Influence of treatment duration on audiogenic seizure susceptibility during barbiturate withdrawal in rats

Barbiturate withdrawal seizure susceptibility in rats increased with increasing duration of treatment during a 15-day treatment period in which the animals were given an i.p. dose of sodium barbital every 12 h. This method of producing dependence has clear advantages over previously described methods.     

Insights from retinitis pigmentosa into the roles of isocitrate dehydrogenases in the Krebs cycle

Here we describe two families with retinitis pigmentosa, a hereditary neurodegeneration of rod and cone photoreceptors in the retina. Affected family members were homozygous for loss-of-function mutations in IDH3B, encoding the beta-subunit of NAD-specific isocitrate dehydrogenase (NAD-IDH, or IDH3), which is believed to catalyze the oxidation of isocitrate to alpha-ketoglutarate in the citric acid cycle. Cells from affected individuals had a substantial reduction of NAD-IDH activity, with about a 300-fold increase in the K(m) for NAD. NADP-specific isocitrate dehydrogenase (NADP-IDH, or IDH2), an enzyme that catalyzes the same reaction, was normal in affected individuals, and they had no health problems associated with the enzyme deficiency except for retinitis pigmentosa. These findings support the hypothesis that mitochondrial NADP-IDH, rather than NAD-IDH, serves as the main catalyst for this reaction in the citric acid cycle outside the retina, and that the retina has a particular requirement for NAD-IDH.     

Genome-wide variation and identification of vaccine targets in the Plasmodium falciparum genome

One goal in sequencing the Plasmodium falciparum genome, the agent of the most lethal form of malaria, is to discover vaccine and drug targets. However, identifying those targets in a genome in which approximately 60% of genes have unknown functions is an enormous challenge. Because the majority of known malaria antigens and drug-resistant genes are highly polymorphic and under various selective pressures, genome-wide analysis for signatures of selection may lead to discovery of new vaccine and drug candidates. Here we surveyed 3,539 P. falciparum genes ( approximately 65% of the predicted genes) for polymorphisms and identified various highly polymorphic loci and genes, some of which encode new antigens that we confirmed using human immune sera. Our collections of genome-wide SNPs ( approximately 65% nonsynonymous) and polymorphic microsatellites and indels provide a high-resolution map (one marker per approximately 4 kb) for mapping parasite traits and studying parasite populations. In addition, we report new antigens, providing urgently needed vaccine candidates for disease control.     

Characteristics of swift fox dens in northwest Texas

The swift fox ( Vulpes velox ) was classified in 1995 as a candidate for listing under the Endangered Species Act. Since then, several studies have addressed survey methods for monitoring swift fox populations. The purpose of this paper is to assist field researchers in documenting the presence of swift foxes by identification of recently active den sites. We propose that swift foxes have unique external den characteristics that can be distinguished during aerial surveys. We collected data from 30 swift fox den complexes on both continuous rangeland and landscapes fragmented by cropland in northwest Texas. There were no differences in den characteristics between landscape types ( P > 0.10). The number of openings per den ranged from 1 to 8 and had an average opening height of 20 cm. As number of openings increased, the maximum distance between openings also increased ( r = 0.88, P Canis latrans ) and red foxes ( Vulpes vulpes ), 2 species that can be sympatric with swift foxes. We suggest that aerial den searching followed by ground verification may be an effective technique for determining presence of swift foxes in areas of short-grass prairies and fragmented habitats.     

A point mutation of the rhodopsin gene in one form of retinitis pigmentosa

The gene for autosomal dominant retinitis pigmentosa in a large pedigree of Irish origin has recently been found to be linked to an anonymous polymorphic sequence, D3S47 (C17), from the long arm of chromosome 3. As the gene coding for rhodopsin is also assigned to the long arm of chromosome 3 and is expressed in rod photoreceptors that are affected early in this blinding disease, we searched for a mutation of the rhodopsin gene in patients with autosomal dominant retinitis pigmentosa. We found a C----A transversion in codon 23 (corresponding to a proline----histidine substitution) in 17 of 148 unrelated patients and not in any of 102 unaffected individuals. This result, coupled with the fact that the proline normally present at position 23 is highly conserved among the opsins and related G-protein receptors, indicates that this mutation could be the cause of one form of autosomal dominant retinitis pigmentosa.