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https://www.readbyqxmd.com/read/28088864/an-integrated-high-throughput-multi-omics-platform-enables-data-driven-construction-of-cellular-responses-and-reveals-global-drug-mechanisms-of-action
#1
Jeremy L Norris, Melissa A Farrow, Danielle B Gutierrez, Lauren D Palmer, Nicole Muszynski, Stacy D Sherrod, James C Pino, Jamie L Allen, Jeffrey M Spraggins, Alex L R Lubbock, Ashley T Jordan, William Burns, James C Poland, Carrie E Romer, M Lisa Manier, Yuan-Wei Nei, Boone M Prentice, Kristie L Rose, Salisha Hill, Raf Van de Plas, Tina Tsui, Nathaniel M Braman, M Ray Keller, Stacey A Rutherford, Nichole A Lobdell, Carlos F Lopez, D Borden Lacy, John A McLean, John Peter Wikswo, Eric P Skaar, Richard M Caprioli
An understanding of how cells respond to perturbation is essential for biological applications; however, most approaches for profiling cellular response are limited in scope to pre-established targets. Global analysis of molecular mechanism will advance our understanding of the complex networks constituting cellular perturbation and lead to advancements in areas, such as infectious disease pathogenesis, developmental biology, pathophysiology, pharmacology, and toxicology. We have developed a high-throughput multi-omics platform for comprehensive, de novo characterization of cellular mechanisms of action...
January 14, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28088094/organ-on-a-chip-for-assessing-environmental-toxicants
#2
REVIEW
Soohee Cho, Jeong-Yeol Yoon
Man-made xenobiotics, whose potential toxicological effects are not fully understood, are oversaturating the already-contaminated environment. Due to the rate of toxicant accumulation, unmanaged disposal, and unknown adverse effects to the environment and the human population, there is a crucial need to screen for environmental toxicants. Animal models and in vitro models are ineffective models in predicting in vivo responses due to inter-species difference and/or lack of physiologically-relevant 3D tissue environment...
January 11, 2017: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/28073536/microelectrode-array-mea-platform-as-a-sensitive-tool-to-detect-and-evaluate-ostreopsis-cf-ovata-toxicity
#3
Susanna Alloisio, Valentina Giussani, Mario Nobile, Mariachiara Chiantore, Antonio Novellino
In the last decade, the occurrence of harmful dinoflagellate blooms of the genus Ostreopsis has increased both in frequency and in geographic distribution with adverse impacts on public health and the economy. Ostreopsis species are producers of palytoxin-like toxins (putative palytoxin and ovatoxins) which are among the most potent natural non-protein compounds known to date, exhibiting extreme toxicity in mammals, including humans. Most existing toxicological data are derived from in vivo mouse assay and are related to acute effects of pure palytoxin, without considering that the toxicity mechanism of dinoflagellates can be dependent on the varying composition of complex biotoxins mixture and on the presence of cellular components...
May 2016: Harmful Algae
https://www.readbyqxmd.com/read/28032149/dtni-a-novel-toxicogenomics-data-analysis-tool-for-identifying-the-molecular-mechanisms-underlying-the-adverse-effects-of-toxic-compounds
#4
Diana M Hendrickx, Terezinha Souza, Danyel G J Jennen, Jos C S Kleinjans
Unravelling gene regulatory networks (GRNs) influenced by chemicals is a major challenge in systems toxicology. Because toxicant-induced GRNs evolve over time and dose, the analysis of global gene expression data measured at multiple time points and doses will provide insight in the adverse effects of compounds. Therefore, there is a need for mathematical methods for GRN identification from time-over-dose-dependent data. One of the current approaches for GRN inference is Time Series Network Identification (TSNI)...
December 28, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/28028702/field-evidence-of-bird-poisonings-by-imidacloprid-treated-seeds-a-review-of-incidents-reported-by-the-french-sagir-network-from-1995-to-2014
#5
Florian Millot, Anouk Decors, Olivier Mastain, Thomas Quintaine, Philippe Berny, Danièle Vey, Romain Lasseur, Elisabeth Bro
The large-scale use of neonicotinoid insecticides has raised growing concerns about their potential adverse effects on farmland birds, and more generally on biodiversity. Imidacloprid, the first neonicotinoid commercialized, has been identified as posing a risk for seed-eating birds when it is used as seed treatment of some crops since the consumption of a few dressed seeds could cause mortality. But evidence of direct effects in the field is lacking. Here, we reviewed the 103 wildlife mortality incidents reported by the French SAGIR Network from 1995 to 2014, for which toxicological analyses detected imidacloprid residues...
December 27, 2016: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28005974/bibliometrics-for-social-validation
#6
Daniel J Hicks
This paper introduces a bibliometric, citation network-based method for assessing the social validation of novel research, and applies this method to the development of high-throughput toxicology research at the US Environmental Protection Agency. Social validation refers to the acceptance of novel research methods by a relevant scientific community; it is formally independent of the technical validation of methods, and is frequently studied in history, philosophy, and social studies of science using qualitative methods...
2016: PloS One
https://www.readbyqxmd.com/read/27979774/gene-regulatory-networks-in-differentiation-and-direct-reprogramming-of-hepatic-cells
#7
REVIEW
Claude Gérard, Janne Tys, Frédéric P Lemaigre
Liver development proceeds by sequential steps during which gene regulatory networks (GRNs) determine differentiation and maturation of hepatic cells. Characterizing the architecture and dynamics of these networks is essential for understanding how cell fate decisions are made during development, and for recapitulating these processes during in vitro production of liver cells for toxicology studies, disease modelling and regenerative therapy. Here we review the GRNs that control key steps of liver development and lead to differentiation of hepatocytes and cholangiocytes in mammals...
December 12, 2016: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/27978797/prediction-of-chemical-multi-target-profiles-and-adverse-outcomes-with-systems-toxicology
#8
Henri Wathieu, Abiola Ojo, Sivanesan Dakshanamurthy
The field of systems biology, termed systems toxicology when applied to the characterization of adverse outcomes following chemical exposure, seeks to develop biological networks to explain phenotypic responses. Ideally, these are qualitatively and quantitatively similar to the actual network of biological entities that have functional consequences in living organisms. In this review, we outline computational tools for predicting chemical-protein interactions of multi-target compounds. Then, we discuss how the methods of systems toxicology currently draw on those interactions to predict resulting adverse outcomes which include diseases, adverse drug reactions, and toxic endpoints...
December 14, 2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/27933809/development-and-validation-of-a-computational-model-for-androgen-receptor-activity
#9
Nicole C Kleinstreuer, Patricia Ceger, Eric D Watt, Matthew Martin, Keith Houck, Patience Browne, Russell S Thomas, Warren M Casey, David J Dix, David Allen, Srilatha Sakamuru, Menghang Xia, Ruili Huang, Richard Judson
Testing thousands of chemicals to identify potential androgen receptor (AR) agonists or antagonists would cost millions of dollars and take decades to complete using current validated methods. High-throughput in vitro screening (HTS) and computational toxicology approaches can more rapidly and inexpensively identify potential androgen-active chemicals. We integrated 11 HTS ToxCast/Tox21 in vitro assays into a computational network model to distinguish true AR pathway activity from technology-specific assay interference...
December 9, 2016: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/27901397/a-systems-toxicology-approach-reveals-the-wnt-mapk-crosstalk-pathway-mediated-reproductive-failure-in-caenorhabditis-elegans-exposed-to-graphene-oxide-go-but-not-to-reduced-graphene-oxide-rgo
#10
Nivedita Chatterjee, Youngho Kim, Jisu Yang, Carlos P Roca, Sang-Woo Joo, Jinhee Choi
The potential hazards of graphene nanomaterials were investigated by exposing the nematode Caenorhabditis elegans to graphene oxide (GO) and reduced graphene oxide (rGO). The underlying mechanisms of the nano-bio interaction were addressed with an integrated systems toxicology approach using global transcriptomics, network-based pathway analysis, and experimental validation of the in-silico-derived hypotheses. Graphene oxide was found to reduce the worms' reproductive health to a greater degree than rGO, but it did not affect survival (24 h endpoint)...
December 20, 2016: Nanotoxicology
https://www.readbyqxmd.com/read/27890000/reproductive-toxicity-of-t-cells-in-early-life-abnormal-immune-development-and-postnatal-diseases
#11
Han-Xiao Liu, Aifang Jiang, Ting Chen, Wen Qu, Hui-Yi Yan, Jie Ping
Immunity is a balanced status with adequate biological defenses to recognize and fight "non-self", as well as adequate tolerance to recognize "self". To maintain this immune homeostasis, a well-organized T cell immune network is required, which in part depends on the well-controlled development of alternative effector T cells, with different cytokine repertoires. Recent research has pointed that developing fetal T cells network is a remarkably sensitive toxicological target for adverse factors in early life...
November 24, 2016: Current Drug Targets
https://www.readbyqxmd.com/read/27865774/a-systems-toxicology-approach-for-comparative-assessment-biological-impact-of-an-aerosol-from-a-candidate-modified-risk-tobacco-product-and-cigarette-smoke-on-human-organotypic-bronchial-epithelial-cultures
#12
Anita R Iskandar, Carole Mathis, Walter K Schlage, Stefan Frentzel, Patrice Leroy, Yang Xiang, Alain Sewer, Shoaib Majeed, Laura Ortega-Torres, Stephanie Johne, Emmanuel Guedj, Keyur Trivedi, Gilles Kratzer, Celine Merg, Ashraf Elamin, Florian Martin, Nikolai V Ivanov, Manuel C Peitsch, Julia Hoeng
This study reports a comparative assessment of the biological impact of a heated tobacco aerosol from the tobacco heating system (THS) 2.2 and smoke from a combustible 3R4F cigarette. Human organotypic bronchial epithelial cultures were exposed to an aerosol from THS2.2 (a candidate modified-risk tobacco product) or 3R4F smoke at similar nicotine concentrations. A systems toxicology approach was applied to enable a comprehensive exposure impact assessment. Culture histology, cytotoxicity, secreted pro-inflammatory mediators, ciliary beating, and genome-wide mRNA/miRNA profiles were assessed at various time points post-exposure...
March 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/27848238/a-tractable-method-for-measuring-nanomaterial-risk-using-bayesian-networks
#13
Finbarr Murphy, Barry Sheehan, Martin Mullins, Hans Bouwmeester, Hans J P Marvin, Yamine Bouzembrak, Anna L Costa, Rasel Das, Vicki Stone, Syed A M Tofail
While control banding has been identified as a suitable framework for the evaluation and the determination of potential human health risks associated with exposure to nanomaterials (NMs), the approach currently lacks any implementation that enjoys widespread support. Large inconsistencies in characterisation data, toxicological measurements and exposure scenarios make it difficult to map and compare the risk associated with NMs based on physicochemical data, concentration and exposure route. Here we demonstrate the use of Bayesian networks as a reliable tool for NM risk estimation...
December 2016: Nanoscale Research Letters
https://www.readbyqxmd.com/read/27832950/the-chick-embryo-chorioallantoic-membrane-cam-assay
#14
Domenico Ribatti
During avian development the mesodermal layers of the allantois and chorion fuse to form the chorioallantoic membrane (CAM). This structure rapidly expands generating a rich vascular network that provides an interface for gas and waste exchange. The CAM allows to study tissue grafts, tumor growth and metastasis, drugs delivery and toxicologic analysis, and angiogenic and anti-angiogenic molecules. The CAM is relatively simple, quick, and low-cost model that allows screening of a large number of pharmacological samples in a short time; does not require administrative procedures for obtaining ethics committee approval for animal experimentation...
November 7, 2016: Reproductive Toxicology
https://www.readbyqxmd.com/read/27799056/toxicity-of-graphene-family-nanoparticles-a-general-review-of-the-origins-and-mechanisms
#15
REVIEW
Lingling Ou, Bin Song, Huimin Liang, Jia Liu, Xiaoli Feng, Bin Deng, Ting Sun, Longquan Shao
Due to their unique physicochemical properties, graphene-family nanomaterials (GFNs) are widely used in many fields, especially in biomedical applications. Currently, many studies have investigated the biocompatibility and toxicity of GFNs in vivo and in intro. Generally, GFNs may exert different degrees of toxicity in animals or cell models by following with different administration routes and penetrating through physiological barriers, subsequently being distributed in tissues or located in cells, eventually being excreted out of the bodies...
October 31, 2016: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/27793746/evaluation-of-the-tobacco-heating-system-2-2-part-4-90-day-oecd-413-rat-inhalation-study-with-systems-toxicology-endpoints-demonstrates-reduced-exposure-effects-compared-with-cigarette-smoke
#16
Ee Tsin Wong, Ulrike Kogel, Emilija Veljkovic, Florian Martin, Yang Xiang, Stephanie Boue, Gregory Vuillaume, Patrice Leroy, Emmanuel Guedj, Gregory Rodrigo, Nikolai V Ivanov, Julia Hoeng, Manuel C Peitsch, Patrick Vanscheeuwijck
The objective of the study was to characterize the toxicity from sub-chronic inhalation of test atmospheres from the candidate modified risk tobacco product (MRTP), Tobacco Heating System version 2.2 (THS2.2), and to compare it with that of the 3R4F reference cigarette. A 90-day nose-only inhalation study on Sprague-Dawley rats was performed, combining classical and systems toxicology approaches. Reduction in respiratory minute volume, degree of lung inflammation, and histopathological findings in the respiratory tract organs were significantly less pronounced in THS2...
November 30, 2016: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/27772743/electrophysiological-characterization-of-nsc-34-cell-line-using-microelectrode-array
#17
K R Sabitha, D Sanjay, B Savita, T R Raju, T R Laxmi
Neurons communicate with each other through intricate network to evolve higher brain functions. The electrical activity of the neurons plays a crucial role in shaping the connectivity. With motor neurons being vulnerable to neurodegenerative diseases, understanding the electrophysiological properties of motor neurons is the need of the hour, in order to comprehend the impairment of connectivity in these diseases. NSC-34 cell line serves as an excellent model to study the properties of motor neurons as they express Choline acetyltransferase (ChAT)...
November 15, 2016: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/27768803/human-environmental-disease-network-a-computational-model-to-assess-toxicology-of-contaminants
#18
Olivier Taboureau, Karine Audouze
During the past decades, many epidemiological, toxicological and biological studies have been performed to assess the role of environmental chemicals as potential toxicants for diverse human disorders. However, the relationships between diseases based on chemical exposure have been rarely studied by computational biology. We developed a human environmental disease network (EDN) to explore and suggest novel disease-disease and chemical-disease relationships. The presented scored EDN model is built upon the integration on systems biology and chemical toxicology using chemical contaminants information and their disease relationships from the reported TDDB database...
October 21, 2016: ALTEX
https://www.readbyqxmd.com/read/27760991/identification-of-a-regulation-network-in-response-to-cadmium-toxicity-using-blood-clam-tegillarca-granosa-as-model
#19
Yongbo Bao, Xiao Liu, Weiwei Zhang, Jianping Cao, Wei Li, Chenghua Li, Zhihua Lin
Clam, a filter-feeding lamellibranch mollusk, is capable to accumulate high levels of trace metals and has therefore become a model for investigation the mechanism of heavy metal toxification. In this study, the effects of cadmium were characterized in the gills of Tegillarca granosa during a 96-hour exposure course using integrated metabolomic and proteomic approaches. Neurotoxicity and disturbances in energy metabolism were implicated according to the metabolic responses after Cd exposure, and eventually affected the osmotic function of gill tissue...
October 20, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27757495/evaluation-of-the-cytotoxic-properties-gene-expression-profiles-and-secondary-signalling-responses-of-cultured-cells-exposed-to-fumonisin-b1-deoxynivalenol-and-zearalenone-mycotoxins
#20
Johannes F Wentzel, Martani J Lombard, Lissinda H Du Plessis, Lizelle Zandberg
Mycotoxins are toxic secondary metabolites produced by a range of fungi and are common contaminants of agricultural crops. These toxins are chemically diverse and structurally stable, enabling them to enter the food chain which can lead to numerous adverse health effects in animals and humans. Although mycotoxin exposure is associated with the development of several cancers, it has proved challenging to show a direct connection between exposure and oncogenic change. This study investigates the in vitro cytotoxicity, molecular mechanisms and secondary signalling responses associated with the exposure to three major mycotoxins, fumonisin B1 (FB1), deoxynivalenol (Don) and zearalenone (Zea)...
October 18, 2016: Archives of Toxicology
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