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

Resource utilisation in the national parks of the Canadian Arctic

The national parks of northern Canada provide a useful reflection of the evolving attitude towards conservation of a fragile ecosystem, in a situation complicated by a background of political, social and economic transition. This thesis examines how this transition, in particular that of land claim settlements, has affected the role and function of northern national parks. Through examining the evolution and general principles behind conservation, particularly that of protected areas, an analysis is made of the different uses and perceptions of the northern national parks. The conflicts that can arise from these different uses, primarily between native hunting and trapping, tourism and potential industrial development, is examined. Consideration is also given to the different perceptions of the role and function of northern national parks which stem from a multicultural society. In conclusion three issues which are posed in Chapter 1, namely: is there still a place and use for national parks in northern ·Canada; have the aims and objectives altered from those voiced initially; and with the changing political circumstances in northern Canada, what are the future prospects for national parks, are discussed. The main purpose of this thesis is to assess to what extent the national parks in the north fulfil the Canadian Parks Service objective "to protect for all time ... this natural heritage so as to leave it unimpaired for future generations"

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

Cyclic hypoxia exposure accelerates the progression of amoebic gill disease

Amoebic gill disease (AGD), caused by the amoeba Neoparamoeba perurans, has led to considerable economic losses in every major Atlantic salmon producing country, and is increasing in frequency. The most serious infections occur during summer and autumn, when temperatures are high and poor dissolved oxygen (DO) conditions are most common. Here, we tested if exposure to cyclic hypoxia at DO saturations of 40–60% altered the course of infection with N. perurans compared to normoxic controls maintained at ≥90% DO saturation. Although hypoxia exposure did not increase initial susceptibility to N. perurans, it accelerated progression of the disease. By 7 days post-inoculation, amoeba counts estimated from qPCR analysis were 1.7 times higher in the hypoxic treatment than in normoxic controls, and cumulative mortalities were twice as high (16 ± 4% and 8 ± 2%), respectively. At 10 days post-inoculation, however, there were no differences between amoeba counts in the hypoxic and normoxic treatments, nor in the percentage of filaments with AGD lesions (control = 74 ± 2.8%, hypoxic = 69 ± 3.3%), or number of lamellae per lesion (control = 30 ± 0.9%, hypoxic = 27.9 ± 0.9%) as determined by histological examination. Cumulative mortalities at the termination of the experiment were similarly high in both treatments (hypoxic = 60 ± 2%, normoxic = 53 ± 11%). These results reveal that exposure to cyclic hypoxia in a diel pattern, equivalent to what salmon are exposed to in marine aquaculture cages, accelerated the progression of AGD in post-smolts

Barley staining

GRAIN discolouration or staining is a quality defect in W.A. barley which substantially reduces the marketable value oi the crop. It also causes heavy losses to individual growers whose grain is docked or rejected

Examples of individual supported living for adults with intellectual disability

Background: This article provides a qualitative account of four models of support for adults with intellectual disability in individual supported living (ISL) arrangements. Materials and Methods: Completion of the first 50 evaluations of 150 arrangements for the third phase of the ISL project provided the examples. Results: Four approaches are described: living alone, co-residency, relationship and host family. Within each type, wide variations occur particularly based on security of tenure, formal and informal support and management variations. Conclusion: Fifty evaluations so far illustrated a wide range of approaches to ISL, providing evidence of the critical importance of the formal and informal support environment and reinforcing the contention that ISL is appropriate for people with high support needs

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

Decreased soluble guanylate cyclase contributes to cardiac dysfunction induced by chronic doxorubicin treatment in mice

Aims: The use of doxorubicin, a potent chemotherapeutic agent, is limited by cardiotoxicity. We tested the hypothesis that decreased soluble guanylate cyclase (sGC) enzyme activity contributes to the development of doxorubicin-induced cardiotoxicity. Results: Doxorubicin administration (20 mg/kg, intraperitoneally [IP]) reduced cardiac sGC activity in wild-type (WT) mice. To investigate whether decreased sGC activity contributes to doxorubicin-induced cardiotoxicity, we studied mice with cardiomyocyte-specific deficiency of the sGC alpha 1-subunit (mice with cardiomyocyte-specific deletion of exon 6 of the sGC alpha 1 allele [sGC alpha 1(-/-CM)]). After 12 weeks of doxorubicin administration (2 mg/kg/week IP), left ventricular (LV) systolic dysfunction was greater in sGC alpha 1(-/-CM) than WT mice. To further assess whether reduced sGC activity plays a pathogenic role in doxorubicin-induced cardiotoxicity, we studied a mouse model in which decreased cardiac sGC activity was induced by cardiomyocyte-specific expression of a dominant negative sGC alpha 1 mutant (DNsGC alpha 1) upon doxycycline removal (Tet-off). After 8 weeks of doxorubicin administration, DNsGC alpha 1(tg/+), but not WT, mice displayed LV systolic dysfunction and dilatation. The difference in cardiac function and remodeling between DNsGC alpha 1(tg/+) and WT mice was even more pronounced after 12 weeks of treatment. Further impairment of cardiac function was attenuated when DNsGC alpha 1 gene expression was inhibited (beginning at 8 weeks of doxorubicin treatment) by administering doxycycline. Furthermore, doxorubicin-associated reactive oxygen species generation was higher in sGC alpha 1-deficient than WT hearts. Innovation and Conclusion: These data demonstrate that a reduction in cardiac sGC activity worsens doxorubicin-induced cardiotoxicity in mice and identify sGC as a potential therapeutic target. Various pharmacological sGC agonists are in clinical development or use and may represent a promising approach to limit doxorubicin-associated cardiotoxicity

Observational evidence for the convective transport of dust over the central United States

Bulk aerosol composition and aerosol size distributions measured aboard the DC-8 aircraft during the Deep Convective Clouds and Chemistry Experiment mission in May/June 2012 were used to investigate the transport of mineral dust through nine storms encountered over Colorado and Oklahoma. Measurements made at low altitudes (\u3c5 km mean sea level (MSL)) in the storm inflow region were compared to those made in cirrus anvils (altitude \u3e 9 km MSL). Storm mean outflow Ca2+ mass concentrations and total coarse (1 µm \u3c diameter \u3c 5 µm) aerosol volume (Vc) were comparable to mean inflow values as demonstrated by average outflow/inflow ratios greater than 0.5. A positive relationship between Ca2+, Vc, ice water content, and large (diameter \u3e 50 µm) ice particle number concentrations was not evident; thus, the influence of ice shatter on these measurements was assumed small. Mean inflow aerosol number concentrations calculated over a diameter range (0.5 µm \u3c diameter \u3c 5.0 µm) relevant for proxy ice nuclei (NPIN) were ~15–300 times higher than ice particle concentrations for all storms. Ratios of predicted interstitial NPIN (calculated as the difference between inflow NPIN and ice particle concentrations) and inflow NPIN were consistent with those calculated for Ca2+ and Vc and indicated that on average less than 10% of the ingested NPIN were activated as ice nuclei during anvil formation. Deep convection may therefore represent an efficient transport mechanism for dust to the upper troposphere where these particles can function as ice nuclei cirrus forming in situ