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.

Multivalent benzoboroxole functionalized polymers as gp120 glycan targeted microbicide entry inhibitors.

Microbicides are women-controlled prophylactics for sexually transmitted infections. The most important class of microbicides target HIV-1 and contain antiviral agents formulated for topical vaginal delivery. Identification of new viral entry inhibitors that target the HIV-1 envelope is important because they can inactivate HIV-1 in the vaginal lumen before virions can come in contact with CD4+ cells in the vaginal mucosa. Carbohydrate binding agents (CBAs) demonstrate the ability to act as entry inhibitors due to their ability to bind to glycans and prevent gp120 binding to CD4+ cells. However, as proteins they present significant challenges in regard to economical production and formulation for resource-poor environments. We have synthesized water-soluble polymer CBAs that contain multiple benzoboroxole moieties. A benzoboroxole-functionalized monomer was synthesized and incorporated into linear oligomers with 2-hydroxypropylmethacrylamide (HPMAm) at different feed ratios using free radical polymerization. The benzoboroxole small molecule analogue demonstrated weak affinity for HIV-1BaL gp120 by SPR; however, the 25 mol % functionalized benzoboroxole oligomer demonstrated a 10-fold decrease in the K(D) for gp120, suggesting an increased avidity for the multivalent polymer construct. High molecular weight polymers functionalized with 25, 50, and 75 mol % benzoboroxole were synthesized and tested for their ability to neutralize HIV-1 entry for two HIV-1 clades and both R5 and X4 coreceptor tropism. All three polymers demonstrated activity against all viral strains tested with EC(50)s that decrease from 15000 nM (1500 microg mL(-1)) for the 25 mol % functionalized polymers to 11 nM (1 microg mL(-1)) for the 75 mol % benzoboroxole-functionalized polymers. These polymers exhibited minimal cytotoxicity after 24 h exposure to a human vaginal cell line.

Multiple phenotypic changes in mice after knockout of the B3gnt5 gene, encoding Lc3 synthase--a key enzyme in lacto-neolacto ganglioside synthesis.

BACKGROUND: Ganglioside biosynthesis occurs through a multi-enzymatic pathway which at the lactosylceramide step is branched into several biosynthetic series. Lc3 synthase utilizes a variety of galactose-terminated glycolipids as acceptors by establishing a glycosidic bond in the beta-1,3-linkage to GlcNaAc to extend the lacto- and neolacto-series gangliosides. In order to examine the lacto-series ganglioside functions in mice, we used gene knockout technology to generate Lc3 synthase gene B3gnt5-deficient mice by two different strategies and compared the phenotypes of the two null mouse groups with each other and with their wild-type counterparts. RESULTS: B3gnt5 gene knockout mutant mice appeared normal in the embryonic stage and, if they survived delivery, remained normal during early life. However, about 9% developed early-stage growth retardation, 11% died postnatally in less than 2 months, and adults tended to die in 5-15 months, demonstrating splenomegaly and notably enlarged lymph nodes. Without lacto-neolacto series gangliosides, both homozygous and heterozygous mice gradually displayed fur loss or obesity, and breeding mice demonstrated reproductive defects. Furthermore, B3gnt5 gene knockout disrupted the functional integrity of B cells, as manifested by a decrease in B-cell numbers in the spleen, germinal center disappearance, and less efficiency to proliferate in hybridoma fusion. CONCLUSIONS: These novel results demonstrate unequivocally that lacto-neolacto series gangliosides are essential to multiple physiological functions, especially the control of reproductive output, and spleen B-cell abnormality. We also report the generation of anti-IgG response against the lacto-series gangliosides 3'-isoLM1 and 3',6'-isoLD1.

A switch in the control of growth of the wing imaginal disks of Manduca sexta.

BACKGROUND: Insulin and ecdysone are the key extrinsic regulators of growth for the wing imaginal disks of insects. In vitro tissue culture studies have shown that these two growth regulators act synergistically: either factor alone stimulates only limited growth, but together they stimulate disks to grow at a rate identical to that observed in situ. It is generally thought that insulin signaling links growth to nutrition, and that starvation stops growth because it inhibits insulin secretion. At the end of larval life feeding stops but the disks continue to grow, so at that time disk growth has become uncoupled from nutrition. We sought to determine at exactly what point in development this uncoupling occurs. METHODOLOGY: Growth and cell proliferation in the wing imaginal disks and hemolymph carbohydrate concentrations were measured at various stages in the last larval instar under experimental conditions of starvation, ligation, rescue, and hormone treatment. PRINCIPAL FINDINGS: Here we show that in the last larval instar of M. sexta, the uncoupling of nutrition and growth occurs as the larva passes the critical weight. Before this time, starvation causes a decline in hemolymph glucose and trehalose and a cessation of wing imaginal disks growth, which can be rescued by injections of trehalose. After the critical weight the trehalose response to starvation disappears, and the expression of insulin becomes decoupled from nutrition. After the critical weight the wing disks loose their sensitivity to repression by juvenile hormone, and factors from the abdomen, but not the brain, are required to drive continued growth. CONCLUSIONS: During the last larval instar imaginal disk growth becomes decoupled from somatic growth at the time that the endocrine events of metamorphosis are initiated. These regulatory changes ensure that disk growth continues uninterrupted when the nutritive and endocrine signals undergo the drastic changes associated with metamorphosis.

The effect of differences in methodology among some recent applications of shearing quotients.

A shearing quotient (SQ) is a way of quantitatively representing the Phase I shearing edges on a molar tooth. Ordinary or phylogenetic least squares regression is fit to data on log molar length (independent variable) and log sum of measured shearing crests (dependent variable). The derived linear equation is used to generate an 'expected' shearing crest length from molar length of included individuals or taxa. Following conversion of all variables to real space, the expected value is subtracted from the observed value for each individual or taxon. The result is then divided by the expected value and multiplied by 100. SQs have long been the metric of choice for assessing dietary adaptations in fossil primates. Not all studies using SQ have used the same tooth position or crests, nor have all computed regression equations using the same approach. Here we focus on re-analyzing the data of one recent study to investigate the magnitude of effects of variation in 1) shearing crest inclusion, and 2) details of the regression setup. We assess the significance of these effects by the degree to which they improve or degrade the association between computed SQs and diet categories. Though altering regression parameters for SQ calculation has a visible effect on plots, numerous iterations of statistical analyses vary surprisingly little in the success of the resulting variables for assigning taxa to dietary preference. This is promising for the comparability of patterns (if not casewise values) in SQ between studies. We suggest that differences in apparent dietary fidelity of recent studies are attributable principally to tooth position examined.

Inter-annual variability of precipitation constrains the production response of boreal Pinus sylvestris to nitrogen fertilization

© 2015 Published by Elsevier B.V.Tree growth resources and the efficiency of resource-use for biomass production determine the productivity of forest ecosystems. In nutrient-limited forests, nitrogen (N)-fertilization increases foliage [N], which may increase photosynthetic rates, leaf area index (L), and thus light interception (IC). The product of such changes is a higher gross primary production and higher net primary production (NPP). However, fertilization may also alter carbohydrate partitioning from below- to aboveground, increasing aboveground NPP (ANPP). We analyzed effects of long-term N-fertilization on NPP, and that of long-term carbon storing organs (NPPS) in a Pinus sylvestris forest on sandy soil, a wide-ranging forest type in the boreal region. We based our analyses on a combination of destructive harvesting, consecutive mensuration, and optical measurements of canopy openness. After eight-year fertilization with a total of 70gNm^-2, ANPP was 27±7% higher in the fertilized (F) relative to the reference (R) stand, but although L increased relative to its pre-fertilization values, IC was not greater than in R. On the seventh year after the treatment initiation, the increase of ANPP was matched by the decrease of belowground NPP (78 vs. 92gCm^-2yr^-1; ~17% of NPP) and, given the similarity of IC, suggests that the main effect of N-fertilization was changed carbon partitioning rather than increased canopy photosynthesis. Annual NPPS increased linearly with growing season temperature (T) in both treatments, with an upward shift of 70.2gCm^-2yr^-1 by fertilization, which also caused greater amount of unexplained variation (r²=0.53 in R, 0.21 in F). Residuals of the NPPS-T relationship of F were related to growing season precipitation (P, r²=0.48), indicating that T constrains productivity at this site regardless of fertility, while P is important in determining productivity where N-limitation is alleviated. We estimated that, in a growing season average T (11.5±1.0°C; 33-year-mean), NPPS response to N-fertilization will be nullified with P 31mm less than the mean (325±85mm), and would double with P 109mm greater than the mean. These results suggest that inter-annual variation in climate, particularly in P, may help explaining the reported large variability in growth responses to fertilization of pine stands on sandy soils. Furthermore, forest management of long-rotation systems, such as those of boreal and northern temperate forests, must consider the efficiency of fertilization in terms of wood production in the context of changes in climate predicted for the region.