Development of reading proficiency in English by bilingual children and their monolingual peers.

The semantic, syntactic, and graphophonic cueing techniques employed by 55 bilingual children and 39 monolingual peers when reading aloud in English were identified through miscue analysis. In contrast to earlier research in 1999 by Cline and Cozens no significant differences were found between the two groups on any of the techniques. Both bilingual and monolingual readers consistently used more graphophonic cues than syntactic or semantic cues but not significantly so. The authors discuss possible extraneous variables which may account in part for this unexpected result.

From neuronal inclusions to neurodegeneration: neuropathological investigation of a transgenic mouse model of Huntington's disease.

Huntington's disease (HD) is an inherited progressive neurodegenerative disease caused by the expansion of a polyglutamine repeat sequence within a novel protein. Recent work has shown that abnormal intranuclear inclusions of aggregated mutant protein within neurons is a characteristic feature shared by HD and several other diseases involving glutamine repeat expansion. This suggests that in each of the these disorders the affected nerve cells degenerate as a result of these abnormal inclusions. A transgenic mouse model of HD has been generated by introducing exon 1 of the HD gene containing a highly expanded CAG sequence into the mouse germline. These mice develop widespread neuronal intranuclear inclusions and neurodegeneration specifically within those areas of the brain known to degenerate in HD. We have investigated the sequence of pathological changes that occur after the formation of nuclear inclusions and that precede neuronal cell death in these cells. Although the relation between inclusion formation and neurodegeneration has recently been questioned, a full characterization of the pathways linking protein aggregation and cell death will resolve some of these controversies and will additionally provide new targets for potential therapies.

Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation.

Huntington's disease (HD) is one of an increasing number of human neurodegenerative disorders caused by a CAG/polyglutamine-repeat expansion. The mutation occurs in a gene of unknown function that is expressed in a wide range of tissues. The molecular mechanism responsible for the delayed onset, selective pattern of neuropathology, and cell death observed in HD has not been described. We have observed that mice transgenic for exon 1 of the human HD gene carrying (CAG)115 to (CAG)156 repeat expansions develop pronounced neuronal intranuclear inclusions, containing the proteins huntingtin and ubiquitin, prior to developing a neurological phenotype. The appearance in transgenic mice of these inclusions, followed by characteristic morphological change within neuronal nuclei, is strikingly similar to nuclear abnormalities observed in biopsy material from HD patients.

Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice.

Huntington's disease (HD) is one of an increasing number of neurodegenerative disorders caused by a CAG/polyglutamine repeat expansion. Mice have been generated that are transgenic for the 5' end of the human HD gene carrying (CAG)115-(CAG)150 repeat expansions. In three lines, the transgene is ubiquitously expressed at both mRNA and protein level. Transgenic mice exhibit a progressive neurological phenotype that exhibits many of the features of HD, including choreiform-like movements, involuntary stereotypic movements, tremor, and epileptic seizures, as well as nonmovement disorder components. This transgenic model will greatly assist in an eventual understanding of the molecular pathology of HD and may open the way to the testing of intervention strategies.

Size and shape of rabbit skeletal muscle calsequestrin.

Calsequestrin, a calcium-binding protein isolated from rabbit skeletal muscle sarcoplasmic reticulum, was subjected to physiochemical analysis using sodium dodecyl sulfate gel electrophoresis, gel filtration, sedimentation, viscosity, and circular dichroism techniques. The effects of sodium dodecyl sulfate, alkaline pH, guanidine hydrochloride, and calcium ions on the hydrodynamic properties of the protein were studied. Calsequestrin, in the absence of calcium, had a random coil conformation with an alpha-helical content of 11%. Calsequestrin bound 1.7 mg of sodium dodecyl sulfate per mg of protein resulting in an increase in the alpha-helical content to 20%. The protein was completely random coil in guanidine hydrochloride and had a molecular weight of 42,000 as determined by gel filtration in the presence of this denaturant. Sedimentation equilibrium studies showed that calsequestrin was not subjected to aggregation and had a molecular weight of 38,000. Calsequestrin had a low sedimentation coefficient (2.20 S), a high Stokes radius (45 A), and a high intrinsic viscosity (27.1 ml/g) that increased slightly to 32 ml/g in the presence of guanidine hydrochloride, all indicative of a highly extended structure. Similar studies, performed at pH 9.5, revealed that the protein was even more asymmetric at alkaline pH. Calsequestrin bound 50 mol of calcium ions per mol of protein with an affinity of 1 mM as determined by gel filtration. Calcium binding was accompanied by a change of the protein from a highly extended structure (Rs = 45 A) to a much more compact structure (Rs = 35 A).