Androgens regulate the mammalian homologues of invertebrate sex determination genes tra-2 and fox-1.

Androgens, like other steroid hormones, exert profound effects on cell growth and survival by modulating the expression of target genes. In vertebrates, androgens play a critical role downstream of the testis determination pathway, influencing the expression of sexually dimorphic traits. Among cells of the nervous system, motor neurons respond to trophic effects of androgen stimulation, with a subpopulation of spinal motor neurons exhibiting sexually dimorphic survival. To study the mechanisms of androgen action in these cells, we performed a subtractive screen for genes upregulated by androgen in a motor neuron cell line. We show androgen-inducible expression of two RNA-binding proteins that are the mammalian homologues of invertebrate sex determination genes. Androgens upregulate the expression of tra-2alpha, an enhancer of RNA splicing homologous to Drosophila tra-2, and promote redistribution of the protein from a diffuse to a speckled pattern within the nucleus. Similarly, androgens upregulate the expression of a novel gene homologous to Caenorhabditis elegans fox-1. These data indicate that androgens exert their effects, in part, by modulating the expression and function of genes involved in RNA processing, and identify homologues of invertebrate sex determination genes as androgen-responsive genes in mammals.

Cloning and genomic organization of the mouse gene slc23a1 encoding a vitamin C transporter.

Vitamin C is known to exist in particularly high concentrations in brain tissue, and its free radical scavenging function is thought to represent a major antioxidative defense system. We have cloned, sequenced and analyzed the genomic structure of a mouse sodium-dependent vitamin C transporter gene, Slc23a1 (also known as Svct2). The mouse Slc23a1 cDNA is 6.4 kb long and was cloned directly from a mouse brain RNA preparation. Hybridization screening of a mouse genomic BAC library identified BAC 53L21 which contains at least the entire coding sequence of the mouse Slc23a1 gene. Determination of the exon-intron structure of the gene revealed 17 exons ranging from 58 bp to 4407 bp extending over 50 kb of the mouse genome, with the translation start codon located in exon 3. Its 1944 nucleotide open reading frame encodes a polypeptide of 647 aa, which is highly similar to rat and human orthologs. The mouse gene was assigned to chromosome 2qG2 by fluorescence in situ hybridization analysis. Expression of this gene was demonstrated in a wide range of tissues, with especially high levels in brain. Neurodegenerative diseases with an established role for oxidative stress in the cytoplasm may therefore be conditions of SLC23A1 dysfunction. Key words: gene structure; Vitamin C; transporter; oxidative stress

Workforce demand for neurosurgeons in the United States of America: a 13-year retrospective study.

OBJECT: The workforce demand for neurosurgeons was quantified by a review and an analysis of journal recruitment advertisements published over the past 13 years. METHODS: A retrospective analysis of recruitment advertisements from July 1985 through June 1998 was performed by examining issues of the Journal of Neurosurgery and Neurosurgery. Advertisement information that appeared in each journal during the last 3 years was collected from alternating months (July to May); information that appeared prior to that time was collected from alternating recruitment years back to 1985. The authors examined the following workforce parameters: practice venue, subspecialization, and practice size. They found no significant decrease in neurosurgical recruitment advertisements. There was an average of 102.7+/-22.4 (standard deviation) advertised positions per year during the most recent 3 years compared with 92.6+/-17.9 advertised positions per year during the preceding decade. Similarly, there has been no decline in advertised positions either in academic (33+/-6.1/year for the most recent 3 years compared with 32.8+/-5.9/year for 1985-1995) or private practice (69.7+/-21.6/year for the most recent 3 years compared with 59.8+/-13.4/year for 1985-1995). A shift in demand toward subspecialty neurosurgery was observed. During the past 3 years, 31.2+/-5.9% of advertised positions called for subspecialty expertise, compared with 18.5+/-2.8% for the preceding decade (p < 0.05). The largest number of subspecialty advertisements designated positions for spine and pediatric neurosurgeons. Private practice advertisements increasingly sought to add neurosurgeons to group practices. CONCLUSIONS: Contrary to previous reports and a prevailing myth, our data show no decrease in workforce demand for neurosurgeons in the United States over the past 3 years compared with the prior decade. A shift toward subspecialist recruitment, particularly for spine neurosurgeons, has been demonstrated in both academic and private practice venues.

Autosomal dominant distal spinal muscular atrophy type V (dSMA-V) and Charcot-Marie-Tooth disease type 2D (CMT2D) segregate within a single large kindred and map to a refined region on chromosome 7p15.

Two separate disorders, autosomal dominant distal spinal muscular atrophy type V (dSMA-V) characterized by marked bilateral weakness in the hands and atrophy of thenar eminence and the first interosseous muscle, and Charcot-Marie-Tooth disease type 2D (CMT2D) characterized by sensory deficits in addition to the upper limb weakness and wasting, have been independently linked to chromosome 7p. We identified a multigenerational Mongolian kindred with 17 members affected with either dSMA-V or CMT2D and mapped both syndromes to the same region on chromosome 7p15. A maximum two-point lod score of 4.74 at recombination fraction zero was obtained with marker D7S474. Tight linkage without recombination was also detected with markers D7S526 and D7S632. A multipoint lod score of 6.07 suggested that the gene is located between markers D7S526 and D7S474. A single conserved haplotype was associated with dSMA-V and CMT2D. Based on informative recombination events, the disease locus was placed between markers D7S516 and D7S1514 within the 7p15 band. Data obtained from this study suggest that a single gene is responsible for both syndromes, dSMA-V and CMT2D, and extend our knowledge of the candidate region.