Isolation of encephalomyocarditis virus among stillborn and post-weaning pigs in Quebec

Summary Encephalomyocarditis (EMC) virus was isolated from aborted fetuses and lungs of suckling pigs from three Quebec pig farms that experienced outbreaks of reproductive failure in sows and respiratory problems in suckling and post-weaning piglets. Multifocal interstitial pneumonia and mild non-suppurative myocarditis and meningoencephalitis were the more significant histopathological lesions observed in piglets. Vero cells were found to be more sensitive than BHK-21 cells and pig cell lines for primary isolation of EMC virus. The Quebec EMC virus isolates were highly virulent for mice and were antigenically related to reference strain of EMC virus as demonstrated by indirect immunofluorescence, seroneutralization and Western immunoblotting. Specific virus neutralization antibody titers up to 1:12,800 were detected in samples of thoracic or abdominal fluids of the aborted fetuses.     

ETV6/RUNX1 fusion at diagnosis and relapse: some prognostic indications

This study was undertaken in order to compare the interphase and metaphase cytogenetics of 28 patients with ETV6/RUNX1 positive acute lymphoblastic leukemia, at diagnosis and relapse. The median time to relapse was 26 months. The significant fusion positive population heterogeneity revealed at interphase by a commercial probe for ETV6/RUNX1 fusion has not been described before. Six diagnostic samples had a single abnormal population; others had up to five each, which differed in the numbers of RUNX1 signals, and in the retention or loss of the second ETV6 signal. In contrast, the number of fusion signals was more constant. At relapse, there were fewer populations; the largest or unique clone was sometimes a re-emergence of a minor, diagnostic one, with a retained copy of ETV6 and the most RUNX1 signals. Abnormal, fusion negative clones were identified in bone marrow samples at extra-medullary relapse. Variant three or four-way translocations, which involved chromosomes 12 and 21, were prominent among the complex rearrangements revealed by metaphase FISH. The frequency of their occurrence at diagnosis and reappearance at relapse, sometimes accompanied by minor clonal evolution, was another new observation. Other recurrent cytogenetic features included a second copy of the fusion signal in six cases, partial duplication of the long arm of the X chromosome in two cases, and trisomy 10 in three cases. In comparing our data with previously reported cases, a picture is beginning to emerge of certain diagnostic features, which may provide circumstantial evidence of an increased risk of relapse.     

Impairment of a cortical event-related desynchronisation during a bimanual load-lifting task in children with autistic disorder

In autism, the abilities of communication are affected, associated with abnormalities of cognitive, sensorial and motor development. In a previous study based on a load-lifting task, we showed impairment of anticipation in children with autism as evidenced by kinematics and eletromyographic recordings [Neurosci. Lett. 348 (2003) 17]. In the present study, we assessed the cortical counterparts of the use of anticipatory postural adjustments in a group of control children and in a group of children with autism. The tasks required maintaining a stable forearm position despite imposed or voluntary lifting of an object placed either on the controlateral forearm or on a support. We investigated the differences between the two groups of children on the Event-Related Desynchronisation (ERD) which precedes movement onset in adults [Electroencephalogr. Clin. Neurophysiol. 46 (1979) 138]. Electroencephalogram (EEG) power evolution of a 6-8-Hz frequency band was averaged before and after imposed or voluntary movement onset. EEG reactivity of control and autistic children did not differ during the imposed unloading condition, but significant differences appeared in the voluntary unloading situations. Before lifting the object, control children showed an ERD above the left motor areas. An ERD also occurred above the right motor areas when the object was placed on their forearm. This indicates that the ERD can also translate the use of anticipatory postural adjustments. By contrast, children with autism did not show an ERD in the two voluntary situations. This suggests a central deficit of anticipation in both postural and motor control in children with autism.     

Inter- and intra-muscle comparisons of MAPK mechanosensitivity: evidence for the absence of fibre-type dependency

Muscle phenotype is regulated by mechanical forces. However, it is not well understood how these forces are translated into intracellular signalling that influences gene expression. The purpose of this study was to test the hypothesis that muscles displaying a wide range of metabolic profiles and fibre-type composition exhibit differences in the detection and transmission of mechanical stimuli. A mechanical challenge in the form of passive stretch normalized to 3 N/g muscle weight was applied to the rat extensor digitorum longus (EDL), soleus (SOL), and plantaris (PLN) in situ for 5 min, following which activities of the mechanically-responsive p54 c-jun NH(2)-terminal kinase (JNK) and extracellular-regulated kinase (ERK) 1/2 were measured. EDL, SOL, and PLN were not different in their stretch-induced JNK (4.5, 5.2 and 6-fold baseline, respectively) or ERK (2.2, 2.2 and 1.9-fold baseline, respectively) responses, in spite of differing fibre-type compositions. The medial gastrocnemius (MG), a compartmentalized muscle with red (MGr) and white (MGw) regions, was subjected to the same normalized mechanical stretch protocol. The resulting JNK and ERK activities were significantly higher in MGr (13 and 4.5-fold baseline, respectively) than in MGw (5 and 1.2-fold baseline, respectively) and all other muscles. In contrast to stimulation by passive stretch, stimulation of the MG by isometric contractile activity did not result in a heterogeneous response between compartments. This study demonstrates an absence of difference among muscles of varying phenotype in their ability to transmit mechanical stimuli to the mitogen-activated protein kinase signalling pathways, and hence in their mechanosensitivity. Furthermore, the results highlight the importance of considering aspects of the functional organization of different muscles, such as compartmentalization and architecture, when studying mechanical signalling in vivo.     

doublecortin is the major gene causing X-linked subcortical laminar heterotopia (SCLH)

Subcortical laminar heterotopia (SCLH), or 'double cortex', is a cortical dysgenesis disorder associated with a defect in neuronal migration. Clinical manifestations are epilepsy and mental retardation. This disorder, which mainly affects females, can be inherited in a single pedigree with lissencephaly, a more severe disease which affects the male individuals. This clinical entity has been described as X- SCLH/LIS syndrome. Recently we have demonstrated that the doublecortin gene, which is localized on the X chromosome, is implicated in this disorder. We have now performed a systematic mutation analysis of doublecortin in 11 unrelated females with SCLH (one familial and 10 sporadic cases) and have identified mutations in 10/11 cases. The sequence differences include nonsense, splice site and missense mutations and these were found throughout the gene. These results provide strong evidence that loss of function of doublecortin is the major cause of SCLH. The absence of phenotype-genotype correlations suggests that X-inactivation patterns of neuronal precursor cells are likely to contribute to the variable clinical severity of this disorder in females.      

Expression and folding of an antibody fragment selected in vivo for high expression levels in Escherichia coli cytoplasm

In this review, we summarize some of our results on folding and directed evolution of an antibody fragment in Escherichia coli cytoplasm. We will also discuss some attempts to construct other antibodies active in this cellular compartment.     

Regulation of cognitive activity and early communication development in young autistic, mentally retarded, and young normal children

Based on the Piagetian framework, this study examined regulation of cognitive activity and developmental communication profiles and their interrelationship in groups of autistic, mentally retarded, and normal children of comparable overall, verbal, and oculo-manual developmental ages (from 6 to 24 months). Regulation of activity was assessed with both an object permanence test and an original behavior grid, and development of communication skills with the Guidetti-Tourrette scales (French adaptation of the Seibert-Hogan scales). The results showed evidence of certain types of dysregulation of cognitive activity and a general delay in communication ability in autistic children compared to the other two groups. Moreover, although the intensity of some of these disorders decreased in relation to the developmental levels of social interaction and joint attention in normal children, they were related to both high and low levels of development of social interaction only in autistic children. These findings raise the hypothesis of a relationship between a disorder of disengaging from an activity and developmental levels of social interaction noted at two transitory periods of early development (12 and 24 months) only in children with autism. Developmental and neuropsychological interpretations of this particular pattern are proposed.