Search PubMed⌕ Search

Biomedical subjects

J D Moore

Publications and source records attributed to J D Moore.

At least 109 records · Page 6Linked to original sources

Nuclear import of Cdk/cyclin complexes: identification of distinct mechanisms for import of Cdk2/cyclin E and Cdc2/cyclin B1.

Reversible phosphorylation of nuclear proteins is required for both DNA replication and entry into mitosis. Consequently, most cyclin-dependent kinase (Cdk)/cyclin complexes are localized to the nucleus when active. Although our understanding of nuclear transport processes has been greatly enhanced by the recent identification of nuclear targeting sequences and soluble nuclear import factors with which they interact, the mechanisms used to target Cdk/cyclin complexes to the nucleus remain obscure; this is in part because these proteins lack obvious nuclear localization sequences. To elucidate the molecular mechanisms responsible for Cdk/cyclin transport, we examined nuclear import of fluorescent Cdk2/cyclin E and Cdc2/cyclin B1 complexes in digitonin-permeabilized mammalian cells and also examined potential physical interactions between these Cdks, cyclins, and soluble import factors. We found that the nuclear import machinery recognizes these Cdk/cyclin complexes through direct interactions with the cyclin component. Surprisingly, cyclins E and B1 are imported into nuclei via distinct mechanisms. Cyclin E behaves like a classical basic nuclear localization sequence-containing protein, binding to the alpha adaptor subunit of the importin-alpha/beta heterodimer. In contrast, cyclin B1 is imported via a direct interaction with a site in the NH2 terminus of importin-beta that is distinct from that used to bind importin-alpha.

Animals↗

Radiation exposure to children during coil occlusion of the patent ductus arteriosus.

The risks of excessive exposure to ionizing radiation are well described and measures are routinely taken to limit such exposure to both patient and personnel in the catheterization laboratory. Coll occlusion of the patent ductus arteriosus (PDA) as well as other more complex pediatric interventions has raised concern regarding radiation exposure, particularly as minimally invasive surgical techniques are being developed which lack such exposure risk. In eight consecutive patients, aged 0.7-7 years (median, 2.3 years), coil occlusion of a PDA was performed and surface entrance radiation dose determined by thermoluminescent dosimetry (TD). Total cumulative doses (PA + lateral dose) were also calculated for each patient. Entrance and cumulative dose was likewise measured in 12 patients undergoing standard diagnostic catheterization (DC) and in 5 consecutive patients undergoing pulmonary balloon valvuloplasty (PBV). The groups were comparable in age, weight, and body surface area (BSA). Total cumulative dose in the PDA patients was 97 +/- 25 mGy (mean +/- SE). There was no significant difference between the three groups in entrance dose absorbed at each location or in total cumulative dose. The mean total fluoroscopy time in the PDA occlusion group was significantly less than that of the PBV group (10.1 +/- 1.81 min vs. 19.3 +/- 2.29 min, P < 0.05) but was comparable to the DC group (13.2 +/- 1.5 min, P = NS). When the subjects were analyzed collectively, no correlation between fluoroscopy time and measured entrance dose was observed. The strongest correlates of total cumulative dose were patient weight (r = 0.67, P < 0.001) and BSA (r = 0.62, P = 0.001). Patients undergoing coil occlusion of a PDA are not exposed to increased radiation entrance dose compared to those undergoing standard DC and PBV. Furthermore, surface entrance radiation dose as determined by TD varies according to patient size for a given fluoroscopy time.

Body Height↗

Transient rheology of a polyethylene melt under shear.

Using nonequilibrium molecular dynamics simulation, we have studied the response of a C100 model polymer melt to a step change from equilibrium to a constant, high shear rate flow. The transient shear stress of the model polymer melt exhibits pronounced overshoot at the strain value predicted by the reptation model, in striking similarity to melts of longer, entangled polymer governed by reptation motion. At the maximum of shear stress overshoot, the molecular orientational order and the alignment angle are found to be midway between those characteristic of Newtonian flow and full alignment with the flow. The Doi-Edwards theory is found to be applicable but only by taking into account the shear-rate-dependence of the terminal relaxation time. We further analyze the molecular origins of such behavior in short polymer chains by decomposing the total stress into the contributions from various molecular interactions.

Journal Article↗