Unravelling Molecular and Cellular Disease Mechanisms in Infantile Neuronal Ceroid Lipofuscinosis (INCL)

Studying neurodegeneration provides an opportunity to gain insights into normal cell physiology, and not just pathophysiology. In this thesis work the focus is on Infantile Neuronal Ceroid Lipofuscinosis (INCL). It is a recessively inherited lysosomal storage disorder. The disease belongs to the neuronal ceroid lipofuscinoses (NCLs), a group of common progressive neurodegenerative diseases of the childhood. Characteristic accumulation of autofluorescent storage material is seen in most tissues but only neurons of the central nervous system are damaged and eventually lost during the course of the disease leaving most other cell types unaffected. The disease is caused by mutations in the CLN1 gene, but the physiological function of the corresponding protein the palmitoyl protein thioesterase (PPT1) has remained elusive. The aim of this thesis work was to shed light on the molecular and cell biological mechanisms behind INCL. This study pinpointed the localization of PPT1 in axonal presynapses of neurons. It also established the role of PPT1 in early neuronal maturation as well as importance in mature neuronal synapses. This study revealed an endocytic defect in INCL patient cells manifesting itself as delayed trafficking of receptor and non-receptor mediated endocytic markers. Furthermore, this study was the first to connect the INCL storage proteins the sphingolipid activator proteins (SAPs) A and D to pathological events on the cellular level. Abnormal endocytic processing and intracellular re-localization was demonstrated in patient cells and disease model knock-out mouse neurons. To identify early affected cellular and metabolic pathways in INCL, knock-out mouse neurons were studied by global transcript profiling and functional analysis. The gene expression analysis revealed changes in neuronal maturation and cell communication strongly associated with the regulated secretory system. Furthermore, cholesterol metabolic pathways were found to be affected. Functional studies with the knock-out mouse model revealed abnormalities in neuronal maturation as well as key neuronal functions including abnormalities in intracellular calcium homeostasis and cholesterol metabolism. Together the findings, introduced in this thesis work, support the essential role of PPT1 in developing neurons as well as synaptic sites of mature neurons. Results of this thesis also elucidate early events in INCL pathogenesis revealing defective pathways ultimately leading to the neurodegenerative process. These results contribute to the understanding of the vital physiological function of PPT1 and broader knowledge of common cellular mechanisms behind neurodegeneration. These results add to the knowledge of these severe diseases offering basis for new approaches in treatment strategies.

Representations of the Natural World in Old English Poetry

Review of Representations of the Natural World in Old English Poetry, by Jennifer Neville (Cambridge UP, 1999).

Charles I : unhero of royalist poetry

During the English Civil War, Charles I appeared as a character in Royalist poetry, both directly and allegorically. These depictions drew on ancient Roman epic poems, particularly Lucan’s De Bello Civili, in their treatment of the subject matter of civil war and Charles as an epic hero. Though the authors of these poems supported Charles, their depictions of him and his reign reveal anxiety about his weakness as a ruler. In comparison to the cults of personality surrounding his predecessors and the heroes of De Bello Civili, his cult appears bland and forced. The lack of enthusiasm surrounding Charles I may help to explain his downfall at the hands of his Parliamentarian opponents.  

Reflective writing: The student nurse's perspective on reflective writing and poetry writing.

Summary Background Reflective writing is a mandatory part of nurse education but how students develop their skills and use reflection as part of their experiential learning remains relatively unknown. Understanding reflective writing in all forms from the perspective of a student nurse is therefore important. Objectives To explore the use of reflective writing and the use of poetry in pre-registered nursing students. Design A qualitative design was employed to explore reflective writing in pre-registered nursing students. Setting A small university in Scotland. Participants BSc (Hons) Adult and Mental Health Pre-registration Student Nurses. Methods Two focus groups were conducted with 10 student nurses during March 2012. Data was analysed thematically using the framework of McCarthy (1999). Results Students found the process of reflective writing daunting but valued it over time. Current educational methods, such as assessing reflective accounts, often lead to the ‘narrative’ being watered down and the student feeling judged. Despite this, reflection made students feel responsible for their own learning and research on the topic. Some students felt the use of models of reflection constricting, whilst poetry freed up their expression allowing them to demonstrate the compassion for their patient under their care. Conclusions Poetry writing gives students the opportunity for freedom of expression, personal satisfaction and a closer connection with their patients, which the more formal approach to reflective writing did not offer. There is a need for students to have a safe and supportive forum in which to express and have their experiences acknowledged without the fear of being judged.

Where the People Are: Language and Community in the Poetry of W.S. Graham

Francis, Matthew, Language and Community in the Poetry of W.S. Graham (Cambridge: Salt Publishing, 2004) RAE2008

The Poetics of the Limit : Ethics and Politics in Modern and Contemporary American Poetry

Woods, Timothy, The Poetics of the Limit (New York: Palgrave Macmillan, 2003) RAE2008

'Preferring the wrong way': Mapping the Ethical Diversity of US Twentieth-Century Poetry

Woods, T. (2006). 'Preferring the wrong way': Mapping the Ethical Diversity of US Twentieth-Century Poetry. In C. Bigsby (Ed.), The Cambridge Companion to Modern American Culture (pp.450-468). Cambridge: Cambridge University Press. RAE2008

A ?Perfect Circle'? Alchemy in the Poetry of Hester Pulter

Archer, Jayne, 'A ?Perfect Circle'? Alchemy in the Poetry of Hester Pulter', Literature Compass (2005) 2(1) pp.1-14 RAE2008

The Four Branches of the Mabinogi and Medieval Welsh Poetry

Hughes, I. (2006). The Four Branches of the Mabinogi and Medieval Welsh Poetry. Studi Celtici. 4, pp.155-193. RAE2008

Absolute forms in the poetry of the Gogynfeirdd: functionally obsolete archaisms or working system?

Rodway, S. (2002). Absolute forms in the poetry of the Gogynfeirdd: functionally obsolete archaisms or working system? Journal of Celtic Linguistics. 7, pp.63-84. RAE2008

Phenotypic overlap between infantile systemic lupus erythematosus and Aicardi-Goutières syndrome.

Case Reports

Andrew Marvell's Latin Poetry: From Text to Context (356pp.)

David Norbrook, Review of English Studies 56 (Sept. 2005), 675-6.
‘We have waited a long time for a study of Marvell’s Latin poetry; fortunately, Estelle Haan’s monograph generously makes good the loss ... One of her most intriguing suggestions … is that Marvell may have presented paired poems like ‘Ros’ and ‘On a Drop of Dew’, and the poems to the obligingly named Dr Witty, to his student Maria Fairfax as his own patterns for the pedagogical practice of double translation. Perhaps the most original parts of the book, however, move beyond the familiar canon to cover the generic range of the Latin verse. Haan offers a very full contextualization of the early Horatian Ode to Charles I in seventeenth-century exercises in parodia. In a rewarding reading of the poem to Dr Ingelo she shows how Marvell deploys the language of Ovid’s Tristia to present Sweden as a place of shivering exile, only to subvert this model with a neo-Virgilian celebration of Christina as a virtuous, city-building Dido. She draws extensively on historical as well as literary sources to offer very detailed contextualizations of the poem to Maniban and ‘Scaevola Scotto-Britannus’... This monograph opens up many new ways into the Latin verse, not least because it is rounded off with new texts and prose translations of the Latin poems. These make a substantial contribution in their own right. They are the best and most accurate translations to date (those in Smith’s edition having some lapses); they avoid poeticisms but bring out the structure of the poems' wordplay very clearly. This book brings us a lot closer to seeing Marvell whole.'