Quantitative assessment of the expanding complementarity between public and commercial databases of bioactive compounds

<p>Abstract</p> <p>Background</p> <p>Since 2004 public cheminformatic databases and their collective functionality for exploring relationships between compounds, protein sequences, literature and assay data have advanced dramatically. In parallel, commercial sources that extract and curate such relationships from journals and patents have also been expanding. This work updates a previous comparative study of databases chosen because of their bioactive content, availability of downloads and facility to select informative subsets.</p> <p>Results</p> <p>Where they could be calculated, extracted compounds-per-journal article were in the range of 12 to 19 but compound-per-protein counts increased with document numbers. Chemical structure filtration to facilitate standardised comparisons typically reduced source counts by between 5% and 30%. The pair-wise overlaps between 23 databases and subsets were determined, as well as changes between 2006 and 2008. While all compound sets have increased, PubChem has doubled to 14.2 million. The 2008 comparison matrix shows not only overlap but also unique content across all sources. Many of the detailed differences could be attributed to individual strategies for data selection and extraction. While there was a big increase in patent-derived structures entering PubChem since 2006, GVKBIO contains over 0.8 million unique structures from this source. Venn diagrams showed extensive overlap between compounds extracted by independent expert curation from journals by GVKBIO, WOMBAT (both commercial) and BindingDB (public) but each included unique content. In contrast, the approved drug collections from GVKBIO, MDDR (commercial) and DrugBank (public) showed surprisingly low overlap. Aggregating all commercial sources established that while 1 million compounds overlapped with PubChem 1.2 million did not.</p> <p>Conclusion</p> <p>On the basis of chemical structure content <it>per se </it>public sources have covered an increasing proportion of commercial databases over the last two years. However, commercial products included in this study provide links between compounds and information from patents and journals at a larger scale than current public efforts. They also continue to capture a significant proportion of unique content. Our results thus demonstrate not only an encouraging overall expansion of data-supported bioactive chemical space but also that both commercial and public sources are complementary for its exploration.</p

Mutagens in contaminated soil: a review

The intentional and accidental discharges of toxic pollutants into the lithosphere results in soil contamination. In some cases (e.g., wood preserving wastes, coal-tar, airborne combustion by-products), the contaminated soil constitutes a genotoxic hazard. This work is a comprehensive review of published information on soil mutagenicity. In total, 1312 assessments of genotoxic activity from 118 works were examined. The majority of the assessments (37.6%) employed the Salmonella mutagenicity test with strains TA98 and/or TA100. An additional 37.6% of the assessments employed a variety of plant species (e.g., Tradescantia clone 4430, Vicia faba, Zea mays, Allium cepa) to assess mutagenic activity. The compiled data on Salmonella mutagenicity indicates significant differences (p \u3c 0.0001) in mean potency (revertents per gram dry weight) between industrial, urban, and rural/agricultural sites. Additional analyses showed significant empirical relationships between S9-activated TA98 mutagenicity and soil polycyclic aromatic hydrocarbon (PAH) concentration (r2 = 0.19 to 0.25, p \u3c 0.0001), and between direct-acting TA98 mutagenicity and soil dinitropyrene (DNP) concentration (r2 = 0.87, p \u3c 0.0001). The plant assay data revealed excellent response ranges and significant differences between heavily contaminated, industrial, rural/agricultural, and reference sites, for the anaphase aberration in Allium cepa (direct soil contact) and the waxy locus mutation assay in Zea mays (direct soil contact). The Tradescantia assays appeared to be less responsive, particularly for exposures to aqueous soil leachates. Additional data analyses showed empirical relationships between anaphase aberrations in Allium, or mutations in Arabidopsis, and the 137Cs contamination of soils. Induction of micronuclei in Tradescantia is significantly related to the soil concentration of several metals (e.g., Sb, Cu, Cr, As, Pb, Cd, Ni, Zn). Review of published remediation exercises showed effective removal of genotoxic petrochemical wastes within one year. Remediation of more refractory genotoxic material (e.g., explosives, creosote) frequently showed increases in mutagenic hazard that remained for extended periods. Despite substantial contamination and mutagenic hazards, the risk of adverse effect (e.g., mutation, cancer) in humans or terrestrial biota is difficult to quantify

Acute-Contact and Chronic-Systemic In Vivo Bioassays: Regional Monitoring of Susceptibility to Thiamethoxam in Soybean Aphid (Hemiptera: Aphididae) Populations From the North Central United States

The risks associated with soybean aphid, Aphis glycines Matsumura (Hemiptera: Aphididae), in the North Central soybean systems has fostered the adoption of prophylactic chemical control practices, such as planting seeds treated with neonicotinoid insecticides, especially thiamethoxam. Consequently, there is a concern that increased selection pressure imposed on the arthropod–pest complex by this insecticide may lead to resistance. Therefore, in vivo bioassays were conducted to determine the susceptibility of soybean aphid to thiamethoxam among North Central U.S. populations. Concentration-mortality data were collected using contact glass-vial and detached-leaf systemic bioassays. The results of these experiments indicate that both bioassays were reliable to detect shifts in susceptibility between different soybean aphid clones. The LC50s of field populations of soybean aphid were significantly different when mortality was recorded in contact and systemic exposure assays. Nevertheless, the magnitude of the resistance ratios was consistent in both methods. In addition, a significant increase in the LC50 and EC50 values was observed among field populations tested in detached-leaf systemic bioassays. These results represent the first extensive efforts to identify the variability in susceptibility of soybean aphid to thiamethoxam in the North Central United States Therefore, our results provide a baseline for future assessment and contribute to a better understanding of the applicability of in vivo bioassays for susceptibility monitoring and resistance detection of soybean aphid to thiamethoxam

Acute-Contact and Chronic-Systemic In Vivo Bioassays: Regional Monitoring of Susceptibility to Thiamethoxam in Soybean Aphid (Hemiptera: Aphididae) Populations From the North Central United States

The risks associated with soybean aphid, Aphis glycines Matsumura (Hemiptera: Aphididae), in the North Central soybean systems has fostered the adoption of prophylactic chemical control practices, such as planting seeds treated with neonicotinoid insecticides, especially thiamethoxam. Consequently, there is a concern that increased selection pressure imposed on the arthropod–pest complex by this insecticide may lead to resistance. Therefore, in vivo bioassays were conducted to determine the susceptibility of soybean aphid to thiamethoxam among North Central U.S. populations. Concentration-mortality data were collected using contact glass-vial and detached-leaf systemic bioassays. The results of these experiments indicate that both bioassays were reliable to detect shifts in susceptibility between different soybean aphid clones. The LC50s of field populations of soybean aphid were significantly different when mortality was recorded in contact and systemic exposure assays. Nevertheless, the magnitude of the resistance ratios was consistent in both methods. In addition, a significant increase in the LC50 and EC50 values was observed among field populations tested in detached-leaf systemic bioassays. These results represent the first extensive efforts to identify the variability in susceptibility of soybean aphid to thiamethoxam in the North Central United States Therefore, our results provide a baseline for future assessment and contribute to a better understanding of the applicability of in vivo bioassays for susceptibility monitoring and resistance detection of soybean aphid to thiamethoxam

New Strategies for the Detection of <i>Fusarium</i> Infection and Mycotoxin Contamination of Cereals and Maize

Phytopathogene Fusarium spp.treten weltweit in landwirtschaftlichen Kulturen auf und führen häufig zur Ertragsreduktion, Verschlechterung der Produktqualität sowie Kontaminationen der Erntegüter mit toxischen Sekundärmetaboliten, sog. Mykotoxinen. Die durch Fusarium spp. hervorgerufene partielle Taubährigkeit (FHB) des Weizens und anderer Getreidearten sowie die Fusarium Kolbenfäule an Mais sind aus ökonomischer Sicht von besonderer Bedeutung. Im Rahmen dieser Arbeit wurde die Verwendung von volatilen organischen Verbindungen (VOCs) zur Detektion von Fusariosen an Sommerweizen und Hybridmais unter Gewächshausbedingungen untersucht. Maiskolben wurden mit F. graminearum, F. verticillioides und F. subglutinans infiziert, während Weizenähren mit Sporensuspensionen von F. graminearum, F. avenaceum und F. poae inokuliert wurden. Auch Mischinfektionen wurden durchgeführt. Für die Sammlung der VOCs wurde ein statisches Verfahren (Festphasenmikroextraktion, SPME) sowie ein dynamisches Verfahren (open-loop stripping, OLS) eingesetzt. Die Analyse erfolgte in beiden Fällen mittels GC-MS. Ein nichtparametrischer Test (Kruskal-Wallis) wurde zur Identifikation von spezifischen volatilen Markern herangezogen. Auf diese Weise konnte an Mais ein Set aus 27 volatilen Biomarkern für die Infektion mit Fusarium spp. ermittelt werden. Die Kombination der VOCs ermöglichte hier die Unterscheidung zwischen Infektionen mit F. graminearum und F. verticillioides. An Weizen konnte ein Set aus 13 charakteristischen VOCs für den Fusarium Befall ermittelt werden. Die selektierten volatilen Marker beinhalteten sowohl einfache Moleküle mit 5 bis 8 Kohlenstoffatomen (C5 - C8), welche häufig von Pflanzen und Mikroorganismen emittiert werden, als auch infektionsspezifische Sesquiterpene (C15H24). In Zeitreihenversuchen konnte gezeigt werden, dass ein Großteil der relevanten VOCs bereits nach kurzer Zeit emittiert wird. So waren in Mais volatile Biomarker detektierbar, bevor Symptome am Kolben erkennbar waren (4 – 8 Tage nach der Inokulation). Ein Monitoring von VOC Profilen im Hinblick auf volatile Marker könnte eine schnelle und nicht-destruktive Detektion von Fusarium Infektionen (ggf. auch Risikoabschätzung zur Mykotoxinbelastung), z.B. im Feld oder Lager, ermöglichen. Hierfür stehen transportable Detektoren zur Verfügung. Das makrozyklische Lacton Zearalenon (ZEN) wird von mehreren Fusarium spp. produziert und besitzt eine östrogene Wirkung auf den menschlichen und tierischen Organismus. Schweine gelten diesbezüglich als besonders anfällig. ZEN wird in gemäßigten Klimazonen regelmäßig in Lebens- und Futtermitteln nachgewiesen. Bislang wurden zahlreiche Bioassays für die Detektion von ZEN beschrieben. Sie basieren meist auf den menschlichen Östrogenrezeptoren α und β und reagieren unspezifisch auf eine Vielzahl von östrogenen Substanzen (z.B. Genistein, 17β-Estradiol). Die vorliegende Arbeit beschreibt erstmalig ein Bioassay zur spezifischen Detektion von ZEN sowie dem kritischen Metabolit α-Zearalenol (α-ZOL). Das Assay basiert auf einer zes2::gfp Mutante des Mykoparasiten Gliocladium roseum und ermöglicht eine Detektion von ZEN in Feldproben (z.B. kontaminierter Mais). Schritte zur Probenvorbereitung und Extraktion, einschließlich Aufreinigung mit Immunoaffinitätssäulen, sowie die Kultur des Inditaktorstammes wurden optimiert. Das Assay eignet sich für die qualitative Detektion von ZEN in einem weiten Konzentrationsbereich sowie für eine quantitative ZEN Bestimmung in kontaminierten Mais Feldproben im Bereich zwischen 0,9 mg kg-1 und 90 mg kg-1. Neben der Detektion in Feldproben, konnte das Bioassay erfolgreich für ein Screening von Pilzstämmen zur Identifikation von ZEN-Produzenten eingesetzt werden. Das hier beschriebene G. roseum zes2::gfp Bioassay kann mit einer einfachen Laborausstattung durchgeführt werden und eignet sich möglicherweise für die Anwendung in Entwicklungsländern

Challenges of connecting chemistry to pharmacology: perspectives from curating the IUPHAR/BPS Guide to PHARMACOLOGY

Connecting chemistry to pharmacology (c2p) has been an objective of GtoPdb and its precursor IUPHAR-DB since 2003. This has been achieved by populating our database with expert-curated relationships between documents, assays, quantitative results, chemical structures, their locations within the documents and the protein targets in the assays (D-A-R-C-P). A wide range of challenges associated with this are described in this perspective, using illustrative examples from GtoPdb entries. Our selection process begins with judgements of pharmacological relevance and scientific quality. Even though we have a stringent focus for our small-data extraction we note that assessing the quality of papers has become more difficult over the last 15 years. We discuss ambiguity issues with the resolution of authors’ descriptions of A-R-C-P entities to standardised identifiers. We also describe developments that have made this somewhat easier over the same period both in the publication ecosystem as well as enhancements of our internal processes over recent years. This perspective concludes with a look at challenges for the future including the wider capture of mechanistic nuances and possible impacts of text mining on automated entity extractio

Working with Mycorrhizas in Forestry and Agriculture

Crop Production/Industries,

Radiological health aspects of uranium milling

This report describes the operation of conventional and unconventional uranium milling processes, the potential for occupational exposure to ionizing radiation at the mill, methods for radiological safety, methods of evaluating occupational radiation exposures, and current government regulations for protecting workers and ensuring that standards for radiation protection are adhered to. In addition, a survey of current radiological health practices is summarized

Aerospace medicine and biology: A continuing bibliography with indexes, supplement 197, September 1979

This bibliography lists 193 reports, articles, and other documents introduced into the NASA scientific and technical information system in August 1979