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"Temperley, Nicholas"
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Molecular evolution of the vertebrate TLR1 gene family - a complex history of gene duplication, gene conversion, positive selection and co-evolution
Background
The Toll-like receptors represent a large superfamily of type I transmembrane glycoproteins, some common to a wide range of species and others are more restricted in their distribution. Most members of the Toll-like receptor superfamily have few paralogues; the exception is the TLR1 gene family with four closely related genes in mammals TLR1, TLR2, TLR6 and TLR10, and four in birds TLR1A, TLR1B, TLR2A and TLR2B. These genes were previously thought to have arisen by a series of independent gene duplications. To understand the evolutionary pattern of the TLR1 gene family in vertebrates further, we cloned the sequences of TLR1A, TLR1B, TLR2A and TLR2B in duck and turkey, constructed phylogenetic trees, predicted codons under positive selection and identified co-evolutionary amino acid pairs within the TLR1 gene family using sequences from 4 birds, 28 mammals, an amphibian and a fish.
Results
This detailed phylogenetic analysis not only clarifies the gene gains and losses within the TLR1 gene family of birds and mammals, but also defines orthologues between these vertebrates. In mammals, we predict amino acid sites under positive selection in TLR1, TLR2 and TLR6 but not TLR10. We detect co-evolution between amino acid residues in TLR2 and the other members of this gene family predicted to maintain their ability to form functional heterodimers. In birds, we predict positive selection in the TLR2A and TLR2B genes at functionally significant amino acid residues. We demonstrate that the TLR1 gene family has mostly been subject to purifying selection but has also responded to directional selection at a few sites, possibly in response to pathogen challenge.
Conclusions
Our phylogenetic and structural analyses of the vertebrate TLR1 family have clarified their evolutionary origins and predict amino acid residues likely to be important in the host's defense against invading pathogens.
Journal Article
Small molecule screening in zebrafish: an in vivo approach to identifying new chemical tools and drug leads
In the past two decades, zebrafish genetic screens have identified a wealth of mutations that have been essential to the understanding of development and disease biology. More recently, chemical screens in zebrafish have identified small molecules that can modulate specific developmental and behavioural processes. Zebrafish are a unique vertebrate system in which to study chemical genetic systems, identify drug leads, and explore new applications for known drugs. Here, we discuss some of the advantages of using zebrafish in chemical biology, and describe some important and creative examples of small molecule screening, drug discovery and target identification.
Journal Article
Victims of Compromise: The Elizabethan Psalm Tunes
The music of The Whole Book of Psalms (first printed in 1562) was not a product of English tradition, but a new congregational system brought home from Geneva. Psalm tunes in Edward VI’s time had been secular, iambic and based on dance rhythms; in so far as Thomas Sternhold’s metrical psalms were sung in church, they were chanted by choirs to Sarum tones. The tunes created for congregational use by the Marian exiles had to satisfy Calvin’s principle that they must be distinct from secular songs. They avoided strong rhythms and imitated the Huguenot psalter, which catered for a very different French prosody. Elizabethan congregations were enthusiastic about singing, but did not take to many of these tunes. Evidence shows a growing tendency for the printed tunes to be ignored in practice, and to be replaced by orally transmitted ‘common tunes’ restoring the secular Edwardian idiom. These, rather than the Elizabethan tunes, became the lasting model for the English hymn tune.
Journal Article
Music and Performance Culture in Nineteenth-Century Britain
This is the first book to focus upon aspects of performance in the broader context of nineteenth-century British musical culture. An introduction explores Nicholas Temperley's vast contribution to musicology, highlighting his seminal importance in creating the field of nineteenth-century British music studies, and a bibliography provides an up-to-date list of his publications, including books and monographs, book chapters, journal articles, editions, reviews, critical editions, arrangements and compositions.
eBook
'All skillful praises sing': how congregations sang the psalms in early modern England
The tunes of The Whole Book of Psalms would become the foundation of congregational singing in England. But when Thomas Sternhold published his first collection of paraphrases (circa 1548) he expected them to be sung in a private domestic context, and the few extant Edwardian settings do not differ in character from secular songs and dances of the time. There is no record of congregational singing until it was adopted by the Marian exiles under the direct influence of Calvin. The first tunes were printed as part of the 1556 Anglo-Genevan service book. They were clearly modelled on the grandly solemn tunes of the French Psalter, but the fundamental differences between French and English prosody created a conflict that was too much for anyone in the small English colonies to resolve satisfactorily. Nevertheless, congregational singing of ‘Geneva psalms’ was rapidly adopted in English churches from 1559 onwards. The tune selection was revised and enlarged, and had settled into a permanent ‘canon’ by the time the 1565 edition of The Whole Book of Psalms appeared. Metrical psalm-singing soon became popular well beyond the Puritan faction, both in church and in private settings. The tunes, like the psalms, were reprinted with only minor changes for the rest of Elizabeth’s reign. There is evidence, however, that by the 1590s many of them had been abandoned in practice as too difficult, or perhaps too tedious, as they slowed down year after year. They were largely replaced by a handful of short, simple tunes of unknown authorship, which became known as the ‘common tunes’ because they were not tied to specific texts. In some respects the common tunes were a return to the more popular idiom of Edwardian times. Many of them outlived the psalm paraphrases themselves and are still in widespread use as hymn tunes today.
Journal Article
The Piano in Nineteenth-Century British Culture
Since the publication of The London Pianoforte School (ed. Nicholas Temperley) twenty years ago, research has proliferated in the area of music for the piano during the late eighteenth and nineteenth centuries and into developments in the musical life of London, for a time the centre of piano manufacturing, publishing and performance. But none has focused on the piano exclusively within Britain. The eleven chapters in this volume explore major issues surrounding the instrument, its performers and music within an expanded geographical context created by the spread of the instrument and the growth of concert touring. Topics covered include: the piano trade and how piano manufacturing affected a major provincial town; the reception of Bach's Well-Tempered Clavier and Clementi's Gradus ad Parnassum during the nineteenth century; the shift from composer-pianists to pianist-interpreters in the first half of the century that triggered crucial changes in piano performance and concert structure; the growth of musical life in the peripheries outside major musical centres; the pianist as advocate for contemporary composers as well as for historical repertory; the status of British pianists both in relation to foreigners on tour in Britain and as welcomed star performers in outposts of the Empire; marketing forces that had an impact on piano sales, concerts and piano careers; leading virtuosos, writers and critics; the important role played by women pianists and the development of the recording industry, bringing the volume into the early twentieth century.
eBook
William Sterndale Bennett: Imitator or Original?
Sterndale Bennett has often been characterized as an imitator of Mendelssohn. While it is true and unsurprising that there are similarities in the two composers’ musical language, actual imitation is difficult to substantiate. Bennett’s reputation as a composer has passed through several phases in the last 200 years. It was high in his lifetime in Germany as well as in Britain, when resemblance to Mendelssohn was counted as a positive asset, but later assailed by promoters of the ‘English Musical Renaissance’, who needed a preceding dark age and tended to dismiss early Victorians as copiers of Mendelssohn. Recent writers have shown a more positive attitude to the Victorian period in general. Bennett’s individuality has in fact been fully recognized from the first by such widely differing commentators as Mendelssohn himself, Robert Schumann, Henry Heathcote Statham, Frederick Ouseley, Charles Gounod, Charles Stanford, Geoffrey Bush, Peter Horton and Larry Todd. His style was founded on the Austro-German classical tradition and the London Pianoforte School headed by Clementi and Cramer, through his teacher Cipriani Potter, as is confirmed by early sources. This article surveys some of Bennett’s most characteristic piano pieces, and ends by analysing notably original features of his harmonic style that owe nothing to Mendelssohn, such as the inverted pedal note, evaded resolution of dissonance, and harmonic anticipation.
Journal Article