Behavioural characterization of Vitamin D receptor knockout mice

Vitamin D (calcitriol) is a nuclear transcription regulator acting via a nuclear hormone receptor (VDR). In addition to its role in the regulation of calcium and phosphate horneostasis and in bone formation, Vitamin D is also thought to be involved in brain function. The aim of this study was to behaviourally phenotype VDR knockout mice. We characterized the behaviour of VDR null mutant mice and wildtype littermate controls by subjecting them to a range of tests including a primary behavioural screen (using the SHIRPA protocol), rotarod, gait analysis, Y-maze, marble burying test, bedding test, holeboard test, elevated plus maze, open field test and prepulse inhibition of the acoustic startle response. There were no effects of genotype on most of the scores from the SHIRPA protocol except that VDR -/- mice had alopecia, were shorter and weighed less than VDR +/+ mice. VDR -/- mice had a shorter gait as well as impairments on the rotarod, in the bedding test and impaired habituation in both the open field and on the acoustic startle response. The VDR -/- mice had normal acoustic startle responses but had impaired PPI at long (256 ms) but not short (64 ms) prepulse to pulse intervals. The VDR -/- mice were less active in the open field and buried fewer marbles in the marble burying test. However, there were no differences in the time spent on the open arms of the elevated plus maze or in working memory as assessed by repeat arm entries on the Y-maze. Therefore, it appears that VDR -/- mice have muscular and motor impairments that significantly affects locomotor behaviour but seemingly no impairments in cognition as indicated by exploration, working memory or anxiety. (C) 2004 Elsevier B.V. All rights reserved.

Genetic basis of human testicular germ cell cancer: insights from the fruitfly and mouse

The prevalence of tumours of the germ line is increasing in the male population. This complex disease has a complex aetiology. We examine the contribution of genetic mutations to the development of germ line tumours in this review. In particular, we concentrate on fly and mouse experimental systems in order to demonstrate that mutations in some conserved genes cause pathologies typical of certain human germ cell tumours, whereas other mutations elicit phenotypes that are unique to the experimental model. Despite these experimental systems being imperfect, we show that they are useful models of human testicular germ cell tumourigenesis.

Akrasia and the Aesthetic: Human Agency and the Site of Literature, 1760-1820

This study focuses on a series of foundational stylistic and formal innovations in eighteenth-century and Romantic literature, and argues that they can be cumulatively attributed to the distinct challenges authors faced in representing human action and the will. The study focuses in particular on cases of “acting against better judgment” or “failing to do what one knows one ought to do” – concepts originally theorized as “akrasia” and “weakness of the will” in ancient Greek and Scholastic thought. During the Enlightenment, philosophy increasingly conceives of human minds and bodies like systems and machines, and consequently fails to address such cases except as intractable or incoherent. Yet eighteenth-century and Romantic narratives and poetry consistently engage the paradoxes and ambiguities of action and volition in representations of akrasia. As a result, literature develops representational strategies that distinguish the epistemic capacities of literature as privileged over those of philosophy.

The study begins by centering on narratives of distempered selves from the 1760s. Jean-Jacques Rousseau’s Confessions and Laurence Sterne’s A Sentimental Journey narrate cases of knowingly and weakly acting against better judgment, and in so doing, reveal the limitations of the “philosophy of the passions” that famously informed sentimental literature at the time. These texts find that the interpretive difficulties of action demand a non-systematic and hermeneutic approach to interpreting a self through the genre of narrative. Rousseau’s narrative in particular informs William Godwin’s realist novels of distempered subjects. Departing from his mechanistic philosophy of mind and action, Godwin develops the technique of free indirect discourse in his third novel Fleetwood (1805) as a means of evoking the ironies and self-deceptions in how we talk about willing.

Romantic poetry employs the literary trope of weakness of will primarily through the problem of regretted inaction – a problem which I argue motivates the major poetic innovations of William Wordsworth and John Keats. While Samuel Taylor Coleridge sought to characterize his weakness of will in philosophical writing, Wordsworth turns to poetry with The Prelude (1805), revealing poetry itself to be a self-deceiving and disappointing form of procrastination. More explicitly than Wordsworth, John Keats identifies indolence as the prime symbol and basis of what he calls “negative capability.” In his letters and poems such as “On Seeing the Elgin Marbles��� (1817) and “Ode on Indolence” (1819), Keats reveals how the irreducibly contradictory qualities of human agency speak to the particular privilege of “disinterested aesthetics” – a genre fitted for the modern era for its ability to disclose contradictions without seeking to resolve or explain them in terms of component parts.

The effect of dissolved magnesium on diffusion creep in calcite

We experimentally tested a series of synthetic calcite marbles with varying amounts of dissolved magnesium in a standard triaxial deformation machine at 300 MPa confining pressure, temperatures between 700 and 850°C, stresses between 2 and 100 MPa, and strain rates between 10−7 and 10−3 s−1. The samples were fabricated by hot isostatic pressing of a mixture of calcite and dolomite at 850°C and 300 MPa. The fabrication protocol resulted in a homogeneous, fine-grained high-magnesian calcite aggregate with minimal porosity and with magnesium contents between 0.07 and 0.17 mol% MgCO3. At stresses below 40 MPa the samples deformed with linear viscosity that depended inversely on grain size to the 3.26±0.51 power, suggesting that the mechanisms of deformation were some combination of grain boundary diffusion and grain boundary sliding. Because small grain sizes tended to occur in the high-magnesium calcite, the strength also appeared to vary inversely with magnesium content. However, the strength at constant grain size does not depend on the amount of dissolved magnesium, and thus, the impurity effect seems to be indirect. At stresses higher than 40 MPa, the aggregates become non-linearly viscous, a regime we interpret to be dislocation creep. The transition between the two regimes depends on grain size, as expected. The activation energy for diffusion creep is 200±30 kJ/mol and is quite similar to previous measurements in natural and synthetic marbles deformed at similar conditions with no added magnesium.

87Sr/86Sr ratios discrimination applied to the main Paleozoic carbonate sedimentation in Ossa-Morena Zone

The carbonated sedimentation in Ossa-Morena Zone during the Palaeozoic is formed, at least, by two main episodes. However, some chronological questions remain open, due to lack of biostratigraphic data in some carbonates. Sr isotope analysis was performed in selected limestones and marbles of Ossa-Morena Zone, in order to discriminate the Sr signature of the two main carbonate sedimentation episodes. The Sr isotopic data from the analyzed carbonate show two clusters of 87Sr/86Sr ratios, one related with the Lower Cambrian and other with the Lower-Middle Devonian carbonates.