Identification of drug-specific pathways based on gene expression data: application to drug induced lung injury

Identification of signaling pathways that are functional in a specific biological context is a major challenge in systems biology, and could be instrumental to the study of complex diseases and various aspects of drug discovery. Recent approaches have attempted to combine gene expression data with prior knowledge of protein connectivity in the form of a PPI network, and employ computational methods to identify subsets of the protein–protein-interaction (PPI) network that are functional, based on the data at hand. However, the use of undirected networks limits the mechanistic insight that can be drawn, since it does not allow for following mechanistically signal transduction from one node to the next. To address this important issue, we used a directed, signaling network as a scaffold to represent protein connectivity, and implemented an Integer Linear Programming (ILP) formulation to model the rules of signal transduction from one node to the next in the network. We then optimized the structure of the network to best fit the gene expression data at hand. We illustrated the utility of ILP modeling with a case study of drug induced lung injury. We identified the modes of action of 200 lung toxic drugs based on their gene expression profiles and, subsequently, merged the drug specific pathways to construct a signaling network that captured the mechanisms underlying Drug Induced Lung Disease (DILD). We further demonstrated the predictive power and biological relevance of the DILD network by applying it to identify drugs with relevant pharmacological mechanisms for treating lung injury.Institute for Collaborative Biotechnologies (Grant W911NF-09-0001

Using bioassays for testing seawater quality in Greece

The purpose of this study is to show the seawater quality in the Thermaikos Gulf, the Pagassitikos Gulf and Skiathos island in the Northern Aegean Sea. The assessment of coastal water quality presented here is based on two bioassays that use marine organisms as indicators of seawater quality, the invertebrate Artemia franciscana and the marine bioluminescent bacterium Vibrio fischeri. Bioassays are necessary in water pollution evaluations as physical and chemical tests alone are not sufficient to assess potential effects on aquatic organisms. According to our results, there was an improvement in coastal water quality in the Thermaikos Gulf between September 1997 and April- May 2000. In the Pagassitikos Gulf the coastal water quality was generally good in April- May 2000, while in October 1999 it was generally poor. Between the two bioassays that we used in this study, the Microtox test, which uses the marine bacterium Vibrio fischeri as a test organism, was more sensitive in detecting toxicity in seawater

Removal of pollutants from poor quality coals by pyrolysis

Combustion of poor quality coals and wastes is used today worldwide for energy production. However, this entails significant environmental risks due to the presence of polluting compounds in them, i. e. S, N, Hg, and Cl. In the complex environment of combustion these substances are forming conventional (i. e. SOx, NOx) and toxic (PCDD/Fs) pollutants, while, the highly toxic Hg is volatilized in the gas phase mainly as elemental mercury. Aiming to meet the recently adopted strict environmental standards, and the need of affordable in cost clean power production, a preventive fuels pre-treatment technique, based on low temperature carbonization, has been tested. Clean coals were produced from two poor quality Greek coals (Ptolemais and Megalopolis) and an Australian coal sample, in a lab-scale fixed bed reactor under helium atmosphere and ambient pressure. The effect of carbonization temperature (200-900 °C) and residence time (5-120 minutes) on the properties of the chars, obtained after pyrolysis, was investigated. Special attention was paid to the removal of pollutants such as S, N, Hg, and Cl. To account for possible mineral matter effects, mainly on sulphur removal, tests were also performed with demineralized coal. Reactivity variation of produced clean coals was evaluated by performing non-isothermal combustion tests in a TA Q600 thermo gravimetric analyzer. Results showed that the low temperature carbonization technique might contribute to clean coal production by effectively removing the major part of the existing polluting compounds contained in coal. Therefore, depending on coal type, nitrogen, mercury, and chlorine abatement continuously increases with temperature, while sulphur removal seems to reach a plateau above 500-600 °C. More-over, the prolongation of carbonization time above 20 minutes does not affect the elemental conversion of the pollutants and carbonization at 500-600 °C for ~20 minutes may be considered sufficient for clean coal production from poor quality coals. Clean coal production at higher pyrolysis temperatures results in observed higher initial combustion temperature, mainly due to lower volatile content in produced chars