David Thomas

Bio: David Thomas is an academic researcher from University of Birmingham. The author has contributed to research in topics: History of religions & Islam. The author has an hindex of 12, co-authored 66 publications receiving 622 citations. Previous affiliations of David Thomas include Spanish National Research Council & Brill Publishers.

The interplay between PolyQ and protein context delays aggregation by forming a reservoir of protofibrils.

Abstract: Polyglutamine (polyQ) diseases are inherited neurodegenerative disorders caused by the expansion of CAG codon repeats, which code for polyQ in the corresponding gene products. These diseases are associated with the presence of amyloid-like protein aggregates, induced by polyQ expansion. It has been suggested that the soluble aggregates rather than the mature fibrillar aggregates are the toxic species, and that the aggregation properties of polyQ can be strongly modulated by the surrounding protein context. To assess the importance of the protein carrier in polyQ aggregation, we have studied the misfolding pathway and the kinetics of aggregation of polyQ of lengths above (Q41) and below (Q22) the pathological threshold fused to the well-characterized protein carrier glutathione S-transferase (GST). This protein, chosen as a model system, is per se able to misfold and aggregate irreversibly, thus mimicking the behaviour of domains of naturally occurring polyQ proteins. We prove that, while it is generally accepted that the aggregation kinetics of polyQ depend on its length and are faster for longer polyQ tracts, the presence of GST alters the polyQ aggregation pathway and reverses this trend. Aggregation occurs through formation of a reservoir of soluble intermediates whose populations and kinetic stabilities increase with polyQ length. Our results provide a new model that explains the toxicity of expanded polyQ proteins, in which the interplay between polyQ regions and other aggregation-prone domains plays a key role in determining the aggregation pathway.

Anti-Christian polemic in early Islam : Abū ʿĪsā al-Warrāq's "Against the Trinity"

Abstract: Preface INTRODUCTION 1. Early Islamic theological investigations 2. Abu Isa's life and thought 3. Early Islamic refutations of Christianity 4. The structure and contents of Abu Isa's Radd ala al-Nasara THE REFUTATION OF THE TRINITY THE FIRST PART OF THE REFUTATION OF THE THREE CHRISTIAN SECTS The teachings of the Christian sects The question of the relationship between the substance and hypostases The question of the substance as one and the hypostases as three The question of the different characteristics of the hypostases Notes Bibliography

Syrian Christians Under Islam: The First Thousand Years

Abstract: This volume contains papers from the Third Woodbrooke-Mingana Symposium on Arab Christianity and Islam on the theme of "Arab Christianity in 'Greater Syria' in the pre-Ottoman Period". It presents aspects of Syrian Christian life and thought during the first millennium of Islamic rule. Among the eight contributing scholars are Sidney Griffith on ninth-century Christological controversies, Samir K. Samir on the Prophet Muhammed seen through Arab Christian eyes, Lawrence Conrad on the physician Ibn Butlan, and Lucy-Anne Hunt on Muslim influence on Christian book illustrations. There is also a foreword by the Syrian Orthodox Archbishop of Aleppo. The picture that emerges is of community life developing in its own way and finding a distinctive character, as Christians responded to the social and intellectual influences of Islam.

The Bible in early Muslim anti‐Christian polemic

Abstract: During the early centuries of Islam, the Bible did not usually receive specific attention from Muslim polemicists. Among those who did refer to it, some rejected the text on the grounds that it was corrupt, and developed accounts of how the original injil had been lost and replaced by the canonical Gospels. The majority, however, have left no expressed view, but do not appear to have experienced difficulty in employing suitable verses in their arguments as illustrations and proofs. A few scholars were in a position to use the Biblical texts to good effect in their arguments. The Christian convert cAli b. Rabban al‐Tabari employed a distinctively Muslim method of exegesis, and demonstrated how predictions of the coming of Muhammad and Islam are scattered throughout the biblical books. The Zaydi theologian al‐Qasim ibn Ibrahim al‐Rassi followed a more radical method in translating parts of Matthew's Gospel into Arabic, and altering words and phrases and omitting sections in order to make the origin...

Self-assembly of polyglutamine-containing huntingtin fragments into amyloid-like fibrils: Implications for Huntington's disease pathology (huntingtinyglutamine repeatyaggregation)

Abstract: Huntington's disease is a progressive neuro- degenerative disorder caused by a polyglutamine (poly(Q)) repeat expansion in the first exon of the huntingtin protein. Previously, we showed that N-terminal huntingtin peptides with poly(Q) tracts in the pathological range (51-122 glu- tamines), but not with poly(Q) tracts in the normal range (20 and 30 glutamines), form high molecular weight protein aggregates with a fibrillar or ribbon-like morphology, remi- niscent of scrapie prion rods and b-amyloid fibrils in Alzhei- mer's disease. Here we report that the formation of amyloid- like huntingtin aggregates in vitro not only depends on poly(Q) repeat length but also critically depends on protein concen- tration and time. Furthermore, the in vitro aggregation of huntingtin can be seeded by preformed fibrils. Together, these results suggest that amyloid fibrillogenesis in Huntington's disease, like in Alzheimer's disease, is a nucleation-dependent polymerization.

Polyglutamine disruption of the huntingtin exon 1 N terminus triggers a complex aggregation mechanism

Abstract: Simple polyglutamine (polyQ) peptides aggregate in vitro via a nucleated growth pathway directly yielding amyloid-like aggregates. We show here that the 17 amino acid flanking sequence (httNT) N-terminal to the polyQ in the toxic huntingtin exon1 fragment imparts onto this peptide a complex alternative aggregation mechanism. In isolation the httNT peptide is a compact coil that resists aggregation. When polyQ is fused to this sequence, it induces in httNT, in a repeat-length dependent fashion, a more extended conformation that greatly enhances its aggregation into globular oligomers with httNT cores and exposed polyQ. In a second step, a new, amyloid-like aggregate is formed with a core composed of both httNT and polyQ. The results indicate unprecedented complexity in how primary sequence controls aggregation within a substantially disordered peptide, and have implications for the molecular mechanism of Huntington's disease.

Critical nucleus size for disease-related polyglutamine aggregation is repeat-length dependent

Abstract: The formation of aggregates of polyglutamine (polyQ) sequences is initiated by nucleated growth polymerization. New results show that over a short repeat length range from Q26 to Q23 the size of the nucleus changes from monomeric to dimeric to tetrameric, suggesting aggregation nucleus size has a role in pathogenicity.