Wilson disease (WD) is an autosomal recessive disorder of copper metabolism manifesting with hepatic, neurological and psychiatric symptoms. The limitations of the currently available therapy for WD (particularly in the management of neuropsychiatric disease), together with our limited understanding of key aspects of this illness (e.g. neurological vs. hepatic presentation) justify the ongoing need to study WD in suitable animal models. Four animal models of WD have been established: the Long-Evans Cinnamon rat, the toxic-milk mouse, the Atp7b knockout mouse and the Labrador retriever. The existing models of WD all show good similarity to human hepatic WD and have been helpful in developing an improved understanding of the human disease. As mammals, the mouse, rat and canine models also benefit from high homology to the human genome. However, important differences exist between these mammalian models and human disease, particularly the absence of a convincing neurological phenotype. This review will first provide an overview of our current knowledge of the orthologous genes encoding ATP7B and the closely related ATP7A protein in C. elegans, Drosophila and zebrafish (Danio rerio) and then summarise key characteristics of rodent and larger mammalian models of ATP7B-deficiency.

AbstractProfanity has attracted much scholarly attention for the reason that swearing, oaths, and insults “manifest language use in its most highly charged state” (Taavitsainen 1997: 815). This article examines the possible functions of swearing per membra Christi [by Christ’s limbs], starting with a particularly revealing example from a group of late medieval pedagogical dialogues, the Manières de langage. Taking the perlocutionary reaction to this utterance as a starting point, the wider phenomenon of swearing on the body parts of Christ in both Middle English and Anglo Norman will be explored. This behaviour was initially conceptualised (and widely condemned) as an act of blasphemy, the notion of dismembering Jesus being especially widespread. However, this article also concerns itself with the emotive interjectory function of swearing oaths on God and Christ, and will posit that this behaviour is caught in a long process of pragmaticalisation during the high and late Middle Ages. This research supports the view of a bidirectional channel of influence between Middle English and Anglo Norman, and suggests a similar trajectory of both pragmatic development and language attitudes.

BackgroundSporadic Parkinson’s disease (sPD) is an aetiologically heterogeneous disorder. Identification of distinct pathogenic mechanisms causing sPD will be crucial to develop future “Precision Medicine” approaches. 31P-MRS is a non-invasive tool that can quantify key bionenergetic metabolites in individual patients.ObjectiveTo determine whether 31P-MRS can identify mitochondrial dysfunction in the midbrain/sub- stantia nigra of individual PD patients and correlates with trial-relevant clinical aspects of PD.Methods31P-MRS spectra were obtained from 35 sPD patients and 25 healthy, age-matched controls. Spectra were analysed using the jMRUI software package and AMARES spectral fitting algorithm. Clinical assessment included widely utilised clinical rating scales, genetic analysis and the calculation of predicted risk of rapid disease progression.ResultsThere was a significantly broader variance in 31P-MRS midbrain ATP with 1/3 of all PD patients having ATP levels > 2 standard deviations outside the mean control values (p=0.0030). Higher midbrain phosphocreatine was associated with greater risk of rapid disease progression (p= 0.0384).Conclusions31P-MRS may help to identify a subgroup of sPD with significant mitochondrial dysfunction or at higher risk of more rapid progression and facilitate stratification for future precision medicine neu- roprotective trials. Longitudinal studies are required to characterise if changes 31P-MRS measures mirror clinical progression.

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This article examines the acquisition of pragmatic competence in L2, applying this stimulating area of research to premodern texts in a way that has yet to be done (to the author’s knowledge). Specifically, this article discusses the teaching of “challenging” incongruent speech behaviours (such as sarcasm, banter, and irony) in a group of Anglo-Norman dialogues of the late Middle Ages. The present work focuses on the representation of incongruent speech acts in the dialogues, how this representation speaks to a pedagogical method that incorporated humour, and also the possible functions of humour in the pedagogical environment. The topic of incongruent performance and its pedagogical implications will also be considered. By discussing the depiction and role of incongruent speech behaviours in the dialogues, I argue that these texts were sophisticated teaching aides that may have used humour as a pedagogical tool to teach more difficult elements of language use.