C. Simoné

The lethal disease amyotrophic lateral sclerosis (ALS) is characterized by the loss of somatic motor neurons. However, not all motor neurons are equally vulnerable to disease; certain groups are spared, including those in the oculomotor nucleus controlling eye movement. The reasons for this differential vulnerability remain unknown. Here we have identified a protein signature for resistant oculomotor motor neurons and vulnerable hypoglossal and spinal motor neurons in mouse and man and in health and ALS with the aim of understanding motor neuron resistance. Several proteins with implications for motor neuron resistance, including GABAA receptor α1, guanylate cyclase soluble subunit alpha-3 and parvalbumin were persistently expressed in oculomotor neurons in man and mouse. Vulnerable motor neurons displayed higher protein levels of dynein, peripherin and GABAA receptor α2, which play roles in retrograde transport and excitability, respectively. These were dynamically regulated during disease and thus could place motor neurons at an increased risk. From our analysis is it evident that oculomotor motor neurons have a distinct protein signature compared to vulnerable motor neurons in brain stem and spinal cord, which could in part explain their resistance to degeneration in ALS. Our comparison of human and mouse shows the relative conservation of signals across species and infers that transgenic SOD1G93A mice could be used to predict mechanisms of neuronal vulnerability in man.

The need of supporting office work with suitable computer based tools implies the investigation of the deep aspects of cooperation within the office. Cooperation, to the extent that is made up of communication and coordination, can be fully characterized under the assumption that an office is a special linguistic game, constituted by a set of rules defining the conversations possible within it, continuously changing under the perturbations created by the speech acts its member do performing the conversations. Within this conceptual context, a prototypal software package, CHAOS-1, is presented. CHAOS-1 aims both at supporting the conversations and at improving coordination of the office activities.This paper discusses CHAOS-1 with respect to similar proposals, presents its overall architecture, shows some examples of its use and sketches its new releases under development.