Action of fully co-ordinated 1,10-phenanthroline transition metal chelates on the guinea-pig isolated atrium

Zusammenfassung Nachweis, dass vollkoordinierte zweiwertige Kupfer- und Nickelchelate des 3,4,7,8-Tetramethyl-1,10-phenanthrolins Muskelkraft, wie auch Kontraktionsgeschwindigkeit des isolierten Meerschweinchen Atriums, sowie H³-Noradrenalin- und Metabolitenausfluss vermehren. Die durch Chelate veranlasste Senkung des Noradrenalins konnte durch Fluoreszenz-Histochemie bestätigt werden.

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This work was commenced in the Department of Pharmacology, University of Melbourne and was presented in part by H. G. in November 1972 in partial fulfilment for the degree of B. Sc. (Hons) in the University of Melbourne.     

Spectral distribution of the negative potential in the cichlid electroretinogram

Summary A negative potential occurring in the ERG of certain cichlid fishes shows a unique set of properties when evoked by monochromatic light. Spectral distributions determined forCichlasoma octofasciatum andHemichromis bimaculatus show a blue (460–478 nm) maximum, no Purkinje shift upon light adaptation, and secondary peaks correlated with the species' behavioral preferences in reproduction and parental care.     

Extraterrestrial meteors: a martian meteor and its parent comet

Regular meteor showers occur when a planet approaches the orbit of a periodic comet--for example, the Leonid shower is evident around 17 November every year as Earth skims past the dusty trail of comet Tempel-Tuttle. Such showers are expected to occur on Mars as well, and on 7 March last year, the panoramic camera of Spirit, the Mars Exploration Rover, revealed a curious streak across the martian sky. Here we show that the timing and orientation of this streak, and the shape of its light curve, are consistent with the existence of a regular meteor shower associated with the comet Wiseman-Skiff, which could be characterized as martian Cepheids.     

Apolipoprotein E controls cerebrovascular integrity via cyclophilin A

Human apolipoprotein E has three isoforms: APOE2, APOE3 and APOE4. APOE4 is a major genetic risk factor for Alzheimer's disease and is associated with Down's syndrome dementia and poor neurological outcome after traumatic brain injury and haemorrhage. Neurovascular dysfunction is present in normal APOE4 carriers and individuals with APOE4-associated disorders. In mice, lack of Apoe leads to blood-brain barrier (BBB) breakdown, whereas APOE4 increases BBB susceptibility to injury. How APOE genotype affects brain microcirculation remains elusive. Using different APOE transgenic mice, including mice with ablation and/or inhibition of cyclophilin A (CypA), here we show that expression of APOE4 and lack of murine Apoe, but not APOE2 and APOE3, leads to BBB breakdown by activating a proinflammatory CypA-nuclear factor-κB-matrix-metalloproteinase-9 pathway in pericytes. This, in turn, leads to neuronal uptake of multiple blood-derived neurotoxic proteins, and microvascular and cerebral blood flow reductions. We show that the vascular defects in Apoe-deficient and APOE4-expressing mice precede neuronal dysfunction and can initiate neurodegenerative changes. Astrocyte-secreted APOE3, but not APOE4, suppressed the CypA-nuclear factor-κB-matrix-metalloproteinase-9 pathway in pericytes through a lipoprotein receptor. Our data suggest that CypA is a key target for treating APOE4-mediated neurovascular injury and the resulting neuronal dysfunction and degeneration.