Identification, expression analysis, genomic organization and cellular location of a novel protein with a RhoGEF domain.

In this study we describe the identification and characterization of a novel cytosolic protein of the guanine exchange factor (GEF) family. The human cDNA corresponds to predicted human protein FLJ00128/FLJ10357 located on chromosome 14q11.2.

Cocaine exposure decreases GABA neuron migration from the ganglionic eminence to the cerebral cortex in embryonic mice.

Recurrent exposure of the developing fetus to cocaine produces persistent alterations in structure and function of the cerebral cortex. Neurons of the cerebral cortex are derived from two sources: projection neurons from the neuroepithelium of the dorsal pallium and interneurons from the ganglionic eminence of the basal telencephalon. The interneurons are GABAergic and reach the cerebral cortex via a tangential migratory pathway.

Modulation of the membrane-binding projection domain of tau protein: splicing regulation of exon 3.

Tau is a microtubule-associated protein whose transcript undergoes complex regulated splicing in the mammalian nervous system. The N-terminal domain of the protein interacts with the axonal membrane, and is modulated by differential inclusion of exons 2 and 3. These two tau exons are alternatively spliced cassettes, in which exon 3 never appears independently of exon 2.

Viral vector-mediated delivery of competing glycosyltransferases modifies epitope expression cell specifically.

The glycoconjugate epitopes 3-fucosyl-N-acetyllactosamine (CD15) and sulfoglucuronylcarbohydrate (SGC) mediate cell adhesion events in several systems, and are regulated both spatially and temporally during cerebellar development. In cotransfection studies using COS-1 cells, competition between glycosyltransferases that utilize a common precursor involved in the final synthetic steps of these epitopes, can modulate epitope expression. For example, cotransfection of rat alpha1,3-fucosyltransferase IV (Fuc-TIV) and either rat glucuronic acid transferase P (GlcAT) or pig alpha1,3-galactosyltransferase (GalT) resulted in the dominance of either SGC or GalalphaGal epitope expression, respectively, with blockage of CD15 epitope expression.

The splicing determinants of a regulated exon in the axonal MAP tau reside within the exon and in its upstream intron.

Tau is a microtubule-associated protein whose transcript undergoes complex regulated splicing in the mammalian nervous system. Exon 6 of the gene is an alternatively spliced cassette whose expression profile is distinct from that of the other tau regulated exons, implying the utilization of distinct regulatory factors. Previous work had established the use of cryptic splice sites within exon 6 and the influence of flanking exons on the ratio of exon 6 variants.

Restriction of high CD15 expression to a subset of rat cerebellar astroglial cells can be overcome by transduction with adenoviral vectors expressing the rat alpha 1,3-fucosyltransferase IV gene.

Glycoconjugates bearing the epitope 3-fucosyl-N-acetyllactosamine (CD15) are believed to be involved in cell-cell interactions and are temporally and spatially regulated in the brain. In the rat postnatal cerebellum, CD15 is predominantly expressed in the molecular layer by Bergmann glial cells, but little CD15 expression is seen in other astroglia, and the basis for this restricted expression is not known. Adenoviral vectors were shown to efficiently deliver transgenes to cerebellar glial cells and were used to determine whether manipulation of glycosyltransferase activities could enhance the expression of CD15 in these cells.

Complex regulation of tau exon 10, whose missplicing causes frontotemporal dementia.

Tau is a microtubule-associated protein whose transcript undergoes complex regulated splicing in the mammalian nervous system. Exon 10 of the gene is an alternatively spliced cassette that is adult-specific and that codes for a microtubule binding domain. Recently, mutations that affect splicing of exon 10 have been shown to cause inherited frontotemporal dementia (FTDP).

Consideration of alternative accounts of gender-linked speech patterns in individuals with mental retardation.

Several preliminary reports have reported the existence of gender influences on the communication patterns of individuals with mental retardation. This study considers two alternative hypotheses to the conclusion that the reported effects were attributable to gender. Two studies extend a previous analysis by further exploration of the original transcripts (Study 1) and addition of participants (Study 2).

Gender differences in the use of linguistic devices by youths with mental retardation: a preliminary analysis.

One potential influence on communication behavior that is often overlooked in the field of mental retardation is the effect of gender. Two recent studies reporting gender-related differences in social (Wilkinson & Romski, 1995) and semantic (Wilkinson & Murphy, 1998) aspects of communication have underscored the need to examine the role of gender in this population. The relative use by males and females with mental retardation of linguistic (grammatical) devices identified as characteristic of typical female speech (qualifying markers, question styles, and politeness terms) was examined.

Reduction of stimulus overselectivity with nonverbal differential observing responses.

Three individuals with mental retardation exhibited stimulus overselectivity in a delayed matching-to-sample task in which two sample stimuli were displayed on each trial. Intermediate accuracy scores indicated that participants could match one of the samples but not both of them. Accuracy in a baseline condition was compared to accuracy with a differential observing response procedure.

References to people in the communications of female and male youths with mental retardation.

Gender-related differences have consistently been reported in the language of adults and children with no disabilities. One well-replicated finding is that females discuss people and relationships more often than do males, particularly in conversations with other females. These stylistic variations in language are considered to have implications for the adaptive functioning of language users, most particularly females.

Splicing of a regulated exon reveals additional complexity in the axonal microtubule-associated protein tau.

Tau is a microtubule-associated protein whose transcript undergoes complex regulated splicing in the mammalian nervous system. Exon 6 of the gene is an alternatively spliced cassette whose expression pattern and splicing regulation had not been previously analyzed in the human. The expression profile of exon 6 is completely different from that of the better-analyzed exons 2, 3, 4A, and 10, implying the utilization of distinct regulatory factors.

Effect of exogenous GM1 on ethanol sensitivity in selectively bred mouse lines.

Ethanol sensitive long-sleep (LS) and ethanol resistant short-sleep (SS) mice are lines that have been genetically selected for differential central nervous system sensitivities to the hypnotic effect of ethanol. Because they were genetically selected only for differences in sensitivity to ethanol hypnosis, biochemical and physiological differences between them are likely related to their differential ethanol sensitivity. The synaptosomal and whole brain concentration of GM1 ganglioside was previously shown to differ significantly between the lines.

Auditory discrimination reversal learning and assessment of behavioral teratogenesis in rats.

Qualitative auditory discrimination procedures were used to evaluate discrimination acquisition and reversal learning in rats. Twelve adult rats prenatally exposed to ethanol (ETOH) and 12 unexposed isocaloric controls (CON) were given training with a positively reinforced successive discrimination procedure. Most ETOH subjects were impaired relative to CON subjects on accuracy during early training sessions and the number of sessions required to meet an 80% accuracy criterion.

Expression of neolactoglycolipids: sialosyl-, disialosyl-, O-acetyldisialosyl- and fucosyl- derivatives of neolactotetraosyl ceramide and neolactohexaosyl ceramide in the developing cerebral cortex and cerebellum.

The following neolacto glycolipids were identified and their developmental expression was studied in the rat cerebral cortex and cerebellum: Fuc alpha 1-3IIInLcOse4Cer,Fuc alpha 1-3VnLcOse6Cer and (Fuc)2 alpha 1-3III,3VnLcOse6Cer, as well as acidic glycolipids, NeuAc alpha 2-3IVnLcOse4Cer [nLM1], (NeuAc)2 alpha 2-3IVnLcOse4Cer [nLD1], O-acetyl (NeuAc)2 alpha 2-3IVnLcOse4Cer [OAc-nLD1] and their higher neolactosaminyl homologues NeuAc alpha 2-3VlnLcOse6Cer [nHM1] and (NeuAc)2 alpha 2-3VlnLcOse6Cer [nHD1]. These glycolipids were expressed in the cerebral cortex only during embryonic stages and disappeared postnatally. This loss was ascribed to the down regulation of the synthesis of the key precursor LcOse3Cer which is synthesized by the enzyme lactosylceramide: N-acetylglucosaminyl transferase.

Glucuronic acid-conjugated dihydroxy fatty acids in the urine of patients with generalized peroxisomal disorders.

Urine extracts from children diagnosed with generalized peroxisomal disorders were screened by continuous flow-negative ion fast atom bombardment-mass spectrometry. In 45 of 60 children with generalized peroxisomal disorders, we observed one or more intense ions (m/z 489, 505, 461, and others) that are infrequently found in children with cholestatic liver disease or normal children. Compounds giving rise to these ions were isolated using reverse phase and anion exchange chromatography.

Marked heterogeneity in Niemann-Pick disease, type C. Clinical and ultrastructural findings.

Niemann-Pick disease type C (NP-C) is an autosomal recessive lysosomal lipid storage disorder of unknown etiology. Diagnosis of NP-C is based on characteristic clinical findings and reduced fibroblast esterification of LDL-derived cholesterol. We describe three patients who demonstrate the NP-C spectrum of clinical heterogeneity in age of onset, presenting signs, pattern of organ system involvement, and natural history.

Expression of glycosphingolipids in serum-free primary cultures of mouse kidney cells: male-female differences and androgen sensitivity.

The expression of neutral glycosphingolipids was examined in primary kidney cell cultures derived from adult male and female beige mutant mice (C57BL/6J;bgj/bgj) with enrichment for proximal tubule cells during preparation of explants and using defined serum-free medium for the culture conditions. Cells proliferated for 7 days in vitro to provide confluent or nearly confluent monolayers of epithelial-type growth indicative of proximal tubule cells. The male vs female differences in neutral glycosphingolipids seen in the kidney in vivo were retained in these 7 day cultures.

Rat olfactory neurons can utilize the endogenous lectin, L-14, in a novel adhesion mechanism.

L-14 is a divalent, lactosamine-binding lectin expressed in many vertebrate tissues. In the rat nervous system, L-14 expression has been observed previously in restricted neuronal subsets within the dorsal root ganglia and spinal cord. In this study we report that L-14 is expressed by nonneuronal cells in the rat olfactory nerve.

A note on transfer of stimulus control in the delayed-cue procedure: facilitation by an overt differential response.

This case study describes initially unsuccessful attempts to use the delayed-cue procedure to teach conditional discriminations to an individual with moderate mental retardation. The task was matching printed-word comparison stimuli to dictated-name sample stimuli. In three experiments, the subject typically waited for the delayed cue unless differential responses to the dictated samples (repeating the sample names) were required.

N-acetylglucosaminyltransferase regulates the expression of neolactoglycolipids including sulfoglucuronylglycolipids in the developing nervous system.

Lactosylceramide N-acetylglucosaminyltransferase (GlcNac-Tr) in the synthesis of lactotriosylceramide (LcOse3Cer) was characterized in the nervous system. The microsomal membrane GlcNAc-Tr required a divalent metal ion, preferably Mn2+, and a nonionic detergent. The pH optimum was around 7.

Purification and immunological characterization of acid beta-galactosidase from dog liver.

1. Dog liver acid beta-galactosidase was isolated in high yield and purified to homogeneity using a series of chromatographies on Con A-Sepharose, decyl-agarose, anion-exchange HPLC and gel-filtration HPLC. 2.

The accumulation and metabolism of glycosphingolipids in primary kidney cell cultures from beige mice.

In the normal C57BL/6J male mouse a specific subset of the kidney glycosphingolipids which is associated with multilamellar bodies of lysosomal origin and represents about 10% of the total kidney glycolipids, is excreted into the urine each day. This excretion is blocked and glycosphingolipids accumulate in the kidney of bgJ/bgJ mutants of this strain. To examine this process in vitro, glycosphingolipid metabolism and excretion were studied in beige mouse kidney cell cultures.