Influence of end-capping on the self-assembly of model amyloid peptide fragments

The influence of charge and aromatic stacking interactions on the self-assembly of a series of four model amyloid peptides has been examined. The four model peptides are based on the KLVFF motif from the amyloid Beta peptide, ABeta(16-20) extended at the N terminus with two Beta-alanine residues. We have studied NH2-BetaABetaAKLVFF-COOH (FF), NH2-BetaABetaAKLVFCOOH (F), CH3CONH-BetaABetaAKLVFF-CONH2 (CapF), and CH3CONH-BetaABetaAKLVFFCONH2 (CapFF). The former two are uncapped (net charge plus 2) and differ by one hydrophobic phenylalanine residue; the latter two are the analogous capped peptides (net charge plus 1). The self-assembly characteristics of these peptides are remarkably different and strongly dependent on concentration. NMR shows a shift from carboxylate to carboxylic acid forms upon increasing concentration. Saturation transfer measurements of solvent molecules indicate selective involvement of phenylalanine residues in driving the self-assembly process of CapFF due presumably to the effect of aromatic stacking interactions. FTIR spectroscopy reveals beta-sheet features for the two peptides containing two phenylalanine residues but not the single phenylalanine residue, pointing again to the driving force for self-assembly. Circular dichroism (CD) in dilute solution reveals the polyproline II conformation, except for F which is disordered. We discuss the relationship of this observation to the significant pH shift observed for this peptide when compared the calculated value. Atomic force microscopy and cryogenic-TEM reveals the formation of twisted fibrils for CapFF, as previously also observed for FF. The influence of salt on the self-assembly of the model beta-sheet forming capped peptide CapFF was investigated by FTIR. Cryo-TEM reveals that the extent of twisting decreases with increased salt concentration, leading to the formation of flat ribbon structures. These results highlight the important role of aggregation-induced pKa shifts in the self-assembly of model beta-sheet peptides.

Phase separation in thin films of end-grafted block copolymers

An atomic force microscopy investigation was carried out on various thick (30–120 nm) polymethyl methacrylate-bpolystyrene and poly(2-(dimethyl amino)ethyl methacrylate)-b-polystyrene films prepared via a grafting-from method. The structure of the films was examined with both topographic and phase imaging. Several different morphologies were observed including a perforated lamellar phase with irregular perforations. In addition, complementary small-angle X-ray scattering and reflectometry results measurements on a non-grafted polymer are presented.

Direct observation of time-resolved polymorphic states in the self-assembly of end-capped heptapeptides

Amyloid fibrils resulting from uncontrolled peptide aggregation are associated with several neurodegenerative diseases. Their polymorphism depends on a number of factors including pH, ionic strength, electrostatic interactions, hydrophobic interactions, hydrogen bonding, aromatic stacking interactions, and chirality. Understanding the mechanism of amyloid fibril formation can improve strategies towards the prevention of fibrillation processes and enable a wide range of potential applications in nanotemplating and nanotechnology.

The death of Osama bin Laden - the end of Al-Qaeda's Pan-Islamic ambition?

This paper evaluates the implications of Osama bin Ladin’s death for the future of al-Qaeda’s global jihad. It critically examines the debate as to the make-up of the group and identifies bin Ladin’s primary role as chief ideologue advocating a defensive jihad to liberate the umma. The rationale and appeal of bin Ladin’s message and Muslims’ reaction to both his statements and al-Qaeda’s increasing use of sectarian violence are assessed in the context of Pan-Islam as political ideology. The paper concludes that while the ideal of Islamic unity and the sentiment of Muslim solidarity are unlikely to vanish, al-Qaeda’s violent jihad has not only failed to achieve these goals but has worked against it, thereby confining it to the political margins.

Like the living end

Seven-part elegy for David Mather (1954-2010)

A largely intolerable combination of two mainly unconnected texts: 1. Description of the Barefoot in the Head event, at BHQU, NY, 12/11/09; 2. Fictioning and the End

An evaluation of the 'Barefoot in the Head' performance event, I co-curated with Alun Rowlands and Mark Beasley, at Bruce High Quality Foundation University, New York, as part of Performa 09 New York, 12 November 2009 - an examination of my own performance and the other performances occurring simultaneously at the event.

Agricultural tenancy reform: the end of law; or a new popular culture?

This paper applies a reading of the postmodernisation of law to the incremental reform of agricultural holdings legislation over the last century. In charting the shifting legal basis of agricultural tenancies, from ‘black letter’ positivism to the cultural contextuality of sumptuary law, the paper theorises that the underlying political imperative has been allied to the changing significance of property ownership and use. Rather than reflecting the long-term official desire to maintain the let sector in British agriculture, however, the paper argues that this process has had other aims. In particular, it has been about an annexation of law to legitimise the retention of landowner power while presenting a rhetorical ‘democratisation’ of farming, away from its plutocratic associations and towards a new narrative of ‘depersonalised’ business.

Urban planning under Major: the end of Thatcherism?

This paper explores the urban planning legacy left by Mrs Thatcher. To what extent has Mr Major continued with her approach? Has he developed new directions? This broad question provides the background for an examination of the changes to the planning system since Mrs Thatcher left office. The main themes covered are the new plan-led emphasis, the increase in the coverage of environmental issues, the question of whether a more people oriented perspective has developed with Major's softer touch and the Citizen's Charter and the property-led approach to urban regeneration. The paper concludes that although the contradictions of Thatcherism have led to the relaxation of certain ideological stances to planning, the central themes of Thatcherism - individualism and centralisation - continue unabated.

Gut microbial catabolism of grape seed flavan-3-ols by human faecal microbiota. Targetted analysis of precursor compounds, intermediate metabolites and end-products.

In vitro batch culture fermentations were conducted with grape seed polyphenols and human faecal microbiota, in order to monitor both changes in precursor flavan-3-ols and the formation of microbial-derived metabolites. By the application of UPLC-DAD-ESI-TQ MS, monomers, and dimeric and trimeric procyanidins were shown to be degraded during the first 10 h of fermentation, with notable inter-individual differences being observed between fermentations. This period (10 h) also coincided with the maximum formation of intermediate metabolites, such as 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone and 4-hydroxy-5-(3′,4′-dihydroxyphenyl)-valeric acid, and of several phenolic acids, including 3-(3,4-dihydroxyphenyl)-propionic acid, 3,4-dihydroxyphenylacetic acid, 4-hydroxymandelic acid, and gallic acid (5–10 h maximum formation). Later phases of the incubations (10–48 h) were characterised by the appearance of mono- and non-hydroxylated forms of previous metabolites by dehydroxylation reactions. Of particular interest was the detection of γ-valerolactone, which was seen for the first time as a metabolite from the microbial catabolism of flavan-3-ols. Changes registered during fermentation were finally summarised by a principal component analysis (PCA). Results revealed that 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone was a key metabolite in explaining inter-individual differences and delineating the rate and extent of the microbial catabolism of flavan-3-ols, which could finally affect absorption and bioactivity of these compounds.