Catalytic asymmetric synthesis of the alkaloid (+)-myrtine

A new protocol for the asymmetric synthesis of trans-2,6-disubstituted-4-piperidones has been developed using a catalytic enantioselective conjugate addition reaction in combination with a diastereoselective lithiation–substitution sequence; an efficient synthesis of (+)-myrtine has been achieved via this route.

A method for determination of retention of silver and cerium oxide manufactured nanoparticles in soils

Methods to study the retention of manufactured nanoparticles (MNP) are lacking for soils that are likely to be increasingly exposed to MNP. In this study we present, for the first time, a method to determine retention values (Kr) of Ag and CeO2 MNP, that can be ranked among solid–liquid partitioning (Kd) values of bulk (micrometre-sized) forms, soluble salts and other possible contaminants of soils. After method optimisation, suspensions containing 1.24 mg kg–1 Ag as Ag MNP and 1.30 mg kg–1 Ce as CeO2 MNP were added to five soils. More than 7% of Ag MNP occurred as soluble AgI after 24 h and the range of Kr values of Ag MNP (77–2165 L kg–1) and CeO2 MNP (1.1–2828 L kg–1) contrasted with Kd values of soluble AgI, CeIII and CeIV salts and bulk Ag and CeO2 powders in different soils.Geert Cornelis, Jason K. Kirby, Douglas Beak, David Chittleborough and Mike J. McLaughli

Annotated bibliography of α-benzildioxime

The references are presented chronologically. The names and configurations used by each author are retained. In this regard it should be noted that the presently accepted configuration of α-benzildioxime (anti) was not proposed until 1921, and was not generally accepted until somewhat later. The syn-configuration was generally used before 1921

Fate of Zinc Oxide Nanoparticles Coated onto Macronutrient Fertilizers in an Alkaline Calcareous Soil

Citation: Milani, N., Hettiarachchi, G. M., Kirby, J. K., Beak, D. G., Stacey, S. P., & McLaughlin, M. J. (2015). Fate of Zinc Oxide Nanoparticles Coated onto Macronutrient Fertilizers in an Alkaline Calcareous Soil. Plos One, 10(5), 16. doi:10.1371/journal.pone.0126275Zinc oxide (ZnO) nanoparticles may provide a more soluble and plant available source of Zn in Zn fertilizers due to their greater reactivity compared to equivalent micron-or millimetresized (bulk) particles. However, the effect of soil on solubility, spatial distribution and speciation of ZnO nanoparticles has not yet been investigated. In this study, we examined the diffusion and solid phase speciation of Zn in an alkaline calcareous soil following application of nanoparticulate and bulk ZnO coated fertilizer products (monoammonium phosphate (MAP) and urea) using laboratory-based x-ray techniques and synchrotron-based mu-x-ray fluorescence (mu-XRF) mapping and absorption fine structure spectroscopy (mu-XAFS). Mapping of the soil-fertilizer reaction zones revealed that most of the applied Zn for all treatments remained on the coated fertilizer granule or close to the point of application after five weeks of incubation in soil. Zinc precipitated mainly as scholzite (CaZn2(PO4)(2)center dot 2H(2)O) and zinc ammonium phosphate (Zn(NH4)PO4) species at the surface of MAP granules. These reactions reduced dissolution and diffusion of Zn from the MAP granules. Although Zn remained as zincite (ZnO) at the surface of urea granules, limited diffusion of Zn from ZnO-coated urea granules was also observed for both bulk and nanoparticulate ZnO treatments. This might be due to either the high pH of urea granules, which reduced solubility of Zn, or aggregation (due to high ionic strength) of released ZnO nanoparticles around the granule/point of application. The relative proportion of Zn(OH)(2) and ZnCO3 species increased for all Zn treatments with increasing distance from coated MAP and urea granules in the calcareous soil. When coated on macronutrient fertilizers, Zn from ZnO nanoparticles (without surface modifiers) was not more mobile or diffusible compared to bulk forms of ZnO. The results also suggest that risk associated with the presence of ZnO NPs in calcareous soils would be the same as bulk sources of ZnO

An Oral Selective Alpha-1A Adrenergic Receptor Agonist Prevents Doxorubicin Cardiotoxicity

Alpha-1 adrenergic receptors (α1-ARs) play adaptive and protective roles in the heart. Dabuzalgron is an oral selective α1A-AR agonist that was well tolerated in multiple clinical trials of treatment for urinary incontinence, but has never been used to treat heart disease in humans or animal models. In this study, the authors administered dabuzalgron to mice treated with doxorubicin (DOX), a widely used chemotherapeutic agent with dose-limiting cardiotoxicity that can lead to heart failure (HF). Dabuzalgron protected against DOX-induced cardiotoxicity, likely by preserving mitochondrial function. These results suggest that activating cardiac α1A-ARs with dabuzalgron, a well-tolerated oral agent, might represent a novel approach to treating HF

Foreign Direct Investment, Aggregate Demand Conditions and Exchange Rate Nexus: A Panel Data Analysis of BRICS Economies

In this study, we attempt to provide underlying theoretical and empirical explanations for exchange rate appreciation due to foreign capital influx and aggregate demand conditions in the BRICS economies. The empirical analysis is based on a panel dataset of BRICS countries over the time period 1992–2013 to substantiate our theoretical findings. For panel co-integration, Pedroni and Johansen-Fisher panel co-integration tests are conducted to compare co-integration among panel countries. We also analyze the results from Dumitrescu-Hurlin panel causality test among variables and use Granger Causality to test for the causal patterns in each of the individual countries. Our findings showed that the exchange rate volatility is directly affected by the flows of FDI, GDP per capita, Capital formulation and House hold consumption. The results have profound implications in terms of exchange rate stability in the BRICS countries and associated risks

Trace Simulation of Bwr Anticipated Transient Without Scram Leading to Emergency Depressurization

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Kinome and Transcriptome Profiling Reveal Broad and Distinct Activities of Erlotinib, Sunitinib, and Sorafenib in the Mouse Heart and Suggest Cardiotoxicity From Combined Signal Transducer and Activator of Transcription and Epidermal Growth Factor Receptor Inhibition

BACKGROUND: Most novel cancer therapeutics target kinases that are essential to tumor survival. Some of these kinase inhibitors are associated with cardiotoxicity, whereas others appear to be cardiosafe. The basis for this distinction is unclear, as are the molecular effects of kinase inhibitors in the heart. METHODS AND RESULTS: We administered clinically relevant doses of sorafenib, sunitinib (cardiotoxic multitargeted kinase inhibitors), or erlotinib (a cardiosafe epidermal growth factor receptor inhibitor) to mice daily for 2 weeks. We then compared the effects of these 3 kinase inhibitors on the cardiac transcriptome using RNAseq and the cardiac kinome using multiplexed inhibitor beads coupled with mass spectrometry. We found unexpectedly broad molecular effects of all 3 kinase inhibitors, suggesting that target kinase selectivity does not define either the molecular response or the potential for cardiotoxicity. Using in vivo drug administration and primary cardiomyocyte culture, we also show that the cardiosafety of erlotinib treatment may result from upregulation of the cardioprotective signal transducer and activator of transcription 3 pathway, as co-treatment with erlotinib and a signal transducer and activator of transcription inhibitor decreases cardiac contractile function and cardiomyocyte fatty acid oxidation. CONCLUSIONS: Collectively our findings indicate that preclinical kinome and transcriptome profiling may predict the cardiotoxicity of novel kinase inhibitors, and suggest caution for the proposed therapeutic strategy of combined signal transducer and activator of transcription/epidermal growth factor receptor inhibition for cancer treatment

Assessment of the effect of sphingosine kinase inhibitors on apoptosis,unfolded protein response and autophagy of T-cell acute lymphoblastic leukemia cells; indications for novel therapeutics

Sphingosine 1-phosphate (S1P) is a bioactive lipid that is formed by the phosphorylation of sphingosine and catalysed by sphingosine kinase 1 (SK1) or sphingosine kinase 2 (SK2). Sphingosine kinases play a fundamental role in many signaling pathways associated with cancer, suggesting that proteins belonging to this signaling network represent potential therapeutic targets. Over the last years, many improvements have been made in the treatment of T-cell acute lymphoblastic leukemia (T-ALL); however, novel and less toxic therapies are still needed, especially for relapsing and chemo-resistant patients. Here, we analyzed the therapeutic potential of SKi and ROMe, a sphingosine kinase 1 and 2 inhibitor and SK2-selective inhibitor, respectively. While SKi induced apoptosis, ROMe initiated an autophagic cell death in our in vitro cell models. SKi treatment induced an increase in SK1 protein levels in Molt-4 cells, whereas it activated the endoplasmic reticulum (ER) stress/unfolded protein response (UPR) pathway in Jurkat and CEM-R cells as protective mechanisms in a sub-population of T-ALL cells. Interestingly, we observed a synergistic effect of SKi with the classical chemotherapeutic drug vincristine. In addition, we reported that SKi affected signaling cascades implicated in survival, proliferation and stress response of cells. These findings indicate that SK1 or SK2 represent potential targets for treating T-ALL