ABSTRACT. Twelve wild born mandrills (Mandrillus sphinx), six males, six females, were studied in a 1.4-ha forest enclosure in Gabon Africa. Seventy-six percent of their food was obtained from the ground (45 ~ unidentified food objects foraged from the leaf litter, 21 ~ from ground plants, and 10 ~o animal matter) while 23 % was taken from arboreal sources (10 ~o from trees, 10 ~o from vines, and 3 % from shrubs). Plant parts eaten include seeds, roots, fruits, stem pith, apical branch ends, mature and immature leaves, nuts, buds, blossoms, and bark. There were significant dietary differences between sexes. There were also individual dietary differences both in preferred foods and arboreal vs terrestrial foraging locations. At nearly all times of the day at least 70 ~ of the study group was on the ground. Sixty-four percent of their time was spent feeding, with females spending more time feeding than males. High rates of feeding were seen throughout the day, with high individual variances, which is explained by individual food preferences and a temporal partitioning of the food resources. These findings are compared to those observed in wild mandrills and other baboons.

The potential for using antisense compounds as therapeutic agents has generated great enthusiasm. Strategies for delivery of these compounds are, therefore, of great interest. Transdermal iontophoresis has been used successfully as an enhancement technique for the transdermal delivery of these compounds in vitro. The effectiveness of using percutaneous penetration as a means to deliver therapeutic levels of these compounds in vivo, however, remains to be demonstrated. The purpose of this work was to demonstrate the ability of iontophoretically delivered compounds to alter enzyme levels in the intact rat. A C5 propyne-modified phosphorothioate oligonucleotide (PS-ODN) targeted to the cytochrome p450-3A2 (CYP3A2) mRNA translational start site and the reverse sequence, used as a control, were synthesized. A patch containing either an oligonucleotide or a buffer control was placed on the animal's back, and an iontophoretic current of 0.5 mA/cm2 was applied for 3.5 hours. Twenty-four hours later, CYP3A2 levels were measured noninvasively using the midazolam-induced sleeping rat model. Liver and small intestinal microsomes were made after completion of sleep studies and assayed for CYP3A2, CYP1A1/2, CYP2B1/2, and CYP2E1. Midozolam-treated animals with antisense to CYP3A2 slept significantly longer than did the controls (p < 0.05). CYP3A2 levels were significantly lower in liver microsomes from antisense-treated animals than in either buffer control (p < 0.001) or reverse sequence animals (p < 0.05). The reverse sequence was also significantly different from the buffer control (p < 0.01), indicating a nonspecific effect of the PS background. Nontarget cytochrome levels were not altered by treatment. There were no significant differences in small intestine CYP3A2 levels between treatment groups. These data demonstrate that transdermally delivered PS-ODN can reach concentrations sufficient to induce changes in specific target enzymes in vivo. Further studies are warranted to investigate potential uses for these molecules.

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The murine E-protein gene ME1 encodes a nontissue-specific, helix-loop-helix transcription factor that is associated with morphological development. ME1 gene expression is regulated by a TATA-less promoter that contains multiple Sp1 consensus elements, E-boxes, and a novel transcription initiation site. In this study, we compared DNA homologous to the ME1 promoter from vertebrate species ranging from frog to human. A region of striking sequence similarity was identified in a region corresponding to the ME1 transcription initiation site (ME1 Inr). Within this region, a poly d(A) tract and a 9-bp inverted repeat (5P-GTCCGCCTG) were highly conserved in all species that were examined. Protein complexes that recognized these DNA elements were present among distant vertebrates (frog, chick, monkey and human), and were able to bend the ME1 Inr to a similar extent (V60³) as the previously described murine MBPK K and MBPL L proteins. Collectively, these results suggest that an ME1 Inr-like element and its associated proteins functioned in an ancestral vertebrate more than 350 million years ago.z 1998 Federation of European Biochemical Societies.