids. The puzzle is a way to provide hydrogen pressure inside the disc from tens to hundred atmospheres. We simulated unsteady processes in massive circumstellar discs around YSO class O and I. In the computational experiments, we have shown that at a certain stage of its evolution the circumstellar discs of gas and solids produces local areas of high pressure. According to the classical heterogeneous catalysis, a wide range of organic and prebiotic compounds could have been synthesized in these areas. Can we capture these areas of high pressure synthesis in observation of circumstellar discs? Due to the small sizes of such areas they can be hardly ever resolved even with the modern telescopes such as ALMA. However, we can try to detect their signatures in the disc, since the gas of the disc keep the set of organic synthesis products. The idea is to define the signature of the process using laboratory experiments. Varying gas temperature and pressure in laboratory setup we can carry out the catalytic high pressure syntheses and specify the set of gaseous products. These sets of organic compounds observed in the discs may serve as indicators of the emergence of high-pressure areas of prebiotic chemistry. Thus, there is a special interest to the study of YSO class 0 and I by means of observational astronomy. For these objects, first data on the presence of individual organic compounds in massive hydrogen-helium component of the discs appear. The origin of the organic compounds that are associated with chemical reactions in the discs should be separated from the set of organic compounds of the initial molecular cloud.

Source chemical characterization of swine odor

USDA-ARS?s Scientific Manuscript database

Odors from swine production have been linked to a host of issues affecting quality of life, property values and potentially human health. Typical compounds and classes of compounds include: sulfides, thiols, acids, phenols, indoles, ammonia and amines. The wide range of compounds assoicated with swi...

VOLATILE ORGANIC COMPOUNDS (VOCS) CHAPTER 31.

EPA Science Inventory

The term "volatile organic compounds' (VOCs) was originally coined to refer, as a class, to carbon-containing chemicals that participate in photochemical reactions in the ambient (outdoor) are. The regulatory definition of VOCs used by the U.S. EPA is: Any compound of carbon, ex...

Molecular mechanisms underlying the antitumor activity of (E)-N-hydroxy-3-(1-(4-methoxyphenylsulfonyl)-1,2,3,4-tetrahydroquinolin-6-yl)acrylamide in human colorectal cancer cells in vitro and in vivo

PubMed Central

Chen, Chun-Han; Lee, Chia-Hwa; Liou, Jing-Ping; Teng, Che-Ming; Pan, Shiow-Lin

2015-01-01

Upregulation of class I histone deacetylases (HDAC) correlates with poor prognosis in colorectal cancer (CRC) patients. Previous study revealed that (E)-N-hydroxy-3-(1-(4-methoxyphenylsulfonyl)-1,2,3,4-tetrahydroquinolin-6-yl)acrylamide (Compound 11) is a potent and selective class I HDAC inhibitor, exhibited significant anti-proliferative activity in various human cancer cell lines. In current study, we demonstrated that compound 11 exhibited significant anti-proliferative and cytotoxic activity in CRC cells. Notably, compound 11 was less potent than SAHA in inhibiting HDAC6 as evident from the lower expression of acetyl-α-tubulin, suggesting higher selectivity for class I HDACs. Mechanistically, compound 11 induced cell-cycle arrest at the G2/M phase, activated both intrinsic- and extrinsic-apoptotic pathways, altered the expression of Bcl-2 family proteins and exerted a potent inhibitory effect on survival signals (p-Akt, p-ERK) in CRC cells. Moreover, we provide evidence that compound 11 suppressed motility, decreased mesenchymal markers (N-cadherin and vimentin) and increased epithelial marker (E-cadherin) through down-regulation of Akt. The anti-tumor activity and underlying molecular mechanisms of compound 11 were further confirmed using the HCT116 xenograft model in vivo. Our findings provide evidence of the significant anti-tumor activity of compound 11 in a preclinical model, supporting its potential as a novel therapeutic agent for CRC. PMID:26462017

Social class and prosocial behavior: current evidence, caveats, and questions.

PubMed

Piff, Paul K; Robinson, Angela R

2017-12-01

This review synthesizes research on social class and prosocial behavior. Individuals of lower social class display increased attention to others and greater sensitivity to others' welfare compared to individuals of higher social class, who exhibit more self-oriented patterns of social cognition. As a result, lower-class individuals are more likely to engage in other-beneficial prosocial behavior, whereas higher-class individuals are more prone to engage in self-beneficial behavior. Although the extant evidence indicates that higher social class standing may tend to undermine prosocial impulses, we propose that the effects of social class on prosocial behavior may also depend on three crucial factors: motivation, identity, and inequality. We discuss how and why these factors may moderate class differences in prosociality and offer promising lines of inquiry for future research. Copyright © 2017 Elsevier Ltd. All rights reserved.

Rational Design Synthesis and Evaluation of New Selective Inhibitors of Microbial Class II (Zinc Dependent) Fructose Bis-phosphate Aldolases

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

R Daher; M Coincon; M Fonvielle

2011-12-31

We report the synthesis and biochemical evaluation of several selective inhibitors of class II (zinc dependent) fructose bis-phosphate aldolases (Fba). The products were designed as transition-state analogues of the catalyzed reaction, structurally related to the substrate fructose bis-phosphate (or sedoheptulose bis-phosphate) and based on an N-substituted hydroxamic acid, as a chelator of the zinc ion present in active site. The compounds synthesized were tested on class II Fbas from various pathogenic microorganisms and, by comparison, on a mammalian class I Fba. The best inhibitor shows Ki against class II Fbas from various pathogens in the nM range, with very highmore » selectivity (up to 105). Structural analyses of inhibitors in complex with aldolases rationalize and corroborate the enzymatic kinetics results. These inhibitors represent lead compounds for the preparation of new synthetic antibiotics, notably for tuberculosis prophylaxis.« less

Highly diverse, massive organic data as explored by a composite QSPR strategy: an advanced study of boiling point.

PubMed

Ivanova, A A; Ivanov, A A; Oliferenko, A A; Palyulin, V A; Zefirov, N S

2005-06-01

An improved strategy of quantitative structure-property relationship (QSPR) studies of diverse and inhomogeneous organic datasets has been proposed. A molecular connectivity term was successively corrected for different structural features encoded in fragmental descriptors. The so-called solvation index 1chis (a weighted Randic index) was used as a "leading" variable and standardized molecular fragments were employed as "corrective" class-specific variables. Performance of the new approach was illustrated by modelling a dataset of experimental normal boiling points of 833 organic compounds belonging to 20 structural classes. Firstly, separate QSPR models were derived for each class and for eight groups of structurally similar classes. Finally, a general model formed by combining all the classes together was derived (r2=0.957, s=12.9degreesC). The strategy outlined can find application in QSPR analyses of massive, highly diverse databases of organic compounds.

Identifying Novel Molecular Structures for Advanced Melanoma by Ligand-Based Virtual Screening

PubMed Central

Wang, Zhao; Lu, Yan; Seibel, William; Miller, Duane D.; Li, Wei

2009-01-01

We recently discovered a new class of thiazole analogs that are highly potent against melanoma cells. To expand the structure-activity relationship study and to explore potential new molecular scaffolds, we performed extensive ligand-based virtual screening against a compound library containing 342,910 small molecules. Two different approaches of virtual screening were carried out using the structure of our lead molecule: 1) connectivity-based search using Scitegic Pipeline Pilot from Accelerys and 2) molecular shape similarity search using Schrodinger software. Using a testing compound library, both approaches can rank similar compounds very high and rank dissimilar compounds very low, thus validating our screening methods. Structures identified from these searches were analyzed, and selected compounds were tested in vitro to assess their activity against melanoma cancer cell lines. Several molecules showed good anticancer activity. While none of the identified compounds showed better activity than our lead compound, they provided important insight into structural modifications for our lead compound and also provided novel platforms on which we can optimize new classes of anticancer compounds. One of the newly synthesized analogs based on this virtual screening has improved potency and selectivity against melanoma. PMID:19445498

Investigation of the enzymology and pharmacology of novel substrates and inhibitors of dopamine beta-monooxygenase

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

Roberts, S.F.

1987-01-01

Dopamine beta-monooxygenase (DBM) was shown to catalyze the selenoxidation of 2-(phenylseleno)ethylamines, selenium-containing analogues of dopamine, by the normal monooxygenase pathway. The compounds 2-(phenylseleno)-ethylamine (PAESe), 2-(4'-hydroxyphenylseleno)ethylamine (pOH PAESe), and 1-(phenylseleno)-2-propylamine (Me PAESe) were synthesized and fully characterized as DBM substrates. Two other classes of compounds were investigated as potential alternate substrates for DBM. The possibility of stereoselective sulfonylation of 2-(phenylsulfenyl)- ethylamine (PAESO) was considered. A unique class of compounds, 2-(phenylthio)ethanols were designed and synthesized as DBM substrates but were found to be a novel class of potent competitive inhibitors of DBM with respect to tyramine. Preliminary experiments were also performed inmore » an effort to demonstrate that the potent antihypertensive and indirect-acting sympathomimetic activity of 2-(phenylthio)ethylamine (PAES) was a result of DBM-oxygenation of this compound in vivo. The specific reserpine-sensitive uptake of (/sup 3/H)-norepinephrine into rat brain synaptosomes was demonstrated as was the synaptosomal conversion of (/sup 3/H)-dopamine to (/sup 3/H)-norepinephrine.« less

Natural products as sources of new fungicides (IV): Synthesis and biological evaluation of isobutyrophenone analogs as potential inhibitors of class-II fructose-1,6-bisphosphate aldolase.

PubMed

Li, Ding; Luong, Tuong Thi Mai; Dan, Wen-Jia; Ren, Yanliang; Nien, Hoang Xuan; Zhang, An-Ling; Gao, Jin-Ming

2018-01-15

Several recently identified antifungal compounds share the backbone structure of acetophenones. The aim of the present study was to develop new isobutyrophenone analogs as new antifungal agents. A series of new 2,4-dihydroxy-5-methyl isobutyrophenone derivatives were prepared and characterized by 1 H, 13 C NMR and MS spectroscopic data. These products were evaluated for in vitro antifungal activities against seven plant fungal pathogens by the mycelial growth inhibitory rate assay. Compounds 3, 4a, 5a, 5b, 5e, 5f and 5g showed a broad-spectrum high antifungal activity. On the other hand, for the first time, these compounds were also assayed as potential inhibitors against Class II fructose-1,6-bisphosphate aldolase (Fba) from the rice blast fungus, Magnaporthe grisea. Compounds 5e and 5g were found to exhibit the inhibition constants (Ki) for 15.12 and 14.27 μM, respectively, as the strongest competitive inhibitors against Fba activity. The possible binding-modes of compounds 5e and 5g were further analyzed by molecular docking algorithms. The results strongly suggested that compound 5g could be a promising lead for the discovery of new fungicides via targeting Class II Fba. Copyright © 2017 Elsevier Ltd. All rights reserved.

From the Test Tube to the Treatment Room

PubMed Central

Del Rosso, James Q.; Plattner, Jacob J.

2014-01-01

The development of new drug classes and novel molecules that are brought to the marketplace has been a formidable challenge, especially for dermatologic drugs. The relative absence of new classes of antimicrobial agents is also readily apparent. Several barriers account for slow drug development, including regulatory changes, added study requirements, commercial pressures to bring drugs to market quickly by developing new generations of established compounds, and the greater potential for failure and higher financial risk when researching new drug classes. In addition, the return on investment is usually much lower with dermatologic drugs as compared to the potential revenue from “blockbuster” drugs for cardiovascular or gastrointestinal disease, hypercholesterolemia, and mood disorders. Nevertheless, some researchers are investigating new therapeutic platforms, one of which is boron-containing compounds. Boron-containing compounds offer a wide variety of potential applications in dermatology due to their unique physical and chemical properties, with several in formal phases of development. Tavaborole, a benzoxaborole compound, has been submitted to the United States Food and Drug Administration for approval for treatment of onychomycosis. This article provides a thorough overview of the history of boron-based compounds in medicine, their scientific rationale, physiochemical and pharmacologic properties, and modes of actions including therapeutic targets. A section dedicated to boron-based compounds in development for treatment of various skin disorders is also included. PMID:24578778

Increasing human Th17 differentiation through activation of orphan nuclear receptor retinoid acid-related orphan receptor γ (RORγ) by a class of aryl amide compounds.

PubMed

Zhang, Wei; Zhang, Jing; Fang, Leiping; Zhou, Ling; Wang, Shuai; Xiang, Zhijun; Li, Yuan; Wisely, Bruce; Zhang, Guifeng; An, Gang; Wang, Yonghui; Leung, Stewart; Zhong, Zhong

2012-10-01

In a screen for small-molecule inhibitors of retinoid acid-related orphan receptor γ (RORγ), we fortuitously discovered that a class of aryl amide compounds behaved as functional activators of the interleukin 17 (IL-17) reporter in Jurkat cells. Three of these compounds were selected for further analysis and found to activate the IL-17 reporter with potencies of ∼0.1 μM measured by EC₅₀. These compounds were shown to directly bind to RORγ by circular dichroism-based thermal stability experiments. Furthermore, they can enhance an in vitro Th17 differentiation process in human primary T cells. As RORγ remains an orphan nuclear receptor, discovery of these aryl amide compounds as functional agonists will now provide pharmacological tools for us to dissect functions of RORγ and facilitate drug discovery efforts for immune-modulating therapies.

Polyphenols and Volatile Compounds in Commercial Chokeberry (Aronia melanocarpa) Products.

PubMed

Romani, Annalisa; Vignolini, Pamela; Ieri, Francesca; Heimler, Daniela

2016-01-01

Aronia melanocarpa (Michx.) Elliott commercial products (dried fruit, juice and compote) were analyzed for their polyphenol content by chromatographic and spectrophotometric analyses in order to ascertain the fate of this group of compounds when fresh fruit is processed and sold in different forms on the market. Different classes of polyphenols were investigated: hydroxycinnamic derivatives ranged from 0.65 mg/g to 4.30 mg/g, flavonoids from 0.36 mg/g to 1.12 mg/g, and anthocyanins from 0.65 to 7.08 mg/g sample. 4-O-Caffeoyl-quinic acid was tentatively identified for the first time in Aronia. In order to characterize better chokeberry juice, a GC profile of aroma compounds was obtained. The aroma juice compounds belong mainly to the chemical classes of alcohols (48.9%) and ketones (30.28%). The most abundant compound is 3-penthen-2-one (23.6%).

Identification of a selective small molecule inhibitor of breast cancer stem cells.

PubMed

Germain, Andrew R; Carmody, Leigh C; Morgan, Barbara; Fernandez, Cristina; Forbeck, Erin; Lewis, Timothy A; Nag, Partha P; Ting, Amal; VerPlank, Lynn; Feng, Yuxiong; Perez, Jose R; Dandapani, Sivaraman; Palmer, Michelle; Lander, Eric S; Gupta, Piyush B; Schreiber, Stuart L; Munoz, Benito

2012-05-15

A high-throughput screen (HTS) with the National Institute of Health-Molecular Libraries Small Molecule Repository (NIH-MLSMR) compound collection identified a class of acyl hydrazones to be selectively lethal to breast cancer stem cell (CSC) enriched populations. Medicinal chemistry efforts were undertaken to optimize potency and selectivity of this class of compounds. The optimized compound was declared as a probe (ML239) with the NIH Molecular Libraries Program and displayed greater than 20-fold selective inhibition of the breast CSC-like cell line (HMLE_sh_Ecad) over the isogenic control line (HMLE_sh_GFP). Copyright © 2012 Elsevier Ltd. All rights reserved.

A new multidimensional stoichiometric classification of compounds: moving beyond the van Krevelen diagram.

NASA Astrophysics Data System (ADS)

Rivas-Ubach, A.; Liu, Y.; Bianchi, T. S.; Tolic, N.; Jansson, C.; Paša-Tolić, L.

2017-12-01

The role of nutrients in organisms, especially primary producers, has been a topic of special interest in ecosystem research for understanding the ecosystem structure and function. The majority of macro-elements in organisms, such as C, H, O, N and P, do not act as single elements but are components of organic compounds (lipids, peptides, carbohydrates, etc), which are more directly related to the physiology of organisms and thus to the ecosystem function. However, accurately deciphering the overall content of the main compound classes (lipids, proteins, carbohydrates,…) in organisms is still a major challenge. van Krevelen (vK) diagrams have been widely used as an estimation of the main compound categories present in environmental samples based on O:C vs H:C molecular ratios, but a stoichiometric classification based exclusively on O:C and H:C ratios is feeble. Different compound classes show large O:C and H:C ratio overlapping and other heteroatoms, such as N and P, should be considered to robustly distinguish the different classes. We propose a new compound classification for biological/environmental samples based on the C:H:O:N:P stoichiometric ratios of thousands of molecular formulas of characterized compounds from 6 different main categories: lipids, peptides, amino-sugars, carbohydrates, nucleotides and phytochemical compounds (oxy-aromatic compounds). This new multidimensional stoichiometric compound constraints classification (MSCC) can be applied to data obtained with high resolution mass spectrometry (HRMS), allowing an accurate overview of the relative abundances of the main compound categories present in organismal samples. The MSCC has been optimized for plants, but it could be also applied to different organisms and serve as a strong starting point to further investigate other environmental complex matrices (soils, aerosols, etc). The proposed MSCC advances environmental research, especially eco-metabolomics, ecophysiology and ecological stoichiometry studies, providing a new tool to understand the ecosystem structure and function at the molecular level.

Characterization of lipopeptides produced by Bacillus licheniformis using liquid chromatography with accurate tandem mass spectrometry.

PubMed

Favaro, Gabriella; Bogialli, Sara; Di Gangi, Iole Maria; Nigris, Sebastiano; Baldan, Enrico; Squartini, Andrea; Pastore, Paolo; Baldan, Barbara

2016-10-30

The plant endophyte Bacillus licheniformis, isolated from leaves of Vitis vinifera, was studied to individuate and characterize the presence of bioactive lipopeptides having amino acidic structures. Crude extracts of liquid cultures were analyzed by ultra-high-performance liquid chromatography (UHPLC) coupled to a quadrupole time-of-flight (QTOF) mass analyzer. Chromatographic conditions were optimized in order to obtain an efficient separation of the different isobaric lipopeptides, avoiding merged fragmentations of co-eluted isomeric compounds and reducing possible cross-talk phenomena. Composition of the amino acids was outlined through the interpretation of the fragmentation behavior in tandem high-resolution mass spectrometry (HRMS/MS) mode, which showed both common-class and peculiar fragment ions. Both [M + H](+) and [M + Na](+) precursor ions were fragmented in order to differentiate some isobaric amino acids, i.e. Leu/Ile. Neutral losses characteristic of the iso acyl chain were also evidenced. More than 90 compounds belonging to the classes of surfactins and lichenysins, known as biosurfactant molecules, were detected. Sequential LC/HRMS/MS analysis was used to identify linear and cyclic lipopeptides, and to single out the presence of a large number of isomers not previously reported. Some critical issues related to the simultaneous selection of different compounds by the quadrupole filter were highlighted and partially solved, leading to tentative assignments of several structures. Linear lichenysins are described here for the first time. The approach was proved to be useful for the characterization of non-target lipopeptides, and proposes a rationale MS experimental scheme aimed to investigate the difference in amino acid sequence and/or in the acyl chain of the various congeners, when standards are not available. Results expanded the knowledge about production of linear and cyclic bioactive compounds from Bacillus licheniformis, clarifying the structures of isomeric forms, and enabling the use of selected endophytes to produce fungicides for eco-friendly biocontrol. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Organic molecular composition of marine aerosols over the Arctic Ocean in summer: contributions of primary emission and secondary aerosol formation

NASA Astrophysics Data System (ADS)

Fu, P. Q.; Kawamura, K.; Chen, J.; Charrière, B.; Sempéré, R.

2013-02-01

Organic molecular composition of marine aerosol samples collected during the MALINA cruise in the Arctic Ocean was investigated by gas chromatography/mass spectrometry. More than 110 individual organic compounds were determined in the samples and were grouped into different compound classes based on the functionality and sources. The concentrations of total quantified organics ranged from 7.3 to 185 ng m-3 (mean 47.6 ng m-3), accounting for 1.8-11.0% (4.8%) of organic carbon in the marine aerosols. Primary saccharides were found to be dominant organic compound class, followed by secondary organic aerosol (SOA) tracers formed from the oxidation of biogenic volatile organic compounds (VOCs) such as isoprene, α-pinene and β-caryophyllene. Mannitol, the specific tracer for airborne fungal spores, was detected as the most abundant organic species in the samples with a concentration range of 0.052-53.3 ng m-3 (9.2 ng m-3), followed by glucose, arabitol, and the isoprene oxidation products of 2-methyltetrols. Biomass burning tracers such as levoglucosan are evident in all samples with trace levels. On the basis of the tracer-based method for the estimation of fungal-spore OC and biogenic secondary organic carbon (SOC), we estimate that an average of 10.7% (up to 26.2%) of the OC in the marine aerosols was due to the contribution of fungal spores, followed by the contribution of isoprene SOC (mean 3.8%) and α-pinene SOC (2.9%). In contrast, only 0.19% of the OC was due to the photooxidation of β-caryophyllene. This study indicates that primary organic aerosols from biogenic emissions, both from long-range transport of mid-latitude aerosols and from sea-to-air emission of marine organics, as well as secondary organic aerosols formed from the photooxidation of biogenic VOCs are important factors controlling the organic chemical composition of marine aerosols in the Arctic Ocean.

Organic molecular composition of marine aerosols over the Arctic Ocean in summer: contributions of primary emission and secondary aerosol formation

NASA Astrophysics Data System (ADS)

Fu, P. Q.; Kawamura, K.; Chen, J.; Charrière, B.; Sempéré, R.

2012-08-01

Organic molecular composition of marine aerosol samples collected during the MALINA cruise in the Arctic Ocean was investigated by gas chromatography/mass spectrometry. More than 110 individual organic compounds were determined in the samples and were grouped into different compound classes based on the functionality and sources. The concentrations of total quantified organics ranged from 7.3 to 185 ng m-3 (mean 47.6 ng m-3), accounting for 1.8-11.0% (4.8%) of organic carbon in the marine aerosols. Primary saccharides were found to be dominant organic compound class, followed by secondary organic aerosol (SOA) tracers formed from the oxidation of biogenic volatile organic compounds (VOCs) such as isoprene, α-pinene and β-caryophyllene. Mannitol, the specific tracer for airborne fungal spores, was detected as the most abundant organic species in the samples with a concentration range of 0.052-53.3 ng m-3 (9.2 ng m-3), followed by glucose, arabitol, and the isoprene oxidation products of 2-methyltetrols. Biomass burning tracers such as levoglucosan are evident in all samples with trace levels. On the basis of the tracer-based method for the estimation of fungal-spore OC and biogenic secondary organic carbon (SOC), we estimate that an average of 10.7% (up to 26.2%) of the OC in the marine aerosols was due to the contribution of fungal spores, followed by the contribution of isoprene SOC (mean 3.8%) and α-pinene SOC (2.9%). In contrast, only 0.19% of the OC was due to the photooxidation of β-caryophyllene. This study indicates that primary organic aerosols from biogenic emissions, both from long-range transport of mid-latitude aerosols and from sea-to-air emission of marine organics, as well as secondary organic aerosols formed from the photooxidation of biogenic VOCs are important factors controlling the organic chemical composition of marine aerosols in the Arctic Ocean.

Inter-individual variability in the production of flavan-3-ol colonic metabolites: preliminary elucidation of urinary metabotypes.

PubMed

Mena, Pedro; Ludwig, Iziar A; Tomatis, Virginia B; Acharjee, Animesh; Calani, Luca; Rosi, Alice; Brighenti, Furio; Ray, Sumantra; Griffin, Julian L; Bluck, Les J; Del Rio, Daniele

2018-04-03

There is much information on the bioavailability of (poly)phenolic compounds following acute intake of various foods. However, there are only limited data on the effects of repeated and combined exposure to specific (poly)phenol food sources and the inter-individual variability in their bioavailability. This study evaluated the combined urinary excretion of (poly)phenols from green tea and coffee following daily consumption by healthy subjects in free-living conditions. The inter-individual variability in the production of phenolic metabolites was also investigated. Eleven participants consumed both tablets of green tea and green coffee bean extracts daily for 8 weeks and 24-h urine was collected on five different occasions. The urinary profile of phenolic metabolites and a set of multivariate statistical tests were used to investigate the putative existence of characteristic metabotypes in the production of flavan-3-ol microbial metabolites. (Poly)phenolic compounds in the green tea and green coffee bean extracts were absorbed and excreted after simultaneous consumption, with green tea resulting in more inter-individual variability in urinary excretion of phenolic metabolites. Three metabotypes in the production of flavan-3-ol microbial metabolites were tentatively defined, characterized by the excretion of different amounts of trihydroxyphenyl-γ-valerolactones, dihydroxyphenyl-γ-valerolactones, and hydroxyphenylpropionic acids. The selective production of microbiota-derived metabolites from flavan-3-ols and the putative existence of characteristic metabotypes in their production represent an important development in the study of the bioavailability of plant bioactives. These observations will contribute to better understand the health effects and individual differences associated with consumption of flavan-3-ols, arguably the main class of flavonoids in the human diet.

Partitioning studies of coal-tar constituents in a two-phase contaminated ground-water system

USGS Publications Warehouse

Rostad, C.E.; Pereira, W.E.; Hult, M.F.

1985-01-01

Organic compounds derived from coal-tar wastes in a contaminated aquifer in St. Louis Park, Minnesota, were identified, and their partition coefficients between the tar phase and aqueous phase were determined and compared with the corresponding n-octanol/water partition coefficients. Coal tar contains numerous polycyclic aromatic compounds, many of which are suspected carcinogens or mutagens. Groundwater contamination by these toxic compounds may pose an environmental health hazard in nearby public water-supply wells. Fluid samples from this aquifer developed two phases upon settling: an upper aqueous phase, and a lower oily-tar phase. After separating the phases, polycyclic aromatic compounds in each phase were isolated using complexation with N-methyl-2-pyrrolidone and identified by fused-silica capillary gas chromatography/mass spectrometry. Thirty-one of the polycyclic aromatic compounds were chosen for further study from four different classes: 12 polycyclic aromatic hydrocarbons, 10 nitrogen heterocycles, 5 sulfur heterocycles, and 4 oxygen heterocycles. Within each compound class, the tar/water partition coefficients of these compounds were reasonably comparable with the respective n-octanol/water partition coefficient.

Bacteriological profiling of diphenylureas as a novel class of antibiotics against methicillin-resistant Staphylococcus aureus

PubMed Central

Younis, Waleed; Ezzat, Hany G.; Peters, Christine E.; AbdelKhalek, Ahmed; Cooper, Bruce; Pogliano, Kit; Pogliano, Joe; Mayhoub, Abdelrahman S.; Seleem, Mohamed N.

2017-01-01

Bacterial resistance to antibiotics remains an imposing global public health challenge. Of the most serious pathogens, methicillin-resistant Staphylococcus aureus (MRSA) is problematic given strains have emerged that exhibit resistance to several antibiotic classes including β-lactams and agents of last resort such as vancomycin. New antibacterial agents composed of unique chemical scaffolds are needed to counter this public health challenge. The present study examines two synthetic diphenylurea compounds 1 and 2 that inhibit growth of clinically-relevant isolates of MRSA at concentrations as low as 4 µg/mL and are non-toxic to human colorectal cells at concentrations up to 128 μg/mL. Both compounds exhibit rapid bactericidal activity, completely eliminating a high inoculum of MRSA within four hours. MRSA mutants exhibiting resistance to 1 and 2 could not be isolated, indicating a low likelihood of rapid resistance emerging to these compounds. Bacterial cytological profiling revealed the diphenylureas exert their antibacterial activity by targeting bacterial cell wall synthesis. Both compounds demonstrate the ability to resensitize vancomycin-resistant Staphylococcus aureus to the effect of vancomycin. The present study lays the foundation for further investigation and development of diphenylurea compounds as a new class of antibacterial agents. PMID:28797064

Classification of auxin plant hormones by interaction property similarity indices

NASA Astrophysics Data System (ADS)

Tomić, Sanja; Gabdoulline, Razif R.; Kojić-Prodić, Biserka; Wade, Rebecca C.

1998-01-01

Although auxins were the first type of plant hormone to be identified, little is known about the molecular mechanism of this important class of plant hormones. We present a classification of a set of about 50 compounds with measured auxin activities, according to their interaction properties. Four classes of compounds were defined: strongly active, weakly active with weak antiauxin behaviour, inactive and inhibitory. All compounds were modeled in two low-energy conformations, `P' and `T', so as to obtain the best match to the `planar' and `tilted' conformations, respectively, of indole 3-acetic acid. Each set of conformers was superimposed separately using several different alignment schemes. Molecular interaction energy fields were computed for each molecule with five different chemical probes and then compared by computing similarity indices. Similarity analysis showed that the classes are on average distinguishable, with better differentiation achieved for the T conformers than the P conformers. This indicates that the T conformation might be the active one. Further, a screening was developed which could distinguish compounds with auxin activity from inactive compounds and most antiauxins using the T conformers. The classifications rationalize ambiguities in activity data found in the literature and should be of value in predicting the activities of new plant growth substances and herbicides.

Pipeline of Known Chemical Classes of Antibiotics

PubMed Central

d’Urso de Souza Mendes, Cristina; de Souza Antunes, Adelaide Maria

2013-01-01

Many approaches are used to discover new antibiotic compounds, one of the most widespread being the chemical modification of known antibiotics. This type of discovery has been so important in the development of new antibiotics that most antibiotics used today belong to the same chemical classes as antibiotics discovered in the 1950s and 1960s. Even though the discovery of new classes of antibiotics is urgently needed, the chemical modification of antibiotics in known classes is still widely used to discover new antibiotics, resulting in a great number of compounds in the discovery and clinical pipeline that belong to existing classes. In this scenario, the present article presents an overview of the R&D pipeline of new antibiotics in known classes of antibiotics, from discovery to clinical trial, in order to map out the technological trends in this type of antibiotic R&D, aiming to identify the chemical classes attracting most interest, their spectrum of activity, and the new subclasses under development. The result of the study shows that the new antibiotics in the pipeline belong to the following chemical classes: quinolones, aminoglycosides, macrolides, oxazolidinones, tetracyclines, pleuromutilins, beta-lactams, lipoglycopeptides, polymyxins and cyclic lipopeptides. PMID:27029317

Spider monkeys (Ateles geoffroyi) are less sensitive to the odor of aliphatic ketones than to the odor of other classes of aliphatic compounds.

PubMed

Eliasson, Moa; Hernandez Salazar, Laura Teresa; Laska, Matthias

2015-10-01

Aliphatic ketones are widely present in body-borne and food odors of primates. Therefore, we used an operant conditioning paradigm and determined olfactory detection thresholds in four spider monkeys for a homologous series of aliphatic 2-ketones (2-butanone to 2-nonanone) and two of their isomers (3- and 4-heptanone). We found that, with the exception of the two shortest-chained ketones, all animals detected concentrations <1 ppm (parts per million), and with five odorants individual animals even reached threshold values <0.1 ppm. Further, we found a significant correlation between olfactory sensitivity of the spider monkeys and carbon chain length of the 2-ketones which can best be described as a U-shaped function. In contrast, no significant correlation was found between olfactory sensitivity and position of the functional carbonyl group. Across-odorant and across-species comparisons revealed the following: spider monkeys are significantly less sensitive to the odors of aliphatic ketones than to the odor of other classes of aliphatic compounds (1-alcohols, n-aldehydes, n-acetic esters, and n-carboxylic acids) sharing the same carbon length. Spider monkeys do not differ significantly in their olfactory sensitivity for aliphatic ketones from squirrel monkeys and pigtail macaques, but are significantly less sensitive to these odorants compared to human subjects and mice. These findings support the notion that neuroanatomical and genetic properties do not allow for reliable predictions with regard to a species' olfactory sensitivity. Further, we conclude that the frequency of occurrence of a class of odorants in a species' chemical environment does not allow for reliable predictions of the species' olfactory sensitivity. Copyright © 2015 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Design of cinnamaldehyde amino acid Schiff base compounds based on the quantitative structure–activity relationship

Treesearch

Hui Wang; Mingyue Jiang; Shujun Li; Chung-Yun Hse; Chunde Jin; Fangli Sun; Zhuo Li

2017-01-01

Cinnamaldehyde amino acid Schiff base (CAAS) is a new class of safe, bioactive compounds which could be developed as potential antifungal agents for fungal infections. To design new cinnamaldehyde amino acid Schiff base compounds with high bioactivity, the quantitative structure–activity relationships (QSARs) for CAAS compounds against Aspergillus niger (A. niger) and...

Composition of the black crusts from the Saint Denis Basilica, France, as revealed by gas chromatography-mass spectrometry.

PubMed

Gaviño, Maria; Hermosin, Bernardo; Vergès-Belmin, Véronique; Nowik, Witold; Saiz-Jimenez, Cesareo

2004-05-01

The organic fraction of black crusts from Saint Denis Basilica, France, is composed of a complex mixture of aliphatic and aromatic compounds. These compounds were studied by two different analytical approaches: tetramethyl ammonium hydroxide (TMAH) thermochemolysis in combination with gas chromatography-mass spectrometry (GC-MS), and solvent extraction, fractionation by silica column, and identification of the fraction components by GC-MS. The first approach, feasible at the microscale level, is able to supply fairly general information on a wide range of compounds. Using the second approach, we were able to separate the complex mixture of compounds into four fractions, enabling a better identification of the extractable compounds. These compounds belong to different classes: aliphatic hydrocarbons (nalkanes, n-alkenes), aliphatic and aromatic carboxylic acids (n-fatty acids, alpha,omega-dicarboxylic acids, and benzenecarboxylic acids), polycyclic aromatic hydrocarbons (PAH), and molecular biomarkers (isoprenoid hydrocarbons, diterpenoids, and triterpenoids). With each approach, similar classes of compounds were identified, although TMAH thermochemolysis failed to identify compounds present at low concentrations in black crusts. The two proposed methodological approaches are complementary, particularly in the study of polar fractions.

Improvement of the Pharmacokinetics and In Vivo Antibacterial Efficacy of a Novel Type IIa Topoisomerase Inhibitor by Formulation in Liposomes

PubMed Central

Newman, Joseph; Goteti, Kosalaram; Beaudoin, Marie-Eve; Harrison, Rane; Hopkins, Sussie; Agrawal, Nikunj; Rivin, Olga

2013-01-01

Several useful properties of liposome-based formulations of various existing antibacterial drugs have been reported. These properties include lower MICs, improved pharmacokinetics, lower toxicity, selective distribution to infected tissues, and enhanced in vivo efficacy. Here we report in vivo studies of a liposomal formulation of a member of a novel class of antibacterial type II topoisomerase inhibitors, others of which have progressed to early phases of clinical trials. The free (i.e., nonliposomal) compound has broad-spectrum MICs but suboptimal pharmacokinetics in rats and mice, characterized by a high volume of distribution and rapid clearance. The liposomal formulation of the compound had essentially unchanged MICs but greatly reduced volume of distribution and clearance in rats and mice. In an in vivo mouse model of Staphylococcus aureus infection of one thigh, the liposomal compound localized preferentially to the infected thigh, whereas the free compound showed no preference for the infected versus the uninfected thigh. Most importantly, the liposomal compound had enhanced efficacy at clearing the infection compared with the free compound. Delivery of this class of compounds as liposomal formulations may offer clinical advantages compared with free compounds. PMID:23877679

Anti-Cancer Properties of a Novel Class of Tetrafluorinated Thalidomide Analogs

PubMed Central

Beedie, Shaunna L.; Peer, Cody J.; Pisle, Steven; Gardner, Erin R.; Mahony, Chris; Barnett, Shelby; Ambrozak, Agnieszka; Gütschow, Michael; Chau, Cindy H.; Vargesson, Neil; Figg, William D.

2015-01-01

Thalidomide has demonstrated clinical activity in various malignancies affecting immunomodulatory and angiogenesis pathways. The development of novel thalidomide analogs with improved efficacy and decreased toxicity is an ongoing research effort. We recently designed and synthesized a new class of compounds, consisting of both tetrafluorinated thalidomide analogs (Gu973 and Gu998) and tetrafluorobenzamides (Gu1029 and Gu992). In this study, we demonstrate the anti-angiogenic properties of these newly synthesized compounds. We examined the specific anti-angiogenic characteristics in vitro using rat aortic rings with carboxyamidotriazole as a positive control. Additionally, further in vitro efficacy was evaluated using HUVECs and PC3 cells treated with 5μM and 10μM doses of each compound. All compounds were seen to reduce microvessel outgrowth in rat aortic rings as well as inhibit HUVECs to a greater extent, at lower concentrations than previously tested thalidomide analogs. The anti-angiogenic properties of the compounds was also examined in vivo in fli1:EGFP zebrafish embryos, where all compounds were seen to inhibit the extent of outgrowth of newly developing blood vessels. In addition, Gu1029 and Gu973 reduced the anti-inflammatory response in mpo:GFP zebrafish embryos, while Gu998 and Gu992 showed no difference. The compounds anti-tumor effects were also explored in vivo using the human prostate cancer PC3 xenograft model. All four compounds were also screened in vivo in chicken embryos to investigate their teratogenic potential. This study establishes these novel thalidomide analogs as a promising immunomodulatory class with anti-cancer effects that warrant further development to characterize their mechanisms of action. PMID:26269604

Cardiac HDAC6 Catalytic Activity is Induced in Response to Chronic Hypertension

PubMed Central

Lemon, Douglas D.; Horn, Todd R.; Cavasin, Maria A.; Jeong, Mark Y.; Haubold, Kurt W.; Long, Carlin S.; Irwin, David C.; McCune, Sylvia A.; Chung, Eunhee; Leinwand, Leslie A.; McKinsey, Timothy A.

2011-01-01

Small molecule histone deacetylase (HDAC) inhibitors block adverse cardiac remodeling in animal models of heart failure. The efficacious compounds target class I, class IIb and, to a lesser extent, class IIa HDACs. It is hypothesized that a selective inhibitor of a specific HDAC class (or an isoform within that class) will provide a favorable therapeutic window for the treatment of heart failure, although the optimal selectivity profile for such a compound remains unknown. Genetic studies have suggested that class I HDACs promote pathological cardiac remodeling, while class IIa HDACs are protective. In contrast, nothing is known about the function or regulation of class IIb HDACs in the heart. We developed assays to quantify catalytic activity of distinct HDAC classes in left and right ventricular cardiac tissue from animal models of hypertensive heart disease. Class I and IIa HDAC activity was elevated in some but not all diseased tissues. In contrast, catalytic activity of the class IIb HDAC, HDAC6, was consistently increased in stressed myocardium, but not in a model of physiologic hypertrophy. HDAC6 catalytic activity was also induced by diverse extracellular stimuli in cultured cardiac myocytes and fibroblasts. These findings suggest an unforeseen role for HDAC6 in the heart, and highlight the need for pre-clinical evaluation of HDAC6-selective inhibitors to determine whether this HDAC isoform is pathological or protective in the setting of cardiovascular disease. PMID:21539845

A Molecular Code for Identity in the Vomeronasal System.

PubMed

Fu, Xiaoyan; Yan, Yuetian; Xu, Pei S; Geerlof-Vidavsky, Ilan; Chong, Wongi; Gross, Michael L; Holy, Timothy E

2015-10-08

In social interactions among mammals, individuals are recognized by olfactory cues, but identifying the key signals among thousands of compounds remains a major challenge. To address this need, we developed a new technique, component-activity matching (CAM), to select candidate ligands that "explain" patterns of bioactivity across diverse complex mixtures. Using mouse urine from eight different sexes and strains, we identified 23 components to explain firing rates in seven of eight functional classes of vomeronasal sensory neurons. Focusing on a class of neurons selective for females, we identified a novel family of vomeronasal ligands, steroid carboxylic acids. These ligands accounted for much of the neuronal activity of urine from some female strains, were necessary for normal levels of male investigatory behavior of female scents, and were sufficient to trigger mounting behavior. CAM represents the first step toward an exhaustive characterization of the molecular cues for natural behavior in a mammalian olfactory system. Copyright © 2015 Elsevier Inc. All rights reserved.

Hormones and the blood-brain barrier.

PubMed

Hampl, Richard; Bičíková, Marie; Sosvorová, Lucie

2015-03-01

Hormones exert many actions in the brain, and brain cells are also hormonally active. To reach their targets in brain structures, hormones must overcome the blood-brain barrier (BBB). The BBB is a unique device selecting desired/undesired molecules to reach or leave the brain, and it is composed of endothelial cells forming the brain vasculature. These cells differ from other endothelial cells in their almost impermeable tight junctions and in possessing several membrane structures such as receptors, transporters, and metabolically active molecules, ensuring their selection function. The main ways how compounds pass through the BBB are briefly outlined in this review. The main part concerns the transport of major classes of hormones: steroids, including neurosteroids, thyroid hormones, insulin, and other peptide hormones regulating energy homeostasis, growth hormone, and also various cytokines. Peptide transporters mediating the saturable transport of individual classes of hormones are reviewed. The last paragraph provides examples of how hormones affect the permeability and function of the BBB either at the level of tight junctions or by various transporters.

Social class at birth and risk of psychosis.

PubMed

O'Donoghue, Brian; Fanning, Felicity; Lyne, John; Renwick, Laoise; Madigan, Kevin; Kinsella, Anthony; Lane, Abbie; Turner, Niall; O'Callaghan, Eadbhard; Clarke, Mary

2015-12-01

Individuals with psychotic disorders are represented more in the lower social classes, yet there is conflicting evidence to whether these individuals drift into the lower social classes or whether lower social class is a risk factor for developing psychosis. The aim of this study was to examine whether the social class at birth is a risk factor for developing psychosis. We included individuals with a first episode of psychosis (FEP) whose social class at birth was determined from birth records. We employed a case-control study design and also compared the distribution of the social classes at birth of the cases to that of the general population. A total of 380 individuals with an FEP and 760 controls were included in the case-control study. The odds ratio for developing an FEP associated with social class (low vs high) was .62 (95% confidence interval (CI): .46-.85, p < .001), indicating that individuals from a lower social class at birth have a reduced risk of psychosis. Individuals born between 1961 and 1980 with an FEP were more likely to be from a higher social class at birth compared to the general population (60.8% vs 36.7%, χ(2) = 60.85, df = 1, p < .001). However, this association was not observed for those born between 1981 and 1990. A higher social class at birth is associated with a greater risk for developing a psychotic disorder; however, this effect may show temporal variation. © The Author(s) 2015.

Synthesis and binding studies of Alzheimer ligands on solid support.

PubMed

Rzepecki, Petra; Geib, Nina; Peifer, Manuel; Biesemeier, Frank; Schrader, Thomas

2007-05-11

Aminopyrazole derivatives constitute the first class of nonpeptidic rationally designed beta-sheet ligands. Here we describe a double solid-phase protocol for both synthesis and affinity testing. The presented solid-phase synthesis of four types of hybrid compounds relies on the Fmoc strategy and circumvents subsequent HPLC purification by precipitating the final product from organic solution in pure form. Hexa- and octapeptide pendants with internal di- and tetrapeptide bridges are now amenable in high yields to combinatorial synthesis of compound libraries for high-throughput screening purposes. Solid-phase peptide synthesis (SPPS) on an acid-resistant PAM allows us, after PMB deprotection, to subject the free aminopyrazole binding sites in an immobilized state to on-bead assays with fluorescence-labeled peptides. From the fluorescence emission intensity decrease, individual binding constants can be calculated via reference curves by simple application of the law of mass action. Gratifyingly, host/guest complexation can be monitored quantitatively even for those ligands, which are almost insoluble in water.

Distribution of some organochlorine compounds (PCB, CBz, and DDE) in beeswax and honey

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

Jan, J.; Cerne, K.

Organochlorines are ranked among the class of prevalent and environmentally persistent synthetic chemicals. Honey bees, beeswax, and honey could be indicators for monitoring environmental pollution by organochlorines such as polychlorobiphenyls (PCBs) and organochloro pesticides. Scarcely any data were reported on the distribution of organochloro compounds between beeswax and honey. Physicochemical factors such as adsorption, volatilization, lipophilicity (octanol-water partition coefficient) and metabolic stability can influence the level of individual organochlorine compounds in beeswax and honey. During wax and honey formation metabolic attack by different enzymes can degrade pollutants. In the PCB and chlorobenzene (CBz) series, biodegradation decreases and bioconcentration increases withmore » increasing degree of chlorine substitution. Regarding the composition of honey (sugars, water, and some organic material and particles such as pollen, organic acid and essential oils in traces), and of beeswax (esters, hydrocarbons, acids and some natural wax from plants as minor components), it is expected that beeswax is more lipophilic and organochlorines could be more enriched in beeswax. However, the presence of particulate matters (e.g., pollen) in honey can increase the level of nonpolar compounds in honey due to sorption processes. This effect has been demonstrated in a similar system where suspended particles can influence the partition coefficient. In this contribution (i) the partition between beeswax and honey of some organochlorine compounds (PCB and CBz isomers, DDE) and (ii) bioconcentration in beeswax and honey from a feeding experiment by administration to honey bees of feed fortified with these compounds is presented and discussed. 17 refs., 3 figs., 1 tab.« less

Cross-Platform Toxicogenomics for the Prediction of Non-Genotoxic Hepatocarcinogenesis in Rat

PubMed Central

Metzger, Ute; Templin, Markus F.; Plummer, Simon; Ellinger-Ziegelbauer, Heidrun; Zell, Andreas

2014-01-01

In the area of omics profiling in toxicology, i.e. toxicogenomics, characteristic molecular profiles have previously been incorporated into prediction models for early assessment of a carcinogenic potential and mechanism-based classification of compounds. Traditionally, the biomarker signatures used for model construction were derived from individual high-throughput techniques, such as microarrays designed for monitoring global mRNA expression. In this study, we built predictive models by integrating omics data across complementary microarray platforms and introduced new concepts for modeling of pathway alterations and molecular interactions between multiple biological layers. We trained and evaluated diverse machine learning-based models, differing in the incorporated features and learning algorithms on a cross-omics dataset encompassing mRNA, miRNA, and protein expression profiles obtained from rat liver samples treated with a heterogeneous set of substances. Most of these compounds could be unambiguously classified as genotoxic carcinogens, non-genotoxic carcinogens, or non-hepatocarcinogens based on evidence from published studies. Since mixed characteristics were reported for the compounds Cyproterone acetate, Thioacetamide, and Wy-14643, we reclassified these compounds as either genotoxic or non-genotoxic carcinogens based on their molecular profiles. Evaluating our toxicogenomics models in a repeated external cross-validation procedure, we demonstrated that the prediction accuracy of our models could be increased by joining the biomarker signatures across multiple biological layers and by adding complex features derived from cross-platform integration of the omics data. Furthermore, we found that adding these features resulted in a better separation of the compound classes and a more confident reclassification of the three undefined compounds as non-genotoxic carcinogens. PMID:24830643

21 CFR 1303.13 - Adjustments of aggregate production quotas.

Code of Federal Regulations, 2011 CFR

2011-04-01

...) Changes in the demand for that class, changes in the national rate of net disposal of the class, and... for that class; (2) Whether any increased demand for that class, the national and/or individual rates... demand for that class can be met through existing inventories, increased individual manufacturing quotas...

New Linear Partitioning Models Based on Experimental Water: Supercritical CO2 Partitioning Data of Selected Organic Compounds.

PubMed

Burant, Aniela; Thompson, Christopher; Lowry, Gregory V; Karamalidis, Athanasios K

2016-05-17

Partitioning coefficients of organic compounds between water and supercritical CO2 (sc-CO2) are necessary to assess the risk of migration of these chemicals from subsurface CO2 storage sites. Despite the large number of potential organic contaminants, the current data set of published water-sc-CO2 partitioning coefficients is very limited. Here, the partitioning coefficients of thiophene, pyrrole, and anisole were measured in situ over a range of temperatures and pressures using a novel pressurized batch-reactor system with dual spectroscopic detectors: a near-infrared spectrometer for measuring the organic analyte in the CO2 phase and a UV detector for quantifying the analyte in the aqueous phase. Our measured partitioning coefficients followed expected trends based on volatility and aqueous solubility. The partitioning coefficients and literature data were then used to update a published poly parameter linear free-energy relationship and to develop five new linear free-energy relationships for predicting water-sc-CO2 partitioning coefficients. A total of four of the models targeted a single class of organic compounds. Unlike models that utilize Abraham solvation parameters, the new relationships use vapor pressure and aqueous solubility of the organic compound at 25 °C and CO2 density to predict partitioning coefficients over a range of temperature and pressure conditions. The compound class models provide better estimates of partitioning behavior for compounds in that class than does the model built for the entire data set.

New Linear Partitioning Models Based on Experimental Water: Supercritical CO 2 Partitioning Data of Selected Organic Compounds

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

Burant, Aniela; Thompson, Christopher; Lowry, Gregory V.

2016-05-17

Partitioning coefficients of organic compounds between water and supercritical CO2 (sc-CO2) are necessary to assess the risk of migration of these chemicals from subsurface CO2 storage sites. Despite the large number of potential organic contaminants, the current data set of published water-sc-CO2 partitioning coefficients is very limited. Here, the partitioning coefficients of thiophene, pyrrole, and anisole were measured in situ over a range of temperatures and pressures using a novel pressurized batch reactor system with dual spectroscopic detectors: a near infrared spectrometer for measuring the organic analyte in the CO2 phase, and a UV detector for quantifying the analyte inmore » the aqueous phase. Our measured partitioning coefficients followed expected trends based on volatility and aqueous solubility. The partitioning coefficients and literature data were then used to update a published poly-parameter linear free energy relationship and to develop five new linear free energy relationships for predicting water-sc-CO2 partitioning coefficients. Four of the models targeted a single class of organic compounds. Unlike models that utilize Abraham solvation parameters, the new relationships use vapor pressure and aqueous solubility of the organic compound at 25 °C and CO2 density to predict partitioning coefficients over a range of temperature and pressure conditions. The compound class models provide better estimates of partitioning behavior for compounds in that class than the model built for the entire dataset.« less

Human exposure to organic arsenic species from seafood.

PubMed

Taylor, Vivien; Goodale, Britton; Raab, Andrea; Schwerdtle, Tanja; Reimer, Ken; Conklin, Sean; Karagas, Margaret R; Francesconi, Kevin A

2017-02-15

Seafood, including finfish, shellfish, and seaweed, is the largest contributor to arsenic (As) exposure in many human populations. In contrast to the predominance of inorganic As in water and many terrestrial foods, As in marine-derived foods is present primarily in the form of organic compounds. To date, human exposure and toxicological assessments have focused on inorganic As, while organic As has generally been considered to be non-toxic. However, the high concentrations of organic As in seafood, as well as the often complex As speciation, can lead to complications in assessing As exposure from diet. In this report, we evaluate the presence and distribution of organic As species in seafood, and combined with consumption data, address the current capabilities and needs for determining human exposure to these compounds. The analytical approaches and shortcomings for assessing these compounds are reviewed, with a focus on the best practices for characterization and quantitation. Metabolic pathways and toxicology of two important classes of organic arsenicals, arsenolipids and arsenosugars, are examined, as well as individual variability in absorption of these compounds. Although determining health outcomes or assessing a need for regulatory policies for organic As exposure is premature, the extensive consumption of seafood globally, along with the preliminary toxicological profiles of these compounds and their confounding effect on assessing exposure to inorganic As, suggests further investigations and process-level studies on organic As are needed to fill the current gaps in knowledge. Copyright © 2016 Elsevier B.V. All rights reserved.

Studies on novel 2-imidazolidinones and tetrahydropyrimidin-2(1H)-ones as potential TACE inhibitors: design, synthesis, molecular modeling, and preliminary biological evaluation.

PubMed

DasGupta, Shirshendu; Murumkar, Prashant R; Giridhar, Rajani; Yadav, Mange Ram

2009-05-15

Compounds belonging to the class of 2-imidazolidinones and tetrahydropyrimidin-2(1H)-ones were synthesized and evaluated for their TACE inhibitory activity. Most of the compounds showed very good TACE inhibitory activity. Docking study clearly indicates importance of the P1' group of the inhibitor for the TACE inhibitory activity. This work proves that these two classes of molecules could be used as potential leads for the development of TACE inhibitors.

Synthesis and Characterization of Functionalized Eight-Membered Cyclic Silicates

DTIC Science & Technology

2009-03-24

arum and thrcc organlc groups are In thc hI class Srllco~) atoms bonded to four onvgen atoms ar t in [he Q class Suhstituted Q, compounds contain...rollowed b:i thc corresponhng dls~loxane in the presence o i Amberlyst 15 ion-exchane;. resini. 1,1.2.2-rctrahydrodccyl)dlmehyIchlorosilan (Gelest...The resulttng solid was dissolved 111 hexnnc and ~ w o water cxriaclionp. were pcrfomrd to rcrnobc rcsidual acld. The compound (1 06 g. 5 1% y~ cbd

Carbonic anhydrase activators: activation of the archaeal beta-class (Cab) and gamma-class (Cam) carbonic anhydrases with amino acids and amines.

PubMed

Innocenti, Alessio; Zimmerman, Sabrina A; Scozzafava, Andrea; Ferry, James G; Supuran, Claudiu T

2008-12-01

Activation of the archaeal beta-class (Cab) and gamma-class (Cam) carbonic anhydrases (CAs, EC 4.2.1.1) with a series of natural and non-natural amino acids and aromatic/heterocyclic amines has been investigated. Cab, Zn-Cam and Co-Cam showed an activation profile with natural, L- and D-amino acids very different of those of the alpha-class enzymes CA I, II and III. Most of these compounds showed medium efficacy as archaeal CA activators, except for D-Phe and L-Tyr which were effective Cab activators (K(A)s of 10.3-10.5 microM), 2-pyridylmethylamine and 1-(2-aminoethyl)-piperazine which effectively activated Zn-Cam (K(A)s of 10.1-11.4 microM) and serotonin, L-adrenaline and 2-pyridylmethylamine which were the best Co-Cam activators (K(A)s of 0.97-8.9 microM). We prove here that the activation mechanisms of the alpha-, beta-, and gamma-class CAs are similar, although the activation profiles with various compounds differ dramatically between these diverse enzymes.

Survey of the class of isovalent antiperovskite alkaline-earth pnictide compounds

NASA Astrophysics Data System (ADS)

Goh, Wen Fong; Pickett, Warren E.

2018-01-01

The few reported members of the antiperovskite structure class A e3P nAP nB of alkaline-earth (A e =Ca , Sr, Ba) pnictide (P n =N , P, As, Sb, Bi) compounds are all based on the B -site anion P nB=N . All can be categorized as narrow-gap semiconductors, making them of interest for several reasons. Because chemical reasoning suggests that more members of this class may be stable, we provide here a density functional theory (DFT)-based survey of this entire class of 3 ×5 ×5 compounds. We determine first the relative energetic stability of the distribution of pairs of P n ions in the A and B sites of the structure, finding that the B site always favors the small pnictogen anion. The trends of the calculated energy gaps versus the A e cation and P n anions are determined, and we study effects of spin-orbit coupling as well as two types of gap corrections to the conventional DFT electronic spectrum. Because there have been suggestions that this class harbors topological insulating phases, we have given this possibility attention and found that energy gap corrections indicate the cubic structures will provide at most a few topological insulators. Structural instability is addressed by calculating phonon dispersion curves for a few compounds, with one outcome being that distorted structures should be investigated further for thermoelectric and topological character. Examples of the interplay between spin-orbit coupling and strain on the topological nature are provided. A case study of Ca3BiP including the effect of strain illustrates how a topological semimetal can be transformed into a topological insulator and Dirac semimetal.

Vibrational spectroscopic analyses of unique yellow feather pigments (spheniscins) in penguins.

PubMed

Thomas, Daniel B; McGoverin, Cushla M; McGraw, Kevin J; James, Helen F; Madden, Odile

2013-06-06

Many animals extract, synthesize and refine chemicals for colour display, where a range of compounds and structures can produce a diverse colour palette. Feather colours, for example, span the visible spectrum and mostly result from pigments in five chemical classes (carotenoids, melanins, porphyrins, psittacofulvins and metal oxides). However, the pigment that generates the yellow colour of penguin feathers appears to represent a sixth, poorly characterized class of feather pigments. This pigment class, here termed 'spheniscin', is displayed by half of the living penguin genera; the larger and richer colour displays of the pigment are highly attractive. Using Raman and mid-infrared spectroscopies, we analysed yellow feathers from two penguin species (king penguin, Aptenodytes patagonicus; macaroni penguin, Eudyptes chrysolophus) to further characterize spheniscin pigments. The Raman spectrum of spheniscin is distinct from spectra of other feather pigments and exhibits 17 distinctive spectral bands between 300 and 1700 cm(-1). Spectral bands from the yellow pigment are assigned to aromatically bound carbon atoms, and to skeletal modes in an aromatic, heterocyclic ring. It has been suggested that the penguin pigment is a pterin compound; Raman spectra from yellow penguin feathers are broadly consistent with previously reported pterin spectra, although we have not matched it to any known compound. Raman spectroscopy can provide a rapid and non-destructive method for surveying the distribution of different classes of feather pigments in the avian family tree, and for correlating the chemistry of spheniscin with compounds analysed elsewhere. We suggest that the sixth class of feather pigments may have evolved in a stem-lineage penguin and endowed modern penguins with a costly plumage trait that appears to be chemically unique among birds.

Vibrational spectroscopic analyses of unique yellow feather pigments (spheniscins) in penguins

PubMed Central

Thomas, Daniel B.; McGoverin, Cushla M.; McGraw, Kevin J.; James, Helen F.; Madden, Odile

2013-01-01

Many animals extract, synthesize and refine chemicals for colour display, where a range of compounds and structures can produce a diverse colour palette. Feather colours, for example, span the visible spectrum and mostly result from pigments in five chemical classes (carotenoids, melanins, porphyrins, psittacofulvins and metal oxides). However, the pigment that generates the yellow colour of penguin feathers appears to represent a sixth, poorly characterized class of feather pigments. This pigment class, here termed ‘spheniscin’, is displayed by half of the living penguin genera; the larger and richer colour displays of the pigment are highly attractive. Using Raman and mid-infrared spectroscopies, we analysed yellow feathers from two penguin species (king penguin, Aptenodytes patagonicus; macaroni penguin, Eudyptes chrysolophus) to further characterize spheniscin pigments. The Raman spectrum of spheniscin is distinct from spectra of other feather pigments and exhibits 17 distinctive spectral bands between 300 and 1700 cm−1. Spectral bands from the yellow pigment are assigned to aromatically bound carbon atoms, and to skeletal modes in an aromatic, heterocyclic ring. It has been suggested that the penguin pigment is a pterin compound; Raman spectra from yellow penguin feathers are broadly consistent with previously reported pterin spectra, although we have not matched it to any known compound. Raman spectroscopy can provide a rapid and non-destructive method for surveying the distribution of different classes of feather pigments in the avian family tree, and for correlating the chemistry of spheniscin with compounds analysed elsewhere. We suggest that the sixth class of feather pigments may have evolved in a stem-lineage penguin and endowed modern penguins with a costly plumage trait that appears to be chemically unique among birds. PMID:23516063

Lead Optimization Studies of Cinnamic Amide EP2 Antagonists

PubMed Central

2015-01-01

Prostanoid receptor EP2 can play a proinflammatory role, exacerbating disease pathology in a variety of central nervous system and peripheral diseases. A highly selective EP2 antagonist could be useful as a drug to mitigate the inflammatory consequences of EP2 activation. We recently identified a cinnamic amide class of EP2 antagonists. The lead compound in this class (5d) displays anti-inflammatory and neuroprotective actions. However, this compound exhibited moderate selectivity to EP2 over the DP1 prostanoid receptor (∼10-fold) and low aqueous solubility. We now report compounds that display up to 180-fold selectivity against DP1 and up to 9-fold higher aqueous solubility than our previous lead. The newly developed compounds also display higher selectivity against EP4 and IP receptors and a comparable plasma pharmacokinetics. Thus, these compounds are useful for proof of concept studies in a variety of models where EP2 activation is playing a deleterious role. PMID:24773616

1,2-Benzisoselenazol-3(2H)-one Derivatives As a New Class of Bacterial Urease Inhibitors.

PubMed

Macegoniuk, Katarzyna; Grela, Ewa; Palus, Jerzy; Rudzińska-Szostak, Ewa; Grabowiecka, Agnieszka; Biernat, Monika; Berlicki, Łukasz

2016-09-08

Urease inhibitors are considered promising compounds for the treatment of ureolytic bacterial infections, particularly infections resulting from Helicobacter pylori in the gastric tract. Herein, we present the synthesis and the inhibitory activity of novel and highly effective organoselenium compounds as inhibitors of Sporosarcina pasteurii and Helicobacter pylori ureases. These studied compounds represent a class of competitive reversible urease inhibitors. The most active compound, 2-phenyl-1,2-benzisoselenazol-3(2H)-one (ebselen), displayed Ki values equal to 2.11 and 226 nM against S. pasteurii and H. pylori enzymes, respectively, indicating ebselen as one of the most potent low-molecular-weight inhibitors of bacterial ureases reported to date. Most of these molecules penetrated through the cell membrane of the Gram-negative bacteria Escherichia coli (pGEM::ureOP) in vitro. Furthermore, whole-cell studies on the H. pylori J99 reference strain confirmed the high efficiency of the examined organoselenium compounds as urease inhibitors against pathogenic bacteria.

Imbalance in chemical space: How to facilitate the identification of protein-protein interaction inhibitors.

PubMed

Kuenemann, Mélaine A; Labbé, Céline M; Cerdan, Adrien H; Sperandio, Olivier

2016-04-01

Protein-protein interactions (PPIs) play vital roles in life and provide new opportunities for therapeutic interventions. In this large data analysis, 3,300 inhibitors of PPIs (iPPIs) were compared to 17 reference datasets of collectively ~566,000 compounds (including natural compounds, existing drugs, active compounds on conventional targets, etc.) using a chemoinformatics approach. Using this procedure, we showed that comparable classes of PPI targets can be formed using either the similarity of their ligands or the shared properties of their binding cavities, constituting a proof-of-concept that not only can binding pockets be used to group PPI targets, but that these pockets certainly condition the properties of their corresponding ligands. These results demonstrate that matching regions in both chemical space and target space can be found. Such identified classes of targets could lead to the design of PPI-class-specific chemical libraries and therefore facilitate the development of iPPIs to the stage of drug candidates.

Pyrazoleamide compounds are potent antimalarials that target Na+ homeostasis in intraerythrocytic Plasmodium falciparum

PubMed Central

Vaidya, Akhil B.; Morrisey, Joanne M.; Zhang, Zhongsheng; Das, Sudipta; Daly, Thomas M.; Otto, Thomas D.; Spillman, Natalie J.; Wyvratt, Matthew; Siegl, Peter; Marfurt, Jutta; Wirjanata, Grennady; Sebayang, Boni F.; Price, Ric N.; Chatterjee, Arnab; Nagle, Advait; Stasiak, Marcin; Charman, Susan A.; Angulo-Barturen, Iñigo; Ferrer, Santiago; Belén Jiménez-Díaz, María; Martínez, María Santos; Gamo, Francisco Javier; Avery, Vicky M.; Ruecker, Andrea; Delves, Michael; Kirk, Kiaran; Berriman, Matthew; Kortagere, Sandhya; Burrows, Jeremy; Fan, Erkang; Bergman, Lawrence W.

2014-01-01

The quest for new antimalarial drugs, especially those with novel modes of action, is essential in the face of emerging drug-resistant parasites. Here we describe a new chemical class of molecules, pyrazoleamides, with potent activity against human malaria parasites and showing remarkably rapid parasite clearance in an in vivo model. Investigations involving pyrazoleamide-resistant parasites, whole-genome sequencing and gene transfers reveal that mutations in two proteins, a calcium-dependent protein kinase (PfCDPK5) and a P-type cation-ATPase (PfATP4), are necessary to impart full resistance to these compounds. A pyrazoleamide compound causes a rapid disruption of Na+ regulation in blood-stage Plasmodium falciparum parasites. Similar effect on Na+ homeostasis was recently reported for spiroindolones, which are antimalarials of a chemical class quite distinct from pyrazoleamides. Our results reveal that disruption of Na+ homeostasis in malaria parasites is a promising mode of antimalarial action mediated by at least two distinct chemical classes. PMID:25422853

Benzoxazine derivatives of phytophenols show anti-plasmodial activity via sodium homeostasis disruption.

PubMed

Sharma, Vijeta; Amarnath, Nagarjuna; Shukla, Swapnil; Ayana, R; Kumar, Naveen; Yadav, Nisha; Kannan, Deepika; Sehrawat, Seema; Pati, Soumya; Lochab, Bimlesh; Singh, Shailja

2018-05-15

Development of new class of anti-malarial drugs is an essential requirement for the elimination of malaria. Bioactive components present in medicinal plants and their chemically modified derivatives could be a way forward towards the discovery of effective anti-malarial drugs. Herein, we describe a new class of compounds, 1,3-benzoxazine derivatives of pharmacologically active phytophenols eugenol (compound 3) and isoeugenol (compound 4) synthesised on the principles of green chemistry, as anti-malarials. Compound 4, showed highest anti-malarial activity with no cytotoxicity towards mammalian cells. Compound 4 induced alterations in the intracellular Na + levels and mitochondrial depolarisation in intraerythrocytic Plasmodium falciparum leading to cell death. Knowing P-type cation ATPase PfATP4 is a regulator for sodium homeostasis, binding of compound 3, compound 4 and eugenol to PfATP4 was analysed by molecular docking studies. Compounds showed binding to the catalytic pocket of PfATP4, however compound 4 showed stronger binding due to the presence of propylene functionality, which corroborates its higher anti-malarial activity. Furthermore, anti-malarial half maximal effective concentration of compound 4 was reduced to 490 nM from 17.54 µM with nanomaterial graphene oxide. Altogether, this study presents anti-plasmodial potential of benzoxazine derivatives of phytophenols and establishes disruption of parasite sodium homeostasis as their mechanism of action. Copyright © 2018 Elsevier Ltd. All rights reserved.

Biodegradation tests of mercaptocarboxylic acids, their esters, related divalent sulfur compounds and mercaptans.

PubMed

Rücker, Christoph; Mahmoud, Waleed M M; Schwartz, Dirk; Kümmerer, Klaus

2018-04-17

Mercaptocarboxylic acids and their esters, a class of difunctional compounds bearing both a mercapto and a carboxylic acid or ester functional group, are industrial chemicals of potential environmental concern. Biodegradation of such compounds was systematically investigated here, both by literature search and by experiments (Closed Bottle Test OECD 301D and Manometric Respirometry Test OECD 301F). These compounds were found either readily biodegradable or at least biodegradable to a significant extent. Some related compounds of divalent sulfur were tested for comparison (mercaptans, sulfides, disulfides). For the two relevant monofunctional compound classes, carboxylic acids/esters and mercaptans, literature data were compiled, and by comparison with structurally similar compounds without these functional groups, the influence of COOH/COOR' and SH groups on biodegradability was evaluated. Thereby, an existing rule of thumb for biodegradation of carboxylic acids/esters was supported by experimental data, and a rule of thumb could be formulated for mercaptans. Concurrent to biodegradation, abiotic processes were observed in the experiments, rapid oxidative formation of disulfides (dimerisation of monomercaptans and cyclisation of dimercaptans) and hydrolysis of esters. Some problems that compromise the reproducibility of biodegradation test results were discussed.

Social class rank, threat vigilance, and hostile reactivity.

PubMed

Kraus, Michael W; Horberg, E J; Goetz, Jennifer L; Keltner, Dacher

2011-10-01

Lower-class individuals, because of their lower rank in society, are theorized to be more vigilant to social threats relative to their high-ranking upper-class counterparts. This class-related vigilance to threat, the authors predicted, would shape the emotional content of social interactions in systematic ways. In Study 1, participants engaged in a teasing interaction with a close friend. Lower-class participants--measured in terms of social class rank in society and within the friendship--more accurately tracked the hostile emotions of their friend. As a result, lower-class individuals experienced more hostile emotion contagion relative to upper-class participants. In Study 2, lower-class participants manipulated to experience lower subjective socioeconomic rank showed more hostile reactivity to ambiguous social scenarios relative to upper-class participants and to lower-class participants experiencing elevated socioeconomic rank. The results suggest that class affects expectations, perception, and experience of hostile emotion, particularly in situations in which lower-class individuals perceive their subordinate rank.

Monitoring of Total Type II Pyrethroid Pesticides in Citrus Oils and Water by Converting to a Common Product 3-Phenoxybenzoic Acid

PubMed Central

McCoy, Mark R.; Yang, Zheng; Fu, Xun; Ahn, Ki Chang; Gee, Shirley J.; Bom, David C.; Zhong, Ping; Chang, Dan; Hammock, Bruce D.

2012-01-01

Pyrethroids are a class of insecticides that are becoming increasingly popular in agricultural and home use applications. Sensitive assays for pyrethroid insecticides in complex matrices are difficult both with instrumental and immunochemical methods. Environmental analysis of the pyrethroids by immunoassay requires either knowing which pyrethroids contaminate the source or the use of non-specific antibodies with cross reactivities to a class of compounds. We describe an alternative method that converts the type-II-pyrethroids to a common chemical product, 3-phenoxybenzoic acid (3-PBA), prior to analysis. This method is much more sensitive than detecting the parent compound, and it is much easier to detect a single compound rather than an entire class of compounds. This is useful in screening for pyrethroids as a class or in situations where a single type of pyrethroid is used. We demonstrated this technique in both citrus oils and environmental water samples with conversion rates of the pyrethroid to 3-PBA that range from 45%-75% and methods that require no extraction steps for either the immunoassay or LC-MS/MS techniques. Limits of detection for this technique applied to orange oil are 5 nM, 2 μM, and 0.8 μM when detected by LC-MS/MS, GC-MS, and immunoassay respectively. The limit of detection for pyrethroids in water when detected by immunoassay was 2 nM. PMID:22486225

Perceived class climate and school-aged children's life satisfaction: The role of the learning environment in classrooms.

PubMed

Rathmann, Katharina; Herke, Max G; Hurrelmann, Klaus; Richter, Matthias

2018-01-01

The aim of this study is to examine the impact of class-level class climate on school-aged children's life satisfaction. Data was derived from the German National Educational Panel Study (NEPS) using sixth grade school-aged children (n = 4,764, 483 classes). Class climate includes indicators of teachers' care and monitoring, demands, interaction, autonomy, as well as school-aged children's attitudes towards schoolwork at the class- and individual-level. Results showed that individual perceived class climate in terms of teachers' care and monitoring and autonomy was positively related to life satisfaction, whereas school-related demands were related to lower life satisfaction. Besides teachers' care and monitoring at class-level, indicators of class climate were not associated with school-aged children's life satisfaction, while the individual perceived class climate is more important for life satisfaction.

Perceived class climate and school-aged children's life satisfaction: The role of the learning environment in classrooms

PubMed Central

Herke, Max G.; Hurrelmann, Klaus; Richter, Matthias

2018-01-01

The aim of this study is to examine the impact of class-level class climate on school-aged children’s life satisfaction. Data was derived from the German National Educational Panel Study (NEPS) using sixth grade school-aged children (n = 4,764, 483 classes). Class climate includes indicators of teachers' care and monitoring, demands, interaction, autonomy, as well as school-aged children's attitudes towards schoolwork at the class- and individual-level. Results showed that individual perceived class climate in terms of teachers' care and monitoring and autonomy was positively related to life satisfaction, whereas school-related demands were related to lower life satisfaction. Besides teachers' care and monitoring at class-level, indicators of class climate were not associated with school-aged children’s life satisfaction, while the individual perceived class climate is more important for life satisfaction. PMID:29420540

Olfactory receptor neuron profiling using sandalwood odorants.

PubMed

Bieri, Stephan; Monastyrskaia, Katherine; Schilling, Boris

2004-07-01

The mammalian olfactory system can discriminate between volatile molecules with subtle differences in their molecular structures. Efforts in synthetic chemistry have delivered a myriad of smelling compounds of different qualities as well as many molecules with very similar olfactive properties. One important class of molecules in the fragrance industry are sandalwood odorants. Sandalwood oil and four synthetic sandalwood molecules were selected to study the activation profile of endogenous olfactory receptors when exposed to compounds from the same odorant family. Dissociated rat olfactory receptor neurons were exposed to the sandalwood molecules and the receptor activation studied by monitoring fluxes in the internal calcium concentration. Olfactory receptor neurons were identified that were specifically stimulated by sandalwood compounds. These neurons expressed olfactory receptors that can discriminate between sandalwood odorants with slight differences in their molecular structures. This is the first study in which an important class of perfume compounds was analyzed for its ability to activate endogenous olfactory receptors in olfactory receptor neurons.

Exploring Cancer Therapeutics with Natural Products from African Medicinal Plants, Part II: Alkaloids, Terpenoids and Flavonoids.

PubMed

Nwodo, Justina N; Ibezim, Akachukwu; Simoben, Conrad V; Ntie-Kang, Fidele

2016-01-01

Cancer stands as second most common cause of disease-related deaths in humans. Resistance of cancer to chemotherapy remains challenging to both scientists and physicians. Medicinal plants are known to contribute significantly to a large population of Africa, which is to a very large extent linked to folkloric claims which is part of their livelihood. In this review paper, the potential of naturally occurring anti-cancer agents from African flora has been explored, with suggested modes of action, where such data is available. Literature search revealed plant-derived compounds from African flora showing anti-cancer and/or cytotoxic activities, which have been tested in vitro and in vivo. This corresponds to 400 compounds (from mildly active to very active) covering various compound classes. However, in this part II, we only discussed the three major compound classes which are: flavonoids, alkaloids and terpenoids.

Observation of unusual topological surface states in half-Heusler compounds LnPtBi (Ln=Lu, Y)

DOE PAGES

Liu, Z. K.; Yang, L. X.; Wu, S. -C.; ...

2016-09-27

Topological quantum materials represent a new class of matter with both exotic physical phenomena and novel application potentials. Many Heusler compounds, which exhibit rich emergent properties such as unusual magnetism, superconductivity and heavy fermion behaviour, have been predicted to host non-trivial topological electronic structures. The coexistence of topological order and other unusual properties makes Heusler materials ideal platform to search for new topological quantum phases (such as quantum anomalous Hall insulator and topological superconductor). By carrying out angle-resolved photoemission spectroscopy and ab initio calculations on rare-earth half-Heusler compounds LnPtBi (Ln=Lu, Y), we directly observe the unusual topological surface states onmore » these materials, establishing them as first members with non-trivial topological electronic structure in this class of materials. Moreover, as LnPtBi compounds are non-centrosymmetric superconductors, our discovery further highlights them as promising candidates of topological superconductors.« less

Observation of unusual topological surface states in half-Heusler compounds LnPtBi (Ln=Lu, Y)

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

Liu, Z. K.; Yang, L. X.; Wu, S. -C.

Topological quantum materials represent a new class of matter with both exotic physical phenomena and novel application potentials. Many Heusler compounds, which exhibit rich emergent properties such as unusual magnetism, superconductivity and heavy fermion behaviour, have been predicted to host non-trivial topological electronic structures. The coexistence of topological order and other unusual properties makes Heusler materials ideal platform to search for new topological quantum phases (such as quantum anomalous Hall insulator and topological superconductor). By carrying out angle-resolved photoemission spectroscopy and ab initio calculations on rare-earth half-Heusler compounds LnPtBi (Ln=Lu, Y), we directly observe the unusual topological surface states onmore » these materials, establishing them as first members with non-trivial topological electronic structure in this class of materials. Moreover, as LnPtBi compounds are non-centrosymmetric superconductors, our discovery further highlights them as promising candidates of topological superconductors.« less

Equivalence-Equivalence: Matching Stimuli with Same Discriminative Functions

ERIC Educational Resources Information Center

Carpentier, Franck; Smeets, Paul M.; Barnes-Holmes, Dermot

2004-01-01

Previous studies have shown that after being trained on A-B and A-C match-to-sample tasks, adults match not only same-class B and C stimuli (equivalence) but also BC compounds with same-class elements and with different-class elements (BC-BC). The assumption was that the BC-BC performances are based on matching equivalence and nonequivalence…

Discovery of New Classes of Compounds that Reactivate Acetylcholinesterase Inhibited by Organophosphates

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

Katz, Francine S.; Pecic, Stevan; Tran, Timothy H.

Acetylcholinesterase (AChE) that has been covalently inhibited by organophosphate compounds (OPCs), such as nerve agents and pesticides, has traditionally been reactivated by using nucleophilic oximes. There is, however, a clearly recognized need for new classes of compounds with the ability to reactivate inhibited AChE with improved in vivo efficacy. Here we describe our discovery of new functional groups—Mannich phenols and general bases—that are capable of reactivating OPC-inhibited AChE more efficiently than standard oximes and we describe the cooperative mechanism by which these functionalities are delivered to the active site. These discoveries, supported by preliminary in vivo results and crystallographic data,more » significantly broaden the available approaches for reactivation of AChE.« less

UV-triggered Affinity Capture Identifies Interactions between the Plasmodium falciparum Multidrug Resistance Protein 1 (PfMDR1) and Antimalarial Agents in Live Parasitized Cells*

PubMed Central

Brunner, Ralf; Ng, Caroline L.; Aissaoui, Hamed; Akabas, Myles H.; Boss, Christoph; Brun, Reto; Callaghan, Paul S.; Corminboeuf, Olivier; Fidock, David A.; Frame, Ithiel J.; Heidmann, Bibia; Le Bihan, Amélie; Jenö, Paul; Mattheis, Corinna; Moes, Suzette; Müller, Ingrid B.; Paguio, Michelle; Roepe, Paul D.; Siegrist, Romain; Voss, Till; Welford, Richard W. D.; Wittlin, Sergio; Binkert, Christoph

2013-01-01

A representative of a new class of potent antimalarials with an unknown mode of action was recently described. To identify the molecular target of this class of antimalarials, we employed a photo-reactive affinity capture method to find parasite proteins specifically interacting with the capture compound in living parasitized cells. The capture reagent retained the antimalarial properties of the parent molecule (ACT-213615) and accumulated within parasites. We identified several proteins interacting with the capture compound and established a functional interaction between ACT-213615 and PfMDR1. We surmise that PfMDR1 may play a role in the antimalarial activity of the piperazine-containing compound ACT-213615. PMID:23754276

Rational design of new electrolyte materials for electrochemical double layer capacitors

NASA Astrophysics Data System (ADS)

Schütter, Christoph; Husch, Tamara; Viswanathan, Venkatasubramanian; Passerini, Stefano; Balducci, Andrea; Korth, Martin

2016-09-01

The development of new electrolytes is a centerpiece of many strategies to improve electrochemical double layer capacitor (EDLC) devices. We present here a computational screening-based rational design approach to find new electrolyte materials. As an example application, the known chemical space of almost 70 million compounds is investigated in search of electrochemically more stable solvents. Cyano esters are identified as especially promising new compound class. Theoretical predictions are validated with subsequent experimental studies on a selected case. These studies show that based on theoretical predictions only, a previously untested, but very well performing compound class was identified. We thus find that our rational design strategy is indeed able to successfully identify completely new materials with substantially improved properties.

The effect of polarity of extractives on the durability of wood

Treesearch

Roderquita K. Moore; Jonathan Smaglick; Erick Arellano-ruiz; Michael Leitch; Doreen Mann

2015-01-01

Extractives are low molecular weight compounds and regarded as nonstructural wood constituents. These compounds are present in trees and can be extracted by organic solvents. Extractives consist of several classes of compounds that diversify the biological function of the tree. Fats are an energy source for the wood cells whereas terpenoids, resin acids, and phenolic...

CLOSED-LOOP STRIPPING ANALYSIS (CLSA) OF SYNTHETIC MUSK COMPOUNDS FROM FISH TISSUES WITH MEASUREMENT BY OC/MS/SIM

EPA Science Inventory

Synthetic musk compounds are used as inexpensive fragrance materials for the production
of perfumes and as additives to soap, detergent, and shampoo. They have been found in surface water, fish tissues, and human breast milk. The ubiquity of this class of compounds in the env...

Methanobactin: a copper binding compound having antibiotic and antioxidant activity isolated from methanotrophic bacteria

DOEpatents

DiSpirito, Alan A [Ames, IA; Zahn, James A [Harbor Beach, MI; Graham, David W [Lawrence, KS; Kim, Hyung J [St. Paul, MN; Alterman, Michail [Lawrence, KS; Larive, Cynthia [Lawrence, KS

2007-04-03

A means and method for treating bacterial infection, providing antioxidant activity, and chelating copper using a copper binding compound produced by methanotrophic bacteria is described. The compound, known as methanobactin, is the first of a new class of antibiotics having gram-positive activity. Methanobactin has been sequenced, and its structural formula determined.

34 CFR 370.6 - What definitions apply?

Code of Federal Regulations, 2010 CFR

2010-07-01

..., in which case it is individual advocacy; (2) More than one individual or a group or class of... advocacy. Class action means a formal legal suit on behalf of a group or class of individuals filed in a... Rico, The United States Virgin Islands, Guam, American Samoa, the Commonwealth of the Northern Mariana...

Synthesis and potent in vitro activity of novel 1H-benzimidazoles as anti-MRSA agents.

PubMed

Karataş, Hacer; Alp, Mehmet; Yildiz, Sulhiye; Göker, Hakan

2012-08-01

A new class of 1H-benzimidazolecarboxamidines was synthesized and evaluated for in vitro antibacterial and antifungal activities, including drug-resistant bacterial strains. The most potent compound (32) has the same ratio of anti-MRSA activity as Vancomycin (minimal inhibitory concentrations value 0.78 μg/mL). The mechanism of action for 1H-benzimidazolecarboxamidine appears to be different from existing antibacterial agents. These compounds have potential for development as a new class of potent anti-MRSA agent. © 2012 John Wiley & Sons A/S.

(PRESENTED AT MORIOKA, JAPAN) PERSISTENT PERFLUORINATED COMPOUNDS IN THE ENVIRONMENT: A BRIEF INTRODUCTION TO THIS IMPORTANT NEW CLASS OF POLLUTANTS

EPA Science Inventory

PowerPoint presentation summarizing method development research involving the persistent perfluorinated organic compounds. Review of data indicating widespread distribution of these materials and the potential for toxicity.

Guest Comment: Polyfluorinated Compounds Focus Issue

EPA Science Inventory

Over the past decade, a great deal has been learned about the perfluoroalkyl acids (PFAAs), a new class of environmental contaminants that includes the now well-known perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), and many other related compounds. These mater...

20 CFR 410.601 - Determinations of disability.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 410.601 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL COAL MINE HEALTH AND SAFETY ACT OF... agreement on behalf of the Commissioner for all individuals in such State, or for such class or classes of... make such determinations, for any class or classes of individuals to which such an agreement is not...

Social class, solipsism, and contextualism: how the rich are different from the poor.

PubMed

Kraus, Michael W; Piff, Paul K; Mendoza-Denton, Rodolfo; Rheinschmidt, Michelle L; Keltner, Dacher

2012-07-01

Social class is shaped by an individual's material resources as well as perceptions of rank vis-à-vis others in society, and in this article, we examine how class influences behavior. Diminished resources and lower rank create contexts that constrain social outcomes for lower-class individuals and enhance contextualist tendencies--that is, a focus on external, uncontrollable social forces and other individuals who influence one's life outcomes. In contrast, abundant resources and elevated rank create contexts that enhance the personal freedoms of upper-class individuals and give rise to solipsistic social cognitive tendencies--that is, an individualistic focus on one's own internal states, goals, motivations, and emotions. Guided by this framework, we detail 9 hypotheses and relevant empirical evidence concerning how class-based contextualist and solipsistic tendencies shape the self, perceptions of the social environment, and relationships to other individuals. Novel predictions and implications for research in other socio-political contexts are considered. Copyright 2012 APA, all rights reserved.

Combinations of Macrolide Resistance Determinants in Field Isolates of Mannheimia haemolytica and Pasteurella multocida▿

PubMed Central

Desmolaize, Benoit; Rose, Simon; Wilhelm, Cornelia; Warrass, Ralf; Douthwaite, Stephen

2011-01-01

Respiratory tract infections in cattle are commonly associated with the bacterial pathogens Mannheimia haemolytica and Pasteurella multocida. These infections can generally be successfully treated in the field with one of several groups of antibiotics, including macrolides. A few recent isolates of these species exhibit resistance to veterinary macrolides with phenotypes that fall into three distinct classes. The first class has type I macrolide, lincosamide, and streptogramin B antibiotic resistance and, consistent with this, the 23S rRNA nucleotide A2058 is monomethylated by the enzyme product of the erm(42) gene. The second class shows no lincosamide resistance and lacks erm(42) and concomitant 23S rRNA methylation. Sequencing of the genome of a representative strain from this class, P. multocida 3361, revealed macrolide efflux and phosphotransferase genes [respectively termed msr(E) and mph(E)] that are arranged in tandem and presumably expressed from the same promoter. The third class exhibits the most marked drug phenotype, with high resistance to all of the macrolides tested, and possesses all three resistance determinants. The combinations of erm(42), msr(E), and mph(E) are chromosomally encoded and intermingled with other exogenous genes, many of which appear to have been transferred from other members of the Pasteurellaceae. The presence of some of the exogenous genes explains recent reports of resistance to additional drug classes. We have expressed recombinant versions of the erm(42), msr(E), and mph(E) genes within an isogenic Escherichia coli background to assess their individually contributions to resistance. Our findings indicate what types of compounds might have driven the selection for these resistance determinants. PMID:21709086

Discriminating toxicant classes by mode of action. 1. (Eco)toxicity profiles.

PubMed

Nendza, Monika; Wenzel, Andrea

2006-05-01

Predictive toxicology, particularly quantitative structure-activity relationships (QSARs), require classification of chemicals by mode of action (MOA). MOA is, however, not a constant property of a compound but it varies between species and may change with concentration and duration of exposure. A battery of MOA-specific in-vitro and low-complexity assays, featuring biomolecular targets for major classes of environmental pollutants, provides characteristic responses for (1.) classification of chemicals by MOA, (2.) identification of (eco)toxicity profiles of chemicals, (3.) identification of chemicals with specific MOAs, (4.) indication of most sensitive species, (5.) identification of chemicals that are outliers in QSARs and (6.) selection of appropriate QSARs for predictions. Chemicals covering nine distinct modes of toxic action (non-polar non-specific toxicants (n=14), polar non-specific toxicants (n=18), uncouplers of oxidative phosphorylation (n=25), inhibitors of photosynthesis (n=15), inhibitors of acetylcholinesterase (n=14), inhibitors of respiration (n=3), thiol-alkylating agents (n=9), reactives (irritants) (n=8), estrogen receptor agonists (n=9)) were tested for cytotoxicity in the neutralred assay, oxygen consumption in isolated mitochondria, oxygen production in algae, inhibition of AChE, reaction with GSH and activity in the yeast estrogen receptor assay. Data on in-vivo aquatic toxicity (LC50, EC50) towards fish, daphnids, algae and bacteria were collected from the literature for reasons of comparison and reference scaling. In the MOA-specific in-vitro test battery, most test chemicals are specifically active at low concentrations, though multiple effects do occur. Graphical and statistical evaluation of the individual classes versus MOA 1 (non-polar non-specific toxicants) identifies interactions related to predominant MOA. Discriminant analyses (DA) on subsets of the data revealed correct classifications between 70% (in-vivo data) and >90% (in-vitro data). Functional similarity of chemical substances is defined in terms of their (eco)toxicity profiles. Within each MOA class, the compounds share some properties related to the rate-limiting interactions, e.g., steric fit to the target site and/or reactivity with target biomolecules, revealing a specific pattern (fingerprint) of characteristic effects. The successful discrimination of toxicant classes by MOA is based on comprehensive characterization of test chemicals' properties related to interactions with target sites. The suite of aquatic in-vivo tests using fish, daphnids, algae and bacteria covers most acute effects, whilst long-term (latent) impacts are generally neglected. With the MOA-specific in-vitro test battery such distinctions are futile, because it focuses on isolated targets, i.e. it indicates the possible targets of a chemical regardless of the timescale of effects. The data analysis indicates that the in-vitro battery covers most effects in vivo and moreover provides additional aspects of the compounds' MOA. Translating in-vitro effects to in-vivo toxicity requires combining physiological and chemical knowledge about underlying processes. Comparison of the specific in-vitro effects of a compound with the respective sensitivities of aquatic organisms indicates particularly sensitive species. Classifications of toxicants by MOA based on physicochemical descriptors provides insight to interactions and directs to mechanistic QSARs.

Organic molecular compositions and temporal variations of summertime mountain aerosols over Mt. Tai, North China Plain

NASA Astrophysics Data System (ADS)

Fu, Pingqing; Kawamura, Kimitaka; Okuzawa, Kazuhiro; Aggarwal, Shankar Gopala; Wang, Gehui; Kanaya, Yugo; Wang, Zifa

2008-10-01

Total suspended particles (TSP) were collected at the summit of Mt. Tai (1534 m above sea level) on a daytime and nighttime basis during a summertime campaign (May-June 2006) and were characterized for organic molecular compositions using solvent extraction/derivatization and gas chromatography/mass spectrometry technique. The n-Alkanes, fatty acids, fatty alcohols, sugars, glycerol and polyacids, and phthalate esters were found as major organic compound classes, whereas lignin and resin products, sterols, aromatic acids, hopanes, and polycyclic aromatic hydrocarbons (PAHs) were detected as minor classes. Sugars (49.8-2115 ng m-3, average 640 ng m-3 in daytime; 18.1-4348 ng m-3, 799 ng m-3 in nighttime) were found to be the dominant compound class. Levoglucosan, a specific cellulose pyrolysis product, was detected as the most abundant single compound, followed by C28 fatty alcohol, diisobutyl and di-n-butyl phthalates, C29n-alkane, C16 and C28 fatty acids, and malic acid. By grouping organic compounds based on their sources, we found that emission of terrestrial plant waxes was the most significant source (30-34%) of the TSP, followed by biomass burning products (25-27%) (e.g., levoglucosan and lignin and resin products), soil resuspension (15-18%) due to agricultural activities, secondary oxidation products (8-10%), plastic emission (3-10%), marine/microbial sources (6%), and urban/industrial emissions from fossil fuel use (4%). However, low molecular weight dicarboxylic acids (such as oxalic acid) of photochemical origin were not included in this study. Malic acid was found to be much higher than those reported in the ground level, suggesting an enhanced photochemical production in the free troposphere over mountain areas. Temporal variations of biomass burning tracers (e.g., levoglucosan, galactosan, mannosan) and some higher plant wax derived compound classes suggested that there were two major (E1 and E2) and one minor (E3) biomass-burning events during this campaign. Most of the compound classes showed higher concentrations in nighttime samples when organic aerosols can be long-range transported from different source regions to the summit of Mt. Tai above the planetary boundary layer (PBL). This study also demonstrates that the free troposphere over Mt. Tai is heavily influenced by field burning of agricultural wastes such as wheat straws in the North China Plain during the harvest season in early summer.

Direct Phenotypic Screening in Mice: Identification of Individual, Novel Antinociceptive Compounds from a Library of 734,821 Pyrrolidine Bis-piperazines.

PubMed

Houghten, Richard A; Ganno, Michelle L; McLaughlin, Jay P; Dooley, Colette T; Eans, Shainnel O; Santos, Radleigh G; LaVoi, Travis; Nefzi, Adel; Welmaker, Greg; Giulianotti, Marc A; Toll, Lawrence

2016-01-11

The hypothesis in the current study is that the simultaneous direct in vivo testing of thousands to millions of systematically arranged mixture-based libraries will facilitate the identification of enhanced individual compounds. Individual compounds identified from such libraries may have increased specificity and decreased side effects early in the discovery phase. Testing began by screening ten diverse scaffolds as single mixtures (ranging from 17,340 to 4,879,681 compounds) for analgesia directly in the mouse tail withdrawal model. The "all X" mixture representing the library TPI-1954 was found to produce significant antinociception and lacked respiratory depression and hyperlocomotor effects using the Comprehensive Laboratory Animal Monitoring System (CLAMS). The TPI-1954 library is a pyrrolidine bis-piperazine and totals 738,192 compounds. This library has 26 functionalities at the first three positions of diversity made up of 28,392 compounds each (26 × 26 × 42) and 42 functionalities at the fourth made up of 19,915 compounds each (26 × 26 × 26). The 120 resulting mixtures representing each of the variable four positions were screened directly in vivo in the mouse 55 °C warm-water tail-withdrawal assay (ip administration). The 120 samples were then ranked in terms of their antinociceptive activity. The synthesis of 54 individual compounds was then carried out. Nine of the individual compounds produced dose-dependent antinociception equivalent to morphine. In practical terms what this means is that one would not expect multiexponential increases in activity as we move from the all-X mixture, to the positional scanning libraries, to the individual compounds. Actually because of the systematic formatting one would typically anticipate steady increases in activity as the complexity of the mixtures is reduced. This is in fact what we see in the current study. One of the final individual compounds identified, TPI 2213-17, lacked significant respiratory depression, locomotor impairment, or sedation. Our results represent an example of this unique approach for screening large mixture-based libraries directly in vivo to rapidly identify individual compounds.

Design and synthesis of N-(3,3-diphenylpropenyl)alkanamides as a novel class of high-affinity MT2-selective melatonin receptor ligands.

PubMed

Bedini, Annalida; Spadoni, Gilberto; Gatti, Giuseppe; Lucarini, Simone; Tarzia, Giorgio; Rivara, Silvia; Lorenzi, Simone; Lodola, Alessio; Mor, Marco; Lucini, Valeria; Pannacci, Marilou; Scaglione, Francesco

2006-12-14

A novel series of melatonin receptor ligands was discovered by opening the cyclic scaffolds of known classes of high affinity melatonin receptor antagonists, while retaining the pharmacophore elements postulated by previously described 3D-QSAR and receptor models. Compounds belonging to the classes of 2,3- and [3,3-diphenylprop(en)yl]alkanamides and of o- or [(m-benzyl)phenyl]ethyl-alkanamides were synthesized and tested on MT(1) and MT(2) receptors. The class of 3,3-diphenyl-propenyl-alkanamides was the most interesting one, with compounds having MT(2) receptor affinity similar to that of MLT, remarkable MT(2) selectivity, and partial agonist or antagonist behavior. In particular, the (E)-m-methoxy cyclobutanecarboxamido derivative 18f and the di-(m-methoxy) acetamido one, 18g, have sub-nM affinity for the MT(2) subtype, with more than 100-fold selectivity over MT(1), 18f being an antagonist and 18g a partial agonist on GTPgammaS test. Docking of 18g into a previously developed MT(2) receptor model showed a binding scheme consistent with that of other antagonists. The MT(2) expected binding affinities of the new compounds were calculated by a previously developed 3D-QSAR CoMFA model, giving satisfactory predictions.

Molecular-level evidence provided by ultrahigh resolution mass spectrometry for oil-derived doc in groundwater at Bemidji, Minnesota

USGS Publications Warehouse

Islam, Ananna; Ahmed, Arif; Hur, Manhoi; Thorn, Kevin A.; Kim, Sunghwan

2016-01-01

Dissolved organic matter samples extracted from ground water at the USGS Bemidji oil spill site in Minnesota were investigated by ultrahigh resolution mass spectrometry. Principle component analysis (PCA) of the elemental composition assignments of the samples showed that the score plots for the contaminated sites were well separated from those for the uncontaminated sites. Additionally, spectra obtained from the same sampling site 7 and 19 years after the spill were grouped together in the score plot, strongly suggesting a steady state of contamination within the 12 year interval. The double bond equivalence (DBE) of Ox class compounds was broader for the samples from the contaminated sites, because of the complex nature of oil and the consequent formation of compounds with saturated and/or aromatic structures from the oxygenated products of oil. In addition, Ox class compounds with a relatively smaller number of x (x < 8; x = number of oxygen) and OxS1 class compounds were more abundant in the samples from the contaminated sites, because of the lower oxygen and higher sulfur contents of the oil compared to humic substances. The molecular-level signatures presented here can be a fundamental basis for in-depth analysis of oil contamination.

(PRESENTED AT TSUKIJI, CHUO-KU, JAPAN) PERSISTENT PERFLUORINATED COMPOUNDS IN THE ENVIRONMENT: A BRIEF INTRODUCTION TO THIS IMPORTANT NEW CLASS OF POLLUTANTS

EPA Science Inventory

PowerPoint presentation summarizing method development research involving the persistent perfluorinated organic compounds. Review of data indicating widespread distribution of these materials and the potential for toxicity.

Compound floating pivot micromechanisms

DOEpatents

Garcia, Ernest J.

2001-04-24

A new class of tilting micromechanical mechanisms have been developed. These new mechanisms use compound floating pivot structures to attain far greater tilt angles than are practical using other micromechanical techniques. The new mechanisms are also capable of bi-directional tilt about multiple axes.

Imidazopyridine derivatives as potent and selective Polo-like kinase (PLK) inhibitors.

PubMed

Sato, Yoshiyuki; Onozaki, Yu; Sugimoto, Tetsuya; Kurihara, Hideki; Kamijo, Kaori; Kadowaki, Chie; Tsujino, Toshiaki; Watanabe, Akiko; Otsuki, Sachie; Mitsuya, Morihiro; Iida, Masato; Haze, Kyosuke; Machida, Takumitsu; Nakatsuru, Yoko; Komatani, Hideya; Kotani, Hidehito; Iwasawa, Yoshikazu

2009-08-15

A novel class of imidazopyridine derivatives was designed as PLK1 inhibitors. Extensive SAR studies supported by molecular modeling afforded a highly potent and selective compound 36. Compound 36 demonstrated good antitumor efficacy in xenograft nude rat model.

Coumarin incorporated triazoles: a new class of anticonvulsants.

PubMed

Bhat, Mashooq A; Al-Omar, Mohammed A

2011-01-01

A series of coumarin incorporated 1,2,4- triazole compounds (1-14) were evaluated for their possible anticonvulsant and neurotoxic properties, log P values, pharmacophoric mapping and three dimensional structure analysis. Compound (6) with para-fluoro substitution showed significant anticonvulsant activity.

Fate and Transport of Select Hydraulic Fracturing Compounds of Potential Concern

EPA Pesticide Factsheets

Use of proprietary mixtures of reagents in fracing fluids injected in deep zones, has led to controversy over potential contamination of drinking water aquifers. This presentation focuses on the different classes of compounds identified in fracing fluids.

Social class, power, and selfishness: when and why upper and lower class individuals behave unethically.

PubMed

Dubois, David; Rucker, Derek D; Galinsky, Adam D

2015-03-01

Are the rich more unethical than the poor? To answer this question, the current research introduces a key conceptual distinction between selfish and unethical behavior. Based on this distinction, the current article offers 2 novel findings that illuminate the relationship between social class and unethical behavior. First, the effects of social class on unethical behavior are not invariant; rather, the effects of social class are moderated by whether unethical behavior benefits the self or others. Replicating past work, social class positively predicted unethical behavior; however, this relationship was only observed when that behavior was self-beneficial. When unethical behavior was performed to benefit others, social class negatively predicted unethical behavior; lower class individuals were more likely than upper class individuals to engage in unethical behavior. Overall, social class predicts people's tendency to behave selfishly, rather than predicting unethical behavior per se. Second, individuals' sense of power drove the effects of social class on unethical behavior. Evidence for this relationship was provided in three forms. First, income, but not education level, predicted unethical behavior. Second, feelings of power mediated the effect of social class on unethical behavior, but feelings of status did not. Third, two distinct manipulations of power produced the same moderation by self-versus-other beneficiary as was found with social class. The current theoretical framework and data both synthesize and help to explain a range of findings in the social class and power literatures. PsycINFO Database Record (c) 2015 APA, all rights reserved.

Physical stability of drugs after storage above and below the glass transition temperature: Relationship to glass-forming ability.

PubMed

Alhalaweh, Amjad; Alzghoul, Ahmad; Mahlin, Denny; Bergström, Christel A S

2015-11-10

Amorphous materials are inherently unstable and tend to crystallize upon storage. In this study, we investigated the extent to which the physical stability and inherent crystallization tendency of drugs are related to their glass-forming ability (GFA), the glass transition temperature (Tg) and thermodynamic factors. Differential scanning calorimetry was used to produce the amorphous state of 52 drugs [18 compounds crystallized upon heating (Class II) and 34 remained in the amorphous state (Class III)] and to perform in situ storage for the amorphous material for 12h at temperatures 20°C above or below the Tg. A computational model based on the support vector machine (SVM) algorithm was developed to predict the structure-property relationships. All drugs maintained their Class when stored at 20°C below the Tg. Fourteen of the Class II compounds crystallized when stored above the Tg whereas all except one of the Class III compounds remained amorphous. These results were only related to the glass-forming ability and no relationship to e.g. thermodynamic factors was found. The experimental data were used for computational modeling and a classification model was developed that correctly predicted the physical stability above the Tg. The use of a large dataset revealed that molecular features related to aromaticity and π-π interactions reduce the inherent physical stability of amorphous drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

25 CFR 522.11 - Individually owned class II gaming operations operating on September 1, 1986.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 2 2010-04-01 2010-04-01 false Individually owned class II gaming operations operating on September 1, 1986. 522.11 Section 522.11 Indians NATIONAL INDIAN GAMING COMMISSION, DEPARTMENT OF THE INTERIOR APPROVAL OF CLASS II AND CLASS III ORDINANCES AND RESOLUTIONS SUBMISSION OF GAMING...

Acculturating Indian immigrant men in New York City: applying the social capital construct to understand their experiences and health.

PubMed

Bhattacharya, Gauri

2008-04-01

This study qualitatively explored social capital available to individuals (N = 17) within a community-based purposive sample of adult male immigrants from India in New York City (NYC). Analysis of in-depth interview data identified possible pathways for social capital's influences upon acculturative stress. The study defined social capital in terms of the participants' social relationships among peers, in the workplace, and with their ethnic community. Their relationships were assessed in terms of support, trust, and reciprocity. Among the recent immigrants, hopelessness and frustration about future work prospects were associated with symptoms of depression and substance abuse. The participants identified wealth as a distinct marker of social class and they described social class as a combination of education and occupation. Social class largely determined the particular peer and community networks each participant joined. Participants relied upon ongoing connections with family in India, despite their geographic separation, to relieve acculturative stress. Social support from peers was the participants' most useful and immediate resource for alleviating acculturative stress. For participants of lower socioeconomic status, acculturative stress was compounded by social-relationship expectations and norms from India that persisted within NYCs immigrant community. Namely, lower-SES participants were more likely to experience frustration and setbacks when they sought out intimate social relationships with women.

Soft gelatin capsules (softgels).

PubMed

Gullapalli, Rampurna Prasad

2010-10-01

It is estimated that more than 40% of new chemical entities (NCEs) coming out of the current drug discovery process have poor biopharmaceutical properties, such as low aqueous solubility and/or permeability. These suboptimal properties pose significant challenges for the oral absorption of the compounds and for the development of orally bioavailable dosage forms. Development of soft gelatin capsule (softgel) dosage form is of growing interest for the oral delivery of poorly water soluble compounds (BCS class II or class IV). The softgel dosage form offers several advantages over other oral dosage forms, such as delivering a liquid matrix designed to solubilize and improve the oral bioavailability of a poorly soluble compound as a unit dose solid dosage form, delivering low and ultra-low doses of a compound, delivering a low melting compound, and minimizing potential generation of dust during manufacturing and thereby improving the safety of production personnel. However, due to the very dynamic nature of the softgel dosage form, its development and stability during its shelf-life are fraught with several challenges. The goal of the current review is to provide an in-depth discussion on the softgel dosage form to formulation scientists who are considering developing softgels for therapeutic compounds.

Inorganic and methane clathrates: Versatility of guest–host compounds for energy harvesting

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

Krishna, Lakshmi; Koh, Carolyn A.

ABSTRACT This review article evaluates the structure–property relations of inorganic clathrates and clathrate hydrates and their potential role in energy harvesting. There is potential cross-fertilization between the two research areas. Guest–host clathrate compounds exhibit unique structural and physical properties, which lead to their versatile roles in energy applications. Prominent classes of clathrate compounds are gas hydrates and inorganic clathrates. That said, there is limited cross-fertilization between the clathrate hydrate and inorganic clathrate communities, with researchers in the respective fields being less informed on the other field. Yet the structures and unique guest–host interactions in both these compounds are common importantmore » features of these clathrates. Common features and procedures can inspire and inform development between the compound classes, which may be important to the technological advancements for the different clathrate materials, e.g., structure characterization techniques and guest–host dynamics in which the “guest” tends to be imprisoned in the host structure, until external forces are applied. Conversely, the diversity in chemical compositions of these two classes of materials leads to the different applications from methane capture and storage to converting waste heat to electricity (thermoelectrics). This article highlights the structural and physical similarities and differences of inorganic and methane clathrates. The most promising state-of-the-art applications of the clathrates are highlighted for harvesting energy from methane (clathrate) hydrate deposits under the ocean and for inorganic clathrates as promising thermoelectric materials.« less

Inorganic and methane clathrates: Versatility of guest–host compounds for energy harvesting

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

Krishna, Lakshmi; Koh, Carolyn A.

2015-01-01

ABSTRACT This review article evaluates the structure–property relations of inorganic clathrates and clathrate hydrates and their potential role in energy harvesting. There is potential cross-fertilization between the two research areas. Guest–host clathrate compounds exhibit unique structural and physical properties, which lead to their versatile roles in energy applications. Prominent classes of clathrate compounds are gas hydrates and inorganic clathrates. That said, there is limited cross-fertilization between the clathrate hydrate and inorganic clathrate communities, with researchers in the respective fields being less informed on the other field. Yet the structures and unique guest–host interactions in both these compounds are common importantmore » features of these clathrates. Common features and procedures can inspire and inform development between the compound classes, which may be important to the technological advancements for the different clathrate materials, e.g., structure characterization techniques and guest–host dynamics in which the “guest” tends to be imprisoned in the host structure, until external forces are applied. Conversely, the diversity in chemical compositions of these two classes of materials leads to the different applications from methane capture and storage to converting waste heat to electricity (thermoelectrics). This article highlights the structural and physical similarities and differences of inorganic and methane clathrates. The most promising state-of-the-art applications of the clathrates are highlighted for harvesting energy from methane (clathrate) hydrate deposits under the ocean and for inorganic clathrates as promising thermoelectric materials.« less

"Plate cherry picking": a novel semi-sequential screening paradigm for cheaper, faster, information-rich compound selection.

PubMed

Crisman, Thomas J; Jenkins, Jeremy L; Parker, Christian N; Hill, W Adam G; Bender, Andreas; Deng, Zhan; Nettles, James H; Davies, John W; Glick, Meir

2007-04-01

This work describes a novel semi-sequential technique for in silico enhancement of high-throughput screening (HTS) experiments now employed at Novartis. It is used in situations in which the size of the screen is limited by the readout (e.g., high-content screens) or the amount of reagents or tools (proteins or cells) available. By performing computational chemical diversity selection on a per plate basis (instead of a per compound basis), 25% of the 1,000,000-compound screening was optimized for general initial HTS. Statistical models are then generated from target-specific primary results (percentage inhibition data) to drive the cherry picking and testing from the entire collection. Using retrospective analysis of 11 HTS campaigns, the authors show that this method would have captured on average two thirds of the active compounds (IC(50) < 10 microM) and three fourths of the active Murcko scaffolds while decreasing screening expenditure by nearly 75%. This result is true for a wide variety of targets, including G-protein-coupled receptors, chemokine receptors, kinases, metalloproteinases, pathway screens, and protein-protein interactions. Unlike time-consuming "classic" sequential approaches that require multiple iterations of cherry picking, testing, and building statistical models, here individual compounds are cherry picked just once, based directly on primary screening data. Strikingly, the authors demonstrate that models built from primary data are as robust as models built from IC(50) data. This is true for all HTS campaigns analyzed, which represent a wide variety of target classes and assay types.

Neural network recognition of chemical class information in mobility spectra obtained at high temperatures

NASA Technical Reports Server (NTRS)

Bell, S.; Nazarov, E.; Wang, Y. F.; Rodriguez, J. E.; Eiceman, G. A.

2000-01-01

A minimal neural network was applied to a large library of high-temperature mobility spectra drawn from 16 chemical classes including 154 substances with 2000 spectra at various concentrations. A genetic algorithm was used to create a representative subset of points from the mobility spectrum as input to a cascade-type back-propagation network. This network demonstrated that significant information specific to chemical class was located in the spectral region near the reactant ions. This network failed to generalize the solution to unfamiliar compounds necessitating the use of complete spectra in network processing. An extended back-propagation network classified unfamiliar chemicals by functional group with a mean for average values of 0.83 without sulfides and 0.79 with sulfides. Further experiments confirmed that chemical class information was resident in the spectral region near the reactant ions. Deconvolution of spectra demonstrated the presence of ions, merged with the reactant ion peaks that originated from introduced samples. The ability of the neural network to generalize the solution to unfamiliar compounds suggests that these ions are distinct and class specific.

Discovery of aliphatic-chain hydroxamates containing indole derivatives with potent class I histone deacetylase inhibitory activities.

PubMed

Chao, Shi-Wei; Chen, Liang-Chieh; Yu, Chia-Chun; Liu, Chang-Yi; Lin, Tony Eight; Guh, Jih-Hwa; Wang, Chen-Yu; Chen, Chun-Yung; Hsu, Kai-Cheng; Huang, Wei-Jan

2018-01-01

Histone deacetylase (HDAC) is a validated drug target for various diseases. This study combined indole recognition cap with SAHA, an FDA-approved HDAC inhibitor used to treat cutaneous T-cell lymphoma (CTCL). The structure activity relationship of the resulting compounds that inhibited HDAC was disclosed as well. Some compounds exhibited much stronger inhibitory activities than SAHA. We identified two meta-series compounds 6j and 6k with a two-carbon linker had IC 50 values of 3.9 and 4.5 nM for HDAC1, respectively. In contrast, the same oriented compounds with longer carbon chain linkers showed weaker inhibition. The result suggests that the linker chain length greatly contributed to enzyme inhibitory potency. In addition, comparison of enzyme-inhibiting activity between the compounds and SAHA showed that compounds 6j and 6k displayed higher inhibiting activity for class I (HDAC1, -2, -3 and -8). The molecular docking and structure analysis revealed structural differences with the inhibitor cap and metal-binding regions between the HDAC isozymes that affect interactions with the inhibitors and play a key role for selectivity. Further biological evaluation showed multiple cellular effects associated with compounds 6j- and 6k-induced HDAC inhibitory activity. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Antimalarial compounds in Phase II clinical development.

PubMed

Held, Jana; Jeyaraj, Sankarganesh; Kreidenweiss, Andrea

2015-03-01

Malaria is a major health problem in endemic countries and chemotherapy remains the most important tool in combating it. Treatment options are limited and essentially rely on a single drug class - the artemisinins. Efforts are ongoing to restrict the evolving threat of artemisinin resistance but declining sensitivity has been reported. Fueled by the ambitious aim of malaria eradication, novel antimalarial compounds, with improved properties, are now in the progressive phase of drug development. Herein, the authors describe antimalarial compounds currently in Phase II clinical development and present the results of these investigations. Thanks to recent efforts, a number of promising antimalarial compounds are now in the pipeline. First safety data have been generated for all of these candidates, although their efficacy as antimalarials is still unclear for most of them. Of particular note are KAE609, KAF156 and DSM265, which are of chemical scaffolds new to malaria chemotherapy and would truly diversify antimalarial options. Apart from SAR97276, which also has a novel chemical scaffold that has had its development stopped, all other compounds in the pipeline belong to already known substance classes, which have been chemically modified. At this moment in time, there is not one standout compound that will revolutionize malaria treatment but several compounds that will add to its control in the future.

Improved BM212 MmpL3 Inhibitor Analogue Shows Efficacy in Acute Murine Model of Tuberculosis Infection

PubMed Central

Alfonso, Salvatore; Cocozza, Martina; Porretta, Giulio Cesare; Ballell, Lluís; Rullas, Joaquin; Ortega, Fátima; De Logu, Alessandro; Agus, Emanuela; La Rosa, Valentina; Pasca, Maria Rosalia; De Rossi, Edda; Wae, Baojie; Franzblau, Scott G.; Manetti, Fabrizio; Botta, Maurizio; Biava, Mariangela

2013-01-01

1,5-Diphenyl pyrroles were previously identified as a class of compounds endowed with high in vitro efficacy against M. tuberculosis. To improve the physical chemical properties and drug-like parameters of this class of compounds, a medicinal chemistry effort was undertaken. By selecting the optimal substitution patterns for the phenyl rings at N1 and C5 and by replacing the thiomorpholine moiety with a morpholine one, a new series of compounds was produced. The replacement of the sulfur with oxygen gave compounds with lower lipophilicity and improved in vitro microsomal stability. Moreover, since the parent compound of this family has been shown to target MmpL3, mycobacterial mutants resistant to two compounds have been isolated and characterized by sequencing the mmpL3 gene; all the mutants showed point mutations in this gene. The best compound identified to date was progressed to dose-response studies in an acute murine TB infection model. The resulting ED99 of 49 mg/Kg is within the range of commonly employed tuberculosis drugs, demonstrating the potential of this chemical series. The in vitro and in vivo target validation evidence presented here adds further weight to MmpL3 as a druggable target of interest for anti-tubercular drug discovery. PMID:23437287

Multiplexed profiling of GPCR activities by combining split TEV assays and EXT-based barcoded readouts.

PubMed

Galinski, Sabrina; Wichert, Sven P; Rossner, Moritz J; Wehr, Michael C

2018-05-25

G protein-coupled receptors (GPCRs) are the largest class of cell surface receptors and are implicated in the physiological regulation of many biological processes. The high diversity of GPCRs and their physiological functions make them primary targets for therapeutic drugs. For the generation of novel compounds, however, selectivity towards a given target is a critical issue in drug development as structural similarities between members of GPCR subfamilies exist. Therefore, the activities of multiple GPCRs that are both closely and distantly related to assess compound selectivity need to be tested simultaneously. Here, we present a cell-based multiplexed GPCR activity assay, termed GPCRprofiler, which uses a β-arrestin recruitment strategy and combines split TEV protein-protein interaction and EXT-based barcode technologies. This approach enables simultaneous measurements of receptor activities of multiple GPCR-ligand combinations by applying massively parallelized reporter assays. In proof-of-principle experiments covering 19 different GPCRs, both the specificity of endogenous agonists and the polypharmacological effects of two known antipsychotics on GPCR activities were demonstrated. Technically, normalization of barcode reporters across individual assays allows quantitative pharmacological assays in a parallelized manner. In summary, the GPCRprofiler technique constitutes a flexible and scalable approach, which enables simultaneous profiling of compound actions on multiple receptor activities in living cells.

Utilization of quantitative structure-activity relationships (QSARs) in risk assessment: Alkylphenols

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

Beck, B.D.; Toole, A.P.; Callahan, B.G.

1991-12-01

Alkylphenols are a class of environmentally pervasive compounds, found both in natural (e.g., crude oils) and in anthropogenic (e.g., wood tar, coal gasification waste) materials. Despite the frequent environmental occurrence of these chemicals, there is a limited toxicity database on alkylphenols. The authors have therefore developed a 'toxicity equivalence approach' for alkylphenols which is based on their ability to inhibit, in a specific manner, the enzyme cyclooxygenase. Enzyme-inhibiting ability for individual alkylphenols can be estimated based on the quantitative structure-activity relationship developed by Dewhirst (1980) and is a function of the free hydroxyl group, electron-donating ring substituents, and hydrophobic aromaticmore » ring substituents. The authors evaluated the toxicological significance of cyclooxygenase inhibition by comparison of the inhibitory capacity of alkylphenols with the inhibitory capacity of acetylsalicylic acid, or aspirin, a compound whose low-level effects are due to cyclooxygenase inhibition. Since nearly complete absorption for alkylphenols and aspirin is predicted, based on estimates of hydrophobicity and fraction of charged molecules at gastrointestinal pHs, risks from alkylphenols can be expressed directly in terms of 'milligram aspirin equivalence,' without correction for absorption differences. They recommend this method for assessing risks of mixtures of alkylphenols, especially for those compounds with no chronic toxicity data.38 references.« less

Co-evolution of Human Leukocyte Antigen (HLA) Class I Ligands with Killer-Cell Immunoglobulin-Like Receptors (KIR) in a Genetically Diverse Population of Sub-Saharan Africans

PubMed Central

Norman, Paul J.; Hollenbach, Jill A.; Nemat-Gorgani, Neda; Guethlein, Lisbeth A.; Hilton, Hugo G.; Pando, Marcelo J.; Koram, Kwadwo A.; Riley, Eleanor M.; Abi-Rached, Laurent; Parham, Peter

2013-01-01

Interactions between HLA class I molecules and killer-cell immunoglobulin-like receptors (KIR) control natural killer cell (NK) functions in immunity and reproduction. Encoded by genes on different chromosomes, these polymorphic ligands and receptors correlate highly with disease resistance and susceptibility. Although studied at low-resolution in many populations, high-resolution analysis of combinatorial diversity of HLA class I and KIR is limited to Asian and Amerindian populations with low genetic diversity. At the other end of the spectrum is the West African population investigated here: we studied 235 individuals, including 104 mother-child pairs, from the Ga-Adangbe of Ghana. This population has a rich diversity of 175 KIR variants forming 208 KIR haplotypes, and 81 HLA-A, -B and -C variants forming 190 HLA class I haplotypes. Each individual we studied has a unique compound genotype of HLA class I and KIR, forming 1–14 functional ligand-receptor interactions. Maintaining this exceptionally high polymorphism is balancing selection. The centromeric region of the KIR locus, encoding HLA-C receptors, is highly diverse whereas the telomeric region encoding Bw4-specific KIR3DL1, lacks diversity in Africans. Present in the Ga-Adangbe are high frequencies of Bw4-bearing HLA-B*53:01 and Bw4-lacking HLA-B*35:01, which otherwise are identical. Balancing selection at key residues maintains numerous HLA-B allotypes having and lacking Bw4, and also those of stronger and weaker interaction with LILRB1, a KIR-related receptor. Correspondingly, there is a balance at key residues of KIR3DL1 that modulate its level of cell-surface expression. Thus, capacity to interact with NK cells synergizes with peptide binding diversity to drive HLA-B allele frequency distribution. These features of KIR and HLA are consistent with ongoing co-evolution and selection imposed by a pathogen endemic to West Africa. Because of the prevalence of malaria in the Ga-Adangbe and previous associations of cerebral malaria with HLA-B*53:01 and KIR, Plasmodium falciparum is a candidate pathogen. PMID:24204327

Characterization of emissions composition for selected household products available in Korea.

PubMed

Kwon, Ki-Dong; Jo, Wan-Kuen; Lim, Ho-Jin; Jeong, Woo-Sik

2007-09-05

The present study investigated the emission composition for 59 household products currently sold in Korea, using a headspace analysis. The chemical composition and concentrations of total volatile organic compounds (VOCs) broadly varied along with products, even within the same product category. Up to 1-17 organic compounds were detected in the headspace gas phase of any one of the products. The chemical composition of certain household products determined in the current study was different from that of other studies from other countries. Between 4 and 37 compounds were detected in the headspace gas phase of each product class. Several compounds were identified in more than one product class. Of the 59 household products analyzed, 58 emitted one or more of the 72 compounds at chromatographic peak areas above 10(4). There were 11 analytes which occurred with a frequency of more than 10%: limonene (44.2%), ethanol (30.5%), acetone (18.6%), alpha-pinene (18.6%), o,m,p-xylenes (18.6%), decane (17.0%), toluene (17.0%), beta-myrcene (11.9%), ammonia (10.2%), ethylbenzene (10.2%), and hexane (10.2%).

Anaphylaxis induced by ingestion of a pollen compound.

PubMed

Chivato, T; Juan, F; Montoro, A; Laguna, R

1996-01-01

We report on the case of a 32-year-old atopic patient who showed a severe anaphylactic reaction due to the ingestion of a pollen compound prepared in an herbalist's. A few minutes after ingestion, generalized pruritus, difuse erythema, facial edema, cough, hoarseness and dysphonia appeared, and the emergency administration of subcutaneous epinephrine and intravenous methylprednisolone was necessary. Skin tests with a battery of inhalants and food allergens were performed. The patient only showed sensitization to Artemisia vulgaris, Taraxacum officinalis and Salix alba. Specific IgE levels were evaluated by FEIA-CAP giving a seric level of CAP class 3 to Artemisia vulgaris and class 2 to Taraxacum officinalis and Salix alba. Samples of the pollen compound were shown in the microscopical analysis to be 93% pollens and 6% fungi. In the qualitative study Taraxacum officinalis (15%), Artemisia vulgaris (5%) and Salix alba (15%) were the main elements identified. In summary, this case study describes a food-induced systemic reaction due to a pollen compound in an atopic patient with a history of allergic rhinitis. Pollinic patients must be informed on the risks that the consumption of these compounds might cause.

High energy expenditure masks low physical activity in obesity.

PubMed

DeLany, J P; Kelley, D E; Hames, K C; Jakicic, J M; Goodpaster, B H

2013-07-01

To investigate energy expenditure in lean and obese individuals, focusing particularly on physical activity and severely obese individuals. Total daily energy expenditure (TDEE) was assessed using doubly labeled water, resting metabolic rate (RMR) by indirect calorimetry, activity energy expenditure (AEE) by difference and time spent in physical activity by multisensor activity monitors. In all, 177 lean, Class I and severely obese individuals (age 31-56 years, body mass index 20-64 kg m(-2)) were analyzed. All components of energy expenditure were elevated in obese individuals. For example, TDEE was 2404±95 kcal per day in lean and 3244±48 kcal per day in Class III obese individuals. After appropriate adjustment, RMR was similar in all groups. Analysis of AEE by body weight and obesity class indicated a lower AEE in obese individuals. Confirming lower physical activity, obese individuals spent less time engaged in moderate-to-vigorous physical activity (2.7±1.3, 1.8±0.6, 2.0±1.4 and 1.2±1.0 h per day in lean, Class I, Class II and Class III individuals) and more time in sedentary behaviors. There was no indication of metabolic efficiency in even the severely obese, as adjusted RMR was similar across all groups. The higher AEE observed in the obese is consistent with a higher cost of activities due to higher body weight. However, the magnitude of the higher AEE (20-25% higher in obese individuals) is lower than expected (weight approximately 100% higher in Class III individuals). Confirming a lower volume of physical activity in the obese, the total time spent in moderate-to-vigorous physical activity and average daily metabolic equivalent of task level were lower with increasing obesity. These findings demonstrate that high body weight in obese individuals leads to a high TDEE and AEE, which masks the fact that they are less physically active, which can be influenced by duration or intensity of activity, than in lean individuals.

Structure optimization and preliminary bioactivity evaluation of N-hydroxybenzamide-based HDAC inhibitors with Y-shaped cap.

PubMed

Yu, Chenggong; He, Feng; Qu, Ying; Zhang, Qiuqiong; Lv, Jiahui; Zhang, Xiangna; Xu, Ana; Miao, Pannan; Wu, Jingde

2018-05-01

Histone deacetylase inhibitors (HDACIs) are effective small molecules in the treatment of human cancers. In our continuing efforts to develop novel N-hydroxyterephthalamide-based HDACIs, herein we report the design and development of a new class of N-hydroxybenzamide-based HDACIs. In this new class of analogs, we inserted an ethylene moiety in the linker and used indole as a part of the Y-shaped cap group. Biological characterization identified compounds 4o, 4p, 4q and 4t to show improved HDAC inhibition, while no isoform selectivity for HDACs was observed. These compounds also exhibited improved anti-proliferative activity against multiple cancer cell lines when compared to their parent compound and positive control SAHA. Copyright © 2018 Elsevier Ltd. All rights reserved.

A Drosophila Gustatory Receptor Required for Strychnine Sensation.

PubMed

Lee, Youngseok; Moon, Seok Jun; Wang, Yijin; Montell, Craig

2015-09-01

Strychnine is a potent, naturally occurring neurotoxin that effectively protects plants from animal pests by deterring feeding behavior. In insects, such as the fruit fly, Drosophila melanogaster, bitter-tasting aversive compounds are detected primarily through a family of gustatory receptors (GRs), which are expressed in gustatory receptor neurons. We previously described multiple GRs that eliminate the behavioral avoidance to all bitter compounds tested, with the exception of strychnine. Here, we report the identity of a strychnine receptor, referred to as GR47a. We generated a mutation in Gr47a and found that it eliminated strychnine repulsion and strychnine-induced action potentials. GR47a was narrowly tuned, as the responses to other avoidance compounds were unaffected in the mutant animals. This analysis supports an emerging model that Drosophila GRs fall broadly into two specificity classes-one class is comprised of core receptors that are broadly required, whereas the other class, which includes GR47a, consists of narrowly tuned receptors that define chemical specificity. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The Compound and Homologous Eruptions from the SAR 11429

NASA Astrophysics Data System (ADS)

Dhakal, Suman Kumar; Zhang, Jie

2016-05-01

Super Active Regions (SARs) are ARs which shows extremely high rate of solar eruptions. NOAA AR 11429 was a SAR which produced 47 C-Class, 15 M-Class and 3 X-Class flares and 8 CMEs during its passage from the front disk of the Sun. This SAR had anti-Hale and delta-spot magnetic configuration and many sub-regions of magnetic flux emergence. With the aid of multi-wavelength observations of the Solar Dynamics Observatory (SDO), the Solar Terrestrial Relations Observatory (STEREO) and nonlinear force-free model for the magnetic field in the solar corona, we found the existence of many magnetic flux structures (flux bundles) in the corona of the AR. The energy released by these co-existing flux bundles within short time, resulted in compound erutpions from the AR on March 9 and 10, 2012. In the period of 38 hours, after the CME eruption on March 9, the continuous shearing and cancellation and new magnetic flux emergence resulted in another CME on March 10. Both of the events showed the compound nature and the similarity of the foot-points and EUV dimming made these eruptions homologous.

Developing novel anthelmintics from plant cysteine proteinases

PubMed Central

Behnke, Jerzy M; Buttle, David J; Stepek, Gillian; Lowe, Ann; Duce, Ian R

2008-01-01

Intestinal helminth infections of livestock and humans are predominantly controlled by treatment with three classes of synthetic drugs, but some livestock nematodes have now developed resistance to all three classes and there are signs that human hookworms are becoming less responsive to the two classes (benzimidazoles and the nicotinic acetylcholine agonists) that are licensed for treatment of humans. New anthelmintics are urgently needed, and whilst development of new synthetic drugs is ongoing, it is slow and there are no signs yet that novel compounds operating through different modes of action, will be available on the market in the current decade. The development of naturally-occurring compounds as medicines for human use and for treatment of animals is fraught with problems. In this paper we review the current status of cysteine proteinases from fruits and protective plant latices as novel anthelmintics, we consider some of the problems inherent in taking laboratory findings and those derived from folk-medicine to the market and we suggest that there is a wealth of new compounds still to be discovered that could be harvested to benefit humans and livestock. PMID:18761736

Tetrahydrocarbazoles are a novel class of potent P-type ATPase inhibitors with antifungal activity

PubMed Central

Bublitz, Maike; Kjellerup, Lasse; Cohrt, Karen O’Hanlon; Gordon, Sandra; Mortensen, Anne Louise; Clausen, Johannes D.; Pallin, Thomas David; Hansen, John Bondo; Fuglsang, Anja Thoe; Dalby-Brown, William

2018-01-01

We have identified a series of tetrahydrocarbazoles as novel P-type ATPase inhibitors. Using a set of rationally designed analogues, we have analyzed their structure-activity relationship using functional assays, crystallographic data and computational modeling. We found that tetrahydrocarbazoles inhibit adenosine triphosphate (ATP) hydrolysis of the fungal H+-ATPase, depolarize the fungal plasma membrane and exhibit broad-spectrum antifungal activity. Comparative inhibition studies indicate that many tetrahydrocarbazoles also inhibit the mammalian Ca2+-ATPase (SERCA) and Na+,K+-ATPase with an even higher potency than Pma1. We have located the binding site for this compound class by crystallographic structure determination of a SERCA-tetrahydrocarbazole complex to 3.0 Å resolution, finding that the compound binds to a region above the ion inlet channel of the ATPase. A homology model of the Candida albicans H+-ATPase based on this crystal structure, indicates that the compounds could bind to the same pocket and identifies pocket extensions that could be exploited for selectivity enhancement. The results of this study will aid further optimization towards selective H+-ATPase inhibitors as a new class of antifungal agents. PMID:29293507

Synthesis of 4-hydroxy-1-methylindole and benzo[b]thiophen-4-ol based unnatural flavonoids as new class of antimicrobial agents.

PubMed

Yadav, Prem P; Gupta, Prasoon; Chaturvedi, A K; Shukla, P K; Maurya, Rakesh

2005-03-01

Synthesis of nitrogen and sulfur heterocyclic mimics of furanoflavonoids have been achieved for the first time. Synthesized flavonoid alkaloids and thiophenyl flavonoids have been screened for antifungal and antibacterial activities. All the test compounds barring 25 exhibited antifungal activity. The compound 19 was the best and showed comparable MICs to the known compound karanjin. Compounds 5, 12, 14 and 22 also showed comparable MIC to karanjin.

A person-centered approach to individualizing a school-based universal preventive intervention.

PubMed

Caldwell, Linda L; Bradley, Stephanie; Coffman, Donna

2009-01-01

This manuscript focuses on how individualized components may be embedded within a universal preventive intervention (TimeWise: Taking Charge of Leisure Time) to make program delivery more effective. Leisure related variables (motivation, boredom/interest and peer and parental influence) were used to suggest ways to individualize the program. Latent Class Analysis was used to develop individualized risk and strength profiles of adolescents (N = 617). Comparisons were made between a treatment and control group. Four classes were identified: undifferentiated high, intrinsic motivation, extrinsic motivation/amotivation, undifferentiated low. These classes were related to substance use. Membership in the intrinsic class was associated with intervention group while the extrinsic class was related to the control group. Results were useful in suggesting ways to tailor a universal prevention program.

Concentration and Particle Size of Airborne Toxic Algae (Brevetoxin) Derived from Ocean Red Tide Events

PubMed Central

Cheng, Yung Sung; Mcdonald, Jacob D.; Kracko, Dean; Irvin, C. Mitch; Zhou, Yue; Pierce, Richard H.; Henry, Michael S.; Bourdelaisa, Andrea; Naar, Jerome; Baden, Daniel G.

2009-01-01

Red tides in the Gulf of Mexico are formed by blooms of the dinoflagellate Karenia brevis, which produces brevetoxins (PbTx). Brevetoxins can be transferred from water to air in the wind-powered whitecapped waves during red tide episodes. Inhalation exposure to marine aerosol containing PbTx causes respiratory problems. A liquid chromatograph/ tandem mass spectrometric method was developed for the detection and quantitation of several PbTxs in ambient samples collected during red tide events. This method was complemented by a previously developed antibody assay that analyzes the entire class of PbTx compounds. The method showed good linearity, accuracy, and reproducibility, allowing quantitation of PbTx compounds in the 10 pg/m3 range. Air concentrations of PbTxs and brevenal for individual samples ranged from 0.01 to 80 ng/m3. The particle size showed a single mode with a mass median diameter between 6 and 10 μm, which was consistent for all of the PbTx species that were measured. Our results imply that individual PbTxs were from the same marine aerosol or from marine aerosol that was produced from the same process. The particle size indicated the likelihood of high deposition efficiency in the respiratory tract with the majority of aerosol deposited in the upper airways and small but not insignificant deposition in the lower airways. PMID:15954221

New class of compounds have very low vapor pressures

NASA Technical Reports Server (NTRS)

Angell, C. A.; Gruen, D. M.

1967-01-01

Magnesium hexahydrate tetrachlorometallates are 50-volume-percent water, have a high melting point and possess a low vapor pressure. These new compounds are relatively noncorrosive, thermally stable, and water soluble but not hygroscopic. They may have potential applications as cooling fluids.

A MODEL FOR DIFFUSION CONTROLLED BIOAVAILABILITY OF CRUDE OIL COMPONENTS

EPA Science Inventory

Crude oil is a complex mixture of several different structural classes of compounds including alkanes, aromatics, heterocyclic polar compounds, and asphaltenes. The rate and extent of microbial degradation of crude oil depends on the interaction between the physical and biochemi...

Phenolic plant metabolites as bioactive food and feed additives

USDA-ARS?s Scientific Manuscript database

Functional additives in food and animal feed formulations are gaining acceptance as consumers and producers recognize the health benefits associated with certain natural plant products. Phenolic compounds in particular have emerged as a class of compounds with antioxidant, antibacterial, and antifun...

The pharmacokinetics and health benefits of orange peel compounds

USDA-ARS?s Scientific Manuscript database

Orange peel is a resource rich in phenolic antioxidants, including several classes of flavonoids and hydroxycinnamates. These compounds have been extensively studied for their biological actions particularly against chronic diseases in humans. Yet, full development of these materials as new, commerc...

FACTORS IN GEOTROPOSPHERIC PARTICLE-GAS TRANSPORT OF SEMIVOLATILE ORGANIC COMPOUNDS

EPA Science Inventory

Semivolatile organic compounds (SVOCs) can exist in solid, liquid, or gas phases under ambient environmental conditions. The geotropospheric transport of SVOCs varies according to the particle type. Two classes of SVOCs and two types of particles were analyzed to determine possib...

Sugar Ester Compounds for Arthropod Control

USDA-ARS?s Scientific Manuscript database

Sugar esters, also known as acyl sugars or polyol esters, are a class of compounds that are internationally recognized as food additives. They are commonly used in bakery goods, drugs, cosmetics, food packaging plastics, and in other applications because of their surfactant and emulsifying properti...

Cross species comparisons of chemical interaction with recombinant steroid receptors in vitro.

EPA Science Inventory

Typically, mammalian receptors are used for in vitro hazard identification and screening for endocrine disrupting compounds. There is concern, however, that differences may exist in the affinities of environmental compounds for steroid receptors from other vertebrate classes. S...

A yeast-based assay identifies drugs that interfere with immune evasion of the Epstein-Barr virus.

PubMed

Voisset, Cécile; Daskalogianni, Chrysoula; Contesse, Marie-Astrid; Mazars, Anne; Arbach, Hratch; Le Cann, Marie; Soubigou, Flavie; Apcher, Sébastien; Fåhraeus, Robin; Blondel, Marc

2014-04-01

Epstein-Barr virus (EBV) is tightly associated with certain human cancers, but there is as yet no specific treatment against EBV-related diseases. The EBV-encoded EBNA1 protein is essential to maintain viral episomes and for viral persistence. As such, EBNA1 is expressed in all EBV-infected cells, and is highly antigenic. All infected individuals, including individuals with cancer, have CD8(+) T cells directed towards EBNA1 epitopes, yet the immune system fails to detect and destroy cells harboring the virus. EBV immune evasion depends on the capacity of the Gly-Ala repeat (GAr) domain of EBNA1 to inhibit the translation of its own mRNA in cis, thereby limiting the production of EBNA1-derived antigenic peptides presented by the major histocompatibility complex (MHC) class I pathway. Here we establish a yeast-based assay for monitoring GAr-dependent inhibition of translation. Using this assay we identify doxorubicin (DXR) as a compound that specifically interferes with the GAr effect on translation in yeast. DXR targets the topoisomerase-II-DNA complexes and thereby causes genomic damage. We show, however, that the genotoxic effect of DXR and various analogs thereof is uncoupled from the effect on GAr-mediated translation control. This is further supported by the observation that etoposide and teniposide, representing another class of topoisomerase-II-DNA targeting drugs, have no effect on GAr-mediated translation control. DXR and active analogs stimulate, in a GAr-dependent manner, EBNA1 expression in mammalian cells and overcome GAr-dependent restriction of MHC class I antigen presentation. These results validate our approach as an effective high-throughput screening assay to identify drugs that interfere with EBV immune evasion and, thus, constitute candidates for treating EBV-related diseases, in particular EBV-associated cancers.

Social Class, Solipsism, and Contextualism: How the Rich Are Different from the Poor

ERIC Educational Resources Information Center

Kraus, Michael W.; Piff, Paul K.; Mendoza-Denton, Rodolfo; Rheinschmidt, Michelle L.; Keltner, Dacher

2012-01-01

Social class is shaped by an individual's material resources as well as perceptions of rank vis-a-vis others in society, and in this article, we examine how class influences behavior. Diminished resources and lower rank create contexts that constrain social outcomes for lower-class individuals and enhance contextualist tendencies--that is, a focus…

Role of species diversity and secondary compound complementarity on diet selection of Mediterranean shrubs by goats.

PubMed

Rogosic, Jozo; Estell, Richard E; Skobic, Dragan; Martinovic, Anita; Maric, Stanislava

2006-06-01

Goats foraging on Mediterranean shrubs containing secondary compounds (toxins) may consume a variety of shrubs that contain different phytotoxins, thereby increasing shrub intake and avoiding toxicosis. We conducted eight experiments to examine whether goats offered different mixtures of shrubs containing different phytotoxins (tannins and saponins) would consume more shrub biomass than goats offered one shrub a single phytotoxin (tannin or saponin). In the first three experiments, goats fed a mixture of three tannin-rich shrubs (Quercus ilex, Arbutus unedo, and Pistacia lentiscus) ate more foliage than goats offered only one shrub (23.2 vs. 10.7 g/kg BW; 25.2 vs. 13.4 g/kg BW, and 27.9 vs. 7.9 g/kg BW), regardless of tannin concentration in individual shrub species. Goats also consumed more foliage when offered the same three tannin-rich shrubs than when offered the saponin-rich shrub Hedera helix (25.4 vs. 8.0 g/kg BW). However, goats offered a mixture of the same three tannin-rich shrubs consumed less foliage than goats offered a mixture of two shrubs containing tannins and saponins: Quercus and Hedera (21.6 vs. 27.1 g/kg BW), Arbutus and Hedera (21.8 vs. 27.1 g/kg BW), and Pistacia and Hedera (19.7 vs. 22.0 g/kg BW). Comparison of intake of shrubs containing only tannins or saponins to intake of shrubs containing both tannins and saponins indicated that goats consumed more total biomass when fed with shrubs with both classes of compounds than with either tannins or saponins alone. Our results suggest that goats can increase intake of Mediterranean shrubs high in secondary compounds by selecting those with different classes of phytotoxins. Simultaneous ingestion of shrubs containing tannins and saponins may promote chemical interactions that inhibit toxic effects of these phytotoxins in the intestinal tract. In addition to complementary interactions between tannins and saponins, biological diversity within Mediterranean maquis vegetation also plays a positive role in increasing shrub intake by goats.

Sorption and desorption of selected non-steroidal anti-inflammatory drugs in an agricultural loam-textured soil.

PubMed

Zhang, Y; Price, G W; Jamieson, R; Burton, D; Khosravi, K

2017-05-01

Non-steroidal, anti-inflammatory drugs (NSAIDs) are widely used pharmaceutical products with analgesic and anti-inflammatory effects that are consistently detected in municipal wastewater systems and in municipal biosolids. Land application of biosolids and irrigation with reclaimed wastewater introduces these compounds into agricultural environments, which is an emerging issue of concern for ecosystem health. In this study, the sorption-desorption behaviour of four commonly consumed NSAIDs, including naproxen (NPX), ibuprofen (IBU), ketoprofen (KTF), and diclofenac (DCF), was examined in a loam textured soil exposed to either an individual-compound or a mixture of the four NSAIDs. The proportion of NSAIDs adsorbed to the soil in the mixture-compound system was 72%, 55%, 50% and 45%, for diclofenac, naproxen, ketoprofen, and ibuprofen, respectively, and differed slightly from the individual compound adsorption. Diclofenac displayed strong sorption and low desorption in both the individual-compound and mixture-compound systems. Naproxen and ibuprofen exhibited significant differences between the adsorption isotherms of the individual-compound and mixture-compound systems. Results of this study highlight differences in the sorption behaviour of NSAIDs, when present as mixtures, possibly through multilayer bonding effects or complexation with cationic metals or organo-clays from the soil. Soil organic matter (SOM) may have played a role in determining some of the interactions between the compounds but other factors associated with the mixture-compound system, such as cation bridging or multilayer cooperative adsorption. Desorption data suggests that the mechanisms involved in binding NSAIDs to the soil surface are also influence by the presence of other compounds in a mixture. A reduction in desorption was observed for all four NSAIDs in the mixture-compound system relative to the individual-compound system, but were greatest for naproxen and ibuprofen. The sorption-desorption hysteresis increased for naproxen and ibuprofen in the mixture-compound system. This study suggests that cooperative adsorption plays a role in the interaction of NSAIDs when present as mixtures rather than as individual compounds. Copyright © 2017 Elsevier Ltd. All rights reserved.

Tannins from Hamamelis virginiana bark extract: characterization and improvement of the antiviral efficacy against influenza A virus and human papillomavirus.

PubMed

Theisen, Linda L; Erdelmeier, Clemens A J; Spoden, Gilles A; Boukhallouk, Fatima; Sausy, Aurélie; Florin, Luise; Muller, Claude P

2014-01-01

Antiviral activity has been demonstrated for different tannin-rich plant extracts. Since tannins of different classes and molecular weights are often found together in plant extracts and may differ in their antiviral activity, we have compared the effect against influenza A virus (IAV) of Hamamelis virginiana L. bark extract, fractions enriched in tannins of different molecular weights and individual tannins of defined structures, including pseudotannins. We demonstrate antiviral activity of the bark extract against different IAV strains, including the recently emerged H7N9, and show for the first time that a tannin-rich extract inhibits human papillomavirus (HPV) type 16 infection. As the best performing antiviral candidate, we identified a highly potent fraction against both IAV and HPV, enriched in high molecular weight condensed tannins by ultrafiltration, a simple, reproducible and easily upscalable method. This ultrafiltration concentrate and the bark extract inhibited early and, to a minor extent, later steps in the IAV life cycle and tannin-dependently inhibited HPV attachment. We observed interesting mechanistic differences between tannin structures: High molecular weight tannin containing extracts and tannic acid (1702 g/mol) inhibited both IAV receptor binding and neuraminidase activity. In contrast, low molecular weight compounds (<500 g/mol) such as gallic acid, epigallocatechin gallate or hamamelitannin inhibited neuraminidase but not hemagglutination. Average molecular weight of the compounds seemed to positively correlate with receptor binding (but not neuraminidase) inhibition. In general, neuraminidase inhibition seemed to contribute little to the antiviral activity. Importantly, antiviral use of the ultrafiltration fraction enriched in high molecular weight condensed tannins and, to a lesser extent, the unfractionated bark extract was preferable over individual isolated compounds. These results are of interest for developing and improving plant-based antivirals.

Tannins from Hamamelis virginiana Bark Extract: Characterization and Improvement of the Antiviral Efficacy against Influenza A Virus and Human Papillomavirus

PubMed Central

Theisen, Linda L.; Erdelmeier, Clemens A. J.; Spoden, Gilles A.; Boukhallouk, Fatima; Sausy, Aurélie; Florin, Luise; Muller, Claude P.

2014-01-01

Antiviral activity has been demonstrated for different tannin-rich plant extracts. Since tannins of different classes and molecular weights are often found together in plant extracts and may differ in their antiviral activity, we have compared the effect against influenza A virus (IAV) of Hamamelis virginiana L. bark extract, fractions enriched in tannins of different molecular weights and individual tannins of defined structures, including pseudotannins. We demonstrate antiviral activity of the bark extract against different IAV strains, including the recently emerged H7N9, and show for the first time that a tannin-rich extract inhibits human papillomavirus (HPV) type 16 infection. As the best performing antiviral candidate, we identified a highly potent fraction against both IAV and HPV, enriched in high molecular weight condensed tannins by ultrafiltration, a simple, reproducible and easily upscalable method. This ultrafiltration concentrate and the bark extract inhibited early and, to a minor extent, later steps in the IAV life cycle and tannin-dependently inhibited HPV attachment. We observed interesting mechanistic differences between tannin structures: High molecular weight tannin containing extracts and tannic acid (1702 g/mol) inhibited both IAV receptor binding and neuraminidase activity. In contrast, low molecular weight compounds (<500 g/mol) such as gallic acid, epigallocatechin gallate or hamamelitannin inhibited neuraminidase but not hemagglutination. Average molecular weight of the compounds seemed to positively correlate with receptor binding (but not neuraminidase) inhibition. In general, neuraminidase inhibition seemed to contribute little to the antiviral activity. Importantly, antiviral use of the ultrafiltration fraction enriched in high molecular weight condensed tannins and, to a lesser extent, the unfractionated bark extract was preferable over individual isolated compounds. These results are of interest for developing and improving plant-based antivirals. PMID:24498245

Quantum Enhanced Imaging by Entangled States

DTIC Science & Technology

2009-07-01

classes of entangled states. In tripartite systems two classes of genuine tripartite entanglement have been discovered, namely, the Greenberger -Horne...D. M. Greenberger , M. Horne and A. Zeilinger, in Bell’s Theorem, Quantum Theory, and Concepts of the Universe, ed. M. Kafatos (Kluwer, Dordrecht 1989...Gallium Indium Arsenide Phosphide (a III-V compound semiconductor) GHZ: Greenberger -Horne-Zeilinger (a class of entangled states) GLAD: General

Contamination levels of human pharmaceutical compounds in French surface and drinking water.

PubMed

Mompelat, S; Thomas, O; Le Bot, B

2011-10-01

The occurrence of 20 human pharmaceutical compounds and metabolites from 10 representative therapeutic classes was analysed from resource and drinking water in two catchment basins located in north-west France. 98 samples were analysed from 63 stations (surface water and drinking water produced from surface water). Of the 20 human pharmaceutical compounds selected, 16 were quantified in both the surface water and drinking water, with 22% of the values above the limit of quantification for surface water and 14% for drinking water). Psychostimulants, non-steroidal anti-inflammatory drugs, iodinated contrast media and anxiolytic drugs were the main therapeutic classes of human pharmaceutical compounds detected in the surface water and drinking water. The results for surface water were close to results from previous studies in spite of differences in prescription rates of human pharmaceutical compounds in different countries. The removal rate of human pharmaceutical compounds at 11 water treatment units was also determined. Only caffeine proved to be resistant to drinking water treatment processes (with a minimum rate of 5%). Other human pharmaceutical compounds seemed to be removed more efficiently (average elimination rate of over 50%) by adsorption onto activated carbon and oxidation/disinfection with ozone or chlorine (not taking account of the disinfection by-products). These results add to the increasing evidence of the occurrence of human pharmaceutical compounds in drinking water that may represent a threat to human beings exposed to a cocktail of human pharmaceutical compounds and related metabolites and by-products in drinking water.

Screen of FDA-approved drug library reveals compounds that protect hair cells from aminoglycosides and cisplatin

PubMed Central

Vlasits, Anna L.; Simon, Julian A.; Raible, David W.; Rubel, Edwin W; Owens, Kelly N.

2012-01-01

Loss of mechanosensory hair cells in the inner ear accounts for many hearing loss and balance disorders. Several beneficial pharmaceutical drugs cause hair cell death as a side effect. These include aminoglycoside antibiotics, such as neomycin, kanamycin and gentamicin, and several cancer chemotherapy drugs, such as cisplatin. Discovering new compounds that protect mammalian hair cells from toxic insults is experimentally difficult because of the inaccessibility of the inner ear. We used the zebrafish lateral line sensory system as an in vivo screening platform to survey a library of FDA-approved pharmaceuticals for compounds that protect hair cells from neomycin, gentamicin, kanamycin and cisplatin. Ten compounds were identified that provide protection from at least two of the four toxins. The resulting compounds fall into several drug classes, including serotonin and dopamine-modulating drugs, adrenergic receptor ligands, and estrogen receptor modulators. The protective compounds show different effects against the different toxins, supporting the idea that each toxin causes hair cell death by distinct, but partially overlapping, mechanisms. Furthermore, some compounds from the same drug classes had different protective properties, suggesting that they might not prevent hair cell death by their known target mechanisms. Some protective compounds blocked gentamicin uptake into hair cells, suggesting that they may block mechanotransduction or other routes of entry. The protective compounds identified in our screen will provide a starting point for studies in mammals as well as further research discovering the cellular signaling pathways that trigger hair cell death. PMID:22967486

Targeting hypoxia in tumors using 2-nitroimidazoles with peptidic chelators for technetium-99m: effect of lipophilicity.

PubMed

Zhang, X; Su, Z F; Ballinger, J R; Rauth, A M; Pollak, A; Thornback, J R

2000-01-01

Tumor hypoxia is an important prognostic factor for response to therapy. Radiolabeled 2-nitroimidazoles have been used for imaging hypoxia, and the octanol/water partition coefficient (P) of these compounds appears to play a crucial role in their suitability for imaging. A series of 11 2-nitroimidazoles coupled to peptidic chelators for (99m)Tc with divergent P was developed and evaluated in an in vitro system. Two classes of N(3)S chelators were used: dialkyl-Gly-Ser-Cys-linker-2-nitroimidazole (Class I) and dialkyl-Gly-Lys(2-nitroimidazole)-Cys (Class II). The chelators were prepared by automated solid-phase peptide synthesis. Xanthine oxidase was able to reduce the 2-nitroimidiazole moiety on the ligands, but the rate of reduction varied 5-fold among the different chelators. The chelators were labeled by transchelation from [(99m)Tc]gluconate at temperatures between 22 and 100 degrees C. The reaction mixtures were analyzed by HPLC and their P values determined. The accumulation of each complex in suspension cultures of Chinese hamster ovary cells incubated under aerobic or extremely hypoxic conditions was determined. Radiochemical yields ranged from 5 to 80% for the 11 compounds. HPLC showed that some of the compounds formed two complexes with (99m)Tc, possibly syn and anti conformations with respect to the Tc=O bond. In general, the Class I chelators labeled more readily than the class II chelators. The P values of the (99m)Tc complexes varied from 0.0002 to 5 and were generally in accordance with predictions based on structure. There were also differences in P as a function of pH; the free acids had a lower P at pH 7.4 than at pH 2.0 due to ionization, whereas the amides did not show this effect. Accumulation levels in aerobic cells were related to P but varied over a narrow range. Four of the 11 compounds showed selective accumulation in hypoxic cells. The peptidic class of 2-nitroimidazoles, with flexible design and convenient solid-phase synthesis, deserves further study as agents for imaging hypoxia in tumors.

Novel 2-aminotetralin and 3-aminochroman derivatives as selective serotonin 5-HT7 receptor agonists and antagonists.

PubMed

Holmberg, Pär; Sohn, Daniel; Leideborg, Robert; Caldirola, Patrizia; Zlatoidsky, Pavel; Hanson, Sverker; Mohell, Nina; Rosqvist, Susanne; Nordvall, Gunnar; Johansson, Anette M; Johansson, Rolf

2004-07-29

The understanding of the physiological role of the G-protein coupled serotonin 5-HT(7) receptor is largely rudimentary. Therefore, selective and potent pharmacological tools will add to the understanding of serotonergic effects mediated through this receptor. In this report, we describe two compound classes, chromans and tetralins, encompassing compounds with nanomolar affinity for the 5-HT(7) receptor and with good selectivity. Within theses classes, we have discovered both agonists and antagonists that can be used for further understanding of the pharmacology of the 5-HT(7) receptor.

Polyethylene Glycol Propionaldehydes

NASA Technical Reports Server (NTRS)

Harris, Joe M.; Sedaghat-Herati, Mohammad R.; Karr, Laurel J.

1992-01-01

New class of compounds derived from polyethylene glycol (PEG's) namely, PEG-propionaldehydes, offers two important advantages over other classes of PEG aldehyde derivatives: compounds exhibit selective chemical reactivity toward amino groups and are stable in aqueous environment. PEG's and derivatives used to couple variety of other molecules, such as, to tether protein molecules to surfaces. Biotechnical and biomedical applications include partitioning of two phases in aqueous media; immobilization of such proteins as enzymes, antibodies, and antigens; modification of drugs; and preparation of protein-rejecting surfaces. In addition, surfaces coated with PEG's and derivatives used to control wetting and electroosmosis. Another potential application, coupling to aminated surfaces.

[Drug innovation and reverse thinking].

PubMed

Guo, Zong-ru

2016-03-01

Drug innovation involves an individual molecular operation, and every new molecular entity features a hard-duplicated track of R&D. The transformation from an active compound to a new medicine carries out almost in a chaotic system devoid of regularity and periodic alteration. Since new millennium the dominant position in drug innovation has been occupied by the first-in-class drugs, yet the number of launched follow-on drugs has been distinctly decreased. The innovation of first-in-class drugs is characterized by a high risk throughout the whole process. To achieve initiative and uniqueness of drug discovery, the strategy and method of the inverse thinking might be a feasible way, because the inertial and conformity thinkings in drug discovery normally lead to ensemble with similar drug category. However, the study from the flipside or opposite of things(e.g. targets or effects) brand new routes might be opened. This article is to describe the strategy of reverse thinking in drug discovery by some examples including opioid receptor antagonist eluxadoline, HSP90 activator, h ERG channel agonist, covalent drugs, and ultra-small drugs.

Synthesis and Biological Evaluation of the First Dual Tyrosyl-DNA Phosphodiesterase I (Tdp1) - Topoisomerase I (Top1) Inhibitors

PubMed Central

Nguyen, Trung Xuan; Morrell, Andrew; Conda-Sheridan, Martin; Marchand, Christophe; Agama, Keli; Bermingam, Alun; Stephen, Andrew G.; Chergui, Adel; Naumova, Alena; Fisher, Robert; O’Keefe, Barry R.; Pommier, Yves; Cushman, Mark

2012-01-01

Substances with dual tyrosyl-DNA phosphodiesterase I - topoisomerase I inhibitory activity in one low molecular weight compound would constitute a unique class of anticancer agents that could potentially have significant advantages over drugs that work against the individual enzymes. The present study demonstrates the successful synthesis and evaluation of the first dual Top1-Tdp1 inhibitors, which are based on the indenoisoquinoline chemotype. One bis(indenoisoquinoline) had significant activity against human Tdp1 (IC50 = 1.52 ± 0.05 μM), and it was also equipotent to camptothecin as a Top1 inhibitor. Significant insights into enzyme-drug interactions were gained via structure-activity relationship studies of the series. The present results also document the failure of the previously reported sulfonyl ester pharmacophore to confer Tdp1 inhibition in this indenoisoquinoline class of inhibitors, even though it was demonstrated to work well for the steroid NSC 88915 (7). The current study will facilitate future efforts to optimize dual Top1-Tdp1 inhibitors. PMID:22536944

A broad cocktail of environmental pollutants found in eggs of three seabird species from remote colonies in Norway.

PubMed

Huber, Sandra; Warner, Nicholas A; Nygård, Torgeir; Remberger, Mikael; Harju, Mikael; Uggerud, Hilde T; Kaj, Lennart; Hanssen, Linda

2015-06-01

Eggs of 3 seabird species, common eider (Somateria mollisima), European shag (Phalacrocorax aristotelis aristotelis), and European herring gull (Larus argentatus), were surveyed for a broad range of legacy and emerging pollutants to assess chemical mixture exposure profiles of seabirds from the Norwegian marine environment. In total, 201 chemical substances were targeted for analysis ranging from metals, organotin compounds, polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs) and associated metabolites, chlorinated paraffins, chlorinated and nonchlorinated organic pesticides, per- and polyfluoroalkyl substances (PFAS), dechlorane plus, octachlorostyrene, brominated flame retardants (BFRs), organophosphorous compounds, brominated and alkyl phenols, cyclic siloxanes, and phthalates. Of the chemicals targeted, 149 substances were found above the detection limits, with metals dominating the contaminant profile and comprising 60% of the total contaminant load. Polychlorinated biphenyls, pesticides, organophosphorous compounds, and PFAS were the dominant contaminant classes of organic pollutants found within the seabird species, with the highest loads occurring in herring gulls, followed by shag, and common eider. New generation pollutants (e.g., PFAS, organophosphorous compounds, and alkylphenols) were detected at similar or higher concentrations than the legacy persistent organic pollutants (POPs). Time trends of reported concentrations of legacy POPs appear to have decreased in recent decades from the Norwegian coastal environment. Concentrations of detected pollutants do not appear to have a negative effect on seabird population development within the sampling area. Additional stress caused by pollutants, however, may affect seabird health more at the individual level. © 2015 SETAC.

Phenolic Profiles and Contribution of Individual Compounds to Antioxidant Activity of Apple Powders.

PubMed

Raudone, Lina; Raudonis, Raimondas; Liaudanskas, Mindaugas; Viskelis, Jonas; Pukalskas, Audrius; Janulis, Valdimaras

2016-05-01

Apples (Malus domestica L.) are the most common source of phenolic compounds in northern European diet. Besides pectins, dietary fibers, vitamins, and oligosaccharides they contain phenolic compounds of different classes. Apple powders are convenient functional forms retaining significant amounts of phenolic antioxidants. In this study reducing and radical scavenging profiles of freeze-dried powders of "Aldas,ˮ "Auksis,ˮ "Connel Red,ˮ "Ligol,ˮ "Lodel,ˮ and "Rajkaˮ were determined and phenolic constituents were identified using ultra high-performance liquid chromatography coupled to quadrupole and time-of-flight mass spectrometers. A negative ionization mode was applied and seventeen compounds: phenolic acids (coumaroylquinic, chlorogenic), flavonoids (quercetin derivatives), and procyanidin derivatives (B1, B2, and C1) were identified in all tested apple samples. Total values of Trolox equivalents varied from 7.72 ± 0.32 up to 20.02 ± 0.52 and from 11.10 ± 0.57 up to 21.42 ± 0.75 μmol/g of dry weight of apple powder in FRAP (ferric reducing antioxidant power) and ABTS (2,2-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) postcolumn assays, respectively. The greatest Trolox equivalent values were determined for apples of "Aldasˮ cultivar. Chlorogenic acid and procyanidin C1 were the most significant contributors to total reducing and radical scavenging activity in all apple cultivars tested, therefore they could be considered as markers of antioxidant activity. © 2016 Institute of Food Technologists®

Seasonal variation in the secondary chemistry of foliar and reproductive tissue of Delphinium nuttallianum

USDA-ARS?s Scientific Manuscript database

Plant secondary compounds are critical in affecting interactions between plants and their herbivores. The norditerpene alkaloids are secondary compounds in Delphinium (larkspur) species which are divided into two classes: the N-(methylsuccinimido) anthranoyllycoctonine (MSAL-type) and non MSAL-type...

SAMPLE EXTRACTION AND GC-MS ANALYSIS FOR POLAR VOLATILE ORGANIC COMPOUNDS (PVOCS) IN LIQUID BIOLOGICAL MEDIA

EPA Science Inventory

Current approaches for assessing the cumulative exposures and effects from broad classes of environmental stressors incorporate the measurement of specific groups of endogenous compounds in human biological fluids. Recent focus has been on interpreting patterns of differentially...

WhichP450: a multi-class categorical model to predict the major metabolising CYP450 isoform for a compound

NASA Astrophysics Data System (ADS)

Hunt, Peter A.; Segall, Matthew D.; Tyzack, Jonathan D.

2018-02-01

In the development of novel pharmaceuticals, the knowledge of how many, and which, Cytochrome P450 isoforms are involved in the phase I metabolism of a compound is important. Potential problems can arise if a compound is metabolised predominantly by a single isoform in terms of drug-drug interactions or genetic polymorphisms that would lead to variations in exposure in the general population. Combined with models of regioselectivities of metabolism by each isoform, such a model would also aid in the prediction of the metabolites likely to be formed by P450-mediated metabolism. We describe the generation of a multi-class random forest model to predict which, out of a list of the seven leading Cytochrome P450 isoforms, would be the major metabolising isoforms for a novel compound. The model has a 76% success rate with a top-1 criterion and an 88% success rate for a top-2 criterion and shows significant enrichment over randomised models.

Bis-Cyclic-Guanidine as a Novel Class of Compounds Potent Against Clostridium Difficile.

PubMed

Li, Chunhui; Teng, Peng; Peng, Zhong; Sang, Peng; Sun, Xingmin; Cai, Jianfeng

2018-05-16

Clostridium difficile infection (CDI) symptoms range from diarrhea to severe toxic megacolon and even death. Due to its rapid acquisition of resistance, C. difficile is listed as an urgent antibiotic-resistant threat, and has surpassed methicillin-resistant Staphylococcus aureus (MRSA) as the most common hospital-acquired infections in the USA. To combat the pathogen, the new structural class of pseudo peptides that exhibit antimicrobial activities could play an important role. Herein, we report that bis-cyclic guanidine compounds that exhibit potent antibacterial activity against C. difficile with decent selectivity. Eight compounds showed high in vitro potency against C. difficile UK6 with MIC of 1.0 μg/mL, and cytotoxic selectivity index (SI) up to 37. Moreover, the most selective compound 13 is also effective upon the treatment of C. difficile-induced diseases in the mouse model of CDI, and appears to be a very promising new candidate for the treatment of CDI. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Discovery and Optimization of Indolyl-Containing 4-Hydroxy-2-Pyridone Type II DNA Topoisomerase Inhibitors Active against Multidrug Resistant Gram-negative Bacteria.

PubMed

Gerasyuto, Aleksey I; Arnold, Michael A; Wang, Jiashi; Chen, Guangming; Zhang, Xiaoyan; Smith, Sean; Woll, Matthew G; Baird, John; Zhang, Nanjing; Almstead, Neil G; Narasimhan, Jana; Peddi, Srinivasa; Dumble, Melissa; Sheedy, Josephine; Weetall, Marla; Branstrom, Arthur A; Prasad, J V N; Karp, Gary M

2018-05-14

There exists an urgent medical need to identify new chemical entities (NCEs) targeting multidrug resistant (MDR) bacterial infections, particularly those caused by Gram-negative pathogens. 4-Hydroxy-2-pyridones represent a novel class of nonfluoroquinolone inhibitors of bacterial type II topoisomerases active against MDR Gram-negative bacteria. Herein, we report on the discovery and structure-activity relationships of a series of fused indolyl-containing 4-hydroxy-2-pyridones with improved in vitro antibacterial activity against fluoroquinolone resistant strains. Compounds 6o and 6v are representative of this class, targeting both bacterial DNA gyrase and topoisomerase IV (Topo IV). In an abbreviated susceptibility screen, compounds 6o and 6v showed improved MIC 90 values against Escherichia coli (0.5-1 μg/mL) and Acinetobacter baumannii (8-16 μg/mL) compared to the precursor compounds. In a murine septicemia model, both compounds showed complete protection in mice infected with a lethal dose of E. coli.

Boronic Acid Transition State Inhibitors Active against KPC and Other Class A β-Lactamases: Structure-Activity Relationships as a Guide to Inhibitor Design

PubMed Central

Rojas, Laura J.; Taracila, Magdalena A.; Papp-Wallace, Krisztina M.; Bethel, Christopher R.; Caselli, Emilia; Romagnoli, Chiara; Winkler, Marisa L.; Spellberg, Brad; Prati, Fabio

2016-01-01

Boronic acid transition state inhibitors (BATSIs) are competitive, reversible β-lactamase inhibitors (BLIs). In this study, a series of BATSIs with selectively modified regions (R1, R2, and amide group) were strategically designed and tested against representative class A β-lactamases of Klebsiella pneumoniae, KPC-2 and SHV-1. Firstly, the R1 group of compounds 1a to 1c and 2a to 2e mimicked the side chain of cephalothin, whereas for compounds 3a to 3c, 4a, and 4b, the thiophene ring was replaced by a phenyl, typical of benzylpenicillin. Secondly, variations in the R2 groups which included substituted aryl side chains (compounds 1a, 1b, 1c, 3a, 3b, and 3c) and triazole groups (compounds 2a to 2e) were chosen to mimic the thiazolidine and dihydrothiazine ring of penicillins and cephalosporins, respectively. Thirdly, the amide backbone of the BATSI, which corresponds to the amide at C-6 or C-7 of β-lactams, was also changed to the following bioisosteric groups: urea (compound 3b), thiourea (compound 3c), and sulfonamide (compounds 4a and 4b). Among the compounds that inhibited KPC-2 and SHV-1 β-lactamases, nine possessed 50% inhibitory concentrations (IC50s) of ≤600 nM. The most active compounds contained the thiopheneacetyl group at R1 and for the chiral BATSIs, a carboxy- or hydroxy-substituted aryl group at R2. The most active sulfonamido derivative, compound 4b, lacked an R2 group. Compound 2b (S02030) was the most active, with acylation rates (k2/K) of 1.2 ± 0.2 × 104 M−1 s−1 for KPC-2 and 4.7 ± 0.6 × 103 M−1 s−1 for SHV-1, and demonstrated antimicrobial activity against Escherichia coli DH10B carrying blaSHV variants and blaKPC-2 or blaKPC-3 and against clinical strains of Klebsiella pneumoniae and E. coli producing different class A β-lactamase genes. At most, MICs decreased from 16 to 0.5 mg/liter. PMID:26729496

Inhibition of dengue virus replication by a class of small-molecule compounds that antagonize dopamine receptor d4 and downstream mitogen-activated protein kinase signaling.

PubMed

Smith, Jessica L; Stein, David A; Shum, David; Fischer, Matthew A; Radu, Constantin; Bhinder, Bhavneet; Djaballah, Hakim; Nelson, Jay A; Früh, Klaus; Hirsch, Alec J

2014-05-01

Dengue viruses (DENV) are endemic pathogens of tropical and subtropical regions that cause significant morbidity and mortality worldwide. To date, no vaccines or antiviral therapeutics have been approved for combating DENV-associated disease. In this paper, we describe a class of tricyclic small-molecule compounds-dihydrodibenzothiepines (DHBTs), identified through high-throughput screening-with potent inhibitory activity against DENV serotype 2. SKI-417616, a highly active representative of this class, displayed activity against all four serotypes of DENV, as well as against a related flavivirus, West Nile virus (WNV), and an alphavirus, Sindbis virus (SINV). This compound was characterized to determine its mechanism of antiviral activity. Investigation of the stage of the viral life cycle affected revealed that an early event in the life cycle is inhibited. Due to the structural similarity of the DHBTs to known antagonists of the dopamine and serotonin receptors, we explored the roles of two of these receptors, serotonin receptor 2A (5HTR2A) and the D4 dopamine receptor (DRD4), in DENV infection. Antagonism of DRD4 and subsequent downstream phosphorylation of epidermal growth factor receptor (EGFR)-related kinase (ERK) were found to impact DENV infection negatively, and blockade of signaling through this network was confirmed as the mechanism of anti-DENV activity for this class of compounds. The dengue viruses are mosquito-borne, reemerging human pathogens that are the etiological agents of a spectrum of febrile diseases. Currently, there are no approved therapeutic treatments for dengue-associated disease, nor is there a vaccine. This study identifies a small molecule, SKI-417616, with potent anti-dengue virus activity. Further analysis revealed that SKI-417616 acts through antagonism of the host cell dopamine D4 receptor and subsequent repression of the ERK phosphorylation pathway. These results suggest that SKI-417616, or other compounds targeting the same cellular pathways, may have therapeutic potential for the treatment of dengue virus infections.

Mesoporous Colloidal Superparticles of Platinum-Group Nanocrystals with Surfactant-Free Surfaces and Enhanced Heterogeneous Catalysis

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

Hu, Yongxing; Liu, Yuzi; Sun, Yugang

2015-01-23

Synthesis of colloidal superparticles (CSPs) of nanocrystals, a class of assembled nanocrystals in the form of colloidal particles, has been emerging as a new frontier in the field of nanotechnology because of their potential novel properties originated from coupling of individual nanocrystals in CSPs. Here, a facile approach is reported for the controlled synthesis of mesoporous CSPs made of various platinum-group nanocrystals that exhibit high colloidal stability and ligand-free surfaces to significantly benefit their applications in solution-phase heterogeneous catalysis. The synthesis relies on self-limiting growth of composite particles through coprecipitation of both Pt-group nanocrystals (or their precursor compounds) and silvermore » halides on sacrificial substrates of colloidal silver particles. The intermediate silver halides in the composite particles play the critical role in limiting the continuous growth (and/or coalescence) of individual Pt-group nanocrystals and they can be selectively dissolved to create nanoscale pores in the resulting CSPs.« less

An in vitro antibacterial study of savory essential oil and geraniol in combination with standard antimicrobials.

PubMed

Miladinović, Dragoljub L; Ilić, Budimir S; Kocić, Branislava D; Miladinović, Marija D

2014-11-01

The chemical composition and antibacterial activity of Satureja kitaibelii Wierzb. ex Heuff. (savory) essential oil were examined, as well as the association between it and standard antimicrobials: tetracycline and chloramphenicol. The antibacterial activities of geraniol, the main constituent of S. kitaibelii oil, individually and in combination with standard antimicrobials were also determined. The interactions of the essential oil and geraniol with antimicrobials toward five selected strains were evaluated using the microdilution checkerboard assay in combination with chemometric methods. Oxygenated monoterpenes were the most abundant compound class in the oil (59.7%), with geraniol (50.4%) as the major compound. The essential oil exhibited in vitro antibacterial activity against all tested bacterial strains, but the activities were lower than those of the standard antimicrobials. The combinations savory oil-chloramphenicol, savory oil-tetracycline and geraniol-chloramphenicol produced predominantly synergistic interactions (FIC indices in the range 0.21-0.87) and substantial reductions in the MIC values of antimicrobials against Gram-negative bacteria, the pharmacological treatment of which is very difficult nowadays. In the PCA and HCA analyses these combinations form a separate group.

Cinnamoyl compounds as simple molecules that inhibit p300 histone acetyltransferase.

PubMed

Costi, Roberta; Di Santo, Roberto; Artico, Marino; Miele, Gaetano; Valentini, Paola; Novellino, Ettore; Cereseto, Anna

2007-04-19

Cinnamoly compounds 1a-c and 2a-d were designed, synthesized, and in vitro tested as p300 inhibitors. At different degrees, all tested compounds were proven to inactivate p300, particularly, derivative 2c was the most active inhibitor, also showing high specificity for p300 as compared to other histone acetyltransferases. Most notably, 2c showed anti-acetylase activity in mammalian cells. These compounds represent a new class of synthetic inhibitors of p300, characterized by simple chemical structures.

Deposit formation in liquid fuels. III - The effect of selected nitrogen compounds on diesel fuel

NASA Technical Reports Server (NTRS)

Worstell, J. H.; Daniel, S. R.; Frauenhoff, G.

1981-01-01

The influence of substituted quinolines, pyrroles, indoles, and pyridines on deposit formation in a diesel fuel is evaluated. Significant increases in deposition rate are found which are dependent upon the basicity of the nitrogen compound within a given compound class. These effects correspond closely with those produced in a Jet A fuel. Removal of highly polar fuel components renders the nitrogen compound influence inoperative. These components are therefore participants in deposit-forming reactions.

Characterization of organic matter in cloud waters sampled at the puy de Dôme mountain using FT-ICR-MS

NASA Astrophysics Data System (ADS)

Bianco, A.; Chaumerliac, N.; Vaitilingom, M.; Deguillaume, L.; Bridoux, M. C.

2017-12-01

The chemical composition of organic matter in cloud water is highly complex. The organic species result from their dissolution from the gas phase or from the soluble fraction of the particle phase. They are also produced by aqueous phase reactivity. Several low molecular weight organic species have been quantified such as aldehydes and carboxylic acids. Recently, amino acids were also detected in cloud water and their presence is related to the presence of microorganisms. Compounds presenting similarities with high molecular weight organic substances or HULIS found in aerosols were also observed in clouds. Overall, these studies mainly focused on individual compounds or functional groups rather than the complex mixture at the molecular level. This study presents a non-targeted approach to characterize the organic matter in clouds. Samples were collected at the puy de Dôme Mountain (France). Two cloud water samples (June & July 2016) were analyzed using high resolution mass spectrometry (ESI-FT-ICR-MS 9.4T). A reversed solid phase extraction (SPE) procedure was performed to concentrate dissolved organic matter components. Composer (v.1.5.3) software was used to filter the mass spectral data, recalibrate externally the dataset and calculate all possible formulas for detected anions. The first cloud sample (June) resulted from air mass coming from the North (North Sea) while the second one (July) resulted from air mass coming from the West (Atlantic Ocean). Thus, both cloud events derived from marine air masses but were characterized by different hydrogen peroxide concentration and dissolved organic carbon content and were sampled at different periods during the day. Elemental compositions of 6487 and 3284 unique molecular species were identified in each sample. Nitrogen-containing compounds (CHNO compounds), sulfur-containing compounds (CHOS & CHNOS compounds) and other oxygen-containing compounds (CHO compounds) with molecular weights up to 800 Da were detected. The main class is CHNO (53% for both samples) while sulfur-containing compounds represent for the two samples respectively 21 & 14% of the total assigned molecular formulas. CHO compounds molecular formulas are respectively 25 & 32%. Among the two samples, only 2490 molecular formulas were found common to the two samples.

Who wants to get to the top? Class and lay theories about power.

PubMed

Belmi, Peter; Laurin, Kristin

2016-10-01

We investigated class-based differences in the propensity to seek positions of power. We first proposed that people's lay theories suggest that acquiring power requires playing politics-manipulating one's way through the social world, relying on a pragmatic and Machiavellian approach to impression management and social relationships to get ahead. Then, drawing on empirical work portraying individuals with relatively low social class as more strongly focused on others and less focused on themselves, we hypothesized that these individuals would show less interest in seeking positions of power than their high-class counterparts, because they feel less comfortable engaging in political behavior. We tested these ideas in 7 studies. Our findings indicated that, even though individuals with relatively low social class see political behavior as necessary and effective for acquiring positions of power, they are reluctant to do it; as a result, they have a weaker tendency to seek positions of power compared to individuals with relatively high social class. Consistent with our theorizing, we also found that individuals with relatively low social class intend to seek positions of power as much as their high-class counterparts when they can acquire it through prosocial means (Study 2), and when they reconstrue power as serving a superordinate goal of helping others (Study 4). Moreover, we checked the robustness of our findings by measuring social class in a number of ways within each study, and examined whether our results held across each measure. Together, our findings suggest that the common belief that political behavior is required for advancement may help explain why class inequalities persist and why creating class-based diversity in upper-level positions poses a serious challenge. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

The undervalued self: social class and self-evaluation

PubMed Central

Kraus, Michael W.; Park, Jun W.

2014-01-01

Social class ranks people on the social ladder of society, and in this research we examine how perceptions of economic standing shape the way that individuals evaluate the self. Given that reminders of one’s own subordinate status in society are an indicator of how society values the self in comparison to others, we predicted that chronic lower perceptions of economic standing vis-à-vis others would explain associations between objective social class and negative self-evaluation, whereas situation-specific reminders of low economic standing would elicit negative self-evaluations, particularly in those from lower-class backgrounds. In Study 1, perceptions of social class rank accounted for the positive relationship between objective material resource measures of social class and self-esteem. In Study 2, lower-class individuals who received a low (versus equal) share of economic resources in an economic game scenario reported more negative self-conscious emotions—a correlate of negative self-evaluation—relative to upper-class individuals. Discussion focused on the implications of this research for understanding class-based cultural models of the self, and for how social class shapes self-evaluations chronically. PMID:25538654

The undervalued self: social class and self-evaluation.

PubMed

Kraus, Michael W; Park, Jun W

2014-01-01

Social class ranks people on the social ladder of society, and in this research we examine how perceptions of economic standing shape the way that individuals evaluate the self. Given that reminders of one's own subordinate status in society are an indicator of how society values the self in comparison to others, we predicted that chronic lower perceptions of economic standing vis-à-vis others would explain associations between objective social class and negative self-evaluation, whereas situation-specific reminders of low economic standing would elicit negative self-evaluations, particularly in those from lower-class backgrounds. In Study 1, perceptions of social class rank accounted for the positive relationship between objective material resource measures of social class and self-esteem. In Study 2, lower-class individuals who received a low (versus equal) share of economic resources in an economic game scenario reported more negative self-conscious emotions-a correlate of negative self-evaluation-relative to upper-class individuals. Discussion focused on the implications of this research for understanding class-based cultural models of the self, and for how social class shapes self-evaluations chronically.

[Detection of organic compounds on Mars].

PubMed

Kobayashi, K

1997-03-01

McKay et al. detected polycyclic aromatic hydrocarbons (PAHs) in Martian meteorite ALH 84001 by two-step laser mass spectrometry. From the presence of PAHs, together with other results, they concluded that there were past life of Mars. On the other hands, no organisms nor organic compounds were detected in Martian regolith in Viking experiments in 1976. In order to obtain solid evidence for organisms or bioorganic compounds compounds on Mars, further analyses of Martian samples are required. There may be four classes of organic compounds on Mars, which are (i) organic compounds abiotically formed from primitive Mars atmosphere, (ii) Organic compounds delivered out of Mars, (iii) Organic compounds biotically formed by Mars organisms, and (iv) Organic compounds abiotically formed from the present Mars atmosphere. Possible organic compounds on Mars and analytical methods for them are discussed.

Teaching innovation in organic chemistry: An inquiry into what happens when the lecturer stops lecturing

NASA Astrophysics Data System (ADS)

Bauer, Richard Charles

1998-12-01

In this dissertation the author presents findings from a study of an organic chemistry class in which the instructor changed his mode of content delivery. Instead of using a traditional lecture, the professor engaged students in discussions about chemical behavior, required students to complete cooperative learning activities in and out of class, and altered his examination format. The purpose of the research was to investigate the implementation of the changes made in content delivery, describe subsequent classroom interactions, and discuss participant responses to the innovations. Because of the research focus the author used a qualitative methodology to investigate this unique organic chemistry course. The study showed that the instructor's belief system and skills played an important role in overcoming barriers to implementation. Analysis of class transcripts revealed that the class was highly interactive with students freely offering responses to the instructor's questions and sometimes submitting insightful comments. The discussion format of the class also revealed some student misunderstanding that other teaching structures may not have identified. In general the instructor was able to pursue some concepts in more depth than allowed by a typical lecture mode of content delivery. Analysis of class transcripts also showed characteristics of organic chemistry teaching by Prof. Loudon that might be described as exemplary. He focused student attention on molecular structure and the chemical behavioral patterns that emerge from organic compounds that are structurally similar. Student response to Prof. Loudon's teaching style was quite favorable. A common remark from students was that his personal knowledge of them contributed to their class preparation and desire to learn. In general, students appreciated the opportunity to discuss exam questions in their groups before individual exam administration. On the final course evaluation, however, a couple students expressed disdain towards the exam format stating that sometimes fellow group members led them astray. Several also said that the discussion contributed to anxiety instead of making the examination period more relaxed as Prof. Loudon had hoped.

Using electroretinograms and multi-model inference to identify spectral classes of photoreceptors and relative opsin expression levels

PubMed Central

2017-01-01

Understanding how individual photoreceptor cells factor in the spectral sensitivity of a visual system is essential to explain how they contribute to the visual ecology of the animal in question. Existing methods that model the absorption of visual pigments use templates which correspond closely to data from thin cross-sections of photoreceptor cells. However, few modeling approaches use a single framework to incorporate physical parameters of real photoreceptors, which can be fused, and can form vertical tiers. Akaike’s information criterion (AICc) was used here to select absorptance models of multiple classes of photoreceptor cells that maximize information, given visual system spectral sensitivity data obtained using extracellular electroretinograms and structural parameters obtained by histological methods. This framework was first used to select among alternative hypotheses of photoreceptor number. It identified spectral classes from a range of dark-adapted visual systems which have between one and four spectral photoreceptor classes. These were the velvet worm, Principapillatus hitoyensis, the branchiopod water flea, Daphnia magna, normal humans, and humans with enhanced S-cone syndrome, a condition in which S-cone frequency is increased due to mutations in a transcription factor that controls photoreceptor expression. Data from the Asian swallowtail, Papilio xuthus, which has at least five main spectral photoreceptor classes in its compound eyes, were included to illustrate potential effects of model over-simplification on multi-model inference. The multi-model framework was then used with parameters of spectral photoreceptor classes and the structural photoreceptor array kept constant. The goal was to map relative opsin expression to visual pigment concentration. It identified relative opsin expression differences for two populations of the bluefin killifish, Lucania goodei. The modeling approach presented here will be useful in selecting the most likely alternative hypotheses of opsin-based spectral photoreceptor classes, using relative opsin expression and extracellular electroretinography. PMID:28740757

Using electroretinograms and multi-model inference to identify spectral classes of photoreceptors and relative opsin expression levels.

PubMed

Lessios, Nicolas

2017-01-01

Understanding how individual photoreceptor cells factor in the spectral sensitivity of a visual system is essential to explain how they contribute to the visual ecology of the animal in question. Existing methods that model the absorption of visual pigments use templates which correspond closely to data from thin cross-sections of photoreceptor cells. However, few modeling approaches use a single framework to incorporate physical parameters of real photoreceptors, which can be fused, and can form vertical tiers. Akaike's information criterion (AIC c ) was used here to select absorptance models of multiple classes of photoreceptor cells that maximize information, given visual system spectral sensitivity data obtained using extracellular electroretinograms and structural parameters obtained by histological methods. This framework was first used to select among alternative hypotheses of photoreceptor number. It identified spectral classes from a range of dark-adapted visual systems which have between one and four spectral photoreceptor classes. These were the velvet worm, Principapillatus hitoyensis , the branchiopod water flea, Daphnia magna , normal humans, and humans with enhanced S-cone syndrome, a condition in which S-cone frequency is increased due to mutations in a transcription factor that controls photoreceptor expression. Data from the Asian swallowtail, Papilio xuthus , which has at least five main spectral photoreceptor classes in its compound eyes, were included to illustrate potential effects of model over-simplification on multi-model inference. The multi-model framework was then used with parameters of spectral photoreceptor classes and the structural photoreceptor array kept constant. The goal was to map relative opsin expression to visual pigment concentration. It identified relative opsin expression differences for two populations of the bluefin killifish, Lucania goodei . The modeling approach presented here will be useful in selecting the most likely alternative hypotheses of opsin-based spectral photoreceptor classes, using relative opsin expression and extracellular electroretinography.

SIMULTANEOUS CONTROL OF HG(0), SO2, AND NOX BY NOVEL OXIDIZED CALCIUM-BASED SORBENTS

EPA Science Inventory

The paper gives results of an investigation of two classes of calcium (Ca)-based sorbents (hydrated limes and silicate compounds). {NOTE: Efforts to develop multipollutant control strategies have demonstrated that adding certain oxidants to different classes of Ca-based sorbents ...

SIMULTANEOUS CONTROL OF HGO, SO2, AND NOX BY NOVEL OXIDIZED CALCIUM-BASED SORBENTS

EPA Science Inventory

The paper gives results of an investigation of two classes of calcium (Ca)-based sorbents (hydrated limes and silicate compounds). (NOTE: Efforts to develop multipollutant control strategies have demonstrated that adding certain oxidants to different classes of Ca-based sorbents...

Characterization of organic aromatic compounds in soils affected by an uncontrolled tire landfill fire through the use of comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry.

PubMed

Escobar-Arnanz, J; Mekni, S; Blanco, G; Eljarrat, E; Barceló, D; Ramos, L

2018-02-09

Discarded vehicle tires have become an increasing concern worldwide due to the enormous amount of wastes generated and the increasing evidence of health problems associated to their disposal and accidental combustion. Previous studies conducted involving either simulated or open uncontrolled tire fires have identified aromatics belonging to two main classes, volatile organic compounds and polycyclic aromatic compounds (PAHs), as the most relevant chemicals generated in these burning processes. As a consequence, and due to their recognized toxicity, most studies reported up to now have mainly focused on these two categories of compounds being information concerning the possible occurrence of other aromatic classes rather limited. In this study, the enhanced separation power and structural confirmation capabilities provided by comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry (GC×GC-ToF MS) has been used, for the first time, for the non-targeted analysis of soils impacted by a tire fire and an ash collected at the scene of the fire. In total, 118 volatile and semi-volatile aromatic compounds have been differentiated. Among them, 104 compounds have been either positively or tentatively identified. PAHs with 3-5 rings and their alkyl-derivatives were the most numerous and relevant classes in the investigated samples. A significant number of sulfur, oxygen- and nitrogen-containing PAHs were also detected in the samples. The application of a script function to the raw GC×GC-ToF MS data allowed the fast filtering and automatic recognition of compounds containing halogens in their structure. This part of the study evidenced that only a limited number of regulated persistent organic pollutants were present in the investigated samples. However, it also revealed the presence of emerging organophosphorous flame retardants, whose levels in tire fire impacted soils are reported for the first time. Copyright © 2017 Elsevier B.V. All rights reserved.

21 CFR 1303.25 - Increase in individual manufacturing quotas.

Code of Federal Regulations, 2010 CFR

2010-04-01

... holds an individual manufacturing quota for a basic class of controlled substance listed in Schedule I... exceeds the aggregate of all the individual manufacturing quotas for the basic class of controlled... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Increase in individual manufacturing quotas. 1303...

Gene expression pattern recognition algorithm inferences to classify samples exposed to chemical agents

NASA Astrophysics Data System (ADS)

Bushel, Pierre R.; Bennett, Lee; Hamadeh, Hisham; Green, James; Ableson, Alan; Misener, Steve; Paules, Richard; Afshari, Cynthia

2002-06-01

We present an analysis of pattern recognition procedures used to predict the classes of samples exposed to pharmacologic agents by comparing gene expression patterns from samples treated with two classes of compounds. Rat liver mRNA samples following exposure for 24 hours with phenobarbital or peroxisome proliferators were analyzed using a 1700 rat cDNA microarray platform. Sets of genes that were consistently differentially expressed in the rat liver samples following treatment were stored in the MicroArray Project System (MAPS) database. MAPS identified 238 genes in common that possessed a low probability (P < 0.01) of being randomly detected as differentially expressed at the 95% confidence level. Hierarchical cluster analysis on the 238 genes clustered specific gene expression profiles that separated samples based on exposure to a particular class of compound.

"Crown Ether" Synthesis: An Organic Laboratory Experiment.

ERIC Educational Resources Information Center

Field, Kurt W.; And Others

1979-01-01

This experiment is designed to acquaint the student with a macromolecular synthesis of a crown ether type compound. The starting materials are readily available and the product, a cyclic polyether, belongs to a class of compounds that has aroused the interest of chemist and biologist alike. (Author/BB)

POSSIBLE MECHANISMS OF THYROID HORMONE DISRUPTION IN MICE BY BDE 47, A MAJOR POLYBROMINATED DIPHENYL ETHER CONGENER

EPA Science Inventory

ABSTRACT Polybromindated diphenyl ethers (PBDEs) are a class of polyhalogenated aromatic compounds commercially used as fire retardants in consumer products. These compounds have been shown to decrease thyroid hormone concentrations in rodents after acute exposures. Based on t...

3-(Methoxycarbonylmethylene)isobenzofuran-1-imines as a new class of potential herbicides.

PubMed

Araniti, Fabrizio; Mancuso, Raffaella; Ziccarelli, Ida; Sunseri, Francesco; Abenavoli, Maria Rosa; Gabriele, Bartolo

2014-06-18

A novel class of potential herbicides, the 3-(methoxycarbonylmethylene) isobenzofuran-1-imines, has been discovered. The herbicidal activity has been tested on two particular molecules, (E)-methyl 2-[3-(butylimino)isobenzofuran-1(3H)-ylidene]acetate (1) and (E)-methyl 2-phenyl-2-[3-(phenylimino)isobenzofuran-1(3H)-ylidene]acetate (2), prepared by palladium-catalyzed oxidative carbonylation of 2-alkynylbenzamides. Both compounds 1 and 2 showed a strong phytotoxic effect on both shoot and root systems of Arabidopsis thaliana. The effects observed on the shoot were similar for both molecules, but while compound 1 showed a stronger effect on root parameters (such as primary root length, root hair and density, showing lower ED50 values), compound 2 caused important malformations in root morphology. Our results indicate that these molecules are very promising synthetic herbicides.

4-Hydroxyphenylpyruvate Dioxygenase and Its Inhibition in Plants and Animals: Small Molecules as Herbicides and Agents for the Treatment of Human Inherited Diseases.

PubMed

Santucci, Annalisa; Bernardini, Giulia; Braconi, Daniela; Petricci, Elena; Manetti, Fabrizio

2017-05-25

This review mainly focuses on the physiological function of 4-hydroxyphenylpyruvate dioxygenase (HPPD), as well as on the development and application of HPPD inhibitors of several structural classes. Among them, one illustrative example is represented by compounds belonging to the class of triketone compounds. They were discovered by serendipitous observations on weed growth and were developed as bleaching herbicides. Informed reasoning on nitisinone (NTBC, 14), a triketone that failed to reach the final steps of the herbicidal design and development process, allowed it to become a curative agent for type I tyrosinemia (T1T) and to enter clinical trials for alkaptonuria. These results boosted the research of new compounds able to interfere with HPPD activity to be used for the treatment of the tyrosine metabolism-related diseases.

Solid-state structure of a Li/F carbenoid: pentafluoroethyllithium.

PubMed

Waerder, Benedikt; Steinhauer, Simon; Neumann, Beate; Stammler, Hans-Georg; Mix, Andreas; Vishnevskiy, Yury V; Hoge, Berthold; Mitzel, Norbert W

2014-10-20

Lithium carbenoids are versatile compounds for synthesis owing to their intriguing ambiphilic behavior. Although this class of compounds has been known for several years, few solid-state structures exist because of their high reactivity and often low thermal stability. Using cryo X-ray techniques, we were now able to elucidate the first solid-state structure of a Li/F alkyl carbenoid, pentafluoroethyllithium (LiC2F5), finally yielding a prototype for investigating structure-reactivity relationships for this class of molecules. The compound forms a diethyl ether-solvated dimer bridged by a rare C-F-Li link. Complementary NMR spectroscopy studies in solution show dynamic processes and indicate rapid exchange of starting material and product. Theoretical investigations help to understand the formation of the observed unusual structural motif. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Characterization of organic material in ice core samples from North America, Greenland, and Antarctica using ultrahigh resolution Fourier transform ion cyclotron resonance mass spectrometry

NASA Astrophysics Data System (ADS)

Catanzano, V.; Grannas, A. M.; Sleighter, R. L.; Hatcher, P. G.

2013-12-01

Historically, it has been an analytical challenge to detect and identify the organic components present in ice cores, due to the low abundance of organic carbon. In order to detect and characterize the small amounts of organic matter in ice cores, ultra high resolution instrumentation is required. Here we report the use of ultrahigh resolution Fourier transform ion cyclotron resonance mass spectrometry, coupled with electrospray ionization, to identify the molecular formulas and compound classes of organic matter in both modern and ancient ice core and glacial samples from Wyoming, Greenland, and Antarctica. A suite of 21 samples were analyzed and thousands of distinct molecular species were identified in each sample, providing clues to the nature and sources of organic matter in these regions. Major biochemical classes of compounds were detected such as lignins, tannins, carbohydrates, proteins, lipids, unsaturated hydrocarbons, and condensed aromatic compounds. We will compare the nature of the organic matter present in the samples in order to determine the differences in dominant organic compound classes and in heteroatom (nitrogen and sulfur) abundance. By analyzing these differences, it is possible to investigate the historical patterns of organic matter deposition/source, and begin to investigate the influence of climate change, volcanism, and onset of the industrial revolution on the nature of organic matter preserved in ice cores.

Activating Student to Learn Chemistry using Chemmy Card 6-1 Game as an Instructional Medium in IUPAC Nomenclature of Inorganic Compounds

NASA Astrophysics Data System (ADS)

Lutfi, A.; Hidayah, R.

2018-01-01

The aim of this study is to know the effect of Internet-assisted Chemmy Card 6-1 game as an instructional medium in IUPAC Nomenclature of Inorganic Compounds material for X grade of senior high school on students’ activity, learning motivation, and learning outcome. The study was conducted at SMA Negeri Sidoarjo, Indonesia, in two different classes. The instruction was done based on the lesson plan made. The observation on students’ activity was conducted during the instruction with the game while test and questionnaire were given after the instruction. The result showed positive activities, which students listened to the teacher’s explanation, actively delivered questions, and enabled to solve problems in naming compounds. It was also effective to avoid the drowsiness. The result of students’ motivation of X MIPA 6 was 74.78% (good) while X MIPA 7 was 83.80% (very good). The pretest results of two classes showed that no students mastered but 100% students mastered and the increase of N-gain scores in two classes was categorized as high, ≥0,7, after the instruction. The result of this study showed that the use of Internet-assisted Chemmy Card 6-1 game in IUPAC nomenclature of inorganic compounds for X grade of senior high school could be pleasant for students to learn and effective in achieving the learning objective.

Analytical method for fast screening and confirmation of multi-class veterinary drug residues in fish and shrimp by LC-MS/MS.

PubMed

Kim, Junghyun; Suh, Joon Hyuk; Cho, Hyun-Deok; Kang, Wonjae; Choi, Yong Seok; Han, Sang Beom

2016-01-01

A multi-class, multi-residue analytical method based on LC-MS/MS detection was developed for the screening and confirmation of 28 veterinary drug and metabolite residues in flatfish, shrimp and eel. The chosen veterinary drugs are prohibited or unauthorised compounds in Korea, which were categorised into various chemical classes including nitroimidazoles, benzimidazoles, sulfones, quinolones, macrolides, phenothiazines, pyrethroids and others. To achieve fast and simultaneous extraction of various analytes, a simple and generic liquid extraction procedure using EDTA-ammonium acetate buffer and acetonitrile, without further clean-up steps, was applied to sample preparation. The final extracts were analysed by ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). The method was validated for each compound in each matrix at three different concentrations (5, 10 and 20 ng g(-1)) in accordance with Codex guidelines (CAC/GL 71-2009). For most compounds, the recoveries were in the range of 60-110%, and precision, expressed as the relative standard deviation (RSD), was in the range of 5-15%. The detection capabilities (CCβs) were below or equal to 5 ng g(-1), which indicates that the developed method is sufficient to detect illegal fishery products containing the target compounds above the residue limit (10 ng g(-1)) of the new regulatory system (Positive List System - PLS).

Variation in phenolic root exudates and rhizosphere carbon cycling among tree species in temperate forest ecosystems

NASA Astrophysics Data System (ADS)

Zwetsloot, Marie; Bauerle, Taryn; Kessler, André; Wickings, Kyle

2017-04-01

Temperate forest tree species composition has been highly dynamic over the past few centuries and is expected to only further change under current climate change predictions. While aboveground changes in forest biodiversity have been widely studied, the impacts on belowground processes are far more challenging to measure. In particular, root exudation - the process through which roots release organic and inorganic compounds into the rhizosphere - has received little scientific attention yet may be the key to understanding root-facilitated carbon cycling in temperate forest ecosystems. The aim of this study was to analyze the extent by which tree species' variation in phenolic root exudate profiles influences soil carbon cycling in temperate forest ecosystems. In order to answer this question, we grew six temperate forest tree species in a greenhouse including Acer saccharum, Alnus rugosa, Fagus grandifolia, Picea abies, Pinus strobus, and Quercus rubra. To collect root exudates, trees were transferred to hydroponic growing systems for one week and then exposed to cellulose acetate strips in individual 800 mL jars with a sterile solution for 24 hours. We analyzed the methanol-extracted root exudates for phenolic composition with high-performance liquid chromatography (HPLC) and determined species differences in phenolic abundance, diversity and compound classes. This information was used to design the subsequent soil incubation study in which we tested the effect of different phenolic compound classes on rhizosphere carbon cycling using potassium hydroxide (KOH) traps to capture soil CO2 emissions. Our findings show that tree species show high variation in phenolic root exudate patterns and that these differences can significantly influence soil CO2 fluxes. These results stress the importance of linking belowground plant traits to ecosystem functioning. Moreover, this study highlights the need for research on root and rhizosphere processes in order to improve terrestrial carbon cycling models and estimate forest ecosystem feedbacks to climate change.

Design, synthesis, and biological evaluation of combretabenzodiazepines: a novel class of anti-tubulin agents.

PubMed

Galli, Ubaldina; Travelli, Cristina; Aprile, Silvio; Arrigoni, Elena; Torretta, Simone; Grosa, Giorgio; Massarotti, Alberto; Sorba, Giovanni; Canonico, Pier Luigi; Genazzani, Armando A; Tron, Gian Cesare

2015-02-12

In the present manuscript, starting from the 1,4-benzodiazepin-2-one nucleus, a privileged structure in medicinal chemistry, we have synthesized a novel class of cis-locked combretastatins named combreatabenzodiazepines. They show similar cytotoxic and antitubulin activity compared to combretastatin A-4 in neuroblastoma cells, showing a better pharmacokinetic profile. This class of compounds has therefore the potential for further development as antitubulin agents.

Validation of an LC-MS/MS method for the quantification of choline-related compounds and phospholipids in foods and tissues.

PubMed

Xiong, Yeping; Zhao, Yuan-Yuan; Goruk, Sue; Oilund, Kirsten; Field, Catherine J; Jacobs, René L; Curtis, Jonathan M

2012-12-12

A hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC LC-MS/MS) method was developed and validated to simultaneously quantify six aqueous choline-related compounds and eight major phospholipids classes in a single run. HILIC chromatography was coupled to positive ion electrospray mass spectrometry. A combination of multiple scan modes including precursor ion scan, neutral loss scan and multiple reaction monitoring was optimized for the determination of each compound or class in a single LC/MS run. This work developed a simplified extraction scheme in which both free choline and related compounds along with phospholipids were extracted into a homogenized phase using chloroform/methanol/water (1:2:0.8) and diluted into methanol for the analysis of target compounds in a variety of sample matrices. The analyte recoveries were evaluated by spiking tissues and food samples with two isotope-labeled internal standards, PC-d(3) and Cho-d(3). Recoveries of between 90% and 115% were obtained by spiking a range of sample matrices with authentic standards containing all 14 of the target analytes. The precision of the analysis ranged from 1.6% to 13%. Accuracy and precision was comparable to that obtained by quantification of selected phospholipid classes using (31)P NMR. A variety of sample matrices including egg yolks, human diets and animal tissues were analyzed using the validated method. The measurements of total choline in selected foods were found to be in good agreement with values obtained from the USDA choline database. Copyright © 2012 Elsevier B.V. All rights reserved.

Measurement of phospholipids by hydrophilic interaction liquid chromatography coupled to tandem mass spectrometry: the determination of choline containing compounds in foods.

PubMed

Zhao, Yuan-Yuan; Xiong, Yeping; Curtis, Jonathan M

2011-08-12

A hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC LC-MS/MS) method using multiple scan modes was developed to separate and quantify 11 compounds and lipid classes including acetylcholine (AcCho), betaine (Bet), choline (Cho), glycerophosphocholine (GPC), lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphocholine (PCho) and sphingomyelin (SM). This includes all of the major choline-containing compounds found in foods. The method offers advantages over other LC methods since HILIC chromatography is readily compatible with electrospray ionization and results in higher sensitivity and improved peak shapes. The LC-MS/MS method allows quantification of all choline-containing compounds in a single run. Tests of method suitability indicated linear ranges of approximately 0.25-25 μg/ml for PI and PE, 0.5-50 μg/ml for PC, 0.05-5 μg/ml for SM and LPC, 0.5-25 μg/ml for LPE, 0.02-5 μg/ml for Cho, and 0.08-8 μg/ml for Bet, respectively. Accuracies of 83-105% with precisions of 1.6-13.2% RSD were achieved for standards over a wide range of concentrations, demonstrating that this method will be suitable for food analysis. 8 polar lipid classes were found in a lipid extract of egg yolk and different species of the same class were differentiated based on their molecular weights and fragment ion information. PC and PE were found to be the most abundant lipid classes consisting of 71% and 18% of the total phospholipids in egg yolk. Copyright © 2011 Elsevier B.V. All rights reserved.

Partial least squares analysis of rocket propulsion fuel data using diaphragm valve-based comprehensive two-dimensional gas chromatography coupled with flame ionization detection.

PubMed

Freye, Chris E; Fitz, Brian D; Billingsley, Matthew C; Synovec, Robert E

2016-06-01

The chemical composition and several physical properties of RP-1 fuels were studied using comprehensive two-dimensional (2D) gas chromatography (GC×GC) coupled with flame ionization detection (FID). A "reversed column" GC×GC configuration was implemented with a RTX-wax column on the first dimension ((1)D), and a RTX-1 as the second dimension ((2)D). Modulation was achieved using a high temperature diaphragm valve mounted directly in the oven. Using leave-one-out cross-validation (LOOCV), the summed GC×GC-FID signal of three compound-class selective 2D regions (alkanes, cycloalkanes, and aromatics) was regressed against previously measured ASTM derived values for these compound classes, yielding root mean square errors of cross validation (RMSECV) of 0.855, 0.734, and 0.530mass%, respectively. For comparison, using partial least squares (PLS) analysis with LOOCV, the GC×GC-FID signal of the entire 2D separations was regressed against the same ASTM values, yielding a linear trend for the three compound classes (alkanes, cycloalkanes, and aromatics), yielding RMSECV values of 1.52, 2.76, and 0.945 mass%, respectively. Additionally, a more detailed PLS analysis was undertaken of the compounds classes (n-alkanes, iso-alkanes, mono-, di-, and tri-cycloalkanes, and aromatics), and of physical properties previously determined by ASTM methods (such as net heat of combustion, hydrogen content, density, kinematic viscosity, sustained boiling temperature and vapor rise temperature). Results from these PLS studies using the relatively simple to use and inexpensive GC×GC-FID instrumental platform are compared to previously reported results using the GC×GC-TOFMS instrumental platform. Copyright © 2016 Elsevier B.V. All rights reserved.

Genes versus environment: geography and phylogenetic relationships shape the chemical profiles of stingless bees on a global scale

PubMed Central

Leonhardt, Sara D.; Rasmussen, Claus; Schmitt, Thomas

2013-01-01

Chemical compounds are highly important in the ecology of animals. In social insects, compounds on the body surface represent a particularly interesting trait, because they comprise different compound classes that are involved in different functions, such as communication, recognition and protection, all of which can be differentially affected by evolutionary processes. Here, we investigate the widely unknown and possibly antagonistic influence of phylogenetic and environmental factors on the composition of the cuticular chemistry of tropical stingless bees. We chose stingless bees because some species are unique in expressing not only self-produced compounds, but also compounds that are taken up from the environment. By relating the cuticular chemistry of 40 bee species from all over the world to their molecular phylogeny and geographical occurrence, we found that distribution patterns of different groups of compounds were differentially affected by genetic relatedness and biogeography. The ability to acquire environmental compounds was, for example, highly correlated with the bees' phylogeny and predominated in evolutionarily derived species. Owing to the presence of environmentally derived compounds, those species further expressed a higher chemical and thus functional diversity. In Old World species, chemical similarity of both environmentally derived and self-produced compounds was particularly high among sympatric species, even when they were less related to each other than to allopatric species, revealing a strong environmental effect even on largely genetically determined compounds. Thus, our findings do not only reveal an unexpectedly strong influence of the environment on the cuticular chemistry of stingless bees, but also demonstrate that even within one morphological trait (an insect's cuticular profile), different components (compound classes) can be differentially affected by different drivers (relatedness and biogeography), depending on the functional context. PMID:23658202

Statistical investigation of simulated intestinal fluid composition on the equilibrium solubility of biopharmaceutics classification system class II drugs.

PubMed

Khadra, Ibrahim; Zhou, Zhou; Dunn, Claire; Wilson, Clive G; Halbert, Gavin

2015-01-25

A drug's solubility and dissolution behaviour within the gastrointestinal tract is a key property for successful administration by the oral route and one of the key factors in the biopharmaceutics classification system. This property can be determined by investigating drug solubility in human intestinal fluid (HIF) but this is difficult to obtain and highly variable, which has led to the development of multiple simulated intestinal fluid (SIF) recipes. Using a statistical design of experiment (DoE) technique this paper has investigated the effects and interactions on equilibrium drug solubility of seven typical SIF components (sodium taurocholate, lecithin, sodium phosphate, sodium chloride, pH, pancreatin and sodium oleate) within concentration ranges relevant to human intestinal fluid values. A range of poorly soluble drugs with acidic (naproxen, indomethacin, phenytoin, and piroxicam), basic (aprepitant, carvedilol, zafirlukast, tadalafil) or neutral (fenofibrate, griseofulvin, felodipine and probucol) properties have been investigated. The equilibrium solubility results determined are comparable with literature studies of the drugs in either HIF or SIF indicating that the DoE is operating in the correct space. With the exception of pancreatin, all of the factors individually had a statistically significant influence on equilibrium solubility with variations in magnitude of effect between the acidic and basic or neutral compounds and drug specific interactions were evident. Interestingly for the neutral compounds pH was the factor with the second largest solubility effect. Around one third of all the possible factor combinations showed a significant influence on equilibrium solubility with variations in interaction significance and magnitude of effect between the acidic and basic or neutral compounds. The least number of significant media component interactions were noted for the acidic compounds with three and the greatest for the neutral compounds at seven, with again drug specific effects evident. This indicates that a drug's equilibrium solubility in SIF is influenced depending upon drug type by between eight to fourteen individual or combinations of media components with some of these drug specific. This illustrates the complex nature of these fluids and provides for individual drugs a visualisation of the possible solubility envelope within the gastrointestinal tract, which may be of importance for modelling in vivo behaviour. In addition the results indicate that the design of experiment approach can be employed to provide greater detail of drug solubility behaviour, possible drug specific interactions and influence of variations in gastrointestinal media components due to disease. The approach is also feasible and amenable to adaptation for high throughput screening of drug candidates. Copyright © 2014 Elsevier B.V. All rights reserved.

Regulation of Compound Leaf Development in Medicago truncatula by Fused Compound Leaf1, a Class M KNOX Gene[C][W

PubMed Central

Peng, Jianling; Yu, Jianbin; Wang, Hongliang; Guo, Yingqing; Li, Guangming; Bai, Guihua; Chen, Rujin

2011-01-01

Medicago truncatula is a legume species belonging to the inverted repeat lacking clade (IRLC) with trifoliolate compound leaves. However, the regulatory mechanisms underlying development of trifoliolate leaves in legumes remain largely unknown. Here, we report isolation and characterization of fused compound leaf1 (fcl1) mutants of M. truncatula. Phenotypic analysis suggests that FCL1 plays a positive role in boundary separation and proximal-distal axis development of compound leaves. Map-based cloning indicates that FCL1 encodes a class M KNOX protein that harbors the MEINOX domain but lacks the homeodomain. Yeast two-hybrid assays show that FCL1 interacts with a subset of Arabidopsis thaliana BEL1-like proteins with slightly different substrate specificities from the Arabidopsis homolog KNATM-B. Double mutant analyses with M. truncatula single leaflet1 (sgl1) and palmate-like pentafoliata1 (palm1) leaf mutants show that fcl1 is epistatic to palm1 and sgl1 is epistatic to fcl1 in terms of leaf complexity and that SGL1 and FCL1 act additively and are required for petiole development. Previous studies have shown that the canonical KNOX proteins are not involved in compound leaf development in IRLC legumes. The identification of FCL1 supports the role of a truncated KNOX protein in compound leaf development in M. truncatula. PMID:22080596

Using operational and defined fractions to assess soil organic matter stabilization and structure

NASA Astrophysics Data System (ADS)

Horwath, W. R.

2015-12-01

Studies on soil organic matter (SOM) began with alkaline solvents revealing a dark colored substance that could be isolated under low pH. Further studies revealed fulvic and humic acids and humin fractions leading to theories on functional groups and metal-clay bridging mechanisms. The fate of isotopes in these fractions revealed soil carbon pools with varying turnover rates with half the soil carbon (C) in humin and acid hydrolyzed fractions over 1000 years old. These results are the basis of the three pool conceptual framework used in many biogeochemical models. Theories on the role of functional groups and compound classes further elaborated concepts on physical (aggregates) and chemical mechanisms of C stabilization. With the advance of analytical instrumentation, the operational fractions were further defined to the compound and molecular levels. These studies confirmed the majority of soil C is microbially derived. Our observation that all microbial groups contributed nonselectively to soil C maintenance independent of mineralogy suggests that compound characteristics within integrated structures are more important than the source of individual compounds for stabilizing soil C. In dissolved organic C floccing studies using Near Edge X-ray Fine Structure analysis, we found that aromatic compounds interacted first with Fe, however, the majority of direct bonds to Fe were polysaccharides, reinforcing that an integrative chemical structure rather than direct bonds imparted stability in organo-metal interactions. Using a novel differential scanning calorimeter coupled to an isotope ratio mass spectrometer setup, we confirmed that the presence of clays (independent of clay type) increased the microbial utilization of calcium stabilized high versus low temperature compounds, asserting that higher temperature compounds (i.e., phenolics) are likely less tightly bound by clay minerals. The integration of operational and defined fractions of SOM remains a legitimate approach to examine SOM structure and stabilization across scales of soil development and management.

Chemical composition and seasonal variations in the amount of secondary compounds in Gentiana lutea leaves and flowers.

PubMed

Menković, N; Savikin-Fodulović, K; Savin, K

2000-03-01

The chemical investigation of MeOH extracts of Gentiana lutea leaves and flowers showed that xanthones were one of the dominant class of compounds. Secoiridoids and flavonoids were also recorded. The amount of secondary metabolites varied depending on development stage. In the phase of flowering, leaves are rich with compounds possessing C-glycoside structures while O-glycoside structures accumulate mainly before flowering.

Selected trace-element and synthetic-organic compound data for streambed sediment from the Clark Fork-Pend Oreille and Spokane River basins, Montana, Idaho, and Washington, 1998

USGS Publications Warehouse

Beckwith, Michael A.

2002-01-01

Most of the analytical results for synthetic organic compounds were reported as either estimated or non-detected values. Phthalates and polycyclic aro­matic hydrocarbons were the most frequently detected classes of synthetic organic compounds in streambed sediment. Organochlorine pesticide residues were detected at two sites. Polychlorinated biphenyls were detected at one site.

Cinacalcet hydrochloride (Amgen).

PubMed

Iqbal, Jameel; Zaidi, Mone; Schneider, Adina E

2003-06-01

Amgen Inc and Kirin Brewery Co Ltd, under license from NPS Pharmaceuticals Inc, are developing cinacalcet hydrochloride, the lead compound in a series of calcimimetics, for the potential treatment of primary and secondary hyperparathyroidism. Tecalcet hydrochloride was the first compound from this class to be extensively studied and most of the pharmacological data disclosed is for this compound. Cinacalcet hydrochloride was developed in an effort to improve on the poor pharmacokinetics and metabolism of tecalcet hydrochloride.

Evaluation of organic compounds and trace elements in Amazon Creek Basin, Oregon, September 1990

USGS Publications Warehouse

Rinella, F.A.

1993-01-01

Water and bottom sediment were collected from Amazon Creek, Oregon during a summer low-flow condition and analyzed for different classes of organic compounds, including many from the U.S. Environmental Protection Agency's priority pollutant list. Bottom sediment also was analyzed for trace elements typically associated with urban runoff. Trace-element concentrations in the less than 63 micrometer fraction of Amazon Creek bottom-sediment samples were compared with baseline concentrations (expected 95 percent confidence range) for soils from the Western United States and with concen- trations found in bottom sediment from the Willamette River Basin. Total-digestion concentrations of antimony, arsenic, cadmium, chromium, cobalt, copper, lead, manganese, mercury, nickel, silver, titanium, and zinc were enriched at some or all sites sampled. Whole-water samples from some sites contained concentrations of several chlorophenoxy-acid herbicides, the organophosphorus insecticide diazinon, and several semivolatile priority pollutants. Classes of compounds not detected in whole-water samples included carbamate insecticides, triazine and other nitrogen-containing herbicides, and purgeable organic compounds. Bottom-sediment samples contained many organochlorine compounds, including chlordane, DDT plus metabolites, dieldrin, endrin, heptachlor epoxide (a metabolite of heptachlor), and PCBs at some or all sites sampled. Twenty-four of 54 semivolatile compounds were detected in bottom- sediment samples at some or all sites sampled.

"I'm Strong within Myself": Gender, Class and Emotional Capital in Childcare

ERIC Educational Resources Information Center

Andrew, Yarrow

2015-01-01

Emotions have received increasing attention in educational circles in the last decade. Drawing on Bourdieu, feminist scholars use emotional capital to illustrate the ways gendered inequalities can compound the disadvantages of social class. This paper examines relationships within childcare services in Australia, showing how emotional capital…

The discriminant pixel approach: a new tool for the rational interpretation of GCxGC-MS chromatograms.

PubMed

Vial, Jérôme; Pezous, Benoît; Thiébaut, Didier; Sassiat, Patrick; Teillet, Béatrice; Cahours, Xavier; Rivals, Isabelle

2011-01-30

GCxGC is now recognized as the most suited analytical technique for the characterization of complex mixtures of volatile compounds; it is implemented worldwide in academic and industrial laboratories. However, in the frame of comprehensive analysis of non-target analytes, going beyond the visual examination of the color plots remains challenging for most users. We propose a strategy that aims at classifying chromatograms according to the chemical composition of the samples while determining the origin of the discrimination between different classes of samples: the discriminant pixel approach. After data pre-processing and time-alignment, the discriminatory power of each chromatogram pixel for a given class was defined as its correlation with the membership to this class. Using a peak finding algorithm, the most discriminant pixels were then linked to chromatographic peaks. Finally, crosschecking with mass spectrometry data enabled to establish relationships with compounds that could consequently be considered as candidate class markers. This strategy was applied to a large experimental data set of 145 GCxGC-MS chromatograms of tobacco extracts corresponding to three distinct classes of tobacco. Copyright © 2010 Elsevier B.V. All rights reserved.

The Role of Physical Activity and Feeding Schedule on the Kinetics of Inhaled and Oral Toluene in Rats

EPA Science Inventory

This manuscript provides new information regarding factors that affect the toxicokinetics of toluene, a hazardous air pollutant with acute neurotoxic activity. Toluene is a prototype compound of the class of volatile organic compounds (VOCs), which have similar CNS activity and k...

Nature's Way to Make the Lantibiotics

ERIC Educational Resources Information Center

Relyea, Heather A.; van der Donk, Wilfred A.

2006-01-01

The biosynthesis and mode of action of a class of compounds called lantibiotics, a peptide with antibacterial activity against multi-drug resistant bacteria as well as food-borne pathogens like Listeria monocytogenes and Clostridium botulinum is described. These peptide-derived compounds are especially interesting because they could be used as…

USE OF BIOASSAY-DIRECTED CHEMICAL ANALYSIS FOR IDENTIFYING MUTAGENIC COMPOUNDS IN URBAN AIR AND COMBUSTION EMISSIONS

EPA Science Inventory

Bioassay-directed chemical analysis fractionation has been used for 30 years to identify mutagenic classes of compounds in complex mixtures. Most studies have used the Salmonella (Ames) mutagenicity assay, and we have recently applied this methodology to two standard reference sa...

RETINOID METABOLISM IN FISH EMBRYOS FROM SENSITIVE AND RESISTANT POPULATIONS EXPOSED TO DIOXIN-LIKE COMPOUNDS

EPA Science Inventory

Early developmental stages of fish are extremely sensitive to a class of toxic and persistent environmental contaminants known as dioxin-like compounds (DLCs). Most of the toxicological actions of DLCs are mediated via the Aryl hydrocarbon Receptor (AhR) that regulates transcript...

A Multiweek Upper-Division Inorganic Laboratory Based on Metallacrowns

ERIC Educational Resources Information Center

Sirovetz, Brian J.; Walters, Nicole E.; Bender, Collin N.; Lenivy, Christopher M.; Troup, Anna S.; Predecki, Daniel P.; Richardson, John N.; Zaleski, Curtis M.

2013-01-01

Metallacrowns are a versatile class of inorganic compounds with uses in several areas of chemistry. Students engage in a multiweek, upper-division inorganic laboratory that explores four different metallacrown compounds: Fe[superscript III](O[subscript 2]CCH[subscript 3])[subscript 3][9-MC[subscript Fe][superscript III][subscript…

Construction of an N-nitroso database for assessing dietary intake

USDA-ARS?s Scientific Manuscript database

Dietary N-nitroso compounds are carcinogens synthesized during food processing from two main classes of precursors, oxides of nitrogen and amines or amides. Quantification of the dietary intake of N-nitroso compounds is significant to human cancers, including those of the stomach and upper gastro-in...

Histone deacetylase inhibitors containing a benzamide functional group and a pyridyl cap are preferentially effective human immunodeficiency virus-1 latency-reversing agents in primary resting CD4+ T cells

PubMed Central

Gélinas, Céline

2017-01-01

Antiretroviral therapy (ART) can control human immunodeficiency virus-1 (HIV-1) replication in infected individuals. Unfortunately, patients remain persistently infected owing to the establishment of latent infection requiring that ART be maintained indefinitely. One strategy being pursued involves the development of latency-reversing agents (LRAs) to eliminate the latent arm of the infection. One class of molecules that has been tested for LRA activity is the epigenetic modulating compounds histone deacetylases inhibitors (HDACis). Previously, initial screening of these molecules typically commenced using established cell models of viral latency, and although certain drugs such as the HDACi suberoylanilide hydroxamic acid demonstrated strong activity in these models, it did not translate to comparable activity with patient samples. Here we developed a primary cell model of viral latency using primary resting CD4+ T cells infected with Vpx-complemented HIV-1 and found that the activation profile using previously described LRAs mimicked that obtained with patient samples. This primary cell model was used to evaluate 94 epigenetic compounds. Not surprisingly, HDACis were found to be the strongest activators. However, within the HDACi class, the most active LRAs with the least pronounced toxicity contained a benzamide functional moiety with a pyridyl cap group, as exemplified by the HDACi chidamide. The results indicate that HDACis with a benzamide moiety and pyridyl cap group should be considered for further drug development in the pursuit of a successful viral clearance strategy. PMID:28113052

Two interpenetrating Cu{sup II}/Ni{sup II}-coordinated polymers based on an unsymmetrical bifunctional N/O-tectonic: Syntheses, structures and magnetic properties

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

Liu, Yong-Liang; Department of Chemistry and Chemical Engineering, Shaanxi Key Laboratory of Comprehensive Utilization of Tailings Resources, Shang Luo University, Shang Luo 726000; Wu, Ya-Pan

2015-03-15

Two new interpenetrating Cu{sup II}/Ni{sup II} coordination polymers, based on a unsymmetrical bifunctional N/O-tectonic 3-(pyrid-4′-yl)-5-(4″-carbonylphenyl)-1,2,4-triazolyl (H{sub 2}pycz), ([Cu-(Hpycz){sub 2}]·2H{sub 2}O){sub n} (1) and ([Ni(Hpycz){sub 2}]·H{sub 2}O){sub n} (2), have been solvothermally synthesized and structure characterization. Single crystal X-ray analysis indicates that compound 1 shows 2-fold parallel interpenetrated 4{sup 4}-sql layers with the same handedness. The overall structure of 1 is achiral—in each layer of doubly interpenetrating nets, the two individual nets have the opposite handedness to the corresponding nets in the adjoining layers—while 2 features a rare 8-fold interpenetrating 6{sup 6}-dia network that belongs to class IIIa interpenetration. In addition,more » compounds 1 and 2 both show similar paramagnetic characteristic properties. - Graphical abstract: Two new Cu(II)/Ni(II) coordination polymers present 2D parallel 2-fold interpenetrated 4{sup 4}-sql layers and a rare 3D 8-fold interpenetrating 6{sup 6}-dia network. In addition, magnetic susceptibility measurements show similar paramagnetic characteristic for two complexes. - Highlights: • A new unsymmetrical bifunctional N/O-tectonic as 4-connected spacer. • A 2-fold parallel interpenetrated sql layer with the same handedness. • A rare 8-fold interpenetrating dia network (class IIIa)« less

TR-DB: an open-access database of compounds affecting the ethylene-induced triple response in Arabidopsis.

PubMed

Hu, Yuming; Callebert, Pieter; Vandemoortel, Ilse; Nguyen, Long; Audenaert, Dominique; Verschraegen, Luc; Vandenbussche, Filip; Van Der Straeten, Dominique

2014-02-01

Small molecules which act as hormone agonists or antagonists represent useful tools in fundamental research and are widely applied in agriculture to control hormone effects. High-throughput screening of large chemical compound libraries has yielded new findings in plant biology, with possible future applications in agriculture and horticulture. To further understand ethylene biosynthesis/signaling and its crosstalk with other hormones, we screened a 12,000 compound chemical library based on an ethylene-related bioassay of dark-grown Arabidopsis thaliana (L.) Heynh. seedlings. From the initial screening, 1313 (∼11%) biologically active small molecules altering the phenotype triggered by the ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC), were identified. Selection and sorting in classes were based on the angle of curvature of the apical hook, the length and width of the hypocotyl and the root. A MySQL-database was constructed (https://chaos.ugent.be/WE15/) including basic chemical information on the compounds, images illustrating the phenotypes, phenotype descriptions and classification. The research perspectives for different classes of hit compounds will be evaluated, and some general screening tips for customized high-throughput screening and pitfalls will be discussed. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Discovery of Quinoline-Derived Trifluoromethyl Alcohols, Determination of Their in vivo Toxicity and Anticancer Activity in a Zebrafish Embryo Model.

PubMed

Sittaramane, Vinoth; Padgett, Jihan; Salter, Philip; Williams, Ashley; Luke, Shauntelle; McCall, Rebecca; Arambula, Jonathan F; Graves, Vincent B; Blocker, Mark; Van Leuven, David; Bowe, Keturah; Heimberger, Julia; Cade, Hannah C; Immaneni, Supriya; Shaikh, Abid

2015-11-01

In this study the rational design, synthesis, and anticancer activity of quinoline-derived trifluoromethyl alcohols were evaluated. Members of this novel class of trifluoromethyl alcohols were identified as potent growth inhibitors in a zebrafish embryo model. Synthesis of these compounds was carried out with an sp(3) -C-H functionalization strategy of methyl quinolines with trifluoromethyl ketones. A zebrafish embryo model was also used to explore the toxicity of ethyl 4,4,4-trifluoro-3-hydroxy-3-(quinolin-2-ylmethyl)butanoate (1), 2-benzyl-1,1,1-trifluoro-3-(quinolin-2-yl)propan-2-ol (2), and trifluoro-3-(isoquinolin-1-yl)-2-(thiophen-2-yl)propan-2-ol (3). Compounds 2 and 3 were found to be more toxic than compound 1; apoptotic staining assays indicated that compound 3 causes increased cell death. In vitro cell proliferation assays showed that compound 2, with an LC50 value of 14.14 μm, has more potent anticancer activity than cisplatin. This novel class of inhibitors provides a new direction in the discovery of effective anticancer agents. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

Felser, Claudia, E-mail: felser@cpfs.mpg.de; Wollmann, Lukas; Chadov, Stanislav

Heusler compounds are a remarkable class of materials with more than 1000 members and a wide range of extraordinary multi-functionalities including halfmetallic high-temperature ferri- and ferromagnets, multi-ferroics, shape memory alloys, and tunable topological insulators with a high potential for spintronics, energy technologies, and magneto-caloric applications. The tunability of this class of materials is exceptional and nearly every functionality can be designed. Co{sub 2}-Heusler compounds show high spin polarization in tunnel junction devices and spin-resolved photoemission. Manganese-rich Heusler compounds attract much interest in the context of spin transfer torque, spin Hall effect, and rare earth free hard magnets. Most Mn{sub 2}-Heuslermore » compounds crystallize in the inverse structure and are characterized by antiparallel coupling of magnetic moments on Mn atoms; the ferrimagnetic order and the lack of inversion symmetry lead to the emergence of new properties that are absent in ferromagnetic centrosymmetric Heusler structures, such as non-collinear magnetism, topological Hall effect, and skyrmions. Tetragonal Heusler compounds with large magneto crystalline anisotropy can be easily designed by positioning the Fermi energy at the van Hove singularity in one of the spin channels. Here, we give a comprehensive overview and a prospective on the magnetic properties of Heusler materials.« less

Identifying unknown by-products in drinking water using comprehensive two-dimensional gas chromatography-quadrupole mass spectrometry and in silico toxicity assessment.

PubMed

Li, Chunmei; Wang, Donghong; Li, Na; Luo, Qian; Xu, Xiong; Wang, Zijian

2016-11-01

Improvements in extraction and detection technologies have increased our abilities to identify new disinfection by-products (DBPs) over the last 40 years. However, most previous studies combined DBP identification and measurement efforts with toxicology to address concerns on a few expected DBPs, making it difficult to better define the health risk from the individual DBPs. In this study, a nontargeted screening method involving comprehensive two-dimensional gas chromatography-quadrupole mass spectrometry (GC × GC-qMS) combined with OECD QSAR Toolbox Ver. 3.2 was developed for identifying and prioritizing of volatile and semi-volatile DBPs in drinking water. The method was successfully applied to analyze DBPs formed during chlorination, chloramination or ozonation of the raw water. Over 500 compounds were tentatively identified in each sample, showing the superior performance of this analytical technique. A total of 170 volatile and semi-volatile DBPs representing fourteen chemical classes were then identified, according to the criteria that the DBP was presented in the duplicate treated samples. The genotoxicity and carcinogenicity of the DBPs were evaluated using Toolbox, and 58 DBPs were found to be actual or potential genotoxicants. The accuracy of the compound identification was determined by comparing 47 identified compounds with commercially available standards. About 90% (41 of the 47) of the compounds that were automatically identified using the library were correct. The results show that GC×GC-qMS coupled with a quantitative structure-activity relationship model is a powerful and fast nontargeted screening technique for compounds. The method and results provide us a new idea for identification and prioritization of DBPs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Prolonged grief and post-traumatic growth after loss: Latent class analysis.

PubMed

Zhou, Ningning; Yu, Wei; Tang, Suqin; Wang, Jianping; Killikelly, Clare

2018-06-06

Bereavement may trigger different psychological outcomes, such as prolonged grief disorder or post-traumatic growth. The relationship between these two outcomes and potential precipitators remain unknown. The current study aimed to identify classes of Chinese bereaved individuals based on prolonged grief symptoms and post-traumatic growth and to examine predictors for these classes. We used data from 273 Chinese individuals who lost a relative due to disease (92.3%), accident (4.4%) and other reasons (1.8%). Latent class analysis revealed three classes: a resilient class, a growth class, and a combined grief/growth class. A higher level of functional impairment was found for the combined grief/growth class than for the other two classes. Membership in the combined grief/growth class was significantly predicted by the younger age of the deceased and the death of a parent, child or spouse. Subjective closeness with the deceased and gender were marginally significant predictors. When the four variables were included in the multinomial regression analysis, death of a parent, child or spouse significantly predicted the membership to the combined grief/growth class. These findings provide valuable information for the development of tailored interventions that may build on the bereaved individuals' personal strengths. Copyright © 2018. Published by Elsevier B.V.

Bioavailability of Plant-Derived Antioxidants

PubMed Central

Abourashed, Ehab A.

2013-01-01

Natural products with antioxidant properties have been extensively utilized in the pharmaceutical and food industry and have also been very popular as health-promoting herbal products. This review provides a summary of the literature published around the first decade of the 21st century regarding the oral bioavailability of carotenoids, polyphenols and sulfur compounds as the three major classes of plant-derived antioxidants. The reviewed original research includes more than 40 compounds belonging to the above mentioned classes of natural antioxidants. In addition, related reviews published during the same period have been cited. A brief introduction to general bioavailability-related definitions, procedures and considerations is also included. PMID:26784467

Nonimaging compound parabolic concentrator-type reflectors with variable extreme direction.

PubMed

Gordon, J M; Rabl, A

1992-12-01

The properties of nonimaging compound parabolic concentrator (CPC)-type devices are examined in which the extreme direction is not constant but rather is a variable that can change along the reflector. One can then retain the maximal concentration or radiative efficiency of the CPC while the flux map on the absorber or target is modified, depending on whether the device is used for optical concentration or for lighting. Two general classes of reflector are derived, and all the nonimaging devices developed to date are shown to be special cases of the general solution. These two classes are the nonimaging analog of converging and diverging devices of imaging optics.

LEDGINs, non-catalytic site inhibitors of HIV-1 integrase: a patent review (2006 - 2014).

PubMed

Demeulemeester, Jonas; Chaltin, Patrick; Marchand, Arnaud; De Maeyer, Marc; Debyser, Zeger; Christ, Frauke

2014-06-01

Integration of the viral genome into the host cell chromatin is a central step in the replication cycle of the HIV. Blocking the viral integrase (IN) enzyme therefore provides an attractive therapeutic strategy, as evidenced by the recent clinical approval of three IN strand transfer inhibitors. Viral resistance and cross-resistance among these inhibitors, however, warrant the search for compounds targeting HIV integration through alternative mechanisms of action. The most potent class of allosteric IN inhibitors was independently identified at the University of Leuven, Belgium, and at Boehringer Ingelheim, Canada. These compounds, coined LEDGINs (after the lens epithelium-derived growth factor/p75 cofactor binding pocket on IN) or non-catalytic site IN inhibitors (NCINIs) by the respective groups, have shown remarkable antiviral activity. This review provides a brief introduction to the compound class and discusses the recent patent literature (2006 to the present). LEDGINs are still early in development. Trials with clinical candidate BI-224436 were put on hold despite promising results. Literature, however, reveals that almost all major pharmaceutical companies active in the treatment of HIV/AIDS have taken a significant interest in this class. As a result, several of these inhibitors may soon enter clinical trials.

Impact of socioeconomic status and subjective social class on overall and health-related quality of life.

PubMed

Kim, Jae-Hyun; Park, Eun-Cheol

2015-08-15

Our objective was to investigate the impact of socioeconomic status and subjective social class on health-related quality of life (HRQOL) vs. overall quality of life (QOL). We performed a longitudinal analysis using data regarding 8250 individuals drawn from the Korean Longitudinal Study of Aging (KLoSA). We analyzed differences between HRQOL and QOL in individuals of various socioeconomic strata (high, middle, or low household income and education levels) and subjective social classes (high, middle, or low) at baseline (2009). Individuals with low household incomes and of low subjective social class had the highest probability of reporting discrepant HRQOL and QOL scores (B: 4.796; P < 0.0001), whereas individuals with high household incomes and high subjective social class had the lowest probability of discrepant HRQOL and QOL scores (B: -3.625; P = 0.000). Similar trends were seen when education was used as a proxy for socioeconomic status. In conclusion, both household income/subjective social class and education/subjective social class were found to have an impact on the degree of divergence between QOL and HRQOL. Therefore, in designing interventions, socioeconomic inequalities should be taken into account through the use of multi-dimensional measurement tools.

Wealth, Poverty, and Happiness: Social Class Is Differentially Associated With Positive Emotions.

PubMed

Piff, Paul K; Moskowitz, Jake P

2017-12-18

Is higher social class associated with greater happiness? In a large nationally representative U.S. sample (N = 1,519), we examined the association between social class (household income) and self-reported tendencies to experience 7 distinct positive emotions that are core to happiness: amusement, awe, compassion, contentment, enthusiasm, love, and pride. Consistent with past research indicating that social class underlies differential patterns of attending to the self versus orienting to others, higher social class was associated with greater self-oriented feelings of contentment and pride, and with greater amusement. In contrast, lower social class was associated with more other-oriented feelings of compassion and love, and with greater awe. There were no class differences in enthusiasm. We discuss that individuals from different social class backgrounds may exhibit different patterns of emotional responding due to their distinct social concerns and priorities. Whereas self-oriented emotions may follow from, foster, and reinforce upper class individuals' desire for independence and self-sufficiency, greater other-oriented emotion may enable lower class individuals to form more interdependent bonds to cope with their more threatening environments. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Quantitative analysis of nitrogen containing compounds in microalgae based bio-oils using comprehensive two-dimensional gas-chromatography coupled to nitrogen chemiluminescence detector and time of flight mass spectrometer.

PubMed

Toraman, Hilal E; Franz, Kristina; Ronsse, Frederik; Van Geem, Kevin M; Marin, Guy B

2016-08-19

Insight in the composition of the algae derived bio-oils is crucial for the development of efficient conversion processes and better upgrading strategies for microalgae. Comprehensive two-dimensional gas chromatography (GC×GC) coupled to nitrogen chemiluminescence detector (NCD) and time-of-flight mass spectrometer (TOF-MS) allows to obtain the detailed quantitative composition of the nitrogen containing compounds in the aqueous and the organic fraction of fast pyrolysis bio-oils from microalgae. Normal phase (apolar×mid-polar) and reverse phase column (polar×apolar) combination are investigated to optimize the separation of the detected nitrogen containing compounds. The reverse phase column combination gives the most detailed information in terms of the nitrogen containing compounds. The combined information from the GC×GC-TOF-MS (qualitative) and GC×GC-NCD (quantitative) with the use of a well-chosen internal standard, i.e. caprolactam, enables the identification and quantification of nitrogen containing compounds belonging to 13 different classes: amines, imidazoles, amides, imides, nitriles, pyrazines, pyridines, indoles, pyrazoles, pyrimidines, quinolines, pyrimidinediones and other nitrogen containing compounds which were not assigned to a specific class. The aqueous fraction mostly consists of amines (4.0wt%) and imidazoles (2.8wt%) corresponding to approximately 80wt% of the total identified nitrogen containing compounds. On the other hand, the organic fraction shows a more diverse distribution of nitrogen containing compounds with the majority of the compounds quantified as amides (3.0wt%), indoles (2.0wt%), amines (1.7wt%) and imides (1.3wt%) corresponding to approximately 65wt% of the total identified nitrogen containing compounds. Copyright © 2016 Elsevier B.V. All rights reserved.

[Once again about "Gregg paradox" and its solution].

PubMed

Mavrodiev, E V

2002-01-01

"Gregg paradox" means that monotypical groups containing the same species (or groups of species) will be equal each other although systematics considers them as different taxa. Thus if the order of placental mammalia Tubilidentata includes one species aardvark Orycteropus after, the order itself, its single family Orycteropodiaceae, single genus of the family Orycteropus and the single species Orycteropus after can be considered as equal to each other. To solve this disagreement the author asserts that taxa of any level can be regarded as an individual according to the taxa of higher rank. Possibility of such interpretation was already suggested by Georg Cantor (1985). He supposed that a set (class) can be regarded as unity by itself. In this case connections between taxa of different levels can be realized by Peano ratio of intrasitive conformities. In this model a genus will consist of species but not individuals, a type--of classes, etc. Thus, if a taxon x as an individual is an element of taxon y, and taxon y as an individual is an element of taxon z, then z according to x will be not only logical class, but class of classes and, hence we could not consider x as an element of z, because the latter consists of indecomposable individual-class y or some similar classes. In this situation "Gregg paradox" does not arise.

Identification and Optimization of Classifier Genes from Multi-Class Earthworm Microarray Dataset

DTIC Science & Technology

2010-10-28

rapid and accurate diagnostic assays. A variety of toxicological effects have been associated with explosive compounds TNT and RDX. One important goal of...analyze toxicological mechanisms for two military- unique explosive compounds 2,4,6-trinitrotolune (TNT) and 1,3,5- trinitro-1,3,5-triazacyclohexane...also known as Royal Demolition eXplosive or RDX) [7,8]. These two compounds exhibit distinctive toxicological properties that are accompanied by

Mo(3)Sb(7-x)Te(x) for Thermoelectric Power Generation

NASA Technical Reports Server (NTRS)

Snyder, G. Jeffrey; Gascoin, Frank S.; Rasmussen, Julia

2009-01-01

Compounds having compositions of Mo(3)Sb(7-x)Te(x) (where x = 1.5 or 1.6) have been investigated as candidate thermoelectric materials. These compounds are members of a class of semiconductors that includes previously known thermoelectric materials. All of these compounds have complex crystalline and electronic structures. Through selection of chemical compositions and processing conditions, it may be possible to alter the structures to enhance or optimize thermoelectric properties.

Selective CB2 receptor agonists. Part 2: Structure-activity relationship studies and optimization of proline-based compounds.

PubMed

Riether, Doris; Zindell, Renee; Wu, Lifen; Betageri, Raj; Jenkins, James E; Khor, Someina; Berry, Angela K; Hickey, Eugene R; Ermann, Monika; Albrecht, Claudia; Ceci, Angelo; Gemkow, Mark J; Nagaraja, Nelamangala V; Romig, Helmut; Sauer, Achim; Thomson, David S

2015-02-01

Through a ligand-based pharmacophore model (S)-proline based compounds were identified as potent cannabinoid receptor 2 (CB2) agonists with high selectivity over the cannabinoid receptor 1 (CB1). Structure-activity relationship investigations for this compound class lead to oxo-proline compounds 21 and 22 which combine an impressive CB1 selectivity profile with good pharmacokinetic properties. In a streptozotocin induced diabetic neuropathy model, 22 demonstrated a dose-dependent reversal of mechanical hyperalgesia. Copyright © 2014 Elsevier Ltd. All rights reserved.

A high-throughput screen against pantothenate synthetase (PanC) identifies 3-biphenyl-4-cyanopyrrole-2-carboxylic acids as a new class of inhibitor with activity against Mycobacterium tuberculosis.

PubMed

Kumar, Anuradha; Casey, Allen; Odingo, Joshua; Kesicki, Edward A; Abrahams, Garth; Vieth, Michal; Masquelin, Thierry; Mizrahi, Valerie; Hipskind, Philip A; Sherman, David R; Parish, Tanya

2013-01-01

The enzyme pantothenate synthetase, PanC, is an attractive drug target in Mycobacterium tuberculosis. It is essential for the in vitro growth of M. tuberculosis and for survival of the bacteria in the mouse model of infection. PanC is absent from mammals. We developed an enzyme-based assay to identify inhibitors of PanC, optimized it for high-throughput screening, and tested a large and diverse library of compounds for activity. Two compounds belonging to the same chemical class of 3-biphenyl-4- cyanopyrrole-2-carboxylic acids had activity against the purified recombinant protein, and also inhibited growth of live M. tuberculosis in manner consistent with PanC inhibition. Thus we have identified a new class of PanC inhibitors with whole cell activity that can be further developed.

Synthesis and In Vitro Activity of Polyhalogenated 2-phenylbenzimidazoles as a New Class of anti-MRSA and Anti-VRE Agents.

PubMed

Göker, Hakan; Karaaslan, Cigdem; Püsküllü, Mustafa Orhan; Yildiz, Sulhiye; Duydu, Yalcin; Üstündağ, Aylin; Yalcin, Can Özgür

2016-01-01

A series of novel polyhalogenated 2-phenylbenzimidazoles have been synthesized and evaluated for in vitro antistaphylococcal activity against drug-resistant bacterial strains (methicillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococcus faecium. Certain compounds inhibit bacterial growth perfectly. 11 was active than vancomycin (0.78 μg/mL) with the lowest MIC values with 0.19 μg/mL against methicillin-resistant Staphylococcus aureus, 8 and 35 exhibited best inhibitory activity against vancomycin-resistant Enterococcus faecium (1.56 μg/mL). The mechanism of action for this class of compounds appears to be different than clinically used antibiotics. These polyhalogenated benzimidazoles have potential for further investigation as a new class of potent anti-methicillin-resistant Staphylococcus aureus and anti-vancomycin-resistant Enterococcus faecium agents. © 2015 John Wiley & Sons A/S.

Volatile pollutants emitted from selected liquid household products.

PubMed

Kwon, Ki-Dong; Jo, Wan-Kuen; Lim, Ho-Jin; Jeong, Woo-Sik

2008-09-01

To identify household products that may be potential sources of indoor air pollution, the chemical composition emitted from the products should be surveyed. Although this kind of survey has been conducted by certain research groups in Western Europe and the USA, there is still limited information in scientific literature. Moreover, chemical components and their proportions of household products are suspected to be different with different manufacturers. Consequently, the current study evaluated the emission composition for 42 liquid household products sold in Korea, focusing on five product classes (deodorizers, household cleaners, color removers, pesticides, and polishes). The present study included two phase experiments. First, the chemical components and their proportions in household products were determined using a gas chromatograph and mass spectrometer system. For the 19 target compounds screened by the first phase of the experiment and other selection criteria, the second phase was done to identify their proportions in the purged-gas phase. The number of chemicals in the household products surveyed ranged from 9 to 113. Eight (product class of pesticides) to 17 (product class of cleaning products) compounds were detected in the purged-gas phase of each product class. Several compounds were identified in more than one product class. Six chemicals (acetone, ethanol, limonene, perchloroethylene (PCE), phenol, and 1-propanol) were identified in all five product classes. There were 13 analytes occurring with a frequency of more than 10% in the household products: limonene (76.2%), ethanol (71.4%), PCE (66.7%), phenol (40.5%), 1-propanol (35.7%), decane (33%), acetone (28.6%), toluene (19.0%), 2-butoxy ethanol (16.7%), o-xylene (16.7%), chlorobenzene (14.3%), ethylbenzene (11.9%), and hexane (11.9%). All of the 42 household products analyzed were found to contain one or more of the 19 compounds. The chemical composition varied broadly along with the product classes or product categories, and it was different from that reported in other studies abroad, although certain target chemicals were identified in both studies. This finding supports an assertion that chemical components emitted from household products may be different in different products and with different manufacturers. The chlorinated pollutants identified in the present study have not been reported to be components of cleaning products in papers published since the early 1990s. Limonene was identified as having the highest occurrence in the household products in the present study, although it was not detected in any of 67 household products sold in the U.S. The emission composition of selected household products was successfully examined by purge-and-trap analysis. Along with other exposure information such as use pattern of household products and the indoor climate, this composition data can be used to estimate personal exposure levels of building occupants. This exposure data can be employed to link environmental exposure to health risk. It is noteworthy that many liquid household products sold in Korea emitted several toxic aromatic and chlorinated organic compounds. Moreover, the current finding suggests that product types and manufacturers should be considered, when evaluating building occupants' exposure to chemical components emitted from household products. The current findings can provide valuable information for the semiquantitative estimation of the population inhalation exposure to these compounds in indoor environments and for the selection of safer household products. However, although the chemical composition is known, the emissions of household products might include compounds formed during the use of the product or compounds not identified as ingredients by this study. Accordingly, further studies are required, and testing must be done to determine the actual composition being emitted. Similar to eco-labeling of shampoos, shower gels, and foam baths proposed by a previous study, eco-labeling of other household products is suggested.

Individual class evaluation and effective teaching characteristics in integrated curricula.

PubMed

Hwang, Jung Eun; Kim, Na Jin; Song, Meiying; Cui, Yinji; Kim, Eun Ju; Park, In Ae; Lee, Hye In; Gong, Hye Jin; Kim, Su Young

2017-12-12

In an integrated curriculum, multiple instructors take part in a course in the form of team teaching. Accordingly, medical schools strive to manage each course run by numerous instructors. As part of the curriculum management, course evaluation is conducted, but a single, retrospective course evaluation does not comprehensively capture student perception of classes by different instructors. This study aimed to demonstrate the need for individual class evaluation, and further to identify teaching characteristics that instructors need to keep in mind when preparing classes. From 2014 to 2015, students at one medical school left comments on evaluation forms after each class. Courses were also assessed after each course. Their comments were categorized by connotation (positive or negative) and by subject. Within each subject category, test scores were compared between positively and negatively mentioned classes. The Mann-Whitney U test was performed to test group differences in scores. The same method was applied to the course evaluation data. Test results for course evaluation showed group difference only in the practice/participation category. However, test results for individual class evaluation showed group differences in six categories: difficulty, main points, attitude, media/contents, interest, and materials. That is, the test scores of classes positively mentioned in six domains were significantly higher than those of negatively mentioned classes. It was proved that individual class evaluation is needed to manage multi-instructor courses in integrated curricula of medical schools. Based on the students' extensive feedback, we identified teaching characteristics statistically related to academic achievement. School authorities can utilize these findings to encourage instructors to develop effective teaching characteristics in class preparation.

Perfluorotributylamine: A novel long-lived greenhouse gas

NASA Astrophysics Data System (ADS)

Hong, Angela C.; Young, Cora J.; Hurley, Michael D.; Wallington, Timothy J.; Mabury, Scott A.

2013-11-01

Perfluorinated compounds impact the Earth's radiative balance. Perfluorotributylamine (PFTBA) belongs to the perfluoroalkyl amine class of compounds; these have not yet been investigated as long-lived greenhouse gases (LLGHGs). Atmospheric measurements of PFTBA made in Toronto, ON, detected a mixing ratio of 0.18 parts per trillion by volume. An instantaneous radiative efficiency of 0.86 W m-2 ppb-1 was calculated from its IR absorption spectra, and a lower limit of 500 years was estimated for its atmospheric lifetime. PFTBA has the highest radiative efficiency of any compound detected in the atmosphere. If the concentration in Toronto is representative of the change in global background concentration since the preindustrial period, then the radiative forcing of PFTBA is 1.5 × 10-4 W m-2. We calculate the global warming potential of PFTBA over a 100 year time horizon to be 7100. Detection of PFTBA demonstrates that perfluoroalkyl amines are a class of LLGHGs worthy of future study.

Does the Chemical Diversity of the Order Haplosclerida (Phylum Porifera: Class Demospongia) Fit with Current Taxonomic Classification?

PubMed

Tribalat, Marie-Aude; Marra, Maria V; McCormack, Grace P; Thomas, Olivier P

2016-06-01

Sponges and their associated microbiota are well known to produce a large diversity of natural products, also called specialized metabolites. In addition to their potential use in the pharmaceutical industry, these rather species-specific compounds may help in the classification of some particular sponge groups. We review herein compounds isolated from haplosclerid sponges (Class Demospongia, Order Haplosclerida) in order to help in the revision of this large group of marine invertebrates. We focus only on 3-alkylpyridine derivatives and polyacetylenic compounds, as these two groups of natural products are characteristic of haplosclerid species and are highly diverse. A close collaboration between chemists and biologists is required in order to fully apply chemotaxonomical approaches, and whenever possible biological data should include morphological and molecular data and some insight into their microbial abundance. Georg Thieme Verlag KG Stuttgart · New York.

Chemical assessment and in vitro antioxidant capacity of Ficus carica latex.

PubMed

Oliveira, Andreia P; Silva, Luís R; Ferreres, Federico; Guedes de Pinho, Paula; Valentão, Patrícia; Silva, Branca M; Pereira, José A; Andrade, Paula B

2010-03-24

Ficus species possess latex-like material within their vasculatures, affording protection and self-healing from physical attacks. In this work, metabolite profiling was performed on Ficus carica latex. Volatiles profile was determined by HS-SPME/GC-IT-MS, with 34 compounds being identified, distributed by distinct chemical classes: 5 aldehydes, 7 alcohols, 1 ketone, 9 monoterpenes, 9 sesquiterpenes and 3 other compounds. Sesquiterpenes constituted the most abundant class in latex (ca. 91% of total identified compounds). Organic acids composition was also characterized, by HPLC-UV, and oxalic, citric, malic, quinic, shikimic and fumaric acids were determined. Malic and shikimic acids were present in higher amounts (ca. 26%, each). The antioxidant potential of this material was checked by distinct in vitro chemical assays. A concentration-dependent activity was noticed against DPPH, nitric oxide and superoxide radicals. Additionally, acetylcholinesterase inhibitory capacity was evaluated, but a weak effect was found.

Thiazolino 2-Pyridone Amide Inhibitors of Chlamydia trachomatis Infectivity.

PubMed

Good, James A D; Silver, Jim; Núñez-Otero, Carlos; Bahnan, Wael; Krishnan, K Syam; Salin, Olli; Engström, Patrik; Svensson, Richard; Artursson, Per; Gylfe, Åsa; Bergström, Sven; Almqvist, Fredrik

2016-03-10

The bacterial pathogen Chlamydia trachomatis is a global health burden currently treated with broad-spectrum antibiotics which disrupt commensal bacteria. We recently identified a compound through phenotypic screening that blocked infectivity of this intracellular pathogen without host cell toxicity (compound 1, KSK 120). Herein, we present the optimization of 1 to a class of thiazolino 2-pyridone amides that are highly efficacious (EC50 ≤ 100 nM) in attenuating infectivity across multiple serovars of C. trachomatis without host cell toxicity. The lead compound 21a exhibits reduced lipophilicity versus 1 and did not affect the growth or viability of representative commensal flora at 50 μM. In microscopy studies, a highly active fluorescent analogue 37 localized inside the parasitiphorous inclusion, indicative of a specific targeting of bacterial components. In summary, we present a class of small molecules to enable the development of specific treatments for C. trachomatis.

Halogenated fatty amides - A brand new class of disinfection by-products.

PubMed

Kosyakov, Dmitry S; Ul'yanovskii, Nikolay V; Popov, Mark S; Latkin, Tomas B; Lebedev, Albert T

2017-12-15

An array of similar halogenated nitrogen-containing compounds with elemental composition C n H 2n NO 2 X, C n H 2n-2 NO 2 X and C n H 2n-1 NOX 2 (X = Cl, Br; n = 16, 18, 22) was detected in drinking water with high performance liquid chromatography - high resolution mass spectrometry (HPLC-HRMS) method. Compounds of this type were never mentioned among disinfection by-products. Tandem mass spectrometry allowed referring them to halohydrines or dihalogenated fatty amides, the products of conjugated electrophilic addition of halogens to the double bonds of unsaturated fatty amides. The proposed structures were confirmed by conducting aqueous chlorination with standard solution of oleamide. These compounds may be considered as a brand new class of disinfection by products, while their toxicities require special study. Copyright © 2017 Elsevier Ltd. All rights reserved.

Exploring Cancer Therapeutics with Natural Products from African Medicinal Plants, Part I: Xanthones, Quinones, Steroids, Coumarins, Phenolics and other Classes of Compounds.

PubMed

Simoben, Conrad V; Ibezim, Akachukwu; Ntie-Kang, Fidele; Nwodo, Justina N; Lifongo, Lydia L

2015-01-01

Cancer is known to be the second most common disease-related cause of death among humans. In drug discovery programs anti-cancer chemotherapy remains quite challenging due to issues related to resistance. Plants used in traditional medicine are known to contribute significantly within a large proportion of the African population. A survey of the literature has led to the identification of ~400 compounds from African medicinal plants, which have shown anti-cancer, anti-proliferation, anti-tumor and/or cytotoxic activities, tested by in vitro and in vivo assays (from mildly active to very active), mainly alkaloids, terpenoids, flavonoids, coumarins, phenolics, polyacetylates, xanthones, quinones, steroids and lignans. The first part of this review series focuses on xanthones, quinones, steroids, coumarins, phenolics and other compound classes, while part II is focused on alkaloids, terpenoids, flavonoids.

Molecular Phenotyping Combines Molecular Information, Biological Relevance, and Patient Data to Improve Productivity of Early Drug Discovery.

PubMed

Drawnel, Faye Marie; Zhang, Jitao David; Küng, Erich; Aoyama, Natsuyo; Benmansour, Fethallah; Araujo Del Rosario, Andrea; Jensen Zoffmann, Sannah; Delobel, Frédéric; Prummer, Michael; Weibel, Franziska; Carlson, Coby; Anson, Blake; Iacone, Roberto; Certa, Ulrich; Singer, Thomas; Ebeling, Martin; Prunotto, Marco

2017-05-18

Today, novel therapeutics are identified in an environment which is intrinsically different from the clinical context in which they are ultimately evaluated. Using molecular phenotyping and an in vitro model of diabetic cardiomyopathy, we show that by quantifying pathway reporter gene expression, molecular phenotyping can cluster compounds based on pathway profiles and dissect associations between pathway activities and disease phenotypes simultaneously. Molecular phenotyping was applicable to compounds with a range of binding specificities and triaged false positives derived from high-content screening assays. The technique identified a class of calcium-signaling modulators that can reverse disease-regulated pathways and phenotypes, which was validated by structurally distinct compounds of relevant classes. Our results advocate for application of molecular phenotyping in early drug discovery, promoting biological relevance as a key selection criterion early in the drug development cascade. Copyright © 2017 Elsevier Ltd. All rights reserved.

Optimization of 2-Anilino 4-Amino Substituted Quinazolines into Potent Antimalarial Agents with Oral in Vivo Activity.

PubMed

Gilson, Paul R; Tan, Cyrus; Jarman, Kate E; Lowes, Kym N; Curtis, Joan M; Nguyen, William; Di Rago, Adrian E; Bullen, Hayley E; Prinz, Boris; Duffy, Sandra; Baell, Jonathan B; Hutton, Craig A; Jousset Subroux, Helene; Crabb, Brendan S; Avery, Vicky M; Cowman, Alan F; Sleebs, Brad E

2017-02-09

Novel antimalarial therapeutics that target multiple stages of the parasite lifecycle are urgently required to tackle the emerging problem of resistance with current drugs. Here, we describe the optimization of the 2-anilino quinazoline class as antimalarial agents. The class, identified from publicly available antimalarial screening data, was optimized to generate lead compounds that possess potent antimalarial activity against P. falciparum parasites comparable to the known antimalarials, chloroquine and mefloquine. During the optimization process, we defined the functionality necessary for activity and improved in vitro metabolism and solubility. The resultant lead compounds possess potent activity against a multidrug resistant strain of P. falciparum and arrest parasites at the ring phase of the asexual stage and also gametocytogensis. Finally, we show that the lead compounds are orally efficacious in a 4 day murine model of malaria disease burden.

Molecular and isotopic analyses of the hydroxy acids, dicarboxylic acids, and hydroxydicarboxylic acids of the Murchison meteorite

NASA Astrophysics Data System (ADS)

Cronin, J. R.; Pizzarello, S.; Epstein, S.; Krishnamurthy, R. V.

1993-10-01

The hydroxymonocarboxylic acids, dicarboxylic acids, and hydroxydicarboxylic acids of the Murchison meteorite were analyzed as their tert-butyldimethylsilyl derivatives using combined gas chromatography-mass spectrometry. The hydroxydicarboxylic acids have not been found previously in meteorites. Each class of compounds is numerous with carbon chains up to C8 or C9 and many, if not all, chain and substitution position isomers represented at each carbon number. The alpha-hydroxycarboxylic acids and alpha-hydroxydicarboxylic acids correspond structurally to many of the known meteoritic alpha-aminocarboxylic acids and alpha-aminodicarboxylic acids, a fact that supports the proposal that a Strecker synthesis was involved in the formation of both classes of compounds. Isotopic analyses show these acids to be D-rich relative to terrestrial organic compounds, as expected; however, the hydroxy acids appear to be isotopically lighter than the amino acids with respect to both carbon and hydrogen.

Best antihypertensive strategies to improve blood pressure control in Latin America: position of the Latin American Society of Hypertension.

PubMed

Coca, Antonio; López-Jaramillo, Patricio; Thomopoulos, Costas; Zanchetti, Alberto

2018-02-01

: Evidence from randomized trials has shown that effective treatment with blood pressure (BP)-lowering medications reduces the risk of cardiovascular morbidity and mortality in patients with hypertension. Therefore, hypertension control and prevention of subsequent morbidity and mortality should be achievable for all patients worldwide. However, many people in Latin America remain undiagnosed, untreated or have inadequately controlled BP, even where this is access to health systems. Barriers to hypertension control in low-income countries include difficulties in transportation to health services; inappropriate opening hours; difficulties in making clinic appointments; inaccessible healthcare facilities, lack of insurance and high treatment costs. After a review of the best recent available evidence on the efficacy and tolerability of antihypertensive drugs and strategies, the Latin American Society of Hypertension experts conclude that all major classes of BP-lowering drugs be available to hypertensive patients, because all have been shown to reduce major cardiovascular outcomes compared with placebo, and have shown to be associated with a comparable risk of major cardiovascular events and mortality when compared between classes. Within each class, no evidence whatsoever is available to show that one compound is more effective than another in outcome prevention. Therefore, the selection of individual drugs may be based mainly on the capacity of Latin American governments to obtain the lowest prices of the different molecules manufactured by companies with high production quality standards.

Maximizing Safety, Social Support, and Participation in Walking/Jogging/Running Classes

ERIC Educational Resources Information Center

Consolo, Kitty A.

2007-01-01

Physical education instructors who teach high school or college walking/jogging/running classes, or who include walking or running as a segment of a wellness class, face a particular challenge in trying to meet each student's individual fitness needs while ensuring safety. This article provides strategies for effectively meeting individual needs…

Class categories and the subjective dimension of class: the case of Denmark.

PubMed

Harrits, Gitte Sommer; Pedersen, Helene Helboe

2018-03-01

Class relations have been proven to affect various aspects of social life, even in modern individualized societies. However, following claims on individualization and the so-called 'death of class' thesis, studying the subjective dimension of class - that is, the way individuals perceive of class relations and their own position within them - has gone out of style. We argue that even in equalized societies, subjective class perceptions may still influence attitudes and behaviour as they evolve to fit modern class relations. To explore the existence as well as structure and content of perceived social classes, this article investigates how people describe society and social groups in focus group discussions. We find that groups in different positions in terms of education and economy all tend to apply hierarchical class categories to describe Danish society, which is normally seen as one of the most equal societies and political systems in the world. In addition, we find that economic resources serve as a baseline for the hierarchical ordering, often supplemented with notions of education, lifestyle and/or occupational profile. Even though people are somewhat uncomfortable with the notion of class, their descriptions of Danish society and classes are surprisingly similar within and across groups. We conclude that not only do class relations matter; people are also highly aware of the existing classes and able to position themselves and others according to their notion of classes. © London School of Economics and Political Science 2017.

Experiential or Material Purchases? Social Class Determines Purchase Happiness.

PubMed

Lee, Jacob C; Hall, Deborah L; Wood, Wendy

2018-05-01

Which should people buy to make themselves happy: experiences or material goods? The answer depends in part on the level of resources already available in their lives. Across multiple studies using a range of methodologies, we found that individuals of higher social class, whose abundant resources make it possible to focus on self-development and self-expression, were made happier by experiential over material purchases. No such experiential advantage emerged for individuals of lower social class, whose lesser resources engender concern with resource management and wise use of limited finances. Instead, lower-class individuals were made happier from material purchases or were equally happy from experiential and material purchases.

Social class, sense of control, and social explanation.

PubMed

Kraus, Michael W; Piff, Paul K; Keltner, Dacher

2009-12-01

Lower social class is associated with diminished resources and perceived subordinate rank. On the basis of this analysis, the authors predicted that social class would be closely associated with a reduced sense of personal control and that this association would explain why lower class individuals favor contextual over dispositional explanations of social events. Across 4 studies, lower social class individuals, as measured by subjective socioeconomic status (SES), endorsed contextual explanations of economic trends, broad social outcomes, and emotion. Across studies, the sense of control mediated the relation between subjective SES and contextual explanations, and this association was independent of objective SES, ethnicity, political ideology, and self-serving biases. Finally, experimentally inducing a higher sense of control attenuated the tendency for lower subjective SES individuals to make more contextual explanations (Study 4). Implications for future research on social class as well as theoretical distinctions between objective SES and subjective SES are discussed.

"Pretty Lights" and Maths! Increasing Student Engagement and Enhancing Learning through the Use of Electronic Voting Systems

ERIC Educational Resources Information Center

King, Samuel O.; Robinson, Carol L.

2009-01-01

University classes in Mathematics are traditionally perceived to be uninspiring and devoid of active student-lecturer communication. Large undergraduate classes further compound the difficulty of engaging students and enabling viable student-lecturer feedback. At the Mathematics Education Centre, Loughborough University, some staff members have…

Ribosomally synthesized and post-translationally modified peptide natural products: overview and recommendations for a universal nomenclature

PubMed Central

Arnison, Paul G.; Bibb, Mervyn J.; Bierbaum, Gabriele; Bowers, Albert A.; Bugni, Tim S.; Bulaj, Grzegorz; Camarero, Julio A.; Campopiano, Dominic J.; Challis, Gregory L.; Clardy, Jon; Cotter, Paul D.; Craik, David J.; Dawson, Michael; Dittmann, Elke; Donadio, Stefano; Dorrestein, Pieter C.; Entian, Karl-Dieter; Fischbach, Michael A.; Garavelli, John S.; Göransson, Ulf; Gruber, Christian W.; Haft, Daniel H.; Hemscheidt, Thomas K.; Hertweck, Christian; Hill, Colin; Horswill, Alexander R.; Jaspars, Marcel; Kelly, Wendy L.; Klinman, Judith P.; Kuipers, Oscar P.; Link, A. James; Liu, Wen; Marahiel, Mohamed A.; Mitchell, Douglas A.; Moll, Gert N.; Moore, Bradley S.; Müller, Rolf; Nair, Satish K.; Nes, Ingolf F.; Norris, Gillian E.; Olivera, Baldomero M.; Onaka, Hiroyasu; Patchett, Mark L.; Piel, Joern; Reaney, Martin J. T.; Rebuffat, Sylvie; Ross, R. Paul; Sahl, Hans-Georg; Schmidt, Eric W.; Selsted, Michael E.; Severinov, Konstantin; Shen, Ben; Sivonen, Kaarina; Smith, Leif; Stein, Torsten; Süssmuth, Roderich D.; Tagg, John R.; Tang, Gong-Li; Truman, Andrew W.; Vederas, John C.; Walsh, Christopher T.; Walton, Jonathan D.; Wenzel, Silke C.; Willey, Joanne M.; van der Donk, Wilfred A.

2014-01-01

This review presents recommended nomenclature for the biosynthesis of ribosomally synthesized and post-translationally modified peptides (RiPPs), a rapidly growing class of natural products. The current knowledge regarding the biosynthesis of the >20 distinct compound classes is also reviewed, and commonalities are discussed. PMID:23165928

Serendipitous Discovery of α-Hydroxyalkyl Esters as β-Lactamase Substrates†

PubMed Central

Pelto, Ryan B.; Pratt, R. F.

2010-01-01

O-(1-Carboxy-1-alkyloxycarbonyl) hydroxamates were found to spontaneously decarboxylate in aqueous neutral buffer to form O-(2-hydroxyalkylcarbonyl) hydroxamates. While the former molecules do not react rapidly with serine β-lactamases, the latter are quite good substrates of representative classes A and C, but not D, enzymes, and particularly of a class C enzyme. The enzymes catalyze hydrolysis of these compounds to a mixture of the α-hydroxyacid and hydroxamate. Analogous compounds containing aryloxy leaving groups rather that hydroxamates are also substrates. Structure-activity experiments showed that the α-hydroxyl group was required for any substantial substrate activity. Although both D- and L-α-hydroxy acid derivatives were substrates, the former were preferred. The response of the class C activity to pH and to alternative nucleophiles (methanol and D-phenylalanine) suggested that the same active site functional groups participated in catalysis as for classical substrates. Molecular modeling was employed to explore how the α-hydroxy group might interact with the class C β-lactamase active site. Incorporation of the α-hydroxyalkyl moiety into novel inhibitors will be of considerable interest. PMID:21087009

Pesticide exposure and risk of Parkinson's disease: A family-based case-control study

PubMed Central

Hancock, Dana B; Martin, Eden R; Mayhew, Gregory M; Stajich, Jeffrey M; Jewett, Rita; Stacy, Mark A; Scott, Burton L; Vance, Jeffery M; Scott, William K

2008-01-01

Background Pesticides and correlated lifestyle factors (e.g., exposure to well-water and farming) are repeatedly reported risk factors for Parkinson's disease (PD), but few family-based studies have examined these relationships. Methods Using 319 cases and 296 relative and other controls, associations of direct pesticide application, well-water consumption, and farming residences/occupations with PD were examined using generalized estimating equations while controlling for age-at-examination, sex, cigarette smoking, and caffeine consumption. Results Overall, individuals with PD were significantly more likely to report direct pesticide application than their unaffected relatives (odds ratio = 1.61; 95% confidence interval, 1.13–2.29). Frequency, duration, and cumulative exposure were also significantly associated with PD in a dose-response pattern (p ≤ 0.013). Associations of direct pesticide application did not vary by sex but were modified by family history of PD, as significant associations were restricted to individuals with no family history. When classifying pesticides by functional type, both insecticides and herbicides were found to significantly increase risk of PD. Two specific insecticide classes, organochlorines and organophosphorus compounds, were significantly associated with PD. Consuming well-water and living/working on a farm were not associated with PD. Conclusion These data corroborate positive associations of broadly defined pesticide exposure with PD in families, particularly for sporadic PD. These data also implicate a few specific classes of pesticides in PD and thus emphasize the need to consider a more narrow definition of pesticides in future studies. PMID:18373838

Antimicrobial activities of natural antimicrobial compounds against susceptible and antibiotic-resistant pathogens in the absence and presence of food

USDA-ARS?s Scientific Manuscript database

In an effort to improve microbial food safety, we are studying the antimicrobial activities of different classes of natural compounds including plant essential oils, apple, grape, olive, and tea extracts, bioactive components, and seashell-derived chitosans against multiple foodborne pathogens in cu...

Heterologous expression of tri5 gene in Trichoderma harzianum: Effect of trichodiene production on Trichoderma environmental interactions

USDA-ARS?s Scientific Manuscript database

Terpenes form a large class of compounds that have a variety of roles in mediating antagonistic and beneficial interactions among organisms. The trichothecenes are phytotoxic sesquiterpenoid compounds that have been extensively studied, mainly in the genus Fusarium, that can act as virulence factors...

EMISSION OF ORGANIC HAZARDOUS AIR POLLUTANTS FROM THE COMBUSION OF PULVERIZED COAL IN A SMALL-SCALE COMBUSTOR

EPA Science Inventory

The emissions of hazardous air pollutants (HAPs) from the combustion of pulverized coal have become an important issue in light of the requirements of Title I11 of the 1990 Clean Air Act Amendments, which impose emission limits on 189 compounds and compound classes. Although pre...

SPECIATION OF NON-PESTICIDAL ORGANOTIN COMPOUNDS USING GAS CHROMATOGRAPHY WITH INDUCTIVELY COUPLED PLASMA-MASS SPECTROMETRY

EPA Science Inventory

Organotins can be classified into a broad class of compounds referred to as endocrine disruptors and are presently being used in many applications such as UV stabilizers in polyvinyl chloride (PVC) pipes, antifoulants in marine paints, and as fungicides to name a few. The organo...

λ5-Phosphorus-Containing α-Diazo Compounds: A Valuable Tool for Accessing Phosphorus-Functionalized Molecules.

PubMed

Marinozzi, Maura; Pertusati, Fabrizio; Serpi, Michaela

2016-11-23

The compounds characterized by the presence of a λ 5 -phosphorus functionality at the α-position with respect to the diazo moiety, here referred to as λ 5 -phosphorus-containing α-diazo compounds (PCDCs), represent a vast class of extremely versatile reagents in organic chemistry and are particularly useful in the preparation of phosphonate- and phosphinoxide-functionalized molecules. Indeed, thanks to the high reactivity of the diazo moiety, PCDCs can be induced to undergo a wide variety of chemical transformations. Among them are carbon-hydrogen, as well as heteroatom-hydrogen insertion reactions, cyclopropanation, ylide formation, Wolff rearrangement, and cycloaddition reactions. PCDCs can be easily prepared from readily accessible precursors by a variety of different methods, such as diazotization, Bamford-Stevens-type elimination, and diazo transfer reactions. This evidence along with their relative stability and manageability make them appealing tools in organic synthesis. This Review aims to demonstrate the ongoing utility of PCDCs in the modern preparation of different classes of phosphorus-containing compounds, phosphonates, in particular. Furthermore, to address the lack of precedent collective papers, this Review also summarizes the methods for PCDCs preparation.

Utilization of Boron Compounds for the Modification of Suberoyl Anilide Hydroxamic Acid as Inhibitor of Histone Deacetylase Class II Homo sapiens

PubMed Central

Bakri, Ridla; Parikesit, Arli Aditya; Satriyanto, Cipta Prio; Kerami, Djati; Tambunan, Usman Sumo Friend

2014-01-01

Histone deacetylase (HDAC) has a critical function in regulating gene expression. The inhibition of HDAC has developed as an interesting anticancer research area that targets biological processes such as cell cycle, apoptosis, and cell differentiation. In this study, an HDAC inhibitor that is available commercially, suberoyl anilide hydroxamic acid (SAHA), has been modified to improve its efficacy and reduce the side effects of the compound. Hydrophobic cap and zinc-binding group of these compounds were substituted with boron-based compounds, whereas the linker region was substituted with p-aminobenzoic acid. The molecular docking analysis resulted in 8 ligands with ΔG binding value more negative than the standards, SAHA and trichostatin A (TSA). That ligands were analyzed based on the nature of QSAR, pharmacological properties, and ADME-Tox. It is conducted to obtain a potent inhibitor of HDAC class II Homo sapiens. The screening process result gave one best ligand, Nova2 (513246-99-6), which was then further studied by molecular dynamics simulations. PMID:25214833

Biomolecules and Natural Medicine Preparations: Analysis of New Sources of Bioactive Compounds from Ribes and Rubus spp. Buds.

PubMed

Donno, Dario; Mellano, Maria Gabriella; Cerutti, Alessandro Kim; Beccaro, Gabriele Loris

2016-02-05

It is well known that plants are important sources for the preparation of natural remedies as they contain many biologically active compounds. In particular, polyphenols, terpenic compounds, organic acids, and vitamins are the most widely occurring groups of phytochemicals. Some endemic species may be used for the production of herbal preparations containing phytochemicals with significant bioactivity, as antioxidant activity and anti-inflammatory capacities, and health benefits. Blackberry sprouts and blackcurrant buds are known to contain appreciable levels of bioactive compounds, including flavonols, phenolic acids, monoterpenes, vitamin C, and catechins, with several clinical effects. The aim of this research was to perform an analytical study of blackcurrant and blackberry bud-preparations, in order to identify and quantify the main biomarkers, obtaining a specific phytochemical fingerprint to evaluate the single botanical class contribution to total phytocomplex and relative bioactivity, using a High Performance Liquid Chromatograph-Diode Array Detector; the same analyses were performed both on the University laboratory and commercial preparations. Different chromatographic methods were used to determine concentrations of biomolecules in the preparations, allowing for quantification of statistically significant differences in their bioactive compound content both in the case of Ribes nigrum and Rubus cultivated varieties at different harvest stages. In blackcurrant bud-extracts the most important class was organic acids (50.98%) followed by monoterpenes (14.05%), while in blackberry preparations the main bioactive classes were catechins (50.06%) and organic acids (27.34%). Chemical, pharmaceutical and agronomic-environmental knowledge could be important for obtaining label certifications for the valorization of specific genotypes, with high clinical and pharmaceutical value: this study allowed to develop an effective tool for the natural preparation quality control and bioactivity evaluation through the chemical fingerprinting of bud preparations.

Novel ocular antihypertensive compounds in clinical trials

PubMed Central

Chen, June; Runyan, Stephen A; Robinson, Michael R

2011-01-01

Introduction: Glaucoma is a multifactorial disease characterized by progressive optic nerve injury and visual field defects. Elevated intraocular pressure (IOP) is the most widely recognized risk factor for the onset and progression of open-angle glaucoma, and IOP-lowering medications comprise the primary treatment strategy. IOP elevation in glaucoma is associated with diminished or obstructed aqueous humor outflow. Pharmacotherapy reduces IOP by suppressing aqueous inflow and/or increasing aqueous outflow. Purpose: This review focuses on novel non-FDA approved ocular antihypertensive compounds being investigated for IOP reduction in ocular hypertensive and glaucoma patients in active clinical trials within approximately the past 2 years. Methods: The mode of IOP reduction, pharmacology, efficacy, and safety of these new agents were assessed. Relevant drug efficacy and safety trials were identified from searches of various scientific literature databases and clinical trial registries. Compounds with no specified drug class, insufficient background information, reformulations, and fixed-combinations of marketed drugs were not considered. Results: The investigational agents identified comprise those that act on the same targets of established drug classes approved by the FDA (ie, prostaglandin analogs and β-adrenergic blockers) as well as agents belonging to novel drug classes with unique mechanisms of action. Novel targets and compounds evaluated in clinical trials include an actin polymerization inhibitor (ie, latrunculin), Rho-associated protein kinase inhibitors, adenosine receptor analogs, an angiotensin II type 1 receptor antagonist, cannabinoid receptor agonists, and a serotonin receptor antagonist. Conclusion: The clinical value of novel compounds for the treatment of glaucoma will depend ultimately on demonstrating favorable efficacy and benefit-to-risk ratios relative to currently approved prostaglandin analogs and β-blockers and/or having complementary modes of action. PMID:21629573

S-glutathionyl-(chloro)hydroquinone reductases: a new class of glutathione transferases functioning as oxidoreductases

PubMed Central

Belchik, Sara M.; Xun, Luying

2011-01-01

Glutathione transferases (GSTs) are best known for transferring glutathione (GSH) to hydrophobic organic compounds, making the conjugates more soluble. However, the omega-class GSTs of animals and the lambda-class GSTs and dehydroascorbate reductases (DHARs) of plants have little or no activity for GSH transfer. Instead, they catalyze GSH-dependent oxidoreductions. The lambda-class GSTs reduce disulfide bonds, the DHARs reduce the disulfide bonds and dehydroascorbate, and the omega-class GSTs can reduce more substrates, including disulfide bonds, dehydroascorbate, and dimethylarsinate. Glutathionyl-(chloro)hydroquinone reductases (GS-HQRs) are the newest class of GSTs that mainly catalyze oxidoreductions. Besides the activities of the other three classes, GS-HQRs also reduce GS-hydroquinones, including GS-trichloro-p-hydroquinone, GS-dichloro-p-hydroquinone, GS-2-hydroxy-p-hydroquinone, and GS-p-hydroquinone. They are conserved and widely distributed in bacteria, fungi, protozoa, and plants, but not in animals. The four classes are phylogenetically more related to each other than to other GSTs, and they share a Cys-Pro motif at the GSH-binding site. Hydroquinones are metabolic intermediates of certain aromatic compounds. They can be auto-oxidized by O2 to benzoquinones, which spontaneously react with GSH to form GS-hydroquinones via Michael’s addition. GS-HQRs are expected to channel GS-hydroquinones, formed spontaneously or enzymatically, back to hydroquinones. When the released hydroquinones are intermediates of metabolic pathways, GS-HQRs play a maintenance role for the pathways. Further, the common presence of GS-HQRs in plants, green algae, cyanobacteria, and halobacteria suggest a beneficial role in the light-using organisms. PMID:21425927

Achiral and Chiral Separations Using Micellar Electrokinetic Chromatography, Polyelectrolyte Multilayer Coatings, and Mixed Mode Separation Techniques with Molecular Micelles

PubMed Central

Luces, Candace A.; Warner, Isiah M.

2014-01-01

Mixed mode separation using a combination of micellar electrokinetic chromatography (MEKC) and polyelectrolyte multilayer (PEM) coatings is herein reported for the separation of achiral and chiral analytes. Many analytes are difficult to separate by MEKC and PEM coatings alone. Therefore, the implementation of a mixed mode separation provides several advantages for overcoming the limitations of these well-established methods. In this study, it was observed that achiral separations using MEKC and PEM coatings individually resulted in partial resolution of 8 very similar aryl ketones when the molecular micelle (sodium poly(N-undecanoyl-l-glycinate) (poly-SUG)) concentration was varied from 0.25% – 1.00% (w/v) and the bilayer number varied from 2 – 4. However, when mixed mode separation was introduced, baseline resolution was achieved for all 8 analytes. In the case of chiral separations, temazepam, aminoglutethimide, benzoin, benzoin methyl ether and coumachlor were separated using the three separation techniques. For chiral separations, the chiral molecular micelle, sodium poly(N-undecanoyl-l-leucylvalinate) (poly-l-SULV), was employed at concentrations of 0.25–1.50% (w/v) for both MEKC and PEM coatings. Overall, the results revealed partial separation with MEKC and PEM coatings individually. However, mixed mode separation enabled baseline separation of each chiral mixture. The separation of achiral and chiral compounds from different compound classes demonstrates the versatility of this mixed mode approach. PMID:20155738

Analyzing Responses of Chemical Sensor Arrays

NASA Technical Reports Server (NTRS)

Zhou, Hanying

2007-01-01

NASA is developing a third-generation electronic nose (ENose) capable of continuous monitoring of the International Space Station s cabin atmosphere for specific, harmful airborne contaminants. Previous generations of the ENose have been described in prior NASA Tech Briefs issues. Sensor selection is critical in both (prefabrication) sensor material selection and (post-fabrication) data analysis of the ENose, which detects several analytes that are difficult to detect, or that are at very low concentration ranges. Existing sensor selection approaches usually include limited statistical measures, where selectivity is more important but reliability and sensitivity are not of concern. When reliability and sensitivity can be major limiting factors in detecting target compounds reliably, the existing approach is not able to provide meaningful selection that will actually improve data analysis results. The approach and software reported here consider more statistical measures (factors) than existing approaches for a similar purpose. The result is a more balanced and robust sensor selection from a less than ideal sensor array. The software offers quick, flexible, optimal sensor selection and weighting for a variety of purposes without a time-consuming, iterative search by performing sensor calibrations to a known linear or nonlinear model, evaluating the individual sensor s statistics, scoring the individual sensor s overall performance, finding the best sensor array size to maximize class separation, finding optimal weights for the remaining sensor array, estimating limits of detection for the target compounds, evaluating fingerprint distance between group pairs, and finding the best event-detecting sensors.

Reaction capacity characterization of shallow sedimentary deposits in geologically different regions of the Netherlands.

PubMed

Griffioen, Jasper; Klein, Janneke; van Gaans, Pauline F M

2012-01-01

Quantitative insight into the reaction capacity of porous media is necessary to assess the buffering capacity of the subsurface against contaminant input via groundwater recharge. Here, reaction capacity is to be considered as a series of geochemical characteristics that control acid/base conditions, redox conditions and sorption intensity. Using existing geochemical analyses, a statistical regional assessment of the reaction capacity was performed for two geologically different areas in the Netherlands. The first area is dominated by Pleistocene aquifer sediments only, in the second area a heterogeneous Holocene confining layer is found on top of the Pleistocene aquifer sediments. Within both areas, two or more regions can be distinguished that have a distinctly different geological build-up of the shallow subsurface. The reactive compounds considered were pyrite, reactive Fe other than pyrite, sedimentary organic matter, carbonate and clay content. This characterization was complemented by the analysis of a dataset of samples newly collected, from two regions within the Pleistocene area, where the sedimentary facies of samples was additionally distinguished. The statistical assessment per area was executed at the levels of region, geological formation and lithology class. For both areas, significant differences in reaction capacities were observed between: 1. different lithology classes within a geological formation in a single region, 2. identical geological formations in different regions and 3. various geological formations within a single region. Here, the reaction capacity is not only controlled by lithostratigraphy, but also by post-depositional diagenesis and paleohydrology. Correlation coefficients among the reactive compounds were generally higher for sand than for clay, but insufficiently high to allow good estimation of reactive compounds from each other. For the sandy Pleistocene aquifer sediments, the content of reactive compounds was frequently observed to be below detection limits. From this, future characterization of sediment reaction capacity is best performed at the sublevel of lithology class, being the geochemically near-uniform unit identifiable for individual geological formations within geographic regions. Additional subdivision on facies provides particular insight in the spatial entity where relatively high reaction capacities may be encountered. To obtain quantitative insight into the reaction capacity of aquifer sediments, non-sandy minor subunits should be well characterised on their reaction capacity as well as their spatial occurrence in the geological formations. A straightforward approach is presented in which the regional statistics on geochemical reactivity become combined with a 3-dimensional geological voxel model. This results into 3-dimensional data fields on reactivity, which are suitable for, for example, groundwater transport modelling. The sedimentological architecture of the deposits becomes well maintained in the geochemical data field, which is an advantage in itself. Copyright © 2011 Elsevier B.V. All rights reserved.

The complexity of intestinal permeability: Assigning the correct BCS classification through careful data interpretation.

PubMed

Zur, Moran; Hanson, Allison S; Dahan, Arik

2014-09-30

While the solubility parameter is fairly straightforward when assigning BCS classification, the intestinal permeability (Peff) is more complex than generally recognized. In this paper we emphasize this complexity through the analysis of codeine, a commonly used antitussive/analgesic drug. Codeine was previously classified as a low-permeability compound, based on its lower LogP compared to metoprolol, a marker for the low-high permeability class boundary. In contrast, high fraction of dose absorbed (Fabs) was reported for codeine, which challenges the generally recognized Peff-Fabs correlation. The purpose of this study was to clarify this ambiguity through elucidation of codeine's BCS solubility/permeability class membership. Codeine's BCS solubility class was determined, and its intestinal permeability throughout the small intestine was investigated, both in vitro and in vivo in rats. Codeine was found to be unequivocally a high-solubility compound. All in vitro studies indicated that codeine's permeability is higher than metoprolol's. In vivo studies in rats showed similar permeability for both drugs throughout the entire small-intestine. In conclusion, codeine was found to be a BCS Class I compound. No Peff-Fabs discrepancy is involved in its absorption; rather, it reflects the risk of assigning BCS classification based on merely limited physicochemical characteristics. A thorough investigation using multiple experimental methods is prudent before assigning a BCS classification, to avoid misjudgment in various settings, e.g., drug discovery, formulation design, drug development and regulation. Copyright © 2013 Elsevier B.V. All rights reserved.

The low/high BCS permeability class boundary: physicochemical comparison of metoprolol and labetalol.

PubMed

Zur, Moran; Gasparini, Marisa; Wolk, Omri; Amidon, Gordon L; Dahan, Arik

2014-05-05

Although recognized as overly conservative, metoprolol is currently the common low/high BCS permeability class boundary reference compound, while labetalol was suggested as a potential alternative. The purpose of this study was to identify the various characteristics that the optimal marker should exhibit, and to investigate the suitability of labetalol as the permeability class reference drug. Labetalol's BCS solubility class was determined, and its physicochemical properties and intestinal permeability were thoroughly investigated, both in vitro and in vivo in rats, considering the complexity of the whole of the small intestine. Labetalol was found to be unequivocally a high-solubility compound. In the pH range throughout the small intestine (6.5-7.5), labetalol exhibited pH-dependent permeability, with higher permeability at higher pH values. While in vitro octanol-buffer partitioning (Log D) values of labetalol were significantly higher than those of metoprolol, the opposite was evident in the in vitro PAMPA permeability assay. The results of the in vivo perfusion studies in rats lay between the two contradictory in vitro studies; metoprolol was shown to have moderately higher rat intestinal permeability than labetalol. Theoretical distribution of the ionic species of the drugs was in corroboration with the experimental in vitro and the in vivo data. We propose three characteristics that the optimal permeability class reference drug should exhibit: (1) fraction dose absorbed in the range of 90%; (2) the optimal marker drug should be absorbed largely via passive transcellular permeability, with no/negligible carrier-mediated active intestinal transport (influx or efflux); and (3) the optimal marker drug should preferably be nonionizable. The data presented in this paper demonstrate that neither metoprolol nor labetalol can be regarded as optimal low/high-permeability class boundary standard. While metoprolol is too conservative due to its complete absorption, labetalol has been shown to be a substrate for P-gp-mediated efflux transport, and both drugs exhibit significant segmental-dependent permeability along the gastrointestinal tract. Nevertheless, the use of metoprolol as the marker compound does not carry a risk of bioinequivalence: Peff value similar to or higher than metoprolol safely indicates high-permeability classification. On the other hand, a more careful data analysis is needed if labetalol is used as the reference compound.

Replacement Non-Toxic Sealants for Standard Chromated Sealants

DTIC Science & Technology

2005-02-01

material’s mechanical or physical properties and resistance to degradation. As sealant formulations for the Class B-2 worklife were developed by PRC...results ofthis testing, Class B-1I2 and C-12 worklife materials were formulated and are being tested. In addition to the testing that UDRI conducted, two...successfully accomplished in this program. An optimized Class B-2 worklife of the sealant compound designated RW3758-71, Lot no. RT0946, completed

People with stroke spend more time in active task practice, but similar time in walking practice, when physiotherapy rehabilitation is provided in circuit classes compared to individual therapy sessions: an observational study.

PubMed

English, Coralie; Hillier, Susan; Kaur, Gurpreet; Hundertmark, Laura

2014-03-01

Do people with stroke spend more time in active task practice during circuit class therapy sessions versus individual physiotherapy sessions? Do people with stroke practise different tasks during circuit class therapy sessions versus individual physiotherapy sessions? Prospective, observational study. Twenty-nine people with stroke in inpatient rehabilitation settings. Individual therapy sessions and circuit class therapy sessions provided within a larger randomised controlled trial. Seventy-nine therapy sessions were video-recorded and the footage was analysed for time spent engaged in various categories of activity. In a subsample of 28 videos, the number of steps taken by people with stroke per therapy session was counted. Circuit class therapy sessions were of a longer duration (mean difference 38.0minutes, 95% CI 29.9 to 46.1), and participants spent more time engaged in active task practice (mean difference 23.8minutes, 95% CI 16.1 to 31.4) compared with individual sessions. A greater percentage of time in circuit class therapy sessions was spent practising tasks in sitting (mean difference 5.3%, 95% CI 2.4 to 8.2) and in sit-to-stand practice (mean difference 2.7%, 95% CI 1.4 to 4.1), and a lower percentage of time in walking practice (mean difference 19.1%, 95% CI 10.0 to 28.1) compared with individual sessions. PARTICIPANTS took an average of 371 steps (SD 418) during therapy sessions and this did not differ significantly between group and individual sessions. People with stroke spent more time in active task practice, but a similar amount of time in walking practice when physiotherapy was offered in circuit class therapy sessions versus individual therapy sessions. There is a need for effective strategies to increase the amount of walking practice during physiotherapy sessions for people after stroke. Copyright © 2014 Australian Physiotherapy Association. Published by Elsevier B.V. All rights reserved.

Purification of antilisterial bacteriocins.

PubMed

Berjeaud, Jean-Marc; Cenatiempo, Yves

2004-01-01

In recent years, numerous contamination outbreaks, involving various pathogens (i.e., Listeria and Salmonella), have increased concern over food preservation. Research efforts have focused on the discovery of new molecules targeting such foodborne pathogens and therefore able to inhibit and or kill them. Lactic acid bacteria (LAB) extensively used in fermented foods for thousands of years not only improve their flavor and texture but also inhibit pathogenic and spoilage microorganisms. LAB inhibitory activity is primarily owing to pH decrease and competition for substrates. Antagonistic activity of LAB also depends on secreted antimicrobial compounds with a poor selectivity, such as metabolic compounds (i.e., hydrogen peroxide, acetoin, and others) or more specific ones like bacteriocins. The latter are proteinaceous compounds, ribosomally synthesized and subsequently secreted by Gram-positive as well as Gram-negative bacteria. Their antimicrobial activity is generally restricted to strains phylogenetically related to the producers.A classification of bacteriocins produced by LAB was first proposed by Klaenhammer in 1993 and was modified by Nes et al. in 1996; class I and class II bacteriocins are the most abundant and thoroughly studied. Bacteriocins from both classes exhibit antilisterial activity. Class I bacteriocins, namely, lantibiotics, have been widely studied, and among them, nisin is used in many countries as a preservative in food products. These bacteriocins are characterized by the presence, in their primary structure, of post-translationally modified amino acid residues (i.e., lanthionine and methylanthionine) that are formed. Class II bacteriocins, containing three subclasses, consist of small peptides that do not bear any modified amino acid residue. The most studied subclass corresponds to class IIa, also termed anti-Listeria bacteriocins. These peptides share strong structural homologies in their N-terminal domain, with the presence of one disulfide bond and a net positive charge. Their C-terminal domain is more variable but appears quite hydrophobic. Moreover, some of these bacteriocins, namely, sakacin G, pediocin PA-1, enterocin A, coagulin, and divercin V41, are characterized by the presence of a second disulfide bond in the C-terminal region.

Identification and quantification of homologous series of compound in complex mixtures: autocovariance study of GC/MS chromatograms.

PubMed

Pietrogrande, Maria Chiara; Zampolli, Maria Grazia; Dondi, Francesco

2006-04-15

The paper describes a method for determining homologous classes of compounds in a multicomponent complex chromatogram obtained under programming elution conditions. The method is based on the computation of the autocovariance function of the experimental chromatogram (EACVF). The EACVF plot, if properly interpreted, can be regarded as a "class chromatogram" i.e., a virtual chromatogram formed by peaks whose positions and heights allow identification and quantification of the different homologous series, even if they are embedded in a random complex chromatogram. Theoretical models were developed to describe complex chromatograms displaying random retention pattern, ordered sequences or a combination of them. On the basis of theoretical autocovariance function, the properties of the chromatogram can be experimentally evaluated, under well-defined conditions: in particular, the two components of the chromatogram, ordered and random, can be identified. Moreover, the total number of single components (SCs) and the separated number of the SCs belonging to the random and ordered components can be determined, when the two components display the same concentration. If the mixture contains several homologous series with common frequency and different phase values, the number and identity of the different homologous series as well as the number of SCs belonging to each of them can be evaluated. Moreover, the power of the EACVF method can be magnified by applying it to the single ion monitoring (SIM) signals to selectively detect specific compound classes in order to identify the different homologous series. By this way, a full "decoding" of the complex multicomponent chromatogram is achieved. The method was validated on synthetic mixtures containing known amount of SCs belonging to homologous series of hydrocarbon, alcohols, ketones, and aromatic compounds in addition to other not structurally related SCs. The method was applied to both the total ion monitoring (TIC) and the SIM signals, to describe step by step the essence of the procedure. Moreover, the systematic use of both SIM and TIC can simplify the decoding procedure of complex chromatograms by singling out only specific compound classes or by confirming the identification of the different homologous series. The method was further applied to a sample containing unknown number of compounds and homologous series (a petroleum benzin, bp 140-160 degrees C): the results obtained were meaningful in terms of both the identified number of components and identified homologous series.

Characterization of Chemical Constituents of Human Sweat: A Study Based on Indian Population.

PubMed

Moulvi, Aafrinnaz; Minz, Pooja; Rath, Subrata; Ashma, Richa

2018-06-01

There is a strong evidence in the literature that human odor is unique to an individual; therefore, the focus of this study was to strengthen this evidence through the testing of sweat samples on unrelated individuals with the same ethnicity. Sweat samples were collected from 42 unrelated Indian males and females residing in the same city to determine the chemical constituents in human sweat. The volatile compounds of sweat were subsequently analyzed and identified using gas chromatography-mass spectrometry, and a National Institute of Standards and Technology library was used for individual profiling. A total of 78 compounds were identified in human sweat tested with 22 compounds found to be unique to the individual (frequency of occurrence one). A scent profile, or "chexmotype," unique to the sweat of each individual was obtained. This is the first extensive study on an Indian population with 36 new compounds detected in human sweat.

Sulfated steroids as natural ligands of mouse pheromone-sensing neurons.

PubMed

Nodari, Francesco; Hsu, Fong-Fu; Fu, Xiaoyan; Holekamp, Terrence F; Kao, Lung-Fa; Turk, John; Holy, Timothy E

2008-06-18

Among mice, pheromones and other social odor cues convey information about sex, social status, and identity; however, the molecular nature of these cues is essentially unknown. To identify these cues, we screened chromatographic fractions of female mouse urine for their ability to cause reproducible firing rate increases in the pheromone-detecting vomeronasal sensory neurons (VSNs) using multielectrode array (MEA) recording. Active compounds were found to be remarkably homogenous in their basic properties, with most being of low molecular weight, moderate hydrophobicity, low volatility, and possessing a negative electric charge. Purification and structural analysis of active compounds revealed multiple sulfated steroids, of which two were identified as sulfated glucocorticoids, including corticosterone 21-sulfate. Sulfatase-treated urine extracts lost >80% of their activity, indicating that sulfated compounds are the predominant VSN ligands in female mouse urine. As measured by MEA recording, a collection of 31 synthetic sulfated steroids triggered responses 30-fold more frequently than did a similarly sized stimulus set containing the majority of all previously reported VSN ligands. Collectively, VSNs detected all major classes of sulfated steroids, but individual neurons were sensitive to small variations in chemical structure. VSNs from both males and females detected sulfated steroids, but knock-outs for the sensory transduction channel TRPC2 did not detect these compounds. Urine concentrations of the two sulfated glucocorticoids increased many fold in stressed animals, indicating that information about physiological status is encoded by the urine concentration of particular sulfated steroids. These results provide an unprecedented characterization of the signals available for chemical communication among mice.

Sulfated steroids as natural ligands of mouse pheromone-sensing neurons

PubMed Central

Nodari, Francesco; Hsu, Fong-Fu; Fu, Xiaoyan; Holekamp, Terrence F.; Kao, Lung-Fa; Turk, John; Holy, Timothy E.

2009-01-01

Among mice, pheromones and other social odor cues convey information about sex, social status, and identity; however, the molecular nature of these cues is largely unknown. To identify these cues, we screened chromatographic fractions of female mouse urine for their ability to cause reproducible firing rate increases in the pheromone-detecting vomeronasal sensory neurons (VSNs) using multielectrode array (MEA) recording. Active compounds were found to be remarkably homogenous in their basic properties, with most being of low molecular weight, moderate hydrophobicity, low volatility, and possessing a negative electric charge. Purification and structural analysis of active compounds revealed multiple sulfated steroids, of which two were identified as sulfated glucocorticoids, including corticosterone 21-sulfate. Sulfatase-treated urine extracts lost more than 80% of their activity, indicating that sulfated compounds are the predominant VSN ligands in female mouse urine. As measured by MEA recording, a collection of 31 synthetic sulfated steroids triggered responses 30-fold more frequently than did a similarly-sized stimulus set containing the majority of all previously-reported VSN ligands. Collectively, VSNs detected all major classes of sulfated steroids, but individual neurons were sensitive to small variations in chemical structure. VSNs from both males and females detected sulfated steroids, but knockouts for the sensory transduction channel TRPC2 did not detect these compounds. Urine concentrations of the two sulfated glucocorticoids increased many-fold in stressed animals, indicating that information about physiological status is encoded by the urine concentration of particular sulfated steroids. These results provide an unprecedented characterization of the signals available for chemical communication among mice. PMID:18562612

Identification of Anxiety Sensitivity Classes and Clinical Cut-Scores in a Sample of Adult Smokers: Results from a Factor Mixture Model

PubMed Central

Allan, Nicholas P.; Raines, Amanda M.; Capron, Daniel W.; Norr, Aaron M.; Zvolensky, Michael J.; Schmidt, Norman B.

2014-01-01

Anxiety sensitivity (AS), a multidimensional construct, has been implicated in the development and maintenance of anxiety and related disorders. Recent evidence suggests that AS is a dimensional-categorical construct within individuals. Factor mixture modeling was conducted in a sample of 579 adult smokers (M age = 36.87 years, SD = 13.47) to examine the underlying structure. Participants completed the Anxiety Sensitivity Index-3 and were also given a Structured Clinical Interview for DSM-IV-TR. Three classes of individuals emerged, a high AS (5.2% of the sample), a moderate AS (19.0%), and a normative AS class (75.8%). A cut-score of 23 to identify high AS individuals, and a cut-score of 17 to identify moderate-to-high AS individuals were supported in this study. In addition, the odds of having a concurrent anxiety disorder (controlling for other Axis I disorders) were the highest in the high AS class and the lowest in the normative AS class. PMID:25128664

78 FR 77716 - Agency Information Collection Activities; Submission for OMB Review; Comment Request; Prohibited...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-24

... for OMB Review; Comment Request; Prohibited Transaction Class Exemption 1992-6: Sale of Individual...) titled, ``Prohibited Transaction Class Exemption 1992-6: Sale of Individual Life Insurance or Annuity... to the sale of individual life insurance or annuity contracts by a plan (PTE 1992-6). More...

A Qualitative Study of the Dislocated Working Class

ERIC Educational Resources Information Center

Fouad, Nadya A.; Cotter, Elizabeth W.; Carter, Laura; Bernfeld, Steven; Gray, India; Liu, Jane P.

2012-01-01

This qualitative study examines factors that influence the career decisions of dislocated workers. The research focuses on individuals identified as working class, as this group has been relatively ignored in past research compared to individuals from higher socioeconomic statuses. Participants include 13 individuals (10 females and 3 males)…

Optimization of an extraction protocol for organic matter from soils and sediments using high resolution mass spectrometry: selectivity and biases

NASA Astrophysics Data System (ADS)

Chu, R. K.; Tfaily, M. M.; Tolic, N.; Kyle, J. E.; Robinson, E. R.; Hess, N. J.; Paša-Tolić, L.

2015-12-01

Soil organic matter (SOM) is a complex mixture of above and belowground plant litter and microbial residues, and is a key reservoir for carbon (C) and nutrient biogeochemical cycling in different ecosystems. A limited understanding of the molecular composition of SOM prohibits the ability to routinely decipher chemical processes within soil and predict how terrestrial C fluxes will response to changing climatic conditions. Here, we present that the choice of solvent can be used to selectively extract different compositional fractions from SOM to either target a specific class of compounds or gain a better understanding of the entire composition of the soil sample using 12T Fourier transform ion cyclotron resonance mass spectrometry. Specifically, we found that hexane and chloroform were selective for lipid-like compounds with very low O:C ratios; water was selective for carbohydrates with high O:C ratios; acetonitrile preferentially extracts lignin, condensed structures, and tannin polyphenolic compounds with O:C > 0.5; methanol has higher selectivity towards lignin and lipid compounds characterized with relatively low O:C < 0.5. Hexane, chloroform, methanol, acetonitrile and water increase the number and types of organic molecules extracted from soil for a broader range of chemically diverse soil types. Since each solvent extracts a selective group of compounds, using a suite of solvents with varying polarity for analysis results in more comprehensive representation of the diversity of organic molecules present in soil and a better representation of the whole spectrum of available substrates for microorganisms. Moreover, we have developed a sequential extraction protocol that permits sampling diverse classes of organic compounds while minimizing ionization competition during ESI while increasing sample throughput and decreasing sample volume. This allowed us to hypothesize about possible chemical reactions relating classes of organic molecules that reflect abiotic and biotic processes impacting SOM composition.

Mentor Social Capital, Individual Agency and Working-Class Student Learning Outcomes: Revisiting the Structure/Agency Dialectic

ERIC Educational Resources Information Center

Lovett, Trevor William

2014-01-01

This investigation explores factors that contributed to the disparate learning identities of two white baby-boomer brothers from the same working-class family. The research, part of a broader phenomenological study into the influences of working-class masculinities and schooling offers an insight into the individual family members' differential…

Technology and Teaching: Promoting Active Learning Using Individual Response Technology in Large Introductory Psychology Classes

ERIC Educational Resources Information Center

Poirier, Christopher R.; Feldman, Robert S.

2007-01-01

Individual response technology (IRT), in which students use wireless handsets to communicate real-time responses, permits the recording and display of aggregated student responses during class. In comparison to a traditional class that did not employ IRT, students using IRT performed better on exams and held positive attitudes toward the…

Genotype-phenotype correlation and functional studies in patients with cystic fibrosis bearing CFTR complex alleles.

PubMed

Terlizzi, Vito; Castaldo, Giuseppe; Salvatore, Donatello; Lucarelli, Marco; Raia, Valeria; Angioni, Adriano; Carnovale, Vincenzo; Cirilli, Natalia; Casciaro, Rosaria; Colombo, Carla; Di Lullo, Antonella Miriam; Elce, Ausilia; Iacotucci, Paola; Comegna, Marika; Scorza, Manuela; Lucidi, Vincenzina; Perfetti, Anna; Cimino, Roberta; Quattrucci, Serena; Seia, Manuela; Sofia, Valentina Maria; Zarrilli, Federica; Amato, Felice

2017-04-01

The effect of complex alleles in cystic fibrosis (CF) is poorly defined for the lack of functional studies. To describe the genotype-phenotype correlation and the results of either in vitro and ex vivo studies performed on nasal epithelial cells (NEC) in a cohort of patients with CF carrying cystic fibrosis transmembrane conductance regulator ( CFTR ) complex alleles. We studied 70 homozygous, compound heterozygous or heterozygous for CFTR mutations: p.[Arg74Trp;Val201Met;Asp1270Asn], n=8; p.[Ile148Thr;Ile1023_Val1024del], n=5; p.[Arg117Leu;Leu997Phe], n=6; c.[1210-34TG[12];1210-12T[5];2930C>T], n=3; p.[Arg74Trp;Asp1270Asn], n=4; p.Asp1270Asn, n=2; p.Ile148Thr, n=6; p.Leu997Phe, n=36. In 39 patients, we analysed the CFTR gating activity on NEC in comparison with patients with CF (n=8) and carriers (n=4). Finally, we analysed in vitro the p.[Arg74Trp;Val201Met;Asp1270Asn] complex allele. The p.[Ile148Thr;Ile1023_Val1024del] caused severe CF in five compound heterozygous with a class I-II mutation. Their CFTR activity on NEC was comparable with patients with two class I-II mutations (mean 7.3% vs 6.9%). The p.[Arg74Trp;Asp1270Asn] and the p.Asp1270Asn have scarce functional effects, while p.[Arg74Trp;Val201Met;Asp1270Asn] caused mild CF in four of five subjects carrying a class I-II mutation in trans , or CFTR-related disorders (CFTR-RD) in three having in trans a class IV-V mutation. The p.[Arg74Trp;Val201Met;Asp1270Asn] causes significantly (p<0.001) higher CFTR activity compared with compound heterozygous for class I-II mutations. Furthermore, five of six compounds heterozygous with the p.[Arg117Leu;Leu997Phe] had mild CF, whereas the p.Leu997Phe, in trans with a class I-II CFTR mutation, caused CFTR-RD or a healthy status (CFTR activity: 21.3-36.9%). Finally, compounds heterozygous for the c.[1210-34TG[12];1210-12T[5];2930C>T] and a class I-II mutation had mild CF or CFTR-RD (gating activity: 18.5-19.0%). The effect of complex alleles partially depends on the mutation in trans . Although larger studies are necessary, the CFTR activity on NEC is a rapid contributory tool to classify patients with CFTR dysfunction. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Discovery of Novel Nonactive Site Inhibitors of the Prothrombinase Enzyme Complex.

PubMed

Kapoor, Karan; McGill, Nicole; Peterson, Cynthia B; Meyers, Harold V; Blackburn, Michael N; Baudry, Jerome

2016-03-28

The risk of serious bleeding is a major liability of anticoagulant drugs that are active-site competitive inhibitors targeting the Factor Xa (FXa) prothrombin (PT) binding site. The present work identifies several new classes of small molecule anticoagulants that can act as nonactive site inhibitors of the prothrombinase (PTase) complex composed of FXa and Factor Va (FVa). These new classes of anticoagulants were identified, using a novel agnostic computational approach to identify previously unrecognized binding pockets at the FXa-FVa interface. From about three million docking calculations of 281,128 compounds in a conformational ensemble of FXa heavy chains identified by molecular dynamics (MD) simulations, 97 compounds and their structural analogues were selected for experimental validation, through a series of inhibition assays. The compound selection was based on their predicted binding affinities to FXa and their ability to successfully bind to multiple protein conformations while showing selectivity for particular binding sites at the FXa/FVa interface. From these, thirty-one (31) compounds were experimentally identified as nonactive site inhibitors. Concentration-based assays further identified 10 compounds represented by four small-molecule families of inhibitors that achieve dose-independent partial inhibition of PTase activity in a nonactive site-dependent and self-limiting mechanism. Several compounds were identified for their ability to bind to protein conformations only seen during MD, highlighting the importance of accounting for protein flexibility in structure-based drug discovery approaches.

Boronated tartrolon antibiotic produced by symbiotic cellulose-degrading bacteria in shipworm gills.

PubMed

Elshahawi, Sherif I; Trindade-Silva, Amaro E; Hanora, Amro; Han, Andrew W; Flores, Malem S; Vizzoni, Vinicius; Schrago, Carlos G; Soares, Carlos A; Concepcion, Gisela P; Distel, Dan L; Schmidt, Eric W; Haygood, Margo G

2013-01-22

Shipworms are marine wood-boring bivalve mollusks (family Teredinidae) that harbor a community of closely related Gammaproteobacteria as intracellular endosymbionts in their gills. These symbionts have been proposed to assist the shipworm host in cellulose digestion and have been shown to play a role in nitrogen fixation. The genome of one strain of Teredinibacter turnerae, the first shipworm symbiont to be cultivated, was sequenced, revealing potential as a rich source of polyketides and nonribosomal peptides. Bioassay-guided fractionation led to the isolation and identification of two macrodioloide polyketides belonging to the tartrolon class. Both compounds were found to possess antibacterial properties, and the major compound was found to inhibit other shipworm symbiont strains and various pathogenic bacteria. The gene cluster responsible for the synthesis of these compounds was identified and characterized, and the ketosynthase domains were analyzed phylogenetically. Reverse-transcription PCR in addition to liquid chromatography and high-resolution mass spectrometry and tandem mass spectrometry revealed the transcription of these genes and the presence of the compounds in the shipworm, suggesting that the gene cluster is expressed in vivo and that the compounds may fulfill a specific function for the shipworm host. This study reports tartrolon polyketides from a shipworm symbiont and unveils the biosynthetic gene cluster of a member of this class of compounds, which might reveal the mechanism by which these bioactive metabolites are biosynthesized.

Effects of competitor spacing in a new class of individual-tree indices of competition: semidistance-independent indices computed for Bitterlich versus fixed-area plots

Treesearch

Albert R. Stage; Thomas Ledermann

2008-01-01

We illustrate effects of competitor spacing for a new class of individual-tree indices of competition that we call semi-distance-independent. This new class is similar to the class of distance-independent indices except that the index is computed independently at each subsampling plot surrounding a subject tree for which growth is to be modelled. We derive the effects...

Impact of the gap between socioeconomic stratum and subjective social class on depressive symptoms: unique insights from a longitudinal analysis.

PubMed

Kim, Jae-Hyun; Lee, Sang Gyu; Shin, Jaeyong; Park, Eun-Cheol

2014-11-01

Our objective was to investigate whether gaps between socioeconomic stratum and subjective social class affect the prevalence of depressive symptoms. We collected data from the Korean Health Panel Survey, years 2009 and 2011, and performed a longitudinal analysis of 12,357 individuals at baseline (2009), estimating the prevalence of depressive symptoms among individuals with disparate socioeconomic stratum (High, Middle, or Low household income and education level, respectively) and subjective social class (High, Middle, or Low). The odds ratio for depressive symptoms among individuals with High household income and High social class, or Low household income and Low social class, was 0.537 and 1.877, respectively (p<0.0001), and that among individuals with High education level and High social class, or Low education and Low social class, was 0.700 and 1.597, respectively (p: 0.001, p<0.0001, respectively). The likelihood of having depressive symptoms increased within each level of income and education, as the subjective social class decreased from High to Low. The adjusted effect of the gap between socioeconomic stratum and subjective social class on depressive symptoms deteriorated, as a whole, across the socioeconomic spectrum. The gap between socioeconomic stratum and perceived position in the social hierarchy explains a substantial part of inequalities in the prevalence of depressive symptoms. It is important to consider the impact of discrepancies between different measures of socioeconomic well-being on depressive symptoms rather than looking at the subjective social class alone. Copyright © 2014 The Authors. Published by Elsevier Ltd. All rights reserved.

A modified physiological BCS for prediction of intestinal absorption in drug discovery.

PubMed

Zaki, Noha M; Artursson, Per; Bergström, Christel A S

2010-10-04

In this study, the influence of physiologically relevant media on the compound position in a biopharmaceutical classification system (BCS) which resembled the intestinal absorption was investigated. Both solubility and permeability limited compounds (n = 22) were included to analyze the importance of each of these on the final absorption. Solubility was determined in three different dissolution media, phosphate buffer pH 6.5 (PhB 6.5), fasted state simulated intestinal fluid (FaSSIF), and fed state simulated intestinal fluid (FeSSIF) at 37 °C, and permeability values were determined using the 2/4/A1 cell line. The solubility data and membrane permeability values were used for sorting the compounds into a BCS modified to reflect the fasted and fed state. Three of the seven compounds sorted as BCS II in PhB 6.5 (high permeability, low solubility) changed their position to BCS I when dissolved in FaSSIF and/or FeSSIF (high permeability, high solubility). These were low dosed (20 mg or less) lipophilic molecules displaying solvation limited solubility. In contrast, compounds having solid-state limited solubility had a minor increase in solubility when dissolved in FaSSIF and/or FeSSIF. Although further studies are needed to enable general cutoff values, our study indicates that low dosed BCS Class II compounds which have solubility normally restricted by poor solvation may behave as BCS Class I compounds in vivo. The large series of compounds investigated herein reveals the importance of investigating solubility and dissolution under physiologically relevant conditions in all stages of the drug discovery process to push suitable compounds forward, to select proper formulations, and to reduce the risk of food effects.

High intraspecific variability in the functional niche of a predator is associated with ontogenetic shift and individual specialization

PubMed Central

Zhao, Tian; Villéger, Sébastien; Lek, Sovan; Cucherousset, Julien

2014-01-01

Investigations on the functional niche of organisms have primarily focused on differences among species and tended to neglect the potential effects of intraspecific variability despite the fact that its potential ecological and evolutionary importance is now widely recognized. In this study, we measured the distribution of functional traits in an entire population of largemouth bass (Micropterus salmoides) to quantify the magnitude of intraspecific variability in functional traits and niche (size, position, and overlap) between age classes. Stable isotope analyses (δ13C and δ15N) were also used to determine the association between individual trophic ecology and intraspecific functional trait variability. We observed that functional traits were highly variable within the population (mean coefficient variation: 15.62% ± 1.78% SE) and predominantly different between age classes. In addition, functional and trophic niche overlap between age classes was extremely low. Differences in functional niche between age classes were associated with strong changes in trophic niche occurring during ontogeny while, within age classes, differences among individuals were likely driven by trophic specialization. Each age class filled only a small portion of the total functional niche of the population and age classes occupied distinct portions in the functional space, indicating the existence of ontogenetic specialists with different functional roles within the population. The high amplitude of intraspecific variability in functional traits and differences in functional niche position among individuals reported here supports the recent claims for an individual-based approach in functional ecology. PMID:25558359

Assessing the risk associated with the presence of emerging organic contaminants in sludge-amended soil: A country-level analysis.

PubMed

Thomaidi, Vasiliki S; Stasinakis, Athanasios S; Borova, Viola L; Thomaidis, Nikolaos S

2016-04-01

Greece was used as case study and the environmental risk associated with the existence of 99 emerging organic contaminants (EOCs) in sludge-amended soil was estimated using risk quotient (RQ) approach. Data on the concentration levels of EOCs in sewage sludge was collected after literature review. Chemical analyses were also conducted for 50 pharmaceuticals and illicit drugs in sludge samples from Athens Sewage Treatment Plant. Risk assessment was based on both terrestrial and aquatic acute toxicity data, using both the maximum and the average measured concentrations of the target compounds. EC50/LC50 values were collected through literature review or using the ECOSAR program in cases that experimental values were not available. Triclosan seems to pose an environmental risk on the soil environment, as its RQ values exceeded 1, both in terrestrial and aquatic toxicity data based risk assessment. Calculations based on aquatic toxicity data showed that another eleven compounds had RQs higher than 1, most of them belonging to the classes of synthetic phenolic compounds and siloxanes. Tetradecamethylhexasiloxane presented the highest RQ, while high RQs were also calculated for decamethylcyclopentasiloxane and caffeine. No environmental risk for the terrestrial environment is expected due to the individual action of illicit drugs, perfluorinated compounds and benzotriazoles. The sludge source and the day of sampling affected the estimated threat due to nonylphenolic compounds; however these factors did not affect the estimated risk for siloxanes, caffeine and ofloxacin. Calculation of RQ values for the mixture of EOCs, using either the maximum or the average concentrations, far exceeded 1 (253 and 209, respectively), indicating a presumable threat for the terrestrial environment due to the baseline toxicity of these compounds. Countries that reuse sludge for agricultural purposes should include specific EOCs in national monitoring campaigns and study more thoroughly on their effects to the terrestrial environment. Copyright © 2016 Elsevier B.V. All rights reserved.

Applications of Palladium-Catalyzed C-N Cross-Coupling Reactions.

PubMed

Ruiz-Castillo, Paula; Buchwald, Stephen L

2016-10-12

Pd-catalyzed cross-coupling reactions that form C-N bonds have become useful methods to synthesize anilines and aniline derivatives, an important class of compounds throughout chemical research. A key factor in the widespread adoption of these methods has been the continued development of reliable and versatile catalysts that function under operationally simple, user-friendly conditions. This review provides an overview of Pd-catalyzed N-arylation reactions found in both basic and applied chemical research from 2008 to the present. Selected examples of C-N cross-coupling reactions between nine classes of nitrogen-based coupling partners and (pseudo)aryl halides are described for the synthesis of heterocycles, medicinally relevant compounds, natural products, organic materials, and catalysts.

Laser action benzimidazoles in various aggregate states

NASA Astrophysics Data System (ADS)

Gruzinskii, V. V.; Degtiarenko, K. M.; Shalaev, V. K.; Kopylova, T. N.; Verkhovskii, V. S.; Tarasenko, V. F.; Melchenko, S. V.

1983-04-01

Lasing has been obtained in solutions of benzimidazole (Bi) derivatives: 2-phenyl-Bi (with the band maximum lambda-r-max = 341-347 nm), 2-n-tolyl-Bi (344 nm), and 2-(4'-biphenilyl) Bi (366-374 nm). It is found that compounds of this class provide a basis for laser radiation covering a wide region of the spectrum. Lasing has been obtained on the vapors of 2-(4'-biphenilyl) Bi (361.2 nm) and 2-(n-tolyl) Bi (336.5 nm) with a pentane stabilizer of the excited states. High volatility, photostability, and lasing in wide ranges of concentration determine the efficiency of using this new class of compounds (chain arylbenzimidazoles) in lasers using the vapors of complex molecules.

Applications of Palladium-Catalyzed C–N Cross-Coupling Reactions

PubMed Central

2016-01-01

Pd-catalyzed cross-coupling reactions that form C–N bonds have become useful methods to synthesize anilines and aniline derivatives, an important class of compounds throughout chemical research. A key factor in the widespread adoption of these methods has been the continued development of reliable and versatile catalysts that function under operationally simple, user-friendly conditions. This review provides an overview of Pd-catalyzed N-arylation reactions found in both basic and applied chemical research from 2008 to the present. Selected examples of C–N cross-coupling reactions between nine classes of nitrogen-based coupling partners and (pseudo)aryl halides are described for the synthesis of heterocycles, medicinally relevant compounds, natural products, organic materials, and catalysts. PMID:27689804

Risk-Based Evaluation of Total Petroleum Hydrocarbons in Vapor Intrusion Studies

PubMed Central

Brewer, Roger; Nagashima, Josh; Kelley, Michael; Heskett, Marvin; Rigby, Mark

2013-01-01

This paper presents a quantitative method for the risk-based evaluation of Total Petroleum Hydrocarbons (TPH) in vapor intrusion investigations. Vapors from petroleum fuels are characterized by a complex mixture of aliphatic and, to a lesser extent, aromatic compounds. These compounds can be measured and described in terms of TPH carbon ranges. Toxicity factors published by USEPA and other parties allow development of risk-based, air and soil vapor screening levels for each carbon range in the same manner as done for individual compounds such as benzene. The relative, carbon range makeup of petroleum vapors can be used to develop weighted, site-specific or generic screening levels for TPH. At some critical ratio of TPH to a targeted, individual compound, the overwhelming proportion of TPH will drive vapor intrusion risk over the individual compound. This is particularly true for vapors associated with diesel and other middle distillate fuels, but can also be the case for low-benzene gasolines or even for high-benzene gasolines if an adequately conservative, target risk is not applied to individually targeted chemicals. This necessitates a re-evaluation of the reliance on benzene and other individual compounds as a stand-alone tool to evaluate vapor intrusion risk associated with petroleum. PMID:23765191

Synthesis and characterization of sugar based low molecular weight gelators and the preparation of chiral sulfinamides

NASA Astrophysics Data System (ADS)

Mangunuru, Hari Prasad Reddy

Low molecular weight gelators (LMWGs) have received considerable attention in the field of chemistry from last few decades. These compounds form self-assembled fibrous networks like micelles, cylindrical, sheets, fibers, layers and so on. The fibrous network entraps the solvent and forms gel, because of the self-assembly phenomenon and their demonstrated potential uses in a variety of areas, ranging from environmental to medicinal applications. Sugars are good starting materials to synthesize the new class of LMWG's, because these are different from some expensive materials, these are natural products. We have synthesized and characterized the LMGS's based on D-glucose and D-glucosamine. D-glucosamine is the versatile starting material to make different peptoids and triazoles. Several series of compounds were synthesized using compounds 1-3 as starting material and studied the gelation behavior all the compounds. We have studied the self-assembling properties of a new class of tripeptoids, synthesized by one-pot Ugi reaction from simple starting materials. Among the focused library of tripeptoids synthesized, we found that several efficient low molecular weight organogelators were obtained for aqueous DMSO and ethanol mixtures. We have also synthesized and characterized a series of monosaccharide triazole derivatives. These compounds were synthesized from N-acetyl glucosamine and D-glucose via a Cu(I) catalyzed azide/alkyne cycloaddition reaction (CuAAc). The compounds have been screened for their gelation properties and several efficient low molecular weight organo/hydro gelators were obtained, among these compounds, five per-acetyl glucosamine derivatives and one peracetyl glucose derivative were able to form gels in water. These new molecules are expected to be useful in drug delivery and tissue engineering.*. Asymmetric synthesis of chiral amines is a challenging in synthetic organic chemistry. The development of new catalysts for asymmetric organic transformations is a very important research goal in modern synthetic organic chemistry. We have synthesized a new class of chiral oxathiozinone from chiral amino phenol. From this synthesized chiral sulfinamides, ketimines followed by reducing the ketimines synthesized the highly hindered chiral amines. *Please refer to dissertation for diagrams.

Longitudinal relationships between individual and class norms supporting dating violence and perpetration of dating violence.

PubMed

Taylor, Katherine A; Sullivan, Terri N; Farrell, Albert D

2015-03-01

Dating violence is commonly perpetrated in adolescence, making it imperative to understand risk factors in order to inform prevention efforts. Although individual norms supporting dating violence are strongly related to its perpetration, few studies have examined their longitudinal impact. Moreover, the influence of class norms (i.e., norms for students in the same grade, cohort, and school) supporting dating violence on perpetration has rarely been studied. The current study examined longitudinal relationships between individual and class norms supporting dating violence and perpetration of physical and psychological dating violence. Participants were two cohorts of sixth graders from 37 schools who were in dating relationships at Wave 1 and 6 months later at Wave 2 (N = 2,022; 43% female; 52% African American, 21% Latino/a, 20% White, and 7% other). The analyses used a multilevel approach, with students represented at Level 1 and classes (n = 74) at Level 2. The models tested direct effects of Wave 1 individual and class norms supporting dating violence on subsequent changes in perpetration of dating violence at Wave 2 and the extent to which gender moderated these relationships. The findings indicated that greater individual norms supporting male dating violence predicted greater change in perpetration of physical and psychological dating violence and greater individual norms supporting female dating violence predicted greater change in perpetration of psychological dating violence. Greater class norms supporting male dating violence predicted greater change in perpetration of physical dating violence; whereas greater class norms supporting female dating violence predicted less change in perpetration of physical dating violence. These findings highlight the need to address norms in early adolescence.

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

Feenstra, Adam D.; Hansen, Rebecca L.; Lee, Young Jin

Mass spectrometry imaging (MSI) provides high spatial resolution information that is unprecedented in traditional metabolomics analyses; however, the molecular coverage is often limited to a handful of compounds and is insufficient to understand overall metabolomic changes of a biological system. Here, we propose an MSI methodology to increase the diversity of chemical compounds that can be imaged and identified, in order to eventually perform untargeted metabolomic analysis using MSI. We use the desorption/ionization bias of various matrixes for different metabolite classes along with dual polarities and a tandem MSI strategy. The use of multiple matrixes and dual polarities allows usmore » to visualize various classes of compounds, while data-dependent MS/MS spectra acquired in the same MSI scans allow us to identify the compounds directly on the tissue. In a proof of concept application to a germinated corn seed, a total of 166 unique ions were determined to have high-quality MS/MS spectra, without counting structural isomers, of which 52 were identified as unique compounds. According to an estimation based on precursor MSI datasets, we expect over five hundred metabolites could be potentially identified and visualized once all experimental conditions are optimized and an MS/MS library is available. Finally, metabolites involved in the glycolysis pathway and tricarboxylic acid cycle were imaged to demonstrate the potential of this technology to better understand metabolic biology.« less

Transcriptomic analysis in the developing zebrafish embryo after compound exposure: Individual gene expression and pathway regulation

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

Hermsen, Sanne A.B., E-mail: Sanne.Hermsen@rivm.nl; Department of Toxicogenomics, Maastricht University, P.O. Box 616, 6200 MD, Maastricht; Institute for Risk Assessment Sciences

2013-10-01

The zebrafish embryotoxicity test is a promising alternative assay for developmental toxicity. Classically, morphological assessment of the embryos is applied to evaluate the effects of compound exposure. However, by applying differential gene expression analysis the sensitivity and predictability of the test may be increased. For defining gene expression signatures of developmental toxicity, we explored the possibility of using gene expression signatures of compound exposures based on commonly expressed individual genes as well as based on regulated gene pathways. Four developmental toxic compounds were tested in concentration-response design, caffeine, carbamazepine, retinoic acid and valproic acid, and two non-embryotoxic compounds, D-mannitol andmore » saccharin, were included. With transcriptomic analyses we were able to identify commonly expressed genes, which were mostly development related, after exposure to the embryotoxicants. We also identified gene pathways regulated by the embryotoxicants, suggestive of their modes of action. Furthermore, whereas pathways may be regulated by all compounds, individual gene expression within these pathways can differ for each compound. Overall, the present study suggests that the use of individual gene expression signatures as well as pathway regulation may be useful starting points for defining gene biomarkers for predicting embryotoxicity. - Highlights: • The zebrafish embryotoxicity test in combination with transcriptomics was used. • We explored two approaches of defining gene biomarkers for developmental toxicity. • Four compounds in concentration-response design were tested. • We identified commonly expressed individual genes as well as regulated gene pathways. • Both approaches seem suitable starting points for defining gene biomarkers.« less

Secondary ion mass spectrometry imaging and multivariate data analysis reveal co-aggregation patterns of Populus trichocarpa leaf surface compounds on a micrometer scale.

PubMed

Kulkarni, Purva; Dost, Mina; Bulut, Özgül Demir; Welle, Alexander; Böcker, Sebastian; Boland, Wilhelm; Svatoš, Aleš

2018-01-01

Spatially resolved analysis of a multitude of compound classes has become feasible with the rapid advancement in mass spectrometry imaging strategies. In this study, we present a protocol that combines high lateral resolution time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging with a multivariate data analysis (MVA) approach to probe the complex leaf surface chemistry of Populus trichocarpa. Here, epicuticular waxes (EWs) found on the adaxial leaf surface of P. trichocarpa were blotted on silicon wafers and imaged using TOF-SIMS at 10 μm and 1 μm lateral resolution. Intense M +● and M -● molecular ions were clearly visible, which made it possible to resolve the individual compound classes present in EWs. Series of long-chain aliphatic saturated alcohols (C 21 -C 30 ), hydrocarbons (C 25 -C 33 ) and wax esters (WEs; C 44 -C 48 ) were clearly observed. These data correlated with the 7 Li-chelation matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis, which yielded mostly molecular adduct ions of the analyzed compounds. Subsequently, MVA was used to interrogate the TOF-SIMS dataset for identifying hidden patterns on the leaf's surface based on its chemical profile. After the application of principal component analysis (PCA), a small number of principal components (PCs) were found to be sufficient to explain maximum variance in the data. To further confirm the contributions from pure components, a five-factor multivariate curve resolution (MCR) model was applied. Two distinct patterns of small islets, here termed 'crystals', were apparent from the resulting score plots. Based on PCA and MCR results, the crystals were found to be formed by C 23 or C 29 alcohols. Other less obvious patterns observed in the PCs revealed that the adaxial leaf surface is coated with a relatively homogenous layer of alcohols, hydrocarbons and WEs. The ultra-high-resolution TOF-SIMS imaging combined with the MVA approach helped to highlight the diverse patterns underlying the leaf's surface. Currently, the methods available to analyze the surface chemistry of waxes in conjunction with the spatial information related to the distribution of compounds are limited. This study uses tools that may provide important biological insights into the composition of the wax layer, how this layer is repaired after mechanical damage or insect feeding, and which transport mechanisms are involved in deploying wax constituents to specific regions on the leaf surface. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

Go/No-Go Procedure with Compound Stimuli: Effects of Training Structure on the Emergence of Equivalence Classes

ERIC Educational Resources Information Center

Grisante, Priscila C.; Galesi, Fernanda L.; Sabino, Nathali M.; Debert, Paula; Arntzen, Erik; McIlvane, William J.

2013-01-01

When the matching-to-sample (MTS) procedure is used, different training structures imply differences in the successive discriminations required in training and test conditions. When the go/no-go procedure with compound stimuli is used, however, differences in training structures do not imply such differences. This study assessed whether the…

Uptake of Seeds Secondary Metabolites by Virola surinamensis Seedlings

PubMed Central

Kato, Massuo Jorge; Yoshida, Massayoshi; Lopes, Norberto Peporine; da Silva, Denise Brentan; Cavalheiro, Alberto José

2012-01-01

The major secondary metabolites and fatty acids occurring in the seeds of Virola surinamensis were monitored by GC-MS during germination and seedling development. The role as carbon source for seedling development was indicated considering that both classes of compounds were similarly consumed in the seeds and that no selective consumption of compounds could be detected. PMID:22505921

A STUDY IN THE ANALYSIS OF THE HINDI VERB.

ERIC Educational Resources Information Center

BAHL, KALI C.

A CONSTITUENT STRUCTURE OF HINDI WAS FORMULATED TO ACCOUNT FOR THE PHENOMENA OF COMPOUND AND CONJUNCT VERBS IN THE LANGUAGE. THE TRADITIONAL CLASS OF CONJUNCT VERBS OR THE COMPOUND VERBS, CONSISTING OF NOUN OR ADJECTIVE PLUS VERB, WAS REINTERPRETED IN THIS ANALYSIS. THE FOUR SECTIONS OF THE TEXT DEALT WITH (1) THE SUBJECT-PREDICATE KERNEL…

Essential oil composition of Pimpinella cypria and its insecticidal, cytotoxic, and antimicrobial activity

USDA-ARS?s Scientific Manuscript database

A water-distilled essential oil from the aerial parts of Pimpinella cypria Boiss. (Apiaceae), an endemic species in northern Cyprus, was analyzed by GC and GC-MS. Forty-five compounds were identified in the oil and these comprised 81.7% of the total composition. The compound classes in the oil were ...

The Influence of Morphological Structure Information on the Memorization of Chinese Compound Words

ERIC Educational Resources Information Center

Liu, Duo

2017-01-01

The present study investigated the influence of morphological structure information on the memorization of Chinese subordinate and coordinative compound words using the memory conjunction error paradigm. During the Study Phase, Hong Kong Chinese college students were asked to either judge the word class (Exp. 1, N = 25) or the orthographic…

Compound Interest Is As Easy As Pi. Teacher's Guide [and] Student Manual.

ERIC Educational Resources Information Center

Auman, L. Charles

This document provides teaching guidelines and student material for a unit intended for use in 12th grade algebra classes. Time allotment is from four to six hours of classroom time. The objective of this capsule is to teach students how to solve compound interest problems using arithmetic, logorithms, and calculators. Prerequisites for the unit…

Natural Products as a Source of Alzheimer’s Drug Leads

PubMed Central

Sorribas, Analia; Howes, Melanie-Jayne R.

2016-01-01

This review focuses on recent developments in the use of natural products as therapeutics for Alzheimer’s disease. Compounds span a diverse array of structural classes and are organized according to their mechanism of action, with the focus primarily on the major hypotheses. Overall, the review discusses more than 180 compounds and summarizes 393 references. PMID:21072430

Picture of the Week: Hacking the bio-nano interface for better biofuels

Science.gov Websites

) influence electron transfer between the enzyme and the electrode to determine the best placement of enzymes compounds) influence electron transfer between the enzyme and the electrode to determine the best placement studied how three quinones (a class of organic compounds) influence electron transfer between the enzyme

The Compound Atwood Machine Problem

ERIC Educational Resources Information Center

Coelho, R. Lopes

2017-01-01

The present paper accounts for progress in physics teaching in the sense that a problem, which has been closed to students for being too difficult, is gained for the high school curriculum. This problem is the compound Atwood machine with three bodies. Its introduction into high school classes is based on a recent study on the weighing of an…

The compound Atwood machine problem

NASA Astrophysics Data System (ADS)

Lopes Coelho, R.

2017-05-01

The present paper accounts for progress in physics teaching in the sense that a problem, which has been closed to students for being too difficult, is gained for the high school curriculum. This problem is the compound Atwood machine with three bodies. Its introduction into high school classes is based on a recent study on the weighing of an Atwood machine.

Feedback and rewards, part II: formal and informal feedback reviews.

PubMed

Harolds, Jay

2013-02-01

There are 2 major classes of feedback. One class of feedback consists of the informal, numerous conversations between various people in the organization regarding the performance, behavior, and goals of an individual. Another class of feedback consists of formal reviews held once or twice a year between a supervisor and an individual. This article discusses both types of feedback.

Effects of Web-Based Collaborative Writing on Individual L2 Writing Development

ERIC Educational Resources Information Center

Bikowski, Dawn; Vithanage, Ramyadarshanie

2016-01-01

This study investigated the effect of repeated in-class web-based collaborative writing tasks on second language writers' (L2) individual writing scores. A pre-test post-test research model was used in addition to participant surveys, class observations, and teacher interviews. Participants included 59 L2 writers in a writing class at a large U.S.…

Injuries to primary school pupils and secondary school students during physical education classes and in their leisure time.

PubMed

Videmsek, Mateja; Karpljuk, Damir; Mlinar, Suzana; Mesko, Maja; Stihec, Joze

2010-09-01

The study aimed to establish the frequency of injuries in primary and secondary schools during leisure time and physical education classes in school as well as in group and individual sports. The sample included 2842 pupils from nine primary schools and 1235 students from five secondary schools in Slovenia. The data were processed with the SPSS statistical software package and the frequencies and Crosstabs were calculated. The results showed that substantially more pupils and students were injured in their leisure time than during physical education classes. Girls were more frequently injured in group and individual sports practiced during physical education classes and in individual sports practiced in their leisure time, whereas boys suffered more injuries in group sports practiced in their leisure time. As regards group sports, pupils and students were most frequently injured while playing football in their leisure time whereas, during physical education classes, they suffered most injuries in volleyball, followed closely by basketball and football; as regards individual sports, pupils and students were most frequently injured while cycling and rollerblading in their leisure time, whereas during physical education classes they suffered most injuries in athletics.

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

Ijam, M.J.; Qatami, S.Y.A.; Arif, S.F.

For several decades removal of aromatics from crude oil fractions (e.g. kerosene and lubricating oils) has been practiced in oil refining to produce fuels and lubricants of lower aromatic content and hence of improved quality. These aromatics are suitable raw materials for the manufacture of aromatic solvents, aromatic process oils, high octane gasoline, and as basic materials for making detergents, perfumes and dyes. Detailed study of molecular structure and substituent effects on the retention characteristics of aromatic hydrocarbons have been reported on alumina, silica and various chemically bonded silicas containing -C/sub 18/, -NH/sub 2/, -R(NH)/sub 2//sub 2/, -CN, RCN, RONmore » and phenyl-mercuric acetate for the compound class (ring-numbered) high performance liquid chromatography (2, 3, 8, 12, 24, 28). Previous work in this laboratory has demonstrated that individual normal and branched aliphatic hydrocarbons from kerosene and light gas oil were isolated and identified. This paper describes the extension of this work to cover the separation and identification of aromatic ring classes (mono-, di-, and tri-aromatics) in the gas oil fraction of Kuwait petroleum. Characterization and identification of the major components in the dinuclear aromatics is our primary objective in this study.« less

Isolation of phenolic compounds from hop extracts using polyvinylpolypyrrolidone: characterization by high-performance liquid chromatography-diode array detection-electrospray tandem mass spectrometry.

PubMed

Magalhães, Paulo J; Vieira, Joana S; Gonçalves, Luís M; Pacheco, João G; Guido, Luís F; Barros, Aquiles A

2010-05-07

The aim of the present work was the development of a suitable methodology for the separation and determination of phenolic compounds in the hop plant. The developed methodology was based on the sample purification by adsorption of phenolic compounds from the matrix to polyvinylpolypyrrolidone (PVPP) and subsequent desorption of the adsorbed polyphenols with acetone/water (70:30, v/v). At last, the extract was analyzed by HPLC-DAD and HPLC-ESI-MS/MS. The first phase of this work consisted of the study of the adsorption behavior of several classes of phenolic compounds (e.g. phenolic acids, flavonols, and flavanols) by PVPP in model solutions. It has been observed that the process of adsorption of the different phenolic compounds to PVPP (at low concentrations) is differentiated, depending on the structure of the compound (number of OH groups, aromatic rings, and stereochemistry hindrance). For example, within the phenolic acids class (benzoic, p-hydroxybenzoic, protocatechuic and gallic acids) the PVPP adsorption increases with the number of OH groups of the phenolic compound. On the other hand, the derivatization of OH groups (methylation and glycosylation) resulted in a greatly diminished binding. The use of PVPP revealed to be very efficient for adsorption of several phenolic compounds such as catechin, epicatechin, xanthohumol and quercetin, since high adsorption and recovery values were obtained. The methodology was further applied for the extraction and isolation of phenolic compounds from hops. With this methodology, it was possible to obtain high adsorption values (>or=80%) and recovery yield values (>or=70%) for the most important phenolic compounds from hops such as xanthohumol, catechin, epicatechin, quercetin and kaempferol glycosides, and in addition it allows the identification of about 30 phenolic compounds by HPLC-DAD and HPLC-ESI-MS/MS. Copyright (c) 2009 Elsevier B.V. All rights reserved.

The Need for Development of New HIV-1 Reverse Transcriptase and Integrase Inhibitors in the Aftermath of Antiviral Drug Resistance

PubMed Central

Wainberg, Mark A.

2012-01-01

The use of highly active antiretroviral therapy (HAART) involves combinations of drugs to achieve maximal virological response and reduce the potential for the emergence of antiviral resistance. There are two broad classes of reverse transcriptase inhibitors, the nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs). Since the first classes of such compounds were developed, viral resistance against them has necessitated the continuous development of novel compounds within each class. This paper considers the NRTIs and NNRTIs currently in both preclinical and clinical development or approved for second line therapy and describes the patterns of resistance associated with their use, as well as the underlying mechanisms that have been described. Due to reasons of both affordability and availability, some reverse transcriptase inhibitors with low genetic barrier are more commonly used in resource-limited settings. Their use results to the emergence of specific patterns of antiviral resistance and so may require specific actions to preserve therapeutic options for patients in such settings. More recently, the advent of integrase strand transfer inhibitors represents another major step forward toward control of HIV infection, but these compounds are also susceptible to problems of HIV drug resistance. PMID:24278679

Portable spotter for fluorescent contaminants on surfaces

DOEpatents

Schuresko, Daniel D.

1980-01-01

A portable fluorescence-based spotter for polynuclear aromatic hydrocarbon contamination on personnel and work area surfaces under ambient lighting conditions is provided. This instrument employs beam modulation and phase sensitive detection for discriminating between fluorescence from organic materials from reflected background light and inorganic fluorescent material. The device uses excitation and emission filters to provide differentiation between classes of aromatic organic compounds. Certain inorganic fluorescent materials, including heavy metal compounds, may also be distinguished from the organic compounds, despite both having similar optical properties.

Growth of Pure Cultures of Marine Phytoplankton in the Presence of Toxicants

PubMed Central

Ukeles, Ravenna

1962-01-01

The effects of 17 toxicants on the growth of five species of algae in pure culture were studied. The two species displaying the greatest sensitivity to the action of each of the compounds tested were Monochrysis lutheri and Phaeodactylum tricornutum, and the most resistant species was Protococcus. Of eight different classes of toxicants tested, substituted urea compounds and a mercuric compound were most effective in inhibiting growth of all algal species at the lowest concentrations. PMID:13995259

Targeting Ligand-Dependent and Ligand-Independent Androgen Receptor Signaling in Prostate Cancer

DTIC Science & Technology

2013-10-01

that disrupt more selective classes of LxxLL motifs: for example, we have compounds that can block AR-PELP1 and AR- hsp27 interaction through the LxxLL...motif as well as compounds that only block AR-PELP1 (and not AR- hsp27 ). We believe that these compounds will be critical for ascertaining the...IP: AR Input PELP1 PELP1 AR AR Hsp27 hsp27 10 Planned structural modifications of D2-derived peptidomimetics by docking

Chemosignaling diversity in songbirds: chromatographic profiling of preen oil volatiles in different species.

PubMed

Soini, Helena A; Whittaker, Danielle J; Wiesler, Donald; Ketterson, Ellen D; Novotny, Milos V

2013-11-22

Large foraging seabirds are known to navigate to food sources using their excellent sense of smell, but much less is known about the use of olfaction by the songbirds (passerine birds). Some evidence of individual recognition based on the bird preen oil volatile organic compound (VOC) compositions, which is the main odor source in birds, have been reported for dark-eyed junco and house finch. In this study we have investigated preen oil VOCs in 16 different songbird species and two other small bird species in order to determine whether the VOC compositions follow phylogenetic and evolutionary relatedness. We have used the stir bar sorptive extraction (SBSE) methodology followed by gas chromatography-mass spectrometry (GC-MS) to determine preen oil VOCs during the long light summer conditions for mostly wild caught birds. Large diversity among the VOC compositions was observed, while some compound classes were found in almost all species. The divergent VOC profiles did not follow the phylogenetic family lines among the bird species. This suggests that songbirds may use VOC odors as a mate recognition cue. Copyright © 2013 Elsevier B.V. All rights reserved.

Rapid Screening Method for New Psychoactive Substances of Forensic Interest: Electrochemistry and Analytical Determination of Phenethylamines Derivatives (NBOMe) via Cyclic and Differential Pulse Voltammetry.

PubMed

Andrade, Ana Flávia B; Mamo, Samuel Kasahun; Gonzalez-Rodriguez, Jose

2017-02-07

The NBOMe derivatives are phenethylamines derived from the 2C class of hallucinogens. Only a few human pharmacologic studies have been conducted on these drugs, and several cases of intoxication and deaths have been reported. Presently, NBOMe are not a part of the routine drugs-of-abuse screening procedure for many police forces, and there are no rapid immunoassay screening tests that can detect the presence of those compounds. In this Article, the voltammetric behavior of 25B NBOMe and 25I NBOMe were investigated and their electroanalytical characteristics determined for the first time. A novel, fast, and sensitive screening method for the identification of the two most common NBOMes (25B-NBOMe and 25I-NBOMe) in real samples is reported. The method uses the electrochemical oxidation of these molecules to produce an analytical signal that can be related to the NBOMe concentration with an average lower limit of quantitation of 0.01 mg/mL for both of them. The method is selective enough to identify the two compounds individually, even given the great similarity in their structure.

Dynamic relationships between body size, species richness, abundance, and energy use in a shallow marine epibenthic faunal community

PubMed Central

Labra, Fabio A; Hernández-Miranda, Eduardo; Quiñones, Renato A

2015-01-01

We study the temporal variation in the empirical relationships among body size (S), species richness (R), and abundance (A) in a shallow marine epibenthic faunal community in Coliumo Bay, Chile. We also extend previous analyses by calculating individual energy use (E) and test whether its bivariate and trivariate relationships with S and R are in agreement with expectations derived from the energetic equivalence rule. Carnivorous and scavenger species representing over 95% of sample abundance and biomass were studied. For each individual, body size (g) was measured and E was estimated following published allometric relationships. Data for each sample were tabulated into exponential body size bins, comparing species-averaged values with individual-based estimates which allow species to potentially occupy multiple size classes. For individual-based data, both the number of individuals and species across body size classes are fit by a Weibull function rather than by a power law scaling. Species richness is also a power law of the number of individuals. Energy use shows a piecewise scaling relationship with body size, with energetic equivalence holding true only for size classes above the modal abundance class. Species-based data showed either weak linear or no significant patterns, likely due to the decrease in the number of data points across body size classes. Hence, for individual-based size spectra, the SRA relationship seems to be general despite seasonal forcing and strong disturbances in Coliumo Bay. The unimodal abundance distribution results in a piecewise energy scaling relationship, with small individuals showing a positive scaling and large individuals showing energetic equivalence. Hence, strict energetic equivalence should not be expected for unimodal abundance distributions. On the other hand, while species-based data do not show unimodal SRA relationships, energy use across body size classes did not show significant trends, supporting energetic equivalence. PMID:25691966

Social class rank, essentialism, and punitive judgment.

PubMed

Kraus, Michael W; Keltner, Dacher

2013-08-01

Recent evidence suggests that perceptions of social class rank influence a variety of social cognitive tendencies, from patterns of causal attribution to moral judgment. In the present studies we tested the hypotheses that upper-class rank individuals would be more likely to endorse essentialist lay theories of social class categories (i.e., that social class is founded in genetically based, biological differences) than would lower-class rank individuals and that these beliefs would decrease support for restorative justice--which seeks to rehabilitate offenders, rather than punish unlawful action. Across studies, higher social class rank was associated with increased essentialism of social class categories (Studies 1, 2, and 4) and decreased support for restorative justice (Study 4). Moreover, manipulated essentialist beliefs decreased preferences for restorative justice (Study 3), and the association between social class rank and class-based essentialist theories was explained by the tendency to endorse beliefs in a just world (Study 2). Implications for how class-based essentialist beliefs potentially constrain social opportunity and mobility are discussed.

Profiling of volatile fragrant components in a mini-core collection of mango germplasms from seven countries

PubMed Central

Zhan, Ru-Lin; Wu, Hong-Xia; Yao, Quan-Sheng; Xu, Wen-Tian; Luo, Chun; Zhou, Yi-Gang; Liang, Qing-Zhi; Wang, Song-Biao

2017-01-01

Aroma is important in assessing the quality of fresh fruit and their processed products, and could provide good indicators for the development of local cultivars in the mango industry. In this study, the volatile diversity of 25 mango cultivars from China, America, Thailand, India, Cuba, Indonesia, and the Philippines was investigated. The volatile compositions, their relative contents, and the intervarietal differences were detected with headspace solid phase microextraction tandem gas chromatography-mass spectrometer methods. The similarities were also evaluated with a cluster analysis and correlation analysis of the volatiles. The differences in mango volatiles in different districts are also discussed. Our results show significant differences in the volatile compositions and their relative contents among the individual cultivars and regions. In total, 127 volatiles were found in all the cultivars, belonging to various chemical classes. The highest and lowest qualitative abundances of volatiles were detected in ‘Zihua’ and ‘Mallika’ cultivars, respectively. Based on the cumulative occurrence of members of the classes of volatiles, the cultivars were grouped into monoterpenes (16 cultivars), proportion and balanced (eight cultivars), and nonterpene groups (one cultivars). Terpene hydrocarbons were the major volatiles in these cultivars, with terpinolene, 3-carene, caryophyllene and α-Pinene the dominant components depending on the cultivars. Monoterpenes, some of the primary volatile components, were the most abundant aroma compounds, whereas aldehydes were the least abundant in the mango pulp. β-Myrcene, a major terpene, accounted for 58.93% of the total flavor volatile compounds in ‘Xiaofei’ (Philippens). γ-Octanoic lactone was the only ester in the total flavor volatile compounds, with its highest concentration in ‘Guiya’ (China). Hexamethyl cyclotrisiloxane was the most abundant volatile compound in ‘Magovar’ (India), accounting for 46.66% of the total flavor volatiles. A typical aldehydic aroma 2,6-di-tert-butyl-4-sec-butylphenol, was detected in ‘Gleck’. A highly significant positive correlation was detected between Alc and K, Alk and Nt, O and L. Cultivars originating from America, Thailand, Cuba, India, Indonesia and the Philippines were more similar to each other than to those from China. This study provides a high-value dataset for use in development of health care products, diversified mango breeding, and local extension of mango cultivars. PMID:29211747

Clustering of adversity in young adults on disability pension due to mental disorders: a latent class analysis.

PubMed

Joensuu, Matti; Mattila-Holappa, Pauliina; Ahola, Kirsi; Ervasti, Jenni; Kivimäki, Mika; Kivekäs, Teija; Koskinen, Aki; Vahtera, Jussi; Virtanen, Marianna

2016-02-01

Mental disorders are the leading cause of work disability among young adults. This study examined whether distinct classes could be identified among young adults on the basis of medical history before receiving a disability pension due to a mental disorder. Medical history was obtained from pension applications and attached medical certificates for 1163 individuals aged 18-34 years who, in 2008, received a disability pension due to a mental disorder. Using latent class analysis, 10 clinical and individual adversities and their associations with sex, age and diagnostic category were examined. Three classes were identified: childhood adversity (prevalence, 33%), comorbidity (23%), and undefined (44%). The childhood adversity class was characterized by adverse events and symptoms reported during childhood and it associated with depressive disorders. The comorbidity class was characterized by comorbid mental disorders, suicide attempts and substance abuse and associated with younger age and bipolar disorder. The undefined class formed no distinct profile; individuals in this class had the lowest number of adversities and it associated with psychotic disorders. The identification of subgroups characterized by childhood circumstances and comorbidity may help planning of prevention and support practices for young adults with mental disorders and risk of work disability.

School Class Size: Research and Policy

ERIC Educational Resources Information Center

Glass, Gene V.; And Others

This book synthesizes research evidence to demonstrate that 1) class size is strongly related to pupil achievement; 2) smaller classes are more conducive to improved pupil performance than larger classes; 3) smaller classes provide more opportunities to adapt learning programs to individual needs; 4) pupils in smaller classes have more interest in…

Perceptions of hatha yoga amongst persistently depressed individuals enrolled in a trial of yoga for depression.

PubMed

Uebelacker, Lisa A; Kraines, Morganne; Broughton, Monica K; Tremont, Geoffrey; Gillette, L Tom; Epstein-Lubow, Gary; Abrantes, Ana M; Battle, Cynthia; Miller, Ivan W

2017-10-01

To understand depressed individuals' experiences in a 10-week hatha yoga program. In a randomized controlled trial, participants were assigned to either 10 weeks of hatha yoga classes or a health education control group. This report includes responses from participants in yoga classes. At the start of classes, average depression symptom severity level was moderate. After 10 weeks of yoga classes, we asked participants (n=50) to provide written responses to open-ended questions about what they liked about classes, what they did not like or did not find helpful, and what they learned. We analyzed qualitative data using thematic analysis. Elements of yoga classes that may increase acceptability for depressed individuals include having instructors who promote a non-competitive and non-judgmental atmosphere, who are knowledgeable and able to provide individualized attention, and who are kind and warm. Including depression-related themes in classes, teaching mindfulness, teaching breathing exercises, and providing guidance for translating class into home practice may help to make yoga effective for targeting depression. Participants' comments reinforced the importance of aspects of mindfulness, such as attention to the present moment and acceptance of one's self and one's experience, as potential mechanisms of action. Other potential mechanisms include use of breathing practices in everyday life and the biological mechanisms that underlie the positive impact of yogic breathing. The most serious concern highlighted by a few participants was the concern that the yoga classes were too difficult given their physical abilities. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nonsuicidal Self-Injury and Suicidal Behavior: A Latent Class Analysis among Young Adults

PubMed Central

Hamza, Chloe A.; Willoughby, Teena

2013-01-01

Although there is a general consensus among researchers that engagement in nonsuicidal self-injury (NSSI) is associated with increased risk for suicidal behavior, little attention has been given to whether suicidal risk varies among individuals engaging in NSSI. To identify individuals with a history of NSSI who are most at risk for suicidal behavior, we examined individual variability in both NSSI and suicidal behavior among a sample of young adults with a history of NSSI (N = 439, Mage = 19.1). Participants completed self-report measures assessing NSSI, suicidal behavior, and psychosocial adjustment (e.g., depressive symptoms, daily hassles). We conducted a latent class analysis using several characteristics of NSSI and suicidal behaviors as class indicators. Three subgroups of individuals were identified: 1) an infrequent NSSI/not high risk for suicidal behavior group, 2) a frequent NSSI/not high risk for suicidal behavior group, and 3) a frequent NSSI/high risk for suicidal behavior group. Follow-up analyses indicated that individuals in the ‘frequent NSSI/high risk for suicidal behavior’ group met the clinical-cut off score for high suicidal risk and reported significantly greater levels of suicidal ideation, attempts, and risk for future suicidal behavior as compared to the other two classes. Thus, this study is the first to identity variability in suicidal risk among individuals engaging in frequent and multiple methods of NSSI. Class 3 was also differentiated by higher levels of psychosocial impairment relative to the other two classes, as well as a comparison group of non-injuring young adults. Results underscore the importance of assessing individual differences in NSSI characteristics, as well as psychosocial impairment, when assessing risk for suicidal behavior. PMID:23544113

A historical review of additives and modifiers used in paving asphalt refining processes in the United States.

PubMed

Mundt, Diane J; Adams, Robert C; Marano, Kristin M

2009-11-01

The U.S. asphalt paving industry has evolved over time to meet various performance specifications for liquid petroleum asphalt binder (known as bitumen outside the United States). Additives to liquid petroleum asphalt produced in the refinery may affect exposures to workers in the hot mix paving industry. This investigation documented the changes in the composition and distribution of the liquid petroleum asphalt products produced from petroleum refining in the United States since World War II. This assessment was accomplished by reviewing documents and interviewing individual experts in the industry to identify current and historical practices. Individuals from 18 facilities were surveyed; the number of facilities reporting use of any material within a particular class ranged from none to more than half the respondents. Materials such as products of the process stream, polymers, elastomers, and anti-strip compounds have been added to liquid petroleum asphalt in the United States over the past 50 years, but modification has not been generally consistent by geography or time. Modifications made to liquid petroleum asphalt were made generally to improve performance and were dictated by state specifications.

Methods of analysis by the U.S. Geological Survey National Water Quality Laboratory; determination of organochlorine pesticides and polychlorinated biphenyls in bottom sediment by dual capillary-column gas chromatography with electron-capture detection

USGS Publications Warehouse

Foreman, William T.; Connor, Brooke F.; Furlong, Edward T.; Vaught, Deborah G.; Merten, Leslie M.

1995-01-01

A method for the determination of 30 individual organochlorine pesticides, total toxaphene, and total polychlorinated biphenyls (PCBs) in bottom sediment is described. The method isolates the pesticides and PCBs by solvent extraction with dichlorobenzene, removes inorganic sulfur, large naturally occurring molecules, and other unwanted interferences by gel permeation chromatography, and further cleans up and class fractionates the extract using adsorption chromatography. The com- pounds then are instrumentally determined using dual capillary-column gas chromatography with electron-capture detection. Reporting limits range from 1 to 5 micrograms per kilogram for 30 individual pesticides, 50 micrograms per kilogram for total PCBs, and 200 micrograms per kilogram for total toxaphene. The method also is designed to allow the simultaneous isolation of 79 other semivolatile organic compounds from the sediment, which are separately quantified using gas chromatography with mass spectrometric detection. The method was developed in support of the U.S. Geological Survey's National Water-Quality Assessment program.

Simulating real-life exposures to uncover possible risks to human health: A proposed consensus for a novel methodological approach.

PubMed

Tsatsakis, A M; Kouretas, D; Tzatzarakis, M N; Stivaktakis, P; Tsarouhas, K; Golokhvast, K S; Rakitskii, V N; Tutelyan, V A; Hernandez, A F; Rezaee, R; Chung, G; Fenga, C; Engin, A B; Neagu, M; Arsene, A L; Docea, A O; Gofita, E; Calina, D; Taitzoglou, I; Liesivuori, J; Hayes, A W; Gutnikov, S; Tsitsimpikou, C

2017-06-01

In real life, consumers are exposed to complex mixtures of chemicals via food, water and commercial products consumption. Since risk assessment usually focuses on individual compounds, the current regulatory approach doesn't assess the overall risk of chemicals present in a mixture. This study will evaluate the cumulative toxicity of mixtures of different classes of pesticides and mixtures of different classes of pesticides together with food additives (FAs) and common consumer product chemicals using realistic doses after long-term exposure. Groups of Sprague Dawley (CD-SD) rats (20 males and 20 females) will be treated with mixtures of pesticides or mixtures of pesticides together with FAs and common consumer product chemicals in 0.0, 0.25 × acceptable daily intake (ADI)/tolerable daily intake (TDI), ADI/TDI and 5 × ADI/TDI doses for 104 weeks. All animals will be examined every day for signs of morbidity and mortality. Clinical chemistry hematological parameters, serum hormone levels, biomarkers of oxidative stress, cardiotoxicity, genotoxicity, urinalysis and echocardiographic tests will be assessed periodically at 6 month intervals. At 3-month intervals, ophthalmological examination, test for sensory reactivity to different types of stimuli, together with assessment of learning abilities and memory performance of the adult and ageing animals will be conducted. After 24 months, animals will be necropsied, and internal organs will be histopathologically examined. If the hypothesis of an increased risk or a new hazard not currently identified from cumulative exposure to multiple chemicals was observed, this will provide further information to public authorities and research communities supporting the need of replacing current single-compound risk assessment by a more robust cumulative risk assessment paradigm.

Broad screening of illicit ingredients in cosmetics using ultra-high-performance liquid chromatography-hybrid quadrupole-Orbitrap mass spectrometry with customized accurate-mass database and mass spectral library.

PubMed

Meng, Xianshuang; Bai, Hua; Guo, Teng; Niu, Zengyuan; Ma, Qiang

2017-12-15

Comprehensive identification and quantitation of 100 multi-class regulated ingredients in cosmetics was achieved using ultra-high-performance liquid chromatography (UHPLC) coupled with hybrid quadrupole-Orbitrap high-resolution mass spectrometry (Q-Orbitrap HRMS). A simple, efficient, and inexpensive sample pretreatment protocol was developed using ultrasound-assisted extraction (UAE), followed by dispersive solid-phase extraction (dSPE). The cosmetic samples were analyzed by UHPLC-Q-Orbitrap HRMS under synchronous full-scan MS and data-dependent MS/MS (full-scan MS 1 /dd-MS 2 ) acquisition mode. The mass resolution was set to 70,000 FWHM (full width at half maximum) for full-scan MS 1 and 17,500 FWHM for dd-MS 2 stage with the experimentally measured mass deviations of less than 2ppm (parts per million) for quasi-molecular ions and 5ppm for characteristic fragment ions for each individual analyte. An accurate-mass database and a mass spectral library were built in house for searching the 100 target compounds. Broad screening was conducted by comparing the experimentally measured exact mass of precursor and fragment ions, retention time, isotopic pattern, and ionic ratio with the accurate-mass database and by matching the acquired MS/MS spectra against the mass spectral library. The developed methodology was evaluated and validated in terms of limits of detection (LODs), limits of quantitation (LOQs), linearity, stability, accuracy, and matrix effect. The UHPLC-Q-Orbitrap HRMS approach was applied for the analysis of 100 target illicit ingredients in 123 genuine cosmetic samples, and exhibited great potential for high-throughput, sensitive, and reliable screening of multi-class illicit compounds in cosmetics. Copyright © 2017 Elsevier B.V. All rights reserved.

Poor School Satisfaction and Number of Cannabis Using Peers within School Classes as Individual Risk Factors for Cannabis Use among Adolescents

ERIC Educational Resources Information Center

Hoff, Dominic A.; Andersen, Anette; Holstein, Bjorn E.

2010-01-01

There is little information available on the topic of poor school satisfaction as a risk factor for cannabis use among adolescents. We examined if there was an association between poor school satisfaction, school class cannabis use and individual cannabis use. Further, we investigated if many cannabis users within the school class statistically…

Polymorphism at the 5' end flanking region of the insulin gene is associated with reduced insulin secretion in healthy individuals.

PubMed

Cocozza, S; Riccardi, G; Monticelli, A; Capaldo, B; Genovese, S; Krogh, V; Celentano, E; Farinaro, E; Varrone, S; Avvedimento, V E

1988-12-01

Sixty-four unrelated healthy subjects were studied for the detection of a DNA polymorphism at the 5' end of the insulin gene. No significant difference between the groups was found in blood glucose values at fasting and after an oral glucose load. A significant association was found between fasting (P less than 0.05) and after load plasma C-peptide levels (P less than 0.01) and the presence of a 1.6 Kb insertion at the 5' end of the insulin gene. A gene dose-dependent effect was noted, class 3/3 individuals having the lowest after-load C-peptide concentration and class 1/3 an intermediate level (F for the linear trend: P = 0.007). This might suggest that insulin gene polymorphism affects insulin secretion in healthy individuals. In order to confirm this, a subgroup of six class 3/3 and eight class 1/1 individuals subsequently underwent a hyperglycaemic clamp. The tissue sensitivity to insulin was similar in the two groups but glucose-stimulated insulin secretion was markedly impaired in homozygotes for the class 3 allele. In this group, insulin secretion was, on average, only one-third of that in class 1/1 individuals (P less than 0.02). Similarly impaired in class 3/3 persons was the glucose + arginine-stimulated insulin secretion (P less than 0.05). We conclude that the polymorphism at the 5' end of the insulin gene is associated with variations in insulin secretion in healthy humans.

Individual and Class Room Predictors of Same-Cultural Friendship Preferences in Multicultural Schools

ERIC Educational Resources Information Center

Stefanek, Elisabeth; Strohmeier, Dagmar; van de Schoot, Rens

2015-01-01

This study was an investigation of individual and contextual predictors for same-cultural friendship preferences among non-immigrant (N = 125), Turkish (N = 196) and former Yugoslavian (N = 256) immigrant youths (M age = 14.39 years) in 36 multicultural classes. At the individual level age, gender, cultural group, number of friends, and…

Compounding pharmacy: old methods finding a new niche.

PubMed

Matheny, Charlotte; Martin, Caren McHenry

2010-06-01

Pharmaceutical compounding-the process by which a pharmacist combines ingredients into a customized medication for an individual patient-has ancient roots, with popularity that has waxed and waned throughout history. Elderly individuals and other long-term care patients may be among those who need customized medications, so pharmacists should be aware of the current scope and regulations for compounded medications.

A combined Fisher and Laplacian score for feature selection in QSAR based drug design using compounds with known and unknown activities.

PubMed

Valizade Hasanloei, Mohammad Amin; Sheikhpour, Razieh; Sarram, Mehdi Agha; Sheikhpour, Elnaz; Sharifi, Hamdollah

2018-02-01

Quantitative structure-activity relationship (QSAR) is an effective computational technique for drug design that relates the chemical structures of compounds to their biological activities. Feature selection is an important step in QSAR based drug design to select the most relevant descriptors. One of the most popular feature selection methods for classification problems is Fisher score which aim is to minimize the within-class distance and maximize the between-class distance. In this study, the properties of Fisher criterion were extended for QSAR models to define the new distance metrics based on the continuous activity values of compounds with known activities. Then, a semi-supervised feature selection method was proposed based on the combination of Fisher and Laplacian criteria which exploits both compounds with known and unknown activities to select the relevant descriptors. To demonstrate the efficiency of the proposed semi-supervised feature selection method in selecting the relevant descriptors, we applied the method and other feature selection methods on three QSAR data sets such as serine/threonine-protein kinase PLK3 inhibitors, ROCK inhibitors and phenol compounds. The results demonstrated that the QSAR models built on the selected descriptors by the proposed semi-supervised method have better performance than other models. This indicates the efficiency of the proposed method in selecting the relevant descriptors using the compounds with known and unknown activities. The results of this study showed that the compounds with known and unknown activities can be helpful to improve the performance of the combined Fisher and Laplacian based feature selection methods.

A combined Fisher and Laplacian score for feature selection in QSAR based drug design using compounds with known and unknown activities

NASA Astrophysics Data System (ADS)

Valizade Hasanloei, Mohammad Amin; Sheikhpour, Razieh; Sarram, Mehdi Agha; Sheikhpour, Elnaz; Sharifi, Hamdollah

2018-02-01

Quantitative structure-activity relationship (QSAR) is an effective computational technique for drug design that relates the chemical structures of compounds to their biological activities. Feature selection is an important step in QSAR based drug design to select the most relevant descriptors. One of the most popular feature selection methods for classification problems is Fisher score which aim is to minimize the within-class distance and maximize the between-class distance. In this study, the properties of Fisher criterion were extended for QSAR models to define the new distance metrics based on the continuous activity values of compounds with known activities. Then, a semi-supervised feature selection method was proposed based on the combination of Fisher and Laplacian criteria which exploits both compounds with known and unknown activities to select the relevant descriptors. To demonstrate the efficiency of the proposed semi-supervised feature selection method in selecting the relevant descriptors, we applied the method and other feature selection methods on three QSAR data sets such as serine/threonine-protein kinase PLK3 inhibitors, ROCK inhibitors and phenol compounds. The results demonstrated that the QSAR models built on the selected descriptors by the proposed semi-supervised method have better performance than other models. This indicates the efficiency of the proposed method in selecting the relevant descriptors using the compounds with known and unknown activities. The results of this study showed that the compounds with known and unknown activities can be helpful to improve the performance of the combined Fisher and Laplacian based feature selection methods.

Identification of anxiety sensitivity classes and clinical cut-scores in a sample of adult smokers: results from a factor mixture model.

PubMed

Allan, Nicholas P; Raines, Amanda M; Capron, Daniel W; Norr, Aaron M; Zvolensky, Michael J; Schmidt, Norman B

2014-10-01

Anxiety sensitivity (AS), a multidimensional construct, has been implicated in the development and maintenance of anxiety and related disorders. Recent evidence suggests that AS is a dimensional-categorical construct within individuals. Factor mixture modeling was conducted in a sample of 579 adult smokers (M age=36.87 years, SD=13.47) to examine the underlying structure. Participants completed the Anxiety Sensitivity Index-3 and were also given a Structured Clinical Interview for DSM-IV-TR. Three classes of individuals emerged, a high AS (5.2% of the sample), a moderate AS (19.0%), and a normative AS class (75.8%). A cut-score of 23 to identify high AS individuals, and a cut-score of 17 to identify moderate-to-high AS individuals were supported in this study. In addition, the odds of having a concurrent anxiety disorder (controlling for other Axis I disorders) were the highest in the high AS class and the lowest in the normative AS class. Copyright © 2014 Elsevier Ltd. All rights reserved.

Regional-dependent intestinal permeability and BCS classification: elucidation of pH-related complexity in rats using pseudoephedrine.

PubMed

Fairstein, Moran; Swissa, Rotem; Dahan, Arik

2013-04-01

Based on its lower Log P value relative to metoprolol, a marker for the low/high-permeability (P(eff)) class boundary, pseudoephedrine was provisionally classified as BCS low-permeability compound. On the other hand, following oral administration, pseudoephedrine fraction dose absorbed (F(abs)) and systemic bioavailability approaches 100%. This represents a challenge to the generally recognized P(eff)-F(abs) correlation. The purpose of this study was to elucidate the underlying mechanisms behind the confusion in pseudoephedrine's BCS classification. Pseudoephedrine's BCS solubility class was determined, and its physicochemical properties and intestinal permeability were thoroughly investigated, both in vitro and in vivo in rats, considering the complexity of the whole of the small intestine. Pseudoephedrine was found to be unequivocally a high-solubility compound. All of the permeability studies revealed similar phenomenon; at any given intestinal segment/pH, the permeability of metoprolol was higher than that of pseudoephedrine, however, as the intestinal region becomes progressively distal, and the pH gradually increases, pseudoephedrine's permeability rises above that of metoprolol in the former segment. This unique permeability pattern likely explains pseudoephedrine's complete absorption. In conclusion, pseudoephedrine is a BCS Class I compound; no discrepancy between P(eff) and F(abs) is involved in its absorption. Rather, it reflects the complexity behind P(eff) when considering the whole of the intestine. We propose to allow high-permeability classification to drugs with P(eff) that matches/exceeds the low/high class benchmark anywhere throughout the intestinal tract and not restricted necessarily to the jejunum.

Development of metal-chelating inhibitors for the Class II fructose 1,6-bisphosphate (FBP) aldolase.

PubMed

Labbé, Geneviève; Krismanich, Anthony P; de Groot, Sarah; Rasmusson, Timothy; Shang, Muhong; Brown, Matthew D R; Dmitrienko, Gary I; Guillemette, J Guy

2012-07-01

It has long been suggested that the essential and ubiquitous enzyme fructose 1,6-bisphosphate (FBP) aldolase could be a good drug target against bacteria and fungi, since lower organisms possess a metal-dependant (Class II) FBP aldolase, as opposed to higher organisms which possess a Schiff-base forming (Class I) FBP aldolase. We have tested the capacity of derivatives of the metal-chelating compound dipicolinic acid (DPA), as well a thiol-containing compound, to inhibit purified recombinant Class II FBP aldolases from Mycobacterium tuberculosis, Pseudomonas aeruginosa, Bacillus cereus, Bacillus anthracis, and from the Rice Blast causative agent Magnaporthe grisea. The aldolase from M. tuberculosis was the most sensitive to the metal-chelating inhibitors, with an IC(50) of 5.2 μM with 2,3-dimercaptopropanesulfonate (DMPS) and 28 μM with DPA. DMPS and the synthesized inhibitor 6-(phosphonomethyl)picolinic acid inhibited the enzyme in a time-dependent, competitive fashion, with second order rate constants of 273 and 270 M(-1) s(-1) respectively for the binding of these compounds to the M. tuberculosis aldolase's active site in the presence of the substrate FBP (K(M) 27.9 μM). The most potent first generation inhibitors were modeled into the active site of the M. tuberculosis aldolase structure, with results indicating that the metal chelators tested cannot bind the catalytic zinc in a bidentate fashion while it remains in its catalytic location, and that most enzyme-ligand interactions involve the phosphate binding pocket residues. Copyright © 2012 Elsevier Inc. All rights reserved.

Carbon isotope composition of low molecular weight hydrocarbons and monocarboxylic acids from Murchison meteorite

NASA Technical Reports Server (NTRS)

Yuen, G.; Blair, N.; Des Marais, D. J.; Chang, S.

1984-01-01

Carbon isotopic compositions have been measured for individual hydrocarbons and monocarboxylic acids from the Murchison meteorite, a C2 carbonaceous chondrite which fell in Australia in 1969. With few exceptions, notably benzene, the volatile products are substantially isotopically heavier than their terrestrial counterparts, signifying their extraterrestrial origin. For both classes of compounds, the ratio of C-13 to C-12 decreases with increasing carbon number in a roughly parallel manner, and each carboxylic acid exhibits a higher isotopic ratio than the hydrocarbon containing the same number of carbon atoms. These trends are consistent with the kinetically controlled synthesis of higher homologues from lower ones. The results suggest the possibility that the production mechanisms for hydrocarbons and carboxylic acids may be similar, and impose constraints on the identity of the reactant species.

New screening strategy and analysis for identification of allosteric modulators for glucagon-like peptide-1 receptor using GLP-1 (9-36) amide.

PubMed

Nakane, Atsushi; Gotoh, Yusuke; Ichihara, Junji; Nagata, Hidetaka

2015-12-15

The glucagon-like peptide-1 receptor (GLP-1R) is an important physiologic regulator of insulin secretion and a major therapeutic target for diabetes mellitus. GLP-1 (7-36) amide (active form of GLP-1) is truncated to GLP-1 (9-36) amide, which has been described as a weak agonist of GLP-1R and the major form of GLP-1 in the circulation. New classes of positive allosteric modulators (PAMs) for GLP-1R may offer improved therapeutic profiles. To identify these new classes, we developed novel and robust primary and secondary high-throughput screening (HTS) systems in which PAMs were identified to enhance the GLP-1R signaling induced by GLP-1 (9-36) amide. Screening enabled identification of two compounds, HIT-465 and HIT-736, which possessed new patterns of modulation of GLP-1R. We investigated the ability of these compounds to modify GLP-1R signaling enhanced GLP-1 (9-36) amide- and/or GLP-1 (7-36) amide-mediated cyclic adenosine monophosphate (cAMP) accumulation. These compounds also had unique profiles with regard to allosteric modulation of multiple downstream signaling (PathHunter β-arrestin signaling, PathHunter internalization signaling, microscopy-based internalization assay). We found allosteric modulation patterns to be obviously different among HIT-465, HIT-736, and Novo Nordisk compound 2. This work may enable the design of new classes of drug candidates by targeting modulation of GLP-1 (7-36) amide and GLP-1 (9-36) amide. Copyright © 2015 Elsevier Inc. All rights reserved.

Anticancer Properties of Distinct Antimalarial Drug Classes

PubMed Central

Hooft van Huijsduijnen, Rob; Guy, R. Kiplin; Chibale, Kelly; Haynes, Richard K.; Peitz, Ingmar; Kelter, Gerhard; Phillips, Margaret A.; Vennerstrom, Jonathan L.; Yuthavong, Yongyuth; Wells, Timothy N. C.

2013-01-01

We have tested five distinct classes of established and experimental antimalarial drugs for their anticancer potential, using a panel of 91 human cancer lines. Three classes of drugs: artemisinins, synthetic peroxides and DHFR (dihydrofolate reductase) inhibitors effected potent inhibition of proliferation with IC50s in the nM- low µM range, whereas a DHODH (dihydroorotate dehydrogenase) and a putative kinase inhibitor displayed no activity. Furthermore, significant synergies were identified with erlotinib, imatinib, cisplatin, dasatinib and vincristine. Cluster analysis of the antimalarials based on their differential inhibition of the various cancer lines clearly segregated the synthetic peroxides OZ277 and OZ439 from the artemisinin cluster that included artesunate, dihydroartemisinin and artemisone, and from the DHFR inhibitors pyrimethamine and P218 (a parasite DHFR inhibitor), emphasizing their shared mode of action. In order to further understand the basis of the selectivity of these compounds against different cancers, microarray-based gene expression data for 85 of the used cell lines were generated. For each compound, distinct sets of genes were identified whose expression significantly correlated with compound sensitivity. Several of the antimalarials tested in this study have well-established and excellent safety profiles with a plasma exposure, when conservatively used in malaria, that is well above the IC50s that we identified in this study. Given their unique mode of action and potential for unique synergies with established anticancer drugs, our results provide a strong basis to further explore the potential application of these compounds in cancer in pre-clinical or and clinical settings. PMID:24391728

Sexuality Generates Diversity in the Aflatoxin Gene Cluster: Evidence on a Global Scale

PubMed Central

Moore, Geromy G.; Elliott, Jacalyn L.; Singh, Rakhi; Horn, Bruce W.; Dorner, Joe W.; Stone, Eric A.; Chulze, Sofia N.; Barros, German G.; Naik, Manjunath K.; Wright, Graeme C.; Hell, Kerstin; Carbone, Ignazio

2013-01-01

Aflatoxins are produced by Aspergillus flavus and A. parasiticus in oil-rich seed and grain crops and are a serious problem in agriculture, with aflatoxin B1 being the most carcinogenic natural compound known. Sexual reproduction in these species occurs between individuals belonging to different vegetative compatibility groups (VCGs). We examined natural genetic variation in 758 isolates of A. flavus, A. parasiticus and A. minisclerotigenes sampled from single peanut fields in the United States (Georgia), Africa (Benin), Argentina (Córdoba), Australia (Queensland) and India (Karnataka). Analysis of DNA sequence variation across multiple intergenic regions in the aflatoxin gene clusters of A. flavus, A. parasiticus and A. minisclerotigenes revealed significant linkage disequilibrium (LD) organized into distinct blocks that are conserved across different localities, suggesting that genetic recombination is nonrandom and a global occurrence. To assess the contributions of asexual and sexual reproduction to fixation and maintenance of toxin chemotype diversity in populations from each locality/species, we tested the null hypothesis of an equal number of MAT1-1 and MAT1-2 mating-type individuals, which is indicative of a sexually recombining population. All samples were clone-corrected using multi-locus sequence typing which associates closely with VCG. For both A. flavus and A. parasiticus, when the proportions of MAT1-1 and MAT1-2 were significantly different, there was more extensive LD in the aflatoxin cluster and populations were fixed for specific toxin chemotype classes, either the non-aflatoxigenic class in A. flavus or the B1-dominant and G1-dominant classes in A. parasiticus. A mating type ratio close to 1∶1 in A. flavus, A. parasiticus and A. minisclerotigenes was associated with higher recombination rates in the aflatoxin cluster and less pronounced chemotype differences in populations. This work shows that the reproductive nature of the population (more sexual versus more asexual) is predictive of aflatoxin chemotype diversity in these agriculturally important fungi. PMID:24009506

Volatile composition of some Brazilian fruits: umbu-caja (Spondias citherea), camu-camu (Myrciaria dubia), Araça-boi (Eugenia stipitata), and Cupuaçu (Theobroma grandiflorum).

PubMed

Franco, M R; Shibamoto, T

2000-04-01

Twenty-one volatile compounds were identified for the first time by GC-MS in umbu-caja and in camu-camu, plus 30 volatile compounds were identified in araça-boi samples. Terpenic compounds predominated among the volatile compounds in these fruit samples, with the major compounds being identified as cis-beta-ocimene and caryophyllene in the northeastern fruit; alpha-pinene and d-limonene were the most abundant volatile compounds in the headspace of the Amazonian fruit camu-camu. Sesquiterpenes were the most abundant compounds in the araça-boi sample, with germacrene D presenting a higher relative percentage. The chemical class of esters predominated in the cupuaçu sample. Ethyl butyrate and hexanoate were the major compounds in the headspace of this Amazonian fruit.

Investigation of the Anti-Prostate Cancer Properties of Marine-Derived Compounds

PubMed Central

Fan, Meiqi; Nath, Amit Kumar; Tang, Yujiao; Choi, Young-Jin; Debnath, Trishna; Choi, Eun-Ju

2018-01-01

This review focuses on marine compounds with anti-prostate cancer properties. Marine species are unique and have great potential for the discovery of anticancer drugs. Marine sources are taxonomically diverse and include bacteria, cyanobacteria, fungi, algae, and mangroves. Marine-derived compounds, including nucleotides, amides, quinones, polyethers, and peptides are biologically active compounds isolated from marine organisms such as sponges, ascidians, gorgonians, soft corals, and bryozoans, including those mentioned above. Several compound classes such as macrolides and alkaloids include drugs with anti-cancer mechanisms, such as antioxidants, anti-angiogenics, antiproliferatives, and apoptosis-inducing drugs. Despite the diversity of marine species, most marine-derived bioactive compounds have not yet been evaluated. Our objective is to explore marine compounds to identify new treatment strategies for prostate cancer. This review discusses chemically and pharmacologically diverse marine natural compounds and their sources in the context of prostate cancer drug treatment. PMID:29757237

Genomic mechanisms of stress tolerance for the industrial yeast Saccharomyces cerevisiae against the major chemical classes of inhibitors derived from lignocellulosic biomass conversion

USDA-ARS?s Scientific Manuscript database

Scientists at ARS developed tolerant industrial yeast that is able to reduce major chemical classes of inhibitors into less toxic or none toxic compounds while producing ethanol. Using genomic studies, we defined mechanisms of in situ detoxification involved in novel gene functions, vital cofactor r...

Estrogen regulates histone deacetylases to prevent cardiac hypertrophy

PubMed Central

Pedram, Ali; Razandi, Mahnaz; Narayanan, Ramesh; Dalton, James T.; McKinsey, Timothy A.; Levin, Ellis R.

2013-01-01

The development and progression of cardiac hypertrophy often leads to heart failure and death, and important modulators of hypertrophy include the histone deacetylase proteins (HDACs). Estrogen inhibits cardiac hypertrophy and progression in animal models and humans. We therefore investigated the influence of 17-β-estradiol on the production, localization, and functions of prohypertrophic (class I) and antihypertrophic (class II) HDACs in cultured neonatal rat cardiomyocytes. 17-β-Estradiol or estrogen receptor β agonists dipropylnitrile and β-LGND2 comparably suppressed angiotensin II–induced HDAC2 (class I) production, HDAC-activating phosphorylation, and the resulting prohypertrophic mRNA expression. In contrast, estrogenic compounds derepressed the opposite effects of angiotensin II on the same parameters for HDAC4 and 5 (class II), resulting in retention of these deacetylases in the nucleus to inhibit hypertrophic gene expression. Key aspects were confirmed in vivo from the hearts of wild-type but not estrogen receptor β (ERβ) gene–deleted mice administered angiotensin II and estrogenic compounds. Our results identify a novel dual regulation of cardiomyocyte HDACs, shown here for the antihypertrophic sex steroid acting at ERβ. This mechanism potentially supports using ERβ agonists as HDAC modulators to treat cardiac disease. PMID:24152730

New materials and structures for photovoltaics

NASA Astrophysics Data System (ADS)

Zunger, Alex; Wagner, S.; Petroff, P. M.

1993-01-01

Despite the fact that over the years crystal chemists have discovered numerous semiconducting substances, and that modern epitaxial growth techniques are able to produce many novel atomic-scale architectures, current electronic and opto-electronic technologies are based but on a handful of ˜10 traditional semiconductor core materials. This paper surveys a number of yet-unexploited classes of semiconductors, pointing to the much-needed research in screening, growing, and characterizing promising members of these classes. In light of the unmanageably large number of a-priori possibilities, we emphasize the role that structural chemistry and modern computer-aided design must play in screening potentially important candidates. The basic classes of materials discussed here include nontraditional alloys, such as non-isovalent and heterostructural semiconductors, materials at reduced dimensionality, including superlattices, zeolite-caged nanostructures and organic semiconductors, spontaneously ordered alloys, interstitial semiconductors, filled tetrahedral structures, ordered vacancy compounds, and compounds based on d and f electron elements. A collaborative effort among material predictor, material grower, and material characterizer holds the promise for a successful identification of new and exciting systems.