A new role for P2X4 receptors as modulators of lung surfactant secretion

In recent years, P2X receptors have attracted increasing attention as regulators of exocytosis and cellular secretion. In various cell types, P2X receptors have been found to stimulate vesicle exocytosis directly via Ca2+ influx and elevation of the intracellular Ca2+ concentration. Recently, a new role for P2X4 receptors as regulators of secretion emerged. Exocytosis of lamellar bodies (LBs), large storage organelles for lung surfactant, results in a local, fusion-activated Ca2+ entry (FACE) in alveolar type II epithelial cells. FACE is mediated via P2X4 receptors that are located on the limiting membrane of LBs and inserted into the plasma membrane upon exocytosis of LBs. The localized Ca2+ influx at the site of vesicle fusion promotes fusion pore expansion and facilitates surfactant release. In addition, this inward-rectifying cation current across P2X4 receptors mediates fluid resorption from lung alveoli. It is hypothesized that the concomitant reduction in the alveolar lining fluid facilitates insertion of surfactant into the air–liquid interphase thereby “activating” it. These findings constitute a novel role for P2X4 receptors in regulating vesicle content secretion as modulators of the secretory output during the exocytic post-fusion phase

A Learning 2.0 Programme: raising library staff awareness of Web 2.0 at Imperial College London

Published versio

New times, new politics: history and memory during the final years of the CPGB

This article examines the relationship between collective memory, historical interpretation and political identity. It focuses on the dissolution of the Communist Party of Great Britain (CPGB) as constructed through collective narrative memory, and on Marxist interpretations of history. The divisions within the party and the wider Marxist community, stretching from 1956 until 1991, were often framed around questions of historical interpretation. The events of 1989–1991 created an historical and mnemonic crisis for CPGB members who struggled to reconcile their past identities with their present situation. Unlike the outward-facing revisionism of other political parties, this was an intensely personal affair. The solution for many was to emphasise the need to find new ways to progress socialist aims, without relying on a discredited grand narrative. In contrast, other Communist parties, such as the Communist Party of Britain, which had been established (or ‘re-established’) in 1988, fared rather better. By adhering to the international party line of renewal and continued struggle, the party was able to hold its narrative together, condemning the excesses of totalitarian regimes, while reaffirming the need for international class struggle

Functional organisation for verb generation in children with developmental language disorder

Developmental language disorder (DLD) is characterised by difficulties in learning one's native language for no apparent reason. These language difficulties occur in 7% of children and are known to limit future academic and social achievement. Our understanding of the brain abnormalities associated with DLD is limited. Here, we used a simple four-minute verb generation task (children saw a picture of an object and were instructed to say an action that goes with that object) to test children between the ages of 10–15 years (DLD N = 50, typically developing N = 67). We also tested 26 children with poor language ability who did not meet our criteria for DLD. Contrary to our registered predictions, we found that children with DLD did not have (i) reduced activity in language relevant regions such as the left inferior frontal cortex; (ii) dysfunctional striatal activity during overt production; or (iii) a reduction in left-lateralised activity in frontal cortex. Indeed, performance of this simple language task evoked activity in children with DLD in the same regions and to a similar level as in typically developing children. Consistent with previous reports, we found sub-threshold group differences in the left inferior frontal gyrus and caudate nuclei, but only when analysis was limited to a subsample of the DLD group (N = 14) who had the poorest performance on the task. Additionally, we used a two-factor model to capture variation in all children studied (N = 143) on a range of neuropsychological tests and found that these language and verbal memory factors correlated with activity in different brain regions. Our findings indicate a lack of support for some neurological models of atypical language learning, such as the procedural deficit hypothesis or the atypical lateralization hypothesis, at least when using simple language tasks that children can perform. These results also emphasise the importance of controlling for and monitoring task performance

Cell-permeable lanthanide-platinum(iv) anti-cancer prodrugs

Platinum compounds are a vital part of our anti-cancer arsenal, and determining the location and speciation of platinum compounds is crucial. We have synthesised a lanthanide complex bearing a salicylic group (Ln = Gd, Eu) which demonstrates excellent cellular accumulation and minimal cytotoxicity. Derivatisation enabled access to bimetallic lanthanide–platinum(II) and lanthanide–platinum(IV) complexes. Luminescence from the europium–platinum(IV) system was quenched, and reduction to platinum(II) with ascorbic acid resulted in a “switch-on” luminescence enhancement. We used diffusion-based 1H NMR spectroscopic methods to quantify cellular accumulation. The gadolinium–platinum(II) and gadolinium–platinum(IV) complexes demonstrated appreciable cytotoxicity. A longer delay following incubation before cytotoxicity was observed for the gadolinium–platinum(IV) compared to the gadolinium–platinum(II) complex. Functionalisation with octanoate ligands resulted in enhanced cellular accumulation and an even greater latency in cytotoxicity

Super-resolution kinetochore tracking reveals the mechanisms of human sister kinetochore directional switching

The congression of chromosomes to the spindle equator involves the directed motility of bi-orientated sister kinetochores. Sister kinetochores bind bundles of dynamic microtubules and are physically connected through centromeric chromatin. A crucial question is to understand how sister kinetochores are coordinated to generate motility and directional switches. Here, we combine super-resolution tracking of kinetochores with automated switching-point detection to analyse sister switching dynamics over thousands of events. We discover that switching is initiated by both the leading (microtubules depolymerising) or trailing (microtubules polymerising) kinetochore. Surprisingly, trail-driven switching generates an overstretch of the chromatin that relaxes over the following half-period. This rules out the involvement of a tension sensor, the central premise of the long-standing tension-model. Instead, our data support a model in which clocks set the intrinsic-switching time of the two kinetochore-attached microtubule fibres, with the centromeric spring tension operating as a feedback to slow or accelerate the clocks

Identifying Vessel Branching from Fluid Stresses on Microscopic Robots

Objects moving in fluids experience patterns of stress on their surfaces determined by the geometry of nearby boundaries. Flows at low Reynolds number, as occur in microscopic vessels such as capillaries in biological tissues, have relatively simple relations between stresses and nearby vessel geometry. Using these relations, this paper shows how a microscopic robot moving with such flows can use changes in stress on its surface to identify when it encounters vessel branches.Comment: Version 2 has minor clarification

The cultural capitalists: notes on the ongoing reconfiguration of trafficking culture in Asia

Most analysis of the international flows of the illicit art market has described a global situation in which a postcolonial legacy of acquisition and collection exploits cultural heritage by pulling it westwards towards major international trade nodes in the USA and Europe. As the locus of consumptive global economic power shifts, however, these traditional flows are pulled in other directions: notably for the present commentary, towards and within Asia

Poleward energy transport: is the standard definition physically relevant at all time scales?

Poleward energy transport in the atmosphere and oceans constitutes an important branch of the global energy budget, and its role in the climate system has been the subject of many studies. In the atmosphere, the transport is affected by “eddies” and large scale meridional cells, both with zero net mass transport across latitude circles, but also partly by processes associated with a net transport of mass across latitude circles. The latter must cease to operate in steady state, but they may be significant when time variability of the heat budget is considered. Indeed, examination of reanalysis data on short (daily to monthly) timescales shows that mass variations on these timescales result in surprisingly large fluctuations (in excess of 10^15 W = 1 PW) in the poleward heat transport. These fluctuations are referred to as “extensive”, for they primarily alter the mass integrated energy of the region considered, but not its averaged value. It is suggested that extensive fluctuations mask more meaningful climate signals present in the heat transport variability on monthly and interannual timescales, and a new formulation is proposed to isolate the latter. This new formulation is applied successfully to reanalysis data and climate model simulations