Integrated multi-omic data analysis and validation with yeast model show oxidative phosphorylation modulates protein aggregation in amyotrophic lateral sclerosis.

Amyotrophic Lateral Sclerosis is a progressive, incurable amyloid aggregating neurodegenerative disease involving the motor neurons. Identifying potential biomarkers and therapeutic targets can assist in the better management of the disease. We used an integrative approach encompassing analysis of transcriptomic datasets of human and mice from the GEO database. Our analysis of ALS patient datasets showed deregulation in Non-alcoholic fatty acid liver disease and oxidative phosphorylation. Transgenic mice datasets of SOD1, FUS and TDP-43 showed deregulation in oxidative phosphorylation and ribosome-associated pathways. Commonality analysis between the human and mice datasets showed oxidative phosphorylation as a major deregulated pathway. Further, protein-protein and protein-drug interaction network analysis of mitochondrial electron transport chain showed enrichment of proteins and inhibitors of mitochondrial Complex III and IV. The results were further validated using the yeast model system. Inhibitor studies using metformin (Complex-I inhibitor) and malonate (Complex-II inhibitor) did not show any effect in mitigating the amyloids, while antimycin (Complex-III inhibitor) and azide (Complex-IV inhibitor) reduced amyloidogenesis. Knock-out of QCR8 (Complex-III) or COX8 (Complex-IV) cleared the amyloids. Taken together, our results show a critical role for mitochondrial oxidative phosphorylation in amyloidogenesis and as a potential therapeutic target in ALS.Communicated by Ramaswamy H. Sarma.

A combined chemical and biological assessment of industrial contamination in an estuarine system in Kerala, India.

The Cochin Backwaters in India are part of the Vembanad-Kol system, which is a protected wetland and one of the largest estuarine ecosystems in South Asia. The backwaters are a major supplier of fisheries resources and are developed as tourist destination. Periyar River discharges into the northern arm of the system and receives effluents from chemical, petrochemical and metal processing industries which release huge amounts of wastewaters after little treatment. We investigated water and sediment contamination in the industrial vicinity and at one station further away including organic and inorganic contaminants. In total 83 organic contaminants were found, e.g. well known priority pollutants such as endosulfan, hexachlorobenzene, DDT, hexachlorocyclohexane and their metabolites, which likely stem from the industrial manufacturing of organochlorine pesticides. Furthermore, several benzothiazole, dibenzylamine and dicyclohexylamine derivatives were detected, which indicated inputs from rubber producing facilities. Several of these compounds have not been reported as environmental contaminants so far. A comparison of organic contaminant and trace hazardous element concentrations in sediments with reported sediment quality guidelines revealed that adverse effects on benthic species are likely at all stations. The chemical assessment was combined with an investigation of macrobenthic diversity and community composition. Benthic organisms were completely lacking at the site with the highest trace hazardous element concentrations. Highest species numbers, diversity indices and abundances were recorded at the station with the greatest distance to the industrial area. Filter feeders were nearly completely lacking, probably leading to an impairment of the filter function in this area. This study shows that a combination of chemical and biological methods is an innovative approach to achieve a comprehensive characterization of industrial contamination, to evaluate associated risks for bottom dwelling consumers regarding sediment quality guidelines, and to observe related adverse effects on the benthic community directly in the field.

Spatial budgetary evaluation of organochlorine contaminants in the sediments of Cochin Estuary, India.

This paper presents the first detailed investigation on the residual levels of organochlorine insecticide (OCI) concentrations in the Cochin estuarine sediment. It aims in elucidate their distribution and ecological impact on the aquatic system. Concentrations of persistent organochlorine compound (OC) were determined for 17 surface sediment samples which were collected from specific sites of Cochin Estuarine System (CES) over a period of November 2009 and November 2011. The contaminant levels in the CES were compared with other worldwide ecosystems. The sites bearing high concentration of organochlorine compounds are well associated with the complexities and low energy environment. Evaluation of ecotoxicological factors suggests that adverse biological effects are expected in certain areas of CES.