Application of the analytic hierarchy process (AHP) to select the best oil spill cleanup method in marine protected areas for calm sea condition

Oil spill cleanup is a complex and expensive activity. There are several commonly used techniques available today. The paper suggests criteria for the selection of the best available technique that could be employed in case of oil spills in the Mediterranean Sea under specific circumstances, i.e. calm sea and presence of marine protected areas, in order to prevent pollution. Not all the available techniques could be considered. Only three of them could be selected, as these allow the preservation of natural areas, as well as the protection of threatened species and their habitats. The Analytic Hierarchy Process method has been preferred among the great variety in multi-criteria decision making tools for the selection of the best available technique. This is a widespread decision support tool suitable for the selection of the best alternative solution to a particular problem. Twenty professionals with different expertise evaluated, through pair-wise comparisons, the alternative options to choose in a protected area. The selected emergency cleanup technique must be readily available and operational in a short time. The results give a preference to new sorbents, followed closely by the magnetic nanocomposites technique

Redox regulation of mitochondrial fission, protein misfolding, synaptic damage, and neuronal cell death: potential implications for Alzheimer’s and Parkinson’s diseases

Normal mitochondrial dynamics consist of fission and fusion events giving rise to new mitochondria, a process termed mitochondrial biogenesis. However, several neurodegenerative disorders manifest aberrant mitochondrial dynamics, resulting in morphological abnormalities often associated with deficits in mitochondrial mobility and cell bioenergetics. Rarely, dysfunctional mitochondrial occur in a familial pattern due to genetic mutations, but much more commonly patients manifest sporadic forms of mitochondrial disability presumably related to a complex set of interactions of multiple genes (or their products) with environmental factors (G × E). Recent studies have shown that generation of excessive nitric oxide (NO), in part due to generation of oligomers of amyloid-β (Aβ) protein or overactivity of the NMDA-subtype of glutamate receptor, can augment mitochondrial fission, leading to frank fragmentation of the mitochondria. S-Nitrosylation, a covalent redox reaction of NO with specific protein thiol groups, represents one mechanism contributing to NO-induced mitochondrial fragmentation, bioenergetic failure, synaptic damage, and eventually neuronal apoptosis. Here, we summarize our evidence in Alzheimer’s disease (AD) patients and animal models showing that NO contributes to mitochondrial fragmentation via S-nitrosylation of dynamin-related protein 1 (Drp1), a protein involved in mitochondrial fission. These findings may provide a new target for drug development in AD. Additionally, we review emerging evidence that redox reactions triggered by excessive levels of NO can contribute to protein misfolding, the hallmark of a number of neurodegenerative disorders, including AD and Parkinson’s disease. For example, S-nitrosylation of parkin disrupts its E3 ubiquitin ligase activity, and thereby affects Lewy body formation and neuronal cell death

Abstract 3561: The radiosensitizing and cytotoxic effects of PBS-1086, a Rel inhibitor of NF-KB, in breast cancer cells

Abstract Recent RNA interference screening has identified p53 and ras mutations to be synthetic lethal with the canonical and non-canonical pathways of NF-κB. We have synthesized inhibitors that antagonize bindings of RelA (p65), RelB and c-rel to the NF-κB sites and thus inhibit both the canonical and non-canonical paths. One such compound, PBS-1086, is evaluated here as a radiosensitizer in wild type and p65−/− mouse embryonic fibroblasts (MEFs), and as a radiosensitizing and chemotherapeutic agent in the p53 deficient and KRAS (G13D) mutant breast cancer cell line, MDA-MB-231. We found that p65−/− MEFs were ≥ 2-fold more sensitive than p65+/+ MEFs to irradiation (IR) in clonogenic survival assays, thus demonstrating that NF-κB activation conferred radio-resistance. Incubation with PBS-1086 at 1.4 µM, a non-cytotoxic concentration, radiosensitized p65+/+ MEFs (LD50 value of 1.5 Gy for IR + PBS-1086 compared with 2.3 Gy for IR alone). PBS-1086 had no effect on radio-sensitization of p65−/− MEFs, which indicated the radiosensitizing effect of PBS-1086 was mediated through p65. Similar radiosensitizing effects were observed by using RNA interference technique to down-regulate the expression level of p65 by &amp;gt; 95% in p65+/+ MEFs but not in p65−/− MEFs. We also confirmed the inhibition of the NF-κB by PBS-1086 or p65 siRNA in MEFs. NF-κB-dependent luciferase expression increased by 2.5 fold after 10 Gy IR in p65+/+ MEFs. Treatment with PBS-1086 or p65 siRNA reduced luciferase expression significantly. Similarly, IR increased p65+/+ MEFs nuclear extract NF-κB DNA binding activities by 2 fold, which was significantly decreased by either PBS-1086 incubation or p65 siRNA treatment in these cells. Next, we studied PBS-1086 in MDA-MB-231 breast cancer cells with constitutive NF-κB activation. First, we tested PBS-1086 as a single agent on the growth of the breast cancer cells. Significant cytotoxic effect to PBS-1086 was observed with an LD50 value of 0.4 μM to the MDA-MB-231 cells. Then we tested synergistic effect of PBS-1086 with irradiation in these cells. Incubation with 0.2 µM PBS-1086 significantly enhanced radiation effect by 1.5 fold (LD50 value of 1.66 Gy IR for IR + PBS-1086 compare with 2.55 Gy for IR alone). In conclusion, we have demonstrated that a Rel inhibitor of NF-KB can potentiate radioactivity through blocking the canonical pathway. It can also selectively kill tumor cells with p53 and KRAS mutations, perhaps through blocking the canonical and non-canonical pathways. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3561.</jats:p