Comparison of a reduced carbohydrate and reduced fat diet for LDL, HDL, and VLDL subclasses during 9-months of weight maintenance subsequent to weight loss.

OBJECTIVES: This study compared LDL, HDL, and VLDL subclasses in overweight or obese adults consuming either a reduced carbohydrate (RC) or reduced fat (RF) weight maintenance diet for 9 months following significant weight loss. METHODS: Thirty-five (21 RC; 14 RF) overweight or obese middle-aged adults completed a 1-year weight management clinic. Participants met weekly for the first six months and bi-weekly thereafter. Meetings included instruction for diet, physical activity, and behavior change related to weight management. Additionally, participants followed a liquid very low-energy diet of approximately 2092 kJ per day for the first three months of the study. Subsequently, participants followed a dietary plan for nine months that targeted a reduced percentage of carbohydrate (approximately 20%) or fat (approximately 30%) intake and an energy intake level calculated to maintain weight loss. Lipid subclasses using NMR spectroscopy were analyzed prior to weight loss and at multiple intervals during weight maintenance. RESULTS: Body weight change was not significantly different within or between groups during weight maintenance (p>0.05). The RC group showed significant increases in mean LDL size, large LDL, total HDL, large and small HDL, mean VLDL size, and large VLDL during weight maintenance while the RF group showed increases in total HDL, large and small HDL, total VLDL, and large, medium, and small VLDL (p<0.05). Group*time interactions were significant for large and medium VLDL (p>0.05). CONCLUSION: Some individual lipid subclasses improved in both dietary groups. Large and medium VLDL subclasses increased to a greater extent across weight maintenance in the RF group.

Food preferences and weight change during low-fat and low-carbohydrate diets.

UNLABELLED: Understanding associations between food preferences and weight loss during various effective diets could inform efforts to personalize dietary recommendations and provide insight into weight loss mechanisms. We conducted a secondary analysis of data from a clinical trial in which participants were randomized to either a 'choice' arm, in which they were allowed to select between a low-fat diet (n = 44) or low-carbohydrate diet (n = 61), or to a 'no choice' arm, in which they were randomly assigned to a low-fat diet (n = 49) or low-carbohydrate diet (n = 53). All participants were provided 48 weeks of lifestyle counseling. Food preferences were measured at baseline and every 12 weeks thereafter with the Geiselman Food Preference Questionnaire. Participants were 73% male and 51% African American, with a mean age of 55. Baseline food preferences, including congruency of food preferences with diet, were not associated with weight outcomes. In the low-fat diet group, no associations were found between changes in food preferences and weight over time. In the low-carbohydrate diet group, increased preference for low-carbohydrate diet congruent foods from baseline to 12 weeks was associated with weight loss from 12 to 24 weeks. Additionally, weight loss from baseline to 12 weeks was associated with increased preference for low-carbohydrate diet congruent foods from 12 to 24 weeks. Results suggest that basing selection of low-carbohydrate diet or low-fat diet on food preferences is unlikely to influence weight loss. Congruency of food preferences and weight loss may influence each other early during a low-carbohydrate diet but not low-fat diet, possibly due to different features of these diets. CLINICAL TRIAL REGISTRY: NCT01152359.

Dietary quality and encephalization in platyrrhine primates.

The high energetic costs of building and maintaining large brains are thought to constrain encephalization. The 'expensive-tissue hypothesis' (ETH) proposes that primates (especially humans) overcame this constraint through reduction of another metabolically expensive tissue, the gastrointestinal tract. Small guts characterize animals specializing on easily digestible diets. Thus, the hypothesis may be tested via the relationship between brain size and diet quality. Platyrrhine primates present an interesting test case, as they are more variably encephalized than other extant primate clades (excluding Hominoidea). We find a high degree of phylogenetic signal in the data for diet quality, endocranial volume and body size. Controlling for phylogenetic effects, we find no significant correlation between relative diet quality and relative endocranial volume. Thus, diet quality fails to account for differences in platyrrhine encephalization. One taxon, in particular, Brachyteles, violates predictions made by ETH in having a large brain and low-quality diet. Dietary reconstructions of stem platyrrhines further indicate that a relatively high-quality diet was probably in place prior to increases in encephalization. Therefore, it is unlikely that a shift in diet quality was a primary constraint release for encephalization in platyrrhines and, by extrapolation, humans.

Intake, digestibility, and passage of a commercially designed diet by two Propithecus species.

The digestibility and passage of an experimental diet was used to compare the digestive physiology of two Propithecus species: P. verreauxi and P. tattersalli. Though both animals have a similar feeding ecology, the captive status of P. verreauxi is considered more stable than that of P. tattersalli. The test diet included a local tree species, Rhus copallina, at 15% of dry matter intake (DMI) and Mazuri Leafeater Primate Diet at 85% of DMI. The chemical composition of the diet (dry matter basis) was 25% crude protein, 34% neutral detergent fiber (NDF), and 22% acid detergent fiber (ADF) with a gross energy of 4.52 kcal/g. After a 6 week acclimation to the experimental diet, animals were placed in research caging. After a 7 day adjustment period, animals were dosed with chromium mordant and Co-EDTA as markers for digesta passage and all feed refusals and feces were collected at timed intervals for 7 days. Digestibility values, similar for both species, were approximately 65% for dry matter, crude protein, and energy, and 40% and 35% respectively, for NDF and ADF. Transit times (17-18.5 hr) and mean retention times (31-34 hr) were not significantly different between species, and there was no difference between the chromium mordant and Co-EDTA. Serum values for glucose, urea, and non-esterified fatty acids (NEFA) were obtained during four different time periods to monitor nutritional status. While there was no change in serum glucose, serum urea increased over time. The NEFAs increased across all four time periods for P. verreauxi and increased for the first three periods then decreased in the last period for P. tattersalli. Results obtained indicate no difference in digestibility nor digesta passage between species, and that both Propithecus species were similar to other post-gastric folivores.

Stable isotope ratios indicate diet and habitat use in New World monkeys.

This paper demonstrates the use of stable isotope ratios of carbon and nitrogen in animal tissue for indicating aspects of species behavioral strategy. We analyzed hair from individuals representing four species of New World monkeys (Alouatta palliata, the mantled howler; Ateles geoffroyi, the spider monkey; Cebus capucinus, the capuchin; and Brachyteles arachnoides, the woolly-spider monkey or muriqui) for delta 13C and delta 15N using previously developed methods. There are no significant differences in either carbon or nitrogen ratios between sexes, sampling year, or year of analysis. Seasonal differences in delta 13C reached a low level of significance but do not affect general patterns. Variation within species was similar to that recorded previously within single individuals. The omega 13C data show a bimodal distribution with significant difference between the means. The two monkey populations living in an evergreen forest were similar to each other and different from the other two monkey populations that inhabited dry, deciduous forests. This bimodal distribution is independent of any particular species' diet and reflects the level of leaf cover in the two types of forest. The delta 15N data display three significantly different modes. The omnivorous capuchins were most positive reflecting a trophic level offset. The spider monkeys and the muriquis were similar to one another and significantly more positive than the howlers. This distribution among totally herbivorous species correlates with the ingestion of legumes by the howler monkey population. In combination, these data indicate that museum-curated primate material can be analyzed to yield information on forest cover and diet in populations and species lacking behavioral data.

Impaired formation of beta-adrenergic receptor-nucleotide regulatory protein complexes in pseudohypoparathyroidism.

Decreased activity of the guanine nucleotide regulatory protein (N) of the adenylate cyclase system is present in cell membranes of some patients with pseudohypoparathyrodism (PHP-Ia) whereas others have normal activity of N (PHP-Ib). Low N activity in PHP-Ia results in a decrease in hormone (H)-stimulatable adenylate cyclase in various tissues, which might be due to decreased ability to form an agonist-specific high affinity complex composed of H, receptor (R), and N. To test this hypothesis, we compared beta-adrenergic agonist-specific binding properties in erythrocyte membranes from five patients with PHP-Ia (N = 45% of control), five patients with PHP-Ib (N = 97%), and five control subjects. Competition curves that were generated by increasing concentrations of the beta-agonist isoproterenol competing with [125I]pindolol were shallow (slope factors less than 1) and were computer fit to a two-state model with corresponding high and low affinity for the agonist. The agonist competition curves from the PHP-Ia patients were shifted significantly (P less than 0.02) to the right as a result of a significant (P less than 0.01) decrease in the percent of beta-adrenergic receptors in the high affinity state from 64 +/- 22% in PHP-Ib and 56 +/- 5% in controls to 10 +/- 8% in PHP-Ia. The agonist competition curves were computer fit to a "ternary complex" model for the two-step reaction: H + R + N in equilibrium HR + N in equilibrium HRN. The modeling was consistent with a 60% decrease in the functional concentration of N, and was in good agreement with the biochemically determined decrease in erythrocyte N protein activity. These in vitro findings in erythrocytes taken together with the recent observations that in vivo isoproterenol-stimulated adenylate cyclase activity is decreased in patients with PHP (Carlson, H. E., and A. S. Brickman, 1983, J. Clin. Endocrinol. Metab. 56:1323-1326) are consistent with the notion that N is a bifunctional protein interacting with both R and the adenylate cyclase. It may be that in patients with PHP-Ia a single molecular and genetic defect accounts for both decreased HRN formation and decreased adenylate cyclase activity, whereas in PHP-Ib the biochemical lesion(s) appear not to affect HRN complex formation.

Childhood bullying involvement predicts low-grade systemic inflammation into adulthood.

Bullying is a common childhood experience that involves repeated mistreatment to improve or maintain one's status. Victims display long-term social, psychological, and health consequences, whereas bullies display minimal ill effects. The aim of this study is to test how this adverse social experience is biologically embedded to affect short- or long-term levels of C-reactive protein (CRP), a marker of low-grade systemic inflammation. The prospective population-based Great Smoky Mountains Study (n = 1,420), with up to nine waves of data per subject, was used, covering childhood/adolescence (ages 9-16) and young adulthood (ages 19 and 21). Structured interviews were used to assess bullying involvement and relevant covariates at all childhood/adolescent observations. Blood spots were collected at each observation and assayed for CRP levels. During childhood and adolescence, the number of waves at which the child was bullied predicted increasing levels of CRP. Although CRP levels rose for all participants from childhood into adulthood, being bullied predicted greater increases in CRP levels, whereas bullying others predicted lower increases in CRP compared with those uninvolved in bullying. This pattern was robust, controlling for body mass index, substance use, physical and mental health status, and exposures to other childhood psychosocial adversities. A child's role in bullying may serve as either a risk or a protective factor for adult low-grade inflammation, independent of other factors. Inflammation is a physiological response that mediates the effects of both social adversity and dominance on decreases in health.

Statistical analysis of crystallization database links protein physico-chemical features with crystallization mechanisms.

X-ray crystallography is the predominant method for obtaining atomic-scale information about biological macromolecules. Despite the success of the technique, obtaining well diffracting crystals still critically limits going from protein to structure. In practice, the crystallization process proceeds through knowledge-informed empiricism. Better physico-chemical understanding remains elusive because of the large number of variables involved, hence little guidance is available to systematically identify solution conditions that promote crystallization. To help determine relationships between macromolecular properties and their crystallization propensity, we have trained statistical models on samples for 182 proteins supplied by the Northeast Structural Genomics consortium. Gaussian processes, which capture trends beyond the reach of linear statistical models, distinguish between two main physico-chemical mechanisms driving crystallization. One is characterized by low levels of side chain entropy and has been extensively reported in the literature. The other identifies specific electrostatic interactions not previously described in the crystallization context. Because evidence for two distinct mechanisms can be gleaned both from crystal contacts and from solution conditions leading to successful crystallization, the model offers future avenues for optimizing crystallization screens based on partial structural information. The availability of crystallization data coupled with structural outcomes analyzed through state-of-the-art statistical models may thus guide macromolecular crystallization toward a more rational basis.

Potential To Streamline Heterologous DNA Prime and NYVAC/Protein Boost HIV Vaccine Regimens in Rhesus Macaques by Employing Improved Antigens.

UNLABELLED: In a follow-up to the modest efficacy observed in the RV144 trial, researchers in the HIV vaccine field seek to substantiate and extend the results by evaluating other poxvirus vectors and combinations with DNA and protein vaccines. Earlier clinical trials (EuroVacc trials 01 to 03) evaluated the immunogenicity of HIV-1 clade C GagPolNef and gp120 antigens delivered via the poxviral vector NYVAC. These showed that a vaccination regimen including DNA-C priming prior to a NYVAC-C boost considerably enhanced vaccine-elicited immune responses compared to those with NYVAC-C alone. Moreover, responses were improved by using three as opposed to two DNA-C primes. In the present study, we assessed in nonhuman primates whether such vaccination regimens can be streamlined further by using fewer and accelerated immunizations and employing a novel generation of improved DNA-C and NYVAC-C vaccine candidates designed for higher expression levels and more balanced immune responses. Three different DNA-C prime/NYVAC-C+ protein boost vaccination regimens were tested in rhesus macaques. All regimens elicited vigorous and well-balanced CD8(+)and CD4(+)T cell responses that were broad and polyfunctional. Very high IgG binding titers, substantial antibody-dependent cellular cytotoxicity (ADCC), and modest antibody-dependent cell-mediated virus inhibition (ADCVI), but very low neutralization activity, were measured after the final immunizations. Overall, immune responses elicited in all three groups were very similar and of greater magnitude, breadth, and quality than those of earlier EuroVacc vaccines. In conclusion, these findings indicate that vaccination schemes can be simplified by using improved antigens and regimens. This may offer a more practical and affordable means to elicit potentially protective immune responses upon vaccination, especially in resource-constrained settings. IMPORTANCE: Within the EuroVacc clinical trials, we previously assessed the immunogenicity of HIV clade C antigens delivered in a DNA prime/NYVAC boost regimen. The trials showed that the DNA prime crucially improved the responses, and three DNA primes with a NYVAC boost appeared to be optimal. Nevertheless, T cell responses were primarily directed toward Env, and humoral responses were modest. The aim of this study was to assess improved antigens for the capacity to elicit more potent and balanced responses in rhesus macaques, even with various simpler immunization regimens. Our results showed that the novel antigens in fact elicited larger numbers of T cells with a polyfunctional profile and a good Env-GagPolNef balance, as well as high-titer and Fc-functional antibody responses. Finally, comparison of the different schedules indicates that a simpler regimen of only two DNA primes and one NYVAC boost in combination with protein may be very efficient, thus showing that the novel antigens allow for easier immunization protocols.