A pentapeptide as minimal antigenic determinant for MHC class I-restricted T lymphocytes

Peptides that are antigenic for T lymphocytes are ligands for two receptors, the class I or II glycoproteins that are encoded by genes in the major histocompatibility complex, and the idiotypic / chain T-cell antigen receptor1–9. That a peptide must bind to an MHC molecule to interact with a T-cell antigen receptor is the molecular basis of the MHC restriction of antigen-recognition by T lymphocytes10,11. In such a trimolecular interaction the amino-acid sequence of the peptide must specify the contact with both receptors: agretope residues bind to the MHC receptor and epitope residues bind to the T-cell antigen receptor12,13. From a compilation of known antigenic peptides, two algorithms have been proposed to predict antigenic sites in proteins. One algorithm uses linear motifs in the sequence14, whereas the other considers peptide conformation and predicts antigenicity for amphipathic -helices15,16. We report here that a systematic delimitation of an antigenic site precisely identifies a predicted pentapeptide motif as the minimal antigenic determinant presented by a class I MHC molecule and recognized by a cytolytic T lymphocyte clone

Territorial rights and colonial wrongs

What is wrong with colonialism? The standard—albeit often implicit—answer to this question has been that colonialism was wrong because it violated the territorial rights of indigenous peoples, where territorial rights were grounded on acquisition theories. Recently, the standard view has come under attack: according to critics, acquisition based accounts do not provide solid theoretical grounds to condemn colonial relations. Indeed, historically they were used to justify colonialism. Various alternative accounts of the wrong of colonialism have been developed. According to some, colonialism involved a violation of territorial rights grounded on legitimate state theory. Others reject all explanations of colonialism's wrongfulness based on territorial rights, and argue that colonial practices were wrong because they departed from ideals of economic, social, and political association. In this article, we articulate and defend the standard view against critics: colonialism involved a procedural wrong; this wrong is not the violation of standards of equality and reciprocity, but the violation of territorial rights; and the best foundation for such territorial rights is acquisition based, not legitimacy based. We argue that this issue is not just of historical interest, it has relevant implications for the normative evaluation of contemporary inequalities

Reciprocity as a foundation of financial economics

This paper argues that the subsistence of the fundamental theorem of contemporary financial mathematics is the ethical concept ‘reciprocity’. The argument is based on identifying an equivalence between the contemporary, and ostensibly ‘value neutral’, Fundamental Theory of Asset Pricing with theories of mathematical probability that emerged in the seventeenth century in the context of the ethical assessment of commercial contracts in a framework of Aristotelian ethics. This observation, the main claim of the paper, is justified on the basis of results from the Ultimatum Game and is analysed within a framework of Pragmatic philosophy. The analysis leads to the explanatory hypothesis that markets are centres of communicative action with reciprocity as a rule of discourse. The purpose of the paper is to reorientate financial economics to emphasise the objectives of cooperation and social cohesion and to this end, we offer specific policy advice

Workdays, in-between workdays and the weekend: a diary study on effort and recovery

Contains fulltext : 55892.pdf (publisher's version ) (Closed access)16 p

Dynamic Measurements of Membrane Insertion Potential of Synthetic Cell Penetrating Peptides

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Langmuir, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://doi.org/10.1021/la403370p.Cell penetrating peptides (CPPs) have been established as excellent candidates for mediating drug delivery into cells. When designing synthetic CPPs for drug delivery applications, it is important to understand their ability to penetrate the cell membrane. In this paper, anionic or zwitterionic phospholipid monolayers at the air-water interface are used as model cell membranes to monitor the membrane insertion potential of synthetic CPPs. The insertion potential of CPPs having different cationic and hydrophobic amino acids were recorded using a Langmuir monolayer approach that records peptide adsorption to model membranes. Fluorescence microscopy was used to visualize alterations in phospholipid packing due to peptide insertion. All CPPs had the highest penetration potential in the presence of anionic phospholipids. In addition, two of three amphiphilic CPPs inserted into zwitterionic phospholipids, but none of the hydrophilic CPPs did. All the CPPs studied induced disruptions in phospholipid packing and domain morphology, which were most pronounced for amphiphilic CPPs. Overall, small changes to amino acids and peptide sequences resulted in dramatically different insertion potentials and membrane reorganization. Designers of synthetic CPPs for efficient intracellular drug delivery should consider small nuances in CPP electrostatic and hydrophobic properties

Are Hermeneutics and the Austrian Approach Compatible? A Clarifying Analysis

This paper investigates the merging of the Austrian Approach and Hermeneutics under a new light. It defends a middle ground between the standpoint of the Austrian hermeneutists and that of their critics. The latter, especially Rothbard, considered hermeneutics to be incompatible with Austrian School because they confused hermeneutics with what Mises calls "polylogism", i.e. with cognitive nihilism. Their view was incorrect, but their criticism of the Austrian hermeneutists was not completely unfounded. Austrian hermeneutists did not clearly separate what they called hermeneutics from the postmodernist epistemologies of authors such as Derrida, Kuhn, and Rorty. This article demonstrates that hermeneutics as intended by Gadamer, its greatest theorist, has nothing to do with postmodernism. It is a fallibilist theory of the objective truth in the sense of Popper. So it is compatible both with the Austrians' antipolylogism and their methodological individualism

Fighting Conflict: Violent Splits or Healthy Divides?

In this study, we develop a theory to understand how groups with strong divisions may, paradoxically, help members to cope with conflict and injustice. We test our theoretical predictions using a survey methodology and the data from 72 work groups across different industries. Consistent with our hypotheses, we found that group faultlines weakened the positive relationships between injustice and psychological health

Authentic leadership, followership, and psychological capital as antecedents of work engagement

The present study investigated authentic leadership, psychological capital, and followership behaviour influences on work engagement of employees . Respondents were 901 South African employees within the healthcare industry organisation (n = 647) and mining industry (n = 254) . The employees completed questionnaires on authentic leadership, psychological capital, and followership behaviour, and work engagement . Results following structural equation modelling and mediation analysis suggest work engagement to be explained by the psychological capital of the employee rather than by authentic leadership qualities . Improving employee psychological capital has the potential to enhance the levels of work engagement of employees

Distinct Behaviour of the Homeodomain Derived Cell Penetrating Peptide Penetratin in Interaction with Different Phospholipids

Penetratin is a protein transduction domain derived from the homeoprotein Antennapedia. Thereby it is currently used as a cell penetrating peptide to introduce diverse molecules into eukaryotic cells, and it could also be involved in the cellular export of transcription factors. Moreover, it has been shown that it is able to act as an antimicrobial agent. The mechanisms involved in all these processes are quite controversial.In this article, we report spectroscopic, calorimetric and biochemical data on the penetratin interaction with three different phospholipids: phosphatidylcholine (PC) and phosphatidylethanolamine (PE) to mimic respectively the outer and the inner leaflets of the eukaryotic plasma membrane and phosphatidylglycerol (PG) to mimic the bacterial membrane. We demonstrate that with PC, penetratin is able to form vesicle aggregates with no major change in membrane fluidity and presents no well defined secondary structure organization. With PE, penetratin aggregates vesicles, increases membrane rigidity and acquires an α-helical structure. With PG membranes, penetratin does not aggregate vesicles but decreases membrane fluidity and acquires a structure with both α-helical and β–sheet contributions.These data from membrane models suggest that the different penetratin actions in eukaryotic cells (membrane translocation during export and import) and on prokaryotes may result from different peptide and lipid structural arrangements. The data suggest that, for eukaryotic cell penetration, penetratin does not acquire classical secondary structure but requires a different conformation compared to that in solution