Enhanced axonal response of mitochondria to demyelination offers neuroprotection:implications for multiple sclerosis

Axonal loss is the key pathological substrate of neurological disability in demyelinating disorders, including multiple sclerosis (MS). However, the consequences of demyelination on neuronal and axonal biology are poorly understood. The abundance of mitochondria in demyelinated axons in MS raises the possibility that increased mitochondrial content serves as a compensatory response to demyelination. Here, we show that upon demyelination mitochondria move from the neuronal cell body to the demyelinated axon, increasing axonal mitochondrial content, which we term the axonal response of mitochondria to demyelination (ARMD). However, following demyelination axons degenerate before the homeostatic ARMD reaches its peak. Enhancement of ARMD, by targeting mitochondrial biogenesis and mitochondrial transport from the cell body to axon, protects acutely demyelinated axons from degeneration. To determine the relevance of ARMD to disease state, we examined MS autopsy tissue and found a positive correlation between mitochondrial content in demyelinated dorsal column axons and cytochrome c oxidase (complex IV) deficiency in dorsal root ganglia (DRG) neuronal cell bodies. We experimentally demyelinated DRG neuron-specific complex IV deficient mice, as established disease models do not recapitulate complex IV deficiency in neurons, and found that these mice are able to demonstrate ARMD, despite the mitochondrial perturbation. Enhancement of mitochondrial dynamics in complex IV deficient neurons protects the axon upon demyelination. Consequently, increased mobilisation of mitochondria from the neuronal cell body to the axon is a novel neuroprotective strategy for the vulnerable, acutely demyelinated axon. We propose that promoting ARMD is likely to be a crucial preceding step for implementing potential regenerative strategies for demyelinating disorders.</p

Gaze-Assisted Pointing for Wall-Sized Displays

Abstract. Previous studies have argued for the use of gaze-assisted pointing techniques (MAGIC) in improving human-computer interaction. Here, we present experimental findings that were drawn from human performance of two tasks on a wall-sized display. Our results show that a crude adoption of MAGIC across a range of complex tasks does not increase pointing performance. More importantly, a detailed analysis of user behavior revealed several issues that were previously ignored (such as, interference of corrective saccades, increased decision time due to variability of precision, errors due to eye-hand asynchrony, and interference with search behavior) which should influence the development of gaze-assisted technology. Keywords: Eye-Tracking, Eye-Hand Coordination, Multimodal.

Redrawing Foucault's social ontology

I propose that Foucault‟s works, since he wrote Discipline and Punish, rely on an implicit meta-theory that is compatible with the fundamentals of Critical Realism. To this end I examine the status of truth, methodology and social ontology used by Foucault. If this thesis is correct, then a critical realist reading of Michel Foucault would avoid some of the pitfalls that have been attributed to his works - such as constructivism, determinism, localism, and reductionism. Moreover, this understanding of Foucault‟s works would also offer novel and challenging perspectives for researchers adopting a Foucauldian and/or critical realist study of organizations

National context as a predictor of high-performance work system effectiveness in small-to-medium-sized enterprises (SMEs): a UK–French comparative analysis

High-performance work systems (HPWSs), a large firm model, have recently attracted interest within small-to-medium-sized enterprises (SMEs). In addition, institutional settings have been shown as an important determinant in the types of human resource management (HRM) practices adopted by employers. This paper progresses these topics through a comparative analysis of SMEs within Cote d’Opale/Nord Pas de Calais (French) and Kent (UK) regions. Clear divergence is evident in the nature of HPWS. Whilst UK SMEs are found to adopt a wider range of practices, French firms exhibit a higher degree of integration portrayed through a collective range of practices that engender employee participation and commitment