Functional interdependence between septin and actin cytoskeleton

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Abstract Background Septin2 is a member of a highly conserved GTPase family found in fungi and animals. Septins have been implicated in a diversity of cellular processes including cytokinesis, formation of diffusion barriers and vesicle trafficking. Septin2 partially co-localises with actin bundles in mammalian interphase cells and Septin2-filamentmorphology depends upon an intact actin cytoskeleton. How this interaction is regulated is not known. Moreover, evidence that Septin2 is remodelled or redistributed in response to other changes in actin organisation is lacking. Results Septin2 filaments are associated with actin fibres, but Septin2 is not associated with actin at the leading edge of moving cells or in ruffles where actin is highly dynamic. Rather, Septin2 is spatially segregated from these active areas and forms O- and C-shaped structures, similar to those previously observed after latrunculin treatment. FRAP experiments showed that all assemblies formed by Septin2 are highly dynamic with a constant exchange of Septin2 in and out of these structures, and that this property is independent of actin. A combination of RNAi experiments and expression of truncated forms of Septin2 showed that Septin2 plays a significant role in stabilising or maintaining actin bundles. Conclusion We show that Septin2 can form dynamic structures with differing morphologies in living cells, and that these morphologies are dependent on the functional state of the actin cytoskeleton. Our data provide a link between the different morphological states of Septin2 and functions of Septin2 in actin-dynamics, and are consistent with the model proposed by Kinoshita and colleagues, that Septin2 filaments play a role in stabilisation of actin stress fibres thus preventing actin turnover.Published versio

Cutaneous Conditions Leading to Dermatology Consultations in the Emergency Department

<p>Introduction: We established the most common cutaneous diseases that received dermatology consultation in the adult emergency department (ED) and identified differentiating clinical characteristics of dermatoses that required hospital admission.</p> <p>Methods: A retrospective chart review of 204 patients presenting to the ED who received dermatology consultations at Los Angeles County/University of Southern California Medical Center, an urban tertiary care teaching hospital.</p> <p>Results: Of all patients, 18% were admitted to an inpatient unit primarily for their cutaneous disease, whereas 82% were not. Of nonadmitted patients, the most commonly diagnosed conditions were eczematous dermatitis not otherwise specified (8.9%), scabies (7.2%), contact dermatitis (6.6%), cutaneous drug eruption (6.0%), psoriasis vulgaris (4.2%), and basal cell carcinoma (3.6%). Of patients admitted for their dermatoses, the most highly prevalent conditions were erythema multiforme major/Stevens-Johnson syndrome (22%), pemphigus vulgaris (14%), and severe cutaneous drug eruption (11%). When compared with those of nonadmitted patients, admitted skin conditions were more likely to be generalized (92% vs 72%; P = 0.0104), acute in onset (< 1 month duration) (81% vs 51%; P = 0.0005), painful (41% vs 15%; P = 0.0009), blistering (41% vs 7.8%; P < 0.0001), and ulcerated or eroded (46% vs 7.8%; P < 0.0001). They were more likely to involve the mucosa (54% vs 7.2%; P < 0.0001) and less likely to be pruritic (35% vs 58%; P = 0.0169).</p> <p>Conclusion: We have described a cohort of patients receiving dermatologic consultation in the ED of a large urban teaching hospital. These data identify high-risk features of more severe skin disease and may be used to refine curricula in both emergency and nonemergency cutaneous disorders for emergency physicians. [West J Emerg Med. 2011;12(4):551–555.]</p

Dynamics of putative raft-associated proteins at the cell surface

Lipid rafts are conceptualized as membrane microdomains enriched in cholesterol and glycosphingolipid that serve as platforms for protein segregation and signaling. The properties of these domains in vivo are unclear. Here, we use fluorescence recovery after photobleaching to test if raft association affects a protein's ability to laterally diffuse large distances across the cell surface. The diffusion coefficients (D) of several types of putative raft and nonraft proteins were systematically measured under steady-state conditions and in response to raft perturbations. Raft proteins diffused freely over large distances (>4 μm), exhibiting Ds that varied 10-fold. This finding indicates that raft proteins do not undergo long-range diffusion as part of discrete, stable raft domains. Perturbations reported to affect lipid rafts in model membrane systems or by biochemical fractionation (cholesterol depletion, decreased temperature, and cholesterol loading) had similar effects on the diffusional mobility of raft and nonraft proteins. Thus, raft association is not the dominant factor in determining long-range protein mobility at the cell surface

Investigating the Cosmic-Ray Ionization Rate in the Galactic Diffuse Interstellar Medium through Observations of H3+

Observations of H3+ in the Galactic diffuse interstellar medium (ISM) have led to various surprising results, including the conclusion that the cosmic-ray ionization rate (zeta_2) is about 1 order of magnitude larger than previously thought. The present survey expands the sample of diffuse cloud sight lines with H3+ observations to 50, with detections in 21 of those. Ionization rates inferred from these observations are in the range (1.7+-1.3)x10^-16 s^-1<zeta_2<(10.6+-8.2)x10^-16 s^-1 with a mean value of zeta_2=(3.5^+5.3_-3.0)x10^-16 s^-1. Upper limits (3 sigma) derived from non-detections of H3+ are as low as zeta_2<0.4x10^-16 s^-1. These low upper-limits, in combination with the wide range of inferred cosmic-ray ionization rates, indicate variations in zeta_2 between different diffuse cloud sight lines. A study of zeta_2 versus N_H (total hydrogen column density) shows that the two parameters are not correlated for diffuse molecular cloud sight lines, but that the ionization rate decreases when N_H increases to values typical of dense molecular clouds. Both the difference in ionization rates between diffuse and dense clouds and the variation of zeta_2 among diffuse cloud sight lines are likely the result of particle propagation effects. The lower ionization rate in dense clouds is due to the inability of low-energy (few MeV) protons to penetrate such regions, while the ionization rate in diffuse clouds is controlled by the proximity of the observed cloud to a site of particle acceleration.Comment: 48 pages, 19 figures, 4 tables, accepted for publication in Ap

Human cytomegalovirus interactome analysis identifies degradation hubs, domain associations and viral protein functions

Human cytomegalovirus (HCMV) extensively modulates host cells, downregulating >900 human proteins during viral replication and degrading ≥133 proteins shortly after infection. The mechanism of degradation of most host proteins remains unresolved, and the functions of many viral proteins are incompletely characterised. We performed a mass spectrometry-based interactome analysis of 169 tagged, stably-expressed canonical strain Merlin HCMV proteins, and two non-canonical HCMV proteins, in infected cells. This identified a network of >3,400 virus-host and >150 virus-virus protein interactions, providing insights into functions for multiple viral genes. Domain analysis predicted binding of the viral UL25 protein to SH3 domains of NCK Adaptor Protein-1. Viral interacting proteins were identified for 31/133 degraded host targets. Finally, the uncharacterised, non-canonical ORFL147C protein was found to interact with elements of the mRNA splicing machinery, and a mutational study suggested its importance in viral replication. The interactome data will be important for future studies of herpesvirus infection

Listeria monocytogenes Exploits Host Caveolin for Cell-to-Cell Spreading

Listeria monocytogenes moves from one cell to another using actin-rich membrane protrusions that propel the bacterium toward neighboring cells. Despite cholesterol being required for this transfer process, the precise host internalization mechanism remains elusive. Here, we show that caveolin endocytosis is key to this event as bacterial cell-to-cell transfer is severely impaired when cells are depleted of caveolin-1. Only a subset of additional caveolar components (cavin-2 and EHD2) are present at sites of bacterial transfer, and although clathrin and the clathrin-associated proteins Eps15 and AP2 are absent from the bacterial invaginations, efficient L. monocytogenes spreading requires the clathrin-interacting protein epsin-1. We also directly demonstrated that isolated L. monocytogenes membrane protrusions can trigger the recruitment of caveolar proteins in a neighboring cell. The engulfment of these bacterial and cytoskeletal structures through a caveolin-based mechanism demonstrates that the classical nanometer-scale theoretical size limit for this internalization pathway is exceeded by these bacterial pathogens

Pashto Border Literature as Geopolitical Knowledge

In this article I read a selection of Pashto literatures as critical thought about geopolitics. Drawing on Michael Shapiro’s concept of aesthetic subjects, as well as on border theory, I argue that the authors, the content, and the literary networks of these works all comment on global relations of power, ranging from the local bordering effects of geopolitics, to systems of knowledge embedded in the spatiality and temporality of empire. I argue that past and current imperial processes have led to fragmenting effects in Afghan society, and literature both reflects and analyzes this. Beyond that, I argue—through the examples of authors’ lives as well as their work—that literary activity in Pashto has actively negotiated such processes throughout its history, and offers strategies for countervailing notions of global connectivity in action as well as thought. The decentralized and multiperspective images of life in these works sit in counterpoint not only to the systems-oriented views that drive military and other policy in Afghanistan during the ongoing US moment, but also to universalist perspectives upon which disciplines like world history and geopolitics traditionally rely. Additionally, though, Pashto literary networks themselves also produce alternative structures. This contributes to the aesthetic turn in IR by arguing that it is not only the aesthetic vision in works that challenges dominant knowledge; the shape of the Pashto literary formation itself, organic with its content, is an alternate form of knowledge-in-practice about the contemporary world

From Goya to Afghanistan. An essay on the ratio and ethics of medical war pictures

For centuries pictures of the dead and wounded have been part and parcel of war communications. Often the intentions were clear, ranging from medical instructions to anti-war protests. The public's response could coincide with or diverge from the publisher's intention. Following the invention of photography in the nineteenth century, and the subsequent claim of realism, the veracity of medical war images became more complex. Analysing and understanding such photographs have become an ethical obligation with democratic implications. We performed a multidisciplinary analysis of War Surgery (2008), a book containing harsh, full-colour photographs of mutilated soldiers from the Iraq and Afghanistan wars. Our analysis shows that, within the medical context, this book is a major step forward in medical war communication and documentation. In the military context the book can be conceived as an attempt to put matters right given the enormous sacrifice some individuals have suffered. For the public, the relationship between the 'reality' and 'truth' of such photographs is ambiguous, because only looking at the photographs without reading the medical context is limiting. If the observer is not familiar with medical practice, it is difficult for him to fully assess, signify and acknowledge the value and relevance of this book. We therefore assert the importance of the role of professionals and those in the humanities in particular in educating the public and initiating debate. © 2010 Taylor & Francis