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

Linking Adult Reproduction and Larval Density of Invasive Carp in a Large River

Identifying how temporal variation in the environment affects reproductive success of invasive alien species will aid in predicting future establishment and tracking dynamics of established populations. Asian carp Hypophthalmichthys spp. have become a nuisance in recent years in the Mississippi River basin. Their populations are apparently expanding, indicating favorable conditions for reproduction. During 2004 and 2005, we quantified mean density of Asian carp larvae, mean monthly gonadosomatic index (GSI) of adult males and females, and number of eggs within mature females in the lower Illinois River, a major tributary of the Mississippi River. A flood (water velocity ≥ 0.7 m/s) and drought (\u3c0.2 m/s) occurred during apparent spawning in 2004 and 2005, respectively. During 2004, Asian carp larvae were found during 32% of sampling weeks; mean GSI and fecundity were relatively low for adults, probably reflecting partially spawned individuals and perhaps low reproductive investment. During the drought of 2005, larval stages were present during only one (5%) of the sampling weeks, whereas mean GSI and fecundity of adults were high through summer. Females resorbed their eggs instead of spawning during this year. Spawning conditions during low water periods appear to be unsuitable for Asian carps, inhibiting adult spawning and yielding few larvae. Spawning conditions during 2004 were better but still yielded low densities of larvae relative to native fishes. Reproduction in the lower Illinois River appears to be linked to river flow and its impact on adult spawning decisions, but conditions for strong year-class production (i.e., high larval densities) may be rarer than previously expected

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

The Homeodomain Derived Peptide Penetratin Induces Curvature of Fluid Membrane Domains

BACKGROUND:Protein membrane transduction domains that are able to cross the plasma membrane are present in several transcription factors, such as the homeodomain proteins and the viral proteins such as Tat of HIV-1. Their discovery resulted in both new concepts on the cell communication during development, and the conception of cell penetrating peptide vectors for internalisation of active molecules into cells. A promising cell penetrating peptide is Penetratin, which crosses the cell membranes by a receptor and metabolic energy-independent mechanism. Recent works have claimed that Penetratin and similar peptides are internalized by endocytosis, but other endocytosis-independent mechanisms have been proposed. Endosomes or plasma membranes crossing mechanisms are not well understood. Previously, we have shown that basic peptides induce membrane invaginations suggesting a new mechanism for uptake, "physical endocytosis". METHODOLOGY/PRINCIPAL FINDINGS:Herein, we investigate the role of membrane lipid phases on Penetratin induced membrane deformations (liquid ordered such as in "raft" microdomains versus disordered fluid "non-raft" domains) in membrane models. Experimental data show that zwitterionic lipid headgroups take part in the interaction with Penetratin suggesting that the external leaflet lipids of cells plasma membrane are competent for peptide interaction in the absence of net negative charges. NMR and X-ray diffraction data show that the membrane perturbations (tubulation and vesiculation) are associated with an increase in membrane negative curvature. These effects on curvature were observed in the liquid disordered but not in the liquid ordered (raft-like) membrane domains. CONCLUSIONS/SIGNIFICANCE:The better understanding of the internalisation mechanisms of protein transduction domains will help both the understanding of the mechanisms of cell communication and the development of potential therapeutic molecular vectors. Here we showed that the membrane targets for these molecules are preferentially the fluid membrane domains and that the mechanism involves the induction of membrane negative curvature. Consequences on cellular uptake are discussed

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

Mystify me: Coke, terror and the symbolic immortality boost

A panel on “Marketing as Mystification” convened at the 2011 Academy of Marketing conference in Liverpool. Ideas from the Liverpool event were supplemented by commentaries from selected other authors. Each commentary explores the aspects of “mystification” observable in marketing discourses and practices. In what follows, Laufer interprets marketing mystification as modern form of sophism, Dholakia and Firat discuss mystifying ways that inequality is marketed, Varman analyzes the perversion and mystification of “development” via neoliberal marketing of “social entrepreneurship,” Mikkonen explores mystifying marketing representations of gays and lesbians, and Freund and Jacobi present a fascinating interpretation of how Coca-Cola advertising mystically reassures us that our difficult, dangerous lifeworld is actually quite hunky-dory. </jats:p