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D J Dean

Publications and source records attributed to D J Dean.

At least 19 recordsLinked to original sources

Quadrupole deformation of the self-conjugate nucleus 72Kr.

We report on the first determination of the absolute B(E2;0+(1)-->2+(1)) excitation strength in the N=Z nucleus 72Kr. 72Kr is the heaviest N=Z nucleus for which this quantity has been measured and provides a benchmark in a region of the nuclear chart dominated by rapidly changing deformations and shapes mediated by the interplay of strongly oblate and prolate-driving orbitals. The deduced quadrupole deformation strength is in agreement with a variety of self-consistent models that predict an oblate shape for the ground state of 72Kr. Large-scale shell-model Monte Carlo calculations reproduce the experimental B(E2) value and link the result to the occupation of the deformation-driving g9/2 orbit.

Journal Article↗

Ab-initio coupled-cluster study of 16O.

We report converged results for the ground and excited states and matter density of 16O using realistic two-body nucleon-nucleon interactions and coupled-cluster methods and algorithms developed in quantum chemistry. Most of the binding is obtained with the coupled-cluster singles and doubles approach. Additional binding due to three-body clusters (triples) is minimal. The coupled-cluster method with singles and doubles provides a good description of the matter density, charge radius, charge form factor, and excited states of a one-particle, one-hole nature, but it cannot describe the first-excited 0(+) state. Incorporation of triples has no effect on the latter finding.

Journal Article↗

Coupled cluster calculations of ground and excited states of nuclei.

The standard and renormalized coupled cluster methods with singles, doubles, and noniterative triples and their generalizations to excited states, based on the equation of motion coupled cluster approach, are applied to the 4He and 16O nuclei. A comparison of coupled cluster results with the results of the exact diagonalization of the Hamiltonian in the same model space shows that the quantum chemistry inspired coupled cluster approximations provide an excellent description of ground and excited states of nuclei. The bulk of the correlation effects is obtained at the coupled cluster singles and doubles level. Triples, treated noniteratively, provide the virtually exact description.

Journal Article↗

Consequences of nuclear electron capture in core collapse supernovae.

The most important weak nuclear interaction to the dynamics of stellar core collapse is electron capture, primarily on nuclei with masses larger than 60. In prior simulations of core collapse, electron capture on these nuclei has been treated in a highly parametrized fashion, if not ignored. With realistic treatment of electron capture on heavy nuclei come significant changes in the hydrodynamics of core collapse and bounce. We discuss these as well as the ramifications for the postbounce evolution in core collapse supernovae.

Journal Article↗

Electron capture rates on nuclei and implications for stellar core collapse.

Supernova simulations to date have assumed that during core collapse electron captures occur dominantly on free protons, while captures on heavy nuclei are Pauli blocked and are ignored. We have calculated rates for electron capture on nuclei with mass numbers A=65-112 for the temperatures and densities appropriate for core collapse. We find that these rates are large enough so that, in contrast to previous assumptions, electron capture on nuclei dominates over capture on free protons. This leads to significant changes in core collapse simulations.

Journal Article↗

Inhibition of insulin signaling and glycogen synthesis by phorbol dibutyrate in rat skeletal muscle.

Numerous studies have shown a correlation between changes in protein kinase C (PKC) distribution and/or activity and insulin resistance in skeletal muscle. To investigate which PKC isoforms might be involved and how they affect insulin action and signaling, studies were carried out in rat soleus muscle incubated with phorbol esters. Muscles preincubated for 1 h with 1 microM phorbol 12,13-dibutyrate (PDBu) showed an impaired ability of insulin to stimulate glucose incorporation into glycogen and a translocation of PKC-alpha, -betaI, -theta, and -epsilon, and probably -betaII, from the cytosol to membranes. Preincubation with 1 microM PDBu decreased activation of the insulin receptor tyrosine kinase by insulin and to an even greater extent the phosphorylation of Akt/protein kinase B and glycogen synthase kinase-3. However, it failed to diminish the activation of phosphatidylinositol 3'-kinase by insulin. Despite these changes in signaling, the stimulation by insulin of glucose transport (2-deoxyglucose uptake) and glucose incorporation into lipid and oxidation to CO2 was unaffected. The results indicate that preincubation of skeletal muscle with phorbol ester leads to a translocation of multiple conventional and novel PKC isoforms and to an impairment of several, but not all, events in the insulin-signaling cascade. They also demonstrate that these changes are associated with an inhibition of insulin-stimulated glycogen synthesis but that, at the concentration of PDBu used here, glucose transport, its incorporation into lipid, and its oxidation to CO2 are unaffected.

Animals↗

Regulation of fatty acid oxidation and glucose metabolism in rat soleus muscle: effects of AICAR.

Previous studies have shown that 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), a cell-permeable activator of AMP-activated protein kinase, increases the rate of fatty acid oxidation in skeletal muscle of fed rats. The present study investigated the mechanism by which this occurs and, in particular, whether changes in the activity of malonyl-CoA decarboxylase (MCD) and the beta-isoform of acetyl-CoA carboxylase (ACC beta) are involved. In addition, the relationship between changes in fatty acid oxidation induced by AICAR and its effects on glucose uptake and metabolism was examined. In incubated soleus muscles isolated from fed rats, AICAR (2 mM) increased fatty acid oxidation (90%) and decreased ACC beta activity (40%) and malonyl-CoA concentration (50%); however, MCD activity was not significantly altered. In soleus muscles from overnight-fasted rats, AICAR decreased ACC beta activity (40%), as it did in fed rats; however, it had no effect on the already high rate of fatty acid oxidation or the low malonyl-CoA concentration. In keeping with its effect on fatty acid oxidation, AICAR decreased glucose oxidation by 44% in fed rats but did not decrease glucose oxidation in fasted rats. It had no effect on glucose oxidation when fatty acid oxidation was inhibited by 2-bromopalmitate. Surprisingly, AICAR did not significantly increase glucose uptake or assayable AMP-activated protein kinase activity in incubated soleus muscles from fed or fasted rats. These results indicate that, in incubated rat soleus muscle, 1) AICAR does not activate MCD or stimulate glucose uptake as it does in extensor digitorum longus and epitrochlearis muscles, 2) the ability of AICAR to increase fatty acid oxidation and diminish glucose oxidation and malonyl-CoA concentration is dependent on the nutritional status of the rat, and 3) the ability of AICAR to diminish assayable ACC activity is independent of nutritional state.

AMP-Activated Protein Kinases↗

Calorie restriction increases insulin-stimulated tyrosine phosphorylation of insulin receptor and insulin receptor substrate-1 in rat skeletal muscle.

A moderate reduction in calorie intake (calorie restriction, CR) improves insulin-stimulated glucose transport in skeletal muscle. Therefore, we studied muscle insulin signalling in ad libitum (AL) and CR ( approximately 60% AL intake for 20 days) fed rats, which received a control injection (sterile water) or an insulin injection (30 U kg-1 body weight). In control (not insulin-treated) rats, there was no detectable tyrosine phosphorylation of insulin receptor (IR), regardless of diet; no diet effect on tyrosine phosphorylation of insulin receptor substrate-1 (IRS1) or IRS1-associated phosphatidylinositol 3-kinase (PI3K) protein and 21% higher IRS1-associated PI3K activity in AL vs. CR. In insulin-treated rats, tyrosine-phosphorylated IR was 79% higher for CR vs. AL; tyrosine-phosphorylated IRS1 was 109% higher for CR vs. AL; IRS1-associated PI3K protein and IRS1-associated PI3K activity were unaffected by diet. Calorie restriction amplifies early insulin signalling steps without changing IRS1-associated PI3K, suggesting enhanced glucose transport is mediated by altering: IRS1-PI3K localization, PI3K associated with proteins other than IRS1 or post-PI3K events.

Animals↗

Effect of calorie restriction on in vivo glucose metabolism by individual tissues in rats.

We evaluated the effects of 8 mo of calorie restriction [CR: 60% of ad libitum (AL) food intake] on glucose uptake by 14 tissues in unanesthetized, adult (12 mo) F344xBN rats. Glucose metabolism was assessed by the 2-[3H]deoxyglucose tracer technique at 1500 or 2100. Despite an approximately 60% decline in insulinemia with CR, plasma 2-[3H]deoxyglucose clearance for CR was greater than for AL at both times. A small, CR-related decrease in glucose metabolic index (R'g) occurred only at 1500 in the spleen and heart, and this decrease was reversed at 2100. In some tissues (cerebellum, lung, kidney, soleus, and diaphragm), R'g was unaffected by diet, regardless of time. In the other tissues (brown fat, 3 white fat pads, epitrochlearis, plantaris, and gastrocnemius), R'g was higher or tended to be higher for CR vs. AL at one or both times. These findings indicate that 8 mo of CR did not cause a continuous reduction in in vivo glucose uptake by any tissue studied, and, in several insulin-sensitive tissues, glucose uptake was at times greater for CR vs. AL rats.

Adipose Tissue↗

Effect of extracellular palmitate on 2-deoxy-d-glucose uptake in muscle from Ad libitum fed and calorie restricted rats.

We studied the effect of a high physiologic concentration of palmitate (1mM) on in vitro 2-deoxy-D-glucose (2DG) uptake by flexor digitorum brevis (FDB) muscle from ad libitum fed rats (AL) and rats fed 60% of ad libitum intake (CR) for 20 days. CR did not alter muscle 2DG uptake in the absence of insulin, but relative to AL, CR significantly (p<0.01) increased 2DG uptake in the presence of 20,000 microU/ml insulin. This effect of CR persisted in the presence of 1mM palmitate. The presence of 1mM palmitate significantly (p<0.01) impaired 2DG glucose uptake, both in the presence and absence of insulin, to the same extent in AL and CR muscle, despite an 18% decrease in FABPpm expression with CR. Thus, although CR profoundly affects insulin-mediated muscle glucose uptake, it does not alter the ability of extracellular fatty acid to modulate glucose utilization by skeletal muscle.

Animals↗

Comparison of the effects of 20 days and 15 months of calorie restriction on male Fischer 344 rats.

The aim of this study was to compare, in 19-month-old male Fischer 344 rats, the influence of brief (20 days) and prolonged (approximately 15 months) calorie restriction (CR; consuming approximately 60% of ad libitum, AL, intake) on circulating levels of glucose, insulin, C-peptide, and free fatty acids (FFA); age-matched AL rats were also studied. In the prolonged CR group, there was an approximately 85% decline in fat pad masses (epididymal and retroperitoneal) compared to AL and brief CR rats (these latter groups did not differ significantly). Compared to AL levels, glucose was 15% lower with prolonged CR (p < 0.05) while the brief CR values tended to be lower (10%) than AL; the CR groups did not differ significantly. Plasma FFA levels were significantly (p < 0.05) greater (85-106%) in the brief CR group compared to each of the other groups. Plasma insulin concentrations for the CR groups were lower (p < 0.05; approximately 50-60%) than AL levels. Plasma concentrations of C-peptide (an indicator of insulin secretion) were also lower for each CR group vs AL levels, and a high correlation was found between plasma insulin and C-peptide concentrations (r2 = 0.90; p < 0.001). The C-peptide/insulin ratios for the CR groups were similar, and the value of each CR group exceeded that for the AL rats. These results demonstrate that: the CR-induced reduction in plasma insulin is attributable in large part to reduced insulin secretion; these decreases in insulin secretion and concentration are essentially undiminished when brief CR is initiated rather late in life, and the reductions are independent of substantial reductions in body fat.

Adipose Tissue↗

Calorie restriction increases cell surface GLUT-4 in insulin-stimulated skeletal muscle.

Reduced calorie intake [calorie restriction (CR); 60% of ad libitum (AL)] leads to enhanced glucose transport without altering total GLUT-4 glucose transporter abundance in skeletal muscle. Therefore, we tested the hypothesis that CR (20 days) alters the subcellular distribution of GLUT-4. Cell surface GLUT-4 content was higher in insulin-stimulated epitrochlearis muscles from CR vs. AL rats. The magnitude of this increase was similar to the CR-induced increase in glucose transport, and GLUT-4 activity (glucose transport rate divided by cell surface GLUT-4) was unaffected by diet. The CR effect was specific to the insulin-mediated pathway, as evidenced by the observations that basal glucose transport and cell surface GLUT-4 content, as well as hypoxia-stimulated glucose transport, were unchanged by diet. CR did not alter insulin's stimulation of insulin receptor substrate (IRS)-1-associated phosphatidylinositol 3-kinase (PI3K) activity. Muscle abundance of IRS-2 and p85 subunit of PI3K were unaltered by diet, but IRS-1 content was lower in CR vs. AL. These data demonstrate that, despite IRS-1-PI3K activity similar to AL, CR specifically increases insulin's activation of glucose transport by enhancing the steady-state proportion of GLUT-4 residing on the cell surface.

3-O-Methylglucose↗

Brief dietary restriction increases skeletal muscle glucose transport in old Fischer 344 rats.

The primary purpose of this study was to determine the impact of brief dietary restriction (DR; 5 or 20 days) on skeletal muscle glucose transport activity (GTA) of 24-month-old female Fischer 344 rats. Basal GTA of isolated epitrochlearis muscles was unaffected by DR. Insulin-stimulated GTA was significantly increased by DR only at 20 days (51%). We also assessed the influence of DR on energy sources (blood-borne and stored). An approximately 20% decline in glycemia occurred in each DR group, but plasma-free fatty acid and beta-hydroxybutyrate concentrations were unaffected. Plasma insulin was reduced by 50% after 20 days. Hepatic glycogen was rapidly mobilized (-69% at 5 days; -83% at 20 days). The depletions of visceral adipose stores was slower (no significant decline at 5 days; -30% at 20 days), but the eventual reduction accounts for a significant amount of energy. The results demonstrate that muscle from old rats can rapidly upregulate GTA in response to brief DR. The relative magnitude of this increase represents a substantial portion of the increases previously observed after prolonged DR.

3-Hydroxybutyric Acid↗

Glucose transport with brief dietary restriction: heterogenous responses in muscles.

The time course (1, 5, or 20 days) for the effect of dietary restriction (DR; approximately 25% reduction below ad libitum intake) on epitrochlearis and flexor digitorum brevis (FDB) muscle glucose transport activity was studied in female Fischer 344 rats (8 mo old). Epitrochlearis glucose transport activity with 100 microU/ml insulin was increased by 38% after 5 days of DR (P < 0.05) despite no change in glucose transport activity with 0 or 20,000 microU/ml insulin. The increase with 100 microU/ml insulin was not further enhanced by 20 days of DR. DR did not result in a significant increase in the glucose transport activity of the FDB with 0, 100, or 20,000 microU/ml insulin. Abdominal fat content was significantly (P < 0.01) reduced below ad libitum levels only after 20 days of DR. These results demonstrate that DR-induced improvement in epitrochlearis glucose transport activity with a physiological insulin concentration can occur very rapidly, preceding detectable changes in basal or maximal insulin-stimulated glucose transport activity or abdominal fat pad mass, and the enhancement of insulin action does not occur simultaneously in all muscles.

3-O-Methylglucose↗

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Humans↗

The National Institutes of Health Grant mechanisms for anorectal and colonic biomedical research.

Knowledge of the anorectum in health and in disease lags substantially behind that of other regions of the digestive tract. A paucity of fundable grant applications on anorectal research is reflected in a history of the National Institutes of Health (NIH) anorectal research support being disproportionately low. This history is of particular concern recognizing the relative national significance of anorectal diseases and disorders. The National Institute of Arthritis, Diabetes, and Digestive and Kidney Diseases (NIADDK) seeks to broaden research and research training support of: 1) anorectal diseases and disorders, 2) the basic sciences of the anorectum, and 3) the relationship of the anorectum to the more proximal gut. Applications for research and research training grants are encouraged. Potential grant applicants are encouraged to contact NIH staff for information on anorectal programs and on grant application procedures and policies.

Anus Diseases↗