Self-organizing actin waves that simulate phagocytic cup structures

This report deals with actin waves that are spontaneously generated on the planar, substrate-attached surface of Dictyostelium cells. These waves have the following characteristics. (1) They are circular structures of varying shape, capable of changing the direction of propagation. (2) The waves propagate by treadmilling with a recovery of actin incorporation after photobleaching of less than 10 seconds. (3) The waves are associated with actin-binding proteins in an ordered 3-dimensional organization: with myosin-IB at the front and close to the membrane, the Arp2/3 complex throughout the wave, and coronin at the cytoplasmic face and back of the wave. Coronin is a marker of disassembling actin structures. (4) The waves separate two areas of the cell cortex that differ in actin structure and phosphoinositide composition of the membrane. The waves arise at the border of membrane areas rich in phosphatidylinositol (3,4,5) trisphosphate (PIP3). The inhibition of PIP3 synthesis reversibly inhibits wave formation. (5) The actin wave and PIP3 patterns resemble 2-dimensional projections of phagocytic cups, suggesting that they are involved in the scanning of surfaces for particles to be taken up

Marketing madness or financial folly?: Implementing equity crowdfunding in the record industry

Purpose The purpose of this paper is to explore the implementation of equity crowdfunding (ECF) within the record industry in terms of challenges and opportunities, in addition to the marketing and financial implications for independent music artists and major record labels. Design/methodology/approach This study adopted a qualitative methodology consisting of two-stage interview-based research methods. A total of 44 semi-structured in-depth interviews were conducted with the CEOs of ECF platforms in the record industry, other related record industry informants, independent artist managers and senior executives from major record labels. Findings The loyalty aspect of ECF may have significant marketing potential in terms of inconspicuously using the equity platform as a “prosumer” identification mechanism. As this early career stage of artists is delicate in terms of establishing trust and patronage from their fans, these early marketing and ECF ventures should be implemented directly from the artist without external third-party involvement. Research limitations/implications The implications of this paper’s findings and theoretical model are not limited to the two studied stakeholder groups of the record industry. The insights in relation to the obstinate lack of understanding and clarity (particularly for independent artists) which surround ECF are likely to influence short-term strategic approaches by other players throughout the wider music industry. Practical implications The insights regarding negative approaches towards ECF by the labels may influence future “coopetition strategies” for independent labels, as they seek to navigate the changing industry dynamics. Originality/value This paper is the first study to empirically explore the predominantly under-researched area of ECF implementation in the record industry in terms of marketing and financial consequences for artists and labels. </jats:sec

Bistability in the actin cortex

Multi-color fluorescence imaging experiments of wave forming Dictyostelium cells have revealed that actin waves separate two domains of the cell cortex that differ in their actin structure and phosphoinositide composition. We propose a bistable model of actin dynamics to account for these experimental observation. The model is based on the simplifying assumption that the actin cytoskeleton is composed of two distinct network types, a dendritic and a bundled network. The two structurally different states that were observed in experiments correspond to the stable fixed points in the bistable regime of this model. Each fixed point is dominated by one of the two network types. The experimentally observed actin waves can be considered as trigger waves that propagate transitions between the two stable fixed points

Improving the Health of Older Prisoners: Nutrition and Exercise in Correctional Institutions

This qualitative article presents and compares the views of older prisoners and expert stakeholders on the topic of nutrition and exercise. The study highlights measures for improving the health of older prisoners. Older prisoners report the need to improve quality of meals provided in prison. They note that prison food is of poor quality and not adapted to their needs. With regard to exercise, they point out the lack of proper opportunities to engage in exercise and sports, and describe several factors that make physical activities either unsuitable or unfeasible. Expert stakeholders see prison as an opportunity to improve the health of those convicted of crimes. In light of the increasing number of older prisoners, age-appropriate nutritional and exercise interventions should take priority in prisons

The Second Transmembrane Domain of P2X7 Contributes to Dilated Pore Formation

Activation of the purinergic receptor P2X7 leads to the cellular permeability of low molecular weight cations. To determine which domains of P2X7 are necessary for this permeability, we exchanged either the C-terminus or portions of the second transmembrane domain (TM2) with those in P2X1 or P2X4. Replacement of the C-terminus of P2X7 with either P2X1 or P2X4 prevented surface expression of the chimeric receptor. Similarly, chimeric P2X7 containing TM2 from P2X1 or P2X4 had reduced surface expression and no permeability to cationic dyes. Exchanging the N-terminal 10 residues or C-terminal 14 residues of the P2X7 TM2 with the corresponding region of P2X1 TM2 partially restored surface expression and limited pore permeability. To further probe TM2 structure, we replaced single residues in P2X7 TM2 with those in P2X1 or P2X4. We identified multiple substitutions that drastically changed pore permeability without altering surface expression. Three substitutions (Q332P, Y336T, and Y343L) individually reduced pore formation as indicated by decreased dye uptake and also reduced membrane blebbing in response to ATP exposure. Three others substitutions, V335T, S342G, and S342A each enhanced dye uptake, membrane blebbing and cell death. Our results demonstrate a critical role for the TM2 domain of P2X7 in receptor function, and provide a structural basis for differences between purinergic receptors. © 2013 Sun et al

Identification of epitopes recognised by mucosal CD4+ T-cell populations from cattle experimentally colonised with Escherichia coli O157:H7

Additional file 5. Sequence alignment of Intimin epitopes against Intimin sequences from non-O157 EHEC serotypes. Alignment of Intimin CD4+ T-cell epitope sequences with representative Intimin sequences from EHEC serotypes O145, O127, O26, O103, O121, O45 and O111. Percentage values indicate % similarity to the EHEC O157:H7 reference sequence

Comparison between a linear versus a macrocyclic contrast agent for whole body MR angiography in a clinical routine setting

<p>Abstract</p> <p>Background</p> <p>Previous experiences of whole body MR angiography are predominantly available in linear 0.5 M gadolinium-containing contrast agents. The aim of this study was to compare image quality on a four-point scale (range 1–4) and diagnostic accuracy of a 1.0 M macrocyclic contrast agent (gadobutrol, n = 80 patients) with a 0.5 M linear contrast agent (gadopentetate dimeglumine, n = 85 patients) on a 1.5 T whole body MR system. Digital subtraction angiography served as standard of reference.</p> <p>Results</p> <p>All examinations yielded diagnostic image quality. There was no significant difference in image quality (3.76 ± 0.3 versus 3.78 ± 0.3, p = n.s.) and diagnostic accuracy observed. Sensitivity and specificity of the detection of hemodynamically relevant stenoses was 93%/95% in the gadopentetate dimeglumine group and 94%/94% in the gadobutrol group, respectively.</p> <p>Conclusion</p> <p>The high diagnostic accuracy of gadobutrol in the clinical routine setting is of high interest as medical authorities (e.g. the European Agency for the Evaluation of Medicinal Products) recommend macrocyclic contrast agents especially to be used in patients with renal failure or dialysis.</p

Keep them alive! Design and Evaluation of the “Community Fostering Reference Model”

Firms host online communities for commercial purposes, for example in order to integrate customers into ideation for new product development. The success of these firm-hosted online communities depends entirely on the cooperation of a high number of customers that constantly produce valuable knowledge for firms. However, in practice, the majority of successfully implemented communities suffers from stagnation and even a decrease of member activities over time. Literature provides numerous guidelines on how to build and launch these online communities. While these models describe the initial steps of acquiring and activating a community base from scratch very well and explicitly, they neglect continuous member activation and acquistion after a successful launch. Against this background, the authors propose the Community Fostering Reference Model (CoFoRM), which represents a set of general procedures and instruments to continuously foster member activity. In this paper, the authors present the theory-driven design as well as the evaluation of the CoFoRM in a practical use setting. The evaluation results reveal that the CoFoRM represents a valuable instrument in the daily working routine of community managers, since it efficiently helps activating community members especially in the late phases of a community’s LifeCycle

Pharmacology and Surface Electrostatics of the K Channel Outer Pore Vestibule

In spite of a generally well-conserved outer vestibule and pore structure, there is considerable diversity in the pharmacology of K channels. We have investigated the role of specific outer vestibule charged residues in the pharmacology of K channels using tetraethylammonium (TEA) and a trivalent TEA analog, gallamine. Similar to Shaker K channels, gallamine block of Kv3.1 channels was more sensitive to solution ionic strength than was TEA block, a result consistent with a contribution from an electrostatic potential near the blocking site. In contrast, TEA block of another type of K channel (Kv2.1) was insensitive to solution ionic strength and these channels were resistant to block by gallamine. Neutralizing either of two lysine residues in the outer vestibule of these Kv2.1 channels conferred ionic strength sensitivity to TEA block. Kv2.1 channels with both lysines neutralized were sensitive to block by gallamine, and the ionic strength dependence of this block was greater than that for TEA. These results demonstrate that Kv3.1 (like Shaker) channels contain negatively charged residues in the outer vestibule of the pore that influence quaternary ammonium pharmacology. The presence of specific lysine residues in wild-type Kv2.1 channels produces an outer vestibule with little or no net charge, with important consequences for quaternary ammonium block. Neutralizing these key lysines results in a negatively charged vestibule with pharmacological properties approaching those of other types of K channels

An Excitable Cortex and Memory Model Successfully Predicts New Pseudopod Dynamics

Motile eukaryotic cells migrate with directional persistence by alternating left and right turns, even in the absence of external cues. For example, Dictyostelium discoideum cells crawl by extending distinct pseudopods in an alternating right-left pattern. The mechanisms underlying this zig-zag behavior, however, remain unknown. Here we propose a new Excitable Cortex and Memory (EC&M) model for understanding the alternating, zig-zag extension of pseudopods. Incorporating elements of previous models, we consider the cell cortex as an excitable system and include global inhibition of new pseudopods while a pseudopod is active. With the novel hypothesis that pseudopod activity makes the local cortex temporarily more excitable – thus creating a memory of previous pseudopod locations – the model reproduces experimentally observed zig-zag behavior. Furthermore, the EC&M model makes four new predictions concerning pseudopod dynamics. To test these predictions we develop an algorithm that detects pseudopods via hierarchical clustering of individual membrane extensions. Data from cell-tracking experiments agrees with all four predictions of the model, revealing that pseudopod placement is a non-Markovian process affected by the dynamics of previous pseudopods. The model is also compatible with known limits of chemotactic sensitivity. In addition to providing a predictive approach to studying eukaryotic cell motion, the EC&M model provides a general framework for future models, and suggests directions for new research regarding the molecular mechanisms underlying directional persistence