Role of the AP2 beta-appendage hub in recruiting partners for clathrin-coated vesicle assembly

Adaptor protein complex 2 alpha and beta-appendage domains act as hubs for the assembly of accessory protein networks involved in clathrin-coated vesicle formation. We identify a large repertoire of beta-appendage interactors by mass spectrometry. These interact with two distinct ligand interaction sites on the beta-appendage (the "top" and "side" sites) that bind motifs distinct from those previously identified on the alpha-appendage. We solved the structure of the beta-appendage with a peptide from the accessory protein Eps15 bound to the side site and with a peptide from the accessory cargo adaptor beta-arrestin bound to the top site. We show that accessory proteins can bind simultaneously to multiple appendages, allowing these to cooperate in enhancing ligand avidities that appear to be irreversible in vitro. We now propose that clathrin, which interacts with the beta-appendage, achieves ligand displacement in vivo by self-polymerisation as the coated pit matures. This changes the interaction environment from liquid-phase, affinity-driven interactions, to interactions driven by solid-phase stability ("matricity"). Accessory proteins that interact solely with the appendages are thereby displaced to areas of the coated pit where clathrin has not yet polymerised. However, proteins such as beta-arrestin (non-visual arrestin) and autosomal recessive hypercholesterolemia protein, which have direct clathrin interactions, will remain in the coated pits with their interacting receptors.

DED or alive: assembly and regulation of the death effector domain complexes.

Death effector domains (DEDs) are protein-protein interaction domains initially identified in proteins such as FADD, FLIP and caspase-8 involved in regulating apoptosis. Subsequently, these proteins have been shown to have important roles in regulating other forms of cell death, including necroptosis, and in regulating other important cellular processes, including autophagy and inflammation. Moreover, these proteins also have prominent roles in innate and adaptive immunity and during embryonic development. In this article, we review the various roles of DED-containing proteins and discuss recent developments in our understanding of DED complex formation and regulation. We also briefly discuss opportunities to therapeutically target DED complex formation in diseases such as cancer.

The Northern Ireland Assembly Election 2011

Following the first full term of regional government in the province since 1972, the Northern Ireland Assembly election held on 5 May 2011 saw the continuation of several trends. Foremost, the Democratic Unionist Party and Sinn Féin bolstered further their positions as leaders of their respective communities, with the Social Democratic and Labour Party and Ulster Unionist Party losing yet more ground. Building on their decision to enter power-sharing government together in 2007, the two largest parties framed themselves as the progressive choice for voters. As this was the first Assembly election since St Andrews (2006), much of the campaign dialogue centred on the prospect of a Sinn Féin First Minister, a concern highlighted by both unionist parties. The campaign also focused on ‘normal’ socio-economic political issues and possible institutional reform. The absence of inter-party conflict led to the campaign being perceived as the most mundane in living memory, with fears of a record low turnout realised.

An Automated Design Framework for Assembly Task Simulation

This paper presents an automated design framework for the development of individual part forming tools for a composite stiffener. The framework uses parametrically developed design geometries for both the part and its layup tool. The framework has been developed with a functioning user interface where part / tool combinations are passed to a virtual environment for utility based assessment of their features and assemblability characteristics. The work demonstrates clear benefits in process design methods with conventional design timelines reduced from hours and days to minutes and seconds. The methods developed here were able to produce a digital mock up of a component with its associated layup tool in less than 3 minutes. The virtual environment presenting the design to the designer for interactive assembly planning was generated in 20 seconds. Challenges still exist in determining the level of reality required to provide an effective learning environment in the virtual world. Full representation of physical phenomena such as gravity, part clashes and the representation of standard build functions require further work to represent real physical phenomena more accurately.

Resource Efficient Configuration of an Aircraft Assembly Line

The design of efficient assembly systems can significantly contribute to the profitability of products and the competitiveness of manufacturing industries. The configuration of a an efficient assembly line can be supported by suitable methodologies and techniques, such as design for manufacture and assembly, assembly sequence planning, assembly line balancing, lean manufacturing and optimization techniques. In this paper, these methods are applied with reference to the industrial case study of the assembly line of a Skycar light aircraft. The assembly process sequence is identified taking into account the analysis of the assembly structure and the required precedence constraints, and diverse techniques are applied to optimize the assembly line performance. Different line configurations are verified through discrete event simulation to assess the potential increase of efficiency and throughput in a digital environment and propose the most suitable configuration of the assembly line.

Virtual Ergonomics and Time optimization of a Railway Coach Assembly Line

The recent drive towards timely multiple product realizations has caused most Manufacturing Enterprises (MEs) to develop more flexible assembly lines supported by better manufacturing design and planning. The aim of this work is to develop a methodology which will support feasibility analyses of assembly tasks, in order to simulate either a manufacturing process or a single work-cell in which digital human models act. The methodology has been applied in a case study relating to a railway industry. Simulations were applied to help standardize the methodology and suggest new solutions for realizing ergonomic and efficient assembly processes in the railway industry.