Biological Denitrification of High Nitrate Processing Wastewaters from Explosives Production Plant

Wastewater samples originating from an explosives production plant (3,000 mg N l−1 nitrate, 4.8 mg l−1 nitroglycerin, 1.9 mg l−1 nitroglycol and 1,200 mg l−1 chemical oxygen demand) were subjected to biological purification. An attempt to completely remove nitrate and to decrease the chemical oxygen demand was carried out under anaerobic conditions. A soil isolated microbial consortium capable of biodegrading various organic compounds and reduce nitrate to atmospheric nitrogen under anaerobic conditions was used. Complete removal of nitrates with simultaneous elimination of nitroglycerin and ethylene glycol dinitrate (nitroglycol) was achieved as a result of the conducted research. Specific nitrate reduction rate was estimated at 12.3 mg N g−1 VSS h−1. Toxicity of wastewater samples during the denitrification process was studied by measuring the activity of dehydrogenases in the activated sludge. Mutagenicity was determined by employing the Ames test. The maximum mutagenic activity did not exceed 0.5. The obtained results suggest that the studied wastewater samples did not exhibit mutagenic properties

Bioenergetic status modulates motor neuron vulnerability and pathogenesis in a zebrafish model of spinal muscular atrophy

Degeneration and loss of lower motor neurons is the major pathological hallmark of spinal muscular atrophy (SMA), resulting from low levels of ubiquitously-expressed survival motor neuron (SMN) protein. One remarkable, yet unresolved, feature of SMA is that not all motor neurons are equally affected, with some populations displaying a robust resistance to the disease. Here, we demonstrate that selective vulnerability of distinct motor neuron pools arises from fundamental modifications to their basal molecular profiles. Comparative gene expression profiling of motor neurons innervating the extensor digitorum longus (disease-resistant), gastrocnemius (intermediate vulnerability), and tibialis anterior (vulnerable) muscles in mice revealed that disease susceptibility correlates strongly with a modified bioenergetic profile. Targeting of identified bioenergetic pathways by enhancing mitochondrial biogenesis rescued motor axon defects in SMA zebrafish. Moreover, targeting of a single bioenergetic protein, phosphoglycerate kinase 1 (Pgk1), was found to modulate motor neuron vulnerability in vivo. Knockdown of pgk1 alone was sufficient to partially mimic the SMA phenotype in wild-type zebrafish. Conversely, Pgk1 overexpression, or treatment with terazosin (an FDA-approved small molecule that binds and activates Pgk1), rescued motor axon phenotypes in SMA zebrafish. We conclude that global bioenergetics pathways can be therapeutically manipulated to ameliorate SMA motor neuron phenotypes in vivo

Targeting Huntington’s disease through histone deacetylases

Huntington’s disease (HD) is a debilitating neurodegenerative condition with significant burdens on both patient and healthcare costs. Despite extensive research, treatment options for patients with this condition remain limited. Aberrant post-translational modification (PTM) of proteins is emerging as an important element in the pathogenesis of HD. These PTMs include acetylation, phosphorylation, methylation, sumoylation and ubiquitination. Several families of proteins are involved with the regulation of these PTMs. In this review, I discuss the current evidence linking aberrant PTMs and/or aberrant regulation of the cellular machinery regulating these PTMs to HD pathogenesis. Finally, I discuss the evidence suggesting that pharmacologically targeting one of these protein families the histone deacetylases may be of potential therapeutic benefit in the treatment of HD