Copper(I)-Phosphinite Complexes in Click Cycloadditions: Three-Component Reactions and Preparation of 5-Iodotriazoles

© 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.The remarkable activity displayed by copper(I)–phosphinite complexes of general formula [CuBr(L)] in two challenging cycloadditions is reported: a) the one-pot azidonation/cycloaddition of boronic acids, NaN3, and terminal alkynes; b) the cycloaddition of azides and iodoalkynes. These air-stable catalysts led to very good results in both cases and the expected triazoles could be isolated in pure form under ‘Click-suitable’ conditions

Lupin wild types introduced into Western Australia to 1973

Collection site data, preliminary rating of field characteristics and disease reactions, and measurements of seed protein oil contents

Hypoxia and hyperglycaemia determine why some endometrial tumours fail to respond to metformin

High expression of Ki67, a proliferation marker, is associated with reduced endometrial cancer-specific survival. Pre-surgical metformin reduces tumour Ki-67 expression in some women with endometrial cancer. Metformin's anti-cancer activity may relate to effects on cellular energy metabolism. Since tumour hypoxia and glucose availability are major cellular redox determinants, we evaluated their role in endometrial cancer response to metformin. Endometrial cancer biopsies from women treated with pre-surgical metformin were tested for the hypoxia markers, HIF-1α and CA-9. Endometrial cancer cell lines were treated with metformin in variable glucose concentrations in normoxia or hypoxia and cell viability, mitochondrial biogenesis, function and energy metabolism were assessed. In women treated with metformin (n = 28), Ki-67 response was lower in hypoxic tumours. Metformin showed minimal cytostatic effects towards Ishikawa and HEC1A cells in conventional medium (25 mM glucose). In low glucose (5.5 mM), a dose-dependent cytostatic effect was observed in normoxia but attenuated in hypoxia. Tumours treated with metformin showed increased mitochondrial mass (n = 25), while in cultured cells metformin decreased mitochondrial function. Metformin targets mitochondrial respiration, however, in hypoxic, high glucose conditions, there was a switch to glycolytic metabolism and decreased metformin response. Understanding the metabolic adaptations of endometrial tumours may identify patients likely to derive clinical benefit from metformin

Sarcospan Regulates Cardiac Isoproterenol Response and Prevents Duchenne Muscular Dystrophy-Associated Cardiomyopathy.

BackgroundDuchenne muscular dystrophy is a fatal cardiac and skeletal muscle disease resulting from mutations in the dystrophin gene. We have previously demonstrated that a dystrophin-associated protein, sarcospan (SSPN), ameliorated Duchenne muscular dystrophy skeletal muscle degeneration by activating compensatory pathways that regulate muscle cell adhesion (laminin-binding) to the extracellular matrix. Conversely, loss of SSPN destabilized skeletal muscle adhesion, hampered muscle regeneration, and reduced force properties. Given the importance of SSPN to skeletal muscle, we investigated the consequences of SSPN ablation in cardiac muscle and determined whether overexpression of SSPN into mdx mice ameliorates cardiac disease symptoms associated with Duchenne muscular dystrophy cardiomyopathy.Methods and resultsSSPN-null mice exhibited cardiac enlargement, exacerbated cardiomyocyte hypertrophy, and increased fibrosis in response to β-adrenergic challenge (isoproterenol; 0.8 mg/day per 2 weeks). Biochemical analysis of SSPN-null cardiac muscle revealed reduced sarcolemma localization of many proteins with a known role in cardiomyopathy pathogenesis: dystrophin, the sarcoglycans (α-, δ-, and γ-subunits), and β1D integrin. Transgenic overexpression of SSPN in Duchenne muscular dystrophy mice (mdx(TG)) improved cardiomyofiber cell adhesion, sarcolemma integrity, cardiac functional parameters, as well as increased expression of compensatory transmembrane proteins that mediate attachment to the extracellular matrix.ConclusionsSSPN regulates sarcolemmal expression of laminin-binding complexes that are critical to cardiac muscle function and protects against transient and chronic injury, including inherited cardiomyopathy

Comparing methods of barometric efficiency characterisation for specific storage estimation

Groundwater responses to barometric pressure fluctuations are characterized using the concept of barometric efficiency (BE). For semiconfined and confined aquifers, BE values can be used to provide efficient, low-cost estimates of specific storage. This study compares, for the first time, eight existing methods of BE estimation. Comparisons were undertaken using data from the Peel region of Western Australia. Fourier analysis and regression deconvolution methods were used to estimate aquifer confinement status. The former approach was found to be robust and provided a quantitative basis for spatial comparisons of the degree of confinement. The latter approach was confounded by the presence of diurnal and/or semidiurnal signals. For wells at which semiconfined or confined responses were identified, frequency and time domain methods were used to estimate BE values. Most BE estimation methods were similarly confounded by diurnal and/or semidiurnal signals, with the exception of the Acworth et al. (2016) method. Specific storage values calculated from BE values were order-of-magnitude consistent with the results of four historical pumping tests. The methods implemented in this research provide efficient, low-cost alternatives to hydraulic testing for estimating aquifer confinement, as well as the BE and specific storage of semiconfined and confined aquifers. The frequency and duration of observations required by these methods are minimal; for example, typically requiring a minimum of four observations per day over a four month period. In some locations they may allow additional insights to be derived from existing groundwater hydrograph data

Climatic controls on diffuse groundwater recharge across Australia

Reviews of field studies of groundwater recharge have attempted to investigate how climate characteristics control recharge, but due to a lack of data have not been able to draw any strong conclusions beyond that rainfall is the major determinant. This study has used numerical modelling for a range of Köppen-Geiger climate types (tropical, arid and temperate) to investigate the effect of climate variables on recharge for different soil and vegetation types. For the majority of climate types, the correlation between the modelled recharge and total annual rainfall is weaker than the correlation between recharge and the annual rainfall parameters reflecting rainfall intensity. Under similar soil and vegetation conditions for the same annual rainfall, annual recharge in regions with winter-dominated rainfall is greater than in regions with summer-dominated rainfall. The importance of climate parameters other than rainfall in recharge estimation is highest in the tropical climate type. Mean annual values of solar radiation and vapour pressure deficit show a greater importance in recharge estimation than mean annual values of the daily mean temperature. Climate parameters have the lowest relative importance in recharge estimation in the arid climate type (with cold winters) and the temperate climate type. For 75% of all soil, vegetation and climate types investigated, recharge elasticity varies between 2 and 4 indicating a 20% to 40% change in recharge for a 10% change in annual rainfall. Understanding how climate controls recharge under the observed historical climate allows more informed choices of analogue sites if they are to be used for climate change impact assessments