Representing and analysing molecular and cellular function in the computer

Determining the biological function of a myriad of genes, and understanding how they interact to yield a living cell, is the major challenge of the post genome-sequencing era. The complexity of biological systems is such that this cannot be envisaged without the help of powerful computer systems capable of representing and analysing the intricate networks of physical and functional interactions between the different cellular components. In this review we try to provide the reader with an appreciation of where we stand in this regard. We discuss some of the inherent problems in describing the different facets of biological function, give an overview of how information on function is currently represented in the major biological databases, and describe different systems for organising and categorising the functions of gene products. In a second part, we present a new general data model, currently under development, which describes information on molecular function and cellular processes in a rigorous manner. The model is capable of representing a large variety of biochemical processes, including metabolic pathways, regulation of gene expression and signal transduction. It also incorporates taxonomies for categorising molecular entities, interactions and processes, and it offers means of viewing the information at different levels of resolution, and dealing with incomplete knowledge. The data model has been implemented in the database on protein function and cellular processes 'aMAZE' (http://www.ebi.ac.uk/research/pfbp/), which presently covers metabolic pathways and their regulation. Several tools for querying, displaying, and performing analyses on such pathways are briefly described in order to illustrate the practical applications enabled by the model

Open borders, closed minds: the discursive construction of national identity in North Cyprus

The article investigates the discursive construction of a Turkish Cypriot national identity by the newspapers in North Cyprus. It questions the representation and reconstruction processes of national identity within the press and examines the various practices employed to mobilize readers around certain national imaginings. Using Critical Discourse Analysis, the article analyses news reports of the opening of border crossings in Cyprus in 2003, based on their content, the strategies used in the production of national identity and the linguistic means employed in the process. In this way, the nationalist tendencies embedded in news discourses, as well as discriminatory and exclusive practices, are sought out

Influence of correlations on molecular recognition

The influence of the patchiness and correlations in the distribution of hydrophobic and polar residues at the interface between two rigid biomolecules on their recognition ability is investigated in idealised coarse-grained lattice models. A general two-stage approach is utilised where an ensemble of probe molecules is designed first and the recognition ability of the probe ensemble is related to the free energy of association with both the target molecule and a different rival molecule in a second step. The influence of correlation effects are investigated using numerical Monte Carlo techniques and mean field methods. Correlations lead to different optimum characteristic lengths of the hydrophobic and polar patches for the mutual design of the two biomolecules on the one hand and their recognition ability in the presence of other molecules on the other hand.Comment: 15 pages, 5 figure

The role of metaphor in shaping the identity and agenda of the United Nations: the imagining of an international community and international threat

This article examines the representation of the United Nations in speeches delivered by its Secretary General. It focuses on the role of metaphor in constructing a common ‘imagining’ of international diplomacy and legitimising an international organisational identity. The SG legitimises the organisation, in part, through the delegitimisation of agents/actions/events constructed as threatening to the international community and to the well-being of mankind. It is a desire to combat the forces of menace or evil which are argued to motivate and determine the organisational agenda. This is predicated upon an international ideology of humanity in which difference is silenced and ‘working towards the common good’ is emphasised. This is exploited to rouse emotions and legitimise institutional power. Polarisation and antithesis are achieved through the employment of metaphors designed to enhance positive and negative evaluations. The article further points to the constitutive, persuasive and edifying power of topic and situationally-motivated metaphors in speech-making

Fantasies of subjugation: a discourse theoretical account of British policy on the European Union

The decision by the UK government to hold a referendum on Britain’s membership of the European Union (EU) marks an important development in policy towards the EU. Policy changes of this kind must be understood in the historical and political context in which they occur. This includes the framing of the policy issues within public discourse. In the UK, policies are formed in a discursive environment which is overwhelmingly hostile towards the EU. Debates are structured by a predominantly Euroskeptic discourse which emphasizes the UK’s separation and heterogeneity from the rest of the EU. Drawing on the logics of critical explanation, this article examines the structure and affective power of Euroskeptic discourses which dictate the terms of the EU debate. It presents a case study of the recent EU treaty revision process, culminating in the Treaty of Lisbon. In so doing, it enables a deeper understanding of recent policy developments

Maintenance drugs to treat opioid dependence

Extent: 5p.Michael Farrell, Alex Wodak and Linda Gowin

The study of metaphor as part of Critical Discourse Analysis

This article discusses how the study of metaphoric and more generally, figurative language use contributes to critical discourse analysis (CDA). It shows how cognitive linguists’ recognition of metaphor as a fundamental means of concept- and argument-building can add to CDA's account of meaning constitution in the social context. It then discusses discrepancies between the early model of conceptual metaphor theory and empirical data and argues that discursive-pragmatic factors as well as sociolinguistic variation have to be taken into account in order to make cognitive analyses more empirically and socially relevant. In conclusion, we sketch a modified cognitive approach informed by Relevance Theory within CDA

From Teamchef Arminius to Hermann Junior: glocalised discourse about a national foundation myth

If for much of the nineteenth and twentieth centuries, the ‘Battle of the Teutoburg Forest’, fought in 9 CE between Roman armies and Germanic tribes, was predominantly a reference point for nationalist and chauvinist discourses in Germany, the first decade of the twenty-first century has seen attempts to link public remembrance with local/regional identities on the one hand and international/intercultural contact on the other. In the run up to and during the ‘anniversary year’ of 2009, German media, sports institutions and various other official institutions articulating tourist, economic and political interests attempted to create a new ‘glocalised’ version of the public memory of the Teutoburg battle. Combining methods of Cognitive Linguistics and Critical Discourse Analysis, the paper analyses the narrative and argumentative topoi employed in this re-orientation of public memory, with a special emphasis on hybrid, post-national identity-construction. Das zweitausendjährige Gedenkjahr der „Schlacht im Teutoburger Wald“ im Jahr 2009 bot eine günstige Gelegenheit, die bis in die zweite Hälfte des 20. Jahrhunderts dominante Tradition nationalistisch–chauvinistischer Deutungen des Sieges von germanischen Stämmen über drei römische Legionen zu korrigieren und zu überwinden. Der Aufsatz analysiert mit Hilfe diskurslinguistischer Methoden die Anstrengungen regionaler Institutionen und Medien, die nationale Vereinnahmung des historischen Gedenkens kritisch zu thematisieren sowie neue, zum eine lokal situierte, zum andern international orientierte Identifikationsangebote anzubieten. Die Analyse zeigt, dass solche „de-nationalisierten“ Identifikationsangebote zwar teilweise auch früher verwendet wurden, aber heutzutage rekontextualisiert und auf innovative Weise in den Vordergrund gestellt werden

Interplay of buried histidine protonation and protein stability in prion misfolding

Misofolding of mammalian prion proteins (PrP) is believed to be the cause of a group of rare and fatal neurodegenerative diseases. Despite intense scrutiny however, the mechanism of the misfolding reaction remains unclear. We perform nuclear Magnetic Resonance and thermodynamic stability measurements on the C-terminal domains (residues 90–231) of two PrP variants exhibiting different pH-induced susceptibilities to aggregation: the susceptible hamster prion (GHaPrP) and its less susceptible rabbit homolog (RaPrP). The pKa of histidines in these domains are determined from titration experiments, and proton-exchange rates are measured at pH 5 and pH 7. A single buried highly conserved histidine, H187/H186 in GHaPrP/RaPrP, exhibited a markedly down shifted pKa ~5 for both proteins. However, noticeably larger pH-induced shifts in exchange rates occur for GHaPrP versus RaPrP. Analysis of the data indicates that protonation of the buried histidine destabilizes both PrP variants, but produces a more drastic effect in the less stable GHaPrP. This interpretation is supported by urea denaturation experiments performed on both PrP variants at neutral and low pH, and correlates with the difference in disease susceptibility of the two species, as expected from the documented linkage between destabilization of the folded state and formation of misfolded and aggregated species