Kv7 and Kv11 channels in myometrial regulation.

Ion channels play a key role in defining myometrial contractility. Modulation of ion channel populations is proposed to underpin gestational changes in uterine contractility associated with the transition from uterine quiescence to active labour. Of the myriad ion channels present in the uterus, this article will focus upon potassium channels encoded by the KCNQ genes and ether-à-go-go-related (ERG) genes. Voltage-gated potassium channels encoded by KCNQ and ERG (termed Kv7 and Kv11, respectively) are accepted as major determinants of neuronal excitability and the duration of the cardiac action potential. However, there is now growing appreciation that these ion channels have a major functional impact in vascular and non-vascular smooth muscle. Moreover, Kv7 channels may be potential therapeutic targets for the treatment of preterm labour

Dissociable effects of visual crowding on the perception of colour and motion

Our ability to recognise objects in peripheral vision is fundamentally limited by crowding, the deleterious effect of clutter that disrupts the recognition of features ranging from orientation and colour to motion and depth. Prior research is equivocal on whether this reflects a singular process that disrupts all features simultaneously or multiple processes that affect each independently. We examined crowding for motion and colour, two features that allow a strong test of feature independence. ‘Cowhide’ stimuli were presented 15 degrees in peripheral vision, either in isolation or surrounded by flankers to give crowding. Observers reported either the target direction (clockwise/counterclockwise from upwards) or its hue (blue/purple). We first established that both features show systematic crowded errors (predominantly biased towards the flanker identities) and selectivity for target-flanker similarity (with reduced crowding for dissimilar target/flanker elements). The multiplicity of crowding was then tested with observers identifying both features: a singular object-selective mechanism predicts that when crowding is weak for one feature and strong for the other that crowding should be all-or-none for both. In contrast, when crowding was weak for colour and strong for motion, errors were reduced for colour but remained for motion, and vice versa with weak motion and strong colour crowding. This double dissociation reveals that crowding disrupts certain combinations of visual features in a feature-specific manner, ruling out a singular object-selective mechanism. The ability to recognise one aspect of a cluttered scene, like colour, thus offers no guarantees for the correct recognition of other aspects, like motion

Fully Collapsed Imploded Cryptophanes in Solution and in the Solid State

Cryptophanes with flexible linkers derived from (±)‐tris‐(4‐formyl‐phenyl)‐cyclotriguaiacylene with either bisoxydi(ethylamine) or bis(aminopropyl)ether were isolated as single crystals, the crystal structures of which showed the proposed, but previously uncharacterised, out‐in conformation, in which both cyclotriguaiacylene fragments adopt a crown conformation with one crown sitting inside the other. The usual cage‐like out‐out conformation of the cryptophanes was observed when crystals were dissolved upon heating, and the molecules collapsed back to the out‐in isomers over time. In contrast, a cryptophane also derived from (±)‐tris‐(4‐formyl‐phenyl)‐cyclotriguaiacylene but with rigid dibenzalhydrazine linkers was isolated as the more usual out‐out isomer

Could a potential Anthropocene mass extinction define a new geological period?

A key aspect of the current debate about the Anthropocene focuses on defining a new geological epoch. Features of the Anthropocene include a biodiversity crisis with the potential to reach ‘mass extinction’ status alongside increasing global CO₂ and temperature. Previous geological boundaries associated with mass extinctions, rises in atmospheric CO₂ and rises in global temperature are more usually associated with transitions between geological periods. The current rapid increase in species extinctions suggest that a new mass extinction event is most likely imminent in the near-term future. Although CO₂ levels are currently low in comparison with the rest of the Phanerozoic, they are rising rapidly along with global temperatures. This suggests that defining the Anthropocene as a new geological period, rather than a new epoch, may be more consistent with previous geological boundaries in the Phanerozoic

Tris-N-alkylpyridinium-functionalised cyclotriguaiacylene hosts as axles in branched [4]pseudorotaxane formation

A series of [4]pseudorotaxanes composed of three-way axle threads based on the cyclotriguaiacylene family of crown-shaped cavitands and three threaded macrocyclic components has been achieved. These exploit the strong affinity for electron-poor alkyl-pyridinium units to reside within the electron-rich cavity of macrocycles, in this case dimethoxypillar[5]arene (DMP). The branched [4]pseudorotaxane= assemblies {(DMP)3∙L}3+,where L = N-alkylated derivatives of the host molecule (±)-tris-(isonicotinoyl)cyclotriguaiacylene, were characterised by NMR spectroscopy and mass spectrometry, and an energy-minimised structure of {(DMP)3∙(tris-(N-propyl-isonicotinoyl)cyclotriguaiacylene)}3+ was calculated. Crystal structures of N-ethyl-isonicotinoyl)cyclotriguaiacylene hexafluorophosphate and N-propyl-isonicotinoyl)cyclotriguaiacylene hexafluorophosphate each show ‘hand-shake’ self-inclusion motifs occurring between the individual cavitands

Synthesis of layered silicon-graphene hetero-structures by wet jet milling for high capacity anodes in Li-ion batteries

While silicon-based negative electrode materials have been extensively studied, to develop high capacity lithium-ion batteries (LIBs), implementing a large-scale production method that can be easily transferred to industry, has been a crucial challenge. Here, a scalable wet-jet milling method was developed to prepare a silicon-graphene hybrid material to be used as negative electrode in LIBs. This synthesized composite, when used as an anode in lithium cells, demonstrated high Li ion storage capacity, long cycling stability and high-rate capability. In particular, the electrode exhibited a reversible discharge capacity exceeding 1763 mAh g−1 after 450 cycles with a capacity retention of 98% and a coulombic efficiency of 99.85% (with a current density of 358 mA g−1). This significantly supersedes the performance of a Si-dominant electrode structures. The capacity fade rate after 450 cycles was only 0.005% per cycle in the 0.05–1 V range. This superior electrochemical performance is ascribed to the highly layered, silicon-graphene porous structure, as investigated via focused ion beam in conjunction with scanning electron microscopy tomography. The hybrid electrode could retain 89% of its porosity (under a current density of 358 mA g−1) after 200 cycles compared with only 35% in a Si-dominant electrode. Moreover, this morphology can not only accommodate the large volume strains from active silicon particles, but also maintains robust electrical connectivity. This confers faster transportation of electrons and ions with significant permeation of electrolyte within the electrode. Physicochemical characterisations were performed to further correlate the electrochemical performance with the microstructural dynamics. The excellent performance of the hybrid material along with the scalability of the synthesizing process is a step forward to realize high capacity/energy density LIBs for multiple device applications

A common visual metric for approximate number and density.

There is considerable interest in how humans estimate the number of objects in a scene in the context of an extensive literature on how we estimate the density (i.e., spacing) of objects. Here, we show that our sense of number and our sense of density are intertwined. Presented with two patches, observers found it more difficult to spot differences in either density or numerosity when those patches were mismatched in overall size, and their errors were consistent with larger patches appearing both denser and more numerous. We propose that density is estimated using the relative response of mechanisms tuned to low and high spatial frequencies (SFs), because energy at high SFs is largely determined by the number of objects, whereas low SF energy depends more on the area occupied by elements. This measure is biased by overall stimulus size in the same way as human observers, and by estimating number using the same measure scaled by relative stimulus size, we can explain all of our results. This model is a simple, biologically plausible common metric for perceptual number and density

A compact high field magnet system for medical applications

High magnetic field gradients can be used for various medical applications including magnetically targeted drug delivery, magnetic cell separation and controlled local heating for the ablation of tumours. These processes involve the use of biocompatible magnetic nanoparticles directed to the area of interest by the use of a field gradient. The force on the nanoparticle is proportional to the field gradient product, so high fields are required for effective delivery. Bulk superconductors are an attractive solution for both drug delivery and the next generation of low cost magnetic resonance imaging magnets. In particular, MgB2 is seen as an attractive material due to its low cost, simple processing and relatively high transition temperature (∼39 K). This paper describes the development of a breadboard compact delivery system suitable for medical applications. This incorporates a cryogenic stage which utilises long life space-proven technology and state of the art ex-situ processed MgB 2 pellets.EP/P026427/1

Evaluation of chemical strategies for improving the stability and oral toxicity of insecticidal peptides

© 2018 by the authors. Spider venoms are a rich source of insecticidal peptide toxins. Their development as bioinsecticides has, however, been hampered due to concerns about potential lack of stability and oral bioactivity. We therefore systematically evaluated several synthetic strategies to increase the stability and oral potency of the potent insecticidal spider-venom peptide !-HXTX-Hv1a (Hv1a). Selective chemical replacement of disulfide bridges with diselenide bonds and N- to C-terminal cyclization were anticipated to improve Hv1a resistance to proteolytic digestion, and thereby its activity when delivered orally. We found that native Hv1a is orally active in blowflies, but 91-fold less potent than when administered by injection. Introduction of a single diselenide bond had no effect on the susceptibility to scrambling or the oral activity of Hv1a. N- to C-terminal cyclization of the peptide backbone did not significantly improve the potency of Hv1a when injected into blowflies and it led to a significant decrease in oral activity. We show that this is likely due to a dramatically reduced rate of translocation of cyclic Hv1a across the insect midgut, highlighting the importance of testing bioavailability in addition to toxin stability