Dynamics of endosomal trafficking

Endosomes are dynamic vesicular structures which transport cargo molecules internalized into the cell via endocytosis. Endosomal trafficking of cargo involves a large number of individual endosomes that regularly interact with each other via fusion and fission and thus form a dynamic network wherein endocytosed cargo is sorted and transported to various other intracellular compartments. In this study we present a general theoretical framework that takes into account individual endosomes and several key microscopic interaction processes among them. By combining theory with quantitative experiments, we seek to address the fundamental question of how the behaviour of the endosomal network emerges from the interactions among many individual endosomes of different sizes and cargo contents. Our theory is based on distributions of endosomes of various sizes and cargo amount. We compare our theory to experimental time course distributions of LDL, a degradative cargo, in a population of early endosomes. Early endosomes display a broad distribution of cargo with a characteristic power law, which we show is a consequence of stochastic fusion events of cargo carrying early endosomes. A simple model can quantitatively describe time-dependent statistics of LDL distributions in individual early endosomes. From fits of the theory to experimental data we can determine key parameters of endosomal trafficking such as the endosome fusion rate and the fluxes of cargo into and out of the network. Our theory predicts several experimentally confirmed scaling behaviours, which arise as a result of endosome fusion. Our theory provides a link between the dynamics at individual endosome level and average properties of the endosomal network. We show from our theory that some features of the endosomal distributions, which arise from interactions among individual endosomes, are sensitive to alterations in chosen parameters. This provides a direct means to study perturbation experiments wherein the cargo distribution can vary in response to changes of the endocytic system. Our analysis provides a powerful tool for the study of genetic and chemical perturbations that may alter specific systems properties and for extracting various kinetic rates involved in endosomal trafficking from only still images at different points

The Relevance of the Flexible Specialisation Paradigm for Small?Scale Industrial Restructuring in Ghana

Summary This article focuses on a large cluster of small enterprises in Kumasi, Ghana. It suggests that the flexible specialisation paradigm only helps to explain the growth of some of the small enterprises, namely a group of engineering workshops. However, due to deep inter?firm division of labour, their innovation has also raised the capacity of other small firms in the cluster to improve their equipment and output. Nevertheless, in spite of such emerging collective efficiency, the majority of producers have done more to swell the number of firms than to raise overall quantity or quality of output. Résumé La pertinence du paradigme de la spécialisation souple eu égard à la restructuration industrielle de faible envergure au Ghana L'article traite d'un important groupe d'entreprises de petite envergure à Kumasi, au Ghana. L'auteur propose que le paradigme de la spécialisation souple n'expliquerait qu'une partie de la croissance de certaines des petites entreprises, à savoir, celle d'un groupe d'ateliers mécaniques. Toutefois, en raison du partage approfondi de la main?d'oeuvre entre ces entreprises, leur activité novatrice a également servi, dans un même temps, à augmenter les capacités des autres entreprises de petite envergure au sein du groupe d'améliorer leur matériel et leur rendement. Quoiqu'il en soit, et malgré l'apparition d'une telle efficacité collective, la majorité des producteurs ont préféré augmenter le nombre d'entreprises, au lieu d'augmenter la quantité ou la qualité de la production. Resumen La relevancia del modelo de especialización flexible para la reestructuración industrial en pequeña escala en Ghana Se concentra este estudio en un gran grupo de pequeñas empresas en Kumasi, Ghana. Sugiere que el modelo de especialización flexible sólo ayuda a explicar el crecimiento de algunas de estas pequeñas empresas, concretamente talleres de ingeniería. Sin embargo, debido a una profunda división inter?compañías de la mano de obra, su innovación ha incrementado también la capacidad de otras pequeñas empresas del grupo para aumentar su equipamiento y su producción. A pesar de esta emergente eficiencia colectiva la mayoría de los productores han hecho más para engrosar el número de empresas que para acrecentar la calidad y cantidad de la producción

Academic freedom and the professional responsibilities of applied ethicists: a comment on Minerva

Academic freedom is an important good, but it comes with several responsibilities. In this commentary we seek to do two things. First, we argue against Francesca Minerva's view of academic freedom as presented in her article ‘New threats to academic freedom’ on a number of grounds. We reject the nature of the absolutist moral claim to free speech for academics implicit in the article; we reject the elitist role for academics as truth-seekers explicit in her view; and we reject a possible more moderate re-construction of her view based on the harm/offence distinction. Second, we identify some of the responsibilities of applied ethicists, and illustrate how they recommend against allowing for anonymous publication of research. Such a proposal points to the wider perils of a public discourse which eschews the calm and careful discussion of ideas

Complex evolving patterns of mass loss from Antarctica’s largest glacier

Pine Island Glacier has contributed more to sea level rise over the past four decades than any other glacier in Antarctica. Model projections indicate that this will continue in the future but at conflicting rates. Some models suggest that mass loss could dramatically increase over the next few decades, resulting in a rapidly growing contribution to sea level and fast retreat of the grounding line, where the grounded ice meets the ocean. Other models indicate more moderate losses. Resolving this contrasting behaviour is important for sea level rise projections. Here, we use high-resolution satellite observations of elevation change since 2010 to show that thinning rates are now highest along the slow-flow margins of the glacier and that the present-day amplitude and pattern of elevation change is inconsistent with fast grounding-line migration and the associated rapid increase in mass loss over the next few decades. Instead, our results support model simulations that imply only modest changes in grounding-line location over that timescale. We demonstrate how the pattern of thinning is evolving in complex ways both in space and time and how rates in the fast-flowing central trunk have decreased by about a factor five since 2007

Introduction

Cambridge Studies in Nineteenth-Century Literature and Culture No. 45Copyright © 2004 Cambridge University PressFor the Victorian reading public, periodicals played a far greater role than books in shaping their understanding of new discoveries and theories in science, technology and medicine. Such understandings were formed not merely by serious scientific articles, but also by glancing asides in political reports, fictional representations, or humorous attacks in comic magazines. Ranging across diverse forms of periodicals, from top-selling religious and juvenile magazines through to popular fiction-based periodicals, and from the campaigning 'new journalism' of the late century to the comic satire of Punch, this book explores the ways in which scientific ideas and developments were presented to a variety of Victorian audiences. In addition, it offers three case studies of the representation of particular areas of science: 'baby science', scientific biography, and electricity. This intriguing collaborative volume sheds light on issues relating to history and history of science, literature, book history, and cultural and media studies

Reconciling Storegga tsunami sedimentation patterns with modelled wave heights : a discussion from the Shetland Isles field laboratory.

The Shetland Isles represent an ideal field laboratory for tsunami geoscience research. This is due to the widespread preservation of Holocene tsunami sediments in coastal peat deposits. This study uses published accounts of the Holocene Storegga Slide tsunami to illustrate how two different approaches – mapping of tsunami sediments and numerical modelling – produce radically different run‐up heights. The Storegga Slide is one of the world largest submarine slides and took place ca 8150 cal yr bp on the continental slope west of Norway. The tsunami generated by the landslide deposited locally extensive sheets of marine sand and gravel, as well as redeposited clasts of peat across the contemporary land surface. These sediment accumulations have subsequently been buried by peat growth during the Holocene while exposures of the deposits are locally visible in coastal cliff sections. In several areas, the tsunami sediments can be traced upslope and inland within the peat as tapering sediment wedges up to maximum altitudes of between ca 8·1 m and 11·8 m above present sea level. Since reconstructions of palaeo‐sea level for Shetland for ca 8150 cal yr bp suggest an altitude of 20 m below high tide on the day that the tsunami struck, it has been inferred that the minimum tsunami run‐up was locally between 28·1 m (8·1 + 20 m) and 31·8 m (11·8 + 20 m). However, numerical models of the tsunami for Shetland suggest that the wave height may only have reached a highest altitude in the order of +13 m above sea level on the day the tsunami took place. In this paper a description is given of the sedimentary evidence for tsunami run‐up in the Shetland Isles. This is followed by an evaluation of where the palaeo‐sea level was located when the tsunami occurred. Significant differences are highlighted in tsunami inundation estimates between those based on the observed (geological) data and the theoretically‐modelled calculations. This example from the Shetland Isles may have global significance since it exemplifies how two different approaches to the reconstruction of tsunami inundation at the coast can produce radically different results with modelled wave height at the coast being considerably less than the geological estimates of tsunami run‐up