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Norbormide [5-(α-hydroxy-α-2-pyridylbenzyl)-7-(α-2-pyridylbenzylidene)-5-norbornene-2,3-dicarboximide] (NRB, 1), an existing but infrequently used rodenticide, is known to be uniquely toxic to rats, but relatively harmless to other rodents and mammals. As a vasoactive agent, NRB induces a species-specific vasocontractile effect that is restricted to the peripheral arteries of the rat. Despite the precise mechanisms behind this phenomenon having yet to be fully clarified, it is postulated that the molecular target of NRB could be located within the plasma membrane of rat peripheral artery myocytes (e.g. rat caudal artery myocytes). As such, the primary objective of this study was to develop a fluorescently labelled derivative of NRB to investigate its subcellular distribution/localization in both NRB-sensitive (freshly isolated rat caudal artery myocytes, FIRCAMs) and NRB-insensitive (human hepatic stellate, LX2) cells. Of the examples prepared, lead structure endo-NRB-NBD-bPA subsequently demonstrated retention of the parent toxicant's pharmacological profile (in terms of its ability to induce both a vasocontractile response in rat caudal artery rings in vitro, and a lethal end-point in rats in vivo). Endo-NRB-NBD-bPA was also shown to be significantly less permeable (an integral feature in the design of fluorescent probes targeting cell-surface receptors) to both LX2 cells and FIRCAMs. Disappointingly, no fluorescence could be observed on the plasma membrane of FIRCAMs stained with endo-NRB-NBD-bPA., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

In the last decade the use of homogenous gold catalysts has rapidly grown and become a valuable tool for complex natural product synthesis. Spiroketal natural products are valuable targets for total synthesis and medicinal chemistry applications. The use of gold catalysts has emerged as a useful tool to synthesise these privileged scaffolds. This review summarises the application of gold catalysis for the syntheses of spiro, bridged and fused ketal natural products.

The first total synthesis of resorcyclic acid lactone spiroketal citreoviranol (1) is described. The synthesis was completed in nine steps and via Sonogashira cross-coupling, gold-catalyzed cyclization, and an unusual base-induced ketalization. The relative and absolute stereochemistry of citreoviranol was unambiguously confirmed using 2D NMR spectroscopy and X-ray crystallography.

The spiroketal motif occurs in a wide range of biologically active natural products and represents a valuable target in medicinal chemistry and total synthesis. In recent years, innovative new synthetic methods have substantially expanded the range of potential precursors, cyclisation modes and opportunities for asymmetric catalysis and tandem processes. This Perspective aims to highlight recent rapid advances in the use of transition metal catalysis for spiroketal formation, in the context of our own investigations into gold-catalysed asymmetric spiroketalisation.

Handling of micrometer sizes particles, such as biological cells or coated beads, plays a relevant role in the field of life science. A number of devices have been presented in the last years, in which acoustic forces generated by coupling the vibration of a solid structure excited by a piezoelectric transducer to the particle suspension are used to collect particles in lines or position them in clumps on a grid. Following the trend of lab-on-a-chip devices, efforts have been made to shrink the size of such systems, aiming at less reagent consumption and shorter reaction times. The majority of these systems consist of closed fluid filled volumes, typically channels. Here the use of an open fluid volume, a droplet, is examined. By exciting resonances into the droplet positioned on a surface, particles can be gathered into a line, two parallel lines or, as the frequency of excitation is increased, into more complex patterns. Such a concentration process will have useful applications in improved detection sensitivity of low concentration particulate solutions.

D. E. Huber, R. M. Shiffrin, K. B. Lyle, and K. I. Ruys (2001) tested two-alternative, forced-choice (2-AFC) perceptual identification in a short-term priming task. For repetition priming, passive viewing of primes resulted in a preference to choose repeated words, but actively responding to primes resulted in a preference against choosing repeated words. These results were explained with a computational model, responding optimally with unknown sources of evidence (ROUSE), using the offsetting mechanisms of source confusion and discounting. An analysis of ROUSE revealed conditions under which discounting efficacy should diminish, causing a preference for primed words even with active prime processing. Two new studies confirm 2 such conditions: very short target flash durations and very low similarity between primes and primed choice words. These a priori predictions contrast with the a posteriori data fits of a multinomial model developed by R. Ratcliff and G. McKoon (2001).

Huber, Shriffrin, Lyle, and Ruys (2001) measured short-term repetition priming effects in perceptual identification with two-alternative forced-choice testing. There was a preference to choose repeated words following passive viewing of primes and a preference against choosing repeated words following active responding to primes. In this present study, we explored conditions of prime processing that produce this pattern of results. Experiment 1 revealed that increased prime duration under passive viewing instructions produces the active priming pattern. Experiment 2 assessed memory for primes: With poor recognition of primes, there was a strong preference for repeated words; however, with good recognition of primes, this preference was eliminated. These results are modeled by a computational theory of optimal decision making, responding optimally with unknown sources of evidence (ROUSE). In ROUSE, a preference for repeated words results from source confusion between primes and choice words. A reversal in the direction of preference arises from the discounting of words known to have also appeared as primes.

Vaginal flora was studied quantitatively in 29 sexually active women, 16 to 33 years of age, to define the role of C. vaginale in vaginitis. Seventeen were asymptomatic and 12 complained of symptoms of vaginitis. Seven asymptomatic women had scant secretions: four of these seven had C. vaginale at log10 6 to 9 CFU per milliliter, none of whom had "clue" cells; none had trichomonas or candida; six had lactobacilli at log10 7 to 9.7 per milliliter; only one had Bacteroidaceae at greater than log10 5 per milliliter. Ten asymptomatic women had easily collectable secretions; eight of 10 had C. vaginale at log10 6.5 to 9.6 per milliliter, three of whom had "clue" cells; four had trichomonas and none candida; nine had Lactobacilli at log10 7 to 9.3 per milliliter; four had Bacteroidaceae at greater than log10 5 per milliliter. Twelve had vaginitis: five of 12 had C. vaginale at log10 7.9 to 11 per milliliter, one of whom had "clue" cells; nine had either trichomonas or candida or both and three had no pathogen, including C. vaginale; 10 had Lactobacilli at log10 7 to 10 per milliliter; six had Bacteriodaceae at greater than log10 5 per milliliter. Three had "clue" cells in absence of C. vaginale.