Retinoic acid is detected at relatively high levels in the CNS of adult rats

Retinoic acid (RA) is essential for cellular growth and differentiation in developing and adult animals. The central nervous system (CNS) suffers developmental defects if embryonic levels of RA are too high or too low. The production and function of RA in adult brain are unclear. We report that RA is present throughout the brain and spinal cord of adult, vitamin A-deficient (VAD) rats treated with a physiological amount of all-trans-retinol. The hippocampus/cortex contained the highest proportion of RA in the brain (27.2 +/- 2.9% of the organic phase radioactivity, and 23.5 +/- 0.8% of the organic phase radioactivity extracted from spinal cord was RA). RA comprises a higher proportion of the retinoid pool in the CNS compared with amounts reported in other target tissues (E Werner and HF DeLuca. Arch Biochem Biophys 393: 262-270, 2001). However, RA is not preferentially transported from the blood to the brain. There were 2.90 +/- 0.20 fmol RA/g tissue transported to the brain of VAD rats treated with 2.00 nmol [20-(3)H]all-trans-retinoic acid, but higher amounts of RA were delivered to the liver, testis, and spleen. Because RA is not transported preferentially to brain, this tissue likely synthesizes RA more efficiently than other target tissues.     

Roundup: a multi-genome repository of orthologs and evolutionary distances

SUMMARY: We have created a tool for ortholog and phylogenetic profile retrieval called Roundup. Roundup is backed by a massive repository of orthologs and associated evolutionary distances that was built using the reciprocal smallest distance algorithm, an approach that has been shown to improve upon alternative approaches of ortholog detection, such as reciprocal blast. Presently, the Roundup repository contains all possible pair-wise comparisons for over 250 genomes, including 32 Eukaryotes, more than doubling the coverage of any similar resource. The orthologs are accessible through an intuitive web interface that allows searches by genome or gene identifier, presenting results as phylogenetic profiles together with gene and molecular function annotations. Results may be downloaded as phylogenetic matrices for subsequent analysis, including the construction of whole-genome phylogenies based on gene-content data. AVAILABILITY: http://rodeo.med.harvard.edu/tools/roundup.     

Isolation and identification of 24-hydroxyvitamin D2 and 24,25-dihydroxyvitamin D2

The isolation and identification of two metabolites of vitamin D₂ found in mammalian and avian species are reported. They are 24-hydroxyvitamin D₂ and 24,25-dihydroxyvitamin D₂. Their existence suggests that 24-hydroxylation occurs in a sterospecific manner in the 24R position and adds further support to the theory that vitamin D₂ metabolism qualitatively parallels that of vitamin D₃.     

24,24-Difluoro-1,25-dihydroxyvitamin D3: In vitro production,isolation, and biological activity

24,24-Difluoro-1,25-dihydroxyvitamin D₃ has been synthesized by in vitro incubation of vitamin D-deficient chick kidney homogenates with 24,24-difluoro-25-dihydroxyvitamin D₃. The compound produced was isolated and purified by successive high-performance liquid chromatographic steps and then identified by means of ultraviolet absorption spectrophotometry and mass spectrometry. The difluoro analog of 1,25-dihydroxyvitamin D₃ is found to be highly active in stimulating intestinal calcium transport and bone calcium mobilization in vitamin D₃-deficient rats.     

Determination of biological activity of 24,24-difluoro-1,25-dihydroxyvitamin D3 in the chick using a new method for assessing intestinal calcium uptake

Oxygen-dependent calcium uptake by chick duodenal discs has been characterized and used to assay the relative activities of 1,25-dihydroxyvitamin D₃ and its 24,24-difluoro analog. The calcium uptake was found to be stimulated by low sodium (30 mm) and phosphate (0.01–0.3 mm). The rate of oxygen-dependent calcium uptake was found half-maximal at a calcium concentration of 5 mm. At a concentration of 5 mm calcium, the uptake was linear for at least 15 min with approximately a threefold stimulation by prior administration of 1,25-dihydroxyvitamin D₃ (125 ng). This determination, as well as increase in serum calcium and percentage bone ash, was used to assess the biological activities of 1,25-dihydroxyvitamin D₃ and its 24,24-difluoro analog. The difluoro analog is about four to five times more active than 1,25-dihydroxyvitamin D₃ as measured in each of these systems.