Synthesis and Characterization of Imidazolium Salt Derivatives for Anti-Tumor Activity

Several aldehydes (butanal, pentanal, hexanal, 4-hydroxybenzaldehyde) were reacted with 1,3-bis(naphthalen-2-ylmethyl)-imidazolium bromide (1) to produce novel C2 substituted imidazolium salts for the potential use against non-small cell lung cancer in humans. Compounds 2-(1-hydroxypentyl)-1,3-bis(naphthalen-2-ylmethyl)-imidazolium bromide (3) and 2-(1-hydroxyhexyl)-1,3-bis(naphthalen-2-ylmethyl)-imidazolium bromide (5) were successfully synthesized with structures supported by NMR and mass spectrometry. Characterization by 1H NMR showed evidence of 1 in both compounds. The tumor cell growth inhibition of 3 against non-small cell lung cancer lines NCI-A549, NCI-H460, HCC827, and NCI-H1975 was tested and found to be comparable to cisplatin as measured by MTT assay. Compounds were compared by their IC50 values against a panel of human cancer cell lines. The IC50 values for 3 were: 9 μM for A549 cells, 7 μM for H460 cells, 5 μM for HCC827 cells, and 3 μM for H1975 cells. Cisplatin had IC50 values in the range of 3-8 μM for these cell types, indicating that our compound had similar efficiency to a current chemotherapeutic agent. Similar IC50 values for 1 in the literature suggest C2 substituents may not significantly affect tumor cell growth inhibition.1 This may allow for different functional groups to be substituted at the C2 position in order to optimize properties such as water solubility and toxicity while not hindering therapeutic benefits

Legacy Effects of Long-term Manure Applications on Soil-derived Nitrous Oxide Emissions

Termination of the manure application treatments at the Dixon long-term manure research site in Humboldt, Saskatchewan provided a unique opportunity to explore how a change in management regime to annual urea applications would affect nitrous oxide (N2O) emissions. My hypotheses were that long-term manure applications would produce a legacy (or priming) effect that would result in enhanced N2O emissions following the changeover to a more readily available nitrogen source and that this effect would be relatively short-lived. The impacts of long-term manure application and change in fertility management in the sub-humid prairies of Saskatchewan has not been investigated in great depth, this work provided an opportunity for greater insight into changes in N transformation and gaseous N loss from a manured agroecosystem. Nitrous oxide fluxes associated with the long-term manure and fertilizer application from the Dixon site were measured during a 37-month period (i.e., from May 2011 to June 2014). In addition, denitrification enzyme activity (DEA) was measured in a subset of the plots starting in June 2011 and continuing three times per year (i.e., prior to and after the spring fertilizer application and again in early fall). Treatment-induced N2O emissions for the various historical amendment treatments indicate that past management can result in considerable N being lost from the system as N2O. Indeed, summed over the three-year post-manure period (i.e., from fertilizer application in 2011 through the 2014 spring thaw), N2O-N losses accounted for 2% to 6% of the total applied fertilizer-N. Moreover, under environmental conditions that optimize denitrification, N2O-N losses can be even greater. For example, high DEAs coupled with warm moist soil conditions resulted in large N2O emission events following the spring 2013 fertilizer application and during the 2014 spring thaw. As a result, cumulative annual N2O-N losses in 2013/14 were much greater than those in previous years — with emissions from the liquid swine manure (LSM)-amended plots ranging from 3% to 15% of applied N. These data support my earlier hypothesis that long-term applications of manure-N can — especially at high application rates and following frequent application — produce a ‘priming’ effect that exacerbates N2O emission when a more available form of N (e.g., urea fertilizer) is applied to the soil. Moreover, this priming effect appears to be relatively long-lived — persisting in the soil more than four and a half years after the last manure application. In any given year, however, the impact of the priming effect on cumulative N2O emissions depends on environmental conditions — being greatest during years with above average precipitation and temperature during the spring thaw period and a seeding/fertilizer application. Overall, my data demonstrate that management history can have a significant impact on soil N turnover in agricultural soils, and that long-term annual application of manure-N at high rates can produce a N2O ‘priming’ effect that — under appropriate environmental conditions — can significantly intensify N2O emissions long after the manure applications have ceased

Food without sun: Price and life-saving potential

International audienceThe sun could be blocked by an asteroid impact, supervolcanic eruption, or nuclear winter caused by burning of cities during nuclear war. The primary problem in these scenarios is loss of food production. Previous work has shown that alternate foods not dependent on sunlight, such as bacteria grown on natural gas, calories extracted from killed leaves, and cellulose turned into sugar enzymatically, could feed everyone in these catastrophes and preparation for these foods would save lives highly cost-effectively. This study estimates the price of alternate foods during a catastrophe scenario with global trade and information sharing, but no migration, loans, aid or conflict. Without alternate foods, for a five year winter, only ~10% of the population would survive. The price of dry food would rise to ~$100/kg, and the expenditure on this food would be ~$100 trillion over five years. If alternate food were $8/kg, the surviving global population increases to ~70%, saving >4 billion lives. The probability of a loss of civilization and its impact on many future generations would be much lower in this scenario and the total expenditure on food would be halved. Preparation for alternate foods would be a good investment even for wealthy people who would survive without alternate foods. A non-governmental mechanism of coordinating the investments of these rich people may be possible. Identifying companies whose interests align with alternate food preparations may save lives at a negative cost

A Protocol for Metabolic Characterization of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes (iPS-CM)

© 2019 The Authors Recent advances in human induced pluripotent stem cell-derived cardiomyocytes (iPSCM) field offer a novel platform for modeling cardiac metabolism, heart diseases drug candidates screening and cardiac toxicity assessments. These workflows require a fully functional characterization of iPSCMs. Here we report a step by step protocol for iPSCM metabolic characterization. The described assays cover analysis of small metabolites involved in a vital metabolic pathways

The provision of water infrastructure in Aboriginal communities in South Australia

The provision of water supplies to Aboriginal people in South Australia, particularly to communities covered under the Commonwealth–State (South Australia) Bilateral Agreement is considered world class in terms of the suitability of the technology to the remoteness of many of the communities and the harsh arid environment. This article explores the history of domestic water supplies to these Aboriginal communities. The article begins with a brief outline of pre-contact Aboriginal technologies for the maintenance of water supplies and reflects on the continuity of these approaches through the early years of pastoralist and missionary settlement. This is followed by a description of the services offered by the state and federal governments since the late 1970s to the present

Change, Choice, and Commercialization: Backpacker Routes in Southeast Asia

South-East Asia has the oldest and largest backpacker trails. This paper examines the geographies of such flows, drawing upon the largest survey to date of backpackers in Asia using qualitative research to survey the key changes from the 1970s to the 2000s. Backpacker trails have changed significantly and new routes have emerged including the ‘northern trail’ (Bangkok - Cambodia - Vietnam - Laos). It is to be expected that routes change as backpackers constantly seek new places, pioneering for later mass tourism. However, this paper suggests that using institutionalization as a framework, these changing trails and backpacker ‘choices’ can be seen as driven by growing commercialization and institutionalization. This then operates in combination with external variables (travel innovations - low cost airlines, and new transport networks); exogenous shock (political instability, terrorism); and growing regional competition from emerging destinations such as Vietnam and Cambodia

Plasma Krebs Cycle Intermediates in Nonalcoholic Fatty Liver Disease

Nonalcoholic liver disease (NAFLD) is manifested with a wide spectrum of clinical symptoms and is closely associated with the metabolic syndrome, inflammation, and mitochondrial dysfunction. Although the mechanism of mitochondrial dysfunction in NAFLD is still not fully elucidated, multiple studies have demonstrated evidence of molecular, biochemical, and biophysical mitochondrial abnormalities in NAFLD. Given the association between NAFLD and mitochondrial dysfunction, the aim of this study is to analyze circulating levels of Krebs cycle intermediates in a cohort of NAFLD-affected individuals and matching healthy controls and to correlate our findings with the liver function metrics. Standard serum biochemistry and Krebs cycle intermediates were analyzed in NAFLD (n = 22) and matched control (n = 67) cohorts. Circulating levels of isocitrate and citrate were significantly (p \u3c 0.05) elevated in the NAFLD cohort of patients. The area under the curve (AUROC) for these two metabolites exhibited a moderate clinical utility. Correlations between plasma Krebs cycle intermediates and standard clinical plasma metrics were explored by Pearson’s correlation coefficient. The data obtained for plasma Krebs cycle intermediates suggest pathophysiological insights that link mitochondrial dysfunction with NAFLD. Our findings reveal that plasma isocitrate and citrate can discriminate between normal and NAFLD cohorts and can be utilized as noninvasive markers of mitochondrial dysfunction in NAFLD. Future studies with large populations at different NAFLD stages are warranted