Overlapping properties of the short membrane-active peptide BP100 with (i) Polycationic TAT and (ii) α-helical Magainin Family Peptides

Copyright © 2021 Mink, Strandberg, Wadhwani, Melo, Reichert, Wacker, Castanho and Ulrich. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.BP100 is a short, designer-made membrane-active peptide with multiple functionalities: antimicrobial, cell-penetrating, and fusogenic. Consisting of five lysines and 6 hydrophobic residues, BP100 was shown to bind to lipid bilayers as an amphipathic a-helix, but its mechanism of action remains unclear. With these features, BP100 embodies the characteristics of two distinctly different classes of membrane-active peptides, which have been studied in detail and where the mechanism of action is better understood. On the one hand, its amphiphilic helical structure is similar to the pore forming magainin family of antimicrobial peptides, though BP100 is much too short to span the membrane. On the other hand, its length and high charge density are reminiscent of the HIV-TAT family of cell penetrating peptides, for which inverted micelles have been postulated as translocation intermediates, amongst other mechanisms. Assays were performed to test the antimicrobial and hemolytic activity, the induced leakage and fusion of lipid vesicles, and cell uptake. From these results the functional profiles of BP100, HIV-TAT, and the magainin-like peptides magainin 2, PGLa, MSI-103, and MAP were determined and compared. It is observed that the activity of BP100 resembles most closely the much longer amphipathic a-helical magainin-like peptides, with high antimicrobial activity along with considerable fusogenic and hemolytic effects. In contrast, HIV-TAT shows almost no antimicrobial, fusogenic, or hemolytic effects. We conclude that the amphipathic helix of BP100 has a similar membranebased activity as magainin-like peptides and may have a similar mechanism of action.This work was supported financially by the BIF-TM program of the Helmholtz-Gemeinschaft; by the DFG grant INST 121384/58-1 FUGG; and by the DAAD “Portugal - Acções Integradas Luso-Alemãs/DAAD-GRIC” grant D/07/13644.info:eu-repo/semantics/publishedVersio

Temperature‐Dependent Re‐alignment of the Short Multifunctional Peptide BP100 in Membranes Revealed by Solid‐State NMR Spectroscopy and Molecular Dynamics Simulations

BP100 is a cationic undecamer peptide with antimicrobial and cell-penetrating activities. The orientation of this amphiphilic α-helix in lipid bilayers was examined under numerous conditions using solid-state 19F, 15N and 2H NMR. At high temperatures in saturated phosphatidylcholine lipids, BP100 lies flat on the membrane surface, as expected. Upon lowering the temperature towards the lipid phase transition, the helix is found to flip into an upright transmembrane orientation. In thin bilayers, this inserted state was stable at low peptide concentration, but thicker membranes required higher peptide concentrations. In the presence of lysolipids, the inserted state prevailed even at high temperature. Molecular dynamics simulations suggest that BP100 monomer insertion can be stabilized by snorkeling lysine side chains. These results demonstrate that even a very short helix like BP100 can span (and thereby penetrate through) a cellular membrane under suitable conditions

PACT-UK (PAncreatic Cancer reporting Template-UK): A cross-specialty multi-institutional consensus panel development of a standardised radiological reporting proforma for pancreatic cancer

\ua9 Author(s) (or their employer(s)) 2023. Objective: Appropriate staging of pancreatic cancer is essential to ensure patients are offered all treatment options. This multispecialty national collaborative consensus project aimed to develop a succinct radiological reporting template, using the concept of structured reporting, to allow a more standardised means of reporting pancreatic cancer and ultimately optimise both patient care and research protocol design. Methods and analysis: In stage one, a core group of stakeholders (oncologists, radiologists and surgeons) identified the current landscape of radiological reporting, including a blinded radiological validation study and a national survey of consultant HPB surgeons. Stage two used consensus panel development methodology to generate a provisional template draft. Stage three involved trialling the template across all UK HPB units, with feedback assisting the development of a final version of the template. Results: Stage one results identified a core dataset to develop a provisional template. Every UK Hepatopancreatobiliary (HPB) unit trialled this in clinical practice, leading to further refinements via consensus meetings. Ideal factors regarding tumour staging, extent of vascular involvement and response to systemic anticancer therapy were identified. This resulted in the generation of the PACT-UK (PAncreatic Cancer reporting Template-UK) template that is presented within the manuscript, as well as a user guide. Conclusion: This project has successfully produced the first consensus-driven radiological reporting template for pancreatic cancer, with the aim of its use becoming standard practice in the UK, while upcoming workshops facilitated by Royal College of Radiologists/British Society of Gastrointestinal and Abdominal Radiology will establish buy-in from radiologists at all HPB units. Plans for the use of PACT-UK within national audit and clinical trials are underway

New Economy, Old Central Banks?

Proponents of the so-called New Economy claim that it entails a structural change of the economy. Such a change, in turn, would require the central bank to rethink its monetary policy to the extent that traditional relationships between inf1ation and economic growth are no longer valid. But such a rethinking presupposes that prospective advances in information technology and other factors associated with the new economy do not threaten the capacity of central banks to stabilise the general level of prices. It is the aim of this paper to shed some light on the latter, by analysing the monetary transmission mechanism in a 'new economy' environment. We argue that, although the form of central bank instruments and current methods for implementing monetary policy may change, the goals that the policy makers try to achieve by employing these instruments remain valid, and achievable

The Materiality of Absence:Organizing and the case of the incomplete cathedral

This study explores the role of absences in making organizing possible. By engaging with Lefebvre’s spatial triad as the interconnections between conceived (planned), perceived (experienced through practice) and lived (felt and imagined) spaces, we challenge the so-called metaphysics of presence in organization studies. We draw on the insights offered by the project of construction of Siena Cathedral during the period 1259– 1357 and we examine how it provided a space for the actors involved to explore their different (civic, architectural and religious) intentions. We show that, as the contested conceived spaces of the cathedral were connected to architectural practices, religious powers and civic symbols, they revealed the impossibility for these intentions to be fully represented. It was this impossibility that provoked an ongoing search for solutions and guaranteed a combination of dynamism and persistence of both the material architecture of the cathedral and the project of construction. The case of Siena Cathedral therefore highlights the role of absence in producing organizing effects not because absence eventually takes form but because of the impossibility to fully represent it

The Burden of History in the Family Business Organization

In this paper we focus on the study of history through the use of narratives, within the context of the prevalent form of organization worldwide: the family business. Specifically we consider the dilemma of the impossible gift of succession using Nietzsche's discussion of the burden of history and paralleling the story of a family business succession with that of Shakespeare's King Lear. This way, we seek to make a contribution to organizational studies by answering recent calls to engage more with history in studies of business organizations. By implication, the study also initiates an integration of family business studies into organization studies