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D J Forbes

Publications and source records attributed to D J Forbes.

40 records · Page 3Linked to original sources
PubMedDate not supplied

Separate nuclear import pathways converge on the nucleoporin Nup153 and can be dissected with dominant-negative inhibitors.

BACKGROUND: Proteins generally enter or exit the nucleus as cargo of one of a small family of import and export receptors. These receptors bear distant homology to importin beta, a subunit of the receptor for proteins with classical nuclear localisation sequences (NLSs). To understand the mechanism of nuclear transport, the next question involves identifying the nuclear pore proteins that interact with the different transport receptors as they dock at the pore and translocate through it. RESULTS: Two pathways of nuclear import were found to intersect at a single nucleoporin, Nup153, localized on the intranuclear side of the nuclear pore. Nup153 contains separate binding sites for importin alpha/beta, which mediates classical NLS import, and for transportin, which mediates import of different nuclear proteins. Strikingly, a Nup153 fragment containing the importin beta binding site acted as a dominant-negative inhibitor of NLS import, with no effect on transportin-mediated import. Conversely, a Nup153 fragment containing the transportin binding site acted as a strong dominant-negative inhibitor of transportin import, with no effect on classical NLS import. The interaction of transportin with Nup153 could be disrupted by a non-hydrolyzable form of GTP or by a GTPase-deficient mutant of Ran, and was not observed if transportin carried cargo. Neither Nup153 fragment affected binding of the export receptor Crm1 at the nuclear rim. CONCLUSIONS: Two nuclear import pathways, mediated by importin beta and transportin, converge on a single nucleoporin, Nup153. Dominant-negative fragments of Nup153 can now be used to distinguish different nuclear import pathways and, potentially, to dissect nuclear export.

Animals↗
PubMedDate not supplied

Lipid tolerance in the very low birth weight infant on intravenous and enteral feedings.

Nutrition is of critical importance to very low birth weight (VLBW) survival. Intravenous (iv) lipid tolerance has been studied using a soybean or safflower-based lipid emulsion. We studied lipid levels in a group of VLBW infants on both intravenous lipids (soybean-safflower emulsion) and on enteral feedings (24 cal/oz premature formula). Levels were obtained on 1, 2, and 3 g/kg/day of iv lipid and after 3 and 10 days of feeding. Triglyceride (TG) and free fatty acid (FFA) proved the most sensitive indicator of both iv and enteral tolerance. The higher the lipid dose, the more likely there would be elevated lipid levels, especially FFA. Mean lipid levels for the group of enteral-fed infants were normal. Comparison of lipid levels on iv to those on enteral feedings showed significant differences in trough iv levels of TG compared to preprandial TG. FFAs tended to be significantly higher on iv feedings. Monitoring lipid levels on iv and enteral feedings is appropriate to document tolerance.

Drug Tolerance↗