Soliton fractional charge of disordered graphene nanoribbon.

We investigate the properties of the gap-edge states of half-filled interacting disordered zigzag graphene nanoribbons, and find that the midgap states can display a quantized fractional charge of 1/2. These gap-edge states can be represented by topological kinks with their site probability distribution divided between the left and right zigzag edges with different chiralities. In addition, there are numerous spin-split gap-edge states, similar to those in a Mott-Anderson insulator.

Meat Science and Muscle Biology Symposium: manipulating meat tenderness by increasing the turnover of intramuscular connective tissue.

Controlled reduction of the connective tissue contribution to cooked meat toughness is an objective that would have considerable financial impact in terms of added product value. The amount of intramuscular connective tissue in a muscle appears connected to its in vivo function, so reduction of the overall connective tissue content is not thought to be a viable target. However, manipulation of the state of maturity of the collagenous component is a biologically viable target; by increasing connective tissue turnover, less mature structures can be produced that are functional in vivo but more easily broken down on cooking at temperatures above 60°C, thus improving cooked meat tenderness. Recent work using cell culture models of fibroblasts derived from muscle and myoblasts has identified a range of factors that alter the activity of the principal enzymes responsible for connective tissue turnover, the matrix metalloproteinases (MMP). Fibroblasts cultured from 3 different skeletal muscles from the same animal show different cell proliferation and MMP activity, which may relate to the different connective tissue content and architecture in functionally different muscles. Expression of MMP by fibroblasts is increased by vitamins that can counter the negative effects of oxidative stress on new collagen synthesis. Preliminary work using in situ zymography of myotubes in culture also indicates increased MMP activity in the presence of epinephrine and reactive oxidative species. Comparison of the relative changes in MMP expression from muscle cells vs. fibroblasts shows that myoblasts are more responsive to a range of stimuli. Muscle cells are likely to produce more of the total MMP in muscle tissue as a whole, and the expression of latent forms of the enzymes (i.e., pro-MMP) may vary between oxidative and glycolytic muscle fibers within the same muscle. The implication is that the different muscle fiber composition of different muscles eaten as meat may influence the potential for manipulation of their connective tissue turnover.

Epinephrine-induced MMP expression is different between skeletal fibroblasts and myoblasts.

Skeletal fibroblasts and myoblasts are among the cell types currently being considered in cell therapy for ischaemic heart disease. To investigate whether the expression of the tissue-remodelling proteolytic enzymes matrix metalloproteinases (MMPs) and the cellular energy regulator AMP-activated protein kinase (AMPK) is comparable between the two cell lines in response to epinephrine treatment, mouse skeletal fibroblasts (NOR-10) and myoblasts (C2C12) were treated with or without a low (11 nmol·l(-1) ) or high (55 nmol·l(-1) ) dose of epinephrine for 2 or 6 h. Cellular MMP-3 expression was increased by the high-dose epinephrine at both treatment periods in both cell lines. Cellular MMP-2 and MMP-13 expressions were amplified by the 2- or 6-h epinephrine incubation in fibroblasts. However, in myoblasts, such an increase was only seen at the longer treatment time. An elevated AMPKα expression was observed after a 2-h presence of epinephrine in both cell lines, which matches temporally with the early increased cellular MMP-2 and MMP-13 expression in fibroblasts. Activity of secreted MMP-2 increased only after 6-h epinephrine treatment in both cell types. Our data suggest that skeletal fibroblasts respond earlier to epinephrine application in terms of endogenous synthesis of the proteolytic and the energy homeostasis enzymes, whereas such response occurs later and to a milder dose of the beta adrenergic agonist in myoblasts.

Matrix metalloproteinases are less essential for the in-situ gelatinolytic activity in heart muscle than in skeletal muscle.

In order to determine whether the contribution of matrix metalloproteinases (MMPs) to the tissue gelatinolytic activity is similar between myocardium and skeletal muscle tissue, in-situ zymography was applied to myoblasts originated from myocardium or skeletal muscle of rodents as well as tissue sections of heart and soleus muscles of rats. Gelatinolyic activity was observed in cytoplasm and nucleus of both heart and skeletal myoblasts. The chelating agent EDTA blocked much of the gelatinolytic activity and the organomercurial activator of MMPs increased the activity in cells of both muscle origins. However, the inhibition of gelatinolytic activity by a broad spectrum MMP inhibitor was less profound in heart myoblasts than that in skeletal myoblasts. Gelatinolytic activity was also expressed in the endomysium and perimysium of tissue sections of heart and soleus muscles. Similar with findings in the cell studies, the gelatinase activity was increased by the MMP activator, mostly blocked by EDTA and partially inhibited by the MMP inhibitor. In the presence of the MMP inhibitor, the remaining gelatinolytic activity in the tissue sections was again higher in myocardium than that in soleus muscle. This observation was further supported by the gelatinolytic activity examined in tissue homogenates. Our findings suggest that other proteinases, in addition to MMPs, are more responsive for the tissue gelatinolytic activity in heart muscle as compared with that in skeletal muscle.

Modelling quality variations in commercial Ontario pork production.

This study explores the interactions of sensory and nutritional environment with genotype occurring in current commercial pork production in Ontario, Canada, which may interact to result in poor quality meat. The study focussed on identifying factors and signalling mechanisms that contribute to poor meat quality, in order to develop strategies to reduce the incidence of unacceptable product quality. In the first phase of the work reported here, animal behaviour and muscle metabolism studies were related to meat colour, tenderness and water-holding capacity measurements from commercially-produced pigs killed in a commercial packing plant. A partial least squares analysis was used to determine the most important of the principal production variables, peri-mortem biochemical measures and post-mortem carcass condition variables studied, in terms of their influence on water-holding, toughness and colour (L*-value). Variations between producer and kill day at the slaughterhouse were very strong contributors to variability in these three meat quality parameters, followed by pH variations. A second phase of the study is currently underway to characterize patterns of gene expression related to extremes of end-product quality and to reduce quality variations by nutritional and behavioural management strategies.

Phase diagram of a disordered boson Hubbard model in two dimensions.

We study the zero-temperature phase transition of a two-dimensional disordered boson Hubbard model. The phase diagram is constructed in terms of the disorder strength and the chemical potential. Via Monte Carlo simulations, we find a multicritical line separating the weak-disorder regime, where the Mott-insulator-to-superfluid transition occurs, from the strong-disorder regime, where the Bose-glass-to-superfluid transition occurs. On the multicritical line, the insulator-to-superfluid transition has the dynamical critical exponent z = 1.35+/-0.05 and the correlation length critical exponent nu = 0.67+/-0.03. We suggest that the proliferation of the particle-hole pairs screens out the weak-disorder effects.

Synergy of sibutramine and low-dose leptin in treatment of diet-induced obesity in rats.

Tachyphylaxis to the effects of anorexigenic agents, such as sibutramine (S), may be due, in part, to counterregulatory decreases in energy expenditure (EE) and increases in hunger that result from reduced circulating leptin (L) due to loss of body fat and lowered L production/adipocyte. The present study was conducted to test the hypothesis that L administered at low doses sufficient to restore ambient L to preweight loss concentrations would enhance the intercurrent efficacy of S by reducing the strength of physiologic counterregulation to weight loss. Forty male Sprague-Dawley rats were fed a high-fat (HF) diet (45% energy) to induce obesity. After 8 weeks, the obese rats (600 +/- 58 g) were weight-matched into 4 groups (N = 8/group) and implanted subcutaneously (SC) with 2 mL, 7-day Alzet mini-pumps that provided: vehicle (V, saline), L (0.5 mg/kg/d), S (3 mg/kg/d), or L+S. Food intake (FI) on the HF diet was measured daily. On day 7, 24-hour EE was measured by indirect calorimetry, and the animals then killed for body composition analysis. Compared with vehicle, treatment with S alone, but not L alone, produced significant weight loss (-23 +/- 26 v -6 +/- 16 g, P <.01). L alone, or with S, increased fat oxidation (decreased respiratory quotient [RQ]) compared with V (P <.05). The lack of decline in EE with S may be due to its documented effect to stimulate thermogenesis. Administration of L with S synergistically decreased FI and increased weight loss and fractional fat loss. A reduction in plasma L concentration may contribute to the "plateau phenomenon" observed in studies of weight loss therapies. Replacement doses of L during S administration increased weight loss and fractional fat loss by (1) decreasing food intake and (2) by increasing fat oxidation. Such drug combinations may be useful in the treatment of human obesity.

High-fat diet feeding elevates skeletal muscle uncoupling protein 3 levels but not its activity in rats.

OBJECTIVE: The objective of this study is to test the impact of high-fat diet (HFD) feeding on skeletal muscle (SM) uncoupling protein 3 (UCP3) expression and its association with mitochondrial ion permeability and whole-body energy homeostasis. RESEARCH METHODS AND PROCEDURES: Sprague-Dawley rats were fed ad libitum either a HFD (60% of energy from fat, n = 6) or a low-fat diet (12% of energy from fat, n = 6) for 4 weeks. Twenty-four-hour energy expenditure was measured by indirect calorimetry in the last week of the dietary treatment. Blood samples were collected for plasma leptin and free fatty acid assays, and mitochondria were isolated from hindlimb SM for subsequent determinations of UCP3 levels and mitochondrial ion permeability. RESULTS: Plasma leptin levels were higher in rats fed the HFD despite the same body weight in two groups. The same dietary treatment also rendered a 2-fold increase in plasma free fatty acid and SM UCP3 protein levels (Western blot) compared with the group fed the low-fat diet. However, the elevated UCP3 protein levels did not correlate with mitochondrial swelling rates, a measure of mitochondrial chloride, and proton permeability, or with 24-hour energy expenditure. DISCUSSION: The high correlation between the levels of plasma free fatty acid levels and SM UCP3 suggests that circulating free fatty acid may play an important role in UCP3 expression during the HFD feeding. However, the dissociation between the UCP3 protein levels and 24-hour energy expenditure as well as mitochondrial ion permeability suggests that mitochondrial proton leak mediated by muscle UCP3 may not be a major contributor in energy balance in HFD feeding, and other regulatory mechanisms independent of gene regulation may be responsible for the control of UCP3-mediated uncoupling activity.

High-fat hypocaloric diet modifies carbohydrate utilization of obese rats during weight loss.

The effects of fat content in the hypocaloric diet on whole body glucose oxidation and adipocyte glucose transport were investigated in two animal-feeding experiments. Diet-induced obese rats were food restricted to 75% of their previous energy intakes with either a high (45% by calorie) or a low (12% by calorie) corn oil diet for 9 wk (experiment 1) or 10 days (experiment 2). The losses of body weight (P < 0.05) and adipose depot weight (P < 0.05) were less in the 45% compared with the 12% fat group. During the dynamic phase of weight loss (day 10 of food restriction), plasma glucose and insulin concentrations were higher (P < 0.05) in the 45% than those in the 12% fat group. Whole body carbohydrate oxidation rate in response to an oral load of glucose was increased (P < 0.001) by food restriction in both dietary groups; however, carbohydrate oxidation rates were lower (P < 0.01) in the 45% than in the 12% fat-fed rats during the weight loss period. Adipocyte glucose transport was greater (P < 0.02) in the 45% than in the 12% fat group in an intra-abdominal adipose depot but not in subcutaneous fat. These data suggest that dietary fat content modifies whole body glucose oxidation and intra-abdominal adipocyte glucose uptake during weight loss.

Mouse sperm protein sp56 is a component of the acrosomal matrix.

Previously, we identified the guinea pig sperm acrosomal matrix glycoprotein AM67 and demonstrated that it is most closely related to mouse sperm sp56, initially reported to be a cell-surface protein. On the contrary, our studies demonstrated that sp56 is an intra-acrosomal component. Based upon the homology between guinea pig AM67 and mouse sp56, we hypothesized that sp56 was part of the acrosomal matrix, a structure that had yet to be demonstrated to exist in mouse sperm. In this paper, we show that sp56 first appeared in late meiotic cells and accumulated during spermiogenesis, the haploid stage of spermatogenic cell development. Using affinity-purified anti-peptide antisera, we determined that the molecular weight of sp56 in cauda epididymal sperm approximated that of guinea pig AM67 ( approximately 67 000 M:(r)) and that sp56 was present in a high molecular weight, disulfide-linked complex. The forms of sp56 in pachytene spermatocytes and spermatids had higher molecular weights than was found for the sperm form; the size differences were apparently due to alterations in carbohydrate side chains. The sp56 complex could not be solubilized by the nonionic detergent Triton X-100 but remained associated with the dorsal surface of the mouse sperm head, demonstrating that sp56 is a component of the mouse sperm acrosomal matrix.

Energy restriction dilutes the changes related to dietary fat type in membrane phospholipid fatty acid composition in rats.

To investigate liver cell membrane phospholipid (PL) fatty acid (FA) composition in response to the consumption of different types of dietary fat and graded levels of energy intake, rats were fed for 10 weeks on a diet containing either fish oil, safflower oil, or beef tallow. Within each dietary fat group, subgroups were either provided free access to food or energy-restricted to 85% or 70% of the ad libitum intake by reducing the dietary carbohydrate content while keeping other macronutrient intakes constant. Higher (P < .05) proportions of docosahexaenoic acid, linoleic acid, and monounsaturated FA were observed in the membrane PL of the fish oil, safflower oil, and beef tallow groups, respectively, resembling the FA composition in the diets. However, such modifications of dietary FA composition in, membrane PL FA were influenced by body energy status. The higher docosahexaenoic acid and total n-3 FA content in phosphatidylcholine (PC), sphingomyelin (SPH), and phosphatidylserine (PS) of the ad libitum fish oil group compared with the other dietary groups no longer existed when energy supply was restricted. Therefore, reducing energy intake tended to dilute the changes of membrane PL FA composition occurring as a function of dietary FA composition. These data suggest that the influence of dietary fat type on cellular structure and perhaps function becomes increasingly important with progressively positive energy balance.

High-fat diet feeding reduces the diurnal variation of plasma leptin concentration in rats.

To investigate the response of plasma leptin and its diurnal variation to graded levels of dietary fat intake, adult (486.8+/-10.8 g), male rats (N = 52) were fed diets containing 12%, 28%, 44%, and 60% fat for 4 weeks. The body weight gain and abdominal fat pad weight were higher (P < .05) in groups fed diets containing 44% and 60% fat compared with the two diets containing less fat. There were no significant differences in terms of body weight or fat pad weight between animals fed the two diets with higher fat content or between animals fed the two lower-fat diets. Twenty-four-hour energy expenditure was not different among the dietary fat groups. After 3 days on the experimental diets, plasma leptin increased (P < .03) in all dietary groups. The increases in leptin in animals fed 12% and 28% fat diets occurred primarily in the morning. In contrast, in groups fed the two diets containing higher fat content, leptin levels increased mainly in the afternoon. As a result, the daily variation in leptin increased (P < .05) in the two groups fed lower-fat diets, but decreased (P < .04) in animals fed the two higher-fat diets. These data demonstrate that short-term high-fat diet feeding abolished the diurnal fluctuation of plasma leptin levels, which may prevent proper leptin function and eventually contribute to the development of obesity.

Changes in gut mucosal nitric oxide synthase (NOS) activity after thermal injury and its relation with barrier failure.

This study was designed to investigate changes in mucosal NOS activity after burns and its relation to barrier failure. In Experiment 1, female specific pathogen free (SPF) Sprague-Dawley rats underwent 35% total body surface area (TBSA) burn. One to six days after burn, intestinal permeability was determined from the plasma leakage of fluorescein isothiocyanate (FITC)-dextran 4400, intestinal mucosal cNOS and iNOS activity were assayed using Griess' reagent, and the cellular localization of iNOS was examined using immunostaining. In Experiment 2, S-methylisothiourea (SMT) was given (5 mg/kg, i.p. every 12 h) for 2 days to suppress inducible NOS (iNOS) activity after thermal injury. On postburn Day 2, the effect of SMT on gut mucosal NOS activity, intestinal permeability, and barrier function were evaluated. The activity of iNOS increased 24 h after the injury and up to a maximum of twofold on postburn Day 2, and decreased thereafter. The increase in iNOS activity in gut mucosa correlated well with the increase in intestinal permeability, an index for barrier failure (r = .776, p = .0002). Results from iNOS immunostaining showed that changes in mucosal iNOS activity after the burn occurred mainly in the enterocytes rather than in the macrophages. Administration of SMT decreased mucosal iNOS activity, intestinal permeability, and bacterial translocation incidence to mesenteric lymph node concurrently. In conclusion, thermal injury induces intestinal mucosal iNOS, which is principally in the enterocytes. The increased intestinal iNOS activity was closely related to barrier failure. SMT inhibited intestinal mucosal iNOS activity and prevented barrier failure as demonstrated by a decrease in BT occurrence and intestinal permeability.

Failure of IGF-I infusion to promote growth in Zn deficient hypophysectomized rats.

The retarded growth of zinc-deficient rats is associated with low plasma insulin-like growth factor-I (IGF-I). To determine whether the low circulating IGF-I concentrations are responsible for the stunted growth, the growth response of zinc-deficient hypophysectomized rats to supplementation with recombinant human IGF-I (hIGF-I) was investigated. There were three dietary groups: zinc-deficient (0.9 mg zinc/kg diet), controls (66 mg zinc/kg diet) and zinc-adequate pair-fed (66 mg zinc/kg diet). All rats in each group received hIGF-I (150 micrograms/day) by subcutaneous infusion for 12 days, except for half of the animals in the control group which were sham-treated and which received vehicle infusion for the same period of time. The magnitude of the change was small, nevertheless infusion of hIGF-I significantly increased (p < 0.05) the body weight, tail length, liver weight and tibial epiphyseal width of control animals. This growth effect of hIGF-I was inhibited by lack of zinc in the diet, as evidenced by continuous weight loss, no increase in tail length and lowered tibial epiphyseal width in zinc-deficient animals. We conclude that systemic supplementation of hIGF-I can promote growth in hypophysectomized rats. The absence of weight gain and bone growth in zinc-deficient animals during the infusion period suggests that the growth promoting effect of circulating IGF-I is impaired by zinc deficiency.

Dietary fat type and energy restriction interactively influence plasma leptin concentration in rats.

To investigate whether dietary fat source and energy restriction interactively influence plasma leptin levels and its association of leptin with insulin action, rats were fed diets containing either fish, safflower oil, or beef tallow (20% wt/wt) for 10 weeks. Groups of rats consumed each diet ad libitum or at 85% or 70% of ad libitum energy intake in a design that held fat intake constant. Graded levels of energy restriction caused body weight to decrease (P < 0.001) differently according to the dietary fat provided. Plasma leptin concentrations were 60% higher (P < 0.05) in the groups fed fish oil and safflower oil ad libitum compared with those in the beef tallow group, despite smaller perirenal fat mass and fat cell size in the fish oil-fed animals. Energy restriction resulted in a 62% decrease (P < 0.05) in leptin levels in fish oil- and safflower oil-fed rats, whereas no changes were observed in beef tallow-fed animals. Plasma insulin levels were lower (P < 0.05) in the fish oil group fed ad libitum compared with those in the two other diet groups. These data demonstrate a hyperleptinemic effect in animals consuming diets rich in polyunsaturated fatty acid, which can be normalized to the level of saturated fat consumption by mild energy restriction. Thus, dietary fatty acid composition, independent of adipose tissue mass, is an important determinant of circulating leptin level in diet-induced obesity.

Zinc deficiency inhibits the direct growth effect of growth hormone on the tibia of hypophysectomized rats.

The effect of zinc deficiency on the direct-growth effect of growth hormone (GH) on tibia growth in hypophysectomized rats was studied. There were three dietary groups. Zinc deficient (ZD) group (0.9 mg/kg diet), control (C) group (66 mg/kg diet) and zinc adequate pair fed (PF) group (66 mg zinc/kg diet). All rats in each group received local infusion of recombinant human-growth hormone (hGH) (1 microgram/d), except for half of the animals in the control group, which were sham-treated, receiving vehicle infusion only. The substances were infused continuously for 13 d by osmotic minipumps through a catheter implanted into the right femoral artery. Food intake was lower and body weight loss was greater in ZD, and PF animals compared with C animals (p < 0.001). Tissue-zinc concentration and plasma alkaline-phosphatase activity were decreased (p < 0.05) by dietary-zinc deficiency. GH infusion increased the tibial-epiphyseal width of the treated right limb, but not of the noninfused left limb in C and PF animals. However, in ZD rats, no difference was found between the infused and the noninfused limbs. These results demonstrate that zinc deficiency inhibits the direct-growth effect of GH on long-bone growth.

Dietary fat type related changes in tissue cholesterol and fatty acid synthesis are influenced by energy intake level in rats.

OBJECTIVE: To investigate the interaction of dietary fat source and energy intake level on tissue cholesterol and triacylglycerol fatty acid (TG-FA) synthesis. METHODS: Ninety-six rats were randomly divided into 12 groups and fed diets containing fish oil, safflower oil, olive oil or beef tallow, each consumed ad libitum and at 85% and 68% of ad libitum intake for 10 weeks. Cholesterol and TG-FA fractional and absolute synthesis rates in the liver and fractional synthesis rates in the small intestine were determined using deuterium (D) incorporation 2 hours after injecting D2O. RESULTS: Olive oil feeding was associated with higher (p < 0.05) cholesterol and TG-FA synthesis rates in the liver and small intestine compared with other fats. Modifications in cholesterol synthesis by fat type depended on energy intake level. With ad libitum feeding, synthesis rates were lower (p < 0.01) following the safflower oil vs. the olive oil treatment. This effect was not observed in 68% energy restricted animals. However, in the intestine, differences (p < 0.01) in cholesterol synthesis rates between groups fed fish oil and beef tallow ad libitum were not observed with energy restriction. Energy restriction increased (p < 0.05) TG-FA synthesis rates in intestine of fish and safflower oil-fed groups, but not in that of olive oil- and beef tallow-fed animals. CONCLUSIONS: These results demonstrate the possible importance of dietary fat selection to control against hyperlipidemia during consumption of weight-reduction diets.

Differential fatty acid accretion in heart, liver and adipose tissues of rats fed beef tallow, fish oil, olive oil and safflower oils at three levels of energy intake.

To examine interactive effects of dietary fatty acid composition and energy restriction on tissue fatty acid accretion, mature rats consumed diets containing beef tallow, fish oil, olive oil or safflower oil with free access or at 85% or 68% of free access energy intakes. Restriction was accomplished by adjustment of dietary carbohydrate level. After 10 wk, animals were killed, and the fatty acid compositions of liver, heart and adipose tissues were examined. Compared with animals given free access to diets, body weight gains were reduced at wk 10 in fish oil- and olive oil-fed groups consuming 85% (P < 0.01) and in all groups consuming 68% (P < 0.005) of free access energy intake. Liver and heart weights were also lower (P < 0.05) in all groups restricted to 68% of free access energy intake. The type of dietary fat and the level of energy restriction influenced fatty acid composition in all three tissues at wk 10. In liver tissue, graded energy restriction increased (P < 0.02) proportions of stearic acid and decreased (P < 0.03) those of palmitic acid. In heart tissue, palmitic acid levels decreased (P < 0.01) with energy restriction. In adipose tissue, significant energy restriction-related changes in fatty acid composition varied with type of fat consumed. These results emphasize the importance of whole-body energy balance in addition to dietary fatty acid supply in utilization of dietary fatty acids for tissue deposition vs. oxidation.