Dynamics of motor nerve terminal remodeling unveiled using SNARE-cleaving botulinum toxins: the extent and duration are dictated by the sites of SNAP-25 truncation

Nerve sprouts emerge from motor nerve terminals following blockade of exo-endocytosis for more than 3 days by botulinum neurotoxin (BoNT), and form functional synapses, albeit temporary. Upon restoration of synaptic activity to the parent terminal 7 and 90 days after exposure to BoNT/F or A respectively, a concomitant retraction of the outgrowths was observed. BoNT/E caused short-term neuroparalysis, and dramatically accelerated the recovery of BoNT/A-paralyzed muscle by further truncation of SNAP-25 and its replenishment with functional full-length SNARE. The removal of 9 C-terminal residues from SNAP-25 by BoNT/A leads to persistence of the inhibitory product due to the formation of a nonproductive SNARE complex(es) at release sites, whereas deletion of a further 17 amino acids permits replenishment and a speedy recovery. (C) 2003 Elsevier Science (USA). All rights reserved.

Modulation of higher-plant NAD(H)-dependent glutamate dehydrogenase activity in transgenic tobacco via alteration of beta subunit levels

Glutamate dehydrogenase (GDH; EC 1.4.1.2-1.4.1.4) catalyses in vitro the reversible amination of 2-oxoglutarate to glutamate. In vascular plants the in vivo direction(s) of the GDH reaction and hence the physiological role(s) of this enzyme remain obscure. A phylogenetic analysis identified two clearly separated groups of higher-plant GDH genes encoding either the alpha- or beta-subunit of the GDH holoenzyme. To help clarify the physiological role(s) of GDH, tobacco (Nicotiana tabacum L.) was transformed with either an antisense or sense copy of a beta-subunit gene, and transgenic plants recovered with between 0.5- and 34-times normal leaf GDH activity. This large modulation of GDH activity (shown to be via alteration of beta-subunit levels) had little effect on leaf ammonium or the leaf free amino acid pool, except that a large increase in GDH activity was associated with a significant decrease in leaf Asp (similar to 51%, P=0.0045). Similarly, plant growth and development were not affected, suggesting that a large modulation of GDH beta-subunit titre does not affect plant viability under the ideal growing conditions employed. Reduction of GDH activity and protein levels in an antisense line was associated with a large increase in transcripts of a beta-subunit gene, suggesting that the reduction in beta-subunit levels might have been due to translational inhibition. In another experiment designed to detect post-translational up-regulation of GDH activity, GDH over-expressing plants were subjected to prolonged dark-stress. GDH activity increased, but this was found to be due more likely to resistance of the GDH protein to stress-induced proteolysis, rather than to post-translational up-regulation.

Access to written information for people with aphasia

Background: Accessibility is often constructed in terms of physical accessibility. There has been little research into how the environment can accommodate the communicative limitations of people with aphasia. Communication accessibility for people with aphasia is conceptualised in this paper within the World Health Organisation's International Classification of Functioning, Disability and Health (ICF). The focus of accessibility is considered in terms of the relationship between the environment and the person with the disability. Thus: This paper synthesises the results of three Studies that examine the effectiveness of aphasia-friendly written material. Main Contribution: The first study (Rose, Worrall, & McKenna, 2003) found that aphasia-friendly formatting of written health information improves comprehension by people with aphasia, but not everyone prefers aphasia-friendly formatting. Brennan, Worrall, and McKenna (in press) found that the aphasia-friendly strategy of augmenting text with pictures, particularly ClipArt and Internet images, may be distracting rather than helpful. Finally, Egan, Worrall, and Oxenham (2004) found that the use of ail aphasia-friendly written training manual was instrumental in assisting people with aphasia to learn the Internet. Conclusion: Aphasia-friendly formatting appears to improve the accessibility of written material for people with aphasia. Caution is needed when considering the use of illustrations, particularly ClipArt and Internet images, when creating aphasia-friendly materials. A research, practice, and policy agenda for introducing aphasia-friendly formatting is proposed.