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The copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction has proven to be a pivotal advance in chemical ligation strategies with applications ranging from polymer fabrication to bioconjugation. However, application in vivo has been limited by the inherent toxicity of the copper catalyst. Herein, we report the application of heterogeneous copper catalysts in azide-alkyne cycloaddition processes in biological systems ranging from cells to zebrafish, with reactions spanning from fluorophore activation to the first reported in situ generation of a triazole-containing anticancer agent from two benign components, opening up many new avenues of exploration for CuAAC chemistry.

In the dense circulatory system of the kidney, as in all vascularized tissues, pericytes enwrap capillaries and microvessels to regulate angiogenesis, stabilize microvascular networks and control blood flow by vasoconstriction. Specialized renal pericytes known as mesangial cells provide physical support to glomerular capillaries, whereas a subset of juxtaglomerular arteriolar pericytes control the local blood pressure in the glomerulus via contraction and influence systemic blood pressure by secreting renin. Similar to pericytes from many other organs, cultured human renal pericytes give rise to mesenchymal stem/stromal cells, suggesting a role of perivascular cells in renal homeostasis and regeneration. On the other hand, pericytes directly contribute to renal fibrosis, and mesangial cells may have an essential role in the development of glomerulosclerosis and other nephropathies. From their early emergence in the renal embryonic rudiment to their distribution in diverse perivascular niches in the adult organ, we review the anatomy and function of pericytes in the healthy and diseased kidney. Many aspects of the ontogeny, specification and functional specialization of renal pericytes remain elusive. The development of powerful models in the easily accessible and genetically tractable zebrafish will help to uncover the multiple facets of these cells.

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Rider SA, Mullins LJ, Verdon RF, MacRae CA, Mullins JJ. Renin expression in developing zebrafish is associated with angiogenesis and requires the Notch pathway and endothelium. Am J Physiol Renal Physiol 309: F531-F539, 2015. First published July 22, 2015 doi:10.1152/ajprenal.00247.2015.-Although renin is a critical regulatory enzyme of the cardiovascular system, its roles in organogenesis and the establishment of cardiovascular homeostasis remain unclear. Mammalian renin-expressing cells are widespread in embryonic kidneys but are highly restricted, specialized endocrine cells in adults. With a functional pronephros, embryonic zebrafish are ideal for delineating the developmental functions of renin-expressing cells and the mechanisms governing renin transcription. Larval zebrafish renin expression originates in the mural cells of the juxtaglomerular anterior mesenteric artery and subsequently at extrarenal sites. The role of renin was determined by assessing responses to renin-angiotensin system blockade, salinity variation, and renal perfusion ablation. Renin expression did not respond to renal flow ablation but was modulated by inhibition of angiotensin-converting enzyme and altered salinity. Our data in larval fish are consistent with conservation of renin's physiological functions. Using transgenic renin reporter fish, with mindbomb and cloche mutants, we show that Notch signaling and the endothelium are essential for developmental renin expression. After inhibition of angiogenesis, renin-expressing cells precede angiogenic sprouts. Arising from separate lineages, but relying on mutual interplay with endothelial cells, renin-expressing cells are among the earliest mural cells observed in larval fish, performing both endocrine and paracrine functions. renin; zebrafish; notch; endothelium; angiogenesis RENIN is the rate-limiting enzyme of the renin-angiotensin system (RAS). Mammalian ANG II, the effector of the RAS, is principally involved in blood pressure homeostasis by regulation of vasomotor tone and Na ϩ retention. ANG II also regulates cell proliferation and angiogenesis (12,22). Pathological activation of the RAS is associated with cardiovascular diseases, including hypertension and heart failure, and is consequently a major target of therapeutic agents (11).Renin and its cognate cells are required for normal renal development (2), including angiogenesis of the renal vascular tree (59). In mice, ablation of the renin gene or renin-expressing cells leads to renal developmental abnormalities (55,71,79). The vasculature of mammalian embryonic kidneys have a transient but extensive coverage of mural renin-expressing cells (17,31,32,47,63); however, their function is unclear. Adult renin-expressing cells are restricted to the juxtaglomerular apparatus and play a vital role in ion homeostasis by secreting activated renin enzyme via cytoplasmic granules (17,31,36,63). Upon physiological challenge by RAS inhibition or low Na ϩ , prearteriolar vascular smooth muscle cells (VSMC) reestablish their embryonic re...

The bioavailability of trace elements in fishmeal diets is influenced by their chemical forms and dietary anti-nutritional factors. In formulated fish feed, supplemented organically bound minerals may be more bioavailable than inorganic minerals. A 10-week feeding trial was undertaken with rainbow trout (Oncorhynchus mykiss) to determine whether the inclusion of organically bound selenium (Se) and zinc (Zn) improved uptake and assimilation of these elements compared to commonly used inorganic forms. The three diets tested included a control diet, no added Zn or Se; an organic Se-yeast and Zn-proteinate supplemented diet; and an inorganic sodium selenite and Zn-sulphate supplemented diet. The endpoints tested were apparent digestibility, whole body levels, tissue distribution and Se- and Zn-dependent enzyme activities. Digestibility of residual Se in the basal diet was 54.2 +/- 1.0% and supplemented Se-yeast was significantly more digestible than selenite (p < 0.05). Digestibility of residual Zn was 21.9 +/- 2.0% and no significant difference was found between the treatments (p = 0.89). Whole body Se was raised by both Se sources and to a greatest extent by Se-yeast (p < 0.001). Zn-sulphate, and to a lesser extent Zn-proteinate, both raised whole body Zn (p < 0.05). Dietary Zn in the basal diet was found to be above requirements, yet Zn-sulphate had a significantly greater retention than Zn-proteinate in those tissues that responded to Zn supplementation. Se-yeast significantly raised Se in all tissues to a greater extent than selenite, except in the pyloric caeca and liver where the greatest increases were by selenite. Only Se-yeast elevated Se-dependent thioredoxin reductase activity (p < 0.05) and neither forms of Se affected glutathione peroxidise activity (p = 0.059). Alkaline phosphatase and carboxypeptidase B were not affected by Zn supplementation (p = 0.51 and p = 0.88 respectively). In all aspects, Se-yeast was found to be a highly bioavailable form of Se in comparison to selenite. Because of its superior bioavailability, organically bound Se would be a preferred Se source for supplementation of fishmeal trout diets than selenite.

The fecundity and occurrence of intersexuality in the amphipod, Echinogammarus marinus, collected from populations on the east coast of Scotland are reported. Intersex specimens have significantly smaller mean brood sizes than normal specimens. Embryo survival, as measured by the ratio of eggs/embryos in early and late stages of development, is lower in intersex specimens than normal specimens. Greater differences in the number of early stage eggs compared with late stage eggs in intersex specimens is suggested to arise by the active ejection of non-viable eggs, or from the passive loss of eggs through malformed brood plates in females. An apparent reduction in brood sizes between early and late stages of development in ‘normal’ specimens, emphasizes the importance of quantifying different egg/embryo stages in amphipod toxicology and fecundity studies.

The promotion of nutritional strategies that optimize natural defence mechanisms in ¢sh is of critical importance in producing robust juveniles and adult ¢sh. These animals are more capable of minimizing the impact of opportunistic pathogen attack, thus improving liveability and performance characteristics. The importance of the piscine gastrointestinal tract as a major endocrine and osmoregulatory organ is well reported as is its function as a defensive barrier to pathogen attack. Investigations using the inclusion of a speci¢c structural form of mannan oligosaccharide have been shown to improve the performance parameters, immune status, and gut morphology and improve an important aspect of barrier protection through the enhancement of mucal production in a number of aquaculture species. The selenium status of an animal is pivotal in determining the success of the innate and adaptive immune response of the animal, and the use of an organic selenium source, in the form of a selenoyeast, has been shown to improve enzyme function and tissue uptake. The antioxidant role of many of the selenoptroteins and the role of selenium in the glutathione peroxidase enzyme pathways involved in the control of oxidative stress is critical if oxidative damage and cell membrane lipid peroxidation are to be prevented. The use of these compounds as feed additives has important implications for health management in commercial aquaculture facilities. Further research is needed to evaluate the bene¢ts o¡ered by a range of commercial products. E¡ect of diet on mucin kinetics and composition: nutrition and health implications. Nutrition Reviews 62,105^114.Aquaculture Research, 2010, 41, 345^355 Enhancing natural defences in aquaculture species J W Sweetman et al.