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The Rho family GTPases, Cdc42, Rac and Rho, regulate signal transduction pathways via interactions with downstream effector proteins. We report here the solution structure of Cdc42 bound to the GTPase binding domain of alphaPAK, an effector of both Cdc42 and Rac. The structure is compared with those of Cdc42 bound to similar fragments of ACK and WASP, two effector proteins that bind only to Cdc42. The N-termini of all three effector fragments bind in an extended conformation to strand beta2 of Cdc42, and contact helices alpha1 and alpha5. The remaining residues bind to switches I and II of Cdc42, but in a significantly different manner. The structure, together with mutagenesis data, suggests reasons for the specificity of these interactions and provides insight into the mechanism of PAK activation.

A brief battery for mental deterioration assessment was obtained by Discriminant Analysis techniques from the Mental Deterioration Battery (MDB) (1) and yielded 98% correct classifications in a sample of 60 subjects (30 pathological and 30 controls). This battery, named Brief Mental Deterioration Battery (BMDB), both quick and easy to administer, is composed of four tests: Rey's 15 Words Test, Immediate Visual Memory, Barrage, and Simple Analogies Test. MDB was administered to a further sample of 60 normal subjects and, by multivariate statistical techniques, a probabilistic definition of "normality" and consequently of "non-normality" was given. When applied to pathological and control groups, this probabilistic dichotomic classification yielded groups almost identical to the previous ones.

Fatal familial insomnia (FFI) is a familial prion disease linked to a mutation of the prion protein gene. Neuropsychological investigations in seven patients with FFI belonging to two different families showed that the main behavioral and neuropsychological features are (1) early impairment of attention and vigilance, (2) memory deficits, mainly of the working memory, (3) impairment of temporal ordering of events, and (4) a progressive dream-like state with neuropsychological and behavioral features of a confusional state. Neuropathologic examination of six patients showed prominent neuronal loss and gliosis involving the anterior ventral and mediodorsal thalamic nuclei, with additional cerebral cortical involvement in two cases. Clinicopathologic correlations indicate that FFI is associated with a neuropsychological and behavioral syndrome that is distinct from the cortical and subcortical dementias, and Wernicke-Korsakoff syndrome. These findings offer insights into the function of the thalamic nuclei and challenge the notion of thalamic dementia.

Six patients presented with severe adult-onset memory deficit that was subsequently diagnosed as complex partial epilepsy. In three cases acute amnestic episodes also occurred. The seizures were characterized by short losses of contact and oral automatisms. Interictal EEG showed temporal abnormalities of varying degrees. Formal neuropsychological assessment revealed dissociation between the subjective complaint and the test performances that showed a selective impairment in a few long-term verbal memory tests. These patients present a characteristic clinical picture of memory disturbance as the prominent feature of partial seizures.

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Thirty-five patients affected with sporadic motor neuron disease (MND) and without clinically evident mental deterioration were systematically investigated by means of neuropsychological tests, quantitative analysis of EEG and brain CT. The MND patients as a group showed a slight but definite and stereotyped cognitive impairment. Temporal slow EEG activity was increased in the whole MND group and posterior background activity was slower in the more cognitively impaired patients. No significant differences were found in CT measurements of brain atrophy between MND and controls.