Cell motility, morphology, viability and proliferation in response to nanotopography on silicon black

Knowledge of cells' interactions with nanostructured materials is fundamental for bio-nanotechnology. We present results for how individual mouse fibroblasts from cell line NIH3T3 respond to highly spiked surfaces of silicon black that were fabricated by maskless reactive ion etching (RIE). We did standard measurements of cell viability, proliferation, and morphology on various surfaces. We also analyzed the motility of cells on the same surfaces, as recorded in time lapse movies of sparsely populated cell cultures. We find that motility and morphology vary strongly with nano-patterns, while viability and proliferation show little dependence on substrate type. We conclude that motility analysis can show a wide range of cell responses e.g. over a factor of two in cell speed to different nano-topographies, where standard assays, such as viability or proliferation, in the tested cases show much less variation of the order 10-20%.     

Characterization of Oxidative Stability of Fish Oil- and Plant Oil-Enriched Skimmed Milk

The objective of this research was to determine the oxidative stability of fish oil blended with crude plant oils rich in naturally occurring antioxidants, camelina oil and oat oil, respectively, in bulk and after supplementation of 1 wt% of oil blends to skimmed milk emulsions. Ability of crude oat oil and camelina oil to protect fish oil in bulk and as fish oil-enriched skimmed milk emulsions was evaluated. Results of oxidative stability of bulk oils and blends assessed by the Schaal oven weight gain test and by the rancimat method showed significant increase in oxidative stability when oat oil was added to fish oil in only 5 and 10 %, whereas no protective effect of camelina oil was observed when evaluated by these methods. Moreover, fish oil blended with oat oil conferred the lowest PV and lower amounts of volatile compounds during the storage period of 14 days at 4 °C. Surprisingly, skimmed milk supplemented with fish-oat oil blend gave the highest scores for off-flavors in the sensory evaluation, demonstrating that several methods, including sensory analysis, should be combined to illustrate the complete picture of lipid oxidation in emulsions.     

Eicosapentaenoic acid at hypotriglyceridemic dose enhances the hepatic antioxidant defense in mice

The effect of oral administration of purified (95%) eicosapentaenoic acid on serum lipids, hepatic peroxisomal enzymes, antioxidant enzymes and lipid peroxidation was compared with that of palmitic acid fed mice and corresponding controls. After 10 d, a dose of 1000 mg eicosapentaenoic acid per day/kg body weight lowered serum triglycerides by 45%, while no significant change in serum cholesterol level was noted in comparison to palmitic acid fed mice and controls. Hepatic acyl-CoA oxidase and catalase activities increased by 50% and 30%, respectively, in the eicosapentaenoic acid fed group. In addition, the hepatic reduced glutathione content and the activities of glutathione transferase, glutathione peroxidase and glutathione reductase, increased significantly during eicosapentaenoic acid treatment. The levels of hepatic lipid peroxides were lower after eicosapentaenoic acid feeding, while no significant change was noted in the palmitic acid fed mice when compared to the controls. Taken together, the present data demonstrate for the first time that at hypolipidemic doses eicosapentaenoic acid feeding i) enhances the hepatic antioxidant defense, and ii) does not cause a significant differential induction of the two peroxisomal enzymes, acyl-CoA oxidase and catalase, as was noted after administration of hypolipidemic peroxisome proliferating compounds, such as clofibrate in rodents.     

Inactivation of Carcinogenic Diol Epoxides of Dibenzo[ a,l ]pyrene (Dibenzo[ def,p ]chrysene) by Human Alpha Class Glutathione Transferases

Human Alpha class glutathione transferases (hGSTs) have been incubated with the ultimate carcinogenic ( m )- anti - and (+)- syn -diol epoxides (DE) of the nonplanar dibenzo[ a,l ]pyrene (DBP). hGSTA1-1, A2-2, and A3-3 demonstrate activity with both diol epoxides ( R -absolute configuration at the benzylic oxirane carbon) whereas hGSTA4-4 virtually was inactive. (+)- syn -DBPDE was superior as substrate compared to the ( m )- anti enantiomer with hGSTA1-1 as the most efficient enzyme (k cat /K M = 464 mM m 1 s m 1 ) followed by A3-3 and A2-2 (k cat /K M = 190 mM m 1 s m 1 and 30.4 mM m 1 s m 1 , respectively). With ( m )- anti -DBPDE, the k cat /K M values were in general about 10-fold lower. Replacing ( m )- anti -DBPDE with the less complex ( m )- anti -BCDE or the less structurally distorted (+)- anti -BPDE, revealed that GSTA1-1 was 19- and 25-fold less active, respectively. hGSTA1-1 is present in human lung, a primary target tissue for PAH-induced tumors. Considering the great efficiency of this isoform relative to both Pi and Mu-class GSTs toward DBPDE, its presence and extent of expression may play a significant role in protection against this type of highly carcinogenic compounds.     

Fatty acid chain length and degree of unsaturation are inversely associated with serum triglycerides

Little is known about the association between dietary fatty acids and serum triglyceride concentrations. Plasma fatty acids may reflect dietary intake and can be used to study the relationship between concentrations of individual fatty acids and serum lipids. We examined the cross-sectional relationship of plasma fatty acids with serum nonfasting triglyceride and total cholesterol concentrations. Relative concentrations of individual plasma phospholipid fatty acids were determined by gas-liquid chromatography among 4,158 men aged 40–42 yr, who participated in a population study. The pattern of associations between individual fatty acids and cholesterol was different from that between individual fatty acids and triglyceride concentrations. All fatty acids displayed positive associations with total cholesterol concentration except linoleic acid, which was inversely related to cholesterol. In contrast, associations between individual fatty acids and triglyceride concentrations differed in strength and direction depending on both carbon chain length and the degree of unsaturation. Concentrations of very long chain (20 carbon atoms or more) saturated, monounsaturated, and n-3 polyunsaturated fatty acids showed significant inverse associations with triglycerides, whereas shorter fatty acids within these classes were positively associated with triglyceride concentrations. The present data suggest that the associations between concentrations of serum triglycerides and plasma phospholipid fatty acids depend on both fatty acid chain length and the degree of unsaturation.     

A Novel Prophylaxis Strategy Using Liposomal Vaccine Adjuvant CAF09b Protects against Influenza Virus Disease

The SARS-CoV-2 pandemic caused a massive health and societal crisis, although the fast development of effective vaccines reduced some of the impact. To prepare for future respiratory virus pandemics, a pan-viral prophylaxis could be used to control the initial virus outbreak in the period prior to vaccine approval. The liposomal vaccine adjuvant CAF^®09b contains the TLR3 agonist polyinosinic:polycytidylic acid, which induces a type I interferon (IFN-I) response and an antiviral state in the affected tissues. When testing CAF09b liposomes as a potential pan-viral prophylaxis, we observed that intranasal administration of CAF09b liposomes to mice resulted in an influx of innate immune cells into the nose and lungs and upregulation of IFN-I-related gene expression. When CAF09b liposomes were administered prior to challenge with mouse-adapted influenza A/Puerto Rico/8/1934 virus, it protected from severe disease, although the virus was still detectable in the lungs. However, when CAF09b liposomes were administered after influenza challenge, the mice had a similar disease course to controls. In conclusion, CAF09b may be a suitable candidate as a pan-viral prophylactic treatment for epidemic viruses, but must be administered prior to virus exposure to be effective.     

The development and demonstration of integrated models for the evaluation of severe accident management strategies—SAMEM

This study is concerned with the further development of integrated models for the assessment of existing and potential severe accident management (SAM) measures. This paper provides a brief summary of these models, based on Probabilistic Safety Assessment (PSA) methods and the Risk Oriented Accident Analysis Methodology (ROAAM) approach, and their application to a number of case studies spanning both preventive and mitigative accident management regimes. In the course of this study it became evident that the starting point to guide the selection of methodology and any further improvement is the intended application. Accordingly, such features as the type and area of application and the confidence requirement are addressed in this project. The application of an integrated ROAAM approach led to the implementation, at the Loviisa NPP, of a hydrogen mitigation strategy, which requires substantial plant modifications. A revised level 2 PSA model was applied to the Sizewell B NPP to assess the feasibility of the in-vessel retention strategy. Similarly the application of PSA based models was extended to the Barseback and Ringhals 2 NPPs to improve the emergency operating procedures, notably actions related to manual operations. A human reliability analysis based on the Human Cognitive Reliability (HCR) and Technique For Human Error Rate (THERP) models was applied to a case study addressing secondary and primary bleed and feed procedures. Some aspects pertinent to the quantification of severe accident phenomena were further examined in this project. A comparison of the applications of PSA based approach and ROAAM to two severe accident issues, viz hydrogen combustion and in-vessel retention, was made. A general conclusion is that there is no requirement for further major development of the PSA and ROAAM methodologies in the modelling of SAM strategies for a variety of applications as far as the technical aspects are concerned. As is demonstrated in this project, the generic modelling framework was refined to enable a number of applications. Some recommendations have also been made regarding the applicability of these approaches to existing operating reactors and future reactors. The need for further research and development in the area of human reliability quantification was identified.