Maurocalcine is a novel toxin isolated from the venom of the chactid scorpion Scorpio maurus palmatus. It is a 33-mer basic peptide cross-linked by three disulfide bridges, which shares 82% sequence identity with imperatoxin A, a scorpion toxin from the venom of Pandinus imperator. Maurocalcine is peculiar in terms of structural properties since it does not possess any consensus motif reported so far in other scorpion toxins. Due to its low concentration in venom (0.5% of the proteins), maurocalcine was chemically synthesized by means of an optimized solid-phase method, and purified after folding/oxidation by using both C18 reversed-phase and ion exchange highpressure liquid chromatographies. The synthetic product (sMCa) was characterized. The half-cystine pairing pattern of sMCa was identified by enzyme-based cleavage and Edman sequencing. The pairings were Cys3-Cys17, Cys10-Cys21, and Cys16-Cys32. In vivo, the sMCa was lethal to mice following intracerebroventricular inoculation (LD 50 , 20 W Wg/mouse). In vitro, electrophysiological experiments based on recordings of single channels incorporated into planar lipid bilayers showed that sMCa potently and reversibly modifies channel gating behavior of the type 1 ryanodine receptor by inducing prominent subconductance behavior.z 2000 Federation of European Biochemical Societies.

Biallelic NF2 gene inactivation is frequently found in human malignant mesothelioma. In order to assess whether NF2 hemizygosity may enhance susceptibility to asbestos fibres, we investigated the Nf2 status in mesothelioma developed in mice presenting a heterozygous mutation of the Nf2 gene (Nf2 KO3/ þ ), after intraperitoneal inoculation of crocidolite fibres. Asbestos-exposed Nf2 KO3/ þ mice developed tumoural ascites and mesothelioma at a higher frequency than their wild-type (WT) counterparts (Po0.05). Six out of seven mesothelioma cell lines established from neoplastic ascitic fluids of Nf2 KO3/ þ mice exhibited loss of the WT Nf2 allele and no neurofibromatosis type 2 protein expression was found in these cells. The results show the importance of the NF2 gene in mesothelial oncogenesis, the potential association of asbestos exposure and tumour suppressor gene inactivation, and suggest that NF2 gene mutation may be a susceptibility factor to asbestos.

Malignant mesothelioma (MM) is an aggressive tumor with a poor prognosis mainly linked to past asbestos exposure. Murine models of MM based on fiber exposure have been developed to elucidate the mechanism of mesothelioma formation. Genomic alterations in murine MM have now been partially characterized. To gain insight into the pathophysiology of mesothelioma, 16 murine and 35 human mesotheliomas were characterized by array-comparative genomic hybridization and were screened for common genomic alterations. Alteration of the 9p21 human region, often by biallelic deletion, was the most frequent alteration in both species, in agreement with the CDKN2A/CDKN2B locus deletion in human disease and murine models. Other shared aberrations were losses of 1p36.3-p35 and 13q14-q33 and gains of 5p15.3-p13 regions. However, some differences were noted, such as absence of recurrent alterations in mouse regions corresponding to human chromosome 22. Comparison between altered recurrent regions in asbestos-exposed and non-asbestos-exposed patients showed a significant difference in the 14q11.2-q21 region, which was also lost in fiber-induced murine mesothelioma. A correlation was also demonstrated between genomic instability and tumorigenicity of human mesothelioma xenografts in nude mice. Overall, these data show similarities between murine and human disease, and contribute to the understanding of the influence of fibers in the pathogenesis of mesothelioma and validation of the murine model for preclinical testing.

Pi1 is a 35-residue toxin cross-linked by four disulfide bridges that has been isolated from the venom of the chactidae scorpion Pandinus imperator. Due to its very low abundance in the venom, we have chemically synthesized this toxin in order to study its biological activity. Enzyme-based proteolytic cleavage of the synthetic Pi1 (sPi1) demonstrates half-cystine pairings between Cys4±Cys25, Cys10±Cys30, Cys14±Cys32 and Cys20±Cys35, which is in agreement with the disulfide bridge organization initially reported on the natural toxin. In vivo, intracerebroventricular injection of sPi1 in mice produces lethal effects with an LD 50 of 0.2 mg per mouse. In vitro, the application of sPi1 induces drastic inhibition of Shaker B (IC 50 of 23 nm) and rat Kv1.2 channels (IC 50 of 0.44 nm) heterologously expressed in Xenopus laevis oocytes. No effect was observed on rat Kv1.1 and Kv1.3 currents upon synthetic peptide application. Also, sPi1 is able to compete with 125 I-labeled apamin for binding onto rat brain synaptosomes with an IC 50 of 55 pm. Overall, these results demonstrate that sPi1 displays a large spectrum of activities by blocking both SK-and Kv1-types of K 1 channels; a selectivity reminiscent of that of maurotoxin, another structurally related four disulfide-bridged scorpion toxin that exhibits a different half-cystine pairing pattern.

Maurotoxin (MTX) is a 34-residue toxin that has been isolated from the venom of the chactidae scorpion

Pour rechercher le poireau, Acrolepiopsis assectella doit utiliser des stimulus olfactifs issus du végétal‐hôte et notamment les substances soufrées spécifiques. Le pouvoir attractif de l'lQodeurrQ du poireau et celui de différents thiosulfinates et disulfures trouvés dans cette plante sont donc étudiés et comparés par olfactométrie. Le comportement de mâles et de femelles vierges et fécondées est observé, en fonction de l'âge des imagos, pendant la scotophase. Alors qu'un courant d'air sans lQodeurrQ significative déclenche essentiellement l'orientation et l'immobilisation des insectes face au flux, la plus part des mâles et des femelles quel que soit leur état sexuel sont attirés par le courant d'air lorsque celui‐ci transporte l'lQodeurrQ du poireau ou les substances volatiles étudiées. La sensibilité à l'lQodeurrQ de la plante‐hôte semble se modifier avec l'âge des insectes, les mâles âgés et les jeunes femelles étant les plus attirés. Cependant, ces dernières conservent une forte sensibilité une fois fécondées. Aux âges où l'lQodeurrQ du poireau est la plus efficace, les thiosulfinates déclenchent chez les mâles et les femelles vierges une attraction plus importante que les disulfures, le radical propyle étant plus actif que le méthyle. Le thiosulfinate de dipropyle, labile, très abondant dans le poireau, semble donc avoir un rôle informationnel prépondérant.

We explore the implications of the experimental findings of attribution theorists for practice, training, and research in the domain of counseling and psychotherapy. Research literature contains abundant evidence that people engage routinely in inferential processes that are logically deficient and lead to erroneous social judgments. Clinical psychologists, no less than others, are engaged in work that is highly inferential in character and that offers continuous opportunity for error in matters that have the most profound consequences in the lives of their clients. Certain sources of error are explored. Emphasis is given to the question of the accuracy and representativeness of the data about clients' lives and the hypotheses derived from those data. The evidence suggests that an objective of every training program in clinical psychology or psychiatry should be the instruction of students in the rigorous application of principles of inferential reasoning within the systems in which they choose to design their treatment.FLORENT DUMONT received his EdD in counseling psychology from the University of Massachusetts in 1971. He is currently the director of the doctoral program in counseling psychology at McGill University. His research and practice are centered in therapeutic communities and in small-group process. He has had ancillary professional involvement in administration of hospital infection control programs and in school-based mental hygiene programs. CONRAD LECOMTE received his PhD in counseling psychology from the University of California at Santa Barbara in 1974. He is an author of an integrated clinical psychology training program that has been adopted widely in Canada. He is currently a director of practice and internships in the Department of Psychology at the University of Montreal.

Although uncertainty remains about the role of many prognostic factors, we found strong evidence to support the predictive value of clinically significant variables. There is, however, a need for additional research and replication, adopting more homogenous models and measurement methods.