Identification Of Chemicals Research Articles

Chemopreventive Agents Attenuate Rapid Inhibition of Gap Junctional Intercellular Communication Induced by Environmental Toxicants

ABSTRACTAltered gap junctional intercellular communication (GJIC) has been associated with chemical carcinogenesis, where both chemical tumor promoters and chemopreventive agents (CPAs) are known to conversely modulate GJIC. The aim of this study was to investigate whether attenuation of chemically inhibited GJIC represents a common outcome induced by different CPAs, which could be effectively evaluated using in vitro methods. Rat liver epithelial cells WB-F344 were pretreated with a CPA for either 30 min or 24 h, and then exposed to GJIC-inhibiting concentration of a selected tumor promoter or environmental toxicant [12-O-tetradecanoylphorbol-13-acetate (TPA), lindane, fluoranthene, 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (DDT), perfluorooctanoic acid (PFOA), or pentachlorophenol]. Out of nine CPAs tested, quercetin and silibinin elicited the most pronounced effects, preventing the dysregulation of GJIC by all the GJIC inhibitors, but DDT. Metformin and curcumin attenuated the effects of three GJIC inhibitors, whereas the other CPAs prevented the effects of two (diallyl sulfide, emodin) or one (indole-3-carbinol, thymoquinone) GJIC inhibitor. Significant attenuation of chemically induced inhibition of GJIC was observed in 27 (50%) out of 54 possible combinations of nine CPAs and six GJIC inhibitors. Our data demonstrate that in vitro evaluation of GJIC can be used as an effective screening tool for identification of chemicals with potential chemopreventive activity.

Editor's Highlight: Identification and Characterization of Teratogenic Chemicals Using Embryonic Stem Cells Isolated From a Wnt/β-Catenin-Reporter Transgenic Mouse Line.

Embryonic stem cells (ESCs) are commonly used for the analysis of gene function in embryonic development and provide valuable models for human diseases. In recent years, ESCs have also become an attractive tool for toxicological testing, in particular for the identification of teratogenic compounds. We have recently described a Bmp-reporter ESC line as a new tool to identify teratogenic compounds and to characterize the molecular mechanisms mediating embryonic toxicity. Here we describe the use of a Wnt/β-Catenin-reporter ESC line isolated from a previously described mouse line that carries the LacZ reporter gene under the control of a β-Catenin responsive promoter. The reporter ESC line stably differentiates into cardiomyocytes within 12 days. The reporter was endogenously induced between day 3-5 of differentiation reminiscent of its expression in vivo, in which strong LacZ activity is detected around gastrulation. Subsequently its expression becomes restricted to mesodermal cells and cells undergoing an epithelial to mesenchymal transition. The Wnt/β-Catenin-dependent expression of the reporter protein allowed quantification of dose- and time-dependent effects of teratogenic chemicals. In particular, valproic acid reduced reporter activity on day 7 whereas retinoic acid induced reporter activity on day 5 at concentrations comparable to the ones inhibiting the formation of functional cardiomyocytes, the classical read-out of the embryonic stem cell test (EST). In addition, we were also able to show distinct effects of teratogenic chemicals on the Wnt/β-Catenin-reporter compared with the previously described Bmp-reporter ESCs. Thus, different reporter cell lines provide complementary tools for the identification and analysis of potentially teratogenic compounds.

Assessment of petroleum streams for thyroid toxicity.

The thyroid gland, and its associated endocrine hormones, is a growing area of interest in regulatory toxicology due to its important role in metabolism, growth and development. This report presents a review of the toxicology data on chemically complex petroleum streams for thyroid hormone effects. Toxicological summaries and studies from all available published and un-published sources were considered, drawing upon the European REACH regulatory submissions for 19 petroleum streams, with in depth review of 11 individual study reports and 31 published papers on related products or environmental settings. Findings relevant to thyroid pathology or thyroid hormone homeostasis were specifically sought, summarized, and discussed. A total of 349 studies of 28-days or longer duration were considered in the review, including data on mice, rats, rabbits, dogs, humans, and fish. The thyroid was almost invariably not a target organ in these studies. Three rodent studies did find thyroid effects; one on a jet fuel product (JP-8), and two studies on a heavy fuel oil product (F-179). The JP-8 product differs from other fuels due to the presence of additives, and the finding of reduced T4 levels in mice in the study occurred at a dose that is above that expected to occur in environmental settings (e.g. 2000mg/kg). The finding for F-179 involved thyroid inflammation at 10-55mg/kg that co-occurred with liver pathology in rats, indicating a possible secondary effect with questionable relevance to humans. In the few cases where findings did occur, the polycyclic aromatic hydrocarbon (PAH) content was higher than in related substances, and, in support of one possible adverse outcome pathway, one in-vitro study reported reduced thyroid peroxidase (TPO) activity with exposure to some PAH compounds (pyrene, benzo(k)fluoranthene, and benzo(e)pyrene). However, it could not be determined from the data available for this review, whether these specific PAH compounds were substantially higher in the JP-8 or F-179 products than in studies in which thyroid effects were not observed. Thus, a few products may carry a weak potential to affect the thyroid at high doses in rodents, possibly through secondary effects on the rodent liver or possibly through a pathway involving the inhibition of TPO by specific members of the PAH family. Human epidemiology evidence found weak and inconsistent effects on the thyroid but without identification of specific chemicals involved. Two studies in petroleum workers, which found a lower rate of morbidity and mortality overall, reported a statistically significant increase in thyroid cancer, but the small number of cases could not exclude confounding variables as possible explanations for the statistical findings. Overall, the available data indicates a low potential for thyroid hormone effects from exposure to petroleum streams, especially when the aromatic content is low. Because regulatory studies for most chemicals do not include detailed thyroid function or receptor studies, it remains possible that subclinical effects on this system may exist that were not detectable using conventional pathology or hormone measurements.

Identification of chemicals that mimic transcriptional changes associated with autism, brain aging and neurodegeneration.

Environmental factors, including pesticides, have been linked to autism and neurodegeneration risk using retrospective epidemiological studies. Here we sought to prospectively identify chemicals that share transcriptomic signatures with neurological disorders, by exposing mouse cortical neuron-enriched cultures to hundreds of chemicals commonly found in the environment and on food. We find that rotenone, a pesticide associated with Parkinson's disease risk, and certain fungicides, including pyraclostrobin, trifloxystrobin, famoxadone and fenamidone, produce transcriptional changes in vitro that are similar to those seen in brain samples from humans with autism, advanced age and neurodegeneration (Alzheimer's disease and Huntington's disease). These chemicals stimulate free radical production and disrupt microtubules in neurons, effects that can be reduced by pretreating with a microtubule stabilizer, an antioxidant, or with sulforaphane. Our study provides an approach to prospectively identify environmental chemicals that transcriptionally mimic autism and other brain disorders.

Binary classification model to predict developmental toxicity of industrial chemicals in zebrafish

The identification of industrial chemicals, which may cause developmental effects, is of great importance for an early detection of hazardous chemicals. Accordingly, categorical quantitative structure‐activity relationship (QSAR) models were developed, based on developmental toxicity profile data for zebrafish from the ToxCast Phase I testing, to predict the toxicity of a large set of high and low production volume chemicals (H/LPVCs). QSARs were created using linear (LDA), quadratic, and partial least squares‐discriminant analysis with different chemical descriptors. The predictions of the best model (LDA) were compared with those obtained by the freely available QSAR model VEGA, created based on a dataset with a different chemical domain. The results showed that despite similar accuracy (AC) of both models, the LDA model is more specific than VEGA and shows a better agreement between sensitivity (SE) and specificity (SP). Applying a 90% confidence level on the LDA model led to even better predictions showing SE of 0.92, AC of 0.95, and geometric mean of SE and SP (G) of 0.96 for the prediction set. The LDA model predicted 608 H/LPVCs as toxicants among which 123 chemicals fall inside the AD of the VEGA model, which predicted 112 of those as toxicants. Among the 112 chemicals predicted as toxic H/LPVCs, 23 have been previously reported as developmental toxicants. The here presented LDA model could be used to identify and prioritize H/LPVCs for subsequent developmental toxicity assessment, as a screening tool of potential developmental effects of new chemicals, and to guide synthesis of safer alternative chemicals. © 2016 The Authors Journal of Chemometrics Published by John Wiley & Sons Ltd

Fingerprinting of neurotoxic compounds using a mouse embryonic stem cell dual luminescence reporter assay

Identification of neurotoxic drugs and environmental chemicals is an important challenge. However, only few tools to address this topic are available. The aim of this study was to develop a neurotoxicity/developmental neurotoxicity (DNT) test system, using the pluripotent mouse embryonic stem cell line CGR8 (ESCs). The test system uses ESCs at two differentiation stages: undifferentiated ESCs and ESC-derived neurons. Under each condition, concentration–response curves were obtained for three parameters: activity of the tubulin alpha 1 promoter (typically activated in early neurons), activity of the elongation factor 1 alpha promoter (active in all cells), and total DNA content (proportional to the number of surviving cells). We tested 37 compounds from the ESNATS test battery, which includes polypeptide hormones, environmental pollutants (including methylmercury), and clinically used drugs (including valproic acid and tyrosine kinase inhibitors). Different classes of compounds showed distinct concentration–response profiles. Plotting of the lowest observed adverse effect concentrations (LOAEL) of the neuronal promoter activity against the general promoter activity or against cytotoxicity, allowed the differentiation between neurotoxic/DNT substances and non-neurotoxic controls. Reporter activity responses in neurons were more susceptible to neurotoxic compounds than the reporter activities in ESCs from which they were derived. To relate the effective/toxic concentrations found in our study to relevant in vivo concentrations, we used a reverse pharmacokinetic modeling approach for three exemplary compounds (teriflunomide, geldanamycin, abiraterone). The dual luminescence reporter assay described in this study allows high-throughput, and should be particularly useful for the prioritization of the neurotoxic potential of a large number of compounds.

Liquid chromatography coupled to tandem and high resolution mass spectrometry for the characterisation of ofloxacin transformation products after titanium dioxide photocatalysis

The characterization of pharmaceutical drugs and their transformation products have become an important analytical research field because its presence in the environment could induce bacterial resistance. Despite all efforts made by the scientific community, detection and structure identification of unknown chemicals still remains the most challenging task in non-targeted analytics. Given that, the objective of the present study was to develop an untargeted workflow to detect, quantify, identify and characterize ofloxacin and its transformation products (OFX TPs) after photocatalytic treatments based on TiO2 nanoparticles and TiO2 nanofibers. For the characterization and chemical structure assignment of OFX TPs, mass defect filters, mass accurate measurements (HRMS), tandem mass spectrometry in a q-Orbitrap (MS/HRMS) and the photocatalysis of the isotopically labelled ofloxacin (OFX-d3) were used. Since a large set of data was obtained in each run, data treatment based on statistical analysis and mass defect filtering was used to reduce the number of potential TP candidates from 2497m/z peaks to 70. Moreover, ions generated by in-source CID and by redox reactions in the electrospray source (ESI) were also detected and discarded from the TP candidate list. Moreover, the whole kinetics evolution of the generated TPs provided a deeper insight into the degradation mechanism and was used to propose a degradation pathway for the OFX in the aqueous phase. The time evolution of the TPs generated during the photocatalytic process using both types of catalysts (NPs and NFs) and different set-ups (suspended and supported conditions) indicated that OFX was completely removed from the aqueous solution in less than 4h. Among the condition tested TiO2 nanoparticles in suspended conditions showed the fastest kinetics (k: 0.161min−1).

Field identification and spatial determination of hazardous chemicals by Fourier transform infrared imaging

ABSTRACTA hyperspectral imaging device is reported for the remote sensing of hazardous chemical clouds. The device, which is based on Fourier transform spectrometry, displays two-dimensional images of spatially resolved spectral information delivered from a focal-plane-array detector. An algorithm for chemical-cloud detection using the spectrum obtained by the hyperspectral imaging device was also developed. In order to promptly extract results from the large quantity of spectral information, the detection algorithm included approximate and precise detection steps. The performance of the hyperspectral imaging device was characterized in the lab and in the field using the detection algorithm. The real-time distribution of a chemical cloud was successfully observed.

QSAR Toolbox – workflow and major functionalities

The OECD QSAR Toolbox is a software application intended to be used by governments, the chemical industry and other stakeholders in filling gaps in (eco)toxicity data needed for assessing the hazards of chemicals. The development and release of the Toolbox is a cornerstone in the computerization of hazard assessment, providing an ‘all inclusive’ tool for the application of category approaches, such as read-across and trend analysis, in a single software application, free of charge. The Toolbox incorporates theoretical knowledge, experimental data and computational tools from various sources into a logical workflow. The main steps of this workflow are substance identification, identification of relevant structural characteristics and potential toxic mechanisms of interaction (i.e. profiling), identification of other chemicals that have the same structural characteristics and/or mechanism (i.e. building a category), data collection for the chemicals in the category and use of the existing experimental data to fill the data gap(s). The description of the Toolbox workflow and its main functionalities is the scope of the present article.

Systematic analytical characterization of new psychoactive substances: A case study

New psychoactive substances (NPS) are synthesized compounds that are not usually covered by European and/or international laws. With a slight alteration in the chemical structure of existing illegal substances registered in the European Union (EU), these NPS circumvent existing controls and are thus referred to as “legal highs”. They are becoming increasingly available and can easily be purchased through both the internet and other means (smart shops). Thus, it is essential that the identification of NPS keeps up with this rapidly evolving market.In this case study, the Belgian Customs authorities apprehended a parcel, originating from China, containing two samples, declared as being “white pigments”. For routine identification, the Belgian Customs Laboratory first analysed both samples by gas-chromatography mass-spectrometry and Fourier-Transform Infrared spectroscopy. The information obtained by these techniques is essential and can give an indication of the chemical structure of an unknown substance but not the complete identification of its structure. To bridge this gap, scientific and technical support is ensured by the Joint Research Centre (JRC) to the European Commission Directorate General for Taxation and Customs Unions (DG TAXUD) and the Customs Laboratory European Network (CLEN) through an Administrative Arrangement for fast recognition of NPS and identification of unknown chemicals. The samples were sent to the JRC for a complete characterization using advanced techniques and chemoinformatic tools.The aim of this study was also to encourage the development of a science-based policy driven approach on NPS.These samples were fully characterized and identified as 5F-AMB and PX-3 using 1H and 13C nuclear magnetic resonance (NMR), high-resolution tandem mass-spectrometry (HR-MS/MS) and Raman spectroscopy. A chemoinformatic platform was used to manage, unify analytical data from multiple techniques and instruments, and combine it with chemical and structural information.

Identification of chemicals that mimic transcriptional changes associated with autism, brain aging and neurodegeneration

Identification of chemicals that mimic transcriptional changes associated with autism, brain aging and neurodegeneration

A Web-based Tool to Aid the Identification of Chemicals Potentially Posing a Health Risk through Percutaneous Exposure.

Occupational hygiene practitioners typically assess the risk posed by occupational exposure by comparing exposure measurements to regulatory occupational exposure limits (OELs). In most jurisdictions, OELs are only available for exposure by the inhalation pathway. Skin notations are used to indicate substances for which dermal exposure may lead to health effects. However, these notations are either present or absent and provide no indication of acceptable levels of exposure. Furthermore, the methodology and framework for assigning skin notation differ widely across jurisdictions resulting in inconsistencies in the substances that carry notations. The UPERCUT tool was developed in response to these limitations. It helps occupational health stakeholders to assess the hazard associated with dermal exposure to chemicals. UPERCUT integrates dermal quantitative structure-activity relationships (QSARs) and toxicological data to provide users with a skin hazard index called the dermal hazard ratio (DHR) for the substance and scenario of interest. The DHR is the ratio between the estimated 'received' dose and the 'acceptable' dose. The 'received' dose is estimated using physico-chemical data and information on the exposure scenario provided by the user (body parts exposure and exposure duration), and the 'acceptable' dose is estimated using inhalation OELs and toxicological data. The uncertainty surrounding the DHR is estimated with Monte Carlo simulation. Additional information on the selected substances includes intrinsic skin permeation potential of the substance and the existence of skin notations. UPERCUT is the only available tool that estimates the absorbed dose and compares this to an acceptable dose. In the absence of dermal OELs it provides a systematic and simple approach for screening dermal exposure scenarios for 1686 substances.

Hadoop based Text Mining System for Identification of Chemicals Associated with Disease of Interest

With huge amounts of biomedical data being generated day by day extracting statistical information about the chemicals mentioned in such huge databases manually is tedious and time consuming. Our system is mainly designed for naive users, which aims to automate data collection and knowledge extraction from chemical literature in a user friendly and efficient way on the hadoop platform. The system downloads the abstracts related to the disease of interest from Pubmed database. The text of the abstracts is then extensively parsed for chemicals such as protein/gene names and chemical compound names and classified into different classes. This analysis would prove to be helpful in various biomedical and pharmaceutical industries. The extraction of important information will be done using the Ling Pipe API wherein a training dataset is given to this Ling Pipe which classifies the extracted bioentities in the respective classes. The system being deployed on hadoop platform provides a scalable and distributed system which processes huge number of abstracts in a short time and with high efficiency. The system also provides a user friendly user interface for easy use of the hadoop system for non technical users.

A computer vision based technique for identification of acrylamide in potato chips

Acrylamide is a well-known neurotoxin substance commonly found in fried and baked food items such as potato chips, cookies, biscuits & French fries. Identification of such toxic chemicals in fried food is of great importance. Conventional methods of acrylamide identification in food items are time consuming, expensive and may need specialized manpower. The proposed work presents a computer vision based non-destructive method to identify the presence of acrylamide in potato chips. The proposed method is based on analysis and classification of the discriminatory features of the image in spatial domain. The potato chips are automatically segmented from the image followed by statistical and texture features extraction from the segmented image in spatial domain. These statistical features are then analyzed for identification of acrylamide content using support vector machine (SVM) classifier. The discriminatory variation in the features of the image is strategically related to the presence of acrylamide using image processing techniques. The experimental results have shown accuracy over than 94% and sensitivity of 96% indicating that this method could be explored for viable commercial use.

Design of a Mars atmosphere simulation chamber and testing a Raman Laser Spectrometer (RLS) under conditions pertinent to Mars rover missions

Raman spectrometry is a powerful technique for the rapid identification of most minerals and organic chemicals without sample preparation. In this context, the European Space Agency (ESA) and NASA selected a Raman spectrometer in the payload of the future ExoMars and Mars 2020 missions to identify organic compounds and mineral products indicative of biological activity on Mars. Little is known, however, about the effects of Mars atmospheric conditions on instrument performance and on the Raman spectra. The objective of this study was to i) design and construct a versatile simulation chamber to reproduce the atmospheric conditions expected inside a rover on Mars, ii) to test the performance of a previously designed breadboard miniaturized Raman laser spectrometer (RLS) inside the chamber. The Mars Atmosphere Simulation Chamber (MASC) is a temperature and atmosphere controlled chamber. It includes an innovative heating-cooling system to create homogeneous temperatures inside the chamber that can be varied between 243 K and 283 K, while the charged coupled device (CCD) of the Raman spectrometer can be independently cooled (e.g., 233 K). A vacuum and gas control system permits evacuation of the chamber and the subsequent introduction of any (dried) gas mixture at partial pressures between 1 mbar and several bars. The minimum CCD temperature was found to depend on the surrounding MASC temperature and atmosphere. A vertical shift of 3 pixels on the CCD was observed for the Raman signals upon lowering the temperature from 283 to 253 K. We show that the RLS instrument gives reliable Raman spectra over the tested range of temperatures and from a vacuum of 4 x 10−5 mbar to a CO2 atmosphere at pressure relevant to Mars (8 mbar). For example, the Raman spectra of three test minerals, calcite, aragonite and baryte, showed identifiable Raman peaks with Raman shift values within ± 1 cm−1 of those reported in previous works under terrestrial conditions. This confirms that a RLS instrument is useful for the identification of minerals during future missions to Mars; once a necessary detector recalibration was carried out, the system performed well under 8 mbar pressure and 243 – 283 K. The MASC was found to be a versatile instrument; it can provide important information on instrument performance under Martian conditions and other temperatures and atmospheric conditions can also be simulated.

An in vitro human skin test for assessing sensitization potential.

Sensitization to chemicals resulting in an allergy is an important health issue. The current gold-standard method for identification and characterization of skin-sensitizing chemicals was the mouse local lymph node assay (LLNA). However, for a number of reasons there has been an increasing imperative to develop alternative approaches to hazard identification that do not require the use of animals. Here we describe a human in-vitro skin explant test for identification of sensitization hazards and the assessment of relative skin sensitizing potency. This method measures histological damage in human skin as a readout of the immune response induced by the test material. Using this approach we have measured responses to 44 chemicals including skin sensitizers, pre/pro-haptens, respiratory sensitizers, non-sensitizing chemicals (including skin-irritants) and previously misclassified compounds. Based on comparisons with the LLNA, the skin explant test gave 95% specificity, 95% sensitivity, 95% concordance with a correlation coefficient of 0.9. The same specificity and sensitivity were achieved for comparison of results with published human sensitization data with a correlation coefficient of 0.91. The test also successfully identified nickel sulphate as a human skin sensitizer, which was misclassified as negative in the LLNA. In addition, sensitizers and non-sensitizers identified as positive or negative by the skin explant test have induced high/low T cell proliferation and IFNγ production, respectively. Collectively, the data suggests the human in-vitro skin explant test could provide the basis for a novel approach for characterization of the sensitizing activity as a first step in the risk assessment process.

Value of monitoring Nrf2 activity for the detection of chemical and oxidative stress.

Beyond specific limits of exposure, chemical entities can provoke deleterious effects in mammalian cells via direct interaction with critical macromolecules or by stimulating the accumulation of reactive oxygen species (ROS). In particular, these chemical and oxidative stresses can underpin adverse reactions to therapeutic drugs, which pose an unnecessary burden in the clinic and pharmaceutical industry. Novel pre-clinical testing strategies are required to identify, at an earlier stage in the development pathway, chemicals and drugs that are likely to provoke toxicity in humans. Mammalian cells can adapt to chemical and oxidative stress via the action of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), which up-regulates the expression of numerous cell defence genes and has been shown to protect against a variety of chemical toxicities. Here, we provide a brief overview of the Nrf2 pathway and summarize novel experimental models that can be used to monitor changes in Nrf2 pathway activity and thus understand the functional consequences of such perturbations in the context of chemical and drug toxicity. We also provide an outlook on the potential value of monitoring Nrf2 activity for improving the pre-clinical identification of chemicals and drugs with toxic liability in humans.

Introduction to the Symposium--Chemicals that Organize Ecology: Towards a Greater Integration of Chemoreception, Neuroscience, Organismal Biology, and Chemical Ecology.

Ecology as a process is shaped by biotic and abiotic influences. In some cases, a single type of chemical can have effects on an ecosystem, effects that are disproportionate to its relative mass, such that the ecosystem would organize differently in the absence of this type of chemical. The hallmark examples are those ‘‘molecules of keystone significance’’ (Ferrer and Zimmer 2012), such as the biosequestered alkaloid tetrodotoxin. Keystone molecules are analogous to keystone species in their capacity to mediate large ecological effects disproportionate to their mass. Some predators/grazers may evolve the ability to sense toxins being released from potential prey, making the toxin a semiochemical, molecules that serve as information-bearing cues among organisms (Ferrer and Zimmer 2012). Not all semiochemicals may be of keystone significance but they do have a greater effect on ecology that would be predicted, based on their abundance relative to all biomolecules, and could be said to ‘‘organize ecology.’’ Zimmer and Derby (2011) created a conceptual framework relating chemical defenses and neurobiological function in the SICB 2011 symposium entitled ‘‘Neural Determinants of Ecological Processes from Individuals to Ecosystems.’’ They advocated for an approach to defensive chemicals that integrated the isolation and identification of chemicals with study of behavioral responses, sensory and neuronal mechanisms of action, and ecological effects and adaptation. Their goals included learning how defensive chemicals affect the abundance and distribution of organisms and species. An integrative approach would include not only analytical chemistry, illustrating distributions of chemical within individual organs and across trophic levels, but would also attempt to link the chemicals to behavioral and physiological effects, and, ultimately, to reproductive success so as to define the mechanisms of the selective forces that shape ecology. Defensive chemicals can be released and repel competitors or predators/herbivores (van Alstyne et al. 2015, this issue), and one might predict that these competitors would eventually evolve an insensitivity to such cues unless the released chemicals were toxic. Alternatively, defensive chemicals can be accumulated or sequestered and they can affect trophic interactions upon contact or after partial ingestion. Some of these accumulated chemicals, such as saxitoxin (Ferrer et al. 2015, this issue) can be biosequestered over multiple trophic levels and keystone molecules are prime examples (Ferrer and Zimmer 2012). Also, chemicals with less comprehensive roles can also contribute to organizing ecological interactions. Other effects of defensive chemicals include the evolution of counter-measures such as avoidance of, or resistance to, toxins, and evolution of mechanisms of sensation (Lunceford and Kubanek 2015, this issue). One goal of this symposium was to extend the causes of ecology to the exchange of semiochemicals (pheromones, kairomones, allomones, and synomones) (Sbarbati and Osculati 2006). Thus, Integrative and Comparative Biology

High-Throughput and Rapid Screening of Low-Mass Hazardous Compounds in Complex Samples.

Rapid screening and identification of hazardous chemicals in complex samples is of extreme importance for public safety and environmental health studies. In this work, we report a new method for high-throughput, sensitive, and rapid screening of low-mass hazardous compounds in complex media without complicated sample preparation procedures. This method is achieved based on size-selective enrichment on ordered mesoporous carbon followed by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry analysis with graphene as a matrix. The ordered mesoporous carbon CMK-8 can exclude interferences from large molecules in complex samples (e.g., human serum, urine, and environmental water samples) and efficiently enrich a wide variety of low-mass hazardous compounds. The method can work at very low concentrations down to part per trillion (ppt) levels, and it is much faster and more facile than conventional methods. It was successfully applied to rapidly screen and identify unknown toxic substances such as perfluorochemicals in human serum samples from athletes and workers. Therefore, this method not only can sensitively detect target compounds but also can identify unknown hazardous compounds in complex media.

Identification of New Candidate Genes and Chemicals Related to Esophageal Cancer Using a Hybrid Interaction Network of Chemicals and Proteins.

Cancer is a serious disease responsible for many deaths every year in both developed and developing countries. One reason is that the mechanisms underlying most types of cancer are still mysterious, creating a great block for the design of effective treatments. In this study, we attempted to clarify the mechanism underlying esophageal cancer by searching for novel genes and chemicals. To this end, we constructed a hybrid network containing both proteins and chemicals, and generalized an existing computational method previously used to identify disease genes to identify new candidate genes and chemicals simultaneously. Based on jackknife test, our generalized method outperforms or at least performs at the same level as those obtained by a widely used method - the Random Walk with Restart (RWR). The analysis results of the final obtained genes and chemicals demonstrated that they highly shared gene ontology (GO) terms and KEGG pathways with direct and indirect associations with esophageal cancer. In addition, we also discussed the likelihood of selected candidate genes and chemicals being novel genes and chemicals related to esophageal cancer.