Oxygen transfer rate identifies priming compounds in parsley cells.

Science.gov (United States)

Schilling, Jana Viola; Schillheim, Britta; Mahr, Stefan; Reufer, Yannik; Sanjoyo, Sandi; Conrath, Uwe; Büchs, Jochen

2015-11-25

In modern agriculture, the call for an alternative crop protection strategy increases because of the desired reduction of fungicide and pesticide use and the continuously evolving resistance of pathogens and pests to agrochemicals. The direct activation of the plant immune system does not provide a promising plant protection measure because of high fitness costs. However, upon treatment with certain natural or synthetic compounds, plant cells can promote to a fitness cost-saving, primed state of enhanced defense. In the primed state, plants respond to biotic and abiotic stress with faster and stronger activation of defense, and this is often associated with immunity and abiotic stress tolerance. Until now, the identification of chemical compounds with priming-inducing activity (so-called plant activators) relied on tedious and invasive approaches, or required the late detection of secreted furanocoumarin phytoalexins in parsley cell cultures. Thus, simple, fast, straightforward, and noninvasive techniques for identifying priming-inducing compounds for plant protection are very welcome. This report demonstrates that a respiration activity-monitoring system (RAMOS) can identify compounds with defense priming-inducing activity in parsley cell suspension in culture. RAMOS relies on the quasi-continuous, noninvasive online determination of the oxygen transfer rate (OTR). Treatment of parsley culture cells with the known plant activator salicylic acid (SA), a natural plant defense signal, resulted in an OTR increase. Addition of the defense elicitor Pep13, a cell wall peptide of Phythophthora sojae, induced two distinctive OTR peaks that were higher in SA-primed cells than in unprimed cells upon Pep13 challenge. Both, the OTR increase after priming with SA and the Pep13 challenge were dose-dependent. Furthermore, there was a close correlation of a compound's activity to enhance the oxygen consumption in parsley cells and its capacity to prime Pep13-induced furanocoumarin

VOLATILE COMPOUNDS IDENTIFIED IN BARBADOS CHERRY ‘BRS-366 JABURÚ’

Directory of Open Access Journals (Sweden)

Y. M. Garcia

2016-07-01

Full Text Available In foods, the flavor and aroma are very important attributes, thus the main objective of this study was to identify the volatile compounds (VC of the "BRS-366 Jaburú" acerola variety, for which we used the solid phase microextraction method (SPE. The separation and identification of volatile compounds was made using gas chromatography-mass spectrometry (GC-MS. Three fibers were evaluated, Polydimethylsiloxane / Divinylbenzene (PDMS / DVB, 65 micrometres Divinylbenzene / Carboxen / Polydimethylsiloxane (DVB / CAR / PDMS 50/30 m and polyacrylate (PA 85 uM to compare the extraction of its components. Thirty-three volatile compounds were identified and classified into eight chemical classes: carboxylic acids, alcohols, aldehydes, ketones, esters, hydrocarbons, phenylpropanoids and terpenoids. The peak areas of each of the extracted compounds were expressed as percentages to indicate the relative concentration of each, of which ethyl acetate is distinguished by being responsible for the fruity aroma notes. Thus, the fiber PDMS / DVB was the best as it enabled to extract a greater amount of volatile compounds

Leading change: 1--identifying the issue.

Science.gov (United States)

Kerridge, Joanna

To enable sustainable change, nurses need to take the lead in managing it. Recent national initiatives have emphasised the importance of frontline staff in service improvement. The ability to influence and manage change has been identified as an essential skill for delivering new models of care. This article is the first in a three-part series designed to help nurses at all levels develop the knowledge and skills they will need to initiate and manage change. This article focuses on identifying what needs to be changed and why.

Lead application for the stimulation of fusaricidin type compounds by paenibacillus polymyxa SQR-21

International Nuclear Information System (INIS)

Raza, W.; Wu, H.; Qirong, S.

2011-01-01

Paenibacillus polymyxa strains produce fusaricidin type compounds that are active against a wide variety of Gram-positive bacteria and fungi. Growth and production of fusaricidin type antifungal compounds by P. polymyxa SQR-21 were compared in tryptone broth supplemented with three concentrations (200, 400 and 600 mu M) of lead. The data revealed that the growth of P. polymyxa increased by 7-34 % and fusaricidin type compounds production increased by 15-70 % with the increase in concentration of lead ion (Pb/sup 2+/). The increase in Pb/sup 2+/ concentration, decreased the intracellular carbohydrate contents but increased the intracellular protein and lipid contents, however, higher levels of Pb/sup 2+/ inhibited the intracellular protein and lipid contents. On the other hand, extracellular protein contents were decreased and extracellular polysaccharide contents were increased with the increase in Pb/sup 2+/ contents in liquid culture. In addition, the regulatory effects of lead were also reflected by decrease of total RNA and increase of relative expression of the six module-containing non ribosomal peptide synthetase (FusA) when the lead treated experimental samples were compared with the untreated controls. The Pb/sup 2+/ seems to be directly or indirectly correlated with the production of fusaricidin type antifungal compounds. This information will aid in developing fermentation technology for maximum antibiotic production. (author)

Identifying Lead Markets in the European Automotive Industry

DEFF Research Database (Denmark)

Cleff, Thomas; Grimpe, Christoph; Rammer, Christian

2015-01-01

for automobiles and national markets differ considerably in their lead market potential. The German market is found to be most promising to serve as a lead market, while other European countries with a strong automotive tradition like France, Italy, the UK, and Sweden score lower. Our findings suggest that firms......This paper presents an indicator-based methodology to identify lead markets in the European automotive industry. The lead market approach tries to explain why certain countries are better positioned than others for developing and launching new products. While much research stresses the role...... of excellence in technology and interaction among users and producers, the lead market approach focuses on the role of demand characteristics. Based on the concept of innovation design, a lead market is defined as a country where customers prefer that design which subsequently becomes the globally dominant...

Erythrocyte hemolysis by organic tin and lead compounds

Energy Technology Data Exchange (ETDEWEB)

Kleszcynska, H. [Agricultural Univ., Wroclaw (Poland). Dept. of Physics and Biophysics; Hladyszowski, J. [Agricultural Univ., Wroclaw (Poland). Dept. of Physics and Biophysics; Pruchnik, H. [Agricultural Univ., Wroclaw (Poland). Dept. of Physics and Biophysics; Przestalski, S. [Agricultural Univ., Wroclaw (Poland). Dept. of Physics and Biophysics

1997-01-01

The effect of trialkyllead and trialkyltin on pig erythrocyte hemolysis has been studied and compared. The results of experiments showed that the hemolytic activity of organoleads increases with their hydrophobicity and follows the sequence: triethyllead chloride < tri-n-propyllead chloride < tributyllead chloride. And similarly in the case of organotins: triethyltin chloride < tri-n-propyltin chloride < tributyltin chloride. Comparison of the hemolytic activity of organoleads and organotins indicates that the lead compounds exhibit higher hemolytic activity. The methods of quantum chemistry allowed to determine the maximum electric potential of the ions R{sub 3}Pb{sup +} and R{sub 3}Sn{sup +}, and suggest a relationship between the potential and toxicity. (orig.)

Novel curcumin- and emodin-related compounds identified by in silico 2D/3D conformer screening induce apoptosis in tumor cells

International Nuclear Information System (INIS)

Füllbeck, Melanie; Huang, Xiaohua; Dumdey, Renate; Frommel, Cornelius; Dubiel, Wolfgang; Preissner, Robert

2005-01-01

Inhibition of the COP9 signalosome (CSN) associated kinases CK2 and PKD by curcumin causes stabilization of the tumor suppressor p53. It has been shown that curcumin induces tumor cell death and apoptosis. Curcumin and emodin block the CSN-directed c-Jun signaling pathway, which results in diminished c-Jun steady state levels in HeLa cells. The aim of this work was to search for new CSN kinase inhibitors analogue to curcumin and emodin by means of an in silico screening method. Here we present a novel method to identify efficient inhibitors of CSN-associated kinases. Using curcumin and emodin as lead structures an in silico screening with our in-house database containing more than 10 6 structures was carried out. Thirty-five compounds were identified and further evaluated by the Lipinski's rule-of-five. Two groups of compounds can be clearly discriminated according to their structures: the curcumin-group and the emodin-group. The compounds were evaluated in in vitro kinase assays and in cell culture experiments. The data revealed 3 compounds of the curcumin-group (e.g. piceatannol) and 4 of the emodin-group (e.g. anthrachinone) as potent inhibitors of CSN-associated kinases. Identified agents increased p53 levels and induced apoptosis in tumor cells as determined by annexin V-FITC binding, DNA fragmentation and caspase activity assays. Our data demonstrate that the new in silico screening method is highly efficient for identifying potential anti-tumor drugs

Instrumental neutron-activation determination of impurities in lead and titanium compounds

Energy Technology Data Exchange (ETDEWEB)

Popova, I L

1980-01-01

Instrumental neutron-activation analysis was used to determine 22 impurities in lead and titanium compounds (e.g. PbO, Pb/NO3/2, and TiO2) used as raw materials for ferroelectrics. Five elements (Al, V, Mn, Sc, and Se) were determined by short-lived isotopes and 17 elements were determined by long-lived isotopes. The detection limits were 7 x 10 to the -3rd to 2 x 10 to the -8th %. A substantial difference in concentrations of certain impurity elements has been found in different series of lead and titanium oxides of similar purity.

Passive sampling as a tool for identifying micro-organic compounds in groundwater.

Science.gov (United States)

Mali, N; Cerar, S; Koroša, A; Auersperger, P

2017-09-01

The paper presents the use of a simple and cost efficient passive sampling device with integrated active carbon with which to test the possibility of determining the presence of micro-organic compounds (MOs) in groundwater and identifying the potential source of pollution as well as the seasonal variability of contamination. Advantage of the passive sampler is to cover a long sampling period by integrating the pollutant concentration over time, and the consequently analytical costs over the monitoring period can be reduced substantially. Passive samplers were installed in 15 boreholes in the Maribor City area in Slovenia, with two sampling campaigns covered a period about one year. At all sampling sites in the first series a total of 103 compounds were detected, and 144 in the second series. Of all detected compounds the 53 most frequently detected were selected for further analysis. These were classified into eight groups based on the type of their source: Pesticides, Halogenated solvents, Non-halogenated solvents, Domestic and personal, Plasticizers and additives, Other industrial, Sterols and Natural compounds. The most frequently detected MO compounds in groundwater were tetrachloroethene and trichloroethene from the Halogenated solvents group. The most frequently detected among the compound's groups were pesticides. Analysis of frequency also showed significant differences between the two sampling series, with less frequent detections in the summer series. For the analysis to determine the origin of contamination three groups of compounds were determined according to type of use: agriculture, urban and industry. Frequency of detection indicates mixed land use in the recharge areas of sampling sites, which makes it difficult to specify the dominant origin of the compound. Passive sampling has proved to be useful tool with which to identify MOs in groundwater and for assessing groundwater quality. Copyright © 2017 Elsevier B.V. All rights reserved.

A role for fragment-based drug design in developing novel lead compounds for central nervous system targets

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Michael J. Wasko

2015-09-01

Full Text Available Hundreds of millions of U.S. dollars are invested in the research and development of a single drug. Lead compound development is an area ripe for new design strategies. Therapeutic lead candidates have been traditionally found using high-throughput in vitro pharmacologic screening, a costly method for assaying thousands of compounds. This approach has recently been augmented by virtual screening, which employs computer models of the target protein to narrow the search for possible leads. A variant of virtual screening is fragment-based drug design, an emerging in silico lead discovery method that introduces low molecular weight fragments, rather than intact compounds, into the binding pocket of the receptor model. These fragments serve as starting points for growing the lead candidate. Current efforts in virtual fragment-based drug design within central nervous system (CNS targets are reviewed, as is a recent rule-based optimization strategy in which new molecules are generated within a 3D receptor binding pocket using the fragment as a scaffold. This process places special emphasis on creating synthesizable molecules but also exposes computational questions worth addressing. Fragment-based methods provide a viable, relatively low-cost alternative for therapeutic lead discovery and optimization that can be applied to CNS targets to augment current design strategies.

A Role for Fragment-Based Drug Design in Developing Novel Lead Compounds for Central Nervous System Targets.

Science.gov (United States)

Wasko, Michael J; Pellegrene, Kendy A; Madura, Jeffry D; Surratt, Christopher K

2015-01-01

Hundreds of millions of U.S. dollars are invested in the research and development of a single drug. Lead compound development is an area ripe for new design strategies. Therapeutic lead candidates have been traditionally found using high-throughput in vitro pharmacological screening, a costly method for assaying thousands of compounds. This approach has recently been augmented by virtual screening (VS), which employs computer models of the target protein to narrow the search for possible leads. A variant of VS is fragment-based drug design (FBDD), an emerging in silico lead discovery method that introduces low-molecular weight fragments, rather than intact compounds, into the binding pocket of the receptor model. These fragments serve as starting points for "growing" the lead candidate. Current efforts in virtual FBDD within central nervous system (CNS) targets are reviewed, as is a recent rule-based optimization strategy in which new molecules are generated within a 3D receptor-binding pocket using the fragment as a scaffold. This process not only places special emphasis on creating synthesizable molecules but also exposes computational questions worth addressing. Fragment-based methods provide a viable, relatively low-cost alternative for therapeutic lead discovery and optimization that can be applied to CNS targets to augment current design strategies.

Synthesis, crystal structures and properties of lead phosphite compounds

International Nuclear Information System (INIS)

Song, Jun-Ling; Hu, Chun-Li; Xu, Xiang; Kong, Fang; Mao, Jiang-Gao

2015-01-01

Here, we report the preparation and characterization of two lead(II) phosphites, namely, Pb_2(HPO_3)_2 and Pb_2(HPO_3)(NO_3)_2 through hydrothermal reaction or simple solution synthesis, respectively. A new lead phosphite, namely, Pb_2(HPO_3)_2, crystallizes in the noncentrosymmetric space group Cmc2_1 (no. 36), which features 3D framework formed by the interconnection of 2D layer of lead(II) phosphites and 1D chain of [Pb(HPO_3)_5]_∞. The nonlinear optical properties of Pb_2(HPO_3)(NO_3)_2 have been studied for the first time. The synergistic effect of the stereo-active lone-pairs on Pb"2"+ cations and π-conjugated NO_3 units in Pb_2(HPO_3)(NO_3)_2 produces a moderate second harmonic generation (SHG) response of ∼1.8×KDP (KH_2PO_4), which is phase matchable (type I). IR, UV–vis spectra and thermogravimetric analysis (TGA) for the two compounds were also measured. - Graphical abstract: Two lead phosphites Pb_2(HPO_3)_2 and Pb_2(HPO_3)(NO_3)_2 are studied. A new lead phosphite Pb_2(HPO_3)_2 features a unique 3D framework structure and Pb_2(HPO_3)(NO_3)_2 shows a moderate SHG response of ∼1.8×KDP (KH_2PO_4). - Highlights: • A new lead phosphite, Pb_2(HPO_3)_2 is reported. • Pb_2(HPO_3)_2 features a unique 3D framework structure. • NLO property of Pb_2(HPO_3)(NO_3)_2 is investigated. • Pb_2(HPO_3)(NO_3)_2 produces a moderate SHG response of ∼1.8×KDP (KH_2PO_4).

Screening of pharmacologically active small molecule compounds identifies antifungal agents against Candida biofilms

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Takao eWatamoto

2015-12-01

Full Text Available Candida species have emerged as important and common opportunistic human pathogens, particularly in immunocompromised individuals. The current antifungal therapies either have toxic side effects or are insufficiently effect. The aim of this study is develop new small-molecule antifungal compounds by library screening methods using C. albicans, and to evaluate their antifungal effects on Candida biofilms and cytotoxic effects on human cells. Wild-type C. albicans strain SC5314 was used in library screening. To identify antifungal compounds, we screened a small-molecule library of 1,280 pharmacologically active compounds (LOPAC1280TM using an antifungal susceptibility test (AST. To investigate the antifungal effects of the hit compounds, ASTs were conducted using Candida strains in various growth modes, including biofilms. We tested the cytotoxicity of the hit compounds using human gingival fibroblast (hGF cells to evaluate their clinical safety. Only 35 compounds were identified by screening, which inhibited the metabolic activity of C. albicans by >50%. Of these, 26 compounds had fungistatic effects and 9 compounds had fungicidal effects on C. albicans. Five compounds, BAY11-7082, BAY11-7085, sanguinarine chloride hydrate, ellipticine and CV-3988, had strong fungicidal effects and could inhibit the metabolic activity of Candida biofilms. However, BAY11-7082, BAY11-7085, sanguinarine chloride hydrate and ellipticine were cytotoxic to hGF cells at low concentrations. CV-3988 showed no cytotoxicity at a fungicidal concentration.Four of the compounds identified, BAY11-7082, BAY11-7085, sanguinarine chloride hydrate and ellipticine, had toxic effects on Candida strains and hGF cells. In contrast, CV-3988 had fungicidal effects on Candida strains, but low cytotoxic effects on hGF cells. Therefore, this screening reveals agent, CV-3988 that was previously unknown to be antifungal agent, which could be a novel therapies for superficial mucosal

Identifying housing that poisons: a critical step in eliminating childhood lead poisoning.

Science.gov (United States)

Reyes, Nimia L; Wong, Lee-Yang; MacRoy, Patrick M; Curtis, Gerald; Meyer, Pamela A; Evens, Anne; Brown, Mary Jean

2006-01-01

The purpose of our study was to develop a method to identify and prioritize "high-risk" buildings in Chicago that could be targeted for childhood lead poisoning prevention activities. We defined "high-risk" buildings as those where multiple children younger than 6 years with elevated blood lead levels (BLLs) had lived and where lead hazards were previously identified on environmental inspection. By linking 1997-2003 Chicago elevated blood lead surveillance, environmental inspection, and building footprint data, we found that 49,362 children younger than 6 years with elevated BLLs lived at 30,742 buildings. Of those, 67 were "high-risk" buildings and these were associated with 994 children with elevated BLLs. On average, 15 children with elevated BLLs had lived in each building (range: 10-53, median: 13). Almost two thirds (n = 43) of the high-risk buildings had two or more referrals for inspection to the same apartment or housing unit; of those, 40 percent (n = 17) failed to maintain lead-safe status after compliance. Linking blood lead surveillance, environmental inspection, and building footprint databases allowed us to identify individual high-risk buildings. This approach prioritizes lead hazard control efforts and may help health, housing, and environmental agencies in targeting limited resources to increase lead-safe housing for children.

Alkaline earth lead and tin compounds Ae2Pb, Ae2Sn, Ae = Ca, Sr, Ba, as thermoelectric materials

Science.gov (United States)

Parker, David; Singh, David J

2013-01-01

We present a detailed theoretical study of three alkaline earth compounds Ca2Pb, Sr2Pb and Ba2Pb, which have undergone little previous study, calculating electronic band structures and Boltzmann transport and bulk moduli using density functional theory. We also study the corresponding tin compounds Ca2Sn, Sr2Sn and Ba2Sn. We find that these are all narrow band gap semiconductors with an electronic structure favorable for thermoelectric performance, with substantial thermopowers for the lead compounds at temperature ranges from 300 to 800 K. For the lead compounds, we further find very low calculated bulk moduli—roughly half of the values for the lead chalcogenides, suggestive of soft phonons and hence low lattice thermal conductivity. All these facts indicate that these materials merit experimental investigation as potential high performance thermoelectrics. We find good potential for thermoelectric performance in the environmentally friendly stannide materials, particularly at high temperature. PMID:27877610

Alkaline earth lead and tin compounds Ae2Pb, Ae2Sn, Ae = Ca, Sr, Ba, as thermoelectric materials

Directory of Open Access Journals (Sweden)

David Parker and David J Singh

2013-01-01

Full Text Available We present a detailed theoretical study of three alkaline earth compounds Ca2Pb, Sr2Pb and Ba2Pb, which have undergone little previous study, calculating electronic band structures and Boltzmann transport and bulk moduli using density functional theory. We also study the corresponding tin compounds Ca2Sn, Sr2Sn and Ba2Sn. We find that these are all narrow band gap semiconductors with an electronic structure favorable for thermoelectric performance, with substantial thermopowers for the lead compounds at temperature ranges from 300 to 800 K. For the lead compounds, we further find very low calculated bulk moduli—roughly half of the values for the lead chalcogenides, suggestive of soft phonons and hence low lattice thermal conductivity. All these facts indicate that these materials merit experimental investigation as potential high performance thermoelectrics. We find good potential for thermoelectric performance in the environmentally friendly stannide materials, particularly at high temperature.

Identifying a compound modifying a cellular response, comprises attaching cells having a reporter system onto solid supports, releasing a library member, screening and identifying target cells

DEFF Research Database (Denmark)

2011-01-01

The present invention relates to methods for identifying compounds capable of modulating a cellular response. The methods involve attaching living cells to solid supports comprising a library of test compounds. Test compounds modulating a cellular response, for example via a cell surface molecule...... may be identified by selecting solid supports comprising cells, wherein the cellular response of interest has been modulated. The cellular response may for example be changes in signal transduction pathways modulated by a cell surface molecule....

Dual-acting of Hybrid Compounds - A New Dawn in the Discovery of Multi-target Drugs: Lead Generation Approaches.

Science.gov (United States)

Abdolmaleki, Azizeh; Ghasemi, Jahan B

2017-01-01

Finding high quality beginning compounds is a critical job at the start of the lead generation stage for multi-target drug discovery (MTDD). Designing hybrid compounds as selective multitarget chemical entity is a challenge, opportunity, and new idea to better act against specific multiple targets. One hybrid molecule is formed by two (or more) pharmacophore group's participation. So, these new compounds often exhibit two or more activities going about as multi-target drugs (mtdrugs) and may have superior safety or efficacy. Application of integrating a range of information and sophisticated new in silico, bioinformatics, structural biology, pharmacogenomics methods may be useful to discover/design, and synthesis of the new hybrid molecules. In this regard, many rational and screening approaches have followed by medicinal chemists for the lead generation in MTDD. Here, we review some popular lead generation approaches that have been used for designing multiple ligands (DMLs). This paper focuses on dual- acting chemical entities that incorporate a part of two drugs or bioactive compounds to compose hybrid molecules. Also, it presents some of key concepts and limitations/strengths of lead generation methods by comparing combination framework method with screening approaches. Besides, a number of examples to represent applications of hybrid molecules in the drug discovery are included. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Oridonin, a Promising ent-Kaurane Diterpenoid Lead Compound

Directory of Open Access Journals (Sweden)

Dahong Li

2016-08-01

Full Text Available Oridonin belongs to ent-kaurane tetracyclic diterpenoid and was first isolated from Isodon species. It exhibits inhibitory activities against a variety of tumor cells, and pharmacological study shows that oridonin could inhibit cell proliferation, DNA, RNA and protein synthesis of cancer cells, induce apoptosis and exhibit an antimutagenic effect. In addition, the large amount of the commercially-available supply is also very important for the natural lead oridonin. Moreover, the good stability, suitable molecular weight and drug-like property guarantee its further generation of a natural-like compound library. Oridonin has become the hot molecule in recent years, and from the year 2010, more than 200 publications can be found. In this review, we summarize the synthetic medicinal chemistry work of oridonin from the first publication 40 years ago and share our research experience of oridonin for about 10 years, which may provide useful information to those who are interested in this research field.

Effectively identifying compound-protein interactions by learning from positive and unlabeled examples.

Science.gov (United States)

Cheng, Zhanzhan; Zhou, Shuigeng; Wang, Yang; Liu, Hui; Guan, Jihong; Chen, Yi-Ping Phoebe

2016-05-18

Prediction of compound-protein interactions (CPIs) is to find new compound-protein pairs where a protein is targeted by at least a compound, which is a crucial step in new drug design. Currently, a number of machine learning based methods have been developed to predict new CPIs in the literature. However, as there is not yet any publicly available set of validated negative CPIs, most existing machine learning based approaches use the unknown interactions (not validated CPIs) selected randomly as the negative examples to train classifiers for predicting new CPIs. Obviously, this is not quite reasonable and unavoidably impacts the CPI prediction performance. In this paper, we simply take the unknown CPIs as unlabeled examples, and propose a new method called PUCPI (the abbreviation of PU learning for Compound-Protein Interaction identification) that employs biased-SVM (Support Vector Machine) to predict CPIs using only positive and unlabeled examples. PU learning is a class of learning methods that leans from positive and unlabeled (PU) samples. To the best of our knowledge, this is the first work that identifies CPIs using only positive and unlabeled examples. We first collect known CPIs as positive examples and then randomly select compound-protein pairs not in the positive set as unlabeled examples. For each CPI/compound-protein pair, we extract protein domains as protein features and compound substructures as chemical features, then take the tensor product of the corresponding compound features and protein features as the feature vector of the CPI/compound-protein pair. After that, biased-SVM is employed to train classifiers on different datasets of CPIs and compound-protein pairs. Experiments over various datasets show that our method outperforms six typical classifiers, including random forest, L1- and L2-regularized logistic regression, naive Bayes, SVM and k-nearest neighbor (kNN), and three types of existing CPI prediction models. Source code, datasets and

Levels and source apportionment of children's lead exposure: Could urinary lead be used to identify the levels and sources of children's lead pollution?

International Nuclear Information System (INIS)

Cao, Suzhen; Duan, Xiaoli; Zhao, Xiuge; Wang, Beibei; Ma, Jin; Fan, Delong; Sun, Chengye; He, Bin; Wei, Fusheng; Jiang, Guibin

2015-01-01

As a highly toxic heavy metal, the pollution and exposure risks of lead are of widespread concern for human health. However, the collection of blood samples for use as an indicator of lead pollution is not always feasible in most cohort or longitudinal studies, especially those involving children health. To evaluate the potential use of urinary lead as an indicator of exposure levels and source apportionment, accompanying with environmental media samples, lead concentrations and isotopic measurements (expressed as 207 Pb/ 206 Pb, 208 Pb/ 206 Pb and 204 Pb/ 206 Pb) were investigated and compared between blood and urine from children living in the vicinities of a typical coking plant and lead-acid battery factory. The results showed urinary lead might not be a preferable proxy for estimating blood lead levels. Fortunately, urinary lead isotopic measurements could be used as an alternative for identifying the sources of children's lead exposure, which coincided well with the blood lead isotope ratio analysis. - Highlights: • Pb isotopes of environmental media and children's blood and urine were analyzed. • Pb exposure and pollution source were studied in lead-acid battery and coking areas. • Pb isotope ratios in blood and urine were similar to those of food, water and PM. • Urine Pb level may not be used as a proxy for indicating the lead levels in blood. • Urine Pb isotope ratios is an alternative to identify source and exposure pathways. - Urinary lead is not a preferable proxy to estimate blood lead level, but urinary lead isotope ratios could be an alternative for identifying the sources of lead exposure in children

Structure Based Virtual Screening Studies to Identify Novel Potential Compounds for GPR142 and Their Relative Dynamic Analysis for Study of Type 2 Diabetes

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Aman C. Kaushik

2018-02-01

Full Text Available GPR142 (G protein receptor 142 is a novel orphan GPCR (G protein coupled receptor belonging to “Class A” of GPCR family and expressed in β cells of pancreas. In this study, we reported the structure based virtual screening to identify the hit compounds which can be developed as leads for potential agonists. The results were validated through induced fit docking, pharmacophore modeling, and system biology approaches. Since, there is no solved crystal structure of GPR142, we attempted to predict the 3D structure followed by validation and then identification of active site using threading and ab initio methods. Also, structure based virtual screening was performed against a total of 1171519 compounds from different libraries and only top 20 best hit compounds were screened and analyzed. Moreover, the biochemical pathway of GPR142 complex with screened compound2 was also designed and compared with experimental data. Interestingly, compound2 showed an increase in insulin production via Gq mediated signaling pathway suggesting the possible role of novel GPR142 agonists in therapy against type 2 diabetes.

Structure Based Virtual Screening Studies to Identify Novel Potential Compounds for GPR142 and Their Relative Dynamic Analysis for Study of Type 2 Diabetes

Science.gov (United States)

Kaushik, Aman C.; Kumar, Sanjay; Wei, Dong Q.; Sahi, Shakti

2018-02-01

GPR142 (G protein receptor 142) is a novel orphan GPCR (G protein coupled receptor) belonging to ‘Class A’ of GPCR family and expressed in beta cells of pancreas. In this study, we reported the structure based virtual screening to identify the hit compounds which can be developed as leads for potential agonists. The results were validated through induced fit docking, pharmacophore modeling and system biology approaches. Since, there is no solved crystal structure of GPR142, we attempted to predict the 3D structure followed by validation and then identification of active site using threading and ab initio methods. Also, structure based virtual screening was performed against a total of 1171519 compounds from different libraries and only top 20 best hit compounds were screened and analyzed. Moreover, the biochemical pathway of GPR142 complex with screened compound2 was also designed and compared with experimental data. Interestingly, compound2 showed an increase in insulin production via Gq mediated signaling pathway suggesting the possible role of novel GPR142 agonists in therapy against type 2 diabetes.

Identifying anthropogenic uranium compounds using soft X-ray near-edge absorption spectroscopy

Energy Technology Data Exchange (ETDEWEB)

Ward, Jesse D.; Bowden, Mark; Tom Resch, C.; Eiden, Gregory C.; Pemmaraju, C. D.; Prendergast, David; Duffin, Andrew M.

2017-01-01

Uranium ores mined for industrial use are typically acid-leached to produce yellowcake and then converted into uranium halides for enrichment and purification. These anthropogenic chemical forms of uranium are distinct from their mineral counterparts. The purpose of this study is to use soft X-ray absorption spectroscopy to characterize several common anthropogenic uranium compounds important to the nuclear fuel cycle. Non-destructive chemical analyses of these compounds is important for process and environmental monitoring and X-ray absorption techniques have several advantages in this regard, including element-specificity, chemical sensitivity, and high spectral resolution. Oxygen K-edge spectra were collected for uranyl nitrate, uranyl fluoride, and uranyl chloride, and fluorine K-edge spectra were collected for uranyl fluoride and uranium tetrafluoride. Interpretation of the data is aided by comparisons to calculated spectra. These compounds have unique spectral signatures that can be used to identify unknown samples.

Identifying developmental vascular disruptor compounds using a predictive signature and alternative toxicity models

Science.gov (United States)

Identifying Developmental Vascular Disruptor Compounds Using a Predictive Signature and Alternative Toxicity Models Presenting Author: Tamara Tal Affiliation: U.S. EPA/ORD/ISTD, RTP, NC, USA Chemically induced vascular toxicity during embryonic development can result in a wide...

High-Throughput Screening to Identify Compounds That Increase Fragile X Mental Retardation Protein Expression in Neural Stem Cells Differentiated From Fragile X Syndrome Patient-Derived Induced Pluripotent Stem Cells.

Science.gov (United States)

Kumari, Daman; Swaroop, Manju; Southall, Noel; Huang, Wenwei; Zheng, Wei; Usdin, Karen

2015-07-01

: Fragile X syndrome (FXS), the most common form of inherited cognitive disability, is caused by a deficiency of the fragile X mental retardation protein (FMRP). In most patients, the absence of FMRP is due to an aberrant transcriptional silencing of the fragile X mental retardation 1 (FMR1) gene. FXS has no cure, and the available treatments only provide symptomatic relief. Given that FMR1 gene silencing in FXS patient cells can be partially reversed by treatment with compounds that target repressive epigenetic marks, restoring FMRP expression could be one approach for the treatment of FXS. We describe a homogeneous and highly sensitive time-resolved fluorescence resonance energy transfer assay for FMRP detection in a 1,536-well plate format. Using neural stem cells differentiated from an FXS patient-derived induced pluripotent stem cell (iPSC) line that does not express any FMRP, we screened a collection of approximately 5,000 known tool compounds and approved drugs using this FMRP assay and identified 6 compounds that modestly increase FMR1 gene expression in FXS patient cells. Although none of these compounds resulted in clinically relevant levels of FMR1 mRNA, our data provide proof of principle that this assay combined with FXS patient-derived neural stem cells can be used in a high-throughput format to identify better lead compounds for FXS drug development. In this study, a specific and sensitive fluorescence resonance energy transfer-based assay for fragile X mental retardation protein detection was developed and optimized for high-throughput screening (HTS) of compound libraries using fragile X syndrome (FXS) patient-derived neural stem cells. The data suggest that this HTS format will be useful for the identification of better lead compounds for developing new therapeutics for FXS. This assay can also be adapted for FMRP detection in clinical and research settings. ©AlphaMed Press.

Levels and source apportionment of children's lead exposure: could urinary lead be used to identify the levels and sources of children's lead pollution?

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Cao, Suzhen; Duan, Xiaoli; Zhao, Xiuge; Wang, Beibei; Ma, Jin; Fan, Delong; Sun, Chengye; He, Bin; Wei, Fusheng; Jiang, Guibin

2015-04-01

As a highly toxic heavy metal, the pollution and exposure risks of lead are of widespread concern for human health. However, the collection of blood samples for use as an indicator of lead pollution is not always feasible in most cohort or longitudinal studies, especially those involving children health. To evaluate the potential use of urinary lead as an indicator of exposure levels and source apportionment, accompanying with environmental media samples, lead concentrations and isotopic measurements (expressed as (207)Pb/(206)Pb, (208)Pb/(206)Pb and (204)Pb/(206)Pb) were investigated and compared between blood and urine from children living in the vicinities of a typical coking plant and lead-acid battery factory. The results showed urinary lead might not be a preferable proxy for estimating blood lead levels. Fortunately, urinary lead isotopic measurements could be used as an alternative for identifying the sources of children's lead exposure, which coincided well with the blood lead isotope ratio analysis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Identifying organic nitrogen compounds in Rocky Mountain National Park aerosols

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Beem, K. B.; Desyaterik, Y.; Ozel, M. Z.; Hamilton, J. F.; Collett, J. L.

2010-12-01

Nitrogen deposition is an important issue in Rocky Mountain National Park (RMNP). While inorganic nitrogen contributions to the ecosystems in this area have been studied, the sources of organic nitrogen are still largely unknown. To better understand the potential sources of organic nitrogen, filter samples were collected and analyzed for organic nitrogen species. Samples were collected in RMNP using a Thermo Fisher Scientific TSP (total suspended particulate) high-volume sampler with a PM2.5 impactor plate from April - November of 2008. The samples presented the opportunity to compare two different methods for identification of individual organic nitrogen species. The first type of analysis was performed with a comprehensive two dimensional gas chromatography (GCxGC) system using a nitrogen chemiluminescence detector (NCD). The filter samples were spiked with propanil in dichloromethane to use as an internal standard and were then extracted in water followed by solid phase extraction. The GCxGC system was comprised of a volatility based separation (DB5 column) followed by a polarity based separation (RXI-17 column). A NCD was used to specifically detect nitrogen compounds and remove the complex background matrix. Individual standards were used to identify peaks by comparing retention times. This method has the added benefit of an equimolar response for nitrogen so only a single calibration is needed for all species. In the second analysis, a portion of the same filter samples were extracted in DI water and analyzed with liquid chromatography coupled with mass spectroscopy (LC/MS). The separation was performed using a C18 column and a water-methanol gradient elution. Electrospray ionization into a time of flight mass spectrometer was used for detection. High accuracy mass measurement allowed unambiguous assignments of elemental composition of resulting ions. Positive and negative polarities were used since amines tend to show up in positive mode and nitrates in

Studying the effect of nano lead compounds additives on the concrete shielding properties for γ-rays

International Nuclear Information System (INIS)

Hassan, H.E.; Badran, H.M.; Aydarous, A.; Sharshar, T.

2015-01-01

In the present work the effect of concrete incorporation with two types of nano-lead compounds on its γ-ray shielding characteristics is investigated. The concrete samples were prepared according to the local standards of building materials and doped by different percentages of PbO and PbTiO_3 nano powders which were prepared using co-precipitation and oxalate precursor techniques, respectively. In addition, commercial PbO_2 powder additive was used to check the effect of particle size on concrete attenuation properties. The phase composition and particle size of all the lead-oxide additives were confirmed by XRD and TEM imaging. The γ-rays attenuation coefficients were measured as a function of the additive percentage of lead compounds for γ-ray energies of 662, 1173 and 1332 keV using "1"3"7Cs and "6"0Co sources. The microstructure changes occurred in the concrete samples doped with Pb compounds additives were probed using the positron annihilation spectroscopy (PAS) and the results were compared with that for normal concrete. The obtained data revealed that the overall defect density of the investigated samples, as seen by the positrons, decreases with increasing the nano-PbO contents which is in agreement with the determined values of the samples apparent densities. It was found that the γ-ray attenuation coefficient of concrete doped by nano-PbO is improved. The results are explained in the view of the fine structure enhanced modification and its impact on the γ-ray interaction probability at different energies.

The Redox Cycler Plasmodione Is a Fast-Acting Antimalarial Lead Compound with Pronounced Activity against Sexual and Early Asexual Blood-Stage Parasites.

Science.gov (United States)

Ehrhardt, Katharina; Deregnaucourt, Christiane; Goetz, Alice-Anne; Tzanova, Tzvetomira; Gallo, Valentina; Arese, Paolo; Pradines, Bruno; Adjalley, Sophie H; Bagrel, Denyse; Blandin, Stephanie; Lanzer, Michael; Davioud-Charvet, Elisabeth

2016-09-01

Previously, we presented the chemical design of a promising series of antimalarial agents, 3-[substituted-benzyl]-menadiones, with potent in vitro and in vivo activities. Ongoing studies on the mode of action of antimalarial 3-[substituted-benzyl]-menadiones revealed that these agents disturb the redox balance of the parasitized erythrocyte by acting as redox cyclers-a strategy that is broadly recognized for the development of new antimalarial agents. Here we report a detailed parasitological characterization of the in vitro activity profile of the lead compound 3-[4-(trifluoromethyl)benzyl]-menadione 1c (henceforth called plasmodione) against intraerythrocytic stages of the human malaria parasite Plasmodium falciparum We show that plasmodione acts rapidly against asexual blood stages, thereby disrupting the clinically relevant intraerythrocytic life cycle of the parasite, and furthermore has potent activity against early gametocytes. The lead's antiplasmodial activity was unaffected by the most common mechanisms of resistance to clinically used antimalarials. Moreover, plasmodione has a low potential to induce drug resistance and a high killing speed, as observed by culturing parasites under continuous drug pressure. Drug interactions with licensed antimalarial drugs were also established using the fixed-ratio isobologram method. Initial toxicological profiling suggests that plasmodione is a safe agent for possible human use. Our studies identify plasmodione as a promising antimalarial lead compound and strongly support the future development of redox-active benzylmenadiones as antimalarial agents. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Exploring Marine Cyanobacteria for Lead Compounds of Pharmaceutical Importance

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Bushra Uzair

2012-01-01

Full Text Available The Ocean, which is called the “mother of origin of life,” is also the source of structurally unique natural products that are mainly accumulated in living organisms. Cyanobacteria are photosynthetic prokaryotes used as food by humans. They are excellent source of vitamins and proteins vital for life. Several of these compounds show pharmacological activities and are helpful for the invention and discovery of bioactive compounds, primarily for deadly diseases like cancer, acquired immunodeficiency syndrome (AIDS, arthritis, and so forth, while other compounds have been developed as analgesics or to treat inflammation, and so forth. They produce a large variety of bioactive compounds, including substances with anticancer and antiviral activity, UV protectants, specific inhibitors of enzymes, and potent hepatotoxins and neurotoxins. Many cyanobacteria produce compounds with potent biological activities. This paper aims to showcase the structural diversity of marine cyanobacterial secondary metabolites with a comprehensive coverage of alkaloids and other applications of cyanobacteria.

Study on the effect of lead and lead compounds as pollutants on traffic air and traffic policemen

International Nuclear Information System (INIS)

Abd Alrhman, Heba Elyas Khider

2009-05-01

This study was conducted in Khartoum state to determine the magnitude of air pollution, resulting from traffic density, due to lead and lead compounds which had been used as additives for gasoline in the form of tetra-ethyl and tetra methyl lead. The level of lead in ambient air and SPM was determined in 14 samples taken randomly at the intersections and entrances to the bridges using personal sampler (Cassella. UK). The mean concentration of suspended particulate matter (SPM) was found to be 5.77+4.04 mg/m 3 . with range between 0.85-12.50 mg/m 3 including three sites above the limit of 10 mg/m 3 allowed. The samples were analyzed with Atomic Absorption Spectrophotometer for their lead content. The average concentration of lead in the sites is found to be 0.1937±0.1768 mg/m 3 . With range between 0.000-0.5166 mg/m 3 . The concentrations in seven sites were above the limit of 0.15 mg/m 3 permitted internationally. The impact of lead pollution on traffic police men was measured by analyzing blood lead concentration of 30 members exposed to traffic air pollution, from the three cities and (10 samples) from non-exposed ( control). It was found to be 2.4601±1.4065μg/100 ml and 0.3944±1.2471 μg/ 100 ml respectively. The data analysis by used SPSS program. There is no significant difference between the two groups. A questionnaire was designed to find out some data about the exposed members including their knowledge of impact, range of age, duration of their service as traffic police, their previous work, and complaints from some of the health effects. The findings were: average age mean of 35.9 ±7.7 years, 47.48% worked for periods of more than 20 years, 74.19% did not work before joining the traffic police, 51.6% of them believe that there is a problem of high level of air pollution, 45.2% medium and 3.2%, pollution is low. As habits 38.71% are smokers. As for health complains, 61.29% have various complains of headaches, fatigue, abdominal, hypertension and anemia

The use of lead isotope analysis to identify potential sources of lead toxicosis in a juvenile bald eagle (Haliaeetus leucocephalus) with ventricular foreign bodies

Science.gov (United States)

Franzen-Klein, Dana; McRuer, David; Slabe, Vincent; Katzner, Todd

2018-01-01

A male juvenile bald eagle (Haliaeetus leucocephalus) was admitted to the Wildlife Center of Virginia with a left humeral fracture a large quantity of anthropogenic debris in the ventriculus, a blood lead level of 0.616 ppm, and clinical signs consistent with chronic lead toxicosis. Because of the poor prognosis for recovery and release, the eagle was euthanatized. Lead isotope analysis was performed to identify potential anthropogenic sources of lead in this bird. The lead isotope ratios in the eagle's femur (0.8773), liver (0.8761), and kidneys (0.8686) were most closely related to lead paint (0.8925), leaded gasoline (0.8450), and zinc smelting (0.8240). The lead isotope ratios were dissimilar to lead ammunition (0.8179) and the anthropogenic debris in the ventriculus. This case report documents foreign body ingestion in a free-ranging bald eagle and demonstrates the clinical utility of lead isotope analysis to potentially identify or exclude anthropogenic sources of lead poisoning in wildlife patients.

Biosorption of lead phosphates by lead-tolerant bacteria as a mechanism for lead immobilization.

Science.gov (United States)

Rodríguez-Sánchez, Viridiana; Guzmán-Moreno, Jesús; Rodríguez-González, Vicente; Flores-de la Torre, Juan Armando; Ramírez-Santoyo, Rosa María; Vidales-Rodríguez, Luz Elena

2017-08-01

The study of metal-tolerant bacteria is important for bioremediation of contaminated environments and development of green technologies for material synthesis due to their potential to transform toxic metal ions into less toxic compounds by mechanisms such as reduction, oxidation and/or sequestration. In this study, we report the isolation of seven lead-tolerant bacteria from a metal-contaminated site at Zacatecas, México. The bacteria were identified as members of the Staphylococcus and Bacillus genera by microscopic, biochemical and 16S rDNA analyses. Minimal inhibitory concentration of these isolates was established between 4.5 and 7.0 mM of Pb(NO 3 ) 2 in solid and 1.0-4.0 mM of Pb(NO 3 ) 2 in liquid media. A quantitative analysis of the lead associated to bacterial biomass in growing cultures, revealed that the percentage of lead associated to biomass was between 1 and 37% in the PbT isolates. A mechanism of complexation/biosorption of lead ions as inorganic phosphates (lead hydroxyapatite and pyromorphite) in bacterial biomass, was determined by Fourier transform infrared spectroscopy and X-ray diffraction analyses. Thus, the ability of the lead-tolerant isolates to transform lead ions into stable and highly insoluble lead minerals make them potentially useful for immobilization of lead in mining waste.

Identification and characterization of antifungal compounds using a Saccharomyces cerevisiae reporter bioassay.

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Brad Tebbets

Full Text Available New antifungal drugs are urgently needed due to the currently limited selection, the emergence of drug resistance, and the toxicity of several commonly used drugs. To identify drug leads, we screened small molecules using a Saccharomyces cerevisiae reporter bioassay in which S. cerevisiae heterologously expresses Hik1, a group III hybrid histidine kinase (HHK from Magnaporthe grisea. Group III HHKs are integral in fungal cell physiology, and highly conserved throughout this kingdom; they are absent in mammals, making them an attractive drug target. Our screen identified compounds 13 and 33, which showed robust activity against numerous fungal genera including Candida spp., Cryptococcus spp. and molds such as Aspergillus fumigatus and Rhizopus oryzae. Drug-resistant Candida albicans from patients were also highly susceptible to compounds 13 and 33. While the compounds do not act directly on HHKs, microarray analysis showed that compound 13 induced transcripts associated with oxidative stress, and compound 33, transcripts linked with heavy metal stress. Both compounds were highly active against C. albicans biofilm, in vitro and in vivo, and exerted synergy with fluconazole, which was inactive alone. Thus, we identified potent, broad-spectrum antifungal drug leads from a small molecule screen using a high-throughput, S. cerevisiae reporter bioassay.

Use of solid phase microextraction to identify volatile organic compounds in brazilian wines from different grape varieties

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Natália Cristina Morais Fernandes

Full Text Available Abstract The Brazilian wine industry has shown significant growth in recent years and the insertion of new concepts, such as geographical indications as signs of quality, has placed Brazil in tune with the tendencies of world wine production. The aim of this work was to apply the Solid Phase Microextraction technique in combination with Gas Chromatography-Mass Spectrometry to study Brazilian wines made from different grape varieties, in order to separate and identify their volatile organic compounds. These substances were identified by comparisons between the spectra obtained with those presented in the NIST library database, and by comparisons with linear retention indices and literature data. The amounts of the compounds were calculated based on the total peak areas of the chromatograms. Forty-seven volatile compounds were identified and grouped into alcohols, aldehydes, fatty acids, esters, hydrocarbons, ketones and terpenes. Most of them belonged to the ester function, conferring a fruity aroma on the wines. The alcohols may have originated from the yeast metabolism, contributing to the alcoholic and floral aromas. Ethyl lactate, 1-hexanol and diethyl maleate were identified in all the varieties, except Merlot. Decanal, methyl citronellate, (E-2-hexenyl-3-methylbutyrate were only found in Merlot, while 2,3-butanediol was only present in the Tannat wines. 2-Phenylethanol was present in all varieties and is recognized as giving pleasant rose and honey attributes to wines. This study showed that the volatile profile of red wines is mainly characterized by esters and higher alcohols. The statistical analysis of the comparison of averages showed a greater amount of averages significantly different in the relative areas of Merlot wine. The Principal Component Analysis showed one grouping composed only of the Merlot wine samples, and this was probably related to the existence of the volatile organic compounds that were specifically identified in

Lead-oriented synthesis: Investigation of organolithium-mediated routes to 3-D scaffolds and 3-D shape analysis of a virtual lead-like library.

Science.gov (United States)

Lüthy, Monique; Wheldon, Mary C; Haji-Cheteh, Chehasnah; Atobe, Masakazu; Bond, Paul S; O'Brien, Peter; Hubbard, Roderick E; Fairlamb, Ian J S

2015-06-01

Synthetic routes to six 3-D scaffolds containing piperazine, pyrrolidine and piperidine cores have been developed. The synthetic methodology focused on the use of N-Boc α-lithiation-trapping chemistry. Notably, suitably protected and/or functionalised medicinal chemistry building blocks were synthesised via concise, connective methodology. This represents a rare example of lead-oriented synthesis. A virtual library of 190 compounds was then enumerated from the six scaffolds. Of these, 92 compounds (48%) fit the lead-like criteria of: (i) -1⩽AlogP⩽3; (ii) 14⩽number of heavy atoms⩽26; (iii) total polar surface area⩾50Å(2). The 3-D shapes of the 190 compounds were analysed using a triangular plot of normalised principal moments of inertia (PMI). From this, 46 compounds were identified which had lead-like properties and possessed 3-D shapes in under-represented areas of pharmaceutical space. Thus, the PMI analysis of the 190 member virtual library showed that whilst scaffolds which may appear on paper to be 3-D in shape, only 24% of the compounds actually had 3-D structures in the more interesting areas of 3-D drug space. Copyright © 2015 Elsevier Ltd. All rights reserved.

Bioactive Natural Product and Superacid Chemistry for Lead Compound Identification: A Case Study of Selective hCA III and L-Type Ca2+ Current Inhibitors for Hypotensive Agent Discovery

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Hélène Carreyre

2017-05-01

Full Text Available Dodoneine (Ddn is one of the active compounds identified from Agelanthus dodoneifolius, which is a medicinal plant used in African pharmacopeia and traditional medicine for the treatment of hypertension. In the context of a scientific program aiming at discovering new hypotensive agents through the original combination of natural product discovery and superacid chemistry diversification, and after evidencing dodoneine’s vasorelaxant effect on rat aorta, superacid modifications allowed us to generate original analogues which showed selective human carbonic anhydrase III (hCA III and L-type Ca2+ current inhibition. These derivatives can now be considered as new lead compounds for vasorelaxant therapeutics targeting these two proteins.

Identifying natural compounds as multi-target-directed ligands against Alzheimer's disease: an in silico approach.

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Ambure, Pravin; Bhat, Jyotsna; Puzyn, Tomasz; Roy, Kunal

2018-04-23

Alzheimer's disease (AD) is a multi-factorial disease, which can be simply outlined as an irreversible and progressive neurodegenerative disorder with an unclear root cause. It is a major cause of dementia in old aged people. In the present study, utilizing the structural and biological activity information of ligands for five important and mostly studied vital targets (i.e. cyclin-dependant kinase 5, β-secretase, monoamine oxidase B, glycogen synthase kinase 3β, acetylcholinesterase) that are believed to be effective against AD, we have developed five classification models using linear discriminant analysis (LDA) technique. Considering the importance of data curation, we have given more attention towards the chemical and biological data curation, which is a difficult task especially in case of big data-sets. Thus, to ease the curation process we have designed Konstanz Information Miner (KNIME) workflows, which are made available at http://teqip.jdvu.ac.in/QSAR_Tools/ . The developed models were appropriately validated based on the predictions for experiment derived data from test sets, as well as true external set compounds including known multi-target compounds. The domain of applicability for each classification model was checked based on a confidence estimation approach. Further, these validated models were employed for screening of natural compounds collected from the InterBioScreen natural database ( https://www.ibscreen.com/natural-compounds ). Further, the natural compounds that were categorized as 'actives' in at least two classification models out of five developed models were considered as multi-target leads, and these compounds were further screened using the drug-like filter, molecular docking technique and then thoroughly analyzed using molecular dynamics studies. Finally, the most potential multi-target natural compounds against AD are suggested.

Profiling of the Tox21 Chemical Collection for Mitochondrial Function to Identify Compounds that Acutely Decrease Mitochondrial Membrane Potential

Science.gov (United States)

Attene-Ramos, Matias S.; Huang, Ruili; Michael, Sam; Witt, Kristine L.; Richard, Ann; Tice, Raymond R.; Simeonov, Anton; Austin, Christopher P.

2014-01-01

Background: Mitochondrial dysfunction has been implicated in the pathogenesis of a variety of disorders including cancer, diabetes, and neurodegenerative and cardiovascular diseases. Understanding whether different environmental chemicals and druglike molecules impact mitochondrial function represents an initial step in predicting exposure-related toxicity and defining a possible role for such compounds in the onset of various diseases. Objectives: We sought to identify individual chemicals and general structural features associated with changes in mitochondrial membrane potential (MMP). Methods: We used a multiplexed [two end points in one screen; MMP and adenosine triphosphate (ATP) content] quantitative high throughput screening (qHTS) approach combined with informatics tools to screen the Tox21 library of 10,000 compounds (~ 8,300 unique chemicals) at 15 concentrations each in triplicate to identify chemicals and structural features that are associated with changes in MMP in HepG2 cells. Results: Approximately 11% of the compounds (913 unique compounds) decreased MMP after 1 hr of treatment without affecting cell viability (ATP content). In addition, 309 compounds decreased MMP over a concentration range that also produced measurable cytotoxicity [half maximal inhibitory concentration (IC50) in MMP assay/IC50 in viability assay ≤ 3; p Tice RR, Simeonov A, Austin CP, Xia M. 2015. Profiling of the Tox21 chemical collection for mitochondrial function to identify compounds that acutely decrease mitochondrial membrane potential. Environ Health Perspect 123:49–56; http://dx.doi.org/10.1289/ehp.1408642 PMID:25302578

Thermochemistry of some binary lead and transition metal compounds by high temperature direct synthesis calorimetry

Energy Technology Data Exchange (ETDEWEB)

Meschel, S.V., E-mail: meschel@jfi.uchicago.edu [Illinois Institute of Technology,Thermal Processing Technology Center, 10 W. 32nd Street, Chicago, Illinois 60615 (United States); Gordon Center for Integrated Science, 929 E. 57th Street, Chicago, Illinois 60637 (United States); Nash, P. [Illinois Institute of Technology,Thermal Processing Technology Center, 10 W. 32nd Street, Chicago, Illinois 60615 (United States); Chen, X.Q.; Wei, P. [Materials processing Modeling Division, Shenyang National Laboratory for Materials Science, Institute of Metals Research, 72 Wenhua Road, Shenyang City (China)

2015-06-05

Highlights: • Studied binary lead-transition metal alloys by high temperature calorimetry. • Determined the enthalpies of formation of 8 alloys. • Compared the measurements with predictions by the model of Miedema and by the ab initio method. - Abstract: The standard enthalpies of formation of some binary lead and transition metal compounds have been measured by high temperature direct synthesis calorimetry. The reported results are: Pb{sub 3}Sc{sub 5}(−61.3 ± 2.9); PbTi{sub 4}(−16.6 ± 2.4); Pb{sub 3}Y{sub 5}(−64.8 ± 3.6); Pb{sub 3}Zr{sub 5}(−50.6 ± 3.1); PbNb{sub 3}(−10.4 ± 3.4); PbRh(−16.5 ± 3.3); PbPd{sub 3}(−29.6 ± 3.1); PbPt(−34.7 ± 3.3) kJ/mole of atoms. We will compare our results with previously published measurements. We will also compare the experimental measurements with enthalpies of formation of transition metal compounds with elements in the same vertical column in the periodic table. We will compare our measurements with predicted values on the basis of the semi empirical model of Miedema and coworkers and with ab initio values when available.

Detector and sensor devices: fabrication from lead compounds. January 1975-September 1988 (Citations from the INSPEC: Information Services for the Physics and Engineering Communities data base). Report for January 1975-September 1988

International Nuclear Information System (INIS)

1988-10-01

This bibliography contains citations concerning developments, properties, and production of lead compound materials for use in detector- and sensor-device fabrication. Topics include infrared detectors, lead compound heterojunctions and photodiodes, photovoltaic and pyroelectric detectors, epitaxial growth methods, remote sensing, and night vision. Development and preparation of lead sulfide, selenide, telluride, and thallium-monoxide compounds are discussed. Performance analysis and applications of lead compound detectors and sensors are examined. (This updated bibliography contains 229 citations, 19 of which are new entries to the previous edition.)

Predicting chemically-induced skin reactions. Part I: QSAR models of skin sensitization and their application to identify potentially hazardous compounds

Science.gov (United States)

Alves, Vinicius M.; Muratov, Eugene; Fourches, Denis; Strickland, Judy; Kleinstreuer, Nicole; Andrade, Carolina H.; Tropsha, Alexander

2015-01-01

Repetitive exposure to a chemical agent can induce an immune reaction in inherently susceptible individuals that leads to skin sensitization. Although many chemicals have been reported as skin sensitizers, there have been very few rigorously validated QSAR models with defined applicability domains (AD) that were developed using a large group of chemically diverse compounds. In this study, we have aimed to compile, curate, and integrate the largest publicly available dataset related to chemically-induced skin sensitization, use this data to generate rigorously validated and QSAR models for skin sensitization, and employ these models as a virtual screening tool for identifying putative sensitizers among environmental chemicals. We followed best practices for model building and validation implemented with our predictive QSAR workflow using random forest modeling technique in combination with SiRMS and Dragon descriptors. The Correct Classification Rate (CCR) for QSAR models discriminating sensitizers from non-sensitizers were 71–88% when evaluated on several external validation sets, within a broad AD, with positive (for sensitizers) and negative (for non-sensitizers) predicted rates of 85% and 79% respectively. When compared to the skin sensitization module included in the OECD QSAR toolbox as well as to the skin sensitization model in publicly available VEGA software, our models showed a significantly higher prediction accuracy for the same sets of external compounds as evaluated by Positive Predicted Rate, Negative Predicted Rate, and CCR. These models were applied to identify putative chemical hazards in the ScoreCard database of possible skin or sense organ toxicants as primary candidates for experimental validation. PMID:25560674

Synthesis and characterization of nanometer sized thermoelectric lead-antimony-silver-tellurium compounds and related materials

International Nuclear Information System (INIS)

Petri, Denis

2012-01-01

The present dissertation deals with different variants of synthesis and processing of nanocrystalline composites of various thermoelectric compounds based on lead telluride including LAST-m (AgPb m SbTe m+2 ), LASTT-m-x (AgPb m-x Sn x SbTe m+2 ), LABST-m-x (AgPb m Sb 1-x Bi x Te m+2 ), doped LAST-m and (PbTe) m (M 15 2 Te 3 ) and the characterization thereof. A new route of manufacturing nanocrystalline composites was developed. The so called co-ball milling-route includes the synthesis of bi- or multinary compounds by conventional solid state melting methods followed by combined milling of appropriate amounts in a planetary ball mill; a process related to the widely used mechanical alloying of elemental powders. The as produced powders were shortly annealed for one hour and a.erwards compacted either at room temperature followed by pressureless sintering or combined application of high pressure and elevated temperatures via spark-plasma-sintering or short-term-sintering. The ball milling yielded micron-sized agglomerates consisting of crystallites with diameters ranging from 10 to 50 nm. These crystallites exhibited complicated internal nanostructures severe crystal defects as a consequence of the high energy processing. During short-term annealing some grain coarsening occured and the crystal defects partly healed, which was confirmed by TEM and HRTEM investigations as well as profile analysis of XRD powder pattern. Local EDX-analysis showed different compositions at every point as a consequence of synthesis and decomposition of the compounds. Measurements of thermopower, electrical and thermal conductivity were carried out and the values of the figure of merit ZT and the powerfactor were calculated. In general the compounds exhibited larger thermopower than corresponding bulk materials, which might be attributed to energy filtering of charge carriers at partly oxidized grain boundaries. Due to enhanced phonon scattering at grain boundarys, nanoscopic

Recently confirmed apoptosis-inducing lead compounds isolated from marine sponge of potential relevance in cancer treatment

KAUST Repository

Essack, Magbubah; Bajic, Vladimir B.; Archer, John A.C.

2011-01-01

Despite intense efforts to develop non-cytotoxic anticancer treatments, effective agents are still not available. Therefore, novel apoptosis-inducing drug leads that may be developed into effective targeted cancer therapies are of interest to the cancer research community. Targeted cancer therapies affect specific aberrant apoptotic pathways that characterize different cancer types and, for this reason, it is a more desirable type of therapy than chemotherapy or radiotherapy, as it is less harmful to normal cells. In this regard, marine sponge derived metabolites that induce apoptosis continue to be a promising source of new drug leads for cancer treatments. A PubMed query from 01/01/2005 to 31/01/2011 combined with hand-curation of the retrieved articles allowed for the identification of 39 recently confirmed apoptosis-inducing anticancer lead compounds isolated from the marine sponge that are selectively discussed in this review. 2011 by the authors.

Recently confirmed apoptosis-inducing lead compounds isolated from marine sponge of potential relevance in cancer treatment

KAUST Repository

Essack, Magbubah

2011-09-20

Despite intense efforts to develop non-cytotoxic anticancer treatments, effective agents are still not available. Therefore, novel apoptosis-inducing drug leads that may be developed into effective targeted cancer therapies are of interest to the cancer research community. Targeted cancer therapies affect specific aberrant apoptotic pathways that characterize different cancer types and, for this reason, it is a more desirable type of therapy than chemotherapy or radiotherapy, as it is less harmful to normal cells. In this regard, marine sponge derived metabolites that induce apoptosis continue to be a promising source of new drug leads for cancer treatments. A PubMed query from 01/01/2005 to 31/01/2011 combined with hand-curation of the retrieved articles allowed for the identification of 39 recently confirmed apoptosis-inducing anticancer lead compounds isolated from the marine sponge that are selectively discussed in this review. 2011 by the authors.

Using Lead Concentrations and Stable Lead Isotope Ratios to Identify Contamination Events in Alluvial Soils

International Nuclear Information System (INIS)

Saint-Laurent, D.; St-Laurent, J.; Hahni, M.; Chapados, C.; Ghaleb, B.

2010-01-01

Soils contaminated with hydrocarbons (C10,C50), polycyclic aromatic hydrocarbons (PAHs), and other contaminants (e.g., As, Cd, Cu, Pb) were recently discovered on the banks of the Saint-Francois and Massawippi rivers. Alluvial soils are contaminated over a distance of 100 kilometers, and the level of the contaminated-hydrocarbon layer in the soil profiles is among the highest at the Windsor and Richmond sites. Concentrations of lead and stable lead isotope ratios ( 204 Pb/ 206 Pb, 206 Pb/ 207 Pb, 208 Pb/ 20 '6Pb) are also used to identify contamination events. The maximum and minimum values detected in soil profiles for arsenic, cadmium, and lead vary from 3.01 to 37.88?mg kg -1 (As), 0.11 to 0.81?mg kg-1 (Cd) 12.32 to 149.13?mg kg -1 (Pb), respectively, while the 207 Pb/ 206 Pb isotopic ratio values are between 0.8545 and 0.8724 for all the profiles. The highest values of trace elements (As, Pb and Zn) were detected in the hydrocarbon layer (C10,C50), most often located at the bottom of the profiles (160, 200, and 220 cm in depth). The various peaks recorded in the soils and the position of the profiles suggest that various contaminants were transported by the river on several occasions and infiltrated the soil matrix or deposited on flood plains during successive floods. Atmospheric particles which entered the river or deposited on riverbanks must also be considered as another source of pollution recorded in soils

Using Lead Concentrations and Stable Lead Isotope Ratios to Identify Contamination Events in Alluvial Soils

Directory of Open Access Journals (Sweden)

Diane Saint-Laurent

2010-01-01

Full Text Available Soils contaminated with hydrocarbons (C10–C50, polycyclic aromatic hydrocarbons (PAHs, and other contaminants (e.g., As, Cd, Cu, Pb were recently discovered on the banks of the Saint-François and Massawippi rivers. Alluvial soils are contaminated over a distance of 100 kilometers, and the level of the contaminated-hydrocarbon layer in the soil profiles is among the highest at the Windsor and Richmond sites. Concentrations of lead and stable lead isotope ratios (204Pb/206Pb, 207Pb/206Pb, 208Pb/206Pb are also used to identify contamination events. The maximum and minimum values detected in soil profiles for arsenic, cadmium, and lead vary from 3.01 to 37.88 mg kg-1 (As, 0.11 to 0.81 mg kg-1 (Cd 12.32 to 149.13 mg kg-1 (Pb, respectively, while the 207Pb/206Pb isotopic ratio values are between 0.8545 and 0.8724 for all the profiles. The highest values of trace elements (As, Pb and Zn were detected in the hydrocarbon layer (C10–C50, most often located at the bottom of the profiles (160, 200, and 220 cm in depth. The various peaks recorded in the soils and the position of the profiles suggest that various contaminants were transported by the river on several occasions and infiltrated the soil matrix or deposited on floodplains during successive floods. Atmospheric particles which entered the river or deposited on riverbanks must also be considered as another source of pollution recorded in soils.

The role of visual acuity and segmentation cues in compound word identification

Directory of Open Access Journals (Sweden)

Jukka eHyönä

2012-06-01

Full Text Available Studies are reviewed that demonstrate how the foveal area of the eye constrains how compound words are identified during reading. When compound words are short, their letters can be identified during a single fixation, leading to the whole-word route dominating word recognition from early on. Hence, visually marking morpheme boundaries by hyphens slows down processing by encouraging morphological decomposition when holistic processing is a feasible option. In contrast, the decomposition route dominates the early stages of identifying long compound words. Thus, visual marking of morpheme boundaries facilitates processing of long compound words, unless the initial fixation made on the word lands very close to the morpheme boundary. The reviewed pattern of results is explained by the visual acuity principle (Bertram & Hyönä, 2003 and the dual-route framework of morphological processing.

2-(Substituted phenyl-3,4-dihydroisoquinolin-2-iums as Novel Antifungal Lead Compounds: Biological Evaluation and Structure-Activity Relationships

Directory of Open Access Journals (Sweden)

Xin-Juan Yang

2013-08-01

Full Text Available The title compounds are a class of structurally simple analogues of quaternary benzo[c]phenanthridine alkaloids (QBAs. In order to develop novel QBA-like antifungal drugs, in this study, 24 of the title compounds with various substituents on the N-phenyl ring were evaluated for bioactivity against seven phytopathogenic fungi using the mycelial growth rate method and their SAR discussed. Almost all the compounds showed definite activities in vitro against each of the test fungi at 50 μg/mL and a broad antifungal spectrum. In most cases, the mono-halogenated compounds 2–12 exhibited excellent activities superior to the QBAs sanguinarine and chelerythrine. Compound 8 possessed the strongest activities on each of the fungi with EC50 values of 8.88–19.88 µg/mL and a significant concentration-dependent relationship. The SAR is as follows: the N-phenyl group is a high sensitive structural moiety for the activity and the characteristics and position of substituents intensively influence the activity. Generally, electron-withdrawing substituents remarkably enhance the activity while electron-donating substituents cause a decrease of the activity. In most cases, ortha- and para-halogenated isomers were more active than the corresponding m-halogenated isomers. Thus, the title compounds emerged as promising lead compounds for the development of novel biomimetic antifungal agrochemicals. Compounds 8 and 2 should have great potential as new broad spectrum antifungal agents for plant protection.

In search of new lead compounds for trypanosomiasis drug design: A protein structure-based linked-fragment approach

Science.gov (United States)

Verlinde, Christophe L. M. J.; Rudenko, Gabrielle; Hol, Wim G. J.

1992-04-01

A modular method for pursuing structure-based inhibitor design in the framework of a design cycle is presented. The approach entails four stages: (1) a design pathway is defined in the three-dimensional structure of a target protein; (2) this pathway is divided into subregions; (3) complementary building blocks, also called fragments, are designed in each subregion; complementarity is defined in terms of shape, hydrophobicity, hydrogen bond properties and electrostatics; and (4) fragments from different subregions are linked into potential lead compounds. Stages (3) and (4) are qualitatively guided by force-field calculations. In addition, the designed fragments serve as entries for retrieving existing compounds from chemical databases. This linked-fragment approach has been applied in the design of potentially selective inhibitors of triosephosphate isomerase from Trypanosoma brucei, the causative agent of sleeping sickness.

A Yeast/Drosophila Screen to Identify New Compounds Overcoming Frataxin Deficiency

Directory of Open Access Journals (Sweden)

Alexandra Seguin

2015-01-01

Full Text Available Friedreich’s ataxia (FA is a rare neurodegenerative disease which is very debilitating for the patients who progressively lose their autonomy. The lack of efficient therapeutic treatment of the disease strongly argues for urgent need to search for new active compounds that may stop the progression of the disease or prevent the appearance of the symptoms when the genetic defect is diagnosed early enough. In the present study, we used a yeast strain with a deletion of the frataxin homologue gene as a model of FA cells in a primary screen of two chemical libraries, a fraction of the French National Chemical Library (5500 compounds and the Prestwick collection (880 compounds. We ran a secondary screen on Drosophila melanogaster flies expressing reduced levels of frataxin during larval development. Half of the compounds selected in yeast appeared to be active in flies in this developmental paradigm, and one of the two compounds with highest activities in this assay partially rescued the heart dilatation phenotype resulting from heart specific depletion of frataxin. The unique complementarity of these two frataxin-deficient models, unicellular and multicellular, appears to be very efficient to select new compounds with improved selectivity, bringing significant perspectives towards improvements in FA therapy.

Antiviral lead compounds from marine sponges

KAUST Repository

Sagar, Sunil; Kaur, Mandeep; Minneman, Kenneth P.

2010-01-01

). The most important antiviral lead of marine origin reported thus far is nucleoside Ara-A (vidarabine) isolated from sponge Tethya crypta. It inhibits viral DNA polymerase and DNA synthesis of herpes, vaccinica and varicella zoster viruses. However due

Predicting chemically-induced skin reactions. Part I: QSAR models of skin sensitization and their application to identify potentially hazardous compounds

Energy Technology Data Exchange (ETDEWEB)

Alves, Vinicius M. [Laboratory of Molecular Modeling and Design, Faculty of Pharmacy, Federal University of Goiás, Goiânia, GO 74605-220 (Brazil); Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599 (United States); Muratov, Eugene [Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599 (United States); Laboratory of Theoretical Chemistry, A.V. Bogatsky Physical-Chemical Institute NAS of Ukraine, Odessa 65080 (Ukraine); Fourches, Denis [Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599 (United States); Strickland, Judy; Kleinstreuer, Nicole [ILS/Contractor Supporting the NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM), P.O. Box 13501, Research Triangle Park, NC 27709 (United States); Andrade, Carolina H. [Laboratory of Molecular Modeling and Design, Faculty of Pharmacy, Federal University of Goiás, Goiânia, GO 74605-220 (Brazil); Tropsha, Alexander, E-mail: alex_tropsha@unc.edu [Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599 (United States)

2015-04-15

Repetitive exposure to a chemical agent can induce an immune reaction in inherently susceptible individuals that leads to skin sensitization. Although many chemicals have been reported as skin sensitizers, there have been very few rigorously validated QSAR models with defined applicability domains (AD) that were developed using a large group of chemically diverse compounds. In this study, we have aimed to compile, curate, and integrate the largest publicly available dataset related to chemically-induced skin sensitization, use this data to generate rigorously validated and QSAR models for skin sensitization, and employ these models as a virtual screening tool for identifying putative sensitizers among environmental chemicals. We followed best practices for model building and validation implemented with our predictive QSAR workflow using Random Forest modeling technique in combination with SiRMS and Dragon descriptors. The Correct Classification Rate (CCR) for QSAR models discriminating sensitizers from non-sensitizers was 71–88% when evaluated on several external validation sets, within a broad AD, with positive (for sensitizers) and negative (for non-sensitizers) predicted rates of 85% and 79% respectively. When compared to the skin sensitization module included in the OECD QSAR Toolbox as well as to the skin sensitization model in publicly available VEGA software, our models showed a significantly higher prediction accuracy for the same sets of external compounds as evaluated by Positive Predicted Rate, Negative Predicted Rate, and CCR. These models were applied to identify putative chemical hazards in the Scorecard database of possible skin or sense organ toxicants as primary candidates for experimental validation. - Highlights: • It was compiled the largest publicly-available skin sensitization dataset. • Predictive QSAR models were developed for skin sensitization. • Developed models have higher prediction accuracy than OECD QSAR Toolbox. • Putative

Predicting chemically-induced skin reactions. Part I: QSAR models of skin sensitization and their application to identify potentially hazardous compounds

International Nuclear Information System (INIS)

Alves, Vinicius M.; Muratov, Eugene; Fourches, Denis; Strickland, Judy; Kleinstreuer, Nicole; Andrade, Carolina H.; Tropsha, Alexander

2015-01-01

Repetitive exposure to a chemical agent can induce an immune reaction in inherently susceptible individuals that leads to skin sensitization. Although many chemicals have been reported as skin sensitizers, there have been very few rigorously validated QSAR models with defined applicability domains (AD) that were developed using a large group of chemically diverse compounds. In this study, we have aimed to compile, curate, and integrate the largest publicly available dataset related to chemically-induced skin sensitization, use this data to generate rigorously validated and QSAR models for skin sensitization, and employ these models as a virtual screening tool for identifying putative sensitizers among environmental chemicals. We followed best practices for model building and validation implemented with our predictive QSAR workflow using Random Forest modeling technique in combination with SiRMS and Dragon descriptors. The Correct Classification Rate (CCR) for QSAR models discriminating sensitizers from non-sensitizers was 71–88% when evaluated on several external validation sets, within a broad AD, with positive (for sensitizers) and negative (for non-sensitizers) predicted rates of 85% and 79% respectively. When compared to the skin sensitization module included in the OECD QSAR Toolbox as well as to the skin sensitization model in publicly available VEGA software, our models showed a significantly higher prediction accuracy for the same sets of external compounds as evaluated by Positive Predicted Rate, Negative Predicted Rate, and CCR. These models were applied to identify putative chemical hazards in the Scorecard database of possible skin or sense organ toxicants as primary candidates for experimental validation. - Highlights: • It was compiled the largest publicly-available skin sensitization dataset. • Predictive QSAR models were developed for skin sensitization. • Developed models have higher prediction accuracy than OECD QSAR Toolbox. • Putative

Mesua beccariana (Clusiaceae, A Source of Potential Anti-cancer Lead Compounds in Drug Discovery

Directory of Open Access Journals (Sweden)

Soek Sin Teh

2012-09-01

Full Text Available An investigation on biologically active secondary metabolites from the stem bark of Mesua beccariana was carried out. A new cyclodione, mesuadione (1, along with several known constituents which are beccamarin (2, 2,5-dihydroxy-1,3,4-trimethoxy anthraquinone (3, 4-methoxy-1,3,5-trihydroxyanthraquinone (4, betulinic acid (5 and stigmasterol (6 were obtained from this ongoing research. Structures of these compounds were elucidated by extensive spectroscopic methods, including 1D and 2D-NMR, GC-MS, IR and UV techniques. Preliminary tests of the in vitro cytotoxic activities of all the isolated metabolites against a panel of human cancer cell lines Raji (lymphoma, SNU-1 (gastric carcinoma, K562 (erythroleukemia cells, LS-174T (colorectal adenocarcinoma, HeLa (cervical cells, SK-MEL-28 (malignant melanoma cells, NCI-H23 (lung adenocarcinoma, IMR-32 (neuroblastoma and Hep-G2 (hepatocellular liver carcinoma were carried out using an MTT assay. Mesuadione (1, beccamarin (2, betulinic acid (5 and stigmasterol (6 displayed strong inhibition of Raji cell proliferation, while the proliferation rate of SK-MEL-28 and HeLa were strongly inhibited by stigmasterol (6 and beccamarin (2, indicating these secondary metabolites could be anti-cancer lead compounds in drug discovery.

Novel approach of fragment-based lead discovery applied to renin inhibitors.

Science.gov (United States)

Tawada, Michiko; Suzuki, Shinkichi; Imaeda, Yasuhiro; Oki, Hideyuki; Snell, Gyorgy; Behnke, Craig A; Kondo, Mitsuyo; Tarui, Naoki; Tanaka, Toshimasa; Kuroita, Takanobu; Tomimoto, Masaki

2016-11-15

A novel approach was conducted for fragment-based lead discovery and applied to renin inhibitors. The biochemical screening of a fragment library against renin provided the hit fragment which showed a characteristic interaction pattern with the target protein. The hit fragment bound only to the S1, S3, and S3 SP (S3 subpocket) sites without any interactions with the catalytic aspartate residues (Asp32 and Asp215 (pepsin numbering)). Prior to making chemical modifications to the hit fragment, we first identified its essential binding sites by utilizing the hit fragment's substructures. Second, we created a new and smaller scaffold, which better occupied the identified essential S3 and S3 SP sites, by utilizing library synthesis with high-throughput chemistry. We then revisited the S1 site and efficiently explored a good building block attaching to the scaffold with library synthesis. In the library syntheses, the binding modes of each pivotal compound were determined and confirmed by X-ray crystallography and the library was strategically designed by structure-based computational approach not only to obtain a more active compound but also to obtain informative Structure Activity Relationship (SAR). As a result, we obtained a lead compound offering synthetic accessibility as well as the improved in vitro ADMET profiles. The fragments and compounds possessing a characteristic interaction pattern provided new structural insights into renin's active site and the potential to create a new generation of renin inhibitors. In addition, we demonstrated our FBDD strategy integrating highly sensitive biochemical assay, X-ray crystallography, and high-throughput synthesis and in silico library design aimed at fragment morphing at the initial stage was effective to elucidate a pocket profile and a promising lead compound. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of metallic nanoparticle doped flux on the interfacial intermetallic compounds between lead-free solder ball and copper substrate

International Nuclear Information System (INIS)

Sujan, G.K.; Haseeb, A.S.M.A.; Afifi, A.B.M.

2014-01-01

Lead free solders currently in use are prone to develop thick interfacial intermetallic compound layers with rough morphology which are detrimental to the long term solder joint reliability. A novel method has been developed to control the morphology and growth of intermetallic compound layers between lead-free Sn–3.0Ag–0.5Cu solder ball and copper substrate by doping a water soluble flux with metallic nanoparticles. Four types of metallic nanoparticles (nickel, cobalt, molybdenum and titanium) were used to investigate their effects on the wetting behavior and interfacial microstructural evaluations after reflow. Nanoparticles were dispersed manually with a water soluble flux and the resulting nanoparticle doped flux was placed on copper substrate. Lead-free Sn–3.0Ag–0.5Cu solder balls of diameter 0.45 mm were placed on top of the flux and were reflowed at a peak temperature of 240 °C for 45 s. Angle of contact, wetting area and interfacial microstructure were studied by optical microscopy, field emission scanning electron microscopy and energy-dispersive X-ray spectroscopy. It was observed that the angle of contact increased and wetting area decreased with the addition of cobalt, molybdenum and titanium nanoparticles to flux. On the other hand, wettability improved with the addition of nickel nanoparticles. Cross-sectional micrographs revealed that both nickel and cobalt nanoparticle doping transformed the morphology of Cu 6 Sn 5 from a typical scallop type to a planer one and reduced the intermetallic compound thickness under optimum condition. These effects were suggested to be related to in-situ interfacial alloying at the interface during reflow. The minimum amount of nanoparticles required to produce the planer morphology was found to be 0.1 wt.% for both nickel and cobalt. Molybdenum and titanium nanoparticles neither appear to undergo alloying during reflow nor have any influence at the solder/substrate interfacial reaction. Thus, doping of flux

Effects of metallic nanoparticle doped flux on the interfacial intermetallic compounds between lead-free solder ball and copper substrate

Energy Technology Data Exchange (ETDEWEB)

Sujan, G.K., E-mail: sgkumer@gmail.com; Haseeb, A.S.M.A., E-mail: haseeb@um.edu.my; Afifi, A.B.M., E-mail: amalina@um.edu.my

2014-11-15

Lead free solders currently in use are prone to develop thick interfacial intermetallic compound layers with rough morphology which are detrimental to the long term solder joint reliability. A novel method has been developed to control the morphology and growth of intermetallic compound layers between lead-free Sn–3.0Ag–0.5Cu solder ball and copper substrate by doping a water soluble flux with metallic nanoparticles. Four types of metallic nanoparticles (nickel, cobalt, molybdenum and titanium) were used to investigate their effects on the wetting behavior and interfacial microstructural evaluations after reflow. Nanoparticles were dispersed manually with a water soluble flux and the resulting nanoparticle doped flux was placed on copper substrate. Lead-free Sn–3.0Ag–0.5Cu solder balls of diameter 0.45 mm were placed on top of the flux and were reflowed at a peak temperature of 240 °C for 45 s. Angle of contact, wetting area and interfacial microstructure were studied by optical microscopy, field emission scanning electron microscopy and energy-dispersive X-ray spectroscopy. It was observed that the angle of contact increased and wetting area decreased with the addition of cobalt, molybdenum and titanium nanoparticles to flux. On the other hand, wettability improved with the addition of nickel nanoparticles. Cross-sectional micrographs revealed that both nickel and cobalt nanoparticle doping transformed the morphology of Cu{sub 6}Sn{sub 5} from a typical scallop type to a planer one and reduced the intermetallic compound thickness under optimum condition. These effects were suggested to be related to in-situ interfacial alloying at the interface during reflow. The minimum amount of nanoparticles required to produce the planer morphology was found to be 0.1 wt.% for both nickel and cobalt. Molybdenum and titanium nanoparticles neither appear to undergo alloying during reflow nor have any influence at the solder/substrate interfacial reaction. Thus, doping

Urban Airborne Lead: X-Ray Absorption Spectroscopy Establishes Soil as Dominant Source

OpenAIRE

Pingitore, Nicholas E.; Clague, Juan W.; Amaya, Maria A.; Maciejewska, Beata; Reynoso, Jes?s J.

2009-01-01

BACKGROUND: Despite the dramatic decrease in airborne lead over the past three decades, there are calls for regulatory limits on this potent pediatric neurotoxin lower even than the new (2008) US Environmental Protection Agency standard. To achieve further decreases in airborne lead, what sources would need to be decreased and what costs would ensue? Our aim was to identify and, if possible, quantify the major species (compounds) of lead in recent ambient airborne particulate matter collected...

A Novel Mechanistic Approach to Identify New Antifungal Lead ...

African Journals Online (AJOL)

AmB) molecular architecture. Methods: The strategy employed was molecular similarity search and screening based on the molecular constraints of polyene macrolide antibiotics, as well as docking experiments. Several new compounds were ...

A Novel Mechanistic Approach to Identify New Antifungal Lead ...

African Journals Online (AJOL)

Available online at http://www.tjpr.org ... The MIC of the more effective compounds, delta-decalactone and mandelonitrile ... screening which is increasingly used as a cost- ..... AD. Lanomycin and glucolanomycin, antifungal agents produced by ...

Novel inhibitors to Taenia solium Cu/Zn superoxide dismutase identified by virtual screening

Science.gov (United States)

García-Gutiérrez, P.; Landa-Piedra, A.; Rodríguez-Romero, A.; Parra-Unda, R.; Rojo-Domínguez, A.

2011-12-01

We describe in this work a successful virtual screening and experimental testing aimed to the identification of novel inhibitors of superoxide dismutase of the worm Taenia solium ( TsCu/Zn-SOD), a human parasite. Conformers from LeadQuest® database of drug-like compounds were selected and then docked on the surface of TsCu/Zn-SOD. Results were screened looking for ligand contacts with receptor side-chains not conserved in the human homologue, with a subsequent development of a score optimization by a set of energy minimization steps, aimed to identify lead compounds for in vitro experiments. Six out of fifty experimentally tested compounds showed μM inhibitory activity toward TsCu/Zn-SOD. Two of them showed species selectivity since did not inhibit the homologous human enzyme when assayed in vitro.

Lead pollution sources and Impacts

International Nuclear Information System (INIS)

El-Haggar, S.M.; Saad, S.G.; Saleh, S.K.; El-Kady, M.A.

1996-01-01

Despite the medical awareness of lead toxicity, and despite legislation designed to reduce environmental contamination, lead is one of the most widely used heavy metals. Significant human exposure occurs from automobile exhaust fumes, cigarette smoking, lead-based paints and plumbing systems lead spread in the environment can take place in several ways, the most important of which is through the lead compounds released in automobile exhaust as a direct result of the addition of tetraethyl or tetraethyl lead to gasoline as octane boosting agents. Of special is the effect of lead pollution on children, which affects their behavioral and educational attributes considerably. The major channel through through which lead is absorbed is through inhalation of lead compounds in the atmosphere. Lead is a heavy metal characterized its malleability, ductility and poor conduction of electricity. So, it has a wide range of applications ranging from battery manufacturing to glazing ceramics. It is rarely found free in nature but is present in several minerals and compounds. The aim of this paper is to discuss natural and anthropogenic sources of lead together with its distribution and trends with emphasis on egypt. The effects of lead pollution on human health, vegetation and welfare are also presented. It could be concluded that, the excessive release of lead into the environment, especially through the atmosphere, can produce many detrimental and sometimes fatal effects on human, agriculture and zoological life. Besides, it is very plain that there is a serious problem of pollution lead in egypt and specially in cairo. 7 figs

Two luminescent frameworks constructed from lead(II) salts with carboxylate ligands containing dinuclear lead(II) units

International Nuclear Information System (INIS)

Zhu Xiandong; Li Xiaoju; Liu Qingyan; Lue Jian; Guo Zhengang; He Jinrun; Li Yafeng; Cao Rong

2007-01-01

Two luminescent Pb(II) coordination frameworks containing dinuclear lead(II) units, [Pb(PYDC)(H 2 O)] n (1) and [Pb(HPHT)] n (2) have been prepared by the self-assembly of lead(II) salts with pyridinecarboxylate and benzenecarboxylate. Single-crystal X-ray diffraction analyses reveal that compound 1 is a three-dimensional architecture consisting of Pb 2 O 2 dimeric building units, whereas compound 2 is a two-dimensional layer structure containing one-dimensional lead-oxide chains. The luminescent properties of 1 and 2 have been investigated in the solid state at room temperature, indicating structure-dependent photoluminescent properties of the coordination frameworks. - Graphical abstract: Two luminescent Pb(II) coordination frameworks, [Pb(PYDC)(H 2 O)] n (1) and [Pb(HPHT)] n (2) have been prepared. Single-crystal analyses reveal that compound 1 is a three-dimensional architecture consisting of Pb 2 O 2 dimeric building units, whereas compound 2 is a two-dimensional layer structure containing one-dimensional lead-oxide chains. The luminescent properties have been investigated, indicating structure-dependent photoluminescent properties of the coordination frameworks

Natural Compounds from Mexican Medicinal Plants as Potential Drug Leads for Anti-Tuberculosis Drugs

Directory of Open Access Journals (Sweden)

ROCIO GÓMEZ-CANSINO

Full Text Available ABSTRACT In Mexican Traditional Medicine 187 plant species are used in the treatment of respiratory conditions that may be associated with tuberculosis. In this contribution, we review the ethnobotany, chemistry and pharmacology of 63 species whose extracts have been assayed for antimycobacterial activity in vitro. Among these, the most potent is Aristolochia brevipes (MIC= 12.5 µg/mL, followed by Aristolochia taliscana, Citrus sinensis, Chrysactinia mexicana, Persea americana, and Olea europaea (MIC 95%, 50 µg/mL include: Amphipterygium adstringens, Larrea divaricata, and Phoradendron robinsoni. Several active compounds have been identified, the most potent are: Licarin A (isolated from A. taliscana, and 9-amino-9-methoxy-3,4-dihydro-2H-benzo[h]-chromen-2-one (transformation product of 9-methoxytariacuripyrone isolated from Aristolochia brevipes, both with MIC= 3.125 µg/mL, that is 8-fold less potent than the reference drug Rifampicin (MIC= 0.5 µg/mL. Any of the compounds or extracts here reviewed has been studied in clinical trials or with animal models; however, these should be accomplished since several are active against strains resistant to common drugs.

Determination of cadmium and lead species and phytochelatins in pea (Pisum sativum) by HPLC-ICPMS and HPLC-ESIMSn

International Nuclear Information System (INIS)

Baralkiewicz, D.; Magorzata, K.; Piechalak, A.; Tomaszewska, B.

2009-01-01

Full text: Trace elements play an important role in the functioning of life on our planet. Some of them can be highly toxic, whereas others can be essential. These effects are very often related to particular form in which the element is present. Often these different chemical forms of a particular element or its compounds are referred to as 'species'. Cadmium and lead are widespread heavy metal pollutants released into the environment by human activities. The presence of Pb 2+ and Cd 2+ in the environment leads to a numerous disturbances in many metabolic processes in plants. Inhibition of growth is a major symptom. Hyphenated techniques, such as HPLC-ICPMS and HPLC-ESIMSn seem to be the best analytical instruments to study metal speciation in plants. In our study, we used hyphenated techniques to identify compounds engaged in Cd and Pb metabolism and to perform analysis of metal complexes induced in Pisum sativum exposed to cadmium and lead. These identified compounds might be valuable source of information to study metal accumulation mechanism for bioremediation processes. (author)

The Dynamics of Autism Spectrum Disorders: How Neurotoxic Compounds and Neurotransmitters Interact

Directory of Open Access Journals (Sweden)

Margot Van de Bor

2013-08-01

Full Text Available In recent years concern has risen about the increasing prevalence of Autism Spectrum Disorders (ASD. Accumulating evidence shows that exposure to neurotoxic compounds is related to ASD. Neurotransmitters might play a key role, as research has indicated a connection between neurotoxic compounds, neurotransmitters and ASD. In the current review a literature overview with respect to neurotoxic exposure and the effects on neurotransmitter systems is presented. The aim was to identify mechanisms and related factors which together might result in ASD. The literature reported in the current review supports the hypothesis that exposure to neurotoxic compounds can lead to alterations in the GABAergic, glutamatergic, serotonergic and dopaminergic system which have been related to ASD in previous work. However, in several studies findings were reported that are not supportive of this hypothesis. Other factors also might be related, possibly altering the mechanisms at work, such as time and length of exposure as well as dose of the compound. Future research should focus on identifying the pathway through which these factors interact with exposure to neurotoxic compounds making use of human studies.

Lead: Aspects of its ecology and environmental toxicity. [physiological effects of lead compound contamination of environment

Science.gov (United States)

Siegel, S. M.

1973-01-01

An analysis of lead toxicity in the Hawaiian environment was conducted. It was determined that lead enters the environment as an industrial contaminant resulting from the combustion of leaded gasoline. The amount of lead absorbed by the plants in various parts of the Hawaiian Islands is reported. The disposition of lead in the sediments of canals and yacht basins was investigated. The methods for conducting the surveys of lead content are described. Possible consequences of continued environmental pollution by burning leaded gasoline are discussed.

Whole-Exome Sequencing Identified a Novel Compound Heterozygous Mutation of LRRC6 in a Chinese Primary Ciliary Dyskinesia Patient

Directory of Open Access Journals (Sweden)

Lv Liu

2018-01-01

Full Text Available Primary ciliary dyskinesia (PCD is a clinical rare peculiar disorder, mainly featured by respiratory infection, tympanitis, nasosinusitis, and male infertility. Previous study demonstrated it is an autosomal recessive disease and by 2017 almost 40 pathologic genes have been identified. Among them are the leucine-rich repeat- (LRR- containing 6 (LRRC6 codes for a 463-amino-acid cytoplasmic protein, expressed distinctively in motile cilia cells, including the testis cells and the respiratory epithelial cells. In this study, we applied whole-exome sequencing combined with PCD-known genes filtering to explore the genetic lesion of a PCD patient. A novel compound heterozygous mutation in LRRC6 (c.183T>G/p.N61K; c.179-1G>A was identified and coseparated in this family. The missense mutation (c.183T>G/p.N61K may lead to a substitution of asparagine by lysine at position 61 in exon 3 of LRRC6. The splice site mutation (c.179-1G>A may cause a premature stop codon in exon 4 and decrease the mRNA levels of LRRC6. Both mutations were not present in our 200 local controls, dbSNP, and 1000 genomes. Three bioinformatics programs also predicted that both mutations are deleterious. Our study not only further supported the importance of LRRC6 in PCD, but also expanded the spectrum of LRRC6 mutations and will contribute to the genetic diagnosis and counseling of PCD patients.

Screening of the ‘Open Scaffolds’ collection from Compounds Australia identifies a new chemical entity with anthelmintic activities against different developmental stages of the barber's pole worm and other parasitic nematodes

Directory of Open Access Journals (Sweden)

Sarah Preston

2017-12-01

Full Text Available The discovery and development of novel anthelmintic classes is essential to sustain the control of socioeconomically important parasitic worms of humans and animals. With the aim of offering novel, lead-like scaffolds for drug discovery, Compounds Australia released the ‘Open Scaffolds’ collection containing 33,999 compounds, with extensive information available on the physicochemical properties of these chemicals. In the present study, we screened 14,464 prioritised compounds from the ‘Open Scaffolds’ collection against the exsheathed third-stage larvae (xL3s of Haemonchus contortus using recently developed whole-organism screening assays. We identified a hit compound, called SN00797439, which was shown to reproducibly reduce xL3 motility by ≥ 70%; this compound induced a characteristic, “coiled” xL3 phenotype (IC50 = 3.46–5.93 μM, inhibited motility of fourth-stage larvae (L4s; IC50 = 0.31–12.5 μM and caused considerable cuticular damage to L4s in vitro. When tested on other parasitic nematodes in vitro, SN00797439 was shown to inhibit (IC50 = 3–50 μM adults of Ancylostoma ceylanicum (hookworm and first-stage larvae of Trichuris muris (whipworm and eventually kill (>90% these stages. Furthermore, this compound completely inhibited the motility of female and male adults of Brugia malayi (50–100 μM as well as microfilariae of both B. malayi and Dirofilaria immitis (heartworm. Overall, these results show that SN00797439 acts against genetically (evolutionarily distant parasitic nematodes i.e. H. contortus and A. ceylanicum [strongyloids] vs. B. malayi and D. immitis [filarioids] vs. T. muris [enoplid], and, thus, might offer a novel, lead-like scaffold for the development of a relatively broad-spectrum anthelmintic. Our future work will focus on assessing the activity of SN00797439 against other pathogens that cause neglected tropical diseases, optimising analogs with improved biological activities and

Severe Neurotoxicity Following Ingestion of Tetraethyl Lead

OpenAIRE

Wills, Brandon K.; Christensen, Jason; Mazzoncini, Joe; Miller, Michael

2010-01-01

Organic lead compounds are potent neurotoxins which can result in death even from small exposures. Traditionally, these compounds are found in fuel stabilizers, anti-knock agents, and leaded gasoline. Cases of acute organic lead intoxication have not been reported for several decades. We report a case of a 13-year-old Iraqi male who unintentionally ingested a fuel stabilizer containing 80–90% tetraethyl lead, managed at our combat support hospital. The patient developed severe neurologic symp...

Sanskrit Compound Processor

Science.gov (United States)

Kumar, Anil; Mittal, Vipul; Kulkarni, Amba

Sanskrit is very rich in compound formation. Typically a compound does not code the relation between its components explicitly. To understand the meaning of a compound, it is necessary to identify its components, discover the relations between them and finally generate a paraphrase of the compound. In this paper, we discuss the automatic segmentation and type identification of a compound using simple statistics that results from the manually annotated data.

Novel compound heterozygous mutations in the GPR98 (USH2C) gene identified by whole exome sequencing in a Moroccan deaf family.

Science.gov (United States)

Bousfiha, Amale; Bakhchane, Amina; Charoute, Hicham; Detsouli, Mustapha; Rouba, Hassan; Charif, Majida; Lenaers, Guy; Barakat, Abdelhamid

2017-10-01

In the present work, we identified two novel compound heterozygote mutations in the GPR98 (G protein-coupled receptor 98) gene causing Usher syndrome. Whole-exome sequencing was performed to study the genetic causes of Usher syndrome in a Moroccan family with three affected siblings. We identify two novel compound heterozygote mutations (c.1054C > A, c.16544delT) in the GPR98 gene in the three affected siblings carrying post-linguale bilateral moderate hearing loss with normal vestibular functions and before installing visual disturbances. This is the first time that mutations in the GPR98 gene are described in the Moroccan deaf patients.

A call for using natural compounds in the development of new antimalarial treatments – an introduction

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Deharo Eric

2011-03-01

Full Text Available Abstract Natural compounds, mostly from plants, have been the mainstay of traditional medicine for thousands of years. They have also been the source of lead compounds for modern medicine, but the extent of mining of natural compounds for such leads decreased during the second half of the 20th century. The advantage of natural compounds for the development of drugs derives from their innate affinity for biological receptors. Natural compounds have provided the best anti-malarials known to date. Recent surveys have identified many extracts of various organisms (mostly plants as having antiplasmodial activity. Huge libraries of fractionated natural compounds have been screened with impressive hit rates. Importantly, many cases are known where the crude biological extract is more efficient pharmacologically than the most active purified compound from this extract. This could be due to synergism with other compounds present in the extract, that as such have no pharmacological activity. Indeed, such compounds are best screened by cell-based assay where all potential targets in the cell are probed and possible synergies identified. Traditional medicine uses crude extracts. These have often been shown to provide many concoctions that deal better with the overall disease condition than with the causative agent itself. Traditional medicines are used by ~80 % of Africans as a first response to ailment. Many of the traditional medicines have demonstrable anti-plasmodial activities. It is suggested that rigorous evaluation of traditional medicines involving controlled clinical trials in parallel with agronomical development for more reproducible levels of active compounds could improve the availability of drugs at an acceptable cost and a source of income in malaria endemic countries.

Chemical interaction in resistors based on lead ruthenite with additions of niobium(5) oxide compounds

International Nuclear Information System (INIS)

Lozinskij, N.S.; Shevtsova, N.A.; Gruba, A.I.; Volkov, V.I.

1986-01-01

The method of X-ray phase analysis was used to study chemical interaction in isothermal cross-section of Pb 2 RU 2 O 6 -Nb 2 O 5 , Rbsub(2)Rusub(2)Osub(6)-NbWOsub(5.5) and Rb 2 Ru 2 O 6 -Pb 2 Nb 2 O 7 systems at 850 deg C as well as in models of real ruthenium resistors. Chemical interaction is stated to take place in systems with niobium (5) oxide and NbWOsub(5.5). Niobium (5) and tungsten (6) displace ruthenium (4) from its compounds with formation of their lead salts. Similar chemical interactions between current-carrying phase of the resistor and modifiers representing niobium-containing take place in models of components of the studied systems take place in models of resistors

Combined genetic and bioactivity-based prioritization leads to the isolation of an endophyte-derived antimycobacterial compound.

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Alvin, A; Kalaitzis, J A; Sasia, B; Neilan, B A

2016-05-01

To initiate a genetic and bioactivity-based screening programme of culturable endophytes to identify micro-organisms capable of producing bioactive polyketides and peptides. Fungal endophytes were isolated from flowers, leaves and roots of Rhoeo spathacea, revealing a community consisting of Colletotrichum sp., Fusarium sp., Guignardia sp., Phomopsis sp., Phoma sp. and Microdochium sp. Genetic screening showed that all isolates had polyketide synthase (PKS) genes and most had nonribosomal peptide synthetase (NRPS) genes. Ethyl acetate extracts of the fungal isolates exhibited antiproliferative activity against at least one of the seven bacterial and mycobacterial test strains. Nuclear Magnetic Resonance -guided fractionation of the crude extract from a Fusarium sp. strain which exhibited strong antiproliferative activity against Mycobacterium tuberculosis resulted in the isolation of the polyketide javanicin. This compound was active against Myco. tuberculosis (MIC = 25 μg ml(-1)) and Mycobacterium phlei (MIC = 50 μg ml(-1)). The medicinal plant R. spathacea hosts a variety of fungal endophytes capable of producing antibacterial and antimycobacterial compounds. There is a positive correlation between the presence of PKS and/or NRPS encoding genes in endophytes and the bioactivity of their respective organic extracts. This is the first report on the fungal endophytic diversity of R. spathacea, and the isolation of an antimycobacterial compound from the plant which has been traditionally used for the treatment of tuberculosis symptoms. © 2016 The Society for Applied Microbiology.

Molecular docking for thrombolytic activity of some isolated compounds from Clausena lansium.

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Arkajyoti Paul

2017-03-01

Full Text Available Clausena lansium (Family- Rutaceae is commonly known as wampee, is found in fallow lands throughout Bangladesh. Our aim of the study to performed molecular docking studies to identify potential binding affinities of the phytocompounds from Clausena lansium, namely Clausemarin B, Clausenaline C, Clausenaline E, Murrayanine, vanillic acid and Xanthotoxol for searching of lead molecule for thrombolytic activity. A wide range of docking score found during molecular docking by Schrodinger. Clausemarin B , Clausenaline C , Clausenaline E, Murrayanine , vanillic acid and Xanthotoxol showed the docking score -6.926, -4.041, -4.889 , -4.356, -3.007 and -5.816 respectively. Among all the compounds Clausemarin B showed the best docking score. So, Clausemarin B is the best compounds for thrombolytic activity, as it possessed the best value in Molecular docking. Further in vivo investigation need to identify the thrombolytic activity of isolated compounds from Clausena lansium.

Radiogenic lead-208 abundance 88.34 %

International Nuclear Information System (INIS)

Seneda, Jose A.; Abrao, Alcidio; Dias, Mauro S.; Kakazu, Mauricio H.; Salvador, Vera L.R.; Queiroz, Carlos A.S.; Rocha, Soraya M.R. da; Sato, Key

2009-01-01

Brazil has a long tradition in thorium technology, from the monazite ores mining until the production of the nuclear grade thorium compounds. Early in 1969 the Institute of Energy and Nuclear Research (IPEN) designed a project for a pilot plant installation to purify the thorium compounds, based on the solvent extraction technique. Thorium compounds used came from monazite's industrialization. During the course of the operation of this plant, a crude sludge were formed containing thorium not extracted and the whole rare earths, plus minor impurities like sodium, titanium, zirconium, hafnium, iron, silicon, phosphate and the thorium daughters were accumulated. Included is the radiogenic lead-208. This sludge, hereafter named 'RETOTER', was treated with hydrochloric acid and the lead was separated and recovered by anion exchange technology. The lead-208 was analyzed by mass spectrometry (HR-ICPMS) technique. The lead-208 abundance measure was 88.34%, this allowed the calculation of the thermal neutron capture cross section of σ 0 γ = 14,6 +/- 0.7 mb, considerably lower than the σ 0 γ = 174.2 +/- 0.7 mb value of the natural lead. (author)

The discovery of bioisoster compound for plumbagin using the knowledge-based rational method

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Jeong, Seo Hee; Choi, Jung Sup; Ko, Young Kwan; Kang, Nam Sook

2015-04-01

Arabidopsis thaliana 7-Keto-8-AminoPelargonic Acid Synthase (AtKAPAS) is a crucial herbicide target, and AtKAPAS inhibitors are widely available in the agrochemical market. The herbicide plumbagin is known as a potent inhibitor for AtKAPAS but it is extremely toxic. In this study, we identified the metabolic site of plumbagin and also performed a similarity-based library analysis using 2D fingerprints and a docking study. Four compounds as virtual hits were derived from plumbagin. Treatment of Digitaria ciliaris with compound 2, one of four hit compounds, stunted the growth of leaves and the leaf tissue was desiccated or burned within three days. Thus, we expect that compound 2 will be developed as a new herbicide and additionally our strategy will provide helpful information for optimizing lead compounds.

Skin toxicology of lead species evaluated by their permeability and proteomic profiles: a comparison of organic and inorganic lead.

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Pan, Tai-Long; Wang, Pei-Wen; Al-Suwayeh, Saleh A; Chen, Chih-Chieh; Fang, Jia-You

2010-08-01

Lead compounds are known to cause cytotoxicity and genotoxicity. Lead absorption by the skin is an important route through which this metal enters the body. The purpose of this work was to evaluate the skin permeability and toxicological profiles of two lead species, lead acetate and lead nitrate. This study assessed lead-induced toxicity mechanisms by focusing on the histopathology, proteomics, cell growth, and cellular ATP. In vitro skin permeation assays showed that there was no significant difference of lead accumulation within and across the skin between the two lead species. The presence of simulated sweat reduced the skin uptake of lead. The skin deposition of lead acetate was greater than that of lead nitrate with in vivo topical application. On the other hand, lead nitrate produced greater changes in the skin's histology and proteomic profiles compared to lead acetate. Four protein spots which showed significant changes were identified and are discussed in this study. These included glucose-related protein precursor (GRP) 78, K14, alpha-actin, and Rho GDP-dissociation inhibitor 2 (RhoGDI2). These proteins are respectively associated with oxidative stress, apoptosis, wound healing, and proliferation. Lead presented a biphasic pattern on cell growth and intracellular ATP content, with a stimulating effect at low concentrations and an inhibitory effect on cell proliferation at higher concentrations. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Severe neurotoxicity following ingestion of tetraethyl lead.

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Wills, Brandon K; Christensen, Jason; Mazzoncini, Joe; Miller, Michael

2010-03-01

Organic lead compounds are potent neurotoxins which can result in death even from small exposures. Traditionally, these compounds are found in fuel stabilizers, anti-knock agents, and leaded gasoline. Cases of acute organic lead intoxication have not been reported for several decades. We report a case of a 13-year-old Iraqi male who unintentionally ingested a fuel stabilizer containing 80-90% tetraethyl lead, managed at our combat support hospital. The patient developed severe neurologic symptoms including agitation, hallucinations, weakness, and tremor. These symptoms were refractory to escalating doses of benzodiazepines and ultimately required endotracheal intubation and a propofol infusion. Adjunctive therapies included chelation, baclofen, and nutrition provided through a gastrostomy tube. The patient slowly recovered and was discharged in a wheelchair 20 days after ingestion, still requiring tube feeding. Follow-up at 62 days post-ingestion revealed near-resolution of symptoms with residual slurred speech and slight limp. This case highlights the profound neurotoxic manifestations of acute organic lead compounds.

Synthesis and characterization of nanometer sized thermoelectric lead-antimony-silver-tellurium compounds and related materials; Synthese und Charakterisierung nanoskaliger Thermoelektrika der LAST (Lead-Antimony-Silver-Tellurium)-Familie und verwandter Verbindungen

Energy Technology Data Exchange (ETDEWEB)

Petri, Denis

2012-09-10

The present dissertation deals with different variants of synthesis and processing of nanocrystalline composites of various thermoelectric compounds based on lead telluride including LAST-m (AgPb{sub m}SbTe{sub m+2}), LASTT-m-x (AgPb{sub m-x}Sn{sub x}SbTe{sub m+2}), LABST-m-x (AgPb{sub m}Sb{sub 1-x}Bi{sub x}Te{sub m+2}), doped LAST-m and (PbTe){sub m}(M{sup 15}{sub 2}Te{sub 3}) and the characterization thereof. A new route of manufacturing nanocrystalline composites was developed. The so called co-ball milling-route includes the synthesis of bi- or multinary compounds by conventional solid state melting methods followed by combined milling of appropriate amounts in a planetary ball mill; a process related to the widely used mechanical alloying of elemental powders. The as produced powders were shortly annealed for one hour and a.erwards compacted either at room temperature followed by pressureless sintering or combined application of high pressure and elevated temperatures via spark-plasma-sintering or short-term-sintering. The ball milling yielded micron-sized agglomerates consisting of crystallites with diameters ranging from 10 to 50 nm. These crystallites exhibited complicated internal nanostructures severe crystal defects as a consequence of the high energy processing. During short-term annealing some grain coarsening occured and the crystal defects partly healed, which was confirmed by TEM and HRTEM investigations as well as profile analysis of XRD powder pattern. Local EDX-analysis showed different compositions at every point as a consequence of synthesis and decomposition of the compounds. Measurements of thermopower, electrical and thermal conductivity were carried out and the values of the figure of merit ZT and the powerfactor were calculated. In general the compounds exhibited larger thermopower than corresponding bulk materials, which might be attributed to energy filtering of charge carriers at partly oxidized grain boundaries. Due to enhanced phonon

Synergistic interactions between phenolic compounds identified in grape pomace extract with antibiotics of different classes against Staphylococcus aureus and Escherichia coli.

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Sanhueza, Loreto; Melo, Ricardo; Montero, Ruth; Maisey, Kevin; Mendoza, Leonora; Wilkens, Marcela

2017-01-01

Synergy could be an effective strategy to potentiate and recover antibiotics nowadays useless in clinical treatments against multi-resistant bacteria. In this study, synergic interactions between antibiotics and grape pomace extract that contains high concentration of phenolic compounds were evaluated by the checkerboard method in clinical isolates of Staphylococcus aureus and Escherichia coli. To define which component of the extract is responsible for the synergic effect, phenolic compounds were identified by RP-HPLC and their relative abundance was determined. Combinations of extract with pure compounds identified there in were also evaluated. Results showed that the grape pomace extract combined with representatives of different classes of antibiotics as β-lactam, quinolone, fluoroquinolone, tetracycline and amphenicol act in synergy in all S. aureus and E. coli strains tested with FICI values varying from 0.031 to 0.155. The minimal inhibitory concentration (MIC) was reduced 4 to 75 times. The most abundant phenolic compounds identified in the extract were quercetin, gallic acid, protocatechuic acid and luteolin with relative abundance of 26.3, 24.4, 16.7 and 11.4%, respectively. All combinations of the extract with the components also showed synergy with FICI values varying from 0.031 to 0.5 and MIC reductions of 4 to 125 times with both bacteria strains. The relative abundance of phenolic compounds has no correlation with the obtained synergic effect, suggesting that the mechanism by which the synergic effect occurs is by a multi-objective action. It was also shown that combinations of grape pomace extract with antibiotics are not toxic for the HeLa cell line at concentrations in which the synergistic effect was observed (47 μg/mL of extract and 0.6-375 μg/mL antibiotics). Therefore, these combinations are good candidates for testing in animal models in order to enhance the effect of antibiotics of different classes and thus restore the currently unused

Synergistic interactions between phenolic compounds identified in grape pomace extract with antibiotics of different classes against Staphylococcus aureus and Escherichia coli.

Directory of Open Access Journals (Sweden)

Loreto Sanhueza

Full Text Available Synergy could be an effective strategy to potentiate and recover antibiotics nowadays useless in clinical treatments against multi-resistant bacteria. In this study, synergic interactions between antibiotics and grape pomace extract that contains high concentration of phenolic compounds were evaluated by the checkerboard method in clinical isolates of Staphylococcus aureus and Escherichia coli. To define which component of the extract is responsible for the synergic effect, phenolic compounds were identified by RP-HPLC and their relative abundance was determined. Combinations of extract with pure compounds identified there in were also evaluated. Results showed that the grape pomace extract combined with representatives of different classes of antibiotics as β-lactam, quinolone, fluoroquinolone, tetracycline and amphenicol act in synergy in all S. aureus and E. coli strains tested with FICI values varying from 0.031 to 0.155. The minimal inhibitory concentration (MIC was reduced 4 to 75 times. The most abundant phenolic compounds identified in the extract were quercetin, gallic acid, protocatechuic acid and luteolin with relative abundance of 26.3, 24.4, 16.7 and 11.4%, respectively. All combinations of the extract with the components also showed synergy with FICI values varying from 0.031 to 0.5 and MIC reductions of 4 to 125 times with both bacteria strains. The relative abundance of phenolic compounds has no correlation with the obtained synergic effect, suggesting that the mechanism by which the synergic effect occurs is by a multi-objective action. It was also shown that combinations of grape pomace extract with antibiotics are not toxic for the HeLa cell line at concentrations in which the synergistic effect was observed (47 μg/mL of extract and 0.6-375 μg/mL antibiotics. Therefore, these combinations are good candidates for testing in animal models in order to enhance the effect of antibiotics of different classes and thus restore the

High-Throughput Screening Using iPSC-Derived Neuronal Progenitors to Identify Compounds Counteracting Epigenetic Gene Silencing in Fragile X Syndrome.

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Kaufmann, Markus; Schuffenhauer, Ansgar; Fruh, Isabelle; Klein, Jessica; Thiemeyer, Anke; Rigo, Pierre; Gomez-Mancilla, Baltazar; Heidinger-Millot, Valerie; Bouwmeester, Tewis; Schopfer, Ulrich; Mueller, Matthias; Fodor, Barna D; Cobos-Correa, Amanda

2015-10-01

Fragile X syndrome (FXS) is the most common form of inherited mental retardation, and it is caused in most of cases by epigenetic silencing of the Fmr1 gene. Today, no specific therapy exists for FXS, and current treatments are only directed to improve behavioral symptoms. Neuronal progenitors derived from FXS patient induced pluripotent stem cells (iPSCs) represent a unique model to study the disease and develop assays for large-scale drug discovery screens since they conserve the Fmr1 gene silenced within the disease context. We have established a high-content imaging assay to run a large-scale phenotypic screen aimed to identify compounds that reactivate the silenced Fmr1 gene. A set of 50,000 compounds was tested, including modulators of several epigenetic targets. We describe an integrated drug discovery model comprising iPSC generation, culture scale-up, and quality control and screening with a very sensitive high-content imaging assay assisted by single-cell image analysis and multiparametric data analysis based on machine learning algorithms. The screening identified several compounds that induced a weak expression of fragile X mental retardation protein (FMRP) and thus sets the basis for further large-scale screens to find candidate drugs or targets tackling the underlying mechanism of FXS with potential for therapeutic intervention. © 2015 Society for Laboratory Automation and Screening.

Preparation of kinase-biased compounds in the search for lead inhibitors of kinase targets.

Science.gov (United States)

Lai, Justine Y Q; Langston, Steven; Adams, Ruth; Beevers, Rebekah E; Boyce, Richard; Burckhardt, Svenja; Cobb, James; Ferguson, Yvonne; Figueroa, Eva; Grimster, Neil; Henry, Andrew H; Khan, Nawaz; Jenkins, Kerry; Jones, Mark W; Judkins, Robert; Major, Jeremy; Masood, Abid; Nally, James; Payne, Helen; Payne, Lloyd; Raphy, Gilles; Raynham, Tony; Reader, John; Reader, Valérie; Reid, Alison; Ruprah, Parminder; Shaw, Michael; Sore, Hannah; Stirling, Matthew; Talbot, Adam; Taylor, Jess; Thompson, Stephen; Wada, Hiroki; Walker, David

2005-05-01

This work describes the preparation of approximately 13,000 compounds for rapid identification of hits in high-throughput screening (HTS). These compounds were designed as potential serine/threonine or tyrosine kinase inhibitors. The library consists of various scaffolds, e.g., purines, oxindoles, and imidazoles, whereby each core scaffold generally includes the hydrogen bond acceptor/donor properties known to be important for kinase binding. Several of these are based upon literature kinase templates, or adaptations of them to provide novelty. The routes to their preparation are outlined. A variety of automation techniques were used to prepare >500 compounds per scaffold. Where applicable, scavenger resins were employed to remove excess reagents and when necessary, preparative high performance liquid chromatography (HPLC) was used for purification. These compounds were screened against an 'in-house' kinase panel. The success rate in HTS was significantly higher than the corporate compound collection. Copyright (c) 2004 Wiley Periodicals, Inc.

Influence of organic nitro-compounds and of surface active compounds on the inverse voltametric determination of cadmium, lead and copper

Energy Technology Data Exchange (ETDEWEB)

Wahdat, F; Neeb, R

1983-12-01

The influence of surface active agents and of organic nitro-compounds alone and in combination on the potentiometric stripping analysis and anodic-stripping differential-pulse-polarography of Cd, Pb and Cu is investigated. In some cases PSA offers advantages for the determination of these elements in the presence of organic nitro-compounds in comparison with differential pulse-polarography.

Identifying and Solving Lead Issues from Water Systems with Materials/Device Replacement in Schools and other Buildings

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Identifying and assessing lead contamination and exposure potential in single-family residences is difficult enough, but doing the same kind of assessment and remediation in buildings, schools, and day care centers is even more challenging. It is of particular importance because ...

Metabolomic approach to identifying bioactive compounds in berries: advances toward fruit nutritional enhancement.

Science.gov (United States)

Stewart, Derek; McDougall, Gordon J; Sungurtas, Julie; Verrall, Susan; Graham, Julie; Martinussen, Inger

2007-06-01

Plant polyphenolics continue to be the focus of attention with regard to their putative impact on human health. An increasing and ageing human population means that the focus on nutrition and nutritional enhancement or optimisation of our foodstuffs is paramount. Using the raspberry as a model, we have shown how modern metabolic profiling approaches can be used to identify the changes in the level of beneficial polyphenolics in fruit breeding segregating populations and how the level of these components is determined by genetic and/or environmental control. Interestingly, the vitamin C content appeared to be significantly influenced by environment (growth conditions) whilst the content of the polyphenols such as cyanidin, pelargonidin and quercetin glycosides appeared much more tightly regulated, suggesting a rigorous genetic control. Preliminary metabolic profiling showed that the fruit polyphenolic profiles divided into two gross groups segregating on the basis of relative levels of cyanidin-3-sophoroside and cyanidin-3-rutinoside, compounds implicated as conferring human health benefits.

Lead poisoning in cattle and sheep

Energy Technology Data Exchange (ETDEWEB)

Allcroft, R

1951-09-15

The danger of paint and other lead compounds to the bovine is well recognized and has been recorded and discussed fairly extensively from time to time. The literature indicates that the calf is extremely susceptible to lead poisoning, but relatively little has been reported regarding the levels of lead in tissues of animals which have died as a result of lead poisoning, and still less in animals suspected of suffering from sub-lethal doses of lead compounds. In order to provide sufficient data to enable interpretation of figures obtained from tissues in cases of suspected lead poisoning sent in from the field, and to provide information on the metabolic fate of lead in ruminants, investigations were made at Weybridge on the absorption, excretion, retention and general metabolic effects of lead in both cattle and sheep and the results have been published in a series of five papers. In this brief review it is intended to discuss points from these and subsequent investigations which are likely to be of interest to the veterinarian.

Current practices in generation of small molecule new leads.

Science.gov (United States)

Goodnow, R A

2001-01-01

The current drug discovery processes in many pharmaceutical companies require large and growing collections of high quality lead structures for use in high throughput screening assays. Collections of small molecules with diverse structures and "drug-like" properties have, in the past, been acquired by several means: by archive of previous internal lead optimization efforts, by purchase from compound vendors, and by union of separate collections following company mergers. More recently, many drug discovery companies have established dedicated efforts to effect synthesis by internal and/or outsourcing efforts of targeted compound libraries for new lead generation. Although high throughput/combinatorial chemistry is an important component in the process of new lead generation, the selection of library designs for synthesis and the subsequent design of library members has evolved to a new level of challenge and importance. The potential benefits of screening multiple small molecule compound library designs against multiple biological targets offers substantial opportunity to discover new lead structures. Subsequent optimization of such compounds is often accelerated because of the structure-activity relationship (SAR) information encoded in these lead generation libraries. Lead optimization is often facilitated due to the ready applicability of high-throughput chemistry (HTC) methods for follow-up synthesis. Some of the strategies, trends, and critical issues central to the success of lead generation processes are discussed below. Copyright 2002 Wiley-Liss, Inc.

Development of Lead Compounds as Fusion Inhibitors for Dengue Virus

Science.gov (United States)

2009-08-01

mixed stereo chemistry ), but no chemical modification was desired because of the high specificity of the fragment definition. This generation...therefore promising candidates for virtual screening, synthesis and biological testing. Out of the generation process, more than 80% of the...size and biological class of compounds (analogs of peptides, alkaloids , anthracyclines, etc.). We therefore have included the prediction of the effect

Molecular docking, QSAR and ADMET based mining of natural compounds against prime targets of HIV.

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Vora, Jaykant; Patel, Shivani; Sinha, Sonam; Sharma, Sonal; Srivastava, Anshu; Chhabria, Mahesh; Shrivastava, Neeta

2018-01-07

AIDS is one of the multifaceted diseases and this underlying complexity hampers its complete cure. The toxicity of existing drugs and emergence of multidrug-resistant virus makes the treatment worse. Development of effective, safe and low-cost anti-HIV drugs is among the top global priority. Exploration of natural resources may give ray of hope to develop new anti-HIV leads. Among the various therapeutic targets for HIV treatment, reverse transcriptase, protease, integrase, GP120, and ribonuclease are the prime focus. In the present study, we predicted potential plant-derived natural molecules for HIV treatment using computational approach, i.e. molecular docking, quantitative structure activity relationship (QSAR), and ADMET studies. Receptor-ligand binding studies were performed using three different software for precise prediction - Discovery studio 4.0, Schrodinger and Molegrow virtual docker. Docking scores revealed that Mulberrosides, Anolignans, Curcumin and Chebulic acid are promising candidates that bind with multi targets of HIV, while Neo-andrographolide, Nimbolide and Punigluconin were target-specific candidates. Subsequently, QSAR was performed using biologically proved compounds which predicted the biological activity of compounds. We identified Anolignans, Curcumin, Mulberrosides, Chebulic acid and Neo-andrographolide as potential natural molecules for HIV treatment from results of molecular docking and 3D-QSAR. In silico ADMET studies showed drug-likeness of these lead molecules. Structure similarities of identified lead molecules were compared with identified marketed drugs by superimposing both the molecules. Using in silico studies, we have identified few best fit molecules of natural origin against identified targets which may give new drugs to combat HIV infection after wet lab validation.

Natural Products as Lead Compounds for Sodium Glucose Cotransporter (SGLT) Inhibitors.

Science.gov (United States)

Blaschek, Wolfgang

2017-08-01

Glucose homeostasis is maintained by antagonistic hormones such as insulin and glucagon as well as by regulation of glucose absorption, gluconeogenesis, biosynthesis and mobilization of glycogen, glucose consumption in all tissues and glomerular filtration, and reabsorption of glucose in the kidneys. Glucose enters or leaves cells mainly with the help of two membrane integrated transporters belonging either to the family of facilitative glucose transporters (GLUTs) or to the family of sodium glucose cotransporters (SGLTs). The intestinal glucose absorption by endothelial cells is managed by SGLT1, the transfer from them to the blood by GLUT2. In the kidney SGLT2 and SGLT1 are responsible for reabsorption of filtered glucose from the primary urine, and GLUT2 and GLUT1 enable the transport of glucose from epithelial cells back into the blood stream.The flavonoid phlorizin was isolated from the bark of apple trees and shown to cause glucosuria. Phlorizin is an inhibitor of SGLT1 and SGLT2. With phlorizin as lead compound, specific inhibitors of SGLT2 were developed in the last decade and some of them have been approved for treatment mainly of type 2 diabetes. Inhibition of SGLT2 eliminates excess glucose via the urine. In recent times, the dual SGLT1/SGLT2 inhibitory activity of phlorizin has served as a model for the development and testing of new drugs exhibiting both activities.Besides phlorizin, also some other flavonoids and especially flavonoid enriched plant extracts have been investigated for their potency to reduce postprandial blood glucose levels which can be helpful in the prevention and supplementary treatment especially of type 2 diabetes. Georg Thieme Verlag KG Stuttgart · New York.

Phytochemical analysis and docking study of compounds present in a polyherbal preparation used in the treatment of dermatophytosis.

Science.gov (United States)

Simhadri Vsdna, Nagesh; Muniappan, Muthuchamy; Kannan, Iyanar; Viswanathan, Subramanyam

2017-12-01

Soleshine is a polyherbal preparation established in the market for the treatment of cracks and tinea pedis, which is applied externally. This preparation is composed of the extracts of indigenous plants, namely Azadirachta indica, Lawsonia alba, and Shorea robusta , mixed with castor oil and sesame oil. In the present study, an attempt was made to identify the constituents of soleshine and identify some potential drug-like molecules that can inhibit important drug targets of the dermatophytes using molecular docking method. The active ingredients of polyherbal preparation were identified with the aid of gas chromatography-mass spectrometry (GC-MS). Two major compounds were selected based on the retention time and percentage of the area covered in the graph for docking study. The three-dimensional structures of 1,3-β-glucan synthase, chitinase, fungalysin, and lumazine synthase were derived by homology modelling using MODELLER software, version 9.0. The docking of the ligand and receptor was performed using iGEMDOCK and AutodockVina software. The physicochemical properties, lipophilicity, hydrophilicity, and drug likeness properties were obtained from the Swiss ADME online server tool. The GC-MS analysis demonstrated the presence of different phytochemical compounds in the extract of polyherbal preparation. A total of 20 compounds were identified, among which 3,7-dimethyl-2,6-octadienaland 2-pentene-2-methyl were the major compounds. Regarding 3,7-dimethyl-2,6-octadienal, the covered area and height were 40.15% and 46.17%, respectively. These values were 31.90% and 23.33% for 2-pentene-2-methyl, respectively. These two major compounds had an excellent binding affinity and obeyed the rules for the drug likeness and lead likeness. As the findings indicated, the two major ingredients present in soleshine showed a good antifungal activity as they inhibited the enzymes responsible for the survival of fungal organism; furthermore, they were appropriate for the lead

Gene Expression Profiling Identifies Important Genes Affected by R2 Compound Disrupting FAK and P53 Complex

International Nuclear Information System (INIS)

Golubovskaya, Vita M.; Ho, Baotran; Conroy, Jeffrey; Liu, Song; Wang, Dan; Cance, William G.

2014-01-01

Focal Adhesion Kinase (FAK) is a non-receptor kinase that plays an important role in many cellular processes: adhesion, proliferation, invasion, angiogenesis, metastasis and survival. Recently, we have shown that Roslin 2 or R2 (1-benzyl-15,3,5,7-tetraazatricyclo[3.3.1.1~3,7~]decane) compound disrupts FAK and p53 proteins, activates p53 transcriptional activity, and blocks tumor growth. In this report we performed a microarray gene expression analysis of R2-treated HCT116 p53 +/+ and p53 −/− cells and detected 1484 genes that were significantly up- or down-regulated (p < 0.05) in HCT116 p53 +/+ cells but not in p53 −/− cells. Among up-regulated genes in HCT p53 +/+ cells we detected critical p53 targets: Mdm-2, Noxa-1, and RIP1. Among down-regulated genes, Met, PLK2, KIF14, BIRC2 and other genes were identified. In addition, a combination of R2 compound with M13 compound that disrupts FAK and Mmd-2 complex or R2 and Nutlin-1 that disrupts Mdm-2 and p53 decreased clonogenicity of HCT116 p53 +/+ colon cancer cells more significantly than each agent alone in a p53-dependent manner. Thus, the report detects gene expression profile in response to R2 treatment and demonstrates that the combination of drugs targeting FAK, Mdm-2, and p53 can be a novel therapy approach

Xeno-estrogenic compounds in precipitation

NARCIS (Netherlands)

Peters, R.J.B.; Beeltje, H.; Delft, R.J. van

2008-01-01

The exposure to some chemicals can lead to hormone disrupting effects. Presently, much attention is focused on so-called xeno-estrogens, synthetic compounds that interact with hormone receptors causing a number of reactions that eventually lead to effects related to reproduction and development. The

Cajachalcone: An Antimalarial Compound from Cajanus cajan Leaf Extract

Directory of Open Access Journals (Sweden)

E. O. Ajaiyeoba

2013-01-01

Full Text Available Cajanus cajan L, a member of the family Fabaceae, was identified from the Nigerian antimalarial ethnobotany as possessing antimalarial properties. The bioassay-guided fractionation of the crude methanol extract of C. cajan leaves was done in vitro using the multiresistant strain of Plasmodium falciparum (K1 in the parasite lactate dehydrogenase assay. Isolation of compound was achieved by a combination of chromatographic techniques, while the structure of the compound was elucidated by spectroscopy. This led to the identification of a cajachalcone, 2′,6′-dihydroxy-4-methoxy chalcone, as the biologically active constituent from the ethyl acetate fraction. Cajachalcone had an IC50 value of 2.0 μg/mL (7.4 μM and could be a lead for anti-malarial drug discovery.

Analysis and hit filtering of a very large library of compounds screened against Mycobacterium tuberculosis.

Science.gov (United States)

Ekins, Sean; Kaneko, Takushi; Lipinski, Christopher A; Bradford, Justin; Dole, Krishna; Spektor, Anna; Gregory, Kellan; Blondeau, David; Ernst, Sylvia; Yang, Jeremy; Goncharoff, Nicko; Hohman, Moses M; Bunin, Barry A

2010-11-01

There is an urgent need for new drugs against tuberculosis which annually claims 1.7-1.8 million lives. One approach to identify potential leads is to screen in vitro small molecules against Mycobacterium tuberculosis (Mtb). Until recently there was no central repository to collect information on compounds screened. Consequently, it has been difficult to analyze molecular properties of compounds that inhibit the growth of Mtb in vitro. We have collected data from publically available sources on over 300 000 small molecules deposited in the Collaborative Drug Discovery TB Database. A cheminformatics analysis on these compounds indicates that inhibitors of the growth of Mtb have statistically higher mean logP, rule of 5 alerts, while also having lower HBD count, atom count and lower PSA (ChemAxon descriptors), compared to compounds that are classed as inactive. Additionally, Bayesian models for selecting Mtb active compounds were evaluated with over 100 000 compounds and, they demonstrated 10 fold enrichment over random for the top ranked 600 compounds. This represents a promising approach for finding compounds active against Mtb in whole cells screened under the same in vitro conditions. Various sets of Mtb hit molecules were also examined by various filtering rules used widely in the pharmaceutical industry to identify compounds with potentially reactive moieties. We found differences between the number of compounds flagged by these rules in Mtb datasets, malaria hits, FDA approved drugs and antibiotics. Combining these approaches may enable selection of compounds with increased probability of inhibition of whole cell Mtb activity.

Lead (Environmental Health Student Portal)

Science.gov (United States)

... Air Pollution Home Indoor Air Pollution Outdoor Air Pollution Particulate Matter Ozone Chemicals Chemicals Home Mercury Lead Arsenic Volatile Organic Compounds Plastics Pesticides Climate Change ...

Comparison of methods for certification of stannic, stibium and lead traces in reference materials for steel

Directory of Open Access Journals (Sweden)

I. V. Khodakovskaya

2016-01-01

Full Text Available Development and introduction of new metallurgical technologies, new additional chemical compound indexes controlled in metallurgical materials demand to develop the new, more advanced methods of analytical control. The particular attention should be paid to identify the traces of stannic, stinium and lead because of their influence on metal characteristics.

Identifying and Solving Lead Issues from Water Systems with Materials/Device Replacement in Schools and other Buildings - slides

Science.gov (United States)

Identifying and assessing lead contamination and exposure potential in single-family residences is difficult enough, but doing the same kind of assessment and remediation in buildings, schools, and day care centers is even more challenging. It is of particular importance because ...

Solid-phase synthesis of compounds of europium and terbium with nitrogen-containing heterocyclic compounds under mechanical activation

International Nuclear Information System (INIS)

Kalinovskaya, I.V.; Karasev, V.E.

2000-01-01

Effect of solvents and parameters of mechanical treatment on basic regularities of synthesis of rare earth compounds with nitrogen-containing heterocyclic compounds is studied. It is shown that interaction on europium (3) and terbium (3) nitrates with nitrogen-containing heterocyclic compounds leads to formation of compounds of Ln(NO 3 )·2D composition, where Ln=Eu, Tb; D=2,2-dipyridyl, 1,10-phenanthroline, diphenylguanidine. Effect of conditions of mechanical treatment and different additions on process and yield of products is studied. Compounds prepared are characterized by the methods of chemical element analysis, IR spectroscopy and luminescent spectroscopy [ru

Assessment of Inhibition of Ebola Virus Progeny Production by Antiviral Compounds.

Science.gov (United States)

Falzarano, Darryl

2017-01-01

Assessment of small molecule compounds against filoviruses, such as Ebola virus, has identified numerous compounds that appear to have antiviral activity and should presumably be further investigated in animal efficacy trials. However, despite the many compounds that are purported to have good antiviral activity in in vitro studies, there are few instances where any efficacy has been reported in nonhuman primate models. Many of the high-throughput screening assays use reporter systems that only recapitulate a portion of the virus life cycle, while other assays only assess antiviral activity at relatively early time points. Moreover, many assays do not assess virus progeny production. A more in-depth evaluation of small numbers of test compounds is useful to economize resources and to generate higher quality antiviral hits. Assessing virus progeny production as late as 5 days post-infection allows for the elimination of compounds that have initial antiviral effects that are not sustained or where the virus rapidly develops resistance. While this eliminates many potential lead compounds that may be worthy of further structure-activity relationship (SAR) development, it also quickly excludes compounds that in their current form are unlikely to be effective in animal models. In addition, the inclusion of multiple assays that assess both cell viability and cell cytotoxicity, via different mechanisms, provides a more thorough assessment to exclude compounds that are not direct-acting antivirals.

Natural compounds with herbicidal activity

Directory of Open Access Journals (Sweden)

Mariano Fracchiolla

2007-12-01

Full Text Available Research about phytotoxic activity of natural compounds could lead both to find new herbicidal active ingredients and to plan environmental friendly weed control strategies. Particularly, living organisms could be a source of compounds that are impossible, for their complexity, to synthesize artificially. More over, they could have alternative sites of action respect to the known chemical herbicides and, due to their origin, they should be more environmental safe. Many living organism, such as bacteria, fungi, insects, lichens and plants, are able to produce bioactive compounds. They generally are secondary metabolites or simply waste molecules. In this paper we make a review about these compounds, highlighting potential and constraints.

Natural compounds with herbicidal activity

Directory of Open Access Journals (Sweden)

Pasquale Montemurro

2011-02-01

Full Text Available Research about phytotoxic activity of natural compounds could lead both to find new herbicidal active ingredients and to plan environmental friendly weed control strategies. Particularly, living organisms could be a source of compounds that are impossible, for their complexity, to synthesize artificially. More over, they could have alternative sites of action respect to the known chemical herbicides and, due to their origin, they should be more environmental safe. Many living organism, such as bacteria, fungi, insects, lichens and plants, are able to produce bioactive compounds. They generally are secondary metabolites or simply waste molecules. In this paper we make a review about these compounds, highlighting potential and constraints.

The importance of hydration thermodynamics in fragment-to-lead optimization.

Science.gov (United States)

Ichihara, Osamu; Shimada, Yuzo; Yoshidome, Daisuke

2014-12-01

Using a computational approach to assess changes in solvation thermodynamics upon ligand binding, we investigated the effects of water molecules on the binding energetics of over 20 fragment hits and their corresponding optimized lead compounds. Binding activity and X-ray crystallographic data of published fragment-to-lead optimization studies from various therapeutically relevant targets were studied. The analysis reveals a distinct difference between the thermodynamic profile of water molecules displaced by fragment hits and those displaced by the corresponding optimized lead compounds. Specifically, fragment hits tend to displace water molecules with notably unfavorable excess entropies-configurationally constrained water molecules-relative to those displaced by the newly added moieties of the lead compound during the course of fragment-to-lead optimization. Herein we describe the details of this analysis with the goal of providing practical guidelines for exploiting thermodynamic signatures of binding site water molecules in the context of fragment-to-lead optimization. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Next-generation sequencing identifies a novel compound heterozygous mutation in MYO7A in a Chinese patient with Usher Syndrome 1B.

Science.gov (United States)

Wei, Xiaoming; Sun, Yan; Xie, Jiansheng; Shi, Quan; Qu, Ning; Yang, Guanghui; Cai, Jun; Yang, Yi; Liang, Yu; Wang, Wei; Yi, Xin

2012-11-20

Targeted enrichment and next-generation sequencing (NGS) have been employed for detection of genetic diseases. The purpose of this study was to validate the accuracy and sensitivity of our method for comprehensive mutation detection of hereditary hearing loss, and identify inherited mutations involved in human deafness accurately and economically. To make genetic diagnosis of hereditary hearing loss simple and timesaving, we designed a 0.60 MB array-based chip containing 69 nuclear genes and mitochondrial genome responsible for human deafness and conducted NGS toward ten patients with five known mutations and a Chinese family with hearing loss (never genetically investigated). Ten patients with five known mutations were sequenced using next-generation sequencing to validate the sensitivity of the method. We identified four known mutations in two nuclear deafness causing genes (GJB2 and SLC26A4), one in mitochondrial DNA. We then performed this method to analyze the variants in a Chinese family with hearing loss and identified compound heterozygosity for two novel mutations in gene MYO7A. The compound heterozygosity identified in gene MYO7A causes Usher Syndrome 1B with severe phenotypes. The results support that the combination of enrichment of targeted genes and next-generation sequencing is a valuable molecular diagnostic tool for hereditary deafness and suitable for clinical application. Copyright © 2012 Elsevier B.V. All rights reserved.

In-silico analysis of heat shock protein 47 for identifying the novel therapeutic agents in the management of oral submucous fibrosis

Directory of Open Access Journals (Sweden)

Jayasankar P Pillai

2014-01-01

Conclusion: HSP47 can be a potential candidate to target, in order to control the production of abundance collagen in OSF. Hence, the binding sites of HSP47 with collagen are identified and some natural compounds with a potential to bind with these binding receptors are also recognized. These natural compounds might act as anti-HSP47 lead molecules in designing novel therapeutic agents for OSF, which are so far unavailable.

Leaded gasoline - an environmental problem

International Nuclear Information System (INIS)

Petrushevska, Ljubica

2001-01-01

In the European countries it is a clear trend towards the increasing consumption of unleaded gasolines. Driving force of this trend is, on the one hand the high toxicity of lead compounds and on the other, the necessity of purification of exhaust gases by catalytic converters, for which the lead represent a catalyst poison. In Macedonia, the limit lead content in the leaded gasolines is relatively high (0,6 g/l), as well as the consumption of the leaded gasolines. Rapid and complete transition to unleaded gasolines can be realized by the concept of step by step reduction of lead in our gasolines. (Original)

NATURAL POLYACETYLENE COMPOUNDS

Directory of Open Access Journals (Sweden)

A. M. Nasukhova

2014-01-01

Full Text Available In article the review of the initial stage of researches of natural polyacetylene compounds is resulted. The high reactionary ability leading to fast oxidation and degradation of these compounds, especially at influence of Uf-light, oxygen of air, pH and other factors, has caused the serious difficulties connected with an establishment of structure and studying of their physical and chemical properties. Therefore the greatest quantity of works of this stage is connected with studying of essential oils of plants from families Apiaceae, Araliaceae, Asteraceae, Campanulaceae, Olacaceae, Pittosporaceae and Santalaceae where have been found out, basically, diacetylene compounds. About development of physical and chemical methods of the analysis of possibility of similar researches have considerably extended. More than 2000 polyacetylenes are known today, from them more than 1100 are found out in plants fam. Asteraceae. Revolution in the field of molecular biology has allowed to study processes of biosynthesis of these compounds intensively.

46 CFR 153.1025 - Motor fuel antiknock compounds.

Science.gov (United States)

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Motor fuel antiknock compounds. 153.1025 Section 153... Cargo Procedures § 153.1025 Motor fuel antiknock compounds. (a) No person may load or carry any other cargo in a containment system approved for motor fuel antiknock compounds containing lead alkyls except...

Di-hadron correlations with identified leading hadrons in 200 GeV Au + Au and d + Au collisions at STAR

Science.gov (United States)

Adamczyk, L.; Adkins, J. K.; Agakishiev, G.; Aggarwal, M. M.; Ahammed, Z.; Alekseev, I.; Aparin, A.; Arkhipkin, D.; Aschenauer, E. C.; Averichev, G. S.; Bai, X.; Bairathi, V.; Banerjee, A.; Bellwied, R.; Bhasin, A.; Bhati, A. K.; Bhattarai, P.; Bielcik, J.; Bielcikova, J.; Bland, L. C.; Bordyuzhin, I. G.; Bouchet, J.; Brandenburg, D.; Brandin, A. V.; Bunzarov, I.; Butterworth, J.; Caines, H.; Calderón de la Barca Sánchez, M.; Campbell, J. M.; Cebra, D.; Cervantes, M. C.; Chakaberia, I.; Chaloupka, P.; Chang, Z.; Chattopadhyay, S.; Chen, X.; Chen, J. H.; Cheng, J.; Cherney, M.; Christie, W.; Contin, G.; Crawford, H. J.; Das, S.; De Silva, L. C.; Debbe, R. R.; Dedovich, T. G.; Deng, J.; Derevschikov, A. A.; di Ruzza, B.; Didenko, L.; Dilks, C.; Dong, X.; Drachenberg, J. L.; Draper, J. E.; Du, C. M.; Dunkelberger, L. E.; Dunlop, J. C.; Efimov, L. G.; Engelage, J.; Eppley, G.; Esha, R.; Evdokimov, O.; Eyser, O.; Fatemi, R.; Fazio, S.; Federic, P.; Fedorisin, J.; Feng, Z.; Filip, P.; Fisyak, Y.; Flores, C. E.; Fulek, L.; Gagliardi, C. A.; Garand, D.; Geurts, F.; Gibson, A.; Girard, M.; Greiner, L.; Grosnick, D.; Gunarathne, D. S.; Guo, Y.; Gupta, S.; Gupta, A.; Guryn, W.; Hamad, A.; Hamed, A.; Haque, R.; Harris, J. W.; He, L.; Heppelmann, S.; Heppelmann, S.; Hirsch, A.; Hoffmann, G. W.; Hofman, D. J.; Horvat, S.; Huang, T.; Huang, B.; Huang, H. Z.; Huang, X.; Huck, P.; Humanic, T. J.; Igo, G.; Jacobs, W. W.; Jang, H.; Jia, J.; Jiang, K.; Judd, E. G.; Kabana, S.; Kalinkin, D.; Kang, K.; Kauder, K.; Ke, H. W.; Keane, D.; Kechechyan, A.; Khan, Z. H.; Kikoła, D. P.; Kisiel, A.; Kochenda, L.; Koetke, D. D.; Kosarzewski, L. K.; Kraishan, A. F.; Kravtsov, P.; Krueger, K.; Kumar, L.; Lamont, M. A. C.; Landgraf, J. M.; Landry, K. D.; Lauret, J.; Lebedev, A.; Lednicky, R.; Lee, J. H.; Li, X.; Li, W.; Li, Z. M.; Li, Y.; Li, C.; Li, X.; Lisa, M. A.; Liu, F.; Ljubicic, T.; Llope, W. J.; Lomnitz, M.; Longacre, R. S.; Luo, X.; Ma, G. L.; Ma, Y. G.; Ma, R.; Ma, L.; Magdy, N.; Majka, R.; Manion, A.; Margetis, S.; Markert, C.; Masui, H.; Matis, H. S.; McDonald, D.; Meehan, K.; Mei, J. C.; Minaev, N. G.; Mioduszewski, S.; Mishra, D.; Mohanty, B.; Mondal, M. M.; Morozov, D. A.; Mustafa, M. K.; Nandi, B. K.; Nasim, Md.; Nayak, T. K.; Nigmatkulov, G.; Niida, T.; Nogach, L. V.; Noh, S. Y.; Novak, J.; Nurushev, S. B.; Odyniec, G.; Ogawa, A.; Oh, K.; Okorokov, V.; Olvitt, D.; Page, B. S.; Pak, R.; Pan, Y. X.; Pandit, Y.; Panebratsev, Y.; Pawlik, B.; Pei, H.; Perkins, C.; Peterson, A.; Pile, P.; Pluta, J.; Poniatowska, K.; Porter, J.; Posik, M.; Poskanzer, A. M.; Pruthi, N. K.; Putschke, J.; Qiu, H.; Quintero, A.; Ramachandran, S.; Raniwala, R.; Raniwala, S.; Ray, R. L.; Ritter, H. G.; Roberts, J. B.; Rogachevskiy, O. V.; Romero, J. L.; Roy, A.; Ruan, L.; Rusnak, J.; Rusnakova, O.; Sahoo, N. R.; Sahu, P. K.; Sakrejda, I.; Salur, S.; Sandweiss, J.; Sarkar, A.; Schambach, J.; Scharenberg, R. P.; Schmah, A. M.; Schmidke, W. B.; Schmitz, N.; Seger, J.; Seyboth, P.; Shah, N.; Shahaliev, E.; Shanmuganathan, P. V.; Shao, M.; Sharma, B.; Sharma, M. K.; Shen, W. Q.; Shi, S. S.; Shou, Q. Y.; Sichtermann, E. P.; Sikora, R.; Simko, M.; Singha, S.; Skoby, M. J.; Smirnov, N.; Smirnov, D.; Song, L.; Sorensen, P.; Spinka, H. M.; Srivastava, B.; Stanislaus, T. D. S.; Stepanov, M.; Strikhanov, M.; Stringfellow, B.; Sumbera, M.; Summa, B.; Sun, Y.; Sun, Z.; Sun, X. M.; Sun, X.; Surrow, B.; Svirida, D. N.; Szelezniak, M. A.; Tang, A. H.; Tang, Z.; Tarnowsky, T.; Tawfik, A.; Thomas, J. H.; Timmins, A. R.; Tlusty, D.; Todoroki, T.; Tokarev, M.; Trentalange, S.; Tribble, R. E.; Tribedy, P.; Tripathy, S. K.; Tsai, O. D.; Ullrich, T.; Underwood, D. G.; Upsal, I.; Van Buren, G.; van Nieuwenhuizen, G.; Vandenbroucke, M.; Varma, R.; Vasiliev, A. N.; Vertesi, R.; Videbæk, F.; Viyogi, Y. P.; Vokal, S.; Voloshin, S. A.; Vossen, A.; Wang, J. S.; Wang, F.; Wang, H.; Wang, G.; Wang, Y.; Wang, Y.; Webb, G.; Webb, J. C.; Wen, L.; Westfall, G. D.; Wieman, H.; Wissink, S. W.; Witt, R.; Wu, Y. F.; Wu; Xiao, Z. G.; Xie, W.; Xin, K.; Xu, H.; Xu, Z.; Xu, Q. H.; Xu, Y. F.; Xu, N.; Yang, S.; Yang, Y.; Yang, Q.; Yang, Y.; Yang, C.; Yang, Y.; Ye, Z.; Ye, Z.; Yepes, P.; Yi, L.; Yip, K.; Yoo, I.-K.; Yu, N.; Zbroszczyk, H.; Zha, W.; Zhang, Y.; Zhang, Z.; Zhang, J. B.; Zhang, J.; Zhang, X. P.; Zhang, S.; Zhang, J.; Zhao, J.; Zhong, C.; Zhou, L.; Zhu, X.; Zoulkarneeva, Y.

2015-12-01

The STAR Collaboration presents for the first time two-dimensional di-hadron correlations with identified leading hadrons in 200 GeV central Au + Au and minimum-bias d + Au collisions to explore hadronization mechanisms in the quark gluon plasma. The enhancement of the jet-like yield for leading pions in Au + Au data with respect to the d + Au reference and the absence of such an enhancement for leading non-pions (protons and kaons) are discussed within the context of a quark recombination scenario. The correlated yield at large angles, specifically in the ridge region, is found to be significantly higher for leading non-pions than pions. The consistencies of the constituent quark scaling, azimuthal harmonic model and a mini-jet modification model description of the data are tested, providing further constraints on hadronization.

Extraction, Isolation And Characterization Of Bioactive Compounds ...

African Journals Online (AJOL)

Natural products from medicinal plants, either as pure compounds or as standardized extracts, provide unlimited opportunities for new drug leads because of the ... The analysis of bioactive compounds present in the plant extracts involving the applications of common phytochemical screening assays, chromatographic ...

Development of fluorescence imaging-based assay for screening cardioprotective compounds from medicinal plants.

Science.gov (United States)

Wang, Yi; Zhao, Xiaoping; Gao, Xiumei; Nie, Xiaojing; Yang, Yingxin; Fan, Xiaohui

2011-09-19

Medicinal plants have been widely recognized as a renewable resource for the discovery of novel leads and drug. In this study, an approach for screening and identification compounds with cardioprotective activity from medicinal plant extracts by cellular-fluorescence imaging technique was developed. It is a cell-based assay for measuring mitochondrial membrane potential changes in H9c2 cardiac muscle cells exposed to H(2)O(2) by using a fluorescence automatic microscopy screening platform. Rhodamine 123 was used as the fluorescent dye to indicate the change of mitochondrial membrane potential. The sensitivity and linear range of the proposed approach were evaluated and validated using vitamin C, an antioxidative compound. The method was applied to screen active components with potent cardioprotective effects from a traditional Chinese formula. The potential cardioprotective components were identified by liquid chromatography coupled with mass spectrometry (LC/MS). Moreover, the utility of the proposed approach was further validated by three compounds (salvianolic acid B, protocatechuic aldehyde, and tanshinone II A) identified from the formula which showed cardioprotective effects in a dose-dependent manner. These applications suggested that the proposed rapid and sensitive screening approach offers an efficient way to discover active components or compounds from medicinal plants. Copyright © 2011 Elsevier B.V. All rights reserved.

Carcinogenic compounds in alcoholic beverages: an update.

Science.gov (United States)

Pflaum, Tabea; Hausler, Thomas; Baumung, Claudia; Ackermann, Svenja; Kuballa, Thomas; Rehm, Jürgen; Lachenmeier, Dirk W

2016-10-01

The consumption of alcoholic beverages has been classified as carcinogenic to humans by the International Agency for Research on Cancer (IARC) since 1988. More recently, in 2010, ethanol as the major constituent of alcoholic beverages and its metabolite acetaldehyde were also classified as carcinogenic to humans. Alcoholic beverages as multi-component mixtures may additionally contain further known or suspected human carcinogens as constituent or contaminant. This review will discuss the occurrence and toxicology of eighteen carcinogenic compounds (acetaldehyde, acrylamide, aflatoxins, arsenic, benzene, cadmium, ethanol, ethyl carbamate, formaldehyde, furan, glyphosate, lead, 3-MCPD, 4-methylimidazole, N-nitrosodimethylamine, pulegone, ochratoxin A, safrole) occurring in alcoholic beverages as identified based on monograph reviews by the IARC. For most of the compounds of alcoholic beverages, quantitative risk assessment provided evidence for only a very low risk (such as margins of exposure above 10,000). The highest risk was found for ethanol, which may reach exposures in ranges known to increase the cancer risk even at moderate drinking (margin of exposure around 1). Other constituents that could pose a risk to the drinker were inorganic lead, arsenic, acetaldehyde, cadmium and ethyl carbamate, for most of which mitigation by good manufacturing practices is possible. Nevertheless, due to the major effect of ethanol, the cancer burden due to alcohol consumption can only be reduced by reducing alcohol consumption in general or by lowering the alcoholic strength of beverages.

Calorimetric investigations of UPb{sub 3} compound

Energy Technology Data Exchange (ETDEWEB)

Agarwal, Renu, E-mail: arenu@barc.gov.in; Samui, Pradeep; Mukerjee, S.K.

2016-08-10

Highlights: • First time reporting of enthalpy increment and heat capacity data of UPb{sub 3} compound. • First time reporting of high temperature calorimetric determination of enthalpy of formation of UPb{sub 3} compound. • Miedema model was used to calculate enthalpies of formation of UPb{sub 3} and UPb. • Thermodynamic table of the compound UPb{sub 3} was generated. - Abstract: Interaction of uranium based metallic fuels and lead coolant can lead to formation of intermetallic compounds of U-Pb system. To understand U-Pb interactions, it is important to know thermodynamic properties of intermetallic compounds present in this system, UPb{sub 3} and UPb. In the present work, enthalpy increment, heat capacity and enthalpy of formation of UPb{sub 3} intermetallic compound were determined. The enthalpy increment was determined by high temperature Calvet calorimeter and heat capacity was determined using DSC. The heat capacity data was used to calculate thermodynamic parameters of the compound as a function of temperature. The enthalpy of formation at 843 K was determined using successive precipitation method, by direct reaction calorimetry. The enthalpy of formation at 843 K, from Pb(l) and U(l), was −28.9 kJ at-mol{sup −1} and after adjusting enthalpy increments of pure elements and compound, the enthalpy of formation of the compound at 298 K, from Pb(s) and U(α) was found to be −20.0 kJ at-mol{sup −1}.

A survey of synthetic and natural phytotoxic compounds and phytoalexins as potential antimalarial compounds.

Science.gov (United States)

Bajsa, Joanna; Singh, Kshipra; Nanayakkara, Dhammika; Duke, Stephen Oscar; Rimando, Agnes Mamaril; Evidente, Antonio; Tekwani, Babu Lal

2007-09-01

The apicomplexan parasites pathogens such as Plasmodium spp. possess an apicoplast, a plastid organelle similar to those of plants. The apicoplast has some essential plant-like metabolic pathways and processes, making these parasites susceptible to inhibitors of these functions. The main objective of this paper is to determine if phytotoxins with plastid target sites are more likely to be good antiplasmodial compounds than are those with other modes of action. The antiplasmodial activities of some compounds with established phytotoxic action were determined in vitro on a chloroquine (CQ) sensitive (D6, Sierra Leone) strain of Plasmodium falciparum. In this study, we provide in vitro activities of almost 50 such compounds, as well as a few phytoalexins against P. falciparum. Endothall, anisomycin, and cerulenin had sufficient antiplasmodial action to be considered as new lead antimalarial structures. Some derivatives of fusicoccin possessed markedly improved antiplasmodial action than the parent compound. Our results suggest that phytotoxins with plastid targets may not necessarily be better antiplasmodials than those that act at other molecular sites. The herbicides, phytotoxins and the phytoalexins reported here with significant antiplasmodial activity may be useful probes for identification of new antimalarial drug targets and may also be used as new lead structures for new antiplasmodial drug discovery.

Evaluation for leaded and unleaded Gasoline as Hazardous Waste

International Nuclear Information System (INIS)

Abou El Naga, H.H.

1999-01-01

With the phase out of alkyl lead compounds as necessary additives for gasoline in order to raise its octane number , the alternative is to reformulate gasoline to have nearly same octane number but with other chemical structures. Such reformulated gasoline (RFG) is found to contain higher aromatics, benzene, iso paraffins, in comparison to leaded gasoline. Additionally, this reformulated gasoline can also contain oxygenated additives. Accordingly, this paper is aiming at evaluation of emitted hazardous chemical compounds from car engines at fuel combustion. Role of chemical structures for reformulated gasoline in emission of volatile organic compounds (VOC) and poisoning materials are considered

Characterisation of selected volatile organic compounds in ...

African Journals Online (AJOL)

GCMS), was used to identify volatile compounds at three different temperatures. Fifty volatile compounds, inclusive of 14 acids, 14 alcohols, and 22 esters were identified and quantified in the two brands of indigenous banana beer samples. Only 12 ...

Chemical form of selenium differentially influences DNA repair pathways following exposure to lead nitrate.

Science.gov (United States)

McKelvey, Shauna M; Horgan, Karina A; Murphy, Richard A

2015-01-01

Lead, an environmental toxin is known to induce a broad range of physiological and biochemical dysfunctions in humans through a number of mechanisms including the deactivation of antioxidants thus leading to generation of reactive oxygen species (ROS) and subsequent DNA damage. Selenium on the other hand has been proven to play an important role in the protection of cells from free radical damage and oxidative stress, though its effects are thought to be form and dose dependent. As the liver is the primary organ required for metabolite detoxification, HepG2 cells were chosen to assess the protective effects of various selenium compounds following exposure to the genotoxic agent lead nitrate. Initially DNA damage was quantified using a comet assay, gene expression patterns associated with DNA damage and signalling were also examined using PCR arrays and the biological pathways which were most significantly affected by selenium were identified. Interestingly, the organic type selenium compounds (selenium yeast and selenomethionine) conferred protection against lead induced DNA damage in HepG2 cells; this is evident by reduction in the quantity of DNA present in the comet tail of cells cultured in their presence with lead. This trend also followed through the gene expression changes noted in DNA damage pathways analysed. These results were in contrast with those of inorganic sodium selenite which promoted lead induced DNA damage evident in both the comet assay results and the gene expression analysis. Over all this study provided valuable insights into the effects which various selenium compounds had on the DNA damage and signalling pathway indicating the potential for using organic forms of selenium such as selenium enriched yeast to protect against DNA damaging agents. Copyright © 2014 Elsevier GmbH. All rights reserved.

A Panel of Cytochrome P450 BM3 Variants To Produce Drug Metabolites and Diversify Lead Compounds

Science.gov (United States)

Sawayama, Andrew M.; Chen, Michael M. Y.; Kulanthaivel, Palaniappan; Kuo, Ming-Shang; Hemmerle, Horst; Arnold, Frances H.

2011-01-01

Here we demonstrate that a small panel of variants of cytochrome P450 BM3 from Bacillus megaterium covers the breadth of reactivity of human P450s by producing 12 of 13 mammalian metabolites for two marketed drugs, verapamil and astemizole, and one research compound. The most active enzymes support preparation of individual metabolites for preclinical bioactivity and toxicology evaluations. Underscoring their potential utility in drug lead diversification, engineered P450 BM3 variants also produce novel metabolites by catalyzing reactions at carbon centers beyond those targeted by animal and human P450s. Production of a specific metabolite can be improved by directed evolution of the enzyme catalyst. Some variants are more active on the more hydrophobic parent drug than on its metabolites, which limits production of multiply-hydroxylated species, a preference that appears to depend on the evolutionary history of the P450 variant. PMID:19774562

Di-hadron correlations with identified leading hadrons in 200 GeV Au+Au and d+Au collisions at STAR

Directory of Open Access Journals (Sweden)

L. Adamczyk

2015-12-01

Full Text Available The STAR Collaboration presents for the first time two-dimensional di-hadron correlations with identified leading hadrons in 200 GeV central Au+Au and minimum-bias d+Au collisions to explore hadronization mechanisms in the quark gluon plasma. The enhancement of the jet-like yield for leading pions in Au+Au data with respect to the d+Au reference and the absence of such an enhancement for leading non-pions (protons and kaons are discussed within the context of a quark recombination scenario. The correlated yield at large angles, specifically in the ridge region, is found to be significantly higher for leading non-pions than pions. The consistencies of the constituent quark scaling, azimuthal harmonic model and a mini-jet modification model description of the data are tested, providing further constraints on hadronization.

Di-hadron correlations with identified leading hadrons in 200 GeV Au + Au and d + Au collisions at STAR

Energy Technology Data Exchange (ETDEWEB)

Adamczyk, L; Adkins, JK; Agakishiev, G; Aggarwal, MM; Ahammed, Z; Alekseev, I; Aparin, A; Arkhipkin, D; Aschenauer, EC; Averichev, GS; Bai, X; Bairathi, V; Banerjee, A; Bellwied, R; Bhasin, A; Bhati, AK; Bhattarai, P; Bielcik, J; Bielcikova, J; Bland, LC; Bordyuzhin, IG; Bouchet, J; Brandenburg, D; Brandin, AV; Bunzarov, I; Butterworth, J; Caines, H; Calderón de la Barca Sánchez, M; Campbell, JM; Cebra, D; Cervantes, MC; Chakaberia, I; Chaloupka, P; Chang, Z; Chattopadhyay, S; Chen, X; Chen, JH; Cheng, J; Cherney, M; Christie, W; Contin, G; Crawford, HJ; Das, S; De Silva, LC; Debbe, RR; Dedovich, TG; Deng, J; Derevschikov, AA; di Ruzza, B; Didenko, L; Dilks, C; Dong, X; Drachenberg, JL; Draper, JE; Du, CM; Dunkelberger, LE; Dunlop, JC; Efimov, LG; Engelage, J; Eppley, G; Esha, R; Evdokimov, O; Eyser, O; Fatemi, R; Fazio, S; Federic, P; Fedorisin, J; Feng, Z; Filip, P; Fisyak, Y; Flores, CE; Fulek, L; Gagliardi, CA; Garand, D; Geurts, F; Gibson, A; Girard, M; Greiner, L; Grosnick, D; Gunarathne, DS; Guo, Y; Gupta, S; Gupta, A; Guryn, W; Hamad, A; Hamed, A; Haque, R; Harris, JW; He, L; Heppelmann, S; Heppelmann, S; Hirsch, A; Hoffmann, GW; Hofman, DJ; Horvat, S; Huang, T; Huang, B; Huang, HZ; Huang, X; Huck, P

2015-10-23

The STAR Collaboration presents for the first time two-dimensional di-hadron correlations with identified leading hadrons in 200 GeV central Au + Au and minimum-bias d + Au collisions to explore hadronization mechanisms in the quark gluon plasma. The enhancement of the jet-like yield for leading pions in Au + Au data with respect to the d + Au reference and the absence of such an enhancement for leading non-pions (protons and kaons) are discussed within the context of a quark recombination scenario. The correlated yield at large angles, specifically in the ridge region, is found to be significantly higher for leading non-pions than pions. The consistencies of the constituent quark scaling, azimuthal harmonic model and a mini-jet modification model description of the data are tested, providing further constraints on hadronization.

Pharmacokinetic/Toxicity Properties of the New Anti-Staphylococcal Lead Compound SK-03-92

Directory of Open Access Journals (Sweden)

William R. Schwan

2015-11-01

Full Text Available Because of the potential of a new anti-staphylococcal lead compound SK-03-92 as a topical antibiotic, a patch, or an orally active drug, we sought to determine its safety profile and oral bioavailability. SK-03-92 had a high IC50 (125 μg/mL in vitro against several mammalian cell lines, and mice injected intraperiteonally at the highest dose did not exhibit gross toxicity (e.g., altered gait, ungroomed, significant weight loss. Single dose (100 μg/g pharmacokinetic (PK analysis with formulated SK-03-92 showed that peak plasma concentration (1.64 μg/mL was achieved at 20–30 min. Oral relative bioavailability was 8%, and the drug half-life was 20–30 min, demonstrating that SK-03-92 is likely not a candidate for oral delivery. Five-day and two-week PK analyses demonstrated that SK-03-92 plasma levels were low. Multi-dose analysis showed no gross adverse effects to the mice and a SK-03-92 peak plasma concentration of 2.12 μg/mL with the presence of significant concentrations of breakdown products 15 min after dosing. SK-03-92 appeared to be very safe based on tissue culture and mouse gross toxicity determinations, but the peak plasma concentration suggests that a pro-drug of SK-03-92 or preparation of analogs of SK-03-92 with greater bioavailability and longer half-lives are warranted.

Total bremsstrahlung spectra of thick lead compounds produced by {sup 90}Sr beta emitter in photon energy region of 10–100 keV

Energy Technology Data Exchange (ETDEWEB)

Sharma, Suhansar Jit [Department of Physics, B.B.S.B Polytechnic, Fatehgarh Sahib, Punjab (India); Singh, Tajinder, E-mail: tajindersingh2k9@gmail.com [Department of Physics, Mata Gujri College, Fatehgarh Sahib, Punjab (India); Singh, Doordarshi [Department of Mechanical Engineering, B.B.S.B Engineering College, Fatehgarh Sahib, Punjab (India); Singh, Amrit [Department of Physics, Baba Ajay Singh Khalsa College, Gurdas Nangal, Gurdaspur, Punjab (India); Dhaliwal, A.S. [Department of Physics, Sant Longowal Institute of Engineering & Technology, Longowal (Sangrur), Punjab (India)

2017-06-15

Highlights: • Total bremsstrahlung spectra in thick targets of Pb compounds by {sup 90}Sr in energy range 10–100 keV. • Experimental results show better agreement with the model which includes PB in SA up to 30 keV. • At higher photon energy region 30–100 keV the model which describes OB is more accurate. • Experimental results show positive deviations from the entire models at higher energy end spectrum. - Abstract: The total bremsstrahlung spectra in the thick targets of lead acetate trihydrate (Pb(CH{sub 3}COO){sub 2}·3H{sub 2}O), lead nitrate Pb(NO{sub 3}){sub 2} and lead chloride (PbCl{sub 2}) produced by {sup 90}Sr beta particles have been investigated in the photon energy region of 10–100 keV. The experimental bremsstrahlung spectra have been compared with the theoretical models Elwert corrected (non relativistic) Bethe Heitler theory, modified Elwert factor (relativistic) Bethe Heitler theory for ordinary bremsstrahlung and modified Elwert factor (relativistic) Bethe Heitler theory which includes polarization bremsstrahlung in the stripped atom approximation. The experimental results show better agreement with theoretical model that includes polarization bremsstrahlung in stripped approximation in the photon energy region below 30 keV. However, at higher photon energy region 30–100 keV, the theoretical model which describes ordinary bremsstrahlung is more accurate to describe the experimental bremsstrahlung spectra. The experimental results show positive deviations from the entire theoretical models at higher energy end of the spectrum. The results indicate that polarization bremsstrahlung plays important role in the formation of total bremsstrahlung spectra in lead compounds produced by continuous beta particles at low photon energy region of 10–30 keV.

46 CFR 151.50-6 - Motor fuel antiknock compounds.

Science.gov (United States)

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Motor fuel antiknock compounds. 151.50-6 Section 151.50... BARGES CARRYING BULK LIQUID HAZARDOUS MATERIAL CARGOES Special Requirements § 151.50-6 Motor fuel antiknock compounds. When transporting motor fuel antiknock compounds containing tetraethyl lead and...

Punica granatum peel extracts: HPLC fractionation and LC MS analysis to quest compounds having activity against multidrug resistant bacteria.

Science.gov (United States)

Khan, Ilyas; Rahman, Hazir; Abd El-Salam, Nasser M; Tawab, Abdul; Hussain, Anwar; Khan, Taj Ali; Khan, Usman Ali; Qasim, Muhammad; Adnan, Muhammad; Azizullah, Azizullah; Murad, Waheed; Jalal, Abdullah; Muhammad, Noor; Ullah, Riaz

2017-05-03

Medicinal plants are rich source of traditional herbal medicine around the globe. Most of the plant's therapeutic properties are due to the presence of secondary bioactive compounds. The present study analyzed the High Pressure Liquid Chromatography (HPLC) fractions of Puncia granatum (peel) extracts (aqueous, chloroform, ethanol and hexane) against multidrug resistant bacterial pathogens (Acinetobacter baumannii, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus). All the fractions having antibacterial activity was processed for bioactive compounds identification using LC MS/MS analysis. Among total HPLC fractions (n = 30), 4 HPLC fractions of P. granatum (peel) showed potential activity against MDR pathogens. Fraction 1 (F1) and fraction 4 (F4) collected from aqueous extract showed maximum activity against P. aeruginosa. Fraction 2 (F2) of hexane showed antibacterial activity against three pathogens, while ethanol F4 exhibited antibacterial activity against A. baumannii. The active fractions were processed for LC MS/MS analysis to identify bioactive compounds. Valoneic acid dilactone (aqueous F1 and F4), Hexoside (ethanol F4) and Coumaric acid (hexane F2) were identified as bioactive compounds in HPLC fractions. Puncia granatum peel extracts HPLC fractions exhibited potential inhibitory activity against MDR bacterial human pathogens. Several bioactive compounds were identified from the HPLC fractions. Further characterization of these compounds may be helpful to conclude it as therapeutic lead molecules against MDR pathogens.

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

Science.gov (United States)

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.

Directory of Open Access Journals (Sweden)

J K Mansoor

Full Text Available 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.

Identification of novel candidate compounds targeting TrkB to induce apoptosis in neuroblastoma

International Nuclear Information System (INIS)

Nakamura, Yohko; Suganami, Akiko; Fukuda, Mayu; Hasan, Md Kamrul; Yokochi, Tomoki; Takatori, Atsushi; Satoh, Shunpei; Hoshino, Tyuji; Tamura, Yutaka; Nakagawara, Akira

2014-01-01

Neuroblastoma (NB) is one of the most frequent solid tumors in children and its prognosis is still poor. The neurotrophin receptor TrkB and its ligand brain-derived neurotrophic factor (BDNF) are expressed at high levels in high-risk NBs and are involved in defining the poor prognosis of the patients. However, the TrkB targeting therapy has never been realized in the clinic. We performed an in silico screening procedure utilizing an AutoDock/grid computing technology in order to identify novel small chemical compounds targeting the BDNF-binding domain of TrkB. For the first screening, a library of three million synthetic compounds was screened in silico and was ranked according to the Docking energy. The top-ranked 37 compounds were further functionally screened for cytotoxicity by using NB cell lines. We have finally identified seven compounds that kill NB cells with the IC 50 values of 0.07–4.6 μmol/L. The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay showed that these molecules induce apoptosis accompanied by p53 activation in NB cell lines. The candidate compounds and BDNF demonstrated an antagonistic effect on cell growth, invasion, and colony formation, possibly suggesting competition at the BDNF-binding site of TrkB. The candidate compounds had tumor-suppressive activity in xenograft and in vivo toxicity tests (oral and intravenous administrations) using mice, and did not show any abnormal signs. Using in silico Docking screening we have found new candidate TrkB inhibitors against high-risk NBs, which could lead to new anti-cancer drugs

Two cases of acute lead poisoning due to occupational exposure to lead.

Science.gov (United States)

Ogawa, Masanori; Nakajima, Yoshiaki; Kubota, Ryuichi; Endo, Yoko

2008-04-01

We experienced two cases of acute lead poisoning due to occupational exposure to lead. The patients were engaged in stripping off antirust compounds including Pb from a bridge and re-painting it at the same work place. Both patients exhibited colic, arthralgia, and anemia. Blood lead levels were 73.1 microg/dl and 96.3 microg/dl. Intravenous CaEDTA chelation therapy was therefore performed. After chelation, blood lead levels decreased and symptoms gradually disappeared. Although the patients were working with protective equipment, the workplace was in the mountains and there was no water for washing. The patients were thus unable to washing their hands and faces. We assume that they swallowed lead dust left on their hands and faces when they removed their clothing, and believe that this poisoning occurred due to lack of knowledge sufficient for protection.

Urban airborne lead: X-ray absorption spectroscopy establishes soil as dominant source.

Science.gov (United States)

Pingitore, Nicholas E; Clague, Juan W; Amaya, Maria A; Maciejewska, Beata; Reynoso, Jesús J

2009-01-01

Despite the dramatic decrease in airborne lead over the past three decades, there are calls for regulatory limits on this potent pediatric neurotoxin lower even than the new (2008) US Environmental Protection Agency standard. To achieve further decreases in airborne lead, what sources would need to be decreased and what costs would ensue? Our aim was to identify and, if possible, quantify the major species (compounds) of lead in recent ambient airborne particulate matter collected in El Paso, TX, USA. We used synchrotron-based XAFS (x-ray absorption fine structure) to identify and quantify the major Pb species. XAFS provides molecular-level structural information about a specific element in a bulk sample. Pb-humate is the dominant form of lead in contemporary El Paso air. Pb-humate is a stable, sorbed complex produced exclusively in the humus fraction of Pb-contaminated soils; it also is the major lead species in El Paso soils. Thus such soil must be the dominant source, and its resuspension into the air, the transfer process, providing lead particles to the local air. Current industrial and commercial activity apparently is not a major source of airborne lead in El Paso, and presumably other locales that have eliminated such traditional sources as leaded gasoline. Instead, local contaminated soil, legacy of earlier anthropogenic Pb releases, serves as a long-term reservoir that gradually leaks particulate lead to the atmosphere. Given the difficulty and expense of large-scale soil remediation or removal, fugitive soil likely constrains a lower limit for airborne lead levels in many urban settings.

iPSC-Based Compound Screening and In Vitro Trials Identify a Synergistic Anti-amyloid β Combination for Alzheimer’s Disease

Directory of Open Access Journals (Sweden)

Takayuki Kondo

2017-11-01

Full Text Available In the process of drug development, in vitro studies do not always adequately predict human-specific drug responsiveness in clinical trials. Here, we applied the advantage of human iPSC-derived neurons, which offer human-specific drug responsiveness, to screen and evaluate therapeutic candidates for Alzheimer’s disease (AD. Using AD patient neurons with nearly 100% purity from iPSCs, we established a robust and reproducible assay for amyloid β peptide (Aβ, a pathogenic molecule in AD, and screened a pharmaceutical compound library. We acquired 27 Aβ-lowering screen hits, prioritized hits by chemical structure-based clustering, and selected 6 leading compounds. Next, to maximize the anti-Aβ effect, we selected a synergistic combination of bromocriptine, cromolyn, and topiramate as an anti-Aβ cocktail. Finally, using neurons from familial and sporadic AD patients, we found that the cocktail showed a significant and potent anti-Aβ effect on patient cells. This human iPSC-based platform promises to be useful for AD drug development.

Primary microcephaly caused by novel compound heterozygous mutations in ASPM.

Science.gov (United States)

Okamoto, Nobuhiko; Kohmoto, Tomohiro; Naruto, Takuya; Masuda, Kiyoshi; Imoto, Issei

2018-01-01

Autosomal recessive primary microcephaly (microcephaly primary hereditary, MCPH) is a genetically heterogeneous rare developmental disorder that is characterized by prenatal onset of abnormal brain growth, which leads to intellectual disability of variable severity. We report a 5-year-old male who presented with a severe form of primary microcephaly. Targeted panel sequencing revealed compound heterozygous truncating mutations of the abnormal spindle-like microcephaly-associated ( ASPM ) gene, which confirmed the MCPH5 diagnosis. A novel NM_018136.4: c.9742_9745del (p.Lys3248Serfs*13) deletion mutation was identified.

Yeast three-hybrid screen identifies TgBRADIN/GRA24 as a negative regulator of Toxoplasma gondii bradyzoite differentiation.

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Anahi V Odell

Full Text Available Differentiation of the protozoan parasite Toxoplasma gondii into its latent bradyzoite stage is a key event in the parasite's life cycle. Compound 2 is an imidazopyridine that was previously shown to inhibit the parasite lytic cycle, in part through inhibition of parasite cGMP-dependent protein kinase. We show here that Compound 2 can also enhance parasite differentiation, and we use yeast three-hybrid analysis to identify TgBRADIN/GRA24 as a parasite protein that interacts directly or indirectly with the compound. Disruption of the TgBRADIN/GRA24 gene leads to enhanced differentiation of the parasite, and the TgBRADIN/GRA24 knockout parasites show decreased susceptibility to the differentiation-enhancing effects of Compound 2. This study represents the first use of yeast three-hybrid analysis to study small-molecule mechanism of action in any pathogenic microorganism, and it identifies a previously unrecognized inhibitor of differentiation in T. gondii. A better understanding of the proteins and mechanisms regulating T. gondii differentiation will enable new approaches to preventing the establishment of chronic infection in this important human pathogen.

Xenobiotic organic compounds in wastewater

DEFF Research Database (Denmark)

Eriksson, Eva; Baun, Anders; Henze, Mogens

2002-01-01

hundred of XOCs, among them mainly originating from hygiene products: chlorophenols, detergents and phthalates. Several compounds not deriving from hygiene products were also identified e.g. flame-retardants and drugs. A environmental hazard identification showed that a large number of compounds with high...

Chemical-genetic profile analysis of five inhibitory compounds in yeast.

Science.gov (United States)

Alamgir, Md; Erukova, Veronika; Jessulat, Matthew; Azizi, Ali; Golshani, Ashkan

2010-08-06

Chemical-genetic profiling of inhibitory compounds can lead to identification of their modes of action. These profiles can help elucidate the complex interactions between small bioactive compounds and the cell machinery, and explain putative gene function(s). Colony size reduction was used to investigate the chemical-genetic profile of cycloheximide, 3-amino-1,2,4-triazole, paromomycin, streptomycin and neomycin in the yeast Saccharomyces cerevisiae. These compounds target the process of protein biosynthesis. More than 70,000 strains were analyzed from the array of gene deletion mutant yeast strains. As expected, the overall profiles of the tested compounds were similar, with deletions for genes involved in protein biosynthesis being the major category followed by metabolism. This implies that novel genes involved in protein biosynthesis could be identified from these profiles. Further investigations were carried out to assess the activity of three profiled genes in the process of protein biosynthesis using relative fitness of double mutants and other genetic assays. Chemical-genetic profiles provide insight into the molecular mechanism(s) of the examined compounds by elucidating their potential primary and secondary cellular target sites. Our follow-up investigations into the activity of three profiled genes in the process of protein biosynthesis provided further evidence concerning the usefulness of chemical-genetic analyses for annotating gene functions. We termed these genes TAE2, TAE3 and TAE4 for translation associated elements 2-4.

Biological analysis of endocrine disrupting compounds in Tunisian sewage treatment plants

International Nuclear Information System (INIS)

Minif, W.; Dagnino, S.; Pillon, A.; Escande, A.; Fenet, E.; Gomez, E.; Casellas, C.; Duchesne, M. J.; Cavailles, V.

2009-01-01

The endocrine disrupting compounds (EDCs) are frequently found in sewage treatment plant (STPs) works. Natural and synthetic hormones have been identified as the major contributors to the estrogenic activity in sewage. Dosing and identification of EDCs are certainly of great interest and can lead to the improvement of chemicals treatments. With reporter cell lines developed in the laboratory and allowing the detection of nuclear receptor activities, we characterized the endocrine disrupting profile of water, particulate matter and sludge from three Tunisian sewage, treatment plants (STPs). (Author)

Biological analysis of endocrine disrupting compounds in Tunisian sewage treatment plants

Energy Technology Data Exchange (ETDEWEB)

Minif, W.; Dagnino, S.; Pillon, A.; Escande, A.; Fenet, E.; Gomez, E.; Casellas, C.; Duchesne, M. J.; Cavailles, V.

2009-07-01

The endocrine disrupting compounds (EDCs) are frequently found in sewage treatment plant (STPs) works. Natural and synthetic hormones have been identified as the major contributors to the estrogenic activity in sewage. Dosing and identification of EDCs are certainly of great interest and can lead to the improvement of chemicals treatments. With reporter cell lines developed in the laboratory and allowing the detection of nuclear receptor activities, we characterized the endocrine disrupting profile of water, particulate matter and sludge from three Tunisian sewage, treatment plants (STPs). (Author)

Antibacterial Compounds from Red Seaweeds (Rhodophyta

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Noer Kasanah

2015-07-01

Full Text Available Seaweeds produce great variety of metabolites benefit for human. Red seaweeds (Rhodophyta are well known as producer of phycocolloids such agar, agarose, carragenan and great variety of secondary metabolites. This review discusses the red algal secondary metabolites with antibacterial activity. The chemical constituents of red algae are steroid, terpenoid, acetogenin and dominated by halogenated compounds mainly brominated compounds. Novel compounds with intriguing skeleton are also reported such as bromophycolides and neurymenolides. In summary, red seaweeds are potential sources for antibacterial agents and can serve as lead in synthesis of new natural medicines.

Toxic compounds in honey.

Science.gov (United States)

Islam, Md Nazmul; Khalil, Md Ibrahim; Islam, Md Asiful; Gan, Siew Hua

2014-07-01

There is a wealth of information about the nutritional and medicinal properties of honey. However, honey may contain compounds that may lead to toxicity. A compound not naturally present in honey, named 5-hydroxymethylfurfural (HMF), may be formed during the heating or preservation processes of honey. HMF has gained much interest, as it is commonly detected in honey samples, especially samples that have been stored for a long time. HMF is a compound that may be mutagenic, carcinogenic and cytotoxic. It has also been reported that honey can be contaminated with heavy metals such as lead, arsenic, mercury and cadmium. Honey produced from the nectar of Rhododendron ponticum contains alkaloids that can be poisonous to humans, while honey collected from Andromeda flowers contains grayanotoxins, which can cause paralysis of limbs in humans and eventually leads to death. In addition, Melicope ternata and Coriaria arborea from New Zealand produce toxic honey that can be fatal. There are reports that honey is not safe to be consumed when it is collected from Datura plants (from Mexico and Hungary), belladonna flowers and Hyoscamus niger plants (from Hungary), Serjania lethalis (from Brazil), Gelsemium sempervirens (from the American Southwest), Kalmia latifolia, Tripetalia paniculata and Ledum palustre. Although the symptoms of poisoning due to honey consumption may differ depending on the source of toxins, most common symptoms generally include dizziness, nausea, vomiting, convulsions, headache, palpitations or even death. It has been suggested that honey should not be considered a completely safe food. Copyright © 2013 John Wiley & Sons, Ltd.

Affixation and compounding in Hakka

OpenAIRE

Ungsitipoonporn, Siriopen

2014-01-01

This paper aims to present the internal structures of words in the Hakka language. Similar to other languages, affixation and compounding are outstanding in Hakka. In general, prefixes and suffixes are bound morphemes which do not occur independently, but in Hakka they sometimes appear as independent forms. Apart from single words, identifying compound words is of particular interest. Compound nouns can be made up of two or three words (characters) which ...

Implication of Caspase-3 as a Common Therapeutic Target for Multineurodegenerative Disorders and Its Inhibition Using Nonpeptidyl Natural Compounds

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Saif Khan

2015-01-01

Full Text Available Caspase-3 has been identified as a key mediator of neuronal apoptosis. The present study identifies caspase-3 as a common player involved in the regulation of multineurodegenerative disorders, namely, Alzheimer’s disease (AD, Parkinson’s disease (PD, Huntington’s disease (HD, and amyotrophic lateral sclerosis (ALS. The protein interaction network prepared using STRING database provides a strong evidence of caspase-3 interactions with the metabolic cascade of the said multineurodegenerative disorders, thus characterizing it as a potential therapeutic target for multiple neurodegenerative disorders. In silico molecular docking of selected nonpeptidyl natural compounds against caspase-3 exposed potent leads against this common therapeutic target. Rosmarinic acid and curcumin proved to be the most promising ligands (leads mimicking the inhibitory action of peptidyl inhibitors with the highest Gold fitness scores 57.38 and 53.51, respectively. These results were in close agreement with the fitness score predicted using X-score, a consensus based scoring function to calculate the binding affinity. Nonpeptidyl inhibitors of caspase-3 identified in the present study expeditiously mimic the inhibitory action of the previously identified peptidyl inhibitors. Since, nonpeptidyl inhibitors are preferred drug candidates, hence, discovery of natural compounds as nonpeptidyl inhibitors is a significant transition towards feasible drug development for neurodegenerative disorders.

A High-Throughput Cell-Based Screen Identified a 2-[(E)-2-Phenylvinyl]-8-Quinolinol Core Structure That Activates p53.

Science.gov (United States)

Bechill, John; Zhong, Rong; Zhang, Chen; Solomaha, Elena; Spiotto, Michael T

2016-01-01

p53 function is frequently inhibited in cancer either through mutations or by increased degradation via MDM2 and/or E6AP E3-ubiquitin ligases. Most agents that restore p53 expression act by binding MDM2 or E6AP to prevent p53 degradation. However, fewer compounds directly bind to and activate p53. Here, we identified compounds that shared a core structure that bound p53, caused nuclear localization of p53 and caused cell death. To identify these compounds, we developed a novel cell-based screen to redirect p53 degradation to the Skip-Cullin-F-box (SCF) ubiquitin ligase complex in cells expressing high levels of p53. In a multiplexed assay, we coupled p53 targeted degradation with Rb1 targeted degradation in order to identify compounds that prevented p53 degradation while not inhibiting degradation through the SCF complex or other proteolytic machinery. High-throughput screening identified several leads that shared a common 2-[(E)-2-phenylvinyl]-8-quinolinol core structure that stabilized p53. Surface plasmon resonance analysis indicated that these compounds bound p53 with a KD of 200 ± 52 nM. Furthermore, these compounds increased p53 nuclear localization and transcription of the p53 target genes PUMA, BAX, p21 and FAS in cancer cells. Although p53-null cells had a 2.5±0.5-fold greater viability compared to p53 wild type cells after treatment with core compounds, loss of p53 did not completely rescue cell viability suggesting that compounds may target both p53-dependent and p53-independent pathways to inhibit cell proliferation. Thus, we present a novel, cell-based high-throughput screen to identify a 2-[(E)-2-phenylvinyl]-8-quinolinol core structure that bound to p53 and increased p53 activity in cancer cells. These compounds may serve as anti-neoplastic agents in part by targeting p53 as well as other potential pathways.

Novel VEGFR-2 kinase inhibitor identified by the back-to-front approach

Science.gov (United States)

Sanphanya, Kingkan; Phowichit, Suwadee; Wattanapitayakul, Suvara K.; Fokin, Valery V.; Vajragupta, Opa

2013-01-01

Novel lead was developed as VEGFR-2 inhibitor by the back-to-front approach. Docking experiment guided that the 3-chloromethylphenylurea motif occupied the back pocket of the VEGFR-2 kinase. The attempt to enhance the binding affinity of 1 was made by expanding structure to access the front pocket using triazole as linker. A library of 1,4-(disubsituted)-1H-1,2,3-triazoles were screened in silico and one lead compound (VH02) was identified with enzymatic IC50 against VEGFR-2 of 0.56 μM. VH02 showed antiangiogenic effect by inhibiting the tube formation of HUVEC cells (EA.hy926) at 0.3 μM which was 13 times lower than its cytotoxic dose. The enzymatic and cellular activities suggested the potential of VH02 as a lead for further optimization. PMID:23562241

Identification of the sources of organic compounds that decalcify cement concrete and generate alcohols and ammonia gases

Energy Technology Data Exchange (ETDEWEB)

Tomoto, Takashi [Technical Research Institute, Obayashi Road Corporation, 4-640 Shimokiyoto, Kiyose, Tokyo, 204-0011 (Japan); Moriyoshi, Akihiro [Material Science Laboratory, Hokkaido University, 2-1-9-10 Kiyota, Kiyota-ku, Sapporo, 004-0842 (Japan); Sakai, Kiyoshi [Department of Environmental Health, Nagoya City Public Health Research Institute, 1-11 Hagiyama-cho, Mizuho-ku, Nagoya, 467-8615 (Japan); Shibata, Eiji [Department of Health and Psychosocial Medicine, Aichi Medical University School of Medicine, Nagakute-cho, Aichi, 480-1195 (Japan); Kamijima, Michihiro [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550 (Japan)

2009-09-15

This study identifies the emission sources of various types of airborne organic compounds, which deteriorate cement concrete by penetrating into the concrete together with moisture. The study used high-performance liquid chromatography and gas chromatograph mass spectrometry. The results show that the types of organic compounds contained in decalcified cement concrete were very similar to those found in the total suspended compounds in the air, and that the source of the emissions was particles of exhaust from diesel vehicles and radial tires used in summer. Such organic compounds include substances suspected of having endocrine disrupting properties. Hydrolysis occurs when these substances penetrate into highly alkaline cement concrete, and leads to deterioration of the cement concrete and the release of alcohols and ammonia gases which pollute indoor air and may be a cause of the sick building syndrome. (author)

Purification and characterization of antifungal compounds from Lactobacillus plantarum HD1 isolated from kimchi.

Science.gov (United States)

Ryu, Eun Hye; Yang, Eun Ju; Woo, Eun Rhan; Chang, Hae Choon

2014-08-01

Strain HD1 with antifungal activity was isolated from kimchi and identified as Lactobacillus plantarum. Antifungal compounds from Lb. plantarum HD1 were active against food- and feed-borne filamentous fungi and yeasts in a spot-on-the-lawn assay. Antifungal activity of Lb. plantarum HD1 was stronger against filamentous fungi than yeast. Antifungal compounds were purified using solid phase extraction (SPE) and recycling preparative-HPLC. Structures of the antifungal compounds were elucidated by electrospray ionization-mass spectrometry and nuclear magnetic resonance. Active compounds from Lb. plantarum HD1 were identified as 5-oxododecanoic acid (MW 214), 3-hydroxy decanoic acid (MW 188), and 3-hydroxy-5-dodecenoic acid (MW 214). To investigate the potential application of these antifungal compounds for reduction of fungal spoilage in foods, Korean draft rice wine was used as a food model. White film-forming yeasts were observed in control draft rice wine after 11 days of incubation. However, film-forming yeasts were not observed in draft rice wine treated with SPE-prepared culture supernatant of Lb. plantarum HD1 (equivalent to 2.5% addition of culture supernatant) until 27 days of incubation. The addition of antifungal compounds to Korean draft rice wine extended shelf-life up to 27 days at 10 °C without any sterilization process. Therefore, the antifungal activity of Lb. plantarum HD1 may lead to the development of powerful biopreservative systems capable of preventing food- and feed-borne fungal spoilage. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effects of a chronic lead intoxication on the pathophysiological changes in the digestive system and interactions of lead with trace elements

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Michał Dobrakowski

2013-09-01

Full Text Available Lead compounds are still the most dangerous poisons. The effects of lead intoxication occur mainly as a result of environmental exposure through lead paints, dust, soil, potable water. Pathophysiology of lead poisoning is still poorly understood, especially gastrointestinal and hepatological aspects. In consequence, the aim of the paper is to present the most important data concerning the effects of chronic lead exposure on the digestive system and the interactions between lead and selected trace elements.

Investigation of nepetolide as a novel lead compound: Antioxidant, antimicrobial, cytotoxic, anticancer, anti-inflammatory, analgesic activities and molecular docking evaluation

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Tanzeel ur Rehman

2018-03-01

Full Text Available In the present study, we describe various pharmacological effects and computational analysis of nepetolide, a tricyclic clerodane-type diterpene, isolated from Nepeta suavis. Nepetolide concentration-dependently (1.0–1000 µg/mL exhibited 1,1-diphenyl,2-picrylhydrazyl free radical scavenging activity with maximum effect of 87.01 ± 1.85%, indicating its antioxidant potential, as shown by standard drug, ascorbic acid. It was moderately active against bacterial strain of Staphylococcus aureus. In brine shrimp’s lethality model, nepetolide potently showed cytotoxic effect, with LC50 value of 8.7 µg/mL. When evaluated for antitumor activity in potato disc tumor assay, nepetolide exerted tumor inhibitory effect of 56.5 ± 1.5% at maximum tested concentration of 1000 µg/mL. Nepetolide at 20 mg/kg reduced carrageenan-induced inflammation (P < .001 vs. saline group in rat paw. Nepetolide dose-dependently (100–500 mg/kg decreased acetic acid evoked writhes, as exhibited by diclofenac sodium. In-silico investigation of nepetolide was carried out against cyclooxygenase-2, epidermal growth factor receptor and lipoxygenase-2 targets. Virtual screening through Patchdock online docking server identified primarily hydrophobic interactions between ligand nepetolide and receptors proteins. Enhanced hydrogen bonding was predicted with Autodock showing 6–8 hydrogen bonds per target. These results indicate that nepetolide exhibits antioxidant, antibacterial, cytotoxic, anticancer, anti-inflammatory and analgesic activities and should be considered as a lead compound for developing drugs for the remedy of oxidative stress-induced disorders, microbial infections, cancers, inflammations and pain.

Effectiveness of an anti-algal compound in eliminating an aquatic unicellular harmful algal Phaeocystis globosa

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Huajun eZhang

2016-04-01

Full Text Available Phaeocystis globosa blooms can have negative effects on higher trophic levels in the marine ecosystem and consequently influence human activities. Strain KA22, identified as the bacterium Hahella, was isolated from coastal surface water and used to control P. globosa growth. A methanol extract from the bacteral cells showed strong algicidal activity. After purification, the compound showed a similar structure to prodigiosin when identified with Q-Exactive Orbitrap MS and nuclear magnetic resonance spectra. The compound showed algicidal activity against P. globosa with a 50% Lethal Dose (LD50 of 2.24 μg/mL. The prodigiosin was stable under heat and acid environment, and it could be degraded under alkaline environment and natural light condition. The growth rates of strain KA22 was fast in 2216E medium and the content of prodigiosin in this medium was more than 70 μg/mL after 16 h incubation. The compound showed particularly strong algicidal activity against Prorocentrum donghaiense, P. globosa and Heterosigma akashiwo, but having little effect on three other phytoplankton species tested. The results of our research could increase our knowledge on harmful algal bloom control compound and lead to further study on the mechanisms of the lysis effect on harmful algae.

Urban airborne lead: X-ray absorption spectroscopy establishes soil as dominant source.

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Nicholas E Pingitore

Full Text Available BACKGROUND: Despite the dramatic decrease in airborne lead over the past three decades, there are calls for regulatory limits on this potent pediatric neurotoxin lower even than the new (2008 US Environmental Protection Agency standard. To achieve further decreases in airborne lead, what sources would need to be decreased and what costs would ensue? Our aim was to identify and, if possible, quantify the major species (compounds of lead in recent ambient airborne particulate matter collected in El Paso, TX, USA. METHODOLOGY/PRINCIPAL FINDINGS: We used synchrotron-based XAFS (x-ray absorption fine structure to identify and quantify the major Pb species. XAFS provides molecular-level structural information about a specific element in a bulk sample. Pb-humate is the dominant form of lead in contemporary El Paso air. Pb-humate is a stable, sorbed complex produced exclusively in the humus fraction of Pb-contaminated soils; it also is the major lead species in El Paso soils. Thus such soil must be the dominant source, and its resuspension into the air, the transfer process, providing lead particles to the local air. CONCLUSIONS/SIGNIFICANCE: Current industrial and commercial activity apparently is not a major source of airborne lead in El Paso, and presumably other locales that have eliminated such traditional sources as leaded gasoline. Instead, local contaminated soil, legacy of earlier anthropogenic Pb releases, serves as a long-term reservoir that gradually leaks particulate lead to the atmosphere. Given the difficulty and expense of large-scale soil remediation or removal, fugitive soil likely constrains a lower limit for airborne lead levels in many urban settings.

Gut Microbiota Profiling: Metabolomics Based Approach to Unravel Compounds Affecting Human Health.

Science.gov (United States)

Vernocchi, Pamela; Del Chierico, Federica; Putignani, Lorenza

2016-01-01

The gut microbiota is composed of a huge number of different bacteria, that produce a large amount of compounds playing a key role in microbe selection and in the construction of a metabolic signaling network. The microbial activities are affected by environmental stimuli leading to the generation of a wide number of compounds, that influence the host metabolome and human health. Indeed, metabolite profiles related to the gut microbiota can offer deep insights on the impact of lifestyle and dietary factors on chronic and acute diseases. Metagenomics, metaproteomics and metabolomics are some of the meta-omics approaches to study the modulation of the gut microbiota. Metabolomic research applied to biofluids allows to: define the metabolic profile; identify and quantify classes and compounds of interest; characterize small molecules produced by intestinal microbes; and define the biochemical pathways of metabolites. Mass spectrometry and nuclear magnetic resonance spectroscopy are the principal technologies applied to metabolomics in terms of coverage, sensitivity and quantification. Moreover, the use of biostatistics and mathematical approaches coupled with metabolomics play a key role in the extraction of biologically meaningful information from wide datasets. Metabolomic studies in gut microbiota-related research have increased, focusing on the generation of novel biomarkers, which could lead to the development of mechanistic hypotheses potentially applicable to the development of nutritional and personalized therapies.

Screening of Natural Product Derivatives Identifies Two Structurally Related Flavonoids as Potent Quorum Sensing Inhibitors against Gram-Negative Bacteria

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Suvi Manner

2018-05-01

Full Text Available Owing to the failure of conventional antibiotics in biofilm control, alternative approaches are urgently needed. Inhibition of quorum sensing (QS represents an attractive target since it is involved in several processes essential for biofilm formation. In this study, a compound library of natural product derivatives (n = 3040 was screened for anti-quorum sensing activity using Chromobacterium violaceum as reporter bacteria. Screening assays, based on QS-mediated violacein production and viability, were performed in parallel to identify non-bactericidal QS inhibitors (QSIs. Nine highly active QSIs were identified, while 328 compounds were classified as moderately actives and 2062 compounds as inactives. Re-testing of the highly actives at a lower concentration against C. violaceum, complemented by a literature search, led to the identification of two flavonoid derivatives as the most potent QSIs, and their impact on biofilm maturation in Escherichia coli and Pseudomonas aeruginosa was further investigated. Finally, effects of these leads on swimming and swarming motility of P. aeruginosa were quantified. The identified flavonoids affected all the studied QS-related functions at micromolar concentrations. These compounds can serve as starting points for further optimization and development of more potent QSIs as adjunctive agents used with antibiotics in the treatment of biofilms.

Outbreak of fatal childhood lead poisoning related to artisanal gold mining in northwestern Nigeria, 2010.

Science.gov (United States)

Dooyema, Carrie A; Neri, Antonio; Lo, Yi-Chun; Durant, James; Dargan, Paul I; Swarthout, Todd; Biya, Oladayo; Gidado, Saheed O; Haladu, Suleiman; Sani-Gwarzo, Nasir; Nguku, Patrick M; Akpan, Henry; Idris, Sa'ad; Bashir, Abdullahi M; Brown, Mary Jean

2012-04-01

In May 2010, a team of national and international organizations was assembled to investigate children's deaths due to lead poisoning in villages in northwestern Nigeria. Our goal was to determine the cause of the childhood lead poisoning outbreak, investigate risk factors for child mortality, and identify children data. Multivariate logistic regression techniques were used to determine risk factors for childhood mortality. We surveyed 119 family compounds. Of 463 children 45 µg/dL), and incidence of convulsions among children before death (82%) suggest that most of the recent childhood deaths in the two surveyed villages were caused by acute lead poisoning from gold ore-processing activities. Control measures included environmental remediation, chelation therapy, public health education, and control of mining activities.

Identifying non-point sources of endocrine active compounds and their biological impacts in freshwater lakes

Science.gov (United States)

Baker, Beth H.; Martinovic-Weigelt, Dalma; Ferrey, Mark L.; Barber, Larry B.; Writer, Jeffrey H.; Rosenberry, Donald O.; Kiesling, Richard L.; Lundy, James R.; Schoenfuss, Heiko L.

2014-01-01

Contaminants of emerging concern, particularly endocrine active compounds (EACs), have been identified as a threat to aquatic wildlife. However, little is known about the impact of EACs on lakes through groundwater from onsite wastewater treatment systems (OWTS). This study aims to identify specific contributions of OWTS to Sullivan Lake, Minnesota, USA. Lake hydrology, water chemistry, caged bluegill sunfish (Lepomis macrochirus), and larval fathead minnow (Pimephales promelas) exposures were used to assess whether EACs entered the lake through OWTS inflow and the resultant biological impact on fish. Study areas included two OWTS-influenced near-shore sites with native bluegill spawning habitats and two in-lake control sites without nearby EAC sources. Caged bluegill sunfish were analyzed for plasma vitellogenin concentrations, organosomatic indices, and histological pathologies. Surface and porewater was collected from each site and analyzed for EACs. Porewater was also collected for laboratory exposure of larval fathead minnow, before analysis of predator escape performance and gene expression profiles. Chemical analysis showed EACs present at low concentrations at each study site, whereas discrete variations were reported between sites and between summer and fall samplings. Body condition index and liver vacuolization of sunfish were found to differ among study sites as did gene expression in exposed larval fathead minnows. Interestingly, biological exposure data and water chemistry did not match. Therefore, although results highlight the potential impacts of seepage from OWTS, further investigation of mixture effects and life history factor as well as chemical fate is warranted.

Identification of nonvolatile compounds in clove (Syzygium aromaticum) from Manado

Science.gov (United States)

Fathoni, A.; Saepudin, E.; Cahyana, A. H.; Rahayu, D. U. C.; Haib, J.

2017-07-01

Syzygium aromaticum (clove) are native to Indonesia and have been widely used in food industry due to their flavor. Nonvolatile compounds contribute to flavor, mainly in their taste. Currently, there is very little information available about nonvolatile compounds in clove. Identification of nonvolatile compounds is important to improve clove's value. Compound extraction was conducted by maceration in ethanol. Fractionations of the extract were performed by using gravity column chromatography on silica gel and Sephadex LH-20 as stationary phase. Nonvolatile compounds were identified by Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). LC-MS/MS was operated in negative mode with 0.1 % formic acid in water and acetonitrile as mobile phase. Nonvolatile compounds were identified by fragment analysis and compared to references. Several compounds had been identified and characterized asquinic acid, monogalloylglucose, gallic acid, digalloylglucose, isobiflorin, biflorin, ellagic acid, hydroxygallic acid, luteolin, quercetin, naringenin, kaempferol, isorhamnetin, dimethoxyluteolin, and rhamnetin. These compounds had two main flavor perceptions, i.e. astringent, and bitter.

RNA-Seq analysis and annotation of a draft blueberry genome assembly identifies candidate genes involved in fruit ripening, biosynthesis of bioactive compounds, and stage-specific alternative splicing.

Science.gov (United States)

Gupta, Vikas; Estrada, April D; Blakley, Ivory; Reid, Rob; Patel, Ketan; Meyer, Mason D; Andersen, Stig Uggerhøj; Brown, Allan F; Lila, Mary Ann; Loraine, Ann E

2015-01-01

Blueberries are a rich source of antioxidants and other beneficial compounds that can protect against disease. Identifying genes involved in synthesis of bioactive compounds could enable the breeding of berry varieties with enhanced health benefits. Toward this end, we annotated a previously sequenced draft blueberry genome assembly using RNA-Seq data from five stages of berry fruit development and ripening. Genome-guided assembly of RNA-Seq read alignments combined with output from ab initio gene finders produced around 60,000 gene models, of which more than half were similar to proteins from other species, typically the grape Vitis vinifera. Comparison of gene models to the PlantCyc database of metabolic pathway enzymes identified candidate genes involved in synthesis of bioactive compounds, including bixin, an apocarotenoid with potential disease-fighting properties, and defense-related cyanogenic glycosides, which are toxic. Cyanogenic glycoside (CG) biosynthetic enzymes were highly expressed in green fruit, and a candidate CG detoxification enzyme was up-regulated during fruit ripening. Candidate genes for ethylene, anthocyanin, and 400 other biosynthetic pathways were also identified. Homology-based annotation using Blast2GO and InterPro assigned Gene Ontology terms to around 15,000 genes. RNA-Seq expression profiling showed that blueberry growth, maturation, and ripening involve dynamic gene expression changes, including coordinated up- and down-regulation of metabolic pathway enzymes and transcriptional regulators. Analysis of RNA-seq alignments identified developmentally regulated alternative splicing, promoter use, and 3' end formation. We report genome sequence, gene models, functional annotations, and RNA-Seq expression data that provide an important new resource enabling high throughput studies in blueberry.

A simple method to identify radiation and annealing biases that lead to worst-case CMOS static RAM postirradiation response

International Nuclear Information System (INIS)

Fleetwood, D.M.; Dressendorfer, P.V.

1987-01-01

The authors illustrate a simple method to identify bias conditions that lead to worst-case postirradiation speed and timing response for SRAMs. Switching cell states between radiation and anneal should lead to maximum speed and timing degradation for many hardened designs and technologies. The greatest SRAM cell imbalance is also established by these radiation and annealing conditions for the hardened and commercial parts that we have examined. These results should provide insight into the behavior of SRAMs during and after irradiation. The results should also be useful to establishing guidelines for integrated-circuit functionality testing, and SEU and dose-rate upset testing, after total-dose irradiation

Using High Throughput Screens to Identify Lead Compounds for Alzheimer’s Disease Therapeutics

Science.gov (United States)

2008-11-01

and curcumin . Nicotine is suggested to bind to the small, soluble β- sheet aggregate (63). The hormone melatonin has been shown to prevent β-sheet...inhibitors ......................... 11  Figure 1.8. Structure of melatonin, curcumin , and nicotine ............................... 12  Chapter 2...the plaques and fibrils to the soluble oligomers, which have shown to be better correlated with disease symptoms (27-31). More recently, soluble

Chemical-genetic profile analysis of five inhibitory compounds in yeast

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Alamgir Md

2010-08-01

Full Text Available Abstract Background Chemical-genetic profiling of inhibitory compounds can lead to identification of their modes of action. These profiles can help elucidate the complex interactions between small bioactive compounds and the cell machinery, and explain putative gene function(s. Results Colony size reduction was used to investigate the chemical-genetic profile of cycloheximide, 3-amino-1,2,4-triazole, paromomycin, streptomycin and neomycin in the yeast Saccharomyces cerevisiae. These compounds target the process of protein biosynthesis. More than 70,000 strains were analyzed from the array of gene deletion mutant yeast strains. As expected, the overall profiles of the tested compounds were similar, with deletions for genes involved in protein biosynthesis being the major category followed by metabolism. This implies that novel genes involved in protein biosynthesis could be identified from these profiles. Further investigations were carried out to assess the activity of three profiled genes in the process of protein biosynthesis using relative fitness of double mutants and other genetic assays. Conclusion Chemical-genetic profiles provide insight into the molecular mechanism(s of the examined compounds by elucidating their potential primary and secondary cellular target sites. Our follow-up investigations into the activity of three profiled genes in the process of protein biosynthesis provided further evidence concerning the usefulness of chemical-genetic analyses for annotating gene functions. We termed these genes TAE2, TAE3 and TAE4 for translation associated elements 2-4.

Managing, profiling and analyzing a library of 2.6 million compounds gathered from 32 chemical providers.

Science.gov (United States)

Monge, Aurélien; Arrault, Alban; Marot, Christophe; Morin-Allory, Luc

2006-08-01

The data for 3.8 million compounds from structural databases of 32 providers were gathered and stored in a single chemical database. Duplicates are removed using the IUPAC International Chemical Identifier. After this, 2.6 million compounds remain. Each database and the final one were studied in term of uniqueness, diversity, frameworks, 'drug-like' and 'lead-like' properties. This study also shows that there are more than 87 000 frameworks in the database. It contains 2.1 million 'drug-like' molecules among which, more than one million are 'lead-like'. This study has been carried out using 'ScreeningAssistant', a software dedicated to chemical databases management and screening sets generation. Compounds are stored in a MySQL database and all the operations on this database are carried out by Java code. The druglikeness and leadlikeness are estimated with 'in-house' scores using functions to estimate convenience to properties; unicity using the InChI code and diversity using molecular frameworks and fingerprints. The software has been conceived in order to facilitate the update of the database. 'ScreeningAssistant' is freely available under the GPL license.

Identification and quantification of antifungal compounds produced by lactic acid bacteria and propionibacteria.

Science.gov (United States)

Le Lay, Céline; Coton, Emmanuel; Le Blay, Gwenaëlle; Chobert, Jean-Marc; Haertlé, Thomas; Choiset, Yvan; Van Long, Nicolas Nguyen; Meslet-Cladière, Laurence; Mounier, Jérôme

2016-12-19

Fungal growth in bakery products represents the most frequent cause of spoilage and leads to economic losses for industrials and consumers. Bacteria, such as lactic acid bacteria and propionibacteria, are commonly known to play an active role in preservation of fermented food, producing a large range of antifungal metabolites. In a previous study (Le Lay et al., 2016), an extensive screening performed both in vitro and in situ allowed for the selection of bacteria exhibiting an antifungal activity. In the present study, active supernatants against Penicillium corylophilum and Aspergillus niger were analyzed to identify and quantify the antifungal compounds associated with the observed activity. Supernatant treatments (pH neutralization, heating and addition of proteinase K) suggested that organic acids played the most important role in the antifungal activity of each tested supernatant. Different methods (HPLC, mass spectrometry, colorimetric and enzymatic assays) were then applied to analyze the supernatants and it was shown that the main antifungal compounds corresponded to lactic, acetic and propionic acids, ethanol and hydrogen peroxide, as well as other compounds present at low levels such as phenyllactic, hydroxyphenyllactic, azelaic and caproic acids. Based on these results, various combinations of the identified compounds were used to evaluate their effect on conidial germination and fungal growth of P. corylophilum and Eurotium repens. Some combinations presented the same activity than the bacterial culture supernatant thus confirming the involvement of the identified molecules in the antifungal activity. The obtained results suggested that acetic acid was mainly responsible for the antifungal activity against P. corylophilum and played an important role in E. repens inhibition. Copyright © 2016 Elsevier B.V. All rights reserved.

Lead optimization of antimalarial propafenone analogues.

Science.gov (United States)

Lowes, David; Pradhan, Anupam; Iyer, Lalitha V; Parman, Toufan; Gow, Jason; Zhu, Fangyi; Furimsky, Anna; Lemoff, Andrew; Guiguemde, W Armand; Sigal, Martina; Clark, Julie A; Wilson, Emily; Tang, Liang; Connelly, Michele C; Derisi, Joseph L; Kyle, Dennis E; Mirsalis, Jon; Guy, R Kiplin

2012-07-12

Previously reported studies identified analogues of propafenone that had potent antimalarial activity, reduced cardiac ion channel activity, and properties that suggested the potential for clinical development for malaria. Careful examination of the bioavailability, pharmacokinetics, toxicology, and efficacy of this series of compounds using rodent models revealed orally bioavailable compounds that are nontoxic and suppress parasitemia in vivo. Although these compounds possess potential for further preclinical development, they also carry some significant challenges.

Chemical screening identifies filastatin, a small molecule inhibitor of Candida albicans adhesion, morphogenesis, and pathogenesis.

Science.gov (United States)

Fazly, Ahmed; Jain, Charu; Dehner, Amie C; Issi, Luca; Lilly, Elizabeth A; Ali, Akbar; Cao, Hong; Fidel, Paul L; Rao, Reeta P; Kaufman, Paul D

2013-08-13

Infection by pathogenic fungi, such as Candida albicans, begins with adhesion to host cells or implanted medical devices followed by biofilm formation. By high-throughput phenotypic screening of small molecules, we identified compounds that inhibit adhesion of C. albicans to polystyrene. Our lead candidate compound also inhibits binding of C. albicans to cultured human epithelial cells, the yeast-to-hyphal morphological transition, induction of the hyphal-specific HWP1 promoter, biofilm formation on silicone elastomers, and pathogenesis in a nematode infection model as well as alters fungal morphology in a mouse mucosal infection assay. We term this compound filastatin based on its strong inhibition of filamentation, and we use chemical genetic experiments to show that it acts downstream of multiple signaling pathways. These studies show that high-throughput functional assays targeting fungal adhesion can provide chemical probes for study of multiple aspects of fungal pathogenesis.

Advanced cell culture technology for essential oil production and micro array studies leading to discovery of genes for fragrance compounds in Michelia alba (Cempaka Putih)

International Nuclear Information System (INIS)

Rusli Ibrahim; Norazlina Nordin; Edrina Azlan

2006-01-01

Michelia spp. is known to produce high value essential oil for perfumery industry. The essence of world's most expensive perfumes, such as JOY and Jadore, is based on the oil of Michelia spp. One major problem anticipated in this approach, based on our early experiments, is limited amount of fragrance produced in cell cultures. The appropriate strategy is to superimpose DNA micro array studies on top of the cell culture project. The study covers natural flower development phases that led to the identification of genes or sets of genes that regulate the production of the fragrance. Seven developmental stages of Michelia alba flower namely Stage 5 to 11 were investigated for their volatile constituents. The essential oil was isolated by Simultaneous Distillation Extraction technique and the oil obtained was subjected to GC-MS analysis. In total, seventy-seven compounds representing 93-98% of the overall volatiles compounds were identified on the basis of mass spectra and retention indices. Thirty-three of these compounds belonged to isoprenoids group which comprised 30-50% of the total volatile compounds whereas the remaining belonged to fatty acid derivatives, benzenoid, phenylpropanoid and other hydrocarbon compounds. Studies were conducted to optimize culture parameters for scaling-up the production of callus, suspension cell cultures and somatic and product accumulation of essential oils using bioreactor technology. (Author)

Mapping of the Available Chemical Space versus the Chemical Universe of Lead-Like Compounds.

Science.gov (United States)

Lin, Arkadii; Horvath, Dragos; Afonina, Valentina; Marcou, Gilles; Reymond, Jean-Louis; Varnek, Alexandre

2018-03-20

This is, to our knowledge, the most comprehensive analysis to date based on generative topographic mapping (GTM) of fragment-like chemical space (40 million molecules with no more than 17 heavy atoms, both from the theoretically enumerated GDB-17 and real-world PubChem/ChEMBL databases). The challenge was to prove that a robust map of fragment-like chemical space can actually be built, in spite of a limited (≪10 5 ) maximal number of compounds ("frame set") usable for fitting the GTM manifold. An evolutionary map building strategy has been updated with a "coverage check" step, which discards manifolds failing to accommodate compounds outside the frame set. The evolved map has a good propensity to separate actives from inactives for more than 20 external structure-activity sets. It was proven to properly accommodate the entire collection of 40 m compounds. Next, it served as a library comparison tool to highlight biases of real-world molecules (PubChem and ChEMBL) versus the universe of all possible species represented by FDB-17, a fragment-like subset of GDB-17 containing 10 million molecules. Specific patterns, proper to some libraries and absent from others (diversity holes), were highlighted. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Exoproteome and Secretome Derived Broad Spectrum Novel Drug and Vaccine Candidates in Vibrio cholerae Targeted by Piper betel Derived Compounds

Science.gov (United States)

Barh, Debmalya; Barve, Neha; Gupta, Krishnakant; Chandra, Sudha; Jain, Neha; Tiwari, Sandeep; Leon-Sicairos, Nidia; Canizalez-Roman, Adrian; Rodrigues dos Santos, Anderson; Hassan, Syed Shah; Almeida, Síntia; Thiago Jucá Ramos, Rommel; Augusto Carvalho de Abreu, Vinicius; Ribeiro Carneiro, Adriana; de Castro Soares, Siomar; Luiz de Paula Castro, Thiago; Miyoshi, Anderson; Silva, Artur; Kumar, Anil; Narayan Misra, Amarendra; Blum, Kenneth; Braverman, Eric R.; Azevedo, Vasco

2013-01-01

Vibrio cholerae is the causal organism of the cholera epidemic, which is mostly prevalent in developing and underdeveloped countries. However, incidences of cholera in developed countries are also alarming. Because of the emergence of new drug-resistant strains, even though several generic drugs and vaccines have been developed over time, Vibrio infections remain a global health problem that appeals for the development of novel drugs and vaccines against the pathogen. Here, applying comparative proteomic and reverse vaccinology approaches to the exoproteome and secretome of the pathogen, we have identified three candidate targets (ompU, uppP and yajC) for most of the pathogenic Vibrio strains. Two targets (uppP and yajC) are novel to Vibrio, and two targets (uppP and ompU) can be used to develop both drugs and vaccines (dual targets) against broad spectrum Vibrio serotypes. Using our novel computational approach, we have identified three peptide vaccine candidates that have high potential to induce both B- and T-cell-mediated immune responses from our identified two dual targets. These two targets were modeled and subjected to virtual screening against natural compounds derived from Piper betel. Seven compounds were identified first time from Piper betel to be highly effective to render the function of these targets to identify them as emerging potential drugs against Vibrio. Our preliminary validation suggests that these identified peptide vaccines and betel compounds are highly effective against Vibrio cholerae. Currently we are exhaustively validating these targets, candidate peptide vaccines, and betel derived lead compounds against a number of Vibrio species. PMID:23382822

Exoproteome and secretome derived broad spectrum novel drug and vaccine candidates in Vibrio cholerae targeted by Piper betel derived compounds.

Directory of Open Access Journals (Sweden)

Debmalya Barh

Full Text Available Vibrio cholerae is the causal organism of the cholera epidemic, which is mostly prevalent in developing and underdeveloped countries. However, incidences of cholera in developed countries are also alarming. Because of the emergence of new drug-resistant strains, even though several generic drugs and vaccines have been developed over time, Vibrio infections remain a global health problem that appeals for the development of novel drugs and vaccines against the pathogen. Here, applying comparative proteomic and reverse vaccinology approaches to the exoproteome and secretome of the pathogen, we have identified three candidate targets (ompU, uppP and yajC for most of the pathogenic Vibrio strains. Two targets (uppP and yajC are novel to Vibrio, and two targets (uppP and ompU can be used to develop both drugs and vaccines (dual targets against broad spectrum Vibrio serotypes. Using our novel computational approach, we have identified three peptide vaccine candidates that have high potential to induce both B- and T-cell-mediated immune responses from our identified two dual targets. These two targets were modeled and subjected to virtual screening against natural compounds derived from Piper betel. Seven compounds were identified first time from Piper betel to be highly effective to render the function of these targets to identify them as emerging potential drugs against Vibrio. Our preliminary validation suggests that these identified peptide vaccines and betel compounds are highly effective against Vibrio cholerae. Currently we are exhaustively validating these targets, candidate peptide vaccines, and betel derived lead compounds against a number of Vibrio species.

Utility of lead aVR for identifying the culprit lesion in acute myocardial infarction

DEFF Research Database (Denmark)

Kühl, Jørgen Tobias; Berg, Ronan M G

2009-01-01

BACKGROUND: Lead aVR is a neglected, however, potentially useful tool in electrocardiography. Our aim was to evaluate its value in clinical practice, by reviewing existing literature regarding its utility for identifying the culprit lesion in acute myocardial infarction (AMI). METHODS: Based...... on a systematic search strategy, 16 studies were assessed with the intent to pool data; diagnostic test rates were calculated as key results. RESULTS: Five studies investigated if ST-segment elevation (STE) in aVR is valuable for the diagnosis of left main stem stenosis (LMS) in non-ST-segment AMI (NSTEMI......). The studies were too heterogeneous to pool, but the individual studies all showed that STE in aVR has a high negative predictive value (NPV) for LMS. Six studies evaluated if STE in aVR is valuable for distinguishing proximal from distal lesions in the left anterior descending artery (LAD) in anterior ST...

Fig volatile compounds--a first comparative study.

Science.gov (United States)

Grison-Pigé, Laure; Hossaert-McKey, Martine; Greeff, Jaco M; Bessière, Jean-Marie

2002-09-01

We analysed the compounds of volatile blends released by receptive figs of twenty Ficus species to attract their specific pollinating wasps. In all, 99 different compounds were identified. The compounds are mainly terpenoids, aliphatic compounds and products from the shikimic acid pathway. In each species blend, there are few major compounds, which are generally common among floral fragrances. Most species blends also include rare compounds, but generally their proportion in the blend is low. A possible basis for species-specificity of Ficus-wasp interactions is discussed in relation to the patterns of volatiles found in this interspecies comparison. Copyright 2002 Elsevier Science Ltd.

Biophysics: for HTS hit validation, chemical lead optimization, and beyond.

Science.gov (United States)

Genick, Christine C; Wright, S Kirk

2017-09-01

There are many challenges to the drug discovery process, including the complexity of the target, its interactions, and how these factors play a role in causing the disease. Traditionally, biophysics has been used for hit validation and chemical lead optimization. With its increased throughput and sensitivity, biophysics is now being applied earlier in this process to empower target characterization and hit finding. Areas covered: In this article, the authors provide an overview of how biophysics can be utilized to assess the quality of the reagents used in screening assays, to validate potential tool compounds, to test the integrity of screening assays, and to create follow-up strategies for compound characterization. They also briefly discuss the utilization of different biophysical methods in hit validation to help avoid the resource consuming pitfalls caused by the lack of hit overlap between biophysical methods. Expert opinion: The use of biophysics early on in the drug discovery process has proven crucial to identifying and characterizing targets of complex nature. It also has enabled the identification and classification of small molecules which interact in an allosteric or covalent manner with the target. By applying biophysics in this manner and at the early stages of this process, the chances of finding chemical leads with novel mechanisms of action are increased. In the future, focused screens with biophysics as a primary readout will become increasingly common.

Volatile sulfur compounds in tropical fruits

Directory of Open Access Journals (Sweden)

Robert J. Cannon

2018-04-01

Full Text Available Global production and demand for tropical fruits continues to grow each year as consumers are enticed by the exotic flavors and potential health benefits that these fruits possess. Volatile sulfur compounds (VSCs are often responsible for the juicy, fresh aroma of tropical fruits. This poses a challenge for analytical chemists to identify these compounds as most often VSCs are found at low concentrations in most tropical fruits. The aim of this review is to discuss the extraction methods, enrichment techniques, and instrumentation utilized to identify and quantify VSCs in natural products. This will be followed by a discussion of the VSCs reported in tropical and subtropical fruits, with particular attention to the odor and taste attributes of each compound. Finally, the biogenesis and enzymatic formation of specific VSCs in tropical fruits will be highlighted along with the contribution each possesses to the aroma of their respective fruit. Keywords: Tropical fruits, Volatile sulfur compounds, Extraction methods

Crystallographic properties of fertilizer compounds

Energy Technology Data Exchange (ETDEWEB)

Frazier, A.W.; Dillard, E.F.; Thrasher, R.D.; Waerstad, K.R.; Hunter, S.R.; Kohler, J.J.; Scheib, R.M.

1991-02-01

This bulletin is a compilation of crystallographic data collected at NFERC on 450 fertilizer-related compounds. In TVA's fertilizer R and D program, petrographic examination, XRD, and infrared spectroscopy are combined with conventional chemical analysis methods in identifying the individual compounds that occur in fertilizer materials. This handbook brings together the results of these characterization studies and supplemental crystallographic data from the literature. It is in one-compound-per-page, loose-leaf format, ordered alphabetically by IUPAC name. Indexes provided include IUPAC name, formula, group, alternate formula, synonyms, x-ray data, optical data. Tables are given for solids, compounds in commercial MAP and DAP, and matrix materials in phosphate rock.

Maximizing Information from Residential Measurements of Volatile Organic Compounds

Energy Technology Data Exchange (ETDEWEB)

Maddalena, Randy [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Li, Na [Berkeley Analytical Associates, Richmond, CA (United States); Hodgson, Alfred [Berkeley Analytical Associates, Richmond, CA (United States); Offermann, Francis [Indoor Environmental Engineering, San Francisco, CA (United States); Singer, Brett [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

2013-02-01

Continually changing materials used in home construction and finishing can introduce new chemicals or changes in the VOC profile in residential air and the trend towards tighter homes can lead to higher exposure concentrations for many indoor sources. However, the complex mixture of VOCs in residential air makes it difficult to discover emerging contaminants and/or trends in pollutant profiles. The purpose of this study is to prepare a comprehensive library of chemicals found in homes, along with a semi-quantitative approach to maximize the information gained from VOC measurements. We carefully reviewed data from 108 new California homes and identified 238 individual compounds. The majority of the identified VOCs originated indoors. Only 31% were found to have relevant health based exposure guidelines and less than 10% had a chronic reference exposure level (CREL). The finding highlights the importance of extending IAQ studies to include a wider range of VOCs

Antimicrobial susceptibility assessment of compound from ...

African Journals Online (AJOL)

Ethyl acetate extract of the culture filtrate of Aspergillus fumigatus on chromatographic analysis has led to the isolation of the compound, AF-1 which exhibited a significant in vitro antimicrobial activity against the tested pathogenic microorganism. The structure of the isolated compound, AF-1 was identified as ...

In vitro and in vivo studies of lead immobilization by synthetic hydroxyapatite

International Nuclear Information System (INIS)

Arnich, Nathalie; Lanhers, Marie-Claire; Laurensot, Franck; Podor, Renaud; Montiel, Antoine; Burnel, Daniel

2003-01-01

Lead immobilization by solid hydroxyapatite significantly reduces lead concentration and bioavailability in water. - Apatite appears a useful compound for removing lead from water, due to its ability to immobilize the metal by precipitation. In dilute solution, dissolved hydroxyapatite [HA, Ca 10 (PO 4 ) 6 (OH) 2 ] provided phosphates that were reactive with aqueous lead (molar ratio HA/Pb=1/10) forming precipitates at around pH 6. These dissolved at a more acidic pH (3). Solid HA in contact with Pb 2+ ions, led to the formation of pyromorphite [Pb 10 (PO 4 ) 6 (OH) 2 ], identified by X-ray diffraction and insoluble at pH tested (3-8). The amount of pyromorphite increased with the weight ratio of HA/Pb. When this one increased from 1 to 1000, lead precipitated as pyromorphite rose from 19 to 99%. In vivo experiments on rats confirmed the in vitro results. In fact, lead bioavailability assessed by intestinal perfusion was unchanged in the presence of dissolved HA, whereas it was significantly lower in the presence of solid HA, evaluated by gastric intubation, at a weight ratio equal to 10 (amount of lead absorbed decreased by 60%). Apatite could be an effective means of immobilizing lead in drinking or sewage, since accidental pyromorphite ingestion does not yield bioavailable lead

Computerized analysis of the 12-lead electrocardiogram to identify epicardial ventricular tachycardia exit sites.

Science.gov (United States)

Yokokawa, Miki; Jung, Dae Yon; Joseph, Kim K; Hero, Alfred O; Morady, Fred; Bogun, Frank

2014-11-01

Twelve-lead electrocardiogram (ECG) criteria for epicardial ventricular tachycardia (VT) origins have been described. In patients with structural heart disease, the ability to predict an epicardial origin based on QRS morphology is limited and has been investigated only for limited regions in the heart. The purpose of this study was to determine whether a computerized algorithm is able to accurately differentiate epicardial vs endocardial origins of ventricular arrhythmias. Endocardial and epicardial pace-mapping were performed in 43 patients at 3277 sites. The 12-lead ECGs were digitized and analyzed using a mixture of gaussian model (MoG) to assess whether the algorithm was able to identify an epicardial vs endocardial origin of the paced rhythm. The MoG computerized algorithm was compared to algorithms published in prior reports. The computerized algorithm correctly differentiated epicardial vs endocardial pacing sites for 80% of the sites compared to an accuracy of 42% to 66% of other described criteria. The accuracy was higher in patients without structural heart disease than in those with structural heart disease (94% vs 80%, P = .0004) and for right bundle branch block (82%) compared to left bundle branch block morphologies (79%, P = .001). Validation studies showed the accuracy for VT exit sites to be 84%. A computerized algorithm was able to accurately differentiate the majority of epicardial vs endocardial pace-mapping sites. The algorithm is not region specific and performed best in patients without structural heart disease and with VTs having a right bundle branch block morphology. Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Atmospheric Chemistry of Micrometeoritic Organic Compounds

Science.gov (United States)

Kress, M. E.; Belle, C. L.; Pevyhouse, A. R.; Iraci, L. T.

2011-01-01

Micrometeorites approx.100 m in diameter deliver most of the Earth s annual accumulation of extraterrestrial material. These small particles are so strongly heated upon atmospheric entry that most of their volatile content is vaporized. Here we present preliminary results from two sets of experiments to investigate the fate of the organic fraction of micrometeorites. In the first set of experiments, 300 m particles of a CM carbonaceous chondrite were subject to flash pyrolysis, simulating atmospheric entry. In addition to CO and CO2, many organic compounds were released, including functionalized benzenes, hydrocarbons, and small polycyclic aromatic hydrocarbons. In the second set of experiments, we subjected two of these compounds to conditions that simulate the heterogeneous chemistry of Earth s upper atmosphere. We find evidence that meteor-derived compounds can follow reaction pathways leading to the formation of more complex organic compounds.

Copper-catalyzed oxidative desulfurization-oxygenation of thiocarbonyl compounds using molecular oxygen: an efficient method for the preparation of oxygen isotopically labeled carbonyl compounds.

Science.gov (United States)

Shibahara, Fumitoshi; Suenami, Aiko; Yoshida, Atsunori; Murai, Toshiaki

2007-06-21

A novel copper-catalyzed oxidative desulfurization reaction of thiocarbonyl compounds, using molecular oxygen as an oxidant and leading to formation of carbonyl compounds, has been developed, and the utility of the process is demonstrated by its application to the preparation of a carbonyl-18O labeled sialic acid derivative.

Ultratrace analysis for organolead compounds in Greenland snow

International Nuclear Information System (INIS)

Lobinski, R.; Szpunar-Lobinska, J.; Adams, F.C.

1994-01-01

The degradation products of tetraalkyllead compounds used as antiknock additives are unique indicators of automotive environmental pollution by lead. Recent dramatic improvements in species-specific ultrasensitive analytical procedures enabled the identification and quantification of organolead compounds in ancient Greenland snow which is considered as the archives of northern hemispheric pollution records. Organolead species determined in fresh and ancient polar snow demonstrate unambiguously the global range of petrol-related pollution not only with ionic Pb 2+ but also with more toxic metalloorganic compounds. (authors). 9 refs., 5 figs

Novel colchicine-site binders with a cyclohexanedione scaffold identified through a ligand-based virtual screening approach.

Science.gov (United States)

Canela, María-Dolores; Pérez-Pérez, María-Jesús; Noppen, Sam; Sáez-Calvo, Gonzalo; Díaz, J Fernando; Camarasa, María-José; Liekens, Sandra; Priego, Eva-María

2014-05-22

Vascular disrupting agents (VDAs) constitute an innovative anticancer therapy that targets the tumor endothelium, leading to tumor necrosis. Our approach for the identification of new VDAs has relied on a ligand 3-D shape similarity virtual screening (VS) approach using the ROCS program as the VS tool and as query colchicine and TN-16, which both bind the α,β-tubulin dimer. One of the hits identified, using TN-16 as query, has been explored by the synthesis of its structural analogues, leading to 2-(1-((2-methoxyphenyl)amino)ethylidene)-5-phenylcyclohexane-1,3-dione (compound 16c) with an IC50 = 0.09 ± 0.01 μM in HMEC-1 and BAEC, being 100-fold more potent than the initial hit. Compound 16c caused cell cycle arrest in the G2/M phase and interacted with the colchicine-binding site in tubulin, as confirmed by a competition assay with N,N'-ethylenebis(iodoacetamide) and by fluorescence spectroscopy. Moreover, 16c destroyed an established endothelial tubular network at 1 μM and inhibited the migration and invasion of human breast carcinoma cells at 0.4 μM. In conclusion, our approach has led to a new chemotype of promising antiproliferative compounds with antimitotic and potential VDA properties.

Acoustic Sample Deposition MALDI-MS (ASD-MALDI-MS): A Novel Process Flow for Quality Control Screening of Compound Libraries.

Science.gov (United States)

Chin, Jefferson; Wood, Elizabeth; Peters, Grace S; Drexler, Dieter M

2016-02-01

In the early stages of drug discovery, high-throughput screening (HTS) of compound libraries against pharmaceutical targets is a common method to identify potential lead molecules. For these HTS campaigns to be efficient and successful, continuous quality control of the compound collection is necessary and crucial. However, the large number of compound samples and the limited sample amount pose unique challenges. Presented here is a proof-of-concept study for a novel process flow for the quality control screening of small-molecule compound libraries that consumes only minimal amounts of samples and affords compound-specific molecular data. This process employs an acoustic sample deposition (ASD) technique for the offline sample preparation by depositing nanoliter volumes in an array format onto microscope glass slides followed by matrix-assisted laser desorption/ionization mass spectrometric (MALDI-MS) analysis. An initial study of a 384-compound array employing the ASD-MALDI-MS workflow resulted in a 75% first-pass positive identification rate with an analysis time of <1 s per sample. © 2015 Society for Laboratory Automation and Screening.

The Compositional HJ-Biplot—A New Approach to Identifying the Links among Bioactive Compounds of Tomatoes

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Marcos Hernández Suárez

2016-11-01

Full Text Available Tomatoes have been described as a functional food because of their particular composition of different bioactive compounds. In this study, the proximate composition, minerals and trace elements, and antioxidant compounds were determined in two tomato cultivars (Mariana and Dunkan that were grown in Gran Canaria (Spain either conventionally or hydroponically. Although compositional data of this type require being subjected to the specific statistical techniques of compositional analysis, this approach has not usually been considered in this context. In the present case, a compositional Mann–Whitney U test of the data showed significant differences for each factor (cultivar and cultivation system in several of the compositional variables studied. For the differences between cultivars, these parameters were the protein, Mg, lycopene, ascorbic acid, citric acid, and fumaric acid contents. For the differences between cultivation systems, they were mainly those of the mineral and trace elements group. Although one-year data are insufficient to make clear relationship among compounds because more repetitions in several localities and years are necessary, the compositional HJ-biplot (in which the links provide estimates of the linear relationship among variables results agreed with other scientific results about linear relationship among some compounds analyzed.

Large-scale neurochemical metabolomics analysis identifies multiple compounds associated with methamphetamine exposure.

Science.gov (United States)

McClay, Joseph L; Adkins, Daniel E; Vunck, Sarah A; Batman, Angela M; Vann, Robert E; Clark, Shaunna L; Beardsley, Patrick M; van den Oord, Edwin J C G

2013-04-01

Methamphetamine (MA) is an illegal stimulant drug of abuse with serious negative health consequences. The neurochemical effects of MA have been partially characterized, with a traditional focus on classical neurotransmitter systems. However, these directions have not yet led to novel drug treatments for MA abuse or toxicity. As an alternative approach, we describe here the first application of metabolomics to investigate the neurochemical consequences of MA exposure in the rodent brain. We examined single exposures at 3 mg/kg and repeated exposures at 3 mg/kg over 5 days in eight common inbred mouse strains. Brain tissue samples were assayed using high-throughput gas and liquid chromatography mass spectrometry, yielding quantitative data on >300 unique metabolites. Association testing and false discovery rate control yielded several metabolome-wide significant associations with acute MA exposure, including compounds such as lactate ( p = 4.4 × 10 -5 , q = 0.013), tryptophan ( p = 7.0 × 10 -4 , q = 0.035) and 2-hydroxyglutarate ( p = 1.1 × 10 -4 , q = 0.022). Secondary analyses of MA-induced increase in locomotor activity showed associations with energy metabolites such as succinate ( p = 3.8 × 10 -7 ). Associations specific to repeated (5 day) MA exposure included phosphocholine ( p = 4.0 × 10 -4 , q = 0.087) and ergothioneine ( p = 3.0 × 10 -4 , q = 0.087). Our data appear to confirm and extend existing models of MA action in the brain, whereby an initial increase in energy metabolism, coupled with an increase in behavioral locomotion, gives way to disruption of mitochondria and phospholipid pathways and increased endogenous antioxidant response. Our study demonstrates the power of comprehensive MS-based metabolomics to identify drug-induced changes to brain metabolism and to develop neurochemical models of drug effects.

Formation of chemical compounds under vacuum plasma-arc deposition of nickel and its alloy onto piezoceramics

International Nuclear Information System (INIS)

Grinchenko, V.T.; Lyakhovich, T.K.; Prosina, N.I.; Khromov, S.M.

1988-01-01

The phase composition of the transition layer appearing during vacuum-arc coating of nickel and nickel alloy with copper on barium titanate and lead zirconate-titanate is identified. During vacuum plasma-arc coating of nickel and its alloy at the boundary with barium titanate and lead zirconate-titanate the Ni 2 Ti 4 O compound appears which has the crystal lattice type identical with substrate with the parity of lattice parameters. The transition layer contains nickel oxides and NiTiO 3 in the case of barium titanate. When titanate content in substrate increases the zone of reaction diffusion increases in value and becomes more complicate in composition

Hot spot analysis for driving the development of hits into leads in fragment based drug discovery

Science.gov (United States)

Hall, David R.; Ngan, Chi Ho; Zerbe, Brandon S.; Kozakov, Dima; Vajda, Sandor

2011-01-01

Fragment based drug design (FBDD) starts with finding fragment-sized compounds that are highly ligand efficient and can serve as a core moiety for developing high affinity leads. Although the core-bound structure of a protein facilitates the construction of leads, effective design is far from straightforward. We show that protein mapping, a computational method developed to find binding hot spots and implemented as the FTMap server, provides information that complements the fragment screening results and can drive the evolution of core fragments into larger leads with a minimal loss or, in some cases, even a gain in ligand efficiency. The method places small molecular probes, the size of organic solvents, on a dense grid around the protein, and identifies the hot spots as consensus clusters formed by clusters of several probes. The hot spots are ranked based on the number of probe clusters, which predicts the binding propensity of the subsites and hence their importance for drug design. Accordingly, with a single exception the main hot spot identified by FTMap binds the core compound found by fragment screening. The most useful information is provided by the neighboring secondary hot spots, indicating the regions where the core can be extended to increase its affinity. To quantify this information, we calculate the density of probes from mapping, which describes the binding propensity at each point, and show that the change in the correlation between a ligand position and the probe density upon extending or repositioning the core moiety predicts the expected change in ligand efficiency. PMID:22145575

Who Leads China's Leading Universities?

Science.gov (United States)

Huang, Futao

2017-01-01

This study attempts to identify the major characteristics of two different groups of institutional leaders in China's leading universities. The study begins with a review of relevant literature and theory. Then, there is a brief introduction to the selection of party secretaries, deputy secretaries, presidents and vice presidents in leading…

Erythrocyte fluorescence and lead intoxication.

Science.gov (United States)

Clark, K G

1976-01-01

Blood samples from people exposed to inorganic lead were examined by fluorescence microscopy for excess erythrocyte porphyrin. With continued lead absorption, fluorescent erythrocytes appeared in the circulation of workers handling this metal or its compounds, and they progressively increased in number and brilliance. These changes ensued if the blood lead concentration was maintained above 2-42 mumol/l (50 mug/100 ml), and preceded any material fall in the haemoglobin value. At one factory, 62-5% of 81 symptomless workers showed erythrocyte fluorescence attributable to the toxic effects of lead. Excess fluorocytes were found in blood samples from a child with pica and three of her eight siblings. These four were subsequently shown to have slightly increased blood lead concentrations (2-03 to 2-32 mumol/l). Fluorescence microscopy for excess erythrocyte porphyrin is a sensitive method for the detection of chronic lead intoxication. A relatively slight increase in the blood lead is associated with demonstrabel changes in erythrocyte porphyrin content. The procedure requires little blood, and may be performed upon stored samples collected for lead estimation. The results are not readily influenced by contamination, and provide good confirmatory evidence for the absorption of biochemically active lead. PMID:963005

Lead in Glasgow street dirt and soil

Energy Technology Data Exchange (ETDEWEB)

Farmer, J G [Univ. of Glasgow; Lyon, T D.B.

1977-07-01

The levels of lead in city street dirt and in soil from various locations in Glasgow were investigated during spring 1976. Lead concentrations in street dirt ranged from 150 to 2300 ppM, mean 960 ppM, and were significantly elevated with respect to the observed ''natural'' level of 78 ppM. Lead derived from anti-knock compounds in petrol and introduced to the environment via automobile exhausts was clearly implicated as the main source of lead pollution in a series of soil lead measurements at the centre and periphery of eight Glasgow parks. Various chemical leaching techniques were employed and compared. Less than 5 percent of street dirt and soil lead was found to be associated with the organic phase.

Lead Optimization of Anti-Malarial Propafenone Analogs

Science.gov (United States)

Lowes, David; Pradhan, Anupam; Iyer, Lalitha V.; Parman, Toufan; Gow, Jason; Zhu, Fangyi; Furimsky, Anna; Lemoff, Andrew; Guiguemde, W. Armand; Sigal, Martina; Clark, Julie A.; Wilson, Emily; Tang, Liang; Connelly, Michele C.; DeRisi, Joseph L.; Kyle, Dennis E.; Mirsalis, Jon; Guy, R. Kiplin

2015-01-01

Previously reported studies identified analogs of propafenone that had potent antimalarial activity, reduced cardiac ion channel activity, and properties that suggested the potential for clinical development for malaria. Careful examination of the bioavailability, pharmacokinetics, toxicology, and efficacy of this series of compounds using rodent models revealed orally bioavailable compounds that are non-toxic and suppress parasitemia in vivo. Although these compounds possess potential for further preclinical development, they also carry some significant challenges. PMID:22708838

Quercetin - A Flavonoid Compound from Sarcopyramis bodinieri var ...

African Journals Online (AJOL)

The flavonoid compound was identified as quercetin by 1H-. NMR and ESI-MS ... phenolic compounds were isolated, and their .... scored under a fluorescence microscope (Carl. Zeiss .... Antioxidant Properties of Sarcopyramis bodinieri.

Identification of isomers of organometallic compounds

Energy Technology Data Exchange (ETDEWEB)

Mbue, Sona Peter; Cho, Kwang Hwi [Dept. of Bioinformatics and Life Science, School of Systems Biomedical Science, Soongsil University,Seoul (Korea, Republic of)

2015-06-15

The yaChI is a newly suggested chemical naming system. However, yaChI is a derivative of the IUPAC InChI with a modified algorithm that includes additional layers of chemical structure information. Consequently, yaChI string contains more structure details while preserving the original structure file information and can distinctively identify very closely related compounds reducing the chances of ambiguity in chemical compound databases as opposed to the general SMILES, InChI, and InChIKey. This study examines the relative performances of yaChI, SMILES, InChI, and InChIKey in duplication check for isomers. For simplicity, a small data set of 28 organometallic compounds (structural isomers of Rh-containing compounds) subdivided into three major groups (A, B, and C) based on the number and the type of ligands attached to the center atom was used to study the performances of each encoding scheme in describing chemical structures. SMILES, InChI, and InChIKey were generated using Openbabel and RDkit, whereas yaChI strings were generated with in-house program. Strings generated from SMILES, InChI, and InChIKey though different, resulted to only three unique chemical identifiers, with each belonging to one group indicating the presence of only three unique compounds in the study data. However, yaChI results depicted that all structures in each group are indeed unique and differ among themselves as well as those from other groups, mapping each structure with a unique identifier given a total number of 28 unique structures in the study data. This high perception of yaChI probe justifies its accuracy and reliability in duplication check among closely related compounds especially structures exhibiting stereo properties.

Development of a strategy to identify the characteristics of babie‘s rooms associated with volatile organic compounds and with the occurrence of wheezing

Directory of Open Access Journals (Sweden)

Raquel Rodrigues dos Santos

2017-07-01

Full Text Available The air quality in residential contexts is still poorly understood. However, it is assumed to be very important in children's health, especially as a contributor to the onset of respiratory disease. Some volatile organic compounds (VOCs have been associated with the occurrence of asthma and respiratory disease symptoms. The aim of this study was to develop a questionnaire to identify the characteristics of the rooms where babies (0 to 36 months old sleep, potentially associated with exposure to volatile organic compounds and with the occurrence of wheezing. The design of the questionnaire involved bibliographic research, selection of (research articles, definition of appropriate variables and pretesting. As a result, we obtained an instrument comprised of 50 questions, suitable for the analysis of the data sought. This questionnaire also serves as a tool that may be useful in other studies in the scope of indoor air quality.

Antibacterial and Cytotoxic Activity of Compounds Isolated from Flourensia oolepis

Directory of Open Access Journals (Sweden)

Mariana Belén Joray

2015-01-01

Full Text Available The antibacterial and cytotoxic effects of metabolites isolated from an antibacterial extract of Flourensia oolepis were evaluated. Bioguided fractionation led to five flavonoids, identified as 2′,4′-dihydroxychalcone (1, isoliquiritigenin (2, pinocembrin (3, 7-hydroxyflavanone (4, and 7,4′-dihydroxy-3′-methoxyflavanone (5. Compound 1 showed the highest antibacterial effect, with minimum inhibitory concentration (MIC values ranging from 31 to 62 and 62 to 250 μg/mL, against Gram-positive and Gram-negative bacteria, respectively. On further assays, the cytotoxic effect of compounds 1–5 was determined by MTT assay on acute lymphoblastic leukemia (ALL and chronic myeloid leukemia (CML cell lines including their multidrug resistant (MDR phenotypes. Compound 1 induced a remarkable cytotoxic activity toward ALL cells (IC50 = 6.6–9.9 μM and a lower effect against CML cells (IC50 = 27.5–30.0 μM. Flow cytometry was used to analyze cell cycle distribution and cell death by PI-labeled cells and by Annexin V/PI staining, respectively. Upon treatment, 1 induced cell cycle arrest in the G2/M phase accompanied by a strong induction of apoptosis. These results describe for the first time the antibacterial metabolites of F. oolepis extract, with 1 being the most effective. This chalcone also emerges as a selective cytotoxic agent against sensitive and resistant leukemic cells, highlighting its potential as a lead compound.

Exome sequencing identifies compound heterozygous mutations in CYP4V2 in a pedigree with retinitis pigmentosa.

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Yun Wang

Full Text Available Retinitis pigmentosa (RP is a heterogeneous group of progressive retinal degenerations characterized by pigmentation and atrophy in the mid-periphery of the retina. Twenty two subjects from a four-generation Chinese family with RP and thin cornea, congenital cataract and high myopia is reported in this study. All family members underwent complete ophthalmologic examinations. Patients of the family presented with bone spicule-shaped pigment deposits in retina, retinal vascular attenuation, retinal and choroidal dystrophy, as well as punctate opacity of the lens, reduced cornea thickness and high myopia. Peripheral venous blood was obtained from all patients and their family members for genetic analysis. After mutation analysis in a few known RP candidate genes, exome sequencing was used to analyze the exomes of 3 patients III2, III4, III6 and the unaffected mother II2. A total of 34,693 variations shared by 3 patients were subjected to several filtering steps against existing variation databases. Identified variations were verified in the rest family members by PCR and Sanger sequencing. Compound heterozygous c.802-8_810del17insGC and c.1091-2A>G mutations of the CYP4V2 gene, known as genetic defects for Bietti crystalline corneoretinal dystrophy, were identified as causative mutations for RP of this family.

Antibacterial Activity of Phenolic Compounds Against the Phytopathogen Xylella fastidiosa

OpenAIRE

Maddox, Christina E.; Laur, Lisa M.; Tian, Li

2010-01-01

Xylella fastidiosa is a pathogenic bacterium that causes diseases in many crop species, which leads to considerable economic loss. Phenolic compounds (a group of secondary metabolites) are widely distributed in plants and have shown to possess antimicrobial properties. The anti-Xylella activity of 12 phenolic compounds, representing phenolic acid, coumarin, stilbene and flavonoid, was evaluated using an in vitro agar dilution assay. Overall, these phenolic compounds were effective in inhibiti...

Life in the fast lane: high-throughput chemistry for lead generation and optimisation.

Science.gov (United States)

Hunter, D

2001-01-01

The pharmaceutical industry has come under increasing pressure due to regulatory restrictions on the marketing and pricing of drugs, competition, and the escalating costs of developing new drugs. These forces can be addressed by the identification of novel targets, reductions in the development time of new drugs, and increased productivity. Emphasis has been placed on identifying and validating new targets and on lead generation: the response from industry has been very evident in genomics and high throughput screening, where new technologies have been applied, usually coupled with a high degree of automation. The combination of numerous new potential biological targets and the ability to screen large numbers of compounds against many of these targets has generated the need for large diverse compound collections. To address this requirement, high-throughput chemistry has become an integral part of the drug discovery process. Copyright 2002 Wiley-Liss, Inc.

ADME studies and preliminary safety pharmacology of LDT5, a lead compound for the treatment of benign prostatic hyperplasia

Directory of Open Access Journals (Sweden)

F. Noël

Full Text Available This study aimed to estimate the absorption, distribution, metabolism and excretion (ADME properties and safety of LDT5, a lead compound for oral treatment of benign prostatic hyperplasia that has previously been characterized as a multi-target antagonist of α1A-, α1D-adrenoceptors and 5-HT1A receptors. The preclinical characterization of this compound comprised the evaluation of its in vitro properties, including plasma, microsomal and hepatocytes stability, cytochrome P450 metabolism and inhibition, plasma protein binding, and permeability using MDCK-MDR1 cells. De-risking and preliminary safety pharmacology assays were performed through screening of 44 off-target receptors and in vivo tests in mice (rota-rod and single dose toxicity. LDT5 is stable in rat and human plasma, human liver microsomes and hepatocytes, but unstable in rat liver microsomes and hepatocytes (half-life of 11 min. LDT5 is highly permeable across the MDCK-MDR1 monolayer (Papp ∼32×10-6 cm/s, indicating good intestinal absorption and putative brain penetration. LDT5 is not extensively protein-bound and is a substrate of human CYP2D6 and CYP2C19 but not of CYP3A4 (half-life >60 min, and did not significantly influence the activities of any of the human cytochrome P450 isoforms screened. LDT5 was considered safe albeit new studies are necessary to rule out putative central adverse effects through D2, 5-HT1A and 5-HT2B receptors, after chronic use. This work highlights the drug-likeness properties of LDT5 and supports its further preclinical development.

The influence of pressure on diffusion leading to intermetallic compounds

International Nuclear Information System (INIS)

Adda, Y.; Beyeler, M.; Kirianenko, A.; Pernot, B.

1961-01-01

Some investigators A.D. LE CLAIRE, J.L. ZAMBROW, L. CASTLEMAN, have shown that the application of uniaxial pressure parallel to the direction of diffusion may notably modify the kinetics of growth of the intermediate phases which can be formed in this direction. The interpretation of this phenomenon being obscure, an attempt is made to explain it by detailed analysis of the experimental facts. The microscopic studies of the kinetics of growth of the zones formed shows particularly in the couples Uranium-Copper and Uranium-Nickel that it is influenced in a similar manner by a uniaxial pressure and a hydrostatic one. On the other hand the rate of growth of these zones increases as a function of the applied pressure in the systems Uranium-Copper, Uranium-Nickel and Uranium-Aluminium (this effect being particularly marked in Uranium-Aluminium). To determine with precision the limits of the range of stability of the intermetallic compounds, the curves of concentration penetration characteristics of the diffusion have been established by means of the CASTAING electronic microanalyser. The examination of the results indicates that when diffusion takes place without external pressure (couples U-Cu and U-Ni) or with a pressure less than 300 kg/cm 2 (couple U-Al) the concentration varies notably in the compounds obtained, which theoretically are stoichiometric. Thus, when crossing the zone of diffusion of one base metal to another one notes a continual passage of: UCu 4.70 to UCu 5.25 in the couple U-Cu; UNi 4.75 to UNi 5.25 in the couple U-Ni; UAl 2.2 to UAl 3.3 in the couple U-Al. If an uniaxial or hydrostatic pressure above 500 kg/cm 2 is applied to the couples U-Cu and U-Ni, or above 1000 kg/cm 2 for the couple U-Al, the composition is then constant in the zones formed. It corresponds to: UCu 5 in the couple U-Cu; UNi 5 in the couple U-Ni; UAl 3 in the couple U-Al. These results are confirmed by an X-ray diffraction study, mainly in the U-Cu system. Experiments in

Organosulfate Formation through the Heterogeneous Reaction of Sulfur Dioxide with Unsaturated Compounds

Science.gov (United States)

George, C.; Passananti, M.; Kong, L.; Shang, J.; Perrier, S.; Jianmin, C.; Donaldson, D. J.

2016-12-01

The atmospheric formation of organosulfur derivatives through reaction with SO2 is generally mediated by oxidants such as O3, OH; recently we have proposed a direct reaction between SO2 and unsaturated compounds as another possible pathway for organosulfate formation in the troposphere. For the first time it was shown recently that a heterogeneous reaction between SO2 and oleic acid (OA; an unsaturated fatty acid) takes place and leads efficiently to the formation of organosulfur products. Here, we demonstrate that this reaction proceeds on various unsaturated compounds, and may therefore have a general environmental impact. We used different experimental strategies i.e., a coated flow tube (CFT), an aerosol flow tube (AFT) and a DRIFT (diffuse reflectance infrared Fourier transform) cell. The reaction products were analyzed by means of liquid chromatography coupled to a high resolution mass spectrometer (LC-HR-MS). We report indeed that SO2 reacts with large variety of C=C unsaturations and that even in the presence of ozone, SO2 reacts with OA leading to organosulfur products. A strong enhancement in product formation is observed under actinic illumination, increases the atmospheric significance of this chemical pathway. This is probably due to the chromophoric nature of the SO2 adduct with C=C bonds, and means that the contribution of this direct addition of SO2 could be in excess of 5%. The detection in atmospheric aerosols of organosulfur compounds with the same chemical formulae as the products identified here seems to confirm the importance of this reaction in the atmosphere.

Lead uptake, tolerance, and accumulation exhibited by the plants Urtica dioica and Sedum spectabile in contaminated soil without additives

Directory of Open Access Journals (Sweden)

Grubor Milena

2008-01-01

Full Text Available Specimens of Urtica dioica and Sedum spectabile collected from plants growing at uncontaminated sites were transplanted in Pb-contaminated soil without additives (EDTA, HEDTA to identify their natural potential for hyper-tolerance and hyperaccumulation of lead. The total content of Pb in the plants was determined by atomic spectroscopy. Our research showed that the concentrated toxic levels of lead (Pb in Sedum spectabile and Urtica dioica were about 100 or more times higher than those of non-accumulator plants. It can be concluded that these plants have a high natural potential for hypertolerance and hyperaccumulation of lead, since they can hyperaccumulate it without addition of any chelating compounds (EDTA, HEDTA to enhance lead uptake. This makes them very promising plants for use in phytoremediation of Pb-contaminated sites.

Volatile organic compounds in emissions from brown-coal-fired residential stoves

International Nuclear Information System (INIS)

Engewald, W.; Knobloch, T.; Efer, J.

1993-01-01

Volatile organic compounds were determined in stack-gas emissions from the residential burning of brown-coal briquets using adsorptive enrichment on hydrophobic adsorbents, thermal desorption and capillary-gas chromatographic analysis. 152 compounds were identified and quantified. Quantitative emission factors of the identified individual compounds were determined in relation to the amount of the fuel used. These factors permit assessment of the pollution of the city of Leipzig with volatile organic compounds resulting from the burning of indigenous lignite. (orig.) [de

Anti-Pseudomonas aeruginosa compound, 1,2,3,4-tetrahydro-1,3,5-triazine derivative, exerts its action by primarily targeting MreB.

Science.gov (United States)

Yamachika, Shinichiro; Sugihara, Chika; Tsuji, Hayato; Muramatsu, Yasunori; Kamai, Yasuki; Yamashita, Makoto

2012-01-01

In order to find new anti-Pseudomonas agents, we carried out whole-cell based P. aeruginosa growth assay, and identified 1,2,3,4-tetrahydro-1,3,5-triazine (Compound A). This compound showed anti-Pseudomonas activity against wild as well as pumpless strain equally at a same concentration. Also, this compound was structurally very similar to A22, which is known to inhibit the bacterial actin-like protein MreB. By the analysis of resistant strains, the primary target of this compound in P. aeruginosa was definitely confirmed to be MreB. In addition, these compounds showed a bacteriostatic effect, and induced the morphology changes in P. aeruginosa from rod shape to sphere shape, which leads to be clinically favorable in terms of susceptibility to phagocytosis and release of endotoxin. These results display that Compound A is a very attractive compound which shows anti-P. aeruginosa activity based on inhibition of MreB without being affected by efflux pumps, and could provide a new step toward development of new promising anti-Pseudomonas agents, MreB inhibitors.

N-nitrosodimethylamine (NDMA) formation from the ozonation of model compounds.

Science.gov (United States)

Marti, Erica J; Pisarenko, Aleksey N; Peller, Julie R; Dickenson, Eric R V

2015-04-01

Nitrosamines are a class of toxic disinfection byproducts commonly associated with chloramination, of which several were included on the most recent U.S. EPA Contaminant Candidate List. Nitrosamine formation may be a significant barrier to ozonation in water reuse applications, particularly for direct or indirect potable reuse, since recent studies show direct formation during ozonation of natural water and treated wastewaters. Only a few studies have identified precursors which react with ozone to form N-nitrosodimethylamine (NDMA). In this study, several precursor compound solutions, prepared in ultrapure water and treated wastewater, were subjected to a 10 M excess of ozone. In parallel experiments, the precursor solutions in ultrapure water were exposed to gamma radiation to determine NDMA formation as a byproduct of reactions of precursor compounds with hydroxyl radicals. The results show six new NDMA precursor compounds that have not been previously reported in the literature, including compounds with hydrazone and carbamate moieties. Molar yields in deionized water were 61-78% for 3 precursors, 12-23% for 5 precursors and NDMA formation for the other precursors. NDMA formation due to chloramination was minimal compared to formation due to ozonation, suggesting distinct groups of precursor compounds for these two oxidants. Hydroxyl radical reactions with the precursors will produce NDMA, but formation is much greater in the presence of molecular ozone. Also, hydroxyl radical scavenging during ozonation leads to increased NDMA formation. Molar conversion yields were higher for several precursors in wastewater as compared to deionized water, which could be due to catalyzed reactions with constituents found in wastewater or hydroxyl radical scavenging. Copyright © 2014 Elsevier Ltd. All rights reserved.

Structure Modification of an Active Azo-Compound as a Route to New Antimicrobial Compounds

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Simona Concilio

2017-05-01

Full Text Available Some novel (phenyl-diazenylphenols 3a–g were designed and synthesized to be evaluated for their antimicrobial activity. A previously synthesized molecule, active against bacteria and fungi, was used as lead for modifications and optimization of the structure, by introduction/removal or displacement of hydroxyl groups on the azobenzene rings. The aim of this work was to evaluate the consequent changes of the antimicrobial activity and to validate the hypothesis that, for these compounds, a plausible mechanism could involve an interaction with protein receptors, rather than an interaction with membrane. All newly synthesized compounds were analyzed by 1H-NMR, DSC thermal analysis and UV-Vis spectroscopy. The in vitro minimal inhibitory concentrations (MIC of each compound was determined against Gram-positive and Gram-negative bacteria and Candida albicans. Compounds 3b and 3g showed the highest activity against S. aureus and C. albicans, with remarkable MIC values of 10 µg/mL and 3 µg/mL, respectively. Structure-activity relationship studies were capable to rationalize the effect of different substitutions on the phenyl ring of the azobenzene on antimicrobial activity.

Isolation of volatile compounds of Aloe excelsa (Berger ...

African Journals Online (AJOL)

PROMOTING ACCESS TO AFRICAN RESEARCH ... Industrial and pharmacological applications of volatile and non-volatile compounds isolated ... Three commercially important compounds, namely: phenylacetonitrile, carvone and limonene were identified using gas ... EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT

New hybrid lead iodides: From one-dimensional chain to two-dimensional layered perovskite structure

International Nuclear Information System (INIS)

Xiong, Kecai; Liu, Wei; Teat, Simon J.; An, Litao; Wang, Hao; Emge, Thomas J.; Li, Jing

2015-01-01

Two new hybrid lead halides (H 2 BDA)[PbI 4 ] (1) (H 2 BDA=1,4-butanediammonium dication) and (HNPEIM)[PbI 3 ] (2) (HNPEIM=N-​phenyl-ethanimidamidine cation) have been synthesized and structurally characterized. X-ray diffraction analyses reveal that compound 1 features a two-dimensional corner-sharing perovskite layer whereas compound 2 contains one-dimensional edge-sharing double chains. The N-​phenyl-ethanimidamidine cation within compound 2 was generated in-situ under solvothermal conditions. The optical absorption spectra collected at room temperature suggest that both compounds are semiconductors having direct band gaps, with estimated values of 2.64 and 2.73 eV for 1 and 2, respectively. Results from the density functional theory (DFT) calculations are consistent with the experimental data. Density of states (DOS) analysis reveals that in both compounds 1 and 2, the energy states in the valence band maximum region are iodine 5p atomic orbitals with a small contribution from lead 6s, while in the region of conduction band minimum, the major contributions are from the inorganic (Pb 6p atomic orbitals) and organic components (C and N 2p atomic orbitals) in compound 1 and 2, respectively. - Graphical abstract: Two new hybrid lead halides built on one-dimensional edge-sharing double chains and two-dimensional corner-sharing perovskite layers are synthesized and their structural and electronic properties are analyzed. - Highlights: • Two new hybrid lead iodides are designed, synthesized, and characterized. • They are closely related to, but different from, perovskite structures. • The electronic properties of both compounds are analyzed by DFT calculations

New hybrid lead iodides: From one-dimensional chain to two-dimensional layered perovskite structure

Energy Technology Data Exchange (ETDEWEB)

Xiong, Kecai; Liu, Wei [Department of Chemistry and Chemical Biology, Rutgers University, 610 Taylor Road, Piscataway, NJ 08854 (United States); Teat, Simon J. [Advanced Light Source, Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States); An, Litao; Wang, Hao; Emge, Thomas J. [Department of Chemistry and Chemical Biology, Rutgers University, 610 Taylor Road, Piscataway, NJ 08854 (United States); Li, Jing, E-mail: jingli@rutgers.edu [Department of Chemistry and Chemical Biology, Rutgers University, 610 Taylor Road, Piscataway, NJ 08854 (United States)

2015-10-15

Two new hybrid lead halides (H{sub 2}BDA)[PbI{sub 4}] (1) (H{sub 2}BDA=1,4-butanediammonium dication) and (HNPEIM)[PbI{sub 3}] (2) (HNPEIM=N-​phenyl-ethanimidamidine cation) have been synthesized and structurally characterized. X-ray diffraction analyses reveal that compound 1 features a two-dimensional corner-sharing perovskite layer whereas compound 2 contains one-dimensional edge-sharing double chains. The N-​phenyl-ethanimidamidine cation within compound 2 was generated in-situ under solvothermal conditions. The optical absorption spectra collected at room temperature suggest that both compounds are semiconductors having direct band gaps, with estimated values of 2.64 and 2.73 eV for 1 and 2, respectively. Results from the density functional theory (DFT) calculations are consistent with the experimental data. Density of states (DOS) analysis reveals that in both compounds 1 and 2, the energy states in the valence band maximum region are iodine 5p atomic orbitals with a small contribution from lead 6s, while in the region of conduction band minimum, the major contributions are from the inorganic (Pb 6p atomic orbitals) and organic components (C and N 2p atomic orbitals) in compound 1 and 2, respectively. - Graphical abstract: Two new hybrid lead halides built on one-dimensional edge-sharing double chains and two-dimensional corner-sharing perovskite layers are synthesized and their structural and electronic properties are analyzed. - Highlights: • Two new hybrid lead iodides are designed, synthesized, and characterized. • They are closely related to, but different from, perovskite structures. • The electronic properties of both compounds are analyzed by DFT calculations.

Lead(ii) soaps: crystal structures, polymorphism, and solid and liquid mesophases.

Science.gov (United States)

Martínez-Casado, F J; Ramos-Riesco, M; Rodríguez-Cheda, J A; Redondo-Yélamos, M I; Garrido, L; Fernández-Martínez, A; García-Barriocanal, J; da Silva, I; Durán-Olivencia, M; Poulain, A

2017-07-05

The long-chain members of the lead(ii) alkanoate series or soaps, from octanoate to octadecanoate, have been thoroughly characterized by means of XRD, PDF analysis, DSC, FTIR, ssNMR and other techniques, in all their phases and mesophases. The crystal structures at room temperature of all of the members of the series are now solved, showing the existence of two polymorphic forms in the room temperature crystal phase, different to short and long-chain members. Only nonanoate and decanoate present both forms, and this polymorphism is proven to be monotropic. At higher temperature, these compounds present a solid mesophase, defined as rotator, a liquid crystal phase and a liquid phase, all of which have a similar local arrangement. Since some lead(ii) soaps appear as degradation compounds in oil paintings, the solved crystal structures of lead(ii) soaps can now be used as fingerprints for their detection using X-ray diffraction. Pair distribution function analysis on these compounds is very similar in the same phases and mesophases for the different members, showing the same short range order. This observation suggests that this technique could also be used in the detection of these compounds in disordered phases or in the initial stages of formation in paintings.

Aerobic Microbial Degradation of Chlorochromate Compounds Polluting the Environment

International Nuclear Information System (INIS)

Khalil, O.A.A.

2011-01-01

Eight soil and sludge samples which have been polluted with petroleum wastes for more than 41 years were used for isolation of adapted indigenous microbial communities able to mineralize the chloro aromatic compounds [3-chlorobenzoic acid (3-CBA), 2,4-dichlorophenol (2,4-DCP), 2,6-dichlorophenol indole phenol (2,6-DCPP) and 1,2,4-trichlorobenzene (1,2,4-TCB)] and use them as a sole carbon and energy sources. From these communities, the most promising bacterial strain MAM-24 which has the ability to degrade the four chosen aromatic compounds was isolated and identified by comparative sequence analysis for its 16S-rRNA coding genes and it was identified as Bacillus mucilaginosus HQ 013329. Degradation percentage was quantified by HPLC. Degradation products were identified by GC-MS analysis which revealed that the isolated strain and its mutant dechlorinated the four chloro aromatic compounds in the first step forming acetophenone which is considered as the corner stone of the intermediate compounds

Current perspectives in fragment-based lead discovery (FBLD)

Science.gov (United States)

Lamoree, Bas; Hubbard, Roderick E.

2017-01-01

It is over 20 years since the first fragment-based discovery projects were disclosed. The methods are now mature for most ‘conventional’ targets in drug discovery such as enzymes (kinases and proteases) but there has also been growing success on more challenging targets, such as disruption of protein–protein interactions. The main application is to identify tractable chemical startpoints that non-covalently modulate the activity of a biological molecule. In this essay, we overview current practice in the methods and discuss how they have had an impact in lead discovery – generating a large number of fragment-derived compounds that are in clinical trials and two medicines treating patients. In addition, we discuss some of the more recent applications of the methods in chemical biology – providing chemical tools to investigate biological molecules, mechanisms and systems. PMID:29118093

Mutagenicity of New Lead Compounds to Treat Sickle Cell Disease Symptoms in a Salmonella/Microsome Assay

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Chung Man Chin

2010-02-01

Full Text Available A series of phthalimide derivatives planned as drugs candidates to treat the symptoms of sickle cell anemia were evaluated in a mutagenicity test using strains of Salmonella typhimurium TA100 and TA102, without and with addition of S9 mixture, with the aim to identify the best structural requirements for a drug candidate without genotoxic activity. The compounds (1,3-dioxo-1,3-dihydro-2H-isoindol-2-ylmethyl nitrate (1; (1,3-dioxo-1,3-dihydro-2H-isoindol-2-ylethyl nitrate (2; 3-(1,3-dioxo-1,3-dihydro-2H-iso-indol-2-ylbenzyl nitrate (3; 4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl-N-hydroxy-benzenesulfonamide (4; 4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-ylbenzyl nitrate (5 and 2-[4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-ylphenyl]ethyl nitrate (6 presented mutagenic potency ranging between 0-4,803 revertants/μmol. These results allowed us to propose that a methyl spacer linked to a nitrate ester subunit associated to meta aromatic substitution decreases mutagenicity.

Resistance to phenicol compounds following adaptation to quaternary ammonium compounds in Escherichia coli.

Science.gov (United States)

Soumet, C; Fourreau, E; Legrandois, P; Maris, P

2012-07-06

Bacterial adaptation to quaternary ammonium compounds (QACs) is mainly documented for benzalkonium chloride (BC) and few data are available for other QACs. The aim of this study was to assess the effects of repeated exposure to different quaternary ammonium compounds (QACs) on the susceptibility and/or resistance of bacteria to other QACs and antibiotics. Escherichia coli strains (n=10) were adapted by daily exposure to increasingly sub-inhibitory concentrations of a QAC for 7 days. Three QACs were studied. Following adaptation, we found similar levels of reduction in susceptibility to QACs with a mean 3-fold increase in the minimum inhibitory concentration (MIC) compared to initial MIC values, whatever the QAC used during adaptation. No significant differences in antibiotic susceptibility were observed between the tested QACs. Antibiotic susceptibility was reduced from 3.5- to 7.5-fold for phenicol compounds, β lactams, and quinolones. Increased MIC was associated with a shift in phenotype from susceptible to resistant for phenicol compounds (florfenicol and chloramphenicol) in 90% of E. coli strains. Regardless of the QAC used for adaptation, exposure to gradually increasing concentrations of this type of disinfectant results in reduced susceptibility to QACs and antibiotics as well as cross-resistance to phenicol compounds in E. coli strains. Extensive use of QACs at sub-inhibitory concentrations may lead to the emergence of antibiotic-resistant bacteria and may represent a public health risk. Published by Elsevier B.V.

Flavor and taste compounds analysis in Chinese solid fermented ...

African Journals Online (AJOL)

A total of 82 kinds of volatile compounds were identified, including alcohols, acids, esters, aldehydes, ketones, phenols, heterocyclic compounds, alkynes and benzenes. The subtle aroma of the soy sauce seemed to depend not only on particular key compounds but also on a “critical balance” or a “weighted concentration

New benchmark for basic and neutral nitrogen compounds speciation in middle distillates using comprehensive two-dimensional gas chromatography.

Science.gov (United States)

Adam, Frédérick; Bertoncini, Fabrice; Brodusch, Nicolas; Durand, Emmanuelle; Thiébaut, Didier; Espinat, Didier; Hennion, Marie-Claire

2007-04-27

This paper reports an analytical method for the comprehensive two-dimensional gas chromatography (GC x GC) separation and identification of nitrogen compounds (N-compounds) in middle distillates according to their types (basicity). For the evaluation of the best chromatographic conditions, a non-polar x polar approach was chosen. The impact of the second dimension (stationary phase and column length) on the separation of basic and neutral N-compounds was evaluated by mean of two-dimensional resolution. This study revealed that the implementation of polar secondary column having free electron pairs improves drastically the separation of N-compounds. Indeed, the presence of permanent dipole-permanent dipole interactions between neutral N-compounds and the stationary phase was enlightened. The comparison of two different nitrogen chemiluminescence detectors (NCD) was also evaluated for GC x GC selective monitoring of N-compounds. Owing to higher resolution power and enhanced sensitivity achieved using developed chromatographic and detection conditions, it was possible to identify univocally and to quantitate N-compounds (i) by class of compounds and (ii), within a class, by carbon number. Finally, quantitative comparison of GC x GC-NCD with conventional gas chromatography illustrates the benefits of GC x GC leading to an excellent correlation with results obtained by American Society for Testing Materials (ASTM) methods for the determination of basic/neutral nitrogen ratio in diesel samples.

Developmental immunotoxicology of lead

International Nuclear Information System (INIS)

Dietert, Rodney R.; Lee, Ji-Eun; Hussain, Irshad; Piepenbrink, Michael

2004-01-01

The heavy metal, lead, is a known developmental immunotoxicant that has been shown to produce immune alterations in humans as well as other species. Unlike many compounds that exert adverse immune effects, lead exposure at low to moderate levels does not produce widespread loss of immune cells. In contrast, changes resulting from lead exposure are subtle at the immune cell population level but, nevertheless, can be functionally dramatic. A hallmark of lead-induced immunotoxicity is a pronounced shift in the balance in T helper cell function toward T helper 2 responses at the expense of T helper 1 functions. This bias alters the nature and range of immune responses that can be produced thereby influencing host susceptibility to various diseases. Immunotoxic responses to lead appear to differ across life stages not only quantitatively with regard to dose response, but also qualitatively in terms of the spectrum of immune alterations. Experimental studies in several lab animal species suggest the latter stages of gestation are a period of considerable sensitivity for lead-induced immunotoxicity. This review describes the basic characteristics of lead-induced immunotoxicity emphasizing experimental animal results. It also provides a framework for the consideration of toxicant exposure effects across life stages. The existence of and probable basis for developmental windows of immune hyper-susceptibility are presented. Finally, the potential for lead to serve as a perinatal risk factor for childhood asthma as well as other diseases is considered

Prediction of Positions of Active Compounds Makes It Possible To Increase Activity in Fragment-Based Drug Development

Directory of Open Access Journals (Sweden)

Yoshifumi Fukunishi

2011-05-01

Full Text Available We have developed a computational method that predicts the positions of active compounds, making it possible to increase activity as a fragment evolution strategy. We refer to the positions of these compounds as the active position. When an active fragment compound is found, the following lead generation process is performed, primarily to increase activity. In the current method, to predict the location of the active position, hydrogen atoms are replaced by small side chains, generating virtual compounds. These virtual compounds are docked to a target protein, and the docking scores (affinities are examined. The hydrogen atom that gives the virtual compound with good affinity should correspond to the active position and it should be replaced to generate a lead compound. This method was found to work well, with the prediction of the active position being 2 times more efficient than random synthesis. In the current study, 15 examples of lead generation were examined. The probability of finding active positions among all hydrogen atoms was 26%, and the current method accurately predicted 60% of the active positions.

Lead discovery for mammalian elongation of long chain fatty acids family 6 using a combination of high-throughput fluorescent-based assay and RapidFire mass spectrometry assay

International Nuclear Information System (INIS)

Takamiya, Mari; Sakurai, Masaaki; Teranishi, Fumie; Ikeda, Tomoko; Kamiyama, Tsutomu; Asai, Akira

2016-01-01

A high-throughput RapidFire mass spectrometry assay is described for elongation of very long-chain fatty acids family 6 (Elovl6). Elovl6 is a microsomal enzyme that regulates the elongation of C12-16 saturated and monounsaturated fatty acids. Elovl6 may be a new therapeutic target for fat metabolism disorders such as obesity, type 2 diabetes, and nonalcoholic steatohepatitis. To identify new Elovl6 inhibitors, we developed a high-throughput fluorescence screening assay in 1536-well format. However, a number of false positives caused by fluorescent interference have been identified. To pick up the real active compounds among the primary hits from the fluorescence assay, we developed a RapidFire mass spectrometry assay and a conventional radioisotope assay. These assays have the advantage of detecting the main products directly without using fluorescent-labeled substrates. As a result, 276 compounds (30%) of the primary hits (921 compounds) in a fluorescence ultra-high-throughput screening method were identified as common active compounds in these two assays. It is concluded that both methods are very effective to eliminate false positives. Compared with the radioisotope method using an expensive 14 C-labeled substrate, the RapidFire mass spectrometry method using unlabeled substrates is a high-accuracy, high-throughput method. In addition, some of the hit compounds selected from the screening inhibited cellular fatty acid elongation in HEK293 cells expressing Elovl6 transiently. This result suggests that these compounds may be promising lead candidates for therapeutic drugs. Ultra-high-throughput fluorescence screening followed by a RapidFire mass spectrometry assay was a suitable strategy for lead discovery against Elovl6. - Highlights: • A novel assay for elongation of very-long-chain fatty acids 6 (Elovl6) is proposed. • RapidFire mass spectrometry (RF-MS) assay is useful to select real screening hits. • RF-MS assay is proved to be beneficial because of

Remediation of lead contaminated soil

International Nuclear Information System (INIS)

Urban, W.; Krishnamurthy, S.

1992-01-01

Lead contaminated soil in urban area is of major concern because of the potential health risk to children. Many studies have established a direct correlation between lead in soil and elevated blood lead levels in children. In Minneapolis, Minnesota, Mielke et al. (1983) reported that 50% of the Hmong children with lead poisioning were in areas where soil lead levels were between 500 and 1000 micrograms per gram (ug/g), and 40% of the children suffering from lead poisioning lived in areas where soil lead levels exceeded 1000 ug/g. In urban areas, lead pollution in soil has come from many different sources. The sources include lead paint, lead batteries and automobile exhaust. Olson and Skogerbee (1975) found the following lead compounds in soils where the primary source of pollution was from automobiles: lead sulfate, lead oxide, lead dioxide, lead sulfide, and metallic lead. The primary form of lead found was lead sulfate. Lead sulfate, lead tetraoxide, white lead, and other forms of lead have been used in the manufacture of paints for houses. At present, two remediation techniques, solidification and Bureau of Mines fluosilicic acid leaching, are available for lead-contaminated sites. The objective of the present investigation at the Risk Reduction Engineering Laboratory (RREL), Edison, was to try to solubilize the lead species by appropriate reagents and then recover the contaminants by precipitation as lead sulfate, using environmentally acceptable methods. The apparatus used for mixing was a LabMaster mixer, with variable speed and high-shear impeller. Previous work had used nitric acid for dissolving metallic lead. Owing to the environmental concerns, it was decided to use acetic acid in the presence of oxygen. The theoretical justification for this approach is the favorable redox potential for the reaction between metallic lead, acetic acid, and gaseous oxygen

Antifouling Compounds from Marine Macroalgae.

Science.gov (United States)

Dahms, Hans Uwe; Dobretsov, Sergey

2017-08-28

Marine macroalgae produce a wide variety of biologically-active metabolites that have been developed into commercial products, such as antibiotics, immunosuppressive, anti-inflammatory, cytotoxic agents, and cosmetic products. Many marine algae remain clean over longer periods of time, suggesting their strong antifouling potential. Isolation of biogenic compounds and the determination of their structure could provide leads for the development of environmentally-friendly antifouling paints. Isolated substances with potent antifouling activity belong to fatty acids, lipopeptides, amides, alkaloids, lactones, steroids, terpenoids, and pyrroles. It is unclear as yet to what extent symbiotic microorganisms are involved in the synthesis of these compounds. Algal secondary metabolites have the potential to be produced commercially using genetic and metabolic engineering techniques. This review provides an overview of publications from 2010 to February 2017 about antifouling activity of green, brown, and red algae. Some researchers were focusing on antifouling compounds of brown macroalgae, while metabolites of green algae received less attention. Several studies tested antifouling activity against bacteria, microalgae and invertebrates, but in only a few studies was the quorum sensing inhibitory activity of marine macroalgae tested. Rarely, antifouling compounds from macroalgae were isolated and tested in an ecologically-relevant way.

Quantitative high-throughput screen identifies inhibitors of the Schistosoma mansoni redox cascade.

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Anton Simeonov

2008-01-01

Full Text Available Schistosomiasis is a tropical disease associated with high morbidity and mortality, currently affecting over 200 million people worldwide. Praziquantel is the only drug used to treat the disease, and with its increased use the probability of developing drug resistance has grown significantly. The Schistosoma parasites can survive for up to decades in the human host due in part to a unique set of antioxidant enzymes that continuously degrade the reactive oxygen species produced by the host's innate immune response. Two principal components of this defense system have been recently identified in S. mansoni as thioredoxin/glutathione reductase (TGR and peroxiredoxin (Prx and as such these enzymes present attractive new targets for anti-schistosomiasis drug development. Inhibition of TGR/Prx activity was screened in a dual-enzyme format with reducing equivalents being transferred from NADPH to glutathione via a TGR-catalyzed reaction and then to hydrogen peroxide via a Prx-catalyzed step. A fully automated quantitative high-throughput (qHTS experiment was performed against a collection of 71,028 compounds tested as 7- to 15-point concentration series at 5 microL reaction volume in 1536-well plate format. In order to generate a robust data set and to minimize the effect of compound autofluorescence, apparent reaction rates derived from a kinetic read were utilized instead of end-point measurements. Actives identified from the screen, along with previously untested analogues, were subjected to confirmatory experiments using the screening assay and subsequently against the individual targets in secondary assays. Several novel active series were identified which inhibited TGR at a range of potencies, with IC(50s ranging from micromolar to the assay response limit ( approximately 25 nM. This is, to our knowledge, the first report of a large-scale HTS to identify lead compounds for a helminthic disease, and provides a paradigm that can be used to jump

Identification of bitter compounds in whole wheat bread.

Science.gov (United States)

Jiang, Deshou; Peterson, Devin G

2013-11-15

Bitterness in whole wheat bread can negatively influence product acceptability and consumption. The overall goal of this project was to identify the main bitter compounds in a commercial whole wheat bread product. Sensory-guided fractionation of the crust (most bitter portion of the bread sample) utilising liquid-liquid extraction, solid-phase extraction, ultra-filtration and 2-D offline RPLC revealed multiple bitter compounds existed. The compounds with the highest bitterness intensities were selected and structurally elucidated based on accurate mass-TOF, MS/MS, 1D and 2D NMR spectroscopy. Eight bitter compounds were identified: Acortatarins A, Acortatarins C, 5-(hydroxymethyl)furfural(HMF), 2,3-dihydro-3,5-dihydroxy-6-methyl-4(H)-pyran-4-one (DDMP), N-(1-deoxy-d-fructos-1-yl)-l-tryptophan (ARP), Tryptophol (TRO), 2-(2-formyl-5-(hydroxymethyl-1H-pyrrole-1-yl)butanoic acid (PBA) and Tryptophan (TRP). Based on the structures of these compounds, two main mechanisms of bitterness generation in wheat bread were supported, fermentation and Maillard pathways. Copyright © 2013 Elsevier Ltd. All rights reserved.

Volatile flavor compounds in yogurt: a review.

Science.gov (United States)

Cheng, Hefa

2010-11-01

Considerable knowledge has been accumulated on the volatile compounds contributing to the aroma and flavor of yogurt. This review outlines the production of the major flavor compounds in yogurt fermentation and the analysis techniques, both instrumental and sensory, for quantifying the volatile compounds in yogurt. The volatile compounds that have been identified in plain yogurt are summarized, with the few key aroma compounds described in detail. Most flavor compounds in yogurt are produced from lipolysis of milkfat and microbiological transformations of lactose and citrate. More than 100 volatiles, including carbonyl compounds, alcohols, acids, esters, hydrocarbons, aromatic compounds, sulfur-containing compounds, and heterocyclic compounds, are found in yogurt at low to trace concentrations. Besides lactic acid, acetaldehyde, diacetyl, acetoin, acetone, and 2-butanone contribute most to the typical aroma and flavor of yogurt. Extended storage of yogurt causes off-flavor development, which is mainly attributed to the production of undesired aldehydes and fatty acids during lipid oxidation. Further work on studying the volatile flavor compounds-matrix interactions, flavor release mechanisms, and the synergistic effect of flavor compounds, and on correlating the sensory properties of yogurt with the compositions of volatile flavor compounds are needed to fully elucidate yogurt aroma and flavor.

Effects of Methyl Jasmonate on the Composition of Volatile Compounds in Pyropia yezoensis

Science.gov (United States)

He, Lihong; Wang, Liang; Wang, Linfang; Shen, Songdong

2018-04-01

Volatile organic compounds in marine algae have been reported to comprise characteristic flavor of algae and play an important role in their growth, development and defensive response. Yet their biogeneration remain largely unknown. Here we studied the composition of volatile compouds in Pyropia yezoensis and their variations in response to methyl jasmonate (MeJA) and diethyldithiocarbamic acid (DIECA) treatment using gas chromatography-mass spectrometry (GC-MS). A total of 44 compounds belonging to the following chemical classes (n) were identified, including aldehydes (11), alcohols (8), acids and esters (6), alkanes (5), ketones (5), alkenes (3), and S- or N-containing miscellaneous compounds (6). External treatment with plant hormone MeJA increased the content of 1-dodecanol, 4-heptenal, and 2-propenoic acid-2-methyl dodecylester, but decreased the content of phytol, 3-heptadecene, 2-pentadecanone, and isophytol. When pretreated with DIECA, an inhibitor of the octadecanoid pathway leading to the biosynthesis of endogeneous jasmonates and some secondary metabolites, phytol and isophytol were increased, while 4-heptenal, 1-dodecanol, and 2-propenoic acid-2-methyl dodecylester were decreased, both of which were negatively correlated with their variations under MeJA treatment. Collectively, these results suggest that MeJA does affect the volatile composition of P. yezoensis, and the octadecanoid pathway together with endogenous jasmonate pathway may be involved in the biosynthesis of volatile compounds, thereby providing some preliminary envision on the composition and biogeneration of volatile compounds in P. yezoensis.

Making and Breaking of Lead Halide Perovskites

KAUST Repository

Manser, Joseph S.

2016-02-16

A new front-runner has emerged in the field of next-generation photovoltaics. A unique class of materials, known as organic metal halide perovskites, bridges the gap between low-cost fabrication and exceptional device performance. These compounds can be processed at low temperature (typically in the range 80–150 °C) and readily self-assemble from the solution phase into high-quality semiconductor thin films. The low energetic barrier for crystal formation has mixed consequences. On one hand, it enables inexpensive processing and both optical and electronic tunability. The caveat, however, is that many as-formed lead halide perovskite thin films lack chemical and structural stability, undergoing rapid degradation in the presence of moisture or heat. To date, improvements in perovskite solar cell efficiency have resulted primarily from better control over thin film morphology, manipulation of the stoichiometry and chemistry of lead halide and alkylammonium halide precursors, and the choice of solvent treatment. Proper characterization and tuning of processing parameters can aid in rational optimization of perovskite devices. Likewise, gaining a comprehensive understanding of the degradation mechanism and identifying components of the perovskite structure that may be particularly susceptible to attack by moisture are vital to mitigate device degradation under operating conditions. This Account provides insight into the lifecycle of organic–inorganic lead halide perovskites, including (i) the nature of the precursor solution, (ii) formation of solid-state perovskite thin films and single crystals, and (iii) transformation of perovskites into hydrated phases upon exposure to moisture. In particular, spectroscopic and structural characterization techniques shed light on the thermally driven evolution of the perovskite structure. By tuning precursor stoichiometry and chemistry, and thus the lead halide charge-transfer complexes present in solution, crystallization

What is lead-based paint?

International Nuclear Information System (INIS)

Vernon, L.S.

1994-01-01

The number of variety of lead-abatement regulations and requirements make it difficult and confusing to identify and properly respond to dangerous levels of lead in every situation. Definitions of ''lead-based paint'' and three test methods for lead detection are described to help determine when and how to test for the presence of lead

Large Scale Screening of Ethnomedicinal Plants for Identification of Potential Antibacterial Compounds

Directory of Open Access Journals (Sweden)

Sujogya Kumar Panda

2016-03-01

activity. The species listed here were shown to have anti-infective activity against both Gram-positive and Gram-negative bacteria. These results may serve as a guide for selecting plant species that could yield the highest probability of finding promising compounds responsible for the antibacterial activities against a broad spectrum of bacterial species. Further investigation of the phytochemicals from these plants will help to identify the lead compounds for drug discovery.

Large Scale Screening of Ethnomedicinal Plants for Identification of Potential Antibacterial Compounds.

Science.gov (United States)

Panda, Sujogya Kumar; Mohanta, Yugal Kishore; Padhi, Laxmipriya; Park, Young-Hwan; Mohanta, Tapan Kumar; Bae, Hanhong

2016-03-14

listed here were shown to have anti-infective activity against both Gram-positive and Gram-negative bacteria. These results may serve as a guide for selecting plant species that could yield the highest probability of finding promising compounds responsible for the antibacterial activities against a broad spectrum of bacterial species. Further investigation of the phytochemicals from these plants will help to identify the lead compounds for drug discovery.

Organolead compounds shown to be genetically active

Energy Technology Data Exchange (ETDEWEB)

Ahlberg, J; Ramel, C; Wachtmeister, C A

1972-01-01

The purpose of the present investigation was to determine whether alkyllead compounds would cause a genetic effect similar to that caused by alkyl mercury compounds. Experiments were conducted on Allium cepa (onion) in order to determine the effect of lead compounds on the spindle fiber mechanism. Results indicate that disturbances of the spindle fiber mechanism occur even at very low concentrations. The lowest concentration at which such effects are observed seems to be between 10/sup -6/ and 10/sup -7/ M for the organic compounds. Although no effect can be observed on the spindle fibers at lower dosages, the mitotic index is changed even at a dose of 10/sup -7/ M with dimethyllead. A preliminary experiment was made on Drosophila with triethyllead in order to investigate whether the effects which were observed on mitoses in Allium would also be observed in a meiotic cell system in an animal.

Evolution of interstellar organic compounds under asteroidal hydrothermal conditions

Science.gov (United States)

Vinogradoff, V.; Bernard, S.; Le Guillou, C.; Remusat, L.

2018-05-01

Carbonaceous chondrites (CC) contain a diversity of organic compounds. No definitive evidence for a genetic relationship between these complex organic molecules and the simple organic molecules detected in the interstellar medium (ISM) has yet been reported. One of the many difficulties arises from the transformations of organic compounds during accretion and hydrothermal alteration on asteroids. Here, we report results of hydrothermal alteration experiments conducted on a common constituent of interstellar ice analogs, Hexamethylenetetramine (HMT - C6H12N4). We submitted HMT to asteroidal hydrothermal conditions at 150 °C, for various durations (up to 31 days) and under alkaline pH. Organic products were characterized by gas chromatography mass spectrometry, infrared spectroscopy and synchrotron-based X-ray absorption near edge structure spectroscopy. Results show that, within a few days, HMT has evolved into (1) a very diverse suite of soluble compounds dominated by N-bearing aromatic compounds (> 150 species after 31 days), including for instance formamide, pyridine, pyrrole and their polymers (2) an aromatic and N-rich insoluble material that forms after only 7 days of experiment and then remains stable through time. The reaction pathways leading to the soluble compounds likely include HMT dissociation, formose and Maillard-type reactions, e.g. reactions of sugar derivatives with amines. The present study demonstrates that, if interstellar organic compounds such as HMT had been accreted by chondrite parent bodies, they would have undergone chemical transformations during hydrothermal alteration, potentially leading to the formation of high molecular weight insoluble organic molecules. Some of the diversity of soluble and insoluble organic compounds found in CC may thus result from asteroidal hydrothermal alteration.

Lead identification and structure-activity relationships of heteroarylpyrazole arylsulfonamides as allosteric CC-chemokine receptor 4 (CCR4) antagonists.

Science.gov (United States)

Miah, Afjal H; Copley, Royston C B; O'Flynn, Daniel; Percy, Jonathan M; Procopiou, Panayiotis A

2014-03-21

A knowledge-based library of aryl 2,3-dichlorophenylsulfonamides was synthesised and screened as human CCR4 antagonists, in order to identify a suitable hit for the start of a lead-optimisation programme. X-ray diffraction studies were used to identify the pyrazole ring as a moiety that could bring about intramolecular hydrogen bonding with the sulfonamide NH and provide a clip or orthogonal conformation that was believed to be the preferred active conformation. Replacement of the core phenyl ring with a pyridine, and replacement of the 2,3-dichlorobenzenesulfonamide with 5-chlorothiophenesulfonamide provided compound 33 which has excellent physicochemical properties and represents a good starting point for a lead optimisation programme. Electronic structure calculations indicated that the preference for the clip or orthogonal conformation found in the small molecule crystal structures of 7 and 14 was in agreement with the order of potency in the biological assay.

Drawing a different picture with pencil lead as matrix-assisted laser desorption/ionization matrix for fullerene derivatives.

Science.gov (United States)

Nye, Leanne C; Hungerbühler, Hartmut; Drewello, Thomas

2018-02-01

Inspired by reports on the use of pencil lead as a matrix-assisted laser desorption/ionization matrix, paving the way towards matrix-free matrix-assisted laser desorption/ionization, the present investigation evaluates its usage with organic fullerene derivatives. Currently, this class of compounds is best analysed using the electron transfer matrix trans-2-[3-(4-tert-butylphenyl)-2-methyl-2-propenylidene] malononitrile (DCTB), which was employed as the standard here. The suitability of pencil lead was additionally compared to direct (i.e. no matrix) laser desorption/ionization-mass spectrometry. The use of (DCTB) was identified as the by far gentler method, producing spectra with abundant molecular ion signals and much reduced fragmentation. Analytically, pencil lead was found to be ineffective as a matrix, however, appears to be an extremely easy and inexpensive method for producing sodium and potassium adducts.

SDE and SPME Analysis of Flavor Compounds in Jin Xuan Oolong Tea.

Science.gov (United States)

Sheibani, Ershad; Duncan, Susan E; Kuhn, David D; Dietrich, Andrea M; O'Keefe, Sean F

2016-02-01

Simultaneous distillation-extraction (SDE) and solid phase micro extraction (SPME) are procedures used for the isolation of flavor compounds in foods. The purpose of this study was to optimize SDE conditions (solvent and time) and to compare SDE with SPME for the isolation of flavor compounds in Jin Xuan oolong tea using GC-MS and GC-O. The concentration of volatile compounds isolated with diethyl ether was higher (P < 0.05) than for dichloromethane and concentration was higher at 40 min (P < 0.05) than 20 or 60 min extractions. For SDE, 128 volatiles were identified using GC-MS and 45 aroma active compounds using GC-O. Trans-nerolidol was the most abundant compound in oolong tea. The number of volatiles identified using GC-MS was lower in SPME than SDE. For SPME, 59 volatiles and 41 aroma active compounds were identified. The composition of the volatiles isolated by the 2 methods differed considerably but provided complementary information. © 2016 Institute of Food Technologists®

Spontaneous magnetoelastic effects in gadolinium compounds

International Nuclear Information System (INIS)

Lindbaum, A.; Rotter, M.

2002-01-01

Full text: This poster is a short summary of a recently published handbook chapter, where the spontaneous magnetoelastic effects in Gd compounds are reviewed showing that the strain dependence of the magnetic exchange interactions leads to significant effects. These effects are equal in magnitude to well established single ion contributions in other rare earth compounds with non vanishing orbital momentum (coming from the strain dependence of the crystal field). In some cases the exchange contribution can produce giant magnetostriction (GMS) or induce structural phase transitions. In order to extract the influence of the Gd- Gd exchange interactions, we consider only Gd compounds with partner elements showing no or only weak induced magnetic moments. The current status of the theory is presented and compared to measurements performed by temperature dependent x-ray diffraction and results of dilatometric measurements. (author)

Substituted 2-Phenyl-Imidazopyridines: A New Class of Drug Leads for Human African Trypanosomiasis

Science.gov (United States)

Tatipaka, Hari Babu; Gillespie, J. Robert; Chatterjee, Arnab K.; Norcross, Neil R.; Hulverson, Matthew A.; Ranade, Ranae M.; Nagendar, Pendem; Creason, Sharon A.; McQueen, Joshua; Duster, Nicole A.; Nagle, Advait; Supek, Frantisek; Molteni, Valentina; Wenzler, Tanja; Brun, Reto; Glynne, Richard; Buckner, Frederick S.; Gelb, Michael H.

2014-01-01

A phenotypic screen of a compound library for antiparasitic activity on Trypanosoma brucei, the causative agent of human African trypanosomiasis, led to the identification of substituted 2-(3-aminophenyl) oxazolopyridines as a starting point for hit-to-lead medicinal chemistry. A total of 110 analogues were prepared, which led to the identification of 64, a substituted 2-(3-aminophenyl) imidazopyridine. This compound showed antiparasitic activity in vitro with an EC50 of 2 nM and displayed reasonable drug-like properties when tested in a number of in vitro assays. The compound was orally bioavailable and displayed good plasma and brain exposure in mice. Compound 64 cured mice infected with Trypanosoma brucei when dosed orally down to 2.5 mg/kg. Given its potent anti-parasitic properties and its ease of synthesis, compound 64 represents a new lead for the development of drugs to treat human African trypanosomiasis. PMID:24354316

Genotoxicity of two heavy metal compounds: lead nitrate and cobalt chloride in Polychaete Perinereis cultrifera.

Science.gov (United States)

Singh, Nisha; Bhagat, Jacky; Ingole, Baban S

2017-07-01

The present study explores the in vivo and in vitro genotoxic effects of lead nitrate, [Pb(NO 3 ) 2 ] a recognized environmental pollutant and cobalt chloride (CoCl 2 ), an emerging environmental pollutant in polychaete Perinereis cultrifera using comet assay. Despite widespread occurrence and extensive industrial applications, no previous published reports on genotoxicity of these compounds are available in polychaete as detected by comet assay. Polychaetes were exposed in vivo to Pb(NO 3 ) 2 (0, 100, 500, and 1000 μg/l) and CoCl 2 (0, 100, 300, and 500 μg/l) for 5 days. At 100 μg/l Pb(NO 3 ) 2 concentration, tail DNA (TDNA) values in coelomocytes were increase by 1.16, 1.43, and 1.55-fold after day 1, day 3, and day 5, whereas, OTM showed 1.12, 2.33, and 2.10-fold increase in in vivo. Pb(NO 3 ) 2 showed a concentration and time-dependent genotoxicity whereas CoCl 2 showed a concentration-dependent genotoxicity in in vivo. A concentration-dependent increase in DNA damage was observed in in vitro studies for Pb(NO 3 ) 2 and CoCl 2 . DNA damage at 500 μg/L showed almost threefold increase in TDNA and approximately fourfold increase in OTM as compared to control in in vitro. Our studies suggest that Pb(NO 3 ) 2 and CoCl 2 have potential to cause genotoxic damage, with Pb(NO 3 ) 2 being more genotoxic in polychaete and should be used more carefully in industrial and other activities. Graphical abstract.

Automated Lead Optimization of MMP-12 Inhibitors Using a Genetic Algorithm.

Science.gov (United States)

Pickett, Stephen D; Green, Darren V S; Hunt, David L; Pardoe, David A; Hughes, Ian

2011-01-13

Traditional lead optimization projects involve long synthesis and testing cycles, favoring extensive structure-activity relationship (SAR) analysis and molecular design steps, in an attempt to limit the number of cycles that a project must run to optimize a development candidate. Microfluidic-based chemistry and biology platforms, with cycle times of minutes rather than weeks, lend themselves to unattended autonomous operation. The bottleneck in the lead optimization process is therefore shifted from synthesis or test to SAR analysis and design. As such, the way is open to an algorithm-directed process, without the need for detailed user data analysis. Here, we present results of two synthesis and screening experiments, undertaken using traditional methodology, to validate a genetic algorithm optimization process for future application to a microfluidic system. The algorithm has several novel features that are important for the intended application. For example, it is robust to missing data and can suggest compounds for retest to ensure reliability of optimization. The algorithm is first validated on a retrospective analysis of an in-house library embedded in a larger virtual array of presumed inactive compounds. In a second, prospective experiment with MMP-12 as the target protein, 140 compounds are submitted for synthesis over 10 cycles of optimization. Comparison is made to the results from the full combinatorial library that was synthesized manually and tested independently. The results show that compounds selected by the algorithm are heavily biased toward the more active regions of the library, while the algorithm is robust to both missing data (compounds where synthesis failed) and inactive compounds. This publication places the full combinatorial library and biological data into the public domain with the intention of advancing research into algorithm-directed lead optimization methods.

Review and research analysis of computational target methods using BioRuby and in silico screening of herbal lead compounds against pancreatic cancer using R programming.

Science.gov (United States)

Jayadeepa, R M; Ray, Ankita; Naik, Dhaval; Sanyal, Debendra Nath; Shah, Disha

2014-01-01

Plants and their natural components sophisticated with the cornerstone of traditional conventional medicinal system throughout the globe for many years and extend to furnish mankind with latest remedies. Natural Products act as lead molecules for the synthesis of various potent drugs. In the current research a study is conducted on herbal small molecule and their potential binding chemical affinity to the effect or molecules of major diseases such as pancreatic cancer. Clinical studies demonstrate correlation between Cyclin- Dependent Kinase 4 (CDK4) and malignant progression of Pancreatic Cancer. Using Bioruby Gem's we were able to analyze better characteristics of the target protein. VegaZZ and NAMD were used to minimize the energy of the target protein. Therefore identification of effective, well- tolerated targets was analyzed. Further the target protein was subjected to docking with the anti cancer inhibitors which represents a rational chemo preventive strategy using AutoDock Vina. Later using the dock score top ranked phytochemicals were analyzed for Toxicity Analysis. Using the BioRuby gem we were able to measure the distance between the amino acid. Various R scripting libraries were used to hunt the best leads, as in this case the phytochemicals. Phytochemicals such as Wedelolactones and Catechin were analyzed computationally. This study has presented the various effects of naturally occurring anti pancreatic cancer compounds Catechin, Wedelolactones that inhibits Cyclin Dependent Kinase 4. The study results reveal that compounds use less binding energy to CDK4 and inhibit its activity. Future investigation of other various wet lab studies such as cell line studies will confirm results of these two herbal chemical formulations potential ones for treating Pancreatic Cancer.

Organic compounds in radiation fogs in Davis (California)

Science.gov (United States)

Herckes, Pierre; Hannigan, Michael P.; Trenary, Laurie; Lee, Taehyoung; Collett, Jeffrey L.

New stainless steel active fogwater collectors were designed and used in Davis (CA, USA) to collect fogwater for the speciation of organic matter. Organic compounds in fog samples were extracted by liquid-liquid extraction and analyzed by gas chromatography coupled to mass spectrometry. Numerous organic compounds, including various alkanes, polycyclic aromatic hydrocarbons (PAH) and alkanoic acids, have been identified in the fogwater samples. Higher molecular weight (MW) compounds are preferentially associated with an insoluble phase inside the fog drops, whereas lower molecular weight and more polar compounds are found predominantly in the dissolved phase. Concentrations in the dissolved phase were sometimes much higher than estimated by the compounds' aqueous solubilities.

Harmonic force field for nitro compounds.

Science.gov (United States)

Bellido, Edson P; Seminario, Jorge M

2012-06-01

Molecular simulations leading to sensors for the detection of explosive compounds require force field parameters that can reproduce the mechanical and vibrational properties of energetic materials. We developed precise harmonic force fields for alanine polypeptides and glycine oligopeptides using the FUERZA procedure that uses the Hessian tensor (obtained from ab initio calculations) to calculate precise parameters. In this work, we used the same procedure to calculate generalized force field parameters of several nitro compounds. We found a linear relationship between force constant and bond distance. The average angle in the nitro compounds was 116°, excluding the 90° angle of the carbon atoms in the octanitrocubane. The calculated parameters permitted the accurate molecular modeling of nitro compounds containing many functional groups. Results were acceptable when compared with others obtained using methods that are specific for one type of molecule, and much better than others obtained using methods that are too general (these ignore the chemical effects of surrounding atoms on the bonding and therefore the bond strength, which affects the mechanical and vibrational properties of the whole molecule).

Aroma volatile compounds from two fresh pineapple varieties in China.

Science.gov (United States)

Zheng, Liang-Yong; Sun, Guang-Ming; Liu, Yu-Ge; Lv, Ling-Ling; Yang, Wen-Xiu; Zhao, Wei-Feng; Wei, Chang-Bin

2012-01-01

Volatile compounds from two pineapples varieties (Tainong No.4 and No.6) were isolated by headspace solid phase microextraction (HS-SPME) and identified and quantified by gas chromatography-mass spectrometry (GC/MS). In the Tainong No. 4 and No. 6 pineapples, a total of 11 and 28 volatile compounds were identified according to their retention time on capillary columns and their mass spectra, and quantified with total concentrations of 1080.44 μg·kg(-1) and 380.66 μg·kg(-1) in the Tainong No.4 and No. 6 pineapples, respectively. The odor active values (OAVs) of volatile compounds from pineapples were also calculated. According to the OAVs, four compounds were defined as the characteristic aroma compounds for the Tainong No. 4 pineapple, including furaneol, 3-(methylthio)propanoic acid methyl ester, 3-(methylthio)propanoic acid ethyl ester and δ-octalactone. The OAVs of five compounds including ethyl-2-methylbutyrate, methyl-2-methylbutyrate, 3-(methylthio)propanoic acid ethyl ester, ethyl hexanoate and decanal were considered to be the characteristic aroma compounds for the Tainong No. 6 pineapple.

Aroma Volatile Compounds from Two Fresh Pineapple Varieties in China

Directory of Open Access Journals (Sweden)

Chang-Bin Wei

2012-06-01

Full Text Available Volatile compounds from two pineapples varieties (Tainong No.4 and No.6 were isolated by headspace solid phase microextraction (HS-SPME and identified and quantified by gas chromatography-mass spectrometry (GC/MS. In the Tainong No. 4 and No. 6 pineapples, a total of 11 and 28 volatile compounds were identified according to their retention time on capillary columns and their mass spectra, and quantified with total concentrations of 1080.44 µg·kg⁻¹ and 380.66 µg·kg⁻¹ in the Tainong No.4 and No. 6 pineapples, respectively. The odor active values (OAVs of volatile compounds from pineapples were also calculated. According to the OAVs, four compounds were defined as the characteristic aroma compounds for the Tainong No. 4 pineapple, including furaneol, 3-(methylthiopropanoic acid methyl ester, 3-(methylthiopropanoic acid ethyl ester and δ-octalactone. The OAVs of five compounds including ethyl-2-methylbutyrate, methyl-2-methylbutyrate, 3-(methylthiopropanoic acid ethyl ester, ethyl hexanoate and decanal were considered to be the characteristic aroma compounds for the Tainong No. 6 pineapple.

Aroma Volatile Compounds from Two Fresh Pineapple Varieties in China

Science.gov (United States)

Zheng, Liang-Yong; Sun, Guang-Ming; Liu, Yu-Ge; Lv, Ling-Ling; Yang, Wen-Xiu; Zhao, Wei-Feng; Wei, Chang-Bin

2012-01-01

Volatile compounds from two pineapples varieties (Tainong No.4 and No.6) were isolated by headspace solid phase microextraction (HS-SPME) and identified and quantified by gas chromatography-mass spectrometry (GC/MS). In the Tainong No. 4 and No. 6 pineapples, a total of 11 and 28 volatile compounds were identified according to their retention time on capillary columns and their mass spectra, and quantified with total concentrations of 1080.44 μg·kg−1 and 380.66 μg·kg−1 in the Tainong No.4 and No. 6 pineapples, respectively. The odor active values (OAVs) of volatile compounds from pineapples were also calculated. According to the OAVs, four compounds were defined as the characteristic aroma compounds for the Tainong No. 4 pineapple, including furaneol, 3-(methylthio)propanoic acid methyl ester, 3-(methylthio)propanoic acid ethyl ester and δ-octalactone. The OAVs of five compounds including ethyl-2-methylbutyrate, methyl-2-methylbutyrate, 3-(methylthio)propanoic acid ethyl ester, ethyl hexanoate and decanal were considered to be the characteristic aroma compounds for the Tainong No. 6 pineapple. PMID:22837701

Identifying problematic drugs based on the characteristics of their targets.

Science.gov (United States)

Lopes, Tiago J S; Shoemaker, Jason E; Matsuoka, Yukiko; Kawaoka, Yoshihiro; Kitano, Hiroaki

2015-01-01

Identifying promising compounds during the early stages of drug development is a major challenge for both academia and the pharmaceutical industry. The difficulties are even more pronounced when we consider multi-target pharmacology, where the compounds often target more than one protein, or multiple compounds are used together. Here, we address this problem by using machine learning and network analysis to process sequence and interaction data from human proteins to identify promising compounds. We used this strategy to identify properties that make certain proteins more likely to cause harmful effects when targeted; such proteins usually have domains commonly found throughout the human proteome. Additionally, since currently marketed drugs hit multiple targets simultaneously, we combined the information from individual proteins to devise a score that quantifies the likelihood of a compound being harmful to humans. This approach enabled us to distinguish between approved and problematic drugs with an accuracy of 60-70%. Moreover, our approach can be applied as soon as candidate drugs are available, as demonstrated with predictions for more than 5000 experimental drugs. These resources are available at http://sourceforge.net/projects/psin/.

Identifying problematic drugs based on the characteristics of their targets

Directory of Open Access Journals (Sweden)

Tiago Jose eDa Silva Lopes

2015-09-01

Full Text Available Identifying promising compounds during the early stages of drug development is a major challenge for both academia and the pharmaceutical industry. The difficulties are even more pronounced when we consider multi-target pharmacology, where the compounds often target more than one protein, or multiple compounds are used together. Here, we address this problem by using machine learning and network analysis to process sequence and interaction data from human proteins to identify promising compounds. We used this strategy to identify properties that make certain proteins more likely to cause harmful effects when targeted; such proteins usually have domains commonly found throughout the human proteome. Additionally, since currently marketed drugs hit multiple targets simultaneously, we combined the information from individual proteins to devise a score that quantifies the likelihood of a compound being harmful to humans. This approach enabled us to distinguish between approved and problematic drugs with an accuracy of 60%¬–70%. Moreover, our approach can be applied as soon as candidate drugs are available, as demonstrated with predictions for more than 5000 experimental drugs. These resources are available at http://sourceforge.net/projects/psin/.

Determination of arsenic compounds in earthworms

Energy Technology Data Exchange (ETDEWEB)

Geiszinger, A.; Goessler, W.; Kuehnelt, D.; Kosmus, W. [Karl-Franzens-Univ., Graz (Austria). Inst. for Analytical Chemistry; Francesconi, K. [Odense Univ. (Denmark). Inst. of Biology

1998-08-01

Earthworms and soil collected from six sites in Styria, Austria, were investigated for total arsenic concentrations by ICP-MS and for arsenic compounds by HPLC-ICP-MS. Total arsenic concentrations ranged from 3.2 to 17.9 mg/kg dry weight in the worms and from 5.0 to 79.7 mg/kg dry weight in the soil samples. There was no strict correlation between the total arsenic concentrations in the worms and soil. Arsenic compounds were extracted from soil and a freeze-dried earthworm sample with a methanol/water mixture (9:1, v/v). The extracts were evaporated to dryness, redissolved in water, and chromatographed on an anion- and a cation-exchange column. Arsenic compounds were identified by comparison of the retention times with known standards. Only traces of arsenic acid could be extracted from the soil with the methanol/water (9:1, v/v) mixture. The major arsenic compounds detected in the extracts of the earthworms were arsenous acid and arsenic acid. Arsenobetaine was present as a minor constituent, and traces of dimethylarsinic acid were also detected. Two dimethylarsinoyltribosides were also identified in the extracts by co-chromatography with standard compounds. This is the first report of the presence of dimethylarsinoylribosides in a terrestrial organism. Two other minor arsenic species were present in the extract, but their retention times did not match with the retention times of the available standards.

Lead identification of benzimidazolone and azabenzimidazolone arylsulfonamides as CC-chemokine receptor 4 (CCR4) antagonists.

Science.gov (United States)

Miah, Afjal H; Abas, Hossay; Begg, Malcolm; Marsh, Benjamin J; O'Flynn, Daniel E; Ford, Alison J; Percy, Jonathan M; Procopiou, Panayiotis A; Richards, Steve A; Rumley, Sally-Anne

2014-08-01

A knowledge-based library of 2,3-dichlorophenylsulfonyl derivatives of commercially available aryl amines was synthesised and screened as human CCR4 antagonists, in order to identify a suitable hit for the start of a lead-optimisation programme. Hits were required to be more potent than an existing indazole series, have better physicochemical properties (clogP 116 μg/mL), and be stable to acid and light. The benzimidazol-2-one core was identified as a hit suitable for further investigation. Substitution at N1 with small alkyl groups was tolerated; however, these analogues were inactive in the whole blood assay (pA₂ <5). Azabenzimidazolone analogues were all found to be active, with compound 38 exhibiting whole blood activity of 6.1, low molecular weight (389) and chrom logD₇.₄ (2.4), high LE (0.43), and solubility (152 μg/mL). In addition, 38 had human serum albumin binding of around 93% and met all the criteria for progression to lead optimisation. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Environmental lead poisoning from lead-glazed earthenware used for storing drinks].

Science.gov (United States)

Sabouraud, S; Coppéré, B; Rousseau, C; Testud, F; Pulce, C; Tholly, F; Blanc, M; Culoma, F; Facchin, A; Ninet, J; Chambon, P; Medina, B; Descotes, J

2009-12-01

Current unusual environmental sources of lead exposure mainly include traditional medicines, either ayurvedic remedies or others, traditional cosmetics (kohl, surma), and the use of traditional earthenware, for storage or cooking. We report two cases of lead poisoning in adults initially identified by paroxysmal abdominal pain or anemia. In both cases, the environmental investigation evidenced one main source of lead exposure, namely a lead-glazed earthenware jug in which a drink was stored, "kefir" in the first case, and "kombucha" tea in the second one. It is recommended to search for lead intoxication in patients with unexplained anemia. Environmental sources of lead can be multiple. Their relative importance has to be ranked during the environmental investigation and among these, lead-glazed earthenware must be considered as a source of high lead exposure when drinks are stored inside and thus can soak.

Lead optimization of a pyridine-carboxamide series as DGAT-1 inhibitors.

Science.gov (United States)

Ting, Pauline C; Lee, Joe F; Zorn, Nicolas; Kim, Hyunjin M; Aslanian, Robert G; Lin, Mingxiang; Smith, Michelle; Walker, Scott S; Cook, John; Van Heek, Margaret; Lachowicz, Jean

2013-02-15

The structure-activity relationship studies of a novel series of carboxylic acid derivatives of pyridine-carboxamides as DGAT-1 inhibitors is described. The optimization of the initial lead compound 6 based on in vitro and in vivo activity led to the discovery of key compounds 10j and 17h. Copyright © 2013 Elsevier Ltd. All rights reserved.

Protective role of flaxseed oil against lead acetate induced oxidative ...

African Journals Online (AJOL)

Even though the toxic effects of lead compounds had been studied over many years, inconsistent results have been obtained about their oxidative stress in the testes of adult rats. Lead acetate (20 mg/kg) alters the histology of testes as well as enhances lipid peroxidation and nitric oxide production in both serum and testes ...

Bioprospecting Sponge-Associated Microbes for Antimicrobial Compounds.

Science.gov (United States)

Indraningrat, Anak Agung Gede; Smidt, Hauke; Sipkema, Detmer

2016-05-02

Sponges are the most prolific marine organisms with respect to their arsenal of bioactive compounds including antimicrobials. However, the majority of these substances are probably not produced by the sponge itself, but rather by bacteria or fungi that are associated with their host. This review for the first time provides a comprehensive overview of antimicrobial compounds that are known to be produced by sponge-associated microbes. We discuss the current state-of-the-art by grouping the bioactive compounds produced by sponge-associated microorganisms in four categories: antiviral, antibacterial, antifungal and antiprotozoal compounds. Based on in vitro activity tests, identified targets of potent antimicrobial substances derived from sponge-associated microbes include: human immunodeficiency virus 1 (HIV-1) (2-undecyl-4-quinolone, sorbicillactone A and chartarutine B); influenza A (H1N1) virus (truncateol M); nosocomial Gram positive bacteria (thiopeptide YM-266183, YM-266184, mayamycin and kocurin); Escherichia coli (sydonic acid), Chlamydia trachomatis (naphthacene glycoside SF2446A2); Plasmodium spp. (manzamine A and quinolone 1); Leishmania donovani (manzamine A and valinomycin); Trypanosoma brucei (valinomycin and staurosporine); Candida albicans and dermatophytic fungi (saadamycin, 5,7-dimethoxy-4-p-methoxylphenylcoumarin and YM-202204). Thirty-five bacterial and 12 fungal genera associated with sponges that produce antimicrobials were identified, with Streptomyces, Pseudovibrio, Bacillus, Aspergillus and Penicillium as the prominent producers of antimicrobial compounds. Furthemore culture-independent approaches to more comprehensively exploit the genetic richness of antimicrobial compound-producing pathways from sponge-associated bacteria are addressed.

Role of A-site Ca and B-site Zr substitution in BaTiO3 lead-free compounds: Combined experimental and first principles density functional theoretical studies

Science.gov (United States)

Keswani, Bhavna C.; Saraf, Deepashri; Patil, S. I.; Kshirsagar, Anjali; James, A. R.; Kolekar, Y. D.; Ramana, C. V.

2018-05-01

We report on the combined experimental and theoretical simulation results of lead-free ferroelectrics, Ba(1-x)CaxTiO3 (x = 0.0-0.3) and BaTi(1-y)ZryO3 (y = 0.0-0.2), synthesized by standard solid state reaction method. First principles density functional calculations are used to investigate the electronic structure, dynamical charges, and spontaneous polarization of these compounds. In addition, the structural, ferroelectric, piezoelectric, and dielectric properties are studied using extensive experiments. The X-ray diffraction and temperature dependent Raman spectroscopy studies indicate that the calcium (Ca) substituted compositions exhibit a single phase crystal structure, while zirconium (Zr) substituted compositions are biphasic. The scanning electron micrographs reveal the uniform and highly dense microstructure. The presence of polarization-electric field and strain-electric field hysteresis loops confirms the ferroelectric and piezoelectric nature of all the compositions. Our results demonstrate higher values for polarization, percentage strain, piezoelectric coefficients, and electrostrictive coefficient compared to those existing in the literature. For smaller substitutions of Ca and Zr in BaTiO3, a direct piezoelectric coefficient (d33) is enhanced, while the highest d33 value (˜300 pC/N) is observed for BaTi0.96Zr0.04O3 due to the biphasic ferroelectric behavior. Calculation of Born effective charges indicates that doping with Ca or Zr increases the dynamical charges on Ti as well as on O and decreases the dynamical charge on Ba. An increase in the dynamical charges on Ti and O is ascribed to the increase in covalency of Ti-O bond that reduces the polarizability of the crystal. A broader range of temperatures is demonstrated to realize the stable phase in the Ca substituted compounds. The results indicate enhancement in the temperature range of applicability of these compounds for device applications. The combined theoretical and experimental study is

Immobilization of N-Heterocyclic Carbene Compounds: A Synthetic Perspective.

Science.gov (United States)

Zhong, Rui; Lindhorst, Anja C; Groche, Florian J; Kühn, Fritz E

2017-02-08

Over the course of the past 15 years the success story of N-heterocyclic carbene (NHC) compounds in organic, inorganic, and organometallic chemistry has been extended to another dimension. The immobilization of NHC compounds, undergoing continuous diversification, broadens their range of applications and leads to new solutions for challenges in catalytic and synthetic chemistry. This review intends to present a synthetic toolkit for the immobilization of NHC compounds, giving the reader an overview on synthetic techniques and strategies available in the literature. By individually summarizing and assessing the synthetic steps of the immobilization process, a comprehensive picture of the strategies and methodologies for the immobilization of NHC compounds is presented. Furthermore, the characterization of supported NHC compounds is discussed in detail in order to set up necessary criteria for an in-depth analysis of the immobilized derivatives. Finally, the catalytic applications of immobilized NHC compounds are briefly reviewed to illustrate the practical use of this technique for a broad variety of reaction types.

A Multiplexed Assay That Monitors Effects of Multiple Compound Treatment Times Reveals Candidate Immune-Enhancing Compounds.

Science.gov (United States)

Zhao, Ziyan; Henowitz, Liza; Zweifach, Adam

2018-05-01

We previously developed a flow cytometry assay that monitored lytic granule exocytosis in cytotoxic T lymphocytes stimulated by contacting beads coated with activating anti-CD3 antibodies. That assay was multiplexed in that responses of cells that did or did not receive the activating stimulus were distinguished via changes in light scatter accompanying binding of cells to beads, allowing us to discriminate compounds that activate responses on their own from compounds that enhance responses in cells that received the activating stimulus, all within a single sample. Here we add a second dimension of multiplexing by developing means to assess in a single sample the effects of treating cells with test compounds for different times. Bar-coding cells before adding them to test wells lets us determine compound treatment time while also monitoring activation status and response amplitude at the point of interrogation. This multiplexed assay is suitable for screening 96-well plates. We used it to screen compounds from the National Cancer Institute, identifying several compounds that enhance anti-LAMP1 responses. Multiple-treatment-time (MTT) screening enabled by bar-coding and read via high-throughput flow cytometry may be a generally useful method for facilitating the discovery of compounds of interest.

Biogenic volatile organic compounds in the Earth system.

Science.gov (United States)

Laothawornkitkul, Jullada; Taylor, Jane E; Paul, Nigel D; Hewitt, C Nicholas

2009-01-01

Biogenic volatile organic compounds produced by plants are involved in plant growth, development, reproduction and defence. They also function as communication media within plant communities, between plants and between plants and insects. Because of the high chemical reactivity of many of these compounds, coupled with their large mass emission rates from vegetation into the atmosphere, they have significant effects on the chemical composition and physical characteristics of the atmosphere. Hence, biogenic volatile organic compounds mediate the relationship between the biosphere and the atmosphere. Alteration of this relationship by anthropogenically driven changes to the environment, including global climate change, may perturb these interactions and may lead to adverse and hard-to-predict consequences for the Earth system.

Early prosthetic aortic valve infection identified with the use of positron emission tomography in a patient with lead endocarditis.

Science.gov (United States)

Amraoui, Sana; Tlili, Ghoufrane; Sohal, Manav; Bordenave, Laurence; Bordachar, Pierre

2016-12-01

18-Fluorodeoxyglucose positron emission tomography/computerized tomography (FDG PET/CT) scanning has recently been proposed as a diagnostic tool for lead endocarditis (LE). FDG PET/CT might be also useful to localize associated septic emboli in patients with LE. We report an interesting case of a LE patient with a prosthetic aortic valve in whom a trans-esophageal echocardiogram did not show associated aortic endocarditis. FDG PET/CT revealed prosthetic aortic valve infection. A second TEE performed 2 weeks after identified aortic vegetation. A longer duration of antimicrobial therapy with serial follow-up echocardiography was initiated. There was also increased uptake in the sigmoid colon, corresponding to focal polyps resected during a colonoscopy. FDG PET/CT scanning seems to be highly sensitive for prosthetic aortic valve endocarditis diagnosis. This promising diagnostic tool may be beneficial in LE patients, by identifying septic emboli and potential sites of pathogen entry.

Fast Screening of Antibacterial Compounds from Fusaria

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Teis Esben Sondergaard

2016-11-01

Full Text Available Bio-guided screening is an important method to identify bioactive compounds from fungi. In this study we applied a fast digital time-lapse microscopic method for assessment of the antibacterial properties of secondary metabolites from the fungal genus Fusarium. Here antibacterial effects could be detected for antibiotic Y, aurofusarin, beauvericin, enniatins and fusaric acid after six hours of cultivation. The system was then used in a bio-guided screen of extracts from 14 different Fusarium species, which had been fractionated by HPLC. In this screen, fractions containing the red pigments aurofusarin and bikaverin showed effects against strains of Lactobacillus and Bifidobacterium. The IC50 for aurofusarin against Lactobacillus acidophilus was 8 µM, and against Bifidobacterium breve it was 64 µM. Aurofusarin only showed an effect on probiotic bacteria, leading to the speculation that only health-promoting bacteria with a positive effect in the gut system are affected.

Oxygen stabilized rare-earth iron intermetallic compounds

International Nuclear Information System (INIS)

Dariel, M.P.; Malekzadeh, M.; Pickus, M.R.

1975-10-01

A new, oxygen-stabilized intermetallic compound was identified in sintered, pre-alloyed rare-earth iron powder samples. Its composition corresponds to formula R 12 Fe 32 O 2 and its crystal structure belongs to space group Im3m. The presence of these compounds was observed, so far, in several R--Fe--O systems, with R = Gd, Tb, Dy, Ho, Er, and Y

Lead-Binding Proteins: A Review

Directory of Open Access Journals (Sweden)

Harvey C. Gonick

2011-01-01

Full Text Available Lead-binding proteins are a series of low molecular weight proteins, analogous to metallothionein, which segregate lead in a nontoxic form in several organs (kidney, brain, lung, liver, erythrocyte. Whether the lead-binding proteins in every organ are identical or different remains to be determined. In the erythrocyte, delta-aminolevulinic acid dehydratase (ALAD isoforms have commanded the greatest attention as proteins and enzymes that are both inhibitable and inducible by lead. ALAD-2, although it binds lead to a greater degree than ALAD-1, appears to bind lead in a less toxic form. What may be of greater significance is that a low molecular weight lead-binding protein, approximately 10 kDa, appears in the erythrocyte once blood lead exceeds 39 μg/dL and eventually surpasses the lead-binding capacity of ALAD. In brain and kidney of environmentally exposed humans and animals, a cytoplasmic lead-binding protein has been identified as thymosin β4, a 5 kDa protein. In kidney, but not brain, another lead-binding protein has been identified as acyl-CoA binding protein, a 9 kDa protein. Each of these proteins, when coincubated with liver ALAD and titrated with lead, diminishes the inhibition of ALAD by lead, verifying their ability to segregate lead in a nontoxic form.

Interfacial photochemistry of biogenic surfactants: a major source of abiotic volatile organic compounds.

Science.gov (United States)

Brüggemann, Martin; Hayeck, Nathalie; Bonnineau, Chloé; Pesce, Stéphane; Alpert, Peter A; Perrier, Sébastien; Zuth, Christoph; Hoffmann, Thorsten; Chen, Jianmin; George, Christian

2017-08-24

Films of biogenic compounds exposed to the atmosphere are ubiquitously found on the surfaces of cloud droplets, aerosol particles, buildings, plants, soils and the ocean. These air/water interfaces host countless amphiphilic compounds concentrated there with respect to in bulk water, leading to a unique chemical environment. Here, photochemical processes at the air/water interface of biofilm-containing solutions were studied, demonstrating abiotic VOC production from authentic biogenic surfactants under ambient conditions. Using a combination of online-APCI-HRMS and PTR-ToF-MS, unsaturated and functionalized VOCs were identified and quantified, giving emission fluxes comparable to previous field and laboratory observations. Interestingly, VOC fluxes increased with the decay of microbial cells in the samples, indicating that cell lysis due to cell death was the main source for surfactants and VOC production. In particular, irradiation of samples containing solely biofilm cells without matrix components exhibited the strongest VOC production upon irradiation. In agreement with previous studies, LC-MS measurements of the liquid phase suggested the presence of fatty acids and known photosensitizers, possibly inducing the observed VOC production via peroxy radical chemistry. Up to now, such VOC emissions were directly accounted to high biological activity in surface waters. However, the results obtained suggest that abiotic photochemistry can lead to similar emissions into the atmosphere, especially in less biologically-active regions. Furthermore, chamber experiments suggest that oxidation (O 3 /OH radicals) of the photochemically-produced VOCs leads to aerosol formation and growth, possibly affecting atmospheric chemistry and climate-related processes, such as cloud formation or the Earth's radiation budget.

Techniques for Analysis of Plant Phenolic Compounds

Directory of Open Access Journals (Sweden)

Thomas H. Roberts

2013-02-01

Full Text Available Phenolic compounds are well-known phytochemicals found in all plants. They consist of simple phenols, benzoic and cinnamic acid, coumarins, tannins, lignins, lignans and flavonoids. Substantial developments in research focused on the extraction, identification and quantification of phenolic compounds as medicinal and/or dietary molecules have occurred over the last 25 years. Organic solvent extraction is the main method used to extract phenolics. Chemical procedures are used to detect the presence of total phenolics, while spectrophotometric and chromatographic techniques are utilized to identify and quantify individual phenolic compounds. This review addresses the application of different methodologies utilized in the analysis of phenolic compounds in plant-based products, including recent technical developments in the quantification of phenolics.

Methylene-Cycloalkylacetate (MCA) Scaffold-Based Compounds as Novel Neurotropic Agents.

Science.gov (United States)

Lankri, David; Haham, Dikla; Lahiani, Adi; Lazarovici, Philip; Tsvelikhovsky, Dmitry

2018-04-18

One of the main symptoms in degenerative diseases is death of neuronal cell followed by the loss of neuronal pathways. In neuronal cultures, neurite outgrowths are cell sprouts capable of transforming into either axons or dendrites, to further form functional neuronal synaptic connections. Such connections have an important role in brain cognition, neuronal plasticity, neuronal survival, and regeneration. Therefore, drugs that stimulate neurite outgrowth may be found beneficial in ameliorating neural degeneration. Here, we establish the existence of a unique family of methylene-cycloalkylacetate-based molecules (MCAs) that interface with neuronal cell properties and operate as acceptable pharmacophores for a novel neurotropic (neurite outgrowth inducing) lead compounds. Using an established PC12 cell bioassay, we investigated the neurotropic effect of methylene-cycloalkylacetate compounds by comparison to NGF, a known neurotropic factor. Micrographs of the cells were collected by using a light microscope camera, and digitized photographs were analyzed for compound-induced neurotropic activity using an NIH image protocol. The results indicate that the alkene element, integrated within the cycloalkylacetate core, is indispensable for neurotropic activity. The discovered lead compounds need further mechanistic investigation and may be improved toward development of a neurotropic drug.

Antiplasmodial and larvicidal compounds of Toddalia asiatica root ...

Indian Academy of Sciences (India)

From the -hexane, ethyl acetate and methanol extracts of Toddalia asiatica root bark were isolated eight compounds (1-8) which were identified on the basis of both spectroscopic and physical data as well as comparison with already published results. The crude extracts and isolated compounds showed moderate in vitro ...

Materials Chemistry and Performance of Silicone-Based Replicating Compounds.

Energy Technology Data Exchange (ETDEWEB)

Brumbach, Michael T.; Mirabal, Alex James; Kalan, Michael; Trujillo, Ana B; Hale, Kevin

2014-11-01

Replicating compounds are used to cast reproductions of surface features on a variety of materials. Replicas allow for quantitative measurements and recordkeeping on parts that may otherwise be difficult to measure or maintain. In this study, the chemistry and replicating capability of several replicating compounds was investigated. Additionally, the residue remaining on material surfaces upon removal of replicas was quantified. Cleaning practices were tested for several different replicating compounds. For all replicating compounds investigated, a thin silicone residue was left by the replica. For some compounds, additional inorganic species could be identified in the residue. Simple solvent cleaning could remove some residue.

Electrical properties of a novel lead alkoxide precursor: Lead glycolate

International Nuclear Information System (INIS)

Tangboriboon, Nuchnapa; Pakdeewanishsukho, Kittikhun; Jamieson, Alexander; Sirivat, Anuvat; Wongkasemjit, Sujitra

2006-01-01

The reaction of lead acetate trihydrate Pb(CH 3 COO) 2 .3H 2 O and ethylene glycol, using triethylenetetramine (TETA) as a catalyst, provides in one step access to a polymer-like precursor of lead glycolate [-PbOCH 2 CH 2 O-]. On the basis of high-resolution mass spectroscopy, chemical analysis composition, FTIR, 13 C-solid state NMR and TGA, the lead glycolate precursor can be identified as a trimer structure. The FTIR spectrum demonstrates the characteristics of lead glycolate; the peaks at 1086 and 1042 cm -1 can be assigned to the C-O-Pb stretchings. The 13 C-solid state NMR spectrum gives notably only one peak at 68.639 ppm belonging to the ethylene glycol ligand. The phase transformations of lead glycolate and lead acetate trihydrate to lead oxide, their microstructures, and electrical properties were found to vary with increasing temperature. The lead glycolate precursor has superior electrical properties relative to those of lead acetate trihydrate, suggesting that the lead glycolate precursor can possibly be used as a starting material for producing electrical and semiconducting ceramics, viz. ferroelectric, anti-ferroelectric, and piezoelectric materials

Trehalose upregulates progranulin expression in human and mouse models of GRN haploinsufficiency: a novel therapeutic lead to treat frontotemporal dementia.

Science.gov (United States)

Holler, Christopher J; Taylor, Georgia; McEachin, Zachary T; Deng, Qiudong; Watkins, William J; Hudson, Kathryn; Easley, Charles A; Hu, William T; Hales, Chadwick M; Rossoll, Wilfried; Bassell, Gary J; Kukar, Thomas

2016-06-24

Progranulin (PGRN) is a secreted growth factor important for neuronal survival and may do so, in part, by regulating lysosome homeostasis. Mutations in the PGRN gene (GRN) are a common cause of frontotemporal lobar degeneration (FTLD) and lead to disease through PGRN haploinsufficiency. Additionally, complete loss of PGRN in humans leads to neuronal ceroid lipofuscinosis (NCL), a lysosomal storage disease. Importantly, Grn-/- mouse models recapitulate pathogenic lysosomal features of NCL. Further, GRN variants that decrease PGRN expression increase the risk of developing Alzheimer's disease (AD) and Parkinson's disease (PD). Together these findings demonstrate that insufficient PGRN predisposes neurons to degeneration. Therefore, compounds that increase PGRN levels are potential therapeutics for multiple neurodegenerative diseases. Here, we performed a cell-based screen of a library of known autophagy-lysosome modulators and identified multiple novel activators of a human GRN promoter reporter including several common mTOR inhibitors and an mTOR-independent activator of autophagy, trehalose. Secondary cellular screens identified trehalose, a natural disaccharide, as the most promising lead compound because it increased endogenous PGRN in all cell lines tested and has multiple reported neuroprotective properties. Trehalose dose-dependently increased GRN mRNA as well as intracellular and secreted PGRN in both mouse and human cell lines and this effect was independent of the transcription factor EB (TFEB). Moreover, trehalose rescued PGRN deficiency in human fibroblasts and neurons derived from induced pluripotent stem cells (iPSCs) generated from GRN mutation carriers. Finally, oral administration of trehalose to Grn haploinsufficient mice significantly increased PGRN expression in the brain. This work reports several novel autophagy-lysosome modulators that enhance PGRN expression and identifies trehalose as a promising therapeutic for raising PGRN levels to treat

Effect of Strain Rate on Joint Strength and Failure Mode of Lead-Free Solder Joints

Science.gov (United States)

Lin, Jian; Lei, Yongping; Fu, Hanguang; Guo, Fu

2018-03-01

In surface mount technology, the Sn-3.0Ag-0.5Cu solder joint has a shorter impact lifetime than a traditional lead-tin solder joint. In order to improve the impact property of SnAgCu lead-free solder joints and identify the effect of silver content on tensile strength and impact property, impact experiments were conducted at various strain rates on three selected SnAgCu based solder joints. It was found that joint failure mainly occurred in the solder material with large plastic deformation under low strain rate, while joint failure occurred at the brittle intermetallic compound layer without any plastic deformation at a high strain rate. Joint strength increased with the silver content in SnAgCu alloys in static tensile tests, while the impact property of the solder joint decreased with increasing silver content. When the strain rate was low, plastic deformation occurred with failure and the tensile strength of the Sn-3.0Ag-0.5Cu solder joint was higher than that of Sn-0.3Ag-0.7Cu; when the strain rate was high, joint failure mainly occurred at the brittle interface layer and the Sn-0.3Ag-0.7Cu solder joint had a better impact resistance with a thinner intermetallic compound layer.

Biotransformation of major ginsenosides into compound K by a new ...

African Journals Online (AJOL)

Biotransformation of major ginsenosides into compound K by a new Penicillium dipodomyicola ... African Journal of Biotechnology ... ginsenoside Rb1 to minor ginsenosides compound K. The transformation products were identified by thin ...

Are We There Yet? Applying Thermodynamic and Kinetic Profiling on Embryonic Ectoderm Development (EED) Hit-to-Lead Program.

Science.gov (United States)

Wang, Ying; Edalji, Rohinton P; Panchal, Sanjay C; Sun, Chaohong; Djuric, Stevan W; Vasudevan, Anil

2017-10-26

It is advocated that kinetic and thermodynamic profiling of bioactive compounds should be incorporated and utilized as complementary tools for hit and lead optimizations in drug discovery. To assess their applications in the EED hit-to-lead optimization process, large amount of thermodynamic and kinetic data were collected and analyzed via isothermal titration calorimetry (ITC) and surface plasmon resonance (SPR), respectively. Slower dissociation rates (k off ) of the lead compounds were observed as the program progressed. Analysis of the kinetic data indicated that compound cellular activity correlated with both K i and k off . Our analysis revealed that ITC data should be interpreted in the context of chiral purity of the compounds. The thermodynamic signatures of the EED aminopyrrolidine compounds were found to be mainly enthalpy driven with improved enthalpic contributions as the program progressed. Our study also demonstrated that significant challenges still exist in utilizing kinetic and thermodynamic parameters for hit selection.

Small-molecule screening using a human primary cell model of HIV latency identifies compounds that reverse latency without cellular activation

Science.gov (United States)

Yang, Hung-Chih; Xing, Sifei; Shan, Liang; O’Connell, Karen; Dinoso, Jason; Shen, Anding; Zhou, Yan; Shrum, Cynthia K.; Han, Yefei; Liu, Jun O.; Zhang, Hao; Margolick, Joseph B.; Siliciano, Robert F.

2009-01-01

The development of highly active antiretroviral therapy (HAART) to treat individuals infected with HIV-1 has dramatically improved patient outcomes, but HAART still fails to cure the infection. The latent viral reservoir in resting CD4+ T cells is a major barrier to virus eradication. Elimination of this reservoir requires reactivation of the latent virus. However, strategies for reactivating HIV-1 through nonspecific T cell activation have clinically unacceptable toxicities. We describe here the development of what we believe to be a novel in vitro model of HIV-1 latency that we used to search for compounds that can reverse latency. Human primary CD4+ T cells were transduced with the prosurvival molecule Bcl-2, and the resulting cells were shown to recapitulate the quiescent state of resting CD4+ T cells in vivo. Using this model system, we screened small-molecule libraries and identified a compound that reactivated latent HIV-1 without inducing global T cell activation, 5-hydroxynaphthalene-1,4-dione (5HN). Unlike previously described latency-reversing agents, 5HN activated latent HIV-1 through ROS and NF-κB without affecting nuclear factor of activated T cells (NFAT) and PKC, demonstrating that TCR pathways can be dissected and utilized to purge latent virus. Our study expands the number of classes of latency-reversing therapeutics and demonstrates the utility of this in vitro model for finding strategies to eradicate HIV-1 infection. PMID:19805909

Novel chloroacetamido compound CWR-J02 is an anti-inflammatory glutaredoxin-1 inhibitor.

Directory of Open Access Journals (Sweden)

Olga Gorelenkova Miller

Full Text Available Glutaredoxin (Grx1 is a ubiquitously expressed thiol-disulfide oxidoreductase that specifically catalyzes reduction of S-glutathionylated substrates. Grx1 is known to be a key regulator of pro-inflammatory signaling, and Grx1 silencing inhibits inflammation in inflammatory disease models. Therefore, we anticipate that inhibition of Grx1 could be an anti-inflammatory therapeutic strategy. We used a rapid screening approach to test 504 novel electrophilic compounds for inhibition of Grx1, which has a highly reactive active-site cysteine residue (pKa 3.5. From this chemical library a chloroacetamido compound, CWR-J02, was identified as a potential lead compound to be characterized. CWR-J02 inhibited isolated Grx1 with an IC50 value of 32 μM in the presence of 1 mM glutathione. Mass spectrometric analysis documented preferential adduction of CWR-J02 to the active site Cys-22 of Grx1, and molecular dynamics simulation identified a potential non-covalent binding site. Treatment of the BV2 microglial cell line with CWR-J02 led to inhibition of intracellular Grx1 activity with an IC50 value (37 μM. CWR-J02 treatment decreased lipopolysaccharide-induced inflammatory gene transcription in the microglial cells in a parallel concentration-dependent manner, documenting the anti-inflammatory potential of CWR-J02. Exploiting the alkyne moiety of CWR-J02, we used click chemistry to link biotin azide to CWR-J02-adducted proteins, isolating them with streptavidin beads. Tandem mass spectrometric analysis identified many CWR-J02-reactive proteins, including Grx1 and several mediators of inflammatory activation. Taken together, these data identify CWR-J02 as an intracellularly effective Grx1 inhibitor that may elicit its anti-inflammatory action in a synergistic manner by also disabling other pro-inflammatory mediators. The CWR-J02 molecule provides a starting point for developing more selective Grx1 inhibitors and anti-inflammatory agents for therapeutic

Health risk evaluation of certain compounds found in contaminated soil

International Nuclear Information System (INIS)

Dock, L.; Victorin, K.; Vahter, M.; Ahlborg, U.G.

1991-01-01

As part of a redevelopment plan for an old gas works site in Stockholm, the Institute of Environmental Medicine (IEM) at the Karolinska Institute was asked to evaluate the health risks associated with exposure to coal tar, containing polycyclic aromatic hydrocarbons (PAH), phenols, cyanides, sulfur compounds, arsenic, lead, cadmium and mercury in soil and to suggest guide line values for these compounds in residential areas. Our health risk evaluation was limited to possible effects following direct exposure to contaminated soil. Indirect exposure, i.e. through contaminated ground water or home-grown vegetables, was not considered, nor were effects on building material. The routes of exposure considered were ingestion, dermal contact and inhalation of soil dust. Small children were considered the primary risk group. The critical health effect associated with dermal exposure to PAH in soil is skin cancer. Ingestion of phenols, cyanides and sulphur compounds may cause acute health effects. Recommended guide line values for these contaminants were generally obtained by dividing the lowest observed effect levels with appropriate safety factors. The metals considered may cause both acute and chronic health effects. The guide line values for cadmium and mercury in soil were set based on a maximum intake through ingestion of soil corresponding to 10% of the provisional tolerable weekly intake levels (PTWI) set by FAO/WHO. For arsenic, the guide line value corresponds to 5% of the PTWI-value for a child. The suggested guide line level for lead was based on studied on the association between soil lead concentration and blood lead levels in children. The suggested guide line level for lead in soil may increase the blood-lead in a child by less than 10%. (31 refs.) (au)

Debye classes in A15 compounds

International Nuclear Information System (INIS)

Staudenmann, J.; DeFacio, B.; Testardi, L.R.; Werner, S.A.; Fluekiger, R.; Muller, J.

1981-01-01

The comparison between electron charge-density distribution of V 3 Si, Cr 3 Si, and V 3 Ge at room temperature leads us to study the Debye temperatures at 0 0 K THETA 0 from specific-heat measurements for over 100 A15 compounds. A phenomenological THETA 0 (M), M the molecular mass, is obtained from the static scaling relation THETA 0 (M) = aM/sup b/ and this organizes all of the data into five Debye classes: V(V 3 Si), V-G, G(V 3 Ge), G-C, and C(Cr 3 Si). In contrast, the Debye temperature THETA 0 (V), with V as the unit-cell volume does not relate alloys as THETA 0 (M) does, with the exception of the C class. This latter case leads to the surprising result MproportionalV/sup approximately1/3/ and to a Grueneisen constant of 1.6 +- 0.1 for all compounds of this class. In the V class where V 3 Si and Nb 3 Sn are found, THETA 0 (V) labels these two alloys differently, as does their martensitic c/a ratios. With T-bar/sub c/ denoting the average superconducting transition temperature within a Debye class, interesting correlations are shown. One is the maximum of T-bar/sub c/ which exists in the V class where the strongest anharmonicity occurs. Another is the case of compounds formed only by transition elements up to and including Au. This interesting case shows that approx.3.2< T-bar/sub c/< approx.5.0 K in all of the five classes and that there is no correlation between T/sub c/ and the thermal properties. The implications of these observations for creating better models for the A15 compounds are briefly discussed

Anti-photoaging and Photoprotective Compounds Derived from Marine Organisms

Directory of Open Access Journals (Sweden)

Ramjee Pallela

2010-04-01

Full Text Available Marine organisms form a prominent component of the oceanic population, which significantly contribute in the production of cosmeceutical and pharmaceutical molecules with biologically efficient moieties. In addition to the molecules of various biological activities like anti-bacterial, anti-cancerous, anti-inflammatory and anti-oxidative etc., these organisms also produce potential photoprotective or anti-photoaging agents, which are attracting present day researchers. Continuous exposure to UV irradiation (both UV-A and UV-B leads to the skin cancer and other photoaging complications, which are typically mediated by the reactive oxygen species (ROS, generated in the oxidative pathways. Many of the anti-oxidative and anti-photoaging compounds have been identified previously, which work efficiently against photodamage of the skin. Recently, marine originated photoprotective or anti-photoaging behavior was observed in the methanol extracts of Corallina pilulifera (CPM. These extracts were found to exert potent antioxidant activity and protective effect on UV-A-induced oxidative stress in human dermal fibroblast (HDF cells by protecting DNA and also by inhibiting matrix metalloproteinases (MMPs, a key component in photoaging of the skin due to exposure to UV-A. The present review depicts various other photoprotective compounds from algae and other marine sources for further elaborative research and their probable use in cosmeceutical and pharmaceutical industries.

Cantilever torque magnetometry on coordination compounds

DEFF Research Database (Denmark)

Perfetti, Mauro

2017-01-01

compounds, such as quantum computation or information storage. This review enlightens that CTM offers a unique combination of accuracy and precision to disentangle noncollinear contributions inside Single Crystals as well as the sensitivity to detect molecular order of thin films. CTM can also detect......Cantilever Torque Magnetometry (CTM) is one of the leading techniques to deeply understand magnetic anisotropy of coordination compounds. The knowledge of magnetic anisotropy is a mandatory requirement before proceeding with any future application related to the magnetic properties of coordination...... quantum phenomena such as magnetization steps and molecular hysteresis curves. Moreover, it can also provide the energy levels splitting and avefunctions composition, especially if coupled with microwave radiation....

Possible explosive compounds in the Savannah River Site waste tank farm facilities

International Nuclear Information System (INIS)

Hobbs, D.T.

1992-01-01

Based on a comparison of the known constituents in high-level nuclear waste stored at the Savannah River Site (SRS) and explosive compounds reported in the literature, only two classes of explosive compounds (metal NO x compounds and organic compounds) were identified as requiring further work to determine if they exist in the waste, and if so, in what quantities. Of the fourteen classes of explosive compounds identified as conceivably being present in tank farm operations, nine classes (metal fulminates, metal azides, halogen compounds, metal-amine complexes, nitrate/oxalate mixtures, metal oxalates, metal oxohalogenates, metal cyanides/cyanates, and peroxides) are not a hazard because these classes of compounds cannot be formed or accumulated in sufficient quantity, or they are not reactive at the conditions which exist in the tank farm facilities. Three of the classes (flammable gases, metal nitrides, and ammonia compounds and derivatives) are known to have the potential to build up to concentrations at which an observable reaction might occur. Controls have been in place for some time to limit the formation or control the concentration of these classes of compounds. A comprehensive list of conceivable explosive compounds is provided in Appendix 3

Effects of sulfur on lead partitioning during sludge incineration based on experiments and thermodynamic calculations

Energy Technology Data Exchange (ETDEWEB)

Liu, Jing-yong, E-mail: www053991@126.com [School of Environmental Science and Engineering, Guangdong University of Technology, Guangzhou 510006 (China); Huang, Shu-jie; Sun, Shui-yu; Ning, Xun-an; He, Rui-zhe [School of Environmental Science and Engineering, Guangdong University of Technology, Guangzhou 510006 (China); Li, Xiao-ming [Guangdong Testing Institute of Product Quality Supervision, Guangzhou 510330 (China); Chen, Tao [State Key Laboratory of Organic Geochemistry, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640 (China); Luo, Guang-qian [State Key Laboratory of Coal Combustion, Huazhong University of Science and Technology, Wuhan 430074 (China); Xie, Wu-ming; Wang, Yu-jie; Zhuo, Zhong-xu; Fu, Jie-wen [School of Environmental Science and Engineering, Guangdong University of Technology, Guangzhou 510006 (China)

2015-04-15

Highlights: • A thermodynamic equilibrium calculation was carried out. • Effects of three types of sulfurs on Pb distribution were investigated. • The mechanism for three types of sulfurs acting on Pb partitioning were proposed. • Lead partitioning and species in bottom ash and fly ash were identified. - Abstract: Experiments in a tubular furnace reactor and thermodynamic equilibrium calculations were conducted to investigate the impact of sulfur compounds on the migration of lead (Pb) during sludge incineration. Representative samples of typical sludge with and without the addition of sulfur compounds were combusted at 850 °C, and the partitioning of Pb in the solid phase (bottom ash) and gas phase (fly ash and flue gas) was quantified. The results indicate that three types of sulfur compounds (S, Na{sub 2}S and Na{sub 2}SO{sub 4}) added to the sludge could facilitate the volatilization of Pb in the gas phase (fly ash and flue gas) into metal sulfates displacing its sulfides and some of its oxides. The effect of promoting Pb volatilization by adding Na{sub 2}SO{sub 4} and Na{sub 2}S was superior to that of the addition of S. In bottom ash, different metallic sulfides were found in the forms of lead sulfide, aluminosilicate minerals, and polymetallic-sulfides, which were minimally volatilized. The chemical equilibrium calculations indicated that sulfur stabilizes Pb in the form of PbSO{sub 4}(s) at low temperatures (<1000 K). The equilibrium calculation prediction also suggested that SiO{sub 2}, CaO, TiO{sub 2}, and Al{sub 2}O{sub 3} containing materials function as condensed phase solids in the temperature range of 800–1100 K as sorbents to stabilize Pb. However, in the presence of sulfur or chlorine or the co-existence of sulfur and chlorine, these sorbents were inactive. The effect of sulfur on Pb partitioning in the sludge incineration process mainly depended on the gas phase reaction, the surface reaction, the volatilization of products, and the

In vitro functional screening as a means to identify new plasticizers devoid of reproductive toxicity

Energy Technology Data Exchange (ETDEWEB)

Boisvert, Annie; Jones, Steven; Issop, Leeyah [The Research Institute of the McGill University Health Centre, McGill University, Montreal, Quebec, Canada H4A 3J1 (Canada); Department of Medicine, McGill University, Montreal, Quebec, Canada H4A 3J1 (Canada); Erythropel, Hanno C. [Department of Chemical Engineering, McGill University, Montreal, Quebec, Canada H4A 3J1 (Canada); Papadopoulos, Vassilios [The Research Institute of the McGill University Health Centre, McGill University, Montreal, Quebec, Canada H4A 3J1 (Canada); Department of Medicine, McGill University, Montreal, Quebec, Canada H4A 3J1 (Canada); Department of Pharmacology & Therapeutics, McGill University, Montreal, Quebec, Canada H4A 3J1 (Canada); Culty, Martine, E-mail: martine.culty@mcgill.ca [The Research Institute of the McGill University Health Centre, McGill University, Montreal, Quebec, Canada H4A 3J1 (Canada); Department of Medicine, McGill University, Montreal, Quebec, Canada H4A 3J1 (Canada); Department of Pharmacology & Therapeutics, McGill University, Montreal, Quebec, Canada H4A 3J1 (Canada)

2016-10-15

Plasticizers are indispensable additives providing flexibility and malleability to plastics. Among them, several phthalates, including di (2-ethylhexyl) phthalate (DEHP), have emerged as endocrine disruptors, leading to their restriction in consumer products and creating a need for new, safer plasticizers. The goal of this project was to use in vitro functional screening tools to select novel non-toxic plasticizers suitable for further in vivo evaluation. A panel of novel compounds with satisfactory plasticizer properties and biodegradability were tested, along with several commercial plasticizers, such as diisononyl-cyclohexane-1,2-dicarboxylate (DINCH®). MEHP, the monoester metabolite of DEHP was also included as reference compound. Because phthalates target mainly testicular function, including androgen production and spermatogenesis, we used the mouse MA-10 Leydig and C18-4 spermatogonial cell lines as surrogates to examine cell survival, proliferation, steroidogenesis and mitochondrial integrity. The most promising compounds were further assessed on organ cultures of rat fetal and neonatal testes, corresponding to sensitive developmental windows. Dose-response studies revealed the toxicity of most maleates and fumarates, while identifying several dibenzoate and succinate plasticizers as innocuous on Leydig and germ cells. Interestingly, DINCH®, a plasticizer marketed as a safe alternative to phthalates, exerted a biphasic effect on steroid production in MA-10 and fetal Leydig cells. MEHP was the only plasticizer inducing the formation of multinucleated germ cells (MNG) in organ culture. Overall, organ cultures corroborated the cell line data, identifying one dibenzoate and one succinate as the most promising candidates. The adoption of such collaborative approaches for developing new chemicals should help prevent the development of compounds potentially harmful to human health. - Highlights: • Phthalate plasticizers exert toxic effects on male reproduction

In vitro functional screening as a means to identify new plasticizers devoid of reproductive toxicity

International Nuclear Information System (INIS)

Boisvert, Annie; Jones, Steven; Issop, Leeyah; Erythropel, Hanno C.; Papadopoulos, Vassilios; Culty, Martine

2016-01-01

Plasticizers are indispensable additives providing flexibility and malleability to plastics. Among them, several phthalates, including di (2-ethylhexyl) phthalate (DEHP), have emerged as endocrine disruptors, leading to their restriction in consumer products and creating a need for new, safer plasticizers. The goal of this project was to use in vitro functional screening tools to select novel non-toxic plasticizers suitable for further in vivo evaluation. A panel of novel compounds with satisfactory plasticizer properties and biodegradability were tested, along with several commercial plasticizers, such as diisononyl-cyclohexane-1,2-dicarboxylate (DINCH®). MEHP, the monoester metabolite of DEHP was also included as reference compound. Because phthalates target mainly testicular function, including androgen production and spermatogenesis, we used the mouse MA-10 Leydig and C18-4 spermatogonial cell lines as surrogates to examine cell survival, proliferation, steroidogenesis and mitochondrial integrity. The most promising compounds were further assessed on organ cultures of rat fetal and neonatal testes, corresponding to sensitive developmental windows. Dose-response studies revealed the toxicity of most maleates and fumarates, while identifying several dibenzoate and succinate plasticizers as innocuous on Leydig and germ cells. Interestingly, DINCH®, a plasticizer marketed as a safe alternative to phthalates, exerted a biphasic effect on steroid production in MA-10 and fetal Leydig cells. MEHP was the only plasticizer inducing the formation of multinucleated germ cells (MNG) in organ culture. Overall, organ cultures corroborated the cell line data, identifying one dibenzoate and one succinate as the most promising candidates. The adoption of such collaborative approaches for developing new chemicals should help prevent the development of compounds potentially harmful to human health. - Highlights: • Phthalate plasticizers exert toxic effects on male reproduction

An exploratory study of lead recovery in lead-acid battery lifecycle in US market: An evidence-based approach

International Nuclear Information System (INIS)

Genaidy, A.M.; Sequeira, R.; Tolaymat, T.; Kohler, J.; Rinder, M.

2008-01-01

Background: This research examines lead recovery and recycling in lead-acid batteries (LAB) which account for 88% of US lead consumption. We explore strategies to maximize lead recovery and recycling in the LAB lifecycle. Currently, there is limited information on recycling rates for LAB in the published literature and is derived from a single source. Therefore, its recycling efforts in the US has been unclear so as to determine the maximum opportunities for metal recovery and recycling in the face of significant demands for LAB particularly in the auto industry. Objectives: The research utilizes an evidence-based approach to: (1) determine recycling rates for lead recovery in the LAB product lifecycle for the US market; and (2) quantify and identify opportunities where lead recovery and recycling can be improved. Methods: A comprehensive electronic search of the published literature was conducted to gather information on different LAB recycling models and actual data used to calculate recycling rates based on product lifecycle for the US market to identify strategies for increasing lead recovery and recycling. Results: The electronic search yielded five models for calculating LAB recycling rates. The description of evidence was documented for each model. Furthermore, an integrated model was developed to identify and quantify the maximum opportunities for lead recovery and recycling. Results showed that recycling rates declined during the period spanning from 1999 to 2006. Opportunities were identified for recovery and recycling of lead in the LAB product lifecycle. Concluding remarks: One can deduce the following from the analyses undertaken in this report: (1) lead recovery and recycling has been stable between 1999 and 2006; (2) lead consumption has increased at an annual rate of 2.25%, thus, the values derived in this study for opportunities dealing with lead recovery and recycling underestimate the amount of lead in scrap and waste generated; and (3) the

Exploration of Novel Botanical Insecticide Leads: Synthesis and Insecticidal Activity of β-Dihydroagarofuran Derivatives.

Science.gov (United States)

Zhao, Ximei; Xi, Xin; Hu, Zhan; Wu, Wenjun; Zhang, Jiwen

2016-02-24

The discovery of novel leads and new mechanisms of action is of vital significance to the development of pesticides. To explore lead compounds for botanical insecticides, 77 β-dihydroagarofuran derivatives were designed and synthesized. Their structures were mainly confirmed by (1)H NMR, (13)C NMR, DEPT-135°, IR, MS, and HRMS. Their insecticidal activity was evaluated against the third-instar larvae of Mythimna separata Walker, and the results indicated that, of these derivatives, eight exhibited more promising insecticidal activity than the positive control, celangulin-V. Particularly, compounds 5.7, 6.6, and 6.7 showed LD50 values of 37.9, 85.1, and 21.1 μg/g, respectively, which were much lower than that of celangulin-V (327.6 μg/g). These results illustrated that β-dihydroagarofuran ketal derivatives can be promising lead compounds for developing novel mechanism-based and highly effective botanical insecticides. Moreover, some newly discovered structure-activity relationships are discussed, which may provide some important guidance for insecticide development.

Utilization of genomic signatures to identify phenotype-specific drugs.

Directory of Open Access Journals (Sweden)

Seiichi Mori

2009-08-01

Full Text Available Genetic and genomic studies highlight the substantial complexity and heterogeneity of human cancers and emphasize the general lack of therapeutics that can match this complexity. With the goal of expanding opportunities for drug discovery, we describe an approach that makes use of a phenotype-based screen combined with the use of multiple cancer cell lines. In particular, we have used the NCI-60 cancer cell line panel that includes drug sensitivity measures for over 40,000 compounds assayed on 59 independent cells lines. Targets are cancer-relevant phenotypes represented as gene expression signatures that are used to identify cells within the NCI-60 panel reflecting the signature phenotype and then connect to compounds that are selectively active against those cells. As a proof-of-concept, we show that this strategy effectively identifies compounds with selectivity to the RAS or PI3K pathways. We have then extended this strategy to identify compounds that have activity towards cells exhibiting the basal phenotype of breast cancer, a clinically-important breast cancer characterized as ER-, PR-, and Her2- that lacks viable therapeutic options. One of these compounds, Simvastatin, has previously been shown to inhibit breast cancer cell growth in vitro and importantly, has been associated with a reduction in ER-, PR- breast cancer in a clinical study. We suggest that this approach provides a novel strategy towards identification of therapeutic agents based on clinically relevant phenotypes that can augment the conventional strategies of target-based screens.

Superconducting lead particles produced by chemical techniques

Science.gov (United States)

Fariss, T. L.; Nixon, W. E.; Bucelot, T. J.; Deaver, B. S., Jr.; Mitchell, J. W.

1982-09-01

The superconductivity of extremely small lead particles has been studied as a function of size, surface condition, and connectivity using chemical techniques to produce particles of well-controlled size and shape suspended in insulating media. Approximately monodisperse suspensions of equiaxed, rod, and lath-shaped particles of lead halides and other lead compounds suspended in gelatin, polyacrylamide, polyvinylpyrrolidone, polyvinyl alcohol, methyl cellulose, and hydroxyethyl cellulose have been produced. These particles have been reduced to pseudomorphs of lead in the liquid phase or the suspensions have been coated on substrates and dried before reduction. Reducing solutions containing aminoiminomethanesulfinic acid are effective with particles of lead halides, lead phosphate, lead sulfate, and lead tartrate. Suspensions of smaller discrete lead particles have also been produced by direct reduction of solutions of soluble lead salts containing suitable polymers, chelating, and stabilizing agents. Dispersions with mean particle dimensions between 3 nm and 5 μm, and a narrow size-frequency distribution, have been produced. The superconductivity of the particles has been characterized by measurements of the magnetization as a function of temperature and magnetic field. The larger particles have a transition temperature of 7.2 K, the same as bulk lead; however, for particles of characteristic dimensions less than 20 nm, the transition temperature is lower by ˜0.1 K.

Superconducting lead particles produced by chemical techniques

International Nuclear Information System (INIS)

Fariss, T.L.; Nixon, W.E.; Bucelot, T.J.; Deaver, B.S. Jr.; Mitchell, J.W.

1982-01-01

The superconductivity of extremely small lead particles has been studied as a function of size, surface condition, and connectivity using chemical techniques to produce particles of well-controlled size and shape suspended in insulating media. Approximately monodisperse suspensions of equiaxed, rod, and lath-shaped particles of lead halides and other lead compounds suspended in gelatin, polyacrylamide, polyvinylpyrrolidone, polyvinyl alcohol, methyl cellulose, and hydroxyethyl cellulose have been produced. These particles have been reduced to pseudomorphs of lead in the liquid phase or the suspensions have been coated on substrates and dried before reduction. Reducing solutions containing aminoiminomethanesulfinic acid are effective with particles of lead halides, lead phosphate, lead sulfate, and lead tartrate. Suspensions of smaller discrete lead particles have also been produced by direct reduction of solutions of soluble lead salts containing suitable polymers, chelating, and stabilizing agents. Dispersions with mean particle dimensions between 3 nm and 5 μm, and a narrow size-frequency distribution, have been produced. The superconductivity of the particles has been characterized by measurements of the magnetization as a function of temperature and magnetic field. The larger particles have a transition temperature of 7.2 K, the same as bulk lead; however, for particles of characteristic dimensions less than 20 nm, the transition temperature is lower by approx.0.1 K

Ultrasonic-assisted synthesis of nano lead(II) coordination polymer as precursors for preparation of lead(II) oxide nano-structures: Thermal, optical properties and XRD studies.

Science.gov (United States)

Ghavidelaghdam, Elham; Shahverdizadeh, Gholam Hossein; Motameni Tabatabai, Javad; Mirtamizdoust, Babak

2018-04-01

Nano structure of a lead (II) coordination polymer [Pb 2 (C 2 Cl 3 O 2 ) 2 (NO 3 ) 2 (C l2 H 8 N 2 ) 2 ] n (1), has been synthesized by a sonochemical method in different concentrations. The nano particles were characterized by scanning electron microscopy (SEM) X-ray powder diffraction (XRD), FT-IR spectroscopy and elemental analyses. The thermal stability of nano structure is closely investigated via thermal gravimetric (TGA), and compared with crystalline structure. The compounds are then heated to 600 °C to produce PbO nano particles. The resulting PbO is characterized through XRD and SEM analyses. Concentration of initial reagents effects on size and morphology of nano-structured compound 1 have been studied and show that low concentrations of initial reagents decreased particles size and leaded to uniform nano particles morphology. The photoluminescence properties of the prepared compound, as crystalline and as nanoparticles, have been investigated. The result showed a good correlation between the size and emission wavelength. Copyright © 2017. Published by Elsevier B.V.

The reactions of anthronylidene carbene with some heterocyclic compounds

International Nuclear Information System (INIS)

Divisia, Bernadette

1970-01-01

The action of the anthronylidene carbene, generated by photochemical decomposition of 9-diazo 10-anthron, on four heterocyclic compounds (furan, thiophene, 1-methyl-pyrrole and 2,5-dihydrofuran) has been examined. Two classical carbene reactions have been observed: the addition on double bond (furan, thiophene, 1-methylpyrrole) and hydrogen atom abstraction of the heterocyclic compound (2,5-dihydrofuran). In the case of furan and thiophene, the cyclo-propanic compound resulting from the addition is spontaneously transformed into an ethylenic derivative by valence isomerization. The furan derivative undergoes a cis-trans isomerization, while the thiophene one undergoes an extra carbene attack. In the case of 1-methylpyrrole, the corresponding cyclo-propanic compound undergoes a ring cleavage, followed by a hydrogen atom migration leading to the formation of a substituted anthron. Only an allylic hydrogen atom selective abstraction of heterocyclic compound takes place in the reaction of anthronylidene carbene with 2,5-dihydrofuran. The asymmetrical coupling of radicals so obtained yields the corresponding substituted anthron. (author) [fr

Identification of organic sulfur compounds in coal bitumen obtained by different extraction techniques using comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometric detection

Energy Technology Data Exchange (ETDEWEB)

Machado, Maria Elisabete; Cappelli Fontanive, Fernando; Bastos Caramao, Elina; Alcaraz Zini, Claudia [Universidade Federal do Rio Grande do Sul, Instituto de Quimica, Porto Alegre, RS (Brazil); Oliveira, Jose Vladimir de [URI, Universidade Regional Integrada do Alto Uruguai e das Missoes, Erechim, RS (Brazil)

2011-11-15

The determination of organic sulfur compounds (OSC) in coal is of great interest. Technically and operationally these compounds are not easily removed and promote corrosion of equipment. Environmentally, the burning of sulfur compounds leads to the emission of SO{sub x} gases, which are major contributors to acid rain. Health-wise, it is well known that these compounds have mutagenic and carcinogenic properties. Bitumen can be extracted from coal by different techniques, and use of gas chromatography coupled to mass spectrometric detection enables identification of compounds present in coal extracts. The OSC from three different bitumens were tentatively identified by use of three different extraction techniques: accelerated solvent extraction (ASE), ultrasonic extraction (UE), and supercritical-fluid extraction (SFE). Results obtained from one-dimensional gas chromatography (1D GC) coupled to quadrupole mass spectrometric detection (GC-qMS) and from two-dimensional gas chromatography with time-of-flight mass spectrometric detection (GC x GC-TOFMS) were compared. By use of 2D GC, a greater number of OSC were found in ASE bitumen than in SFE and UE bitumens. No OSC were identified with 1D GC-qMS, although some benzothiophenes and dibenzothiophenes were detected by use of EIM and SIM modes. GC x GC-TOFMS applied to investigation of OSC in bitumens resulted in analytical improvement, as more OSC classes and compounds were identified (thiols, sulfides, thiophenes, naphthothiophenes, benzothiophenes, and benzonaphthothiophenes). The roof-tile effect was observed for OSC and PAH in all bitumens. Several co-elutions among analytes and with matrix interferents were solved by use of GC x GC. (orig.)

Leaf enclosure measurement for determining marijuana volatile organic compound emission factors

Science.gov (United States)

Wang, C. T.; Vizuete, W.; Wiedinmyer, C.; Ashworth, K.; Harley, P. C.; Ortega, J. V.

2017-12-01

In 2014, Colorado became the first US state to legalize the industrial-scale cultivation of marijuana plants. There are now more than 700 marijuana cultivation facilities (MCFs) in operation in the greater Denver area. High concentrations of biogenic volatile organic compounds (VOCs), predominantly monoterpenes (C10H16) such as alpha-pinene, myrcene, and limonene have been observed in the grow rooms of MCFs, suggesting MCFs have the potential to release a significant amount of reactive VOCs into the atmosphere. Further, many MCFs are located in the urban core, where other urban emission sources are concentrated, resulting in interactions which can lead to the formation of ozone, impacting air quality. The little research done on marijuana has focused on indoor air quality and occupational exposure, or identification of the compounds associated with the characteristic smells of marijuana plants. We know of no previous studies that have identified or quantified the monoterpene emission rates from marijuana. Here, we collected air samples from leaf enclosures from different marijuana clones at different growth stages onto sorbent cartridges. These samples were analyzed using GC-MS/-FID to identify and quantify the VOCs emitted by growing marijuana plants. These results were then used to estimate basal emission rates at standard conditions (T=30 C, PPFD = 1000 umol/m2/s) using standard algorithms. We discuss the potential impact on air quality from these VOCs emitted into the atmosphere using air quality models.

Gene expression signature analysis identifies vorinostat as a candidate therapy for gastric cancer.

Directory of Open Access Journals (Sweden)

Sofie Claerhout

Full Text Available Gastric cancer continues to be one of the deadliest cancers in the world and therefore identification of new drugs targeting this type of cancer is thus of significant importance. The purpose of this study was to identify and validate a therapeutic agent which might improve the outcomes for gastric cancer patients in the future.Using microarray technology, we generated a gene expression profile of human gastric cancer-specific genes from human gastric cancer tissue samples. We used this profile in the Broad Institute's Connectivity Map analysis to identify candidate therapeutic compounds for gastric cancer. We found the histone deacetylase inhibitor vorinostat as the lead compound and thus a potential therapeutic drug for gastric cancer. Vorinostat induced both apoptosis and autophagy in gastric cancer cell lines. Pharmacological and genetic inhibition of autophagy however, increased the therapeutic efficacy of vorinostat, indicating that a combination of vorinostat with autophagy inhibitors may therapeutically be more beneficial. Moreover, gene expression analysis of gastric cancer identified a collection of genes (ITGB5, TYMS, MYB, APOC1, CBX5, PLA2G2A, and KIF20A whose expression was elevated in gastric tumor tissue and downregulated more than 2-fold by vorinostat treatment in gastric cancer cell lines. In contrast, SCGB2A1, TCN1, CFD, APLP1, and NQO1 manifested a reversed pattern.We showed that analysis of gene expression signature may represent an emerging approach to discover therapeutic agents for gastric cancer, such as vorinostat. The observation of altered gene expression after vorinostat treatment may provide the clue to identify the molecular mechanism of vorinostat and those patients likely to benefit from vorinostat treatment.

Confinement Effects in Low-Dimensional Lead Iodide Perovskite Hybrids

NARCIS (Netherlands)

Kamminga, Machteld E.; Fang, Honghua; Filip, Marina R.; Giustino, Feliciano; Baas, Jacobus; Blake, Graeme R.; Loi, Maria Antonietta; Palstra, Thomas T. M.

2016-01-01

We use a layered solution crystal growth technique to synthesize high-quality single crystals of phenylalkylammonium lead iodide organic/inorganic hybrid compounds. Single-crystal X-ray diffraction reveals low-dimensional structures consisting of inorganic sheets separated by bilayers of the organic

Carcinogenicity assessment of water-soluble nickel compounds.

Science.gov (United States)

Goodman, Julie E; Prueitt, Robyn L; Dodge, David G; Thakali, Sagar

2009-01-01

IARC is reassessing the human carcinogenicity of nickel compounds in 2009. To address the inconsistencies among results from studies of water-soluble nickel compounds, we conducted a weight-of-evidence analysis of the relevant epidemiological, toxicological, and carcinogenic mode-of-action data. We found the epidemiological evidence to be limited, in that some, but not all, data suggest that exposure to soluble nickel compounds leads to increased cancer risk in the presence of certain forms of insoluble nickel. Although there is no evidence that soluble nickel acts as a complete carcinogen in animals, there is limited evidence that suggests it may act as a tumor promoter. The mode-of-action data suggest that soluble nickel compounds will not be able to cause genotoxic effects in vivo because they cannot deliver sufficient nickel ions to nuclear sites of target cells. Although the mode-of-action data suggest several possible non-genotoxic effects of the nickel ion, it is unclear whether soluble nickel compounds can elicit these effects in vivo or whether these effects, if elicited, would result in tumor promotion. The mode-of-action data equally support soluble nickel as a promoter or as not being a causal factor in carcinogenesis at all. The weight of evidence does not indicate that soluble nickel compounds are complete carcinogens, and there is only limited evidence that they could act as tumor promoters.

Leading men

DEFF Research Database (Denmark)

Bekker-Nielsen, Tønnes

2016-01-01

Through a systematic comparison of c. 50 careers leading to the koinarchate or high priesthood of Asia, Bithynia, Galatia, Lycia, Macedonia and coastal Pontus, as described in funeral or honorary inscriptions of individual koinarchs, it is possible to identify common denominators but also disting...

The effect of lead-based paint hazard remediation on blood lead levels of lead poisoned children in New York City.

Science.gov (United States)

Leighton, Jessica; Klitzman, Susan; Sedlar, Slavenka; Matte, Thomas; Cohen, Neal L

2003-07-01

Despite the widespread use of lead paint hazard control for children with lead poisoning, few controlled studies that estimate the effect of such control on children's blood lead levels have been published. This retrospective follow-up study examined the effects of lead hazard remediation and its timing on the blood lead levels of lead-poisoned children. From the New York City child blood lead registry, 221 children were selected who had an initial blood lead level of 20-44 micro g/dL between 1 July 1994 and 31 December 1996; were 6 months to 6 years of age; had a report of a follow-up blood lead test between 10 and 14 months after the initial test; had a lead-based paint hazard identified in the primary dwelling unit prior to the 10- to 14-month follow-up blood lead test; had resided or spent time at only one address with an identified lead-based paint hazard; and were not chelated. The decline in geometric mean blood lead levels from baseline to 10-14 months later was compared for children whose homes were remediated and whose homes were not remediated during the follow-up period. Regardless of remediation, geometric mean blood lead levels declined significantly from 24.3 micro g/dL at the initial diagnosis to 12.3 micro g/dL at the 10- to 14-month follow-up blood lead test (Premediated the geometric mean blood lead levels declined 53% compared to 41% among the 75 children whose homes were not remediated by the follow-up blood lead test, a remediation effect of approximately 20% (Premediation effect was 11%, although it was no longer significant. Race was the only factor that appeared to confound the relationship: Black children had higher follow-up blood lead levels even after controlling for other factors, including the natural logarithm of the initial blood lead level. The effect of remediation appeared to be stronger for younger (10 to remediation (within less than 3 months) appeared to have greater declines in blood lead levels at the follow-up test than

Lead content in household paints in India

International Nuclear Information System (INIS)

Kumar, Abhay; Gottesfeld, Perry

2008-01-01

Lead and its compounds are used in paints not only to impart colour but also to make it durable, corrosion resistant and to improve drying. Adverse health impacts of lead especially on children have led countries to restrict or ban its use in paints. While U.S. and other developed countries instituted measures to limit the use of lead in paints, some developing countries including India have failed to regulate their lead content. The present study was undertaken to determine the levels of lead in new latex (water-based) and enamel paints (oil-based) intended for residential use in India. A total of 69 paint samples (38 latex and 31 enamel samples) from six of the most popular brands were analysed for lead concentrations. While all latex paint samples contained low levels of lead, (i.e., well below 600 ppm as regulated by United States' Consumer Products Safety Commission) the enamel paint samples of all but one brand contained significant concentrations of lead, ranging up to 140,000 ppm. In fact 84% of the enamel paints tested exceeded 600 ppm whereas only 38 % of all samples (including latex and enamel types) exceeded this regulatory level

Identification of sources of lead exposure in French children by lead isotope analysis: a cross-sectional study

Directory of Open Access Journals (Sweden)

Lucas Jean-Paul

2011-08-01

Full Text Available Abstract Background The amount of lead in the environment has decreased significantly in recent years, and so did exposure. However, there is no known safe exposure level and, therefore, the exposure of children to lead, although low, remains a major public health issue. With the lower levels of exposure, it is becoming more difficult to identify lead sources and new approaches may be required for preventive action. This study assessed the usefulness of lead isotope ratios for identifying sources of lead using data from a nationwide sample of French children aged from six months to six years with blood lead levels ≥25 μg/L. Methods Blood samples were taken from 125 children, representing about 600,000 French children; environmental samples were taken from their homes and personal information was collected. Lead isotope ratios were determined using quadrupole ICP-MS (inductively coupled plasma - mass spectrometry and the isotopic signatures of potential sources of exposure were matched with those of blood in order to identify the most likely sources. Results In addition to the interpretation of lead concentrations, lead isotope ratios were potentially of use for 57% of children aged from six months to six years with blood lead level ≥ 25 μg/L (7% of overall children in France, about 332,000 children, with at least one potential source of lead and sufficiently well discriminated lead isotope ratios. Lead isotope ratios revealed a single suspected source of exposure for 32% of the subjects and were able to eliminate at least one unlikely source of exposure for 30% of the children. Conclusions In France, lead isotope ratios could provide valuable additional information in about a third of routine environmental investigations.

Rapid NMR method for the quantification of organic compounds in thin stillage.

Science.gov (United States)

Ratanapariyanuch, Kornsulee; Shen, Jianheng; Jia, Yunhua; Tyler, Robert T; Shim, Youn Young; Reaney, Martin J T

2011-10-12

Thin stillage contains organic and inorganic compounds, some of which may be valuable fermentation coproducts. This study describes a thorough analysis of the major solutes present in thin stillage as revealed by NMR and HPLC. The concentration of charged and neutral organic compounds in thin stillage was determined by excitation sculpting NMR methods (double pulse field gradient spin echo). Compounds identified by NMR included isopropanol, ethanol, lactic acid, 1,3-propanediol, acetic acid, succinic acid, glycerophosphorylcholine, betaine, glycerol, and 2-phenylethanol. The concentrations of lactic and acetic acid determined with NMR were comparable to those determined using HPLC. HPLC and NMR were complementary, as more compounds were identified using both methods. NMR analysis revealed that stillage contained the nitrogenous organic compounds betaine and glycerophosphorylcholine, which contributed as much as 24% of the nitrogen present in the stillage. These compounds were not observed by HPLC analysis.

Parallel screening of drug-like natural compounds using Caco-2 cell permeability QSAR model with applicability domain, lipophilic ligand efficiency index and shape property: A case study of HIV-1 reverse transcriptase inhibitors

Science.gov (United States)

Patel, Rikin D.; Kumar, Sivakumar Prasanth; Patel, Chirag N.; Shankar, Shetty Shilpa; Pandya, Himanshu A.; Solanki, Hitesh A.

2017-10-01

The traditional drug design strategy centrally focuses on optimizing binding affinity with the receptor target and evaluates pharmacokinetic properties at a later stage which causes high rate of attrition in clinical trials. Alternatively, parallel screening allows evaluation of these properties and affinity simultaneously. In a case study to identify leads from natural compounds with experimental HIV-1 reverse transcriptase (RT) inhibition, we integrated various computational approaches including Caco-2 cell permeability QSAR model with applicability domain (AD) to recognize drug-like natural compounds, molecular docking to study HIV-1 RT interactions and shape similarity analysis with known crystal inhibitors having characteristic butterfly-like model. Further, the lipophilic properties of the compounds refined from the process with best scores were examined using lipophilic ligand efficiency (LLE) index. Seven natural compound hits viz. baicalien, (+)-calanolide A, mniopetal F, fagaronine chloride, 3,5,8-trihydroxy-4-quinolone methyl ether derivative, nitidine chloride and palmatine, were prioritized based on LLE score which demonstrated Caco-2 well absorption labeling, encompassment in AD structural coverage, better receptor affinity, shape adaptation and permissible AlogP value. We showed that this integrative approach is successful in lead exploration of natural compounds targeted against HIV-1 RT enzyme.

Anti-BACE1 and Antimicrobial Activities of Steroidal Compounds Isolated from Marine Urechis unicinctus

Directory of Open Access Journals (Sweden)

Yong-Zhe Zhu

2018-03-01

Full Text Available The human β-site amyloid cleaving enzyme (BACE1 has been considered as an effective drug target for treatment of Alzheimer’s disease (AD. In this study, Urechis unicinctus (U. unicinctus, which is a Far East specialty food known as innkeeper worm, ethanol extract was studied by bioassay-directed fractionation and isolation to examine its potential β-site amyloid cleaving enzyme inhibitory and antimicrobial activity. The following compounds were characterized: hecogenin, cholest-4-en-3-one, cholesta-4,6-dien-3-ol, and hurgadacin. These compounds were identified by their mass spectrometry, 1H, and 13C NMR spectral data, comparing those data with NIST/EPA/NIH Mass spectral database (NIST11 and published values. Hecogenin and cholest-4-en-3-one showed significant inhibitory activity against BACE1 with EC50 values of 116.3 and 390.6 µM, respectively. Cholesta-4,6-dien-3-ol and hurgadacin showed broad spectrum antimicrobial activity, particularly strongly against Escherichia coli (E. coli, Salmonella enterica (S. enterica, Pasteurella multocida (P. multocida, and Physalospora piricola (P. piricola, with minimal inhibitory concentration (MIC ranging from 0.46 to 0.94 mg/mL. This is the first report regarding those four known compounds that were isolated from U. unicinctus and their anti-BACE1 and antimicrobial activity, highlighting the fact that known natural compounds may be a critical source of new medicine leads. These findings provide scientific evidence for potential application of those bioactive compounds for the development of AD drugs and antimicrobial agents.

Anti-BACE1 and Antimicrobial Activities of Steroidal Compounds Isolated from Marine Urechis unicinctus.

Science.gov (United States)

Zhu, Yong-Zhe; Liu, Jing-Wen; Wang, Xue; Jeong, In-Hong; Ahn, Young-Joon; Zhang, Chuan-Jie

2018-03-14

The human β-site amyloid cleaving enzyme (BACE1) has been considered as an effective drug target for treatment of Alzheimer's disease (AD). In this study, Urechis unicinctus (U. unicinctus) , which is a Far East specialty food known as innkeeper worm, ethanol extract was studied by bioassay-directed fractionation and isolation to examine its potential β-site amyloid cleaving enzyme inhibitory and antimicrobial activity. The following compounds were characterized: hecogenin, cholest-4- en -3-one, cholesta-4,6- dien -3-ol, and hurgadacin. These compounds were identified by their mass spectrometry, ¹H, and 13 C NMR spectral data, comparing those data with NIST/EPA/NIH Mass spectral database (NIST11) and published values. Hecogenin and cholest-4- en -3-one showed significant inhibitory activity against BACE1 with EC 50 values of 116.3 and 390.6 µM, respectively. Cholesta-4,6- dien -3-ol and hurgadacin showed broad spectrum antimicrobial activity, particularly strongly against Escherichia coli (E. coli) , Salmonella enterica (S. enterica) , Pasteurella multocida (P. multocida) , and Physalospora piricola (P. piricola) , with minimal inhibitory concentration (MIC) ranging from 0.46 to 0.94 mg/mL. This is the first report regarding those four known compounds that were isolated from U. unicinctus and their anti-BACE1 and antimicrobial activity, highlighting the fact that known natural compounds may be a critical source of new medicine leads. These findings provide scientific evidence for potential application of those bioactive compounds for the development of AD drugs and antimicrobial agents.

Assessment of A Simple Compound-Saving Method To Study Insecticidal Activity of Natural Extracts and Pure Compounds Against Mosquito Larvae.

Science.gov (United States)

Falkowski, Michaël; Jahn-Oyac, Arnaud; Ferrero, Emma; Issaly, Jean; Eparvier, Véronique; Girod, Romain; Rodrigues, Alice M S; Stien, Didier; Houël, Emeline; Dusfour, Isabelle

2016-12-01

Research on natural insecticides has intensified with the spread of resistance to chemicals among insects, particularly disease vectors. To evaluate compounds, the World Health Organization (WHO) has published standardized procedures. However, those may be excessively compound-consuming when it comes to assessing the activity of natural extracts and pure compounds isolated in limited amount. As part of our work on the discovery of new mosquito larvicides from Amazonian plants, we developed a compound-saving assay in 5-ml glass tubes instead of WHO larval 100-ml cups. Comparing activity of synthetic and natural chemicals validated the glass tube assay. Raw data, lethal doses that kill 50% (LD 50 ) and 90% (LD 90 ) at 24 and 48 h, were highly correlated (0.68 natural extracts and molecules, identifying active compounds using 10 times less material than in the WHO protocol.

Coumarin Antifungal Lead Compounds from Millettia thonningii and Their Predicted Mechanism of Action

Directory of Open Access Journals (Sweden)

Daniel M. Ayine-Tora

2016-10-01

Full Text Available Fungal pathogens continue to pose challenges to humans and plants despite efforts to control them. Two coumarins, robustic acid and thonningine-C isolated from Millettia thonningii, show promising activity against the fungus Candida albicans with minimum fungicidal concentration of 1.0 and 0.5 mg/mL, respectively. Molecular modelling against the putative bio-molecular target, lanosterol 14α-demethylase (CYP51, revealed a plausible binding mode for the active compounds, in which the hydroxyl group binds with a methionine backbone carboxylic group blocking access to the iron catalytic site. This binding disrupts the synthesis of several important sterols for the survival of fungi.

Generation of shock/discontinuity compound structures through magnetic reconnection in the geomagnetic tail

Energy Technology Data Exchange (ETDEWEB)

Weng, C. J. [Department of Physics, National Cheng Kung University, Tainan 701, Taiwan (China); Institute of Space Science, National Central University, Jungli 320, Taiwan (China); Lin, C. C. [Chemical Systems Research Division, Chung-Shan Institute of Science and Technology, Longtan 325, Taiwan (China); Lee, L. C. [Institute of Earth Science, Academia Sinica, Nankang 115, Taiwan (China); Institute of Space Science, National Central University, Jungli 320, Taiwan (China); Chao, J. K. [Institute of Space Science, National Central University, Jungli 320, Taiwan (China)

2012-12-15

We use 1-D hybrid code to simulate the generation and evolution of MHD discontinuities associated with magnetic reconnection in a current sheet. It is found that the leakage of slow shock (SS) downstream particles to upstream region tends to increase the ion parallel temperature and temperature anisotropy with {beta}{sub i||}/{beta}{sub i Up-Tack } Much-Greater-Than 1, where {beta}{sub i||}({beta}{sub i Up-Tack }) is the ion parallel (perpendicular) beta. As a result, the propagation speed of rotational discontinuity (RD) is highly reduced and RD becomes attached to SS, leading to formation of various compound structures in the reconnection outflow region. Four types of compound structure are found in our simulations: (a) RD-SS compound structure: the RD is attached to the leading part of SS, (b) SS-RD (DD) compound structure: RD is attached to the rear part of SS, (c) SS-RD-SS compound structure: RD is trapped inside SS, and (d) switch-off slow shock (SSS) with a rotational wave train. The type of compound structure generated depends on initial ion beta {beta}{sub i0} and magnetic shear angle {phi}. RD tends to move in front of SS to form an RD-SS compound structure for cases with low {beta}{sub i0}. RD stays behind SS and form an SS-RD (DD) compound structure for large {beta}{sub i0}. The SS-RD-SS compound structure is formed for intermediate values of {beta}{sub i0}. When the shear angle is 180 Degree-Sign , SSS with a wave train is formed.

N-cinnamoylated chloroquine analogues as dual-stage antimalarial leads.

Science.gov (United States)

Pérez, Bianca C; Teixeira, Cátia; Albuquerque, Inês S; Gut, Jiri; Rosenthal, Philip J; Gomes, José R B; Prudêncio, Miguel; Gomes, Paula

2013-01-24

The control of malaria is challenged by drug resistance, and new antimalarial drugs are needed. New drug discovery efforts include consideration of hybrid compounds as potential multitarget antimalarials. Previous work from our group has demonstrated that hybrid structures resulting from cinnamic acid conjugation with heterocyclic moieties from well-known antimalarials present improved antimalarial activity. Now, we report the synthesis and SAR analysis of an expanded series of cinnamic acid derivatives displaying remarkably high activities against both blood- and liver-stage malaria parasites. Two compounds judged most promising, based on their in vitro activity and druglikeness according to the Lipinski rules and Veber filter, were active in vivo against blood-stage rodent malaria parasites. Therefore, the compounds reported represent a new entry as promising dual-stage antimalarial leads.

High-content phenotypic screening and triaging strategy to identify small molecules driving oligodendrocyte progenitor cell differentiation.

Science.gov (United States)

Peppard, Jane V; Rugg, Catherine A; Smicker, Matthew A; Powers, Elaine; Harnish, Erica; Prisco, Joy; Cirovic, Dragan; Wright, Paul S; August, Paul R; Chandross, Karen J

2015-03-01

Multiple Sclerosis is a demyelinating disease of the CNS and the primary cause of neurological disability in young adults. Loss of myelinating oligodendrocytes leads to neuronal dysfunction and death and is an important contributing factor to this disease. Endogenous oligodendrocyte precursor cells (OPCs), which on differentiation are responsible for replacing myelin, are present in the adult CNS. As such, therapeutic agents that can stimulate OPCs to differentiate and remyelinate demyelinated axons under pathologic conditions may improve neuronal function and clinical outcome. We describe the details of an automated, cell-based, morphometric-based, high-content screen that is used to identify small molecules eliciting the differentiation of OPCs after 3 days. Primary screening was performed using rat CG-4 cells maintained in culture conditions that normally support a progenitor cell-like state. From a library of 73,000 diverse small molecules within the Sanofi collection, 342 compounds were identified that increased OPC morphological complexity as an indicator of oligodendrocyte maturation. Subsequent to the primary high-content screen, a suite of cellular assays was established that identified 22 nontoxic compounds that selectively stimulated primary rat OPCs but not C2C12 muscle cell differentiation. This rigorous triaging yielded several chemical series for further expansion and bio- or cheminformatics studies, and their compelling biological activity merits further investigation. © 2014 Society for Laboratory Automation and Screening.

Use of gas chromatography-mass spectrometry-olfactometry and a conventional flask test to identify off-flavor compounds generated from phenylalanine during chlorination of drinking water.

Science.gov (United States)

Matsushita, Taku; Sakuma, Miki; Tazawa, Shiori; Hatase, Taiki; Shirasaki, Nobutaka; Matsui, Yoshihiko

2017-11-15

Off-flavor in drinking water can be caused by transformation products (TPs) generated from organic compounds, such as amino acids, present during chlorination. However, the contributions of many of these TPs to overall off-flavor have not been quantified, mainly because the lack of appropriate chemical standards prevents sensory evaluation by means of a conventional flask test. In the present study, we used gas chromatography-mass spectrometry-olfactometry (GC-MS-O) to identify compounds responsible for the off-flavor generated by chlorination of an aqueous solution of the amino acid phenylalanine, and we propose a sensory evaluation procedure for quantification of the contributions of the identified TPs to the overall off-flavor, regardless of the availability of chemical standards of the TPs. GC-MS-O revealed that two TPs, N-chlorophenylacetaldimine and 2-chloro-2-phenylacetaldehyde, for which chemical standards are not commercially available, were the main components responsible for the off-flavor of the chlorinated solution. By using a sensory evaluation procedure involving a combination of GC-MS-O and a conventional flask test, we quantified the contributions of TPs to the overall off-flavor of the chlorinated solution. Approximately 60% of the off-flavor was attributable to free chlorine (13%), 2-chloro-2-phenylacetaldehyde (13%), trichloramine (12%) phenylacetaldehyde (11%) phenylacetonitrile (8%), and N-chlorophenylacetaldimine (2%). Treatment with powdered activated carbon (PAC) removed the off-flavor. Experiments with chlorination of 15 N-labeled phenylalanine suggested that PAC reductively decomposed trichloramine into N 2 gas and adsorbed all of the other identified TPs. Superfine PAC (median diameter, 0.7 μm) removed the off-flavor more rapidly than normal-size PAC (median diameter, 8.0 μm). Copyright © 2017 Elsevier Ltd. All rights reserved.

Iodide-assisted total lead measurement and determination of different lead fractions in drinking water samples.

Science.gov (United States)

Zhang, Yuanyuan; Ng, Ding-Quan; Lin, Yi-Pin

2012-07-01

Lead and its compounds are toxic and can harm human health, especially the intelligence development in children. Accurate measurement of total lead present in drinking water is crucial in determining the extent of lead contamination and human exposure due to drinking water consumption. The USEPA method for total lead measurement (no. 200.8) is often used to analyze lead levels in drinking water. However, in the presence of high concentration of the tetravalent lead corrosion product PbO(2), the USEPA method was not able to fully recover particulate lead due to incomplete dissolution of PbO(2) particles during strong acid digestion. In this study, a new procedure that integrates membrane separation, iodometric PbO(2) measurement, strong acid digestion and ICP-MS measurement was proposed and evaluated for accurate total lead measurement and quantification of different lead fractions including soluble Pb(2+), particulate Pb(II) carbonate and PbO(2) in drinking water samples. The proposed procedure was evaluated using drinking water reconstituted with spiked Pb(2+), spiked particulate Pb(II) carbonate and in situ formed or spiked PbO(2). Recovery tests showed that the proposed procedure and the USEPA method can achieve 93-112% and 86-103% recoveries respectively for samples containing low PbO(2) concentrations (0.018-0.076 mg Pb per L). For samples containing higher concentrations of PbO(2) (0.089-1.316 mg Pb per L), the USEPA method failed to meet the recovery requirement for total lead (85-115%) while the proposed method can achieve satisfactory recoveries (91-111%) and differentiate the soluble Pb(2+), particulate Pb(II) carbonate and PbO(2).

XPS study of the passive layers formed on lead in aqueous nitrate solutions

International Nuclear Information System (INIS)

Uchida, Miho; Okuwaki, Akitsugu

1997-01-01

The analysis of the lead surface immersed in aqueous nitrate solutions by X-ray photoelectron spectroscopy (XPS) shows the formation of passive oxide layer containing nitrogen compound. The oxide layer formed on the lead surface in aqueous ammonium nitrate solution was hydrolyzed and cracked. (author)

Evaluation and optimization of compound solubilization and delivery methods in a two-tiered ion channel lead optimization triage.

Science.gov (United States)

Hendricson, Adam W; Gallagher, Liz; Matchett, Michele; Ferrante, Meredith; Spence, Steve; Paiva, Tony; Shou, Wilson; Tertyshnikova, Svetlana; Krambis, Mike; Post-Munson, Deborah; Zhang, Litao; Knox, Ron

2012-04-01

Low-volume dispensing of neat dimethyl sulfoxide (DMSO) into plate-based assays conserves compound, assay reagents, and intermediate dilution plate cost and, as we demonstrate here, significantly improves structure-activity relationship resolution. Acoustic dispensing of DMSO solutions into standard volume 384W plates yielded inconsistent results in studies with 2 cell lines because of apparent effects on the integrity of the cell monolayer (increased intracellular Ca⁺⁺ levels as indicated by elevated basal dye fluorescence after acoustic transfer). PocketTip-mediated transfer was successful at increasing apparent potency on a more consistent basis. Notably, the correlation coefficient among fluorescence imaging plate reader (FLIPR):electrophysiology (EP) across a representative ~125 compound collection was increased ~5× via conversion to a PocketTip direct dispensation, indicating a triage assay more predictive of activity in the decisional patch-clamp assay. Very importantly, the EP-benchmarked false-negative rate as measured by compounds with FLIPR EC₅₀ more than the highest concentration tested fell from >11% to 5% assay-wide, and the relative FLIPR:EP rank-order fidelity increased from 55% to 78%. Elimination of the aqueous intermediate step provided additional benefits, including reduced assay cost, decreased cycle time, and reduced wet compound consumption rate. Direct DMSO dispensing has broad applicability to cell-based functional assays of multiple varieties, especially in cases where limit solubility in assay buffer is a recognized impediment to maximizing interassay connectivity.

Effect of γ-irradiation on volatile compounds of dried Welsh onion (Allium fistulosum L.)

International Nuclear Information System (INIS)

Gyawali, Rajendra; Seo, Hye-Young; Lee, Hyun-Ju; Song, Hyun-Pa; Kim, Dong-Ho; Byun, Myung-Woo; Kim, Kyong-Su

2006-01-01

The volatile compounds of γ-irradiated dried Welsh onion were isolated by simultaneous distillation-extraction (SDE) technique and then analyzed by gas chromatography-mass spectrometry (GC-MS) along with their non-irradiated counterparts. A total of 35 volatile compounds were identified in non-irradiated and 1 kGy irradiated samples and 36 volatile compounds were identified in 3, 5, 10 and 20 kGy irradiated samples so far belong to chemical classes of acid, alcohol, aldehyde, ester, furan, ketone and S-containing compound. S-containing compounds were detected as major volatile compounds of all experimental samples. Though the content of several compounds was increased after irradiation, content of major S-containing compounds was found to decreased in the process. Application of high-dose irradiation if required for microbial decontamination of dried Welsh onion is feasible as it enhanced the total concentration of volatile compounds by 31.60% and 24.85% at 10 and 20 kGy, respectively

4-aminopyridyl-based lead compounds targeting CYP51 prevent spontaneous parasite relapse in a chronic model and improve cardiac pathology in an acute model of Trypanosoma cruzi infection.

Science.gov (United States)

Calvet, Claudia Magalhaes; Choi, Jun Yong; Thomas, Diane; Suzuki, Brian; Hirata, Ken; Lostracco-Johnson, Sharon; de Mesquita, Liliane Batista; Nogueira, Alanderson; Meuser-Batista, Marcelo; Silva, Tatiana Araujo; Siqueira-Neto, Jair Lage; Roush, William R; de Souza Pereira, Mirian Claudia; McKerrow, James H; Podust, Larissa M

2017-12-01

Chagas disease, caused by the protozoan Trypanosoma cruzi, is the leading cause of heart failure in Latin America. The clinical treatment of Chagas disease is limited to two 60 year-old drugs, nifurtimox and benznidazole, that have variable efficacy against different strains of the parasite and may lead to severe side effects. CYP51 is an enzyme in the sterol biosynthesis pathway that has been exploited for the development of therapeutics for fungal and parasitic infections. In a target-based drug discovery program guided by x-ray crystallography, we identified the 4-aminopyridyl-based series of CYP51 inhibitors as being efficacious versus T.cruzi in vitro; two of the most potent leads, 9 and 12, have now been evaluated for toxicity and efficacy in mice. Both acute and chronic animal models infected with wild type or transgenic T. cruzi strains were evaluated. There was no evidence of toxicity in the 28-day dosing study of uninfected animals, as judged by the monitoring of multiple serum and histological parameters. In two acute models of Chagas disease, 9 and 12 drastically reduced parasitemia, increased survival of mice, and prevented liver and heart injury. None of the compounds produced long term sterile cure. In the less severe acute model using the transgenic CL-Brenner strain of T.cruzi, parasitemia relapsed upon drug withdrawal. In the chronic model, parasitemia fell to a background level and, as evidenced by the bioluminescence detection of T. cruzi expressing the red-shifted luciferase marker, mice remained negative for 4 weeks after drug withdrawal. Two immunosuppression cycles with cyclophosphamide were required to re-activate the parasites. Although no sterile cure was achieved, the suppression of parasitemia in acutely infected mice resulted in drastically reduced inflammation in the heart. The positive outcomes achieved in the absence of sterile cure suggest that the target product profile in anti-Chagasic drug discovery should be revised in favor of

Identification and Phytotoxicity Assessment of Phenolic Compounds in Chrysanthemoides monilifera subsp. monilifera (Boneseed)

OpenAIRE

Al Harun, Md Abdullah Yousuf; Johnson, Joshua; Uddin, Md Nazim; Robinson, Randall W.

2015-01-01

Chrysanthemoides monilifera subsp. monilifera (boneseed), a weed of national significance in Australia, threatens indigenous species and crop production through allelopathy. We aimed to identify phenolic compounds produced by boneseed and to assess their phytotoxicity on native species. Phenolic compounds in water and methanol extracts, and in decomposed litter-mediated soil leachate were identified using HPLC, and phytotoxicity of identified phenolics was assessed (repeatedly) through a stan...

Neuroprotective Compound from an Endophytic Fungus, Colletotrichum sp. JS-0367.

Science.gov (United States)

Song, Ji Hoon; Lee, Changyeol; Lee, Dahae; Kim, Soonok; Bang, Sunghee; Shin, Myoung-Sook; Lee, Jun; Kang, Ki Sung; Shim, Sang Hee

2018-05-23

Colletotrichum sp. JS-0367 was isolated from Morus alba (mulberry), identified, and cultured on a large scale for chemical investigation. One new anthraquinone (1) and three known anthraquinones (2-4) were isolated and identified using spectroscopic methods including 1D/2D-NMR and HRESIMS. Although the neuroprotective effects of some anthraquinones have been reported, the biological activities of the four anthraquinones isolated in this study have not been reported. Therefore, the neuroprotective effects of these compounds were determined against murine hippocampal HT22 cell death induced by glutamate. Compound 4, evariquinone, showed strong protective effects against HT22 cell death induced by glutamate by the inhibition of intracellular ROS accumulation and Ca 2+ influx triggered by glutamate. Immunoblot analysis revealed that compound 4 reduced the phosphorylation of MAPKs (JNK, ERK1/2, and p38) induced by glutamate. Furthermore, compound 4 strongly attenuated glutamate-mediated apoptotic cell death.

Chronology of lead pollution contained in banded coral skeletons

Energy Technology Data Exchange (ETDEWEB)

Dodge, R E; Gilbert, T R

1984-08-01

The possibility of the annual skeletal growth bands of reef-building corals containing a record of lead additions to the marine environment was investigated using coral skeletons from St. Croix, Virgin Islands. Concentrations of lead within a coral from a polluted reef averaged 395 ng/g, five fold higher than within a coral from a pristine site, 87 ng/g. The lead chronologies of both corals showed a significant increase in concentration towards the present during the past 26 yr. The increase in lead concentration in the coral from the pristine site is suggested to represent the increase in lead availability from global pollution. Coral skeletons offer the probability of development into tools for long term chemical recorders of levels of lead and possibly other metals or compounds in seawater. 50 references, 3 figures, 1 table.

Mechanisms of action of phenolic compounds in olive.

Science.gov (United States)

Rafehi, Haloom; Ververis, Katherine; Karagiannis, Tom C

2012-06-01

Olive oil, an oil rich in monounsaturated fatty acids (MUFCs) and minor constituents including phenolic compounds, is a major component of the Mediterranean diet. The potential health benefits of the Mediterranean diet were highlighted by the seminal Seven Countries Study, and more contemporary research has identified olive oil as a major element responsible for these effects. It is emerging that the phenolic compounds are the most likely candidates accounting for the cardioprotective and cancer preventative effects of extra virgin olive oil (EVOO). In particular, the phenolic compound, hydroxytyrosol has been identified as one of the most potent antioxidants found in olive oil. This review will briefly consider historical aspects of olive oil research and the biological properties of phenolic compounds in olive oil will be discussed. The focus of the discussion will be related to the mechanisms of action of hydroxytyrosol. Studies have demonstrated that hydroxytyrosol induces apoptosis and cell cycle arrest in cancer cells. Further, research has shown that hydroxytyrosol can prevent cardiovascular disease by reducing the expression of adhesion molecules on endothelial cells and preventing the oxidation of low-density lipoprotein (LDL). The molecular mechanisms accounting for these effects are reviewed.

Identification of a potential superhard compound ReCN

International Nuclear Information System (INIS)

Fan, Xiaofeng; Li, M.M.; Singh, David J.; Jiang, Qing; Zheng, W.T.

2015-01-01

Highlights: • We identify a new ternary compound ReCN with theoretical calculation. • The ternary compound ReCN is with two stable structures with P63mc and P3m1. • ReCN is a semiconductor from the calculation of electronic structures. • ReCN is found to possess the outstanding mechanical properties. • ReCN may be synthesized relatively easily. - Abstract: We identify a new ternary compound, ReCN and characterize its properties including structural stability and indicators of hardness using first principles calculations. We find that there are two stable structures with space groups P63mc (HI) and P3m1 (HII), in which there are no C–C and N–N bonds. Both structures, H1 and III are elastically and dynamically stable. The electronic structures show that ReCN is a semiconductor, although the parent compounds, ReC 2 and ReN 2 are both metallic. ReCN is found to possess the outstanding mechanical properties with the large bulk modulus, shear modulus and excellent ideal strengths. In addition, ReCN may perhaps be synthesized relatively easily because it becomes thermodynamic stable with respect to decomposition at very low pressures

The effect of lead-based paint hazard remediation on blood lead levels of lead poisoned children in New York City

International Nuclear Information System (INIS)

Leighton, Jessica; Klitzman, Susan; Sedlar, Slavenka; Matte, Thomas; Cohen, Neal L.

2003-01-01

Despite the widespread use of lead paint hazard control for children with lead poisoning, few controlled studies that estimate the effect of such control on children's blood lead levels have been published. This retrospective follow-up study examined the effects of lead hazard remediation and its timing on the blood lead levels of lead-poisoned children. From the New York City child blood lead registry, 221 children were selected who had an initial blood lead level of 20-44 μg/dL between 1 July 1994 and 31 December 1996; were 6 months to 6 years of age; had a report of a follow-up blood lead test between 10 and 14 months after the initial test; had a lead-based paint hazard identified in the primary dwelling unit prior to the 10- to 14-month follow-up blood lead test; had resided or spent time at only one address with an identified lead-based paint hazard; and were not chelated. The decline in geometric mean blood lead levels from baseline to 10-14 months later was compared for children whose homes were remediated and whose homes were not remediated during the follow-up period. Regardless of remediation, geometric mean blood lead levels declined significantly from 24.3 μg/dL at the initial diagnosis to 12.3 μg/dL at the 10- to 14-month follow-up blood lead test (P<0.01). Among the 146 children whose homes were remediated the geometric mean blood lead levels declined 53% compared to 41% among the 75 children whose homes were not remediated by the follow-up blood lead test, a remediation effect of approximately 20% (P<0.01). After adjusting for potential confounders, the remediation effect was 11%, although it was no longer significant. Race was the only factor that appeared to confound the relationship: Black children had higher follow-up blood lead levels even after controlling for other factors, including the natural logarithm of the initial blood lead level. The effect of remediation appeared to be stronger for younger (10 to <36 months old) than for older (36

Determining tissue-lead levels in large game mammals harvested with lead bullets: human health concerns.

Science.gov (United States)

Tsuji, L J S; Wainman, B C; Jayasinghe, R K; VanSpronsen, E P; Liberda, E N

2009-04-01

Recently, the use of lead isotope ratios has definitively identified lead ammunition as a source of lead exposure for First Nations people, but the isotope ratios for lead pellets and bullets were indistinguishable. Thus, lead-contaminated meat from game harvested with lead bullets may also be contributing to the lead body burden; however, few studies have determined if lead bullet fragments are present in big game carcasses. We found elevated tissue-lead concentrations (up to 5,726.0 microg/g ww) in liver (5/9) and muscle (6/7) samples of big game harvested with lead bullets and radiographic evidence of lead fragments. Thus, we would advise that the tissue surrounding the wound channel be removed and discarded, as this tissue may be contaminated by lead bullet fragments.

Determination of borneol and other chemical compounds of ...

African Journals Online (AJOL)

1Department of Pre-Clinical Sciences, Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Lot PT. 21144, Jalan Sungai Long, .... due to geographical variation of plant species, which lead to difference in environmental and culture conditions. In summary, the compounds detected in this study such as ...

Phytochemical Compounds and Antioxidant Capacity of Tucum-Do-Cerrado (Bactris setosa Mart), Brazil's Native Fruit.

Science.gov (United States)

Rosa, Fernanda R; Arruda, Andréa F; Siqueira, Egle M A; Arruda, Sandra F

2016-02-23

This study identified major phenolic compounds of the tucum-do-cerrado (Bactris setosa) peel, as well as antioxidant activity and total phytochemical compound concentration of different extracts of the peel and pulp of this fruit. Phenolic compounds of the different extracts of tucum-do-cerrado peel were identified and quantified using a high-performance liquid chromatography system coupled to a diode array detector (DAD). Total phytochemical compound content was determined by spectrophotometric assays and the antioxidant activity by ferric reducing antioxidant power and β-carotene/linoleic assays. Total phenolic, flavanols, total anthocyanins and yellow flavonoids concentration of tucum-do-cerrado were 122-, 14-, 264- and 61-fold higher in the peel than in the pulp, respectively. The aqueous, methanolic and ethanolic extracts of the tucum-do-cerrado peel exhibited higher antioxidant activity compared to its pulp. Flavanols, anthocyanins, flavones, phenolic acids and stilbenes were the main phenolic classes identified in the tucum-do-cerrado peel extracts. Results suggest that the antioxidant capacity and the phytochemical compound content of the tucum-do-cerrado are mainly associated with the peel. Although flavonoids are the main compounds identified in tucum-do-cerrado peel, other phenolics identified in minor amounts, such as phenolic acids and stilbenes, may be responsible for the high antioxidant capacity of the fruit.

Impact of Microbial Composition of Cambodian Traditional Dried Starters (Dombea on Flavor Compounds of Rice Wine: Combining Amplicon Sequencing With HP-SPME-GCMS

Directory of Open Access Journals (Sweden)

Sokny Ly

2018-05-01

Full Text Available Dombae is a traditional ferment starter which has been used for starchy based wine production in Cambodia. However, the production technology of rice wine in Cambodia is not optimized. The current study aimed to investigate the microbiota associated in five ferment starters and the effect of a traditional fermentation process using a metagenomics sequencing analysis and HS-SPME-GCMS for the characterization of the aromatic profiles at the end of fermentation. Most of bacteria identified in this study were lactic acid bacteria including Weissella cibaria, Pediococcus sp. MMZ60A, Lactobacillus fermentum, and Lactobacillus plantarum. Saccharomyces cerevisiae and Saccharomycopsis fibuligera were found to be abundant yeasts while the only amylolytic filamentous fungus was Rhizopus oryzae. A total of 25 aromatic compounds were detected and identified as esters, alcohols, acids, ketones and aldehydes. The alcohol group was dominant in each rice wine. Significant changes were observed at the level of microbial communities during fermentation, suggesting microbial succession for the assimilation of starch and subsequently assimilation of fermentation by-products leading to the production of flavor compounds. At this level, the presence of Weissella, Pediococcus, and Lactobacillus genus was strongly correlated with most of the flavor compounds detected.

Impact of Microbial Composition of Cambodian Traditional Dried Starters (Dombea) on Flavor Compounds of Rice Wine: Combining Amplicon Sequencing With HP-SPME-GCMS

Science.gov (United States)

Ly, Sokny; Mith, Hasika; Tarayre, Cédric; Taminiau, Bernard; Daube, Georges; Fauconnier, Marie-Laure; Delvigne, Frank

2018-01-01

Dombae is a traditional ferment starter which has been used for starchy based wine production in Cambodia. However, the production technology of rice wine in Cambodia is not optimized. The current study aimed to investigate the microbiota associated in five ferment starters and the effect of a traditional fermentation process using a metagenomics sequencing analysis and HS-SPME-GCMS for the characterization of the aromatic profiles at the end of fermentation. Most of bacteria identified in this study were lactic acid bacteria including Weissella cibaria, Pediococcus sp. MMZ60A, Lactobacillus fermentum, and Lactobacillus plantarum. Saccharomyces cerevisiae and Saccharomycopsis fibuligera were found to be abundant yeasts while the only amylolytic filamentous fungus was Rhizopus oryzae. A total of 25 aromatic compounds were detected and identified as esters, alcohols, acids, ketones and aldehydes. The alcohol group was dominant in each rice wine. Significant changes were observed at the level of microbial communities during fermentation, suggesting microbial succession for the assimilation of starch and subsequently assimilation of fermentation by-products leading to the production of flavor compounds. At this level, the presence of Weissella, Pediococcus, and Lactobacillus genus was strongly correlated with most of the flavor compounds detected. PMID:29867806

A Novel Polyaminocarboxylate Compound To Treat Murine Pulmonary Aspergillosis by Interfering with Zinc Metabolism.

Science.gov (United States)

Laskaris, Paris; Vicentefranqueira, Rocío; Helynck, Olivier; Jouvion, Grégory; Calera, José Antonio; du Merle, Laurence; Suzenet, Franck; Buron, Frédéric; de Sousa, Rodolphe Alves; Mansuy, Daniel; Cavaillon, Jean-Marc; Latgé, Jean-Paul; Munier-Lehmann, Hélène; Ibrahim-Granet, Oumaima

2018-06-01

Aspergillus fumigatus can cause pulmonary aspergillosis in immunocompromised patients and is associated with a high mortality rate due to a lack of reliable treatment options. This opportunistic pathogen requires zinc in order to grow and cause disease. Novel compounds that interfere with fungal zinc metabolism may therefore be of therapeutic interest. We screened chemical libraries containing 59,223 small molecules using a resazurin assay that compared their effects on an A. fumigatus wild-type strain grown under zinc-limiting conditions and on a zinc transporter knockout strain grown under zinc-replete conditions to identify compounds affecting zinc metabolism. After a first screen, 116 molecules were selected whose inhibitory effects on fungal growth were further tested by using luminescence assays and hyphal length measurements to confirm their activity, as well as by toxicity assays on HeLa cells and mice. Six compounds were selected following a rescreening, of which two were pyrazolones, two were porphyrins, and two were polyaminocarboxylates. All three groups showed good in vitro activity, but only one of the polyaminocarboxylates was able to significantly improve the survival of immunosuppressed mice suffering from pulmonary aspergillosis. This two-tier screening approach led us to the identification of a novel small molecule with in vivo fungicidal effects and low murine toxicity that may lead to the development of new treatment options for fungal infections by administration of this compound either as a monotherapy or as part of a combination therapy. Copyright © 2018 American Society for Microbiology.

Effect of training data size and noise level on support vector machines virtual screening of genotoxic compounds from large compound libraries.

Science.gov (United States)

Kumar, Pankaj; Ma, Xiaohua; Liu, Xianghui; Jia, Jia; Bucong, Han; Xue, Ying; Li, Ze Rong; Yang, Sheng Yong; Wei, Yu Quan; Chen, Yu Zong

2011-05-01

Various in vitro and in-silico methods have been used for drug genotoxicity tests, which show limited genotoxicity (GT+) and non-genotoxicity (GT-) identification rates. New methods and combinatorial approaches have been explored for enhanced collective identification capability. The rates of in-silco methods may be further improved by significantly diversified training data enriched by the large number of recently reported GT+ and GT- compounds, but a major concern is the increased noise levels arising from high false-positive rates of in vitro data. In this work, we evaluated the effect of training data size and noise level on the performance of support vector machines (SVM) method known to tolerate high noise levels in training data. Two SVMs of different diversity/noise levels were developed and tested. H-SVM trained by higher diversity higher noise data (GT+ in any in vivo or in vitro test) outperforms L-SVM trained by lower noise lower diversity data (GT+ in in vivo or Ames test only). H-SVM trained by 4,763 GT+ compounds reported before 2008 and 8,232 GT- compounds excluding clinical trial drugs correctly identified 81.6% of the 38 GT+ compounds reported since 2008, predicted 83.1% of the 2,008 clinical trial drugs as GT-, and 23.96% of 168 K MDDR and 27.23% of 17.86M PubChem compounds as GT+. These are comparable to the 43.1-51.9% GT+ and 75-93% GT- rates of existing in-silico methods, 58.8% GT+ and 79% GT- rates of Ames method, and the estimated percentages of 23% in vivo and 31-33% in vitro GT+ compounds in the "universe of chemicals". There is a substantial level of agreement between H-SVM and L-SVM predicted GT+ and GT- MDDR compounds and the prediction from TOPKAT. SVM showed good potential in identifying GT+ compounds from large compound libraries based on higher diversity and higher noise training data.

Exposure Evaluation for Benzene, Lead and Noise in Vehicle and Equipment Repair Shops

Energy Technology Data Exchange (ETDEWEB)

Sweeney, Lynn C. [Washington State Univ., Pullman, WA (United States)

2013-04-01

An exposure assessment was performed at the equipment and vehicle maintenance repair shops operating at the U. S. Department of Energy Hanford site, in Richland, Washington. The maintenance shops repair and maintain vehicles and equipment used in support of the Hanford cleanup mission. There are three general mechanic shops and one auto body repair shop. The mechanics work on heavy equipment used in construction, cranes, commercial motor vehicles, passenger-type vehicles in addition to air compressors, generators, and farm equipment. Services include part fabrication, installation of equipment, repair and maintenance work in the engine compartment, and tire and brake services. Work performed at the auto body shop includes painting and surface preparation which involves applying body filler and sanding. 8-hour time-weighted-average samples were collected for benzene and noise exposure and task-based samples were collected for lead dust work activities involving painted metal surfaces. Benzene samples were obtained using 3M™ 3520 sampling badges and were analyzed for additional volatile organic compounds. These compounds were selected based on material safety data sheet information for the aerosol products used by the mechanics for each day of sampling. The compounds included acetone, ethyl ether, toluene, xylene, VM&P naphtha, methyl ethyl ketone, and trichloroethylene. Laboratory data for benzene, VM&P naphtha, methyl ethyl ketone and trichloroethylene were all below the reporting detection limit. Airborne concentrations for acetone, ethyl ether, toluene and xylene were all less than 10% of their occupational exposure limit. The task-based samples obtained for lead dusts were submitted for a metal scan analysis to identify other metals that might be present. Laboratory results for lead dusts were all below the reporting detection limit and airborne concentration for the other metals observed in the samples were less than 10% of the occupational exposure limit

Effects of sublethal exposure to lead on levels of energetic compounds in Procambarus clarkii (Girard, 1852)

Energy Technology Data Exchange (ETDEWEB)

Martinez, M.; Torreblanca, A.; Del Ramo, J.; Diaz-Mayans, J. (Univ. of Valencia (Spain))

1994-05-01

Lead is neither essential nor beneficial to living organisms; all existing data show that its metabolic effects are adverse. Lead is toxic to all phyla of aquatic biota. Most of the lead discharged into surface water is rapidly incorporated into suspended and bottom sediments. The American red crayfish, Procambarus clarkii, lives in a wide range of environmental conditions that include highly polluted waters. Lead present in take sediments can be available to aquatic animals such as P. clarkii because it is a detritivor and burrow into the sediment. In fact, we found remarkable levels of lead in tissues of P. clarkii caught in Albufera Lake and kept 15 days in clean water (e. g. 223 [mu]g/g dry weight in gills). Furthermore, P. clarkii has a high capacity for lead accumulation from water, and gills were the most important tissue of lead accumulation. Among effects that contaminants have on the physiology of the organisms, energetic state variables are important, since they will alter both survival and reproduction. Hepatopancreas is a major site for the energetic reserve in crayfish and is a site of lead accumulation, although metal concentration in this organ is not as high as gills. The purpose of this study was to examine changes in energy reserves in hepatopancreas and gills of the crayfish P. clarkii, in response to sublethal exposure to lead. Gills are directly exposed to contaminants in the environment, and they are the first organ showing alterations by the action of the contaminants. Hepatopancreas was also chosen due to both, its relevance in the energetic metabolism and its role in heavy metal detoxification mechanisms.

Characterization and extraction of volatile compounds from pineapple (Ananas comosus L. Merril processing residues

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Lília Calheiros de Oliveira Barretto

2013-12-01

Full Text Available The aim of this study was to extract and identify volatile compounds from pineapple residues generated during concentrated juice processing. Distillates of pineapple residues were obtained using the following techniques: simple hydrodistillation and hydrodistillation by passing nitrogen gas. The volatile compounds present in the distillates were captured by the solid-phase microextraction technique. The volatile compounds were identified in a system of high resolution gas chromatography system coupled with mass spectrometry using a polyethylene glycol polar capillary column as stationary phase. The pineapple residues constituted mostly of esters (35%, followed by ketones (26%, alcohols (18%, aldehydes (9%, acids (3% and other compounds (9%. Odor-active volatile compounds were mainly identified in the distillate obtained using hydrodistillation by passing nitrogen gas, namely decanal, ethyl octanoate, acetic acid, 1-hexanol, and ketones such as γ-hexalactone, γ-octalactone, δ-octalactone, γ-decalactone, and γ-dodecalactone. This suggests that the use of an inert gas and lower temperatures helped maintain higher amounts of flavor compounds. These data indicate that pineapple processing residue contained important volatile compounds which can be extracted and used as aroma enhancing products and have high potential for the production of value-added natural essences.

Antiinflammatory and lipoxygenase inhibitory compounds from Vitex agnus-castus.

Science.gov (United States)

Choudhary, M Iqbal; Jalil, Saima; Nawaz, Sarfraz Ahmad; Khan, Khalid Mohammed; Tareen, Rasool Bakhsh

2009-09-01

Several secondary metabolites, artemetin (1), casticin (2), 3,3'-dihydroxy-5,6,7,4'-tetramethoxy flavon (3), penduletin (4), methyl 4-hydroxybenzoate (5), p-hydroxybenzoic acid (6), methyl 3,4-dihydroxybenzoate (7), 5-hydroxy-2-methoxybenzoic acid (8), vanillic acid (9) and 3,4-dihydroxybenzoic acid (10) were isolated from a folkloric medicinal plant, Vitex agnus-castus. The structures of compounds 1-10 were identified with the help of spectroscopic techniques. Compounds 3-10 were isolated for the first time from this plant. These compounds were screened for their antiinflammatory and lipoxygenase inhibitory activities. Compounds 6, 7 and 10 were found to have significant antiinflammatory activity in a cell-based contemporary assay, whereas compounds 1 and 2 exhibited a potent lipoxygenase inhibition.

Use of Electrohydrodynamic Processing for Encapsulation of Sensitive Bioactive Compounds and Applications in Food

DEFF Research Database (Denmark)

Jacobsen, Charlotte; García Moreno, Pedro Jesús; Mendes, Ana Carina Loureiro

2018-01-01

or in the gastrointestinal tract. For that purpose, efficient encapsulation of the compounds may be required. Spray drying is one of the most commonly used encapsulation techniques in the food industry, but it uses high temperature, which can lead to decomposition of the bioactive compounds. Recently, alternative...

Speciated measurements of semivolatile and intermediate volatility organic compounds (S/IVOCs in a pine forest during BEACHON-RoMBAS 2011

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A. W. H. Chan

2016-02-01

Full Text Available Understanding organic composition of gases and particles is essential to identifying sources and atmospheric processing leading to organic aerosols (OA, but atmospheric chemical complexity and the analytical techniques available often limit such analysis. Here we present speciated measurements of semivolatile and intermediate volatility organic compounds (S/IVOCs using a novel dual-use instrument (SV-TAG-AMS deployed at Manitou Forest, CO, during the Bio-hydro-atmosphere interactions of Energy, Aerosols, Carbon, H2O, Organics & Nitrogen – Rocky Mountain Biogenic Aerosol Study (BEACHON-RoMBAS 2011 campaign. This instrument provides on-line speciation of ambient organic compounds with 2 h time resolution. The species in this volatility range are complex in composition, but their chemical identities reveal potential sources. Observed compounds of biogenic origin include sesquiterpenes with molecular formula C15H24 (e.g., β-caryophyllene and longifolene, which were most abundant at night. A variety of other biogenic compounds were observed, including sesquiterpenoids with molecular formula C15H22, abietatriene and other terpenoid compounds. Many of these compounds have been identified in essential oils and branch enclosure studies but were observed in ambient air for the first time in our study. Semivolatile polycyclic aromatic hydrocarbons (PAHs and alkanes were observed with highest concentrations during the day and the dependence on temperature suggests the role of an evaporative source. Using statistical analysis by positive matrix factorization (PMF, we classify observed S/IVOCs by their likely sources and processes, and characterize them based on chemical composition. The total mass concentration of elutable S/IVOCs was estimated to be on the order of 0.7 µg m−3 and their volatility distributions are estimated for modeling aerosol formation chemistry.

Lead-resistant Providencia alcalifaciens strain 2EA bioprecipitates Pb+2 as lead phosphate.

Science.gov (United States)

Naik, M M; Khanolkar, D; Dubey, S K

2013-02-01

A lead-resistant bacteria isolated from soil contaminated with car battery waste were identified as Providencia alcalifaciens based on biochemical characteristics, FAME profile and 16S rRNA sequencing and designated as strain 2EA. It resists lead nitrate up to 0·0014 mol l(-1) by precipitating soluble lead as insoluble light brown solid. Scanning electron microscopy coupled with energy-dispersive X-ray spectrometric analysis (SEM-EDX) and X-ray diffraction spectroscopy (XRD) revealed extracellular light brown precipitate as lead orthophosphate mineral, that is, Pb(9) (PO(4))(6) catalysed by phosphatase enzyme. This lead-resistant bacterial strain also demonstrated tolerance to high levels of cadmium and mercury along with multiple antibiotic resistance. Providencia alcalifaciens strain 2EA could be used for bioremediation of lead-contaminated environmental sites, as it can efficiently precipitate lead as lead phosphate. © 2012 The Society for Applied Microbiology.

In silico probing and biological evaluation of SETDB1/ESET-targeted novel compounds that reduce tri-methylated histone H3K9 (H3K9me3) level

Science.gov (United States)

Park, Insun; Hwang, Yu Jin; Kim, TaeHun; Viswanath, Ambily Nath Indu; Londhe, Ashwini M.; Jung, Seo Yun; Sim, Kyoung Mi; Min, Sun-Joon; Lee, Ji Eun; Seong, Jihye; Kim, Yun Kyung; No, Kyoung Tai; Ryu, Hoon; Pae, Ae Nim

2017-10-01

ERG-associated protein with the SET domain (ESET/SET domain bifurcated 1/SETDB1/KMT1E) is a histone lysine methyltransferase (HKMT) and it preferentially tri-methylates lysine 9 of histone H3 (H3K9me3). SETDB1/ESET leads to heterochromatin condensation and epigenetic gene silencing. These functional changes are reported to correlate with Huntington's disease (HD) progression and mood-related disorders which make SETDB1/ESET a viable drug target. In this context, the present investigation was performed to identify novel peptide-competitive small molecule inhibitors of the SETDB1/ESET by a combined in silico-in vitro approach. A ligand-based pharmacophore model was built and employed for the virtual screening of ChemDiv and Asinex database. Also, a human SETDB1/ESET homology model was constructed to supplement the data further. Biological evaluation of the selected 21 candidates singled out 5 compounds exhibiting a notable reduction of the H3K9me3 level via inhibitory potential of SETDB1/ESET activity in SETDB1/ESET-inducible cell line and HD striatal cells. Later on, we identified two compounds as final hits that appear to have neuronal effects without cytotoxicity based on the result from MTT assay. These compounds hold the calibre to become the future lead compounds and can provide structural insights into more SETDB1/ESET-focused drug discovery research. Moreover, these SETDB1/ESET inhibitors may be applicable for the preclinical study to ameliorate neurodegenerative disorders via epigenetic regulation.

In silico probing and biological evaluation of SETDB1/ESET-targeted novel compounds that reduce tri-methylated histone H3K9 (H3K9me3) level.

Science.gov (United States)

Park, Insun; Hwang, Yu Jin; Kim, TaeHun; Viswanath, Ambily Nath Indu; Londhe, Ashwini M; Jung, Seo Yun; Sim, Kyoung Mi; Min, Sun-Joon; Lee, Ji Eun; Seong, Jihye; Kim, Yun Kyung; No, Kyoung Tai; Ryu, Hoon; Pae, Ae Nim

2017-10-01

ERG-associated protein with the SET domain (ESET/SET domain bifurcated 1/SETDB1/KMT1E) is a histone lysine methyltransferase (HKMT) and it preferentially tri-methylates lysine 9 of histone H3 (H3K9me3). SETDB1/ESET leads to heterochromatin condensation and epigenetic gene silencing. These functional changes are reported to correlate with Huntington's disease (HD) progression and mood-related disorders which make SETDB1/ESET a viable drug target. In this context, the present investigation was performed to identify novel peptide-competitive small molecule inhibitors of the SETDB1/ESET by a combined in silico-in vitro approach. A ligand-based pharmacophore model was built and employed for the virtual screening of ChemDiv and Asinex database. Also, a human SETDB1/ESET homology model was constructed to supplement the data further. Biological evaluation of the selected 21 candidates singled out 5 compounds exhibiting a notable reduction of the H3K9me3 level via inhibitory potential of SETDB1/ESET activity in SETDB1/ESET-inducible cell line and HD striatal cells. Later on, we identified two compounds as final hits that appear to have neuronal effects without cytotoxicity based on the result from MTT assay. These compounds hold the calibre to become the future lead compounds and can provide structural insights into more SETDB1/ESET-focused drug discovery research. Moreover, these SETDB1/ESET inhibitors may be applicable for the preclinical study to ameliorate neurodegenerative disorders via epigenetic regulation.

Structure-Based Virtual Screening of Commercially Available Compound Libraries.

Science.gov (United States)

Kireev, Dmitri

2016-01-01

Virtual screening (VS) is an efficient hit-finding tool. Its distinctive strength is that it allows one to screen compound libraries that are not available in the lab. Moreover, structure-based (SB) VS also enables an understanding of how the hit compounds bind the protein target, thus laying ground work for the rational hit-to-lead progression. SBVS requires a very limited experimental effort and is particularly well suited for academic labs and small biotech companies that, unlike pharmaceutical companies, do not have physical access to quality small-molecule libraries. Here, we describe SBVS of commercial compound libraries for Mer kinase inhibitors. The screening protocol relies on the docking algorithm Glide complemented by a post-docking filter based on structural protein-ligand interaction fingerprints (SPLIF).

Reaction of acid esters of methylenebis(phosphonous acid) with carbonyl compounds

International Nuclear Information System (INIS)

Novikova, Z.S.; Odinets, I.L.; Lutsenko, I.F.

1987-01-01

The reaction of methylenebis(phosphonites) containing two hydrophosphoryl groupings with aliphatic and aromatic aldehydes and ketones in the presence of alkali metal fluorides leads to methylenebis(α-hydroxyalkylphosphinates). The reaction of methylenebis(phosphonites) containing one hydrophosphoryl groupings with carbonyl compounds in the presence of alkali metal fluorides proceeds with the formation of a new type of heterocyclic phosphorus compound, viz., 1,2λ 3 ,4λ 5 -oxadiphospholanes. The reaction of acid esters of methylenebis(phosphonous) acid with carbonyl compounds in the presence of alkali metal alkoxides or a tertiary amine is accompanied by phosphinate-phosphonate rearrangement of the intermediately formed α-hydroxylalkylphosphinates

In silico identification of anti-cancer compounds and plants from traditional Chinese medicine database

Science.gov (United States)

Dai, Shao-Xing; Li, Wen-Xing; Han, Fei-Fei; Guo, Yi-Cheng; Zheng, Jun-Juan; Liu, Jia-Qian; Wang, Qian; Gao, Yue-Dong; Li, Gong-Hua; Huang, Jing-Fei

2016-05-01

There is a constant demand to develop new, effective, and affordable anti-cancer drugs. The traditional Chinese medicine (TCM) is a valuable and alternative resource for identifying novel anti-cancer agents. In this study, we aim to identify the anti-cancer compounds and plants from the TCM database by using cheminformatics. We first predicted 5278 anti-cancer compounds from TCM database. The top 346 compounds were highly potent active in the 60 cell lines test. Similarity analysis revealed that 75% of the 5278 compounds are highly similar to the approved anti-cancer drugs. Based on the predicted anti-cancer compounds, we identified 57 anti-cancer plants by activity enrichment. The identified plants are widely distributed in 46 genera and 28 families, which broadens the scope of the anti-cancer drug screening. Finally, we constructed a network of predicted anti-cancer plants and approved drugs based on the above results. The network highlighted the supportive role of the predicted plant in the development of anti-cancer drug and suggested different molecular anti-cancer mechanisms of the plants. Our study suggests that the predicted compounds and plants from TCM database offer an attractive starting point and a broader scope to mine for potential anti-cancer agents.

Two new compounds from the flowers of Rhododendron molle.

Science.gov (United States)

Chen, Shao-Nong; Bao, Guan-Hu; Wang, Li-Quan; Qin, Guo-Wei

2013-09-01

To study the chemical constituents of the flowers of Rhododendron molle. Compounds were isolated by repeated chromatography over silica gel and Sephadex LH-20. Structures were elucidated based on spectral techniques, mainly 1D- and 2D-NMR and mass spectrometric analyses. Two compounds (1 and 2) were isolated. Compounds 1 and 2 were identified as two new compounds: 2α, 10α-epoxy-3β, 5β, 6β, 14β, 16α-hexahydroxy-grayanane and benzyl 2, 6-dihydroxybenzoate-6-O-α-L-rhamnopyranosyl-(1→3)-β-D-glucopyranoside, respectively. Copyright © 2013 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Undesirable compounds in oils and fats: analysis and regulation

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Lacoste Florence

2003-03-01

Full Text Available The aim of this paper is to present, for some undesirable compounds representative of the major origins, a comparison between the efficiency of the analytical methods used (sensitivity, precision and existing regulations. An idea of the different origins of the presence of undesirable compounds in oils and fats is given. Then a focus is done on guidelines on contaminant analysis provided by European directives or Codex Alimentarius. The reliability of some existing test methods compared to regulations is also examined: lead, hexane, polycyclic aromatic hydrocarbons, and pesticide residues.

Volatile Organic Compounds (VOCs) in the Ambient Air Of Concentration Unit of Sar-Cheshmeh Copper Complex

International Nuclear Information System (INIS)

Faghihi-Zrandi, A.; Akhgar, M. R.

2016-01-01

Air pollutants including gases, vapors and particles, are emitted from different sources. Volatile organic compounds are the most important pollutants in the ambient air of industries. The present study was carried out to identify and measurement of volatile organic compounds in concentration unit of Sar-Cheshmeh Copper Complex. In this study, sampling of the volatile organic compounds was done by using activated charcoal tube. To identify and measure these compounds gas chromatography/mass spectroscopy were used. Thirteen volatile organic compounds were identified in the ambient air of concentration unit. Among these compounds, the mean value and maximum concentration of isopropyl alcohol and nonane were 255, 640 μg/m3 and 1577, 14400 μg/m3, respectively. By using SPSS software and independent sample t- test, showed that there were no significant difference between mean value concentration of isopropyl alcohol and nonane in the ambient air and TLV values of these compounds (isopropyl alcohol; 200 ppm and nonane; 200 ppm) (P >0.05).

Analysis of volatile compounds from Iberian hams: a review

Directory of Open Access Journals (Sweden)

Narváez-Rivas, M.

2012-10-01

Full Text Available This article provides information on the study of the volatile compounds in raw and dry-cured Iberian hams. Different volatile compounds are identified and studies carried out by different authors are presented. This article reviews the analytical methods that have been used to determine the different volatiles of these samples. Furthermore, all volatile compounds identified (a total of 411 volatiles have been collected in several tables according to different series of compounds: hydrocarbons, aldehydes, ketones, alcohols, esters and ethers, lactones, terpenes and chloride compounds, nitrogenous compounds, sulfur compounds and carboxylic acids. This review can be useful in subsequent research due to the complexity of the study.

En este artículo se proporciona información sobre el estudio de los compuestos volátiles del jamón ibérico tanto fresco como curado. Se presentan los diferentes compuestos volátiles identificados por distintos autores. Además, se evalúan los métodos analíticos que han sido utilizados para determinar dichos compuestos volátiles en este tipo de muestras. Todos los compuestos identificados y descritos en esta revisión (un total de 411 compuestos volátiles han sido agrupados en diversas tablas de acuerdo a las diferentes familias a que pertenecen: hidrocarburos, aldehídos, cetonas, alcoholes, ésteres y éteres, lactonas, terpenos, compuestos halogenados, compuestos nitrogenados, compuestos de azufre y ácidos carboxílicos. Debido a la complejidad de este estudio, la presente revisión puede ser muy útil en investigaciones posteriores.

Non-canonical programmed cell death mechanisms triggered by natural compounds.

Science.gov (United States)

Diederich, Marc; Cerella, Claudia

2016-10-01

Natural compounds are the fundament of pharmacological treatments and more than 50% of all anticancer drugs are of natural origins or at least derived from scaffolds present in Nature. Over the last 25 years, molecular mechanisms triggered by natural anticancer compounds were investigated. Emerging research showed that molecules of natural origins are useful for both preventive and therapeutic purposes by targeting essential hallmarks and enabling characteristics described by Hanahan and Weinberg. Moreover, natural compounds were able to change the differentiation status of selected cell types. One of the earliest response of cells treated by pharmacologically active compounds is the change of its morphology leading to ultra-structural perturbations: changes in membrane composition, cytoskeleton integrity, alterations of the endoplasmic reticulum, mitochondria and of the nucleus lead to formation of morphological alterations that are a characteristic of both compound and cancer type preceding cell death. Apoptosis and autophagy were traditionally considered as the most prominent cell death or cell death-related mechanisms. By now multiple other cell death modalities were described and most likely involved in response to chemotherapeutic treatment. It can be hypothesized that especially necrosis-related phenotypes triggered by various treatments or evolving from apoptotic or autophagic mechanisms, provide a more efficient therapeutic outcome depending on cancer type and genetic phenotype of the patient. In fact, the recent discovery of multiple regulated forms of necrosis and the initial elucidation of the corresponding cell signaling pathways appear nowadays as important tools to clarify the immunogenic potential of non-canonical forms of cell death induction. Copyright © 2016 Elsevier Ltd. All rights reserved.

High-throughput screen of drug repurposing library identifies inhibitors of Sarcocystis neurona growth.

Science.gov (United States)

Bowden, Gregory D; Land, Kirkwood M; O'Connor, Roberta M; Fritz, Heather M

2018-04-01

The apicomplexan parasite Sarcocystis neurona is the primary etiologic agent of equine protozoal myeloencephalitis (EPM), a serious neurologic disease of horses. Many horses in the U.S. are at risk of developing EPM; approximately 50% of all horses in the U.S. have been exposed to S. neurona and treatments for EPM are 60-70% effective. Advancement of treatment requires new technology to identify new drugs for EPM. To address this critical need, we developed, validated, and implemented a high-throughput screen to test 725 FDA-approved compounds from the NIH clinical collections library for anti-S. neurona activity. Our screen identified 18 compounds with confirmed inhibitory activity against S. neurona growth, including compounds active in the nM concentration range. Many identified inhibitory compounds have well-defined mechanisms of action, making them useful tools to study parasite biology in addition to being potential therapeutic agents. In comparing the activity of inhibitory compounds identified by our screen to that of other screens against other apicomplexan parasites, we found that most compounds (15/18; 83%) have activity against one or more related apicomplexans. Interestingly, nearly half (44%; 8/18) of the inhibitory compounds have reported activity against dopamine receptors. We also found that dantrolene, a compound already formulated for horses with a peak plasma concentration of 37.8 ± 12.8 ng/ml after 500 mg dose, inhibits S. neurona parasites at low concentrations (0.065 μM [0.036-0.12; 95% CI] or 21.9 ng/ml [12.1-40.3; 95% CI]). These studies demonstrate the use of a new tool for discovering new chemotherapeutic agents for EPM and potentially providing new reagents to elucidate biologic pathways required for successful S. neurona infection. Copyright © 2018. Published by Elsevier Ltd.

High-throughput screen of drug repurposing library identifies inhibitors of Sarcocystis neurona growth

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Gregory D. Bowden

2018-04-01

Full Text Available The apicomplexan parasite Sarcocystis neurona is the primary etiologic agent of equine protozoal myeloencephalitis (EPM, a serious neurologic disease of horses. Many horses in the U.S. are at risk of developing EPM; approximately 50% of all horses in the U.S. have been exposed to S. neurona and treatments for EPM are 60–70% effective. Advancement of treatment requires new technology to identify new drugs for EPM. To address this critical need, we developed, validated, and implemented a high-throughput screen to test 725 FDA-approved compounds from the NIH clinical collections library for anti-S. neurona activity. Our screen identified 18 compounds with confirmed inhibitory activity against S. neurona growth, including compounds active in the nM concentration range. Many identified inhibitory compounds have well-defined mechanisms of action, making them useful tools to study parasite biology in addition to being potential therapeutic agents. In comparing the activity of inhibitory compounds identified by our screen to that of other screens against other apicomplexan parasites, we found that most compounds (15/18; 83% have activity against one or more related apicomplexans. Interestingly, nearly half (44%; 8/18 of the inhibitory compounds have reported activity against dopamine receptors. We also found that dantrolene, a compound already formulated for horses with a peak plasma concentration of 37.8 ± 12.8 ng/ml after 500 mg dose, inhibits S. neurona parasites at low concentrations (0.065 μM [0.036–0.12; 95% CI] or 21.9 ng/ml [12.1–40.3; 95% CI]. These studies demonstrate the use of a new tool for discovering new chemotherapeutic agents for EPM and potentially providing new reagents to elucidate biologic pathways required for successful S. neurona infection. Keywords: Drug repurposing, High-throughput screen, Sarcocystis neurona, Equine protozoal myeloencephalitis

Magnetostriction of rare earth-Fe2 Laves phase compounds

International Nuclear Information System (INIS)

Clark, A.E.; Abbundi, R.; Savage, H.T.

1977-01-01

Single crystal magnetostriction measurements were made as a function of temperature on TbFe 2 and DyFe 2 . From these, the intrinsic magnetoelastic coupling coefficients were determined for the rare earth-Fe 2 compounds. Employing X-ray techniques, certain multicomponent rare earth-Fe 2 compounds were identified to maximize the magnetostriction to anisotropy ratio. (Auth.)

High-throughput screening in niche-based assay identifies compounds to target preleukemic stem cells

Science.gov (United States)

Gerby, Bastien; Veiga, Diogo F.T.; Krosl, Jana; Nourreddine, Sami; Ouellette, Julianne; Haman, André; Lavoie, Geneviève; Fares, Iman; Tremblay, Mathieu; Litalien, Véronique; Ottoni, Elizabeth; Geoffrion, Dominique; Maddox, Paul S.; Chagraoui, Jalila; Hébert, Josée; Sauvageau, Guy; Kwok, Benjamin H.; Roux, Philippe P.

2016-01-01

Current chemotherapies for T cell acute lymphoblastic leukemia (T-ALL) efficiently reduce tumor mass. Nonetheless, disease relapse attributed to survival of preleukemic stem cells (pre-LSCs) is associated with poor prognosis. Herein, we provide direct evidence that pre-LSCs are much less chemosensitive to existing chemotherapy drugs than leukemic blasts because of a distinctive lower proliferative state. Improving therapies for T-ALL requires the development of strategies to target pre-LSCs that are absolutely dependent on their microenvironment. Therefore, we designed a robust protocol for high-throughput screening of compounds that target primary pre-LSCs maintained in a niche-like environment, on stromal cells that were engineered for optimal NOTCH1 activation. The multiparametric readout takes into account the intrinsic complexity of primary cells in order to specifically monitor pre-LSCs, which were induced here by the SCL/TAL1 and LMO1 oncogenes. We screened a targeted library of compounds and determined that the estrogen derivative 2-methoxyestradiol (2-ME2) disrupted both cell-autonomous and non–cell-autonomous pathways. Specifically, 2-ME2 abrogated pre-LSC viability and self-renewal activity in vivo by inhibiting translation of MYC, a downstream effector of NOTCH1, and preventing SCL/TAL1 activity. In contrast, normal hematopoietic stem/progenitor cells remained functional. These results illustrate how recapitulating tissue-like properties of primary cells in high-throughput screening is a promising avenue for innovation in cancer chemotherapy. PMID:27797342

Leaf, branch, stand and landscape scale measurements of volatile organic compound fluxes from U. S. woodlands

Energy Technology Data Exchange (ETDEWEB)

Guenther, A.; Greenberg, J.; Harley, P.; Helmig, D.; Klinger, L.; Vierling, L.; Zimmerman, P. [National Center for Atmospheric Research, Boulder, CO (United States). Atmospheric Chemistry Div.; Geron, C. [Environmental Protection Agency, Research Triangle Park, NC (United States)

1996-01-01

Natural volatile organic compound (VOC) fluxes were measured in three U.S. woodlands. Fluxes from individual leaves and branches were estimated with enclosure techniques and used to initialize and evaluate VOC emission model estimates. Ambient measurements were used to estimate above canopy fluxes for entire stands. A total of 78 VOCs were identified, with hexenol derivatives being the most commonly observed oxygenated compounds. There was also evidence of high rates of isoprene emission and high rates of monoterpenes in some genera of trees. Model predictions of diurnal variations were within + or - 35 per cent of observed flux variations. Fluxes predicted by a recent version of a biogenic emission model were within 10 per cent to 50 per cent of observed fluxes, leading to the conclusion that existing databases can provide isoprene and monoterpene emission rate potentials within acceptable limits for the dominant plant species at these three woodland sites. 21 refs., 5 tabs., 2 figs.

Identification and Profiling of Active Compounds from Golden Apple Snail’s Egg Pigments

Directory of Open Access Journals (Sweden)

Asadatun Abdullah

2017-08-01

Full Text Available Golden apple snail (Pomacea canaliculata has been known as rice corps pest due to high adaptability and reproductive power. Utilization of Pomacea canaliculata’s eggs as raw materials in the food and health industry is one of the efforts to eradicate the pest snail. This study was aimed to identify the active compounds contained in the extract pigments of Pomacea canaliculata’s eggs. The methods of this study were extraction of pigments using acetone and methanol, analyzing the active compound (secondary metabolite qualitatively, TLC to determine pigment components and LC-MS/MS to identify active compounds semi quantitatively. The results showed that active compounds in the methanol extract contain 11 carotenoid pigments of xanthophyl group, two carotenoid pigments of carotene group, and 2 active compounds in nonpigmented form, whereas the acetone extract contain 11 pigmentcarotenoids of xanthophyl group and 2 compounds active in non-pigment form.

Gene Expression Signature Analysis Identifies Vorinostat as a Candidate Therapy for Gastric Cancer

Science.gov (United States)

Choi, Woonyoung; Park, Yun-Yong; Kim, KyoungHyun; Kim, Sang-Bae; Lee, Ju-Seog; Mills, Gordon B.; Cho, Jae Yong

2011-01-01

Background Gastric cancer continues to be one of the deadliest cancers in the world and therefore identification of new drugs targeting this type of cancer is thus of significant importance. The purpose of this study was to identify and validate a therapeutic agent which might improve the outcomes for gastric cancer patients in the future. Methodology/Principal Findings Using microarray technology, we generated a gene expression profile of human gastric cancer–specific genes from human gastric cancer tissue samples. We used this profile in the Broad Institute's Connectivity Map analysis to identify candidate therapeutic compounds for gastric cancer. We found the histone deacetylase inhibitor vorinostat as the lead compound and thus a potential therapeutic drug for gastric cancer. Vorinostat induced both apoptosis and autophagy in gastric cancer cell lines. Pharmacological and genetic inhibition of autophagy however, increased the therapeutic efficacy of vorinostat, indicating that a combination of vorinostat with autophagy inhibitors may therapeutically be more beneficial. Moreover, gene expression analysis of gastric cancer identified a collection of genes (ITGB5, TYMS, MYB, APOC1, CBX5, PLA2G2A, and KIF20A) whose expression was elevated in gastric tumor tissue and downregulated more than 2-fold by vorinostat treatment in gastric cancer cell lines. In contrast, SCGB2A1, TCN1, CFD, APLP1, and NQO1 manifested a reversed pattern. Conclusions/Significance We showed that analysis of gene expression signature may represent an emerging approach to discover therapeutic agents for gastric cancer, such as vorinostat. The observation of altered gene expression after vorinostat treatment may provide the clue to identify the molecular mechanism of vorinostat and those patients likely to benefit from vorinostat treatment. PMID:21931799

High-throughput respirometric assay identifies predictive toxicophore of mitochondrial injury

Energy Technology Data Exchange (ETDEWEB)

Wills, Lauren P. [MitoHealth Inc., Charleston, SC 29403 (United States); Beeson, Gyda C.; Trager, Richard E.; Lindsey, Christopher C. [Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC 29425 (United States); Beeson, Craig C. [MitoHealth Inc., Charleston, SC 29403 (United States); Peterson, Yuri K. [Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC 29425 (United States); Schnellmann, Rick G., E-mail: schnell@musc.edu [Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC 29425 (United States); Ralph H. Johnson VA Medical Center, Charleston, SC 29401 (United States)

2013-10-15

Many environmental chemicals and drugs negatively affect human health through deleterious effects on mitochondrial function. Currently there is no chemical library of mitochondrial toxicants, and no reliable methods for predicting mitochondrial toxicity. We hypothesized that discrete toxicophores defined by distinct chemical entities can identify previously unidentified mitochondrial toxicants. We used a respirometric assay to screen 1760 compounds (5 μM) from the LOPAC and ChemBridge DIVERSet libraries. Thirty-one of the assayed compounds decreased uncoupled respiration, a stress test for mitochondrial dysfunction, prior to a decrease in cell viability and reduced the oxygen consumption rate in isolated mitochondria. The mitochondrial toxicants were grouped by chemical similarity and two clusters containing four compounds each were identified. Cheminformatic analysis of one of the clusters identified previously uncharacterized mitochondrial toxicants from the ChemBridge DIVERSet. This approach will enable the identification of mitochondrial toxicants and advance the prediction of mitochondrial toxicity for both drug discovery and risk assessment. - Highlights: • Respirometric assay conducted in RPTC to create mitochondrial toxicant database. • Chemically similar mitochondrial toxicants aligned as mitochondrial toxicophores • Mitochondrial toxicophore identifies five novel mitochondrial toxicants.

High-throughput respirometric assay identifies predictive toxicophore of mitochondrial injury

International Nuclear Information System (INIS)

Wills, Lauren P.; Beeson, Gyda C.; Trager, Richard E.; Lindsey, Christopher C.; Beeson, Craig C.; Peterson, Yuri K.; Schnellmann, Rick G.

2013-01-01

Many environmental chemicals and drugs negatively affect human health through deleterious effects on mitochondrial function. Currently there is no chemical library of mitochondrial toxicants, and no reliable methods for predicting mitochondrial toxicity. We hypothesized that discrete toxicophores defined by distinct chemical entities can identify previously unidentified mitochondrial toxicants. We used a respirometric assay to screen 1760 compounds (5 μM) from the LOPAC and ChemBridge DIVERSet libraries. Thirty-one of the assayed compounds decreased uncoupled respiration, a stress test for mitochondrial dysfunction, prior to a decrease in cell viability and reduced the oxygen consumption rate in isolated mitochondria. The mitochondrial toxicants were grouped by chemical similarity and two clusters containing four compounds each were identified. Cheminformatic analysis of one of the clusters identified previously uncharacterized mitochondrial toxicants from the ChemBridge DIVERSet. This approach will enable the identification of mitochondrial toxicants and advance the prediction of mitochondrial toxicity for both drug discovery and risk assessment. - Highlights: • Respirometric assay conducted in RPTC to create mitochondrial toxicant database. • Chemically similar mitochondrial toxicants aligned as mitochondrial toxicophores • Mitochondrial toxicophore identifies five novel mitochondrial toxicants

Fluconazole-Pyridoxine Bis-Triazolium Compounds with Potent Activity against Pathogenic Bacteria and Fungi Including Their Biofilm-Embedded Forms

Directory of Open Access Journals (Sweden)

Marsel R. Garipov

2017-01-01

Full Text Available Two novel quaternary ammonium salts, bis-triazolium derivatives of fluconazole and pyridoxine, were synthesized by reaction of fluconazole with pyridoxine-based synthetic intermediates. The leading compound demonstrated pronounced antimycotic and antibacterial in vitro activity, comparable to or exceeding that of the reference antifungal (fluconazole, terbinafine and antibacterial/antiseptic (miramistin, benzalkonium chloride agents. In contrast to many antimicrobials, the leading compound was also active against biofilm-embedded staphylococci and Escherichia coli. While no biofilm structure destruction occurred, all compounds were able to diffuse into the matrix and reduce the number of colony-forming units by three orders of magnitude at 16 × MBC. The leading compound was significantly less toxic than miramistin and benzalkonium chloride and more toxic than the reference antifungal drugs. The obtained results make the described chemotype a promising starting point for the development of new broad-spectrum antimicrobial therapies with powerful effect on fungal and bacterial pathogens including their biofilm-embedded forms.

Protonation sites of aromatic compounds in (+) atmospheric pressure photoionization

Energy Technology Data Exchange (ETDEWEB)

Kim, Sung Hwan; Ahmed, Arif [Dept. of Chemistry, Kyungpoo k National University, Daegu (Korea, Republic of)

2017-02-15

Reaction enthalpy of hydrogen transfer reactions of aromatic compounds has been observed to be greatly affected by the exact location of the protonation site. Therefore, to clearly identify the protonation location, each candidate protonation site for 43 aromatic compounds were theoretically determined and their location was compared with that determined based on experimental MS data. Only the basic nitrogen atom is favorable as a protonation site for pyridine-type aromatic compounds, whereas carbon atoms are preferable for the protonation of pyrrole-type compounds. The most favorable protonation sites for aniline or methylated aniline-type aromatic compounds are either the nitrogen atom in the amine group or the carbon atom at the para-position to the amine group. Like pyrrole-type compounds, aromatic compounds with amine groups also favor protonation at the carbon atom instead of at the nitrogen atom. In addition, hydrocarbons having an anthracene structural motif without heteroatoms produced higher or equal percentages of protonated ions compared to that achieved with molecular ions. The results of this study can be used to improve the analyses of aromatic compounds.

[Effects of lead exposure on the human body and health implications].

Science.gov (United States)

Moreira, Fátima Ramos; Moreira, Josino Costa

2004-02-01

To review the literature concerning the risks associated with exposure to lead and lead compounds, especially in children and in populations that are occupationally exposed. Using "chumbo" [lead] and "efeitos" [effects] as search terms, two large databases, namely PubMed (United States National Library of Medicine) and LILACS (Literatura Latino-Americana e do Caribe em Ciências da Saúde [Latin American and Caribbean Literature in the Health Sciences]), were searched for studies on lead toxicity from 1988 to 2002. Other sources used to conduct the search include the web page of the United States Agency for Toxic Substances and Disease Registry, in Atlanta, Georgia, and the library of the Toxicology Laboratory of the Center for Workers' Health and Human Ecology at the National School of Public Health [Centro de Estudos da Saúde de Trabalhador e Ecologia Humana, Escola Nacional de Saúde Pública], Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. The toxic effects of lead and lead compounds have been extensively studied for over a century. In recent years, epidemiologic studies have focused primarily on the neurotoxic effects of lead on children, particularly in terms of impaired intellectual ability and behavioral problems. However, there is still insufficient information on the mechanisms of action that account for such toxicity. More in-depth studies are also needed on the effects of lead exposure on bone, the central nervous system, the cardiovascular system, the kidneys, the liver, the male and female reproductive systems, and the endocrine system. The potential teratogenicity and carcinogenicity of lead, as well as its effect on pregnancy outcomes and neonatal growth and development, also require further study.

Ionic Liquids in the Synthesis of Antioxidant Targeted Compounds

NARCIS (Netherlands)

Falkeborg, Mia; Berton-Carabin, Claire C.; Cheong, Ling Zhi

2016-01-01

Oxidation of polyunsaturated lipids is a major cause of degradation of the sensory and nutritional quality of food products. The oxidation reactions lead to formation of volatile compounds generally associated with unpleasant flavors, which damages the sensory quality of foods. Lipid oxidation is

Behaviour of organic sulfur compounds in HPLC

International Nuclear Information System (INIS)

Freyholdt, T.

1982-01-01

The retention behaviour of organic sulfur compounds in the reverse-bonded-phase chromatography is characterized by determining the retention indices according to Kovats. The results of these studies show that the solubility of organic compounds in the eluting agent and the molar sorption surfaces of the solutes are the main factors determining the retention behaviour. Knowledge of the retention indices of above-mentioned compounds allows a quick interpretation of chromatograms obtained through a product analysis of γ-irradiated aqueous solutions of organic sulfur compounds. Dithia compounds of the type CH 3 -S-(CH 2 )sub(n)-S-Ch 3 (1 1. 2,4-Dithiapentane (n = 1) however will yield primarily monothio-S-methyl formate as a stable end product. The formation of oxygenic reaction products proceeds via sulfur-centred radical kations. Spin trapping experiments with nitroxyl radicals show that it is possible to trap radiation-chemically produced radicals of sulfurous substrates, but the thus obtained adducts with half-life periods of 4-5 min. cannot be identified by means of NMR, IR or mass spectroscopy. (orig.) [de

Occurrence and abatement of volatile sulfur compounds during biogas production.

Science.gov (United States)

Andersson, Fräs Annika T; Karlsson, Anna; Svensson, Bo H; Ejlertsson, Jörgen

2004-07-01

Volatile sulfur compounds (VSCs) in biogas originating from a biogas production plant and from a municipal sewage water treatment plant were identified. Samples were taken at various stages of the biogas-producing process, including upgrading the gas to vehicle-fuel quality. Solid-phase microextraction was used for preconcentration of the VSCs, which were subsequently analyzed using gas chromatography in combination with mass spectrometry. Other volatile organic compounds present also were identified. The most commonly occurring VSCs in the biogas were hydrogen sulfide, carbonyl sulfide, methanethiol, dimethyl sulfide, and dimethyl disulfide, and hydrogen sulfide was not always the most abundant sulfur (S) compound. Besides VSCs, oxygenated organic compounds were commonly present (e.g., ketones, alcohols, and esters). The effect of adding iron chloride to the biogas reactor on the occurrence of VSCs also was investigated. It was found that additions of 500-g/m3 substrate gave an optimal removal of VSCs. Also, the use of a prefermentation step could reduce the amount of VSCs formed in the biogas process. Moreover, in the carbon dioxide scrubber used for upgrading the gas, VSCs were removed efficiently, leaving traces (ppbv levels). The scrubber also removed other organic compounds.

Unconventional superconductivity in heavy-fermion compounds

Energy Technology Data Exchange (ETDEWEB)

White, B.D. [Department of Physics, University of California, San Diego, La Jolla, CA 92093 (United States); Center for Advanced Nanoscience, University of California, San Diego, La Jolla, CA 92093 (United States); Thompson, J.D. [Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); Maple, M.B., E-mail: mbmaple@ucsd.edu [Department of Physics, University of California, San Diego, La Jolla, CA 92093 (United States); Center for Advanced Nanoscience, University of California, San Diego, La Jolla, CA 92093 (United States)

2015-07-15

Highlights: • Quasiparticles in heavy-fermion compounds are much heavier than free electrons. • Superconductivity involves pairing of these massive quasiparticles. • Quasiparticle pairing mediated by magnetic or quadrupolar fluctuations. • We review the properties of superconductivity in heavy-fermion compounds. - Abstract: Over the past 35 years, research on unconventional superconductivity in heavy-fermion systems has evolved from the surprising observations of unprecedented superconducting properties in compounds that convention dictated should not superconduct at all to performing explorations of rich phase spaces in which the delicate interplay between competing ground states appears to support emergent superconducting states. In this article, we review the current understanding of superconductivity in heavy-fermion compounds and identify a set of characteristics that is common to their unconventional superconducting states. These core properties are compared with those of other classes of unconventional superconductors such as the cuprates and iron-based superconductors. We conclude by speculating on the prospects for future research in this field and how new advances might contribute towards resolving the long-standing mystery of how unconventional superconductivity works.

Teachers’ knowledge for teaching compound interest

Directory of Open Access Journals (Sweden)

Craig Pournara

2013-11-01

Full Text Available There is increasing acknowledgement that teachers’ knowledge for teaching mathematics is multifaceted and topic specific. Given the paucity of research on the teaching and learning of financial mathematics in general, little can be known about teachers’ knowledge for teaching compound interest. However, since financial mathematics is a component of the school curriculum in South Africa, and an important element of financial literacy more broadly, attention needs to be given to knowledge for teaching financial mathematics, and compound interest in particular. Drawing from a larger study in which the author taught a financial mathematics course to pre-service secondary mathematics teachers, a theoretical elaboration is provided of the underlying mathematics of compound interest, and connections with the world of banking. Based on findings from the study, two key student errors are identified: the over-generalisation of linear thinking in multiplicative scenarios, and the over-generalisation of reversible operations in percentage-change scenarios. Taken together, teachers’ knowledge of relevant mathematics, of the banking context and of learners’ conceptions will contribute to building a knowledge-base for teachers’ knowledge for teaching compound interest.

Screening in larval zebrafish reveals tissue-specific distribution of fifteen fluorescent compounds

Directory of Open Access Journals (Sweden)

Yuxiao Yao

2017-09-01

Full Text Available The zebrafish is a prominent vertebrate model for low-cost in vivo whole organism screening. In our recent screening of the distribution patterns of fluorescent compounds in live zebrafish larvae, fifteen compounds with tissue-specific distributions were identified. Several compounds were observed to accumulate in tissues where they were reported to induce side-effects, and compounds with similar structures tended to be enriched in the same tissues, with minor differences. In particular, we found three novel red fluorescent bone-staining dyes: purpurin, lucidin and 3-hydroxy-morindone; purpurin can effectively label bones in both larval and adult zebrafish, as well as in postnatal mice, without significantly affecting bone mass and density. Moreover, two structurally similar chemotherapeutic compounds, doxorubicin and epirubicin, were observed to have distinct distribution preferences in zebrafish. Epirubicin maintained a relatively higher concentration in the liver, and performed better in inhibiting hepatic hyperplasia caused by the over-expression of krasG12V. In total, our study suggests that the transparent zebrafish larvae serve as valuable tools for identifying tissue-specific distributions of fluorescent compounds.

Two-dimensional materials from high-throughput computational exfoliation of experimentally known compounds

Science.gov (United States)

Mounet, Nicolas; Gibertini, Marco; Schwaller, Philippe; Campi, Davide; Merkys, Andrius; Marrazzo, Antimo; Sohier, Thibault; Castelli, Ivano Eligio; Cepellotti, Andrea; Pizzi, Giovanni; Marzari, Nicola

2018-02-01

Two-dimensional (2D) materials have emerged as promising candidates for next-generation electronic and optoelectronic applications. Yet, only a few dozen 2D materials have been successfully synthesized or exfoliated. Here, we search for 2D materials that can be easily exfoliated from their parent compounds. Starting from 108,423 unique, experimentally known 3D compounds, we identify a subset of 5,619 compounds that appear layered according to robust geometric and bonding criteria. High-throughput calculations using van der Waals density functional theory, validated against experimental structural data and calculated random phase approximation binding energies, further allowed the identification of 1,825 compounds that are either easily or potentially exfoliable. In particular, the subset of 1,036 easily exfoliable cases provides novel structural prototypes and simple ternary compounds as well as a large portfolio of materials to search from for optimal properties. For a subset of 258 compounds, we explore vibrational, electronic, magnetic and topological properties, identifying 56 ferromagnetic and antiferromagnetic systems, including half-metals and half-semiconductors.

Distribution and potential ecological risk of 50 phenolic compounds in three rivers in Tianjin, China.

Science.gov (United States)

Zhong, Wenjue; Wang, Donghong; Wang, Zijian

2018-04-01

Phenolic compounds widely exist in the surface water of many countries; however, few studies have simultaneously analyzed and evaluated broad-spectrum phenolic compounds in various components of the water environment. Therefore this study analyzed the distribution and potential ecological risk of 50 phenolic compounds in the surface water, sediment and suspended particulate matter of three important rivers in Tianjin, the main heavy industry city with high pollution in China. The qualitative results show that phenolic pollution existed extensively in the three rivers and the kinds of phenolic compounds in the water were relatively higher than in both sediment and suspended particulate matter. The quantitative results show that the phenolic pollution in the wet-season samples was serious than dry-season samples. Meanwhile, total concentrations of phenolic compounds in three components from the Dagu Drainage River (DDR) were all much higher than those in the Beitang Drainage River (BDR) and Yongdingxin River (YDXR). The highest total concentrations of phenolic compounds in three components all appeared in wet-season samples in DDR, and the highest total concentration was 1354 μg/L in surface water, 719 μg/kg dw in suspended particulate matter and 2937 μg/kg dw in sediment, respectively. The ecological risk of phenolic compounds in surface water was evaluated using the quotient method, and phenolic compounds with risk quotient (RQ) > 1 (RQ > 0.3 for YDXR) were identified as priority pollutants. Five kinds of phenolic compounds were identified as priority phenolic compounds in BDR, and the order of risk was 2-cresol > 2,4-xylenol > 2-sec-butylphenol > 2-naphthol > 3-cresol. Six kinds of phenolic compounds were identified as priority phenolic compounds in DDR, and the order of risk was 2-naphthol > p-chloro-m-xylenol > 4-cresol > 3-cresol > 2,4-xylenol > 2,3,6-Trimethylphenol. In YDXR, only phenol, 2-naphthol and 2,4-xylenol were identified as

Flavonoid Compounds from the Bark of Aglaia eximia (Meliaceae)

OpenAIRE

Julinton Sianturi; Mayshah Purnamasari; Tri Mayanti; Desi Harneti; Unang Supratman; Khalijah Awang; Hideo Hayashi

2015-01-01

Three flavonoid compounds, kaempferol (1), kaempferol-3-O-α-L-rhamnoside (2), and kaempferol-3-O-β-D-glucosyl-α-L-rhamnoside (3), were isolated from the bark of Aglaia eximia (Meliaceae). The chemical structures of compounds 1–3 were identified with spectroscopic data, including UV, IR, NMR (1H, 13C, DEPT 135°, HMQC, HMBC, 1H-1H-COSY NMR), and MS, as well as a compared with previously reported spectra data. All compounds were evaluated for their cytotoxic effects against P-388 murine leukemia...

High-performance liquid chromatographic method for guanylhydrazone compounds.

Science.gov (United States)

Cerami, C; Zhang, X; Ulrich, P; Bianchi, M; Tracey, K J; Berger, B J

1996-01-12

A high-performance liquid chromatographic method has been developed for a series of aromatic guanylhydrazones that have demonstrated therapeutic potential as anti-inflammatory agents. The compounds were separated using octadecyl or diisopropyloctyl reversed-phase columns, with an acetonitrile gradient in water containing heptane sulfonate, tetramethylammonium chloride, and phosphoric acid. The method was used to reliably quantify levels of analyte as low as 785 ng/ml, and the detector response was linear to at least 50 micrograms/ml using a 100 microliters injection volume. The assay system was used to determine the basic pharmacokinetics of a lead compound, CNI-1493, from serum concentrations following a single intravenous injection in rats.

Organic compounds in hydraulic fracturing fluids and wastewaters: A review.

Science.gov (United States)

Luek, Jenna L; Gonsior, Michael

2017-10-15

High volume hydraulic fracturing (HVHF) of shale to stimulate the release of natural gas produces a large quantity of wastewater in the form of flowback fluids and produced water. These wastewaters are highly variable in their composition and contain a mixture of fracturing fluid additives, geogenic inorganic and organic substances, and transformation products. The qualitative and quantitative analyses of organic compounds identified in HVHF fluids, flowback fluids, and produced waters are reviewed here to communicate knowledge gaps that exist in the composition of HVHF wastewaters. In general, analyses of organic compounds have focused on those amenable to gas chromatography, focusing on volatile and semi-volatile oil and gas compounds. Studies of more polar and non-volatile organic compounds have been limited by a lack of knowledge of what compounds may be present as well as quantitative methods and standards available for analyzing these complex mixtures. Liquid chromatography paired with high-resolution mass spectrometry has been used to investigate a number of additives and will be a key tool to further research on transformation products that are increasingly solubilized through physical, chemical, and biological processes in situ and during environmental contamination events. Diverse treatments have been tested and applied to HVHF wastewaters but limited information has been published on the quantitative removal of individual organic compounds. This review focuses on recently published information on organic compounds identified in flowback fluids and produced waters from HVHF. Copyright © 2017 Elsevier Ltd. All rights reserved.

Identification of potential leads against 4-hydroxytetrahydrodipicolinate synthase from Mycobacterium tuberculosis

Science.gov (United States)

Rehman, Ajijur; Akhtar, Salman; Siddiqui, Mohd Haris; Sayeed, Usman; Ahmad, Syed Sayeed; Arif, Jamal M.; Khan, M. Kalim A.

2016-01-01

4-hydroxy-tetrahydrodipicolinate synthase (DHDPS) is an important enzyme needed for the biosynthesis of lysine and many more key metabolites in Mycobacterium tuberculosis (Mtb). Inhibition of DHDPS is supposed to a promising therapeutic target due to its specific role in sporulation, cross-linking of the peptidiglycan polymers and biosynthesis of amino acids. In this work, a known inhibitor-based similarity search was carried out against a natural products database (Super Natural II) towards identification of more potent phyto-inhibitors. Molecular interaction studies were accomplished using three different tools to understand and establish the participation of active site residues as the key players in stabilizing the binding mode of ligands and target protein. The best phyto-compound deduced on the basis of binding affinity was further used as a template to make similarity scan across the PubChem Compound database (score > = 80 %) to get more divesred leads. In this search 5098 hits were obtained that further reduced to 262 after drug-likeness filtration. These phytochemicallike compounds were docked at the active site of DHDPS.Then, those hits selected from docking analysis that showing stronger binding and forming maximum H-bonds with the active site residues (Thr54, Thr55, Tyr143, Arg148 and Lys171). Finally, we predicted one phytochemical compound (SN00003544), two PubChem-compounds (CID41032023, CID54025334) akin to phytochemical molecule showing better interactions in comaprison of known inhibitors of target protein.These findings might be further useful to gain the structural insight into the designing of novel leads against DapA family. PMID:28293071

Radiograph identifying means

International Nuclear Information System (INIS)

Sheldon, A.D.

1983-01-01

A flexible character-indentable plastics embossing tape is backed by and bonded to a lead strip, not more than 0.025 inches thick, to form a tape suitable for identifying radiographs. The lead strip is itself backed by a relatively thin and flimsy plastics or fabric strip which, when removed, allows the lead plastic tape to be pressure-bonded to the surface to be radiographed. A conventional tape-embossing gun is used to indent the desired characters in succession into the lead-backed tape, without necessarily severing the lead; and then the backing strip is peeled away to expose the layer of adhesive which pressure-bonds the indented tape to the object to be radiographed. X-rays incident on the embossed tape will cause the raised characters to show up dark on the subsequently-developed film, whilst the raised side areas will show up white. Each character will thus stand out on the developed film. (author)

Lead Halide Perovskite Nanocrystals in the Research Spotlight: Stability and Defect Tolerance

Science.gov (United States)

2017-01-01

This Perspective outlines basic structural and optical properties of lead halide perovskite colloidal nanocrystals, highlighting differences and similarities between them and conventional II–VI and III–V semiconductor quantum dots. A detailed insight into two important issues inherent to lead halide perovskite nanocrystals then follows, namely, the advantages of defect tolerance and the necessity to improve their stability in environmental conditions. The defect tolerance of lead halide perovskites offers an impetus to search for similar attributes in other related heavy metal-free compounds. We discuss the origins of the significantly blue-shifted emission from CsPbBr3 nanocrystals and the synthetic strategies toward fabrication of stable perovskite nanocrystal materials with emission in the red and infrared parts of the optical spectrum, which are related to fabrication of mixed cation compounds guided by Goldschmidt tolerance factor considerations. We conclude with the view on perspectives of use of the colloidal perovskite nanocrystals for applications in backlighting of liquid-crystal TV displays. PMID:28920080

A "genome-to-lead" approach for insecticide discovery: pharmacological characterization and screening of Aedes aegypti D(1-like dopamine receptors.

Directory of Open Access Journals (Sweden)

Jason M Meyer

2012-01-01

Full Text Available BACKGROUND: Many neglected tropical infectious diseases affecting humans are transmitted by arthropods such as mosquitoes and ticks. New mode-of-action chemistries are urgently sought to enhance vector management practices in countries where arthropod-borne diseases are endemic, especially where vector populations have acquired widespread resistance to insecticides. METHODOLOGY/PRINCIPAL FINDINGS: We describe a "genome-to-lead" approach for insecticide discovery that incorporates the first reported chemical screen of a G protein-coupled receptor (GPCR mined from a mosquito genome. A combination of molecular and pharmacological studies was used to functionally characterize two dopamine receptors (AaDOP1 and AaDOP2 from the yellow fever mosquito, Aedes aegypti. Sequence analyses indicated that these receptors are orthologous to arthropod D(1-like (Gα(s-coupled receptors, but share less than 55% amino acid identity in conserved domains with mammalian dopamine receptors. Heterologous expression of AaDOP1 and AaDOP2 in HEK293 cells revealed dose-dependent responses to dopamine (EC(50: AaDOP1 = 3.1±1.1 nM; AaDOP2 = 240±16 nM. Interestingly, only AaDOP1 exhibited sensitivity to epinephrine (EC(50 = 5.8±1.5 nM and norepinephrine (EC(50 = 760±180 nM, while neither receptor was activated by other biogenic amines tested. Differential responses were observed between these receptors regarding their sensitivity to dopamine agonists and antagonists, level of maximal stimulation, and constitutive activity. Subsequently, a chemical library screen was implemented to discover lead chemistries active at AaDOP2. Fifty-one compounds were identified as "hits," and follow-up validation assays confirmed the antagonistic effect of selected compounds at AaDOP2. In vitro comparison studies between AaDOP2 and the human D(1 dopamine receptor (hD(1 revealed markedly different pharmacological profiles and identified amitriptyline and doxepin as AaDOP2

Data on volatile compounds in fermented materials used for salmon fish sauce production.

Science.gov (United States)

Nakano, Mitsutoshi; Sagane, Yoshimasa; Koizumi, Ryosuke; Nakazawa, Yozo; Yamazaki, Masao; Watanabe, Toshihiro; Takano, Katsumi; Sato, Hiroaki

2018-02-01

This article describes the analysis of volatile compounds in fermented materials used for salmon fish sauce production via gas chromatography/mass spectrometry (GC/MS). Ten types of fish sauces were produced from raw salmon materials, including various proportions of flesh, viscera, inedible portion (heads, fins, and backbones), and soft roe, by mixing them with salt and allowing them to ferment for up to three months. The volatile compounds were captured by a solid-phase microextraction method and then applied to GC/MS for separation and identification of the compounds in the fish sauce products. The number of volatile compounds identified in the starting materials varied from 15 to 29 depending on the ingredients. The number of compounds in the final fish sauce products was reduced by 3.4-94.7% of that in the original material. The retention times and names of the identified compounds, as well as their relative peak areas, are provided in a Microsoft Excel Worksheet.

Phytochemical Compounds and Antioxidant Capacity of Tucum-Do-Cerrado (Bactris setosa Mart), Brazil’s Native Fruit

Science.gov (United States)

Rosa, Fernanda R.; Arruda, Andréa F.; Siqueira, Egle M. A.; Arruda, Sandra F.

2016-01-01

This study identified major phenolic compounds of the tucum-do-cerrado (Bactris setosa) peel, as well as antioxidant activity and total phytochemical compound concentration of different extracts of the peel and pulp of this fruit. Phenolic compounds of the different extracts of tucum-do-cerrado peel were identified and quantified using a high-performance liquid chromatography system coupled to a diode array detector (DAD). Total phytochemical compound content was determined by spectrophotometric assays and the antioxidant activity by ferric reducing antioxidant power and β-carotene/linoleic assays. Total phenolic, flavanols, total anthocyanins and yellow flavonoids concentration of tucum-do-cerrado were 122-, 14-, 264- and 61-fold higher in the peel than in the pulp, respectively. The aqueous, methanolic and ethanolic extracts of the tucum-do-cerrado peel exhibited higher antioxidant activity compared to its pulp. Flavanols, anthocyanins, flavones, phenolic acids and stilbenes were the main phenolic classes identified in the tucum-do-cerrado peel extracts. Results suggest that the antioxidant capacity and the phytochemical compound content of the tucum-do-cerrado are mainly associated with the peel. Although flavonoids are the main compounds identified in tucum-do-cerrado peel, other phenolics identified in minor amounts, such as phenolic acids and stilbenes, may be responsible for the high antioxidant capacity of the fruit. PMID:26907338

New Approach for Fractioning Metal Compounds Studies in Soils

Science.gov (United States)

Minkina, Tatiana; Motuzova, Galina; Mandzhieva, Saglara; Bauer, Tatiana; Burachevskaya, Marina; Sushkova, Svetlana; Nevidomskaya, Dina; Kalinitchenko, Valeriy

2016-04-01

A combined approach for fractioning metal compounds in soils on the basis of sequential (Tessier, 1979) and parallel extractions (1 N NH4Ac, pH 8; 1% EDTA in NH4Ac; and 1N HCl) is proposed. Metal compounds in sequential and parallel extracts are grouped according to the strength of their bonds with soil components. A given group includes metal compounds with similar strengths of bonds and, hence, with similar migration capacities. The groups of firmly and loosely bound metal compounds can be distinguished. This approach has been used to assess the group composition of Zn, Cu, and Pb compounds in an ordinary chernozem and its changes upon the soil contamination with metals. Contamination of an ordinary chernozem from Rostov oblast with heavy metals caused a disturbance of the natural ratios between the metal compounds. In the natural soil, firmly bound metals predominate (88-95%of the total content), which is mainly caused by the fixation of metals in lattices of silicate minerals (56-83%of the total content). The mobility of the metals in the natural soil is low (5-12%) and is mainly related to metal compounds loosely bound with the soil carbonates. Upon the soil contamination with metals (application rates of 100-300 mg/kg), the content of all the metal compounds increases, but the ratio between them shifts towards a higher portion of the potentially mobile metal compounds (up to 30-40% of the bulk contents of the metals). Organic substances and non-silicate Fe, Al, and Mn minerals become the main carriers of the firmly and loosely bound metals. The strengths of their bonds with Cu, Pb, and Zn differ. Lead in the studied chernozems is mainly fixed in a loosely bound form with organic matter, whereas copper and zinc are fixed both by the organic matter and by the non-silicate Fe, Al, and Mn compounds. Firm fixation of the applied Cu and Pb is mainly ensured by the soil organic matter and non-silicate minerals, whereas firm fixation of Zn is mainly due to non

Gene-set analysis based on the pharmacological profiles of drugs to identify repurposing opportunities in schizophrenia.

Science.gov (United States)

de Jong, Simone; Vidler, Lewis R; Mokrab, Younes; Collier, David A; Breen, Gerome

2016-08-01

Genome-wide association studies (GWAS) have identified thousands of novel genetic associations for complex genetic disorders, leading to the identification of potential pharmacological targets for novel drug development. In schizophrenia, 108 conservatively defined loci that meet genome-wide significance have been identified and hundreds of additional sub-threshold associations harbour information on the genetic aetiology of the disorder. In the present study, we used gene-set analysis based on the known binding targets of chemical compounds to identify the 'drug pathways' most strongly associated with schizophrenia-associated genes, with the aim of identifying potential drug repositioning opportunities and clues for novel treatment paradigms, especially in multi-target drug development. We compiled 9389 gene sets (2496 with unique gene content) and interrogated gene-based p-values from the PGC2-SCZ analysis. Although no single drug exceeded experiment wide significance (corrected pneratinib. This is a proof of principle analysis showing the potential utility of GWAS data of schizophrenia for the direct identification of candidate drugs and molecules that show polypharmacy. © The Author(s) 2016.

Effect of γ-irradiation on the volatile compounds of medicinal herb, Paeoniae Radix

International Nuclear Information System (INIS)

Shim, Sung-Lye; Hwang, In-Min; Ryu, Keun-Young; Jung, Min-Seok; Seo, Hye-young; Kim, Hee-Yeon; Song, Hyun-Pa; Kim, Jae-Hun; Lee, Ju-Woon; Byun, Myung-Woo; Kwon, Joong-Ho; Kim, Kyong-Su

2009-01-01

A study was carried out to find the effect of γ-irradiation on contents of volatile compounds from medicinal herb, Paeoniae Radix (Paenia albiflora Pallas var. trichocarpa Bunge). The volatile compounds of control, 1, 3, 5 and 10 kGy irradiated samples were extracted by simultaneous steam distillation and extraction (SDE) method and analyzed by gas chromatograph-mass spectrometer. The major volatile compounds were paeonol, (E)-carveol, (E,E)-2,4-octadienal, methyl salicylate, myrtanol and eugenol acetate. Volatile compounds belonging to chemical classes of acids, alcohols, aldehydes, esters, hydrocarbons and miscellaneous were identified in all experimental samples. The types of volatile compounds in irradiated samples were similar to those of non-irradiated sample and the concentrations of these compounds differed between treatments. 1,3-Bis (1,1-dimethylethyl)-benzene was identified by using the selected ion monitoring (GC/MS-SIM) mode. The concentration of this compound increased with the increase of irradiation dose level. These results suggest that it could be used as the base data for the effect of γ-irradiation on medicinal herb.

Effect of {gamma}-irradiation on the volatile compounds of medicinal herb, Paeoniae Radix

Energy Technology Data Exchange (ETDEWEB)

Shim, Sung-Lye; Hwang, In-Min; Ryu, Keun-Young; Jung, Min-Seok [Department of Food and Nutrition, Chosun University (Korea, Republic of); Seo, Hye-young [Korea Food Research Institute (Korea, Republic of); Kim, Hee-Yeon [Korea Food and Drug Administration (Korea, Republic of); Song, Hyun-Pa; Kim, Jae-Hun; Lee, Ju-Woon; Byun, Myung-Woo [Advanced Radiation Technology Institute, KAERI, Jeongeup 580-185 (Korea, Republic of); Kwon, Joong-Ho [Department of Food Science and Technology, Kyungpook National University (Korea, Republic of); Kim, Kyong-Su [Korea Food Research Institute (Korea, Republic of)], E-mail: kskim@chosun.ac.kr

2009-07-15

A study was carried out to find the effect of {gamma}-irradiation on contents of volatile compounds from medicinal herb, Paeoniae Radix (Paenia albiflora Pallas var. trichocarpa Bunge). The volatile compounds of control, 1, 3, 5 and 10 kGy irradiated samples were extracted by simultaneous steam distillation and extraction (SDE) method and analyzed by gas chromatograph-mass spectrometer. The major volatile compounds were paeonol, (E)-carveol, (E,E)-2,4-octadienal, methyl salicylate, myrtanol and eugenol acetate. Volatile compounds belonging to chemical classes of acids, alcohols, aldehydes, esters, hydrocarbons and miscellaneous were identified in all experimental samples. The types of volatile compounds in irradiated samples were similar to those of non-irradiated sample and the concentrations of these compounds differed between treatments. 1,3-Bis (1,1-dimethylethyl)-benzene was identified by using the selected ion monitoring (GC/MS-SIM) mode. The concentration of this compound increased with the increase of irradiation dose level. These results suggest that it could be used as the base data for the effect of {gamma}-irradiation on medicinal herb.

Microbial strategy for potential lead remediation: a review study.

Science.gov (United States)

Pan, Xiaohong; Chen, Zhi; Li, Lan; Rao, Wenhua; Xu, Zhangyan; Guan, Xiong

2017-02-01

The extensive exploitation and usage of lead compounds result in severe lead(II) pollution in water and soil environments, even in agricultural land, threatening the health of animals and humans via food chains. The recovery and remediation of lead(II) from water and soil environments have been intensively concerned in recent years. Compared with the traditional physic-chemistry treatment, microbial remediation strategy is a promising alternative to remediate lead(II)-contaminated environments due to its cost-effective and environmentally-friendly properties. Various microorganisms are capable of removing or immobilizing lead(II) from water and soil environments through bioaccumulation, precipitation or accelerated transformation of lead(II) into a very stable mineral, resulting in significant effects on lead(II) mobility and bioavailability. In the present review, we investigated a wide diversity of lead(II) bioremediation induced by different microbes and its multi-mechanisms. Moreover, we also discussed the progress and limitations, summarized the common rules of lead(II)-microbe interaction, and evaluated the environmental significance of microbes in lead biogeochemistry process. In addition, we further deliberated the feasibility and potential application of microbes in developing cost-effective, eco-friendly bioremediation or long-term management strategy for lead(II) contaminated repositories.

Mini-review: Molecular mechanisms of antifouling compounds

KAUST Repository

Qian, Pei-Yuan

2013-04-01

Various antifouling (AF) coatings have been developed to protect submerged surfaces by deterring the settlement of the colonizing stages of fouling organisms. A review of the literature shows that effective AF compounds with specific targets are ones often considered non-toxic. Such compounds act variously on ion channels, quorum sensing systems, neurotransmitters, production/release of adhesive, and specific enzymes that regulate energy production or primary metabolism. In contrast, AF compounds with general targets may or may not act through toxic mechanisms. These compounds affect a variety of biological activities including algal photosynthesis, energy production, stress responses, genotoxic damage, immunosuppressed protein expression, oxidation, neurotransmission, surface chemistry, the formation of biofilms, and adhesive production/release. Among all the targets, adhesive production/release is the most common, possibly due to a more extensive research effort in this area. Overall, the specific molecular targets and the molecular mechanisms of most AF compounds have not been identified. Thus, the information available is insufficient to draw firm conclusions about the types of molecular targets to be used as sensitive biomarkers for future design and screening of compounds with AF potential. In this review, the relevant advantages and disadvantages of the molecular tools available for studying the molecular targets of AF compounds are highlighted briefly and the molecular mechanisms of the AF compounds, which are largely a source of speculation in the literature, are discussed. © 2013 Copyright Taylor and Francis Group, LLC.

Total Synthesis of Marine Cyclic Enol-Phosphotriester Salinipostin Compounds

Science.gov (United States)

Zhao, Mingliang; Wei, Xianfeng; Liu, Xuemeng; Dong, Xueyang; Yu, Rilei; Wan, Shengbiao; Jiang, Tao

2018-06-01

Due to their structural diversity and variety of biological activities, marine natural products have been the subject of extensive study. These compounds, especially phospholipid polycyclic aromatic hydrocarbons, have a wide range of pharmacological applications, including embedded DNA and central nervous system, anti-tumor, anti-virus, anti-parasite, anti-bacterial, and antithrombotic effects. Unfortunately, the insufficient drug sources have limited the development of these compounds. In this study, we isolated salinpostin compounds from a fermentation solution of marine-derived Salinospora sp., which has a common bicyclic enol-phosphotriester core framework, as well as potent and selective antimalarial activities against P. falciparum with EC50 = 50 nmol L-1. The chemical synthesis of these compounds in greater quantities is necessary for their use in bioactivity studies. Thus we explored a short route with high yields and mild reaction conditions, which can generate combinatorial libraries for drug discovery and lead optimization. We developed a new total synthesis method for six cyclic enol-phosphotriester salinipotin compounds and their diastereomers. For the total synthesis of cyclipostin P, we prepared cyclic enol-phosphotriester salinipostin compounds in 10 steps from a readily accessible starting material, 1,3-dihydroxyacetone, and obtained an overall yield of 1.29%. We fully characterized these compounds by proton nuclear magnetic resonance (1H-NMR), carbon-13 NMR (13C-NMR), and high-resolution mass spectrometry (HRMS) analyses, and found they coincide absolutely with the same compounds reported previously.

Screening and identification of phytotoxic volatile compounds in medicinal plants and characterizations of a selected compound, eucarvone.

Science.gov (United States)

Sunohara, Yukari; Baba, Yohei; Matsuyama, Shigeru; Fujimura, Kaori; Matsumoto, Hiroshi

2015-07-01

Screening and identification of phytotoxic volatile compounds were performed using 71 medicinal plant species to find new natural compounds, and the characterization of the promising compound was investigated to understand the mode of action. The volatile compounds from Asarum sieboldii Miq. showed the strongest inhibitory effect on the hypocotyl growth of lettuce seedlings (Lactuca sativa L.cv. Great Lakes 366), followed by those from Schizonepeta tenuifolia Briquet and Zanthoxylum piperitum (L.) DC.. Gas chromatography-mass spectrometry (GC/MS) identified four volatile compounds, α-pinene (2,6,6-trimethylbicyclo[3.1.1]hept-2-ene), β-pinene (6,6-dimethyl-2-methylenebicyclo[3.1.1]heptane), 3-carene (3,7,7-trimethylbicyclo[4.1.0]hept-3-ene), and eucarvone (2,6,6-trimethy-2,4-cycloheptadien-1-one), from A. sieboldii, and three volatile compounds, limonene (1-methyl-4-(1-methylethenyl)-cyclohexene), menthone (5-methyl-2-(propan-2-yl)cyclohexan-1-one), and pulegone (5-methyl-2-propan-2-ylidenecyclohexan-1-one), from S. tenuifolia. Among these volatile compounds, eucarvone, menthone, and pulegone exhibited strong inhibitory effects on both the root and shoot growth of lettuce seedlings. Eucarvone-induced growth inhibition was species-selective. Cell death, the generation of reactive oxygen species (ROS), and lipid peroxidation were induced in susceptible finger millet seedlings by eucarvone treatment, whereas this compound (≤158 μM) did not cause the increase of lipid peroxidation and ROS production in tolerant maize. The results of the present study show that eucarvone can have strong phytotoxic activity, which may be due to ROS overproduction and subsequent oxidative damage in finger millet seedlings.

Whole-exome sequencing identifies novel compound heterozygous mutations in USH2A in Spanish patients with autosomal recessive retinitis pigmentosa.

Science.gov (United States)

Méndez-Vidal, Cristina; González-Del Pozo, María; Vela-Boza, Alicia; Santoyo-López, Javier; López-Domingo, Francisco J; Vázquez-Marouschek, Carmen; Dopazo, Joaquin; Borrego, Salud; Antiñolo, Guillermo

2013-01-01

Retinitis pigmentosa (RP) is an inherited retinal dystrophy characterized by extreme genetic and clinical heterogeneity. Thus, the diagnosis is not always easily performed due to phenotypic and genetic overlap. Current clinical practices have focused on the systematic evaluation of a set of known genes for each phenotype, but this approach may fail in patients with inaccurate diagnosis or infrequent genetic cause. In the present study, we investigated the genetic cause of autosomal recessive RP (arRP) in a Spanish family in which the causal mutation has not yet been identified with primer extension technology and resequencing. We designed a whole-exome sequencing (WES)-based approach using NimbleGen SeqCap EZ Exome V3 sample preparation kit and the SOLiD 5500×l next-generation sequencing platform. We sequenced the exomes of both unaffected parents and two affected siblings. Exome analysis resulted in the identification of 43,204 variants in the index patient. All variants passing filter criteria were validated with Sanger sequencing to confirm familial segregation and absence in the control population. In silico prediction tools were used to determine mutational impact on protein function and the structure of the identified variants. Novel Usher syndrome type 2A (USH2A) compound heterozygous mutations, c.4325T>C (p.F1442S) and c.15188T>G (p.L5063R), located in exons 20 and 70, respectively, were identified as probable causative mutations for RP in this family. Family segregation of the variants showed the presence of both mutations in all affected members and in two siblings who were apparently asymptomatic at the time of family ascertainment. Clinical reassessment confirmed the diagnosis of RP in these patients. Using WES, we identified two heterozygous novel mutations in USH2A as the most likely disease-causing variants in a Spanish family diagnosed with arRP in which the cause of the disease had not yet been identified with commonly used techniques. Our data

Co-remediation of the lead-polluted garden soil by exogenous natural zeolite and humic acids.

Science.gov (United States)

Shi, Wei-yu; Shao, Hong-bo; Li, Hua; Shao, Ming-an; Du, Sheng

2009-08-15

The current study reported the co-remediation effect on the lead-polluted garden soil by zeolite and humic acids (HA), which was from comparing with the remediation of single zeolite in term of the lead fraction of sequential extraction in the soil and the distribution of lead in different parts of rape. Mixed treatment (zeolite and HA) and single treatment (zeolite) were, respectively, applied to the artificially polluted garden soil to examine the difference of their remediation effects in pot experiment. Results indicated that the co-remediation led to significantly greater (plead concentration in plants than by singly adding to zeolite. The co-application of zeolite and HA reduced the available fraction of lead compounds, but slightly increased (plead compounds in the garden soil, compared with the application of single zeolite, especially in the severe lead-polluted soil (> or =1000 mg kg(-1)). This method might be an efficient way to remediate the lead-polluted soils on a large scale, although zeolite is a kind of hazardous material.

A comprehensive approach to identifying repurposed drugs to treat SCN8A epilepsy.

Science.gov (United States)

Atkin, Talia A; Maher, Chani M; Gerlach, Aaron C; Gay, Bryant C; Antonio, Brett M; Santos, Sonia C; Padilla, Karen M; Rader, JulieAnn; Krafte, Douglas S; Fox, Matthew A; Stewart, Gregory R; Petrovski, Slavé; Devinsky, Orrin; Might, Matthew; Petrou, Steven; Goldstein, David B

2018-04-01

Many previous studies of drug repurposing have relied on literature review followed by evaluation of a limited number of candidate compounds. Here, we demonstrate the feasibility of a more comprehensive approach using high-throughput screening to identify inhibitors of a gain-of-function mutation in the SCN8A gene associated with severe pediatric epilepsy. We developed cellular models expressing wild-type or an R1872Q mutation in the Na v 1.6 sodium channel encoded by SCN8A. Voltage clamp experiments in HEK-293 cells expressing the SCN8A R1872Q mutation demonstrated a leftward shift in sodium channel activation as well as delayed inactivation; both changes are consistent with a gain-of-function mutation. We next developed a fluorescence-based, sodium flux assay and used it to assess an extensive library of approved drugs, including a panel of antiepileptic drugs, for inhibitory activity in the mutated cell line. Lead candidates were evaluated in follow-on studies to generate concentration-response curves for inhibiting sodium influx. Select compounds of clinical interest were evaluated by electrophysiology to further characterize drug effects on wild-type and mutant sodium channel functions. The screen identified 90 drugs that significantly inhibited sodium influx in the R1872Q cell line. Four drugs of potential clinical interest-amitriptyline, carvedilol, nilvadipine, and carbamazepine-were further investigated and demonstrated concentration-dependent inhibition of sodium channel currents. A comprehensive drug repurposing screen identified potential new candidates for the treatment of epilepsy caused by the R1872Q mutation in the SCN8A gene. Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.

Soluble Lead and Bismuth Chalcogenidometallates: Versatile Solders for Thermoelectric Materials

Energy Technology Data Exchange (ETDEWEB)

Zhang, Hao [Department; Son, Jae Sung [Department; School; Dolzhnikov, Dmitriy S. [Department; Filatov, Alexander S. [Department; Hazarika, Abhijit [Department; Wang, Yuanyuan [Department; Hudson, Margaret H. [Department; Sun, Cheng-Jun [Advanced; Chattopadhyay, Soma [Physical; Talapin, Dmitri V. [Department; Center

2017-07-27

Here we report the syntheses of largely unexplored lead and bismuth chalcogenidometallates in the solution phase. Using N2H4 as the solvent, new compounds such as K6Pb3Te6·7N2H4 were obtained. These soluble molecular compounds underwent cation exchange processes using resin chemistry, replacing Na+ or K+ by decomposable N2H5+ or tetraethylammonium cations. They also transformed into stoichiometric lead and bismuth chalcogenide nanomaterials with the addition of metal salts. Such a versatile chemistry led to a variety of composition-matched solders to join lead and bismuth chalcogenides and tune their charge transport properties at the grain boundaries. Solution-processed thin films composed of Bi0.5Sb1.5Te3 microparticles soldered by (N2H5)6Bi0.5Sb1.5Te6 exhibited thermoelectric power factors (~28 μW/cm K2) comparable to those in vacuum-deposited Bi0.5Sb1.5Te3 films. The soldering effect can also be integrated with attractive fabrication techniques for thermoelectric modules, such as screen printing, suggesting the potential of these solders in the rational design of printable and moldable thermoelectrics.

Small molecule screening identifies targetable zebrafish pigmentation pathways

DEFF Research Database (Denmark)

Colanesi, Sarah; Taylor, Kerrie L; Temperley, Nicholas D

2012-01-01

Small molecules complement genetic mutants and can be used to probe pigment cell biology by inhibiting specific proteins or pathways. Here, we present the results of a screen of active compounds for those that affect the processes of melanocyte and iridophore development in zebrafish and investig......Small molecules complement genetic mutants and can be used to probe pigment cell biology by inhibiting specific proteins or pathways. Here, we present the results of a screen of active compounds for those that affect the processes of melanocyte and iridophore development in zebrafish...... and investigate the effects of a few of these compounds in further detail. We identified and confirmed 57 compounds that altered pigment cell patterning, number, survival, or differentiation. Additional tissue targets and toxicity of small molecules are also discussed. Given that the majority of cell types...

The identification of lead ammunition as a source of lead exposure in First Nations: The use of lead isotope ratios

International Nuclear Information System (INIS)

Tsuji, Leonard J.S.; Wainman, Bruce C.; Martin, Ian D.; Sutherland, Celine; Weber, Jean-Philippe; Dumas, Pierre; Nieboer, Evert

2008-01-01

The use of lead shotshell to hunt water birds has been associated with lead-contamination in game meat. However, evidence illustrating that lead shotshell is a source of lead exposure in subsistence hunting groups cannot be deemed definitive. This study seeks to determine whether lead shotshell constitutes a source of lead exposure using lead isotope ratios. We examined stable lead isotope ratios for lichens, lead shotshell and bullets, and blood from residents of Fort Albany and Kashechewan First Nations, and the City of Hamilton, Ontario, Canada. Data were analyzed using ANOVA and regression analyses. ANOVA of isotope ratios for blood revealed significant differences with respect to location, but not sex. Hamilton differed from both Kashechewan and Fort Albany; however, the First Nations did not differ from each other. ANOVA of the isotope ratios for lead ammunition and lichens revealed no significant differences between lichen groups (north and south) and for the lead ammunition sources (pellets and bullets). A plot of 206 Pb/ 204 Pb and 206 Pb/ 207 Pb values illustrated that lichens and lead ammunition were distinct groupings and only the 95% confidence ellipse of the First Nations group overlapped that of lead ammunition. In addition, partial correlations between blood-lead levels (adjusted for age) and isotope ratios revealed significant (p 206 Pb/ 204 Pb and 206 Pb/ 207 Pb, and a significant negative correlation for 208 Pb/ 206 Pb, as predicted if leaded ammunition were the source of lead exposure. In conclusion, lead ammunition was identified as a source of lead exposure for First Nations people; however, the isotope ratios for lead shotshell pellets and bullets were indistinguishable. Thus, lead-contaminated meat from game harvested with lead bullets may also be contributing to the lead body burden

Interesting asian plants: their compounds and effects on electrophysiology and behaviour.

Science.gov (United States)

Abdullah, Jafri Malin

2011-10-01

There have been numerous non-scientific reports on the behavioural effects of Asian plants in humans who consumed these plants wholly or part thereof. Knowledge passed from generation to generation informs us of plants that increase effort and stamina, such as during paddy planting after the ingestion of Mitragyna speciosa Korth (ketum) as a tea supplement. Centella asiatica and Myristica fragrans are used as herbs to improve memory and to treat epilepsy, respectively. Zizyphus mauritiana is used to treat headache and burn pain, acts as an antitussive, and reduces rigor mortis immediately after death. These plants, which have been identified to exhibit analgaesic, muscle-relaxing, and nootropic effects, may contain important bio-compounds for medicinal chemistry and pharmaceutical research in Malaysia. The electrophysiology properties of these plants and their effects on epilepsy, behaviour, and pain will lead Malaysia to future new drug discoveries.

Lead immobilization in thermally remediated soils and igneous rocks

International Nuclear Information System (INIS)

Hickmott, D.D.; Carey, J.W.; Stimac, J.; Larocque, A.; Abell, R.; Gauerke, E.; Eppler, A.

1997-01-01

This is the final report for a three-year, Laboratory-Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). The principal goal of this project was to investigate the speciation of lead in the environment at LANL and to determine the feasibility of using thermal remediation methods to immobilize lead in the environment. Lead occurs as pyromorphite [Pb(PO 4 ) 3 (Cl, OH)], cerussite (PbCO 3 ) and galena (PbS) in vapor-phase-altered Bandelier Tuff samples. LANL soils primarily contain cerussite and PbO. Thermal remediation experiments at high temperatures (up to 400 C) suggest that thermal immobilization of highly-reactive Pb compounds in the environment may be feasible, but that this technique is not optimal for more refractory lead phases such as cerussite and PbO

Lead levels in the workers blood at the Toluca bus terminal

International Nuclear Information System (INIS)

Gomez H, S.P.; Garcia G, G.

1998-01-01

The study was carried out in order to detect the levels of lead in blood in exposed workers to the lead in their place of work, in the Toluca bus terminal. The measurement of the levels of lead in blood was carried out in a sample of 31 people of 60 workers for atomic absorption spectrometry. The lead is a general protoplasmic poison that is accumulative and produce great variety of symptoms, the lead could be absorbed inside the body for ingestion, inhalation and through the skin. Organic compounds of the lead as tetraethyl lead, penetrate the cutaneous barrier quickly. From the beginning the personal habits were evaluated, hygienic, nutritious and the environmental conditions by means of a questionnaire. The levels of lead in opposing blood, they were below them you limit permissible for personal exposed, published by the WHO. (Author)

Fruits Bioactive Compounds Characterization from a New Food Product

Directory of Open Access Journals (Sweden)

Valentina Mariana RUS

2014-12-01

Full Text Available The aim of this study was (I to create a new product, smart bar type which can be consumed as protective food by adults and children (II to characterize the bioactive compounds from the designed food. The bioactive compounds were identified from nuts, raw seeds of almonds, dry cranberries, dry plums and flax seeds. Secoisolariciresinol (683 ppm has been identified as a major compound in flax seeds.  The vitamin C was quantified by HPLC in a concentration of 35.02 mg% in cranberries extract. The total phenolic content varied from 7.1 mg/g for walnut to 71.8 mg/g for cranberries. In addition, the antioxidative capability of phenolic compounds was monitored and evaluated using a colored free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH. Almond showed better results than walnut in the antioxidant capacity test. The results obtained in this study collect information that enables the use of nuts, raw seeds of almonds, dry cranberries, dry plums and flax seeds as raw material for the production of smart bar which may serve as a new product for food market.

Chelation therapy in intoxications with mercury, lead and copper

DEFF Research Database (Denmark)

Cao, yang; Skaug, Marit Aralt; Andersen, Ole

2015-01-01

In the present review we provide an update of the appropriate use of chelating agents in the treatment of intoxications with compounds of mercury, lead and copper. The relatively new chelators meso-2,3-dimercaptosuccinic acid (DMSA) and 2,3-dimercapto-propanesulphonate (DMPS) can effectively...... mobilize deposits of mercury as well as of lead into the urine. These drugs can be administered orally and have relatively low toxicity compared to the classical antidote dimercaptopropanol (BAL). d-Penicillamine has been widely used in copper overload, although 2,3-dimercaptosuccinic acid...

Lead-Free Experiment in a Space Environment

Science.gov (United States)

Blanche, J. F.; Strickland, S. M.

2012-01-01

This Technical Memorandum addresses the Lead-Free Technology Experiment in Space Environment that flew as part of the seventh Materials International Space Station Experiment outside the International Space Station for approximately 18 months. Its intent was to provide data on the performance of lead-free electronics in an actual space environment. Its postflight condition is compared to the preflight condition as well as to the condition of an identical package operating in parallel in the laboratory. Some tin whisker growth was seen on a flight board but the whiskers were few and short. There were no solder joint failures, no tin pest formation, and no significant intermetallic compound formation or growth on either the flight or ground units.

Identifying inhibitory compounds in lignocellulosic biomass hydrolysates using an exometabolomics approach

NARCIS (Netherlands)

Zha, Y.; Westerhuis, J.A.; Muilwijk, B.; Overkamp, K.M.; Nijmeijer, B.M.; Coulier, L.; Smilde, A.K.; Punt, P.J.

2014-01-01

Background: Inhibitors are formed that reduce the fermentation performance of fermenting yeast during the pretreatment process of lignocellulosic biomass. An exometabolomics approach was applied to systematically identify inhibitors in lignocellulosic biomass hydrolysates.Results: We studied the

Identifying inhibitory compounds in lignocellulosic biomass hydrolysates using an exometabolomics approach

NARCIS (Netherlands)

Zha, Y.; Westerhuis, J.A.; Muilwijk, B.; Overkamp, K.M.; Nijmeijer, B.M.; Coulier, L.; Smilde, A.K.; Punt, P.J.

2014-01-01

BACKGROUND: Inhibitors are formed that reduce the fermentation performance of fermenting yeast during the pretreatment process of lignocellulosic biomass. An exometabolomics approach was applied to systematically identify inhibitors in lignocellulosic biomass hydrolysates. RESULTS: We studied the

Recycling and management of waste lead-acid batteries: A mini-review.

Science.gov (United States)

Li, Malan; Liu, Junsheng; Han, Wei

2016-04-01

As a result of the wide application of lead-acid batteries to be the power supplies for vehicles, their demand has rapidly increased owing to their low cost and high availability. Accordingly, the amount of waste lead-acid batteries has increased to new levels; therefore, the pollution caused by the waste lead-acid batteries has also significantly increased. Because lead is toxic to the environment and to humans, recycling and management of waste lead-acid batteries has become a significant challenge and is capturing much public attention. Various innovations have been recently proposed to recycle lead and lead-containing compounds from waste lead-acid batteries. In this mini-review article, different recycling techniques for waste lead-acid batteries are highlighted. The present state of such recycling and its future perspectives are also discussed. We hope that this mini-review can provide useful information on recovery and recycling of lead from waste lead-acid batteries in the field of solid waste treatment. © The Author(s) 2016.

Chromatographic and Spectral Analysis of Two Main Extractable Compounds Present in Aqueous Extracts of Laminated Aluminum Foil Used for Protecting LDPE-Filled Drug Vials

Science.gov (United States)

Akapo, Samuel O.; Syed, Sajid; Mamangun, Anicia; Skinner, Wayne

2009-01-01

Laminated aluminum foils are increasingly being used to protect drug products packaged in semipermeable containers (e.g., low-density polyethylene (LDPE)) from degradation and/or evaporation. The direct contact of such materials with primary packaging containers may potentially lead to adulteration of the drug product by extractable or leachable compounds present in the closure system. In this paper, we described a simple and reliable HPLC method for analysis of an aqueous extract of laminated aluminum foil overwrap used for packaging LDPE vials filled with aqueous pharmaceutical formulations. By means of combined HPLC-UV, GC/MS, LC/MS/MS, and NMR spectroscopy, the two major compounds detected in the aqueous extracts of the representative commercial overwraps were identified as cyclic oligomers with molecular weights of 452 and 472 and are possibly formed from poly-condensation of the adhesive components, namely, isophthalic acid, adipic acid, and diethylene glycol. Lower molecular weight compounds that might be associated with the “building blocks” of these compounds were not detected in the aqueous extracts. PMID:20140083

Outbreak of Serratia marcescens bloodstream infections in patients receiving parenteral nutrition prepared by a compounding pharmacy.

Science.gov (United States)

Gupta, Neil; Hocevar, Susan N; Moulton-Meissner, Heather A; Stevens, Kelly M; McIntyre, Mary G; Jensen, Bette; Kuhar, David T; Noble-Wang, Judith A; Schnatz, Rick G; Becker, Shawn C; Kastango, Eric S; Shehab, Nadine; Kallen, Alexander J

2014-07-01

Compounding pharmacies often prepare parenteral nutrition (PN) and must adhere to rigorous standards to avoid contamination of the sterile preparation. In March 2011, Serratia marcescens bloodstream infections (BSIs) were identified in 5 patients receiving PN from a single compounding pharmacy. An investigation was conducted to identify potential sources of contamination and prevent further infections. Cases were defined as S. marcescens BSIs in patients receiving PN from the pharmacy between January and March 2011. We reviewed case patients' clinical records, evaluated pharmacy compounding practices, and obtained epidemiologically directed environmental cultures. Molecular relatedness of available Serratia isolates was determined by pulsed-field gel electrophoresis (PFGE). Nineteen case patients were identified; 9 died. The attack rate for patients receiving PN in March was 35%. No case patients were younger than 18 years. In October 2010, the pharmacy began compounding and filter-sterilizing amino acid solution for adult PN using nonsterile amino acids due to a national manufacturer shortage. Review of this process identified breaches in mixing, filtration, and sterility testing practices. S. marcescens was identified from a pharmacy water faucet, mixing container, and opened amino acid powder. These isolates were indistinguishable from the outbreak strain by PFGE. Compounding of nonsterile amino acid components of PN was initiated due to a manufacturer shortage. Failure to follow recommended compounding standards contributed to an outbreak of S. marcescens BSIs. Improved adherence to sterile compounding standards, critical examination of standards for sterile compounding from nonsterile ingredients, and more rigorous oversight of compounding pharmacies is needed to prevent future outbreaks. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public

Application of INAA to identify lead white in icons from the 15th-18th centuries from south-eastern Poland

International Nuclear Information System (INIS)

Panczyk, E.; Walis, L.; Giemza, J.

2006-01-01

The purpose of the work was to analyse lead white from eighteen icons of the 15 th -18 th centuries, collected in the Orthodox Art Department at the Castle Museum in Lancut, using the neutron activation analysis (NAA) method. 1-3 samples from each object, with a mass from 0.1 to 1 mg were collected after removing the varnish, from the top lights, in order to ensure that they include pure lead white without other pigment additives. Samples were irradiated in the MARIA reactor in Swierk (Poland), in a channel with a 8·10 13 n/cm 2 s thermal neutron flux. 47 standards of determined elements, e.g. Na, K, Sc, Cr, Mn, Fe, Co, Ni, Cu, Zn, Ga ,Ge, As, Se, Br, Rb, Sr, Zr, Mo, Ru, Ag, Cd, Sn, Sb, Te, Cs, Ba, La, Ce, Pr, Nd, Sm, Eu, Tb, Dy, Ho, Er, Yb, Lu, Hf, Ta, W, Ir, Au, Hg, Th and 238 U were simultaneously irradiated. Measurements of activity of the samples and standards were carried out using an HP germanium detector. Ultimately, 28 elements were selected for a multi-parameter statistical analysis aimed at identifying the degree of similarity of analysed icons. Results of the analysis permit for division into groups closely related to chronology of tested icons. Icons from the 15 th and 16 th centuries are much more alike than icons from the 17 th and 18 th centuries. Probably, the applied lead white was obtained from different sources that had changed over time

Mutagenic activities of metal compounds in bacteria

Energy Technology Data Exchange (ETDEWEB)

Nishioka, H

1975-01-01

Environmental contaminations by certain metal compounds are bringing about serious problems to human health, including genetic hazards. It has been reported that some compounds of iron, manganese and mercury induce point mutations in microorganisms. Also it has been observed that those of aluminum, antimony, arsenic, cadmium, lead and tellurium cause chromosome aberrations in plants, insects and cultured human cells. The mechanism of mutation induction by these metals remains, however, still obscure. For screening of chemical mutagens, Kada et al, recently developed a simple and efficient method named rec-assay by observing differential growth sensitivities to drugs in wild and recombination-deficient strains of Bacillus subtilis. When a chemical is more inhibitory for Rec/sup -/ than for Rec/sup +/ cells, it is reasonable to suspect mutagenicity based on its DNA-damaging capacity. In the present report, 56 metal compounds were tested by the rec-assay. Compounds showing positive results in the assay such as potassium dichromate (K/sub 2/Cr/sub 2/O/sub 7/), ammonium molybdate ((NH/sub 4/)/sub 6/Mo/sub 7/O/sub 24/) and sodium arsenite (NaAsO/sub 2/) were then examined as to their capacities to induce reversions in E. coli Trp/sup -/ strains possessing different DNA repair pathways. 11 references, 3 tables.

Lead in the environment

Science.gov (United States)

Pattee, Oliver H.; Pain, Deborah J.; Hoffman, David J.; Rattner, Barnett A.; Burton, G. Allen; Cairns, John

2003-01-01

. and the .reduction of lead in gasoline has resulted in lower tissue lead concentrations in humans and wildlife from many, particularly urban, locations. However, it has been suggested that increasing use of organic lead compounds as catalysts for the production of plastics and as wood preservatives and biocides could adversely affect wildlife. The most significant source of direct wildlife mortality from lead is spent gunshot and fishing sinkers. Elevated mortality from shot ingestion in avian species resulted in the introduction of nontoxic (steel) shot zones along certain flyways in the United States in the mid-1970s and a total ban on the use of lead for waterfowl and coot hunting nationwide by 1992. Several other countries are now following suit and have either banned or are in the process of restricting the use of lead shot for waterfowl hunting. In the United States it has been estimated that since the 1986 hunting season. when the use of nontoxic shot became widespread. over 6 million ducks have not been lost to lead poisoning. Raptors, especially eagles, have also apparently benefited. although lead poisoning from ingestion of bullet fragments remains a problem for the critically threatened California condor. Quantifying reductions in lead mortality rates would be difficult since eagle populations throughout North America are rapidly recovering from other anthropogenic perturbations, especially organochlorine pesticides.