Bias in protein and potassium intake collected with 24-h recalls (EPIC-Soft) is rather comparable across European populations

Purpose: We investigated whether group-level bias of a 24-h recall estimate of protein and potassium intake, as compared to biomarkers, varied across European centers and whether this was influenced by characteristics of individuals or centers. Methods: The combined data from EFCOVAL and EPIC studies included 14 centers from 9 countries (n = 1,841). Dietary data were collected using a computerized 24-h recall (EPIC-Soft). Nitrogen and potassium in 24-h urine collections were used as reference method. Multilevel linear regression analysis was performed, including individual-level (e.g., BMI) and center-level (e.g., food pattern index) variables. Results: For protein intake, no between-center variation in bias was observed in men while it was 5.7% in women. For potassium intake, the between-center variation in bias was 8.9% in men and null in women. BMI was an important factor influencing the biases across centers (p <0.01 in all analyses). In addition, mode of administration (p = 0.06 in women) and day of the week (p = 0.03 in men and p = 0.06 in women) may have influenced the bias in protein intake across centers. After inclusion of these individual variables, between-center variation in bias in protein intake disappeared for women, whereas for potassium, it increased slightly in men (to 9.5%). Center-level variables did not influence the results. Conclusion: The results suggest that group-level bias in protein and potassium (for women) collected with 24-h recalls does not vary across centers and to a certain extent varies for potassium in men. BMI and study design aspects, rather than center-level characteristics, affected the biases across center

Production, characterization, and antigen specificity of recombinant 62-71-3, a candidate monoclonal antibody for rabies prophylaxis in humans

Rabies kills many people throughout the developing world every year. The murine monoclonal antibody (mAb) 62-71-3 was recently identified for its potential application in rabies postexposure prophylaxis (PEP). The purpose here was to establish a plant-based production system for a chimeric mouse-human version of mAb 62-71-3, to characterize the recombinant antibody and investigate at a molecular level its interaction with rabies virus glycoprotein. Chimeric 62-71-3 was successfully expressed in Nicotiana benthamiana. Glycosylation was analyzed by mass spectroscopy; functionality was confirmed by antigen ELISA, as well as rabies and pseudotype virus neutralization. Epitope characterization was performed using pseudotype virus expressing mutagenized rabies glycoproteins. Purified mAb demonstrated potent viral neutralization at 500 IU/mg. A critical role for antigenic site I of the glycoprotein, as well as for two specific amino acid residues (K226 and G229) within site I, was identified with regard to mAb 62-71-3 neutralization. Pseudotype viruses expressing glycoprotein from lyssaviruses known not to be neutralized by this antibody were the controls. The results provide the molecular rationale for developing 62-71-3 mAb for rabies PEP; they also establish the basis for developing an inexpensive plant-based antibody product to benefit low-income families in developing countries.—Both, L., van Dolleweerd, C., Wright, E., Banyard, A. C., Bulmer-Thomas, B., Selden, D., Altmann, F., Fooks, A. R., Ma, J. K.-C. Production, characterization, and antigen specificity of recombinant 62-71-3, a candidate monoclonal antibody for rabies prophylaxis in humans

P-value based visualization of codon usage data

Two important and not yet solved problems in bacterial genome research are the identification of horizontally transferred genes and the prediction of gene expression levels. Both problems can be addressed by multivariate analysis of codon usage data. In particular dimensionality reduction methods for visualization of multivariate data have shown to be effective tools for codon usage analysis. We here propose a multidimensional scaling approach using a novel similarity measure for codon usage tables. Our probabilistic similarity measure is based on P-values derived from the well-known chi-square test for comparison of two distributions. Experimental results on four microbial genomes indicate that the new method is well-suited for the analysis of horizontal gene transfer and translational selection. As compared with the widely-used correspondence analysis, our method did not suffer from outlier sensitivity and showed a better clustering of putative alien genes in most cases

Pervasive carbonation of peridotite to listvenite (Semail Ophiolite, Sultanate of Oman): clues from iron partitioning and chemical zoning

Earth's long-term cycling of carbon is regulated from mid-ocean ridges to convergent plate boundaries by mass transfers involving mantle rocks. Here we examine the conversion of peridotite to listvenite (magnesite + quartz rock) during CO2 metasomatism along the basal thrust of the Semail Ophiolite (Fanja, Sultanate of Oman). At the outcrop scale, this transformation defines reaction zones, from serpentinized peridotites to carbonated serpentinites and listvenites. Based on a detailed petrological and chemical study, we show that carbonation progressed through three main stages involving the development of replacive textures ascribed to early stages, whilst carbonate (± quartz) veining becomes predominant in the last stage. The pervasive replacement of serpentine by magnesite is characterized by the formation of spheroids, among which two types are identified based on the composition of their core regions: Fe-core and Mg-core spheroids. Fe zoning is a type feature of matrix and vein magnesite formed during the onset carbonation (Stage 1). While Fe-rich magnesite is predicted to form at low fluid XCO2 from a poorly to moderately oxidized protolith, our study evidences that the local non-redox destabilization of Fe oxides into Fe-rich magnesite is essential to the development of Fe-core spheroids. The formation of Fe-core spheroids is followed by the pervasive (over-)growth of Mg-rich spheroids and aggregates (Stage 2) at near-equilibrium conditions in response to increasing fluid XCO2. Furthermore, the compositions of carbonates indicate that most siderophile transition elements released by the dissolution of primary minerals are locally trapped in carbonate and oxides during matrix carbonation, while elements with a chalcophile affinity are the most likely to be leached out of reaction zones.</p

Mediation of coffee-induced improvements in human vascular function by chlorogenic acids and its metabolites: two randomized, controlled, crossover intervention trials

Background & aims Polyphenol intake has been linked to improvements in human vascular function, although data on hydroxycinnamates, such as chlorogenic acid (CGA) have not yet been studied. We aimed to investigate the impact of coffee intake rich in chlorogenic acid on human vascular function and whether CGAs are involved in potential effects. Methods Two acute randomized, controlled, cross-over human intervention trials were conducted. The impact of coffee intake, matched for caffeine but differing in CGA content (89, and 310 mg) on flow-mediated dilation (FMD) was assessed in 15 healthy male subjects. In a second intervention trial conducted with 24 healthy male subjects, the impact of pure 5-caffeoylquinic acid (5-CQA), the main CGA in coffee (5-CQA; 450 mg and 900 mg) on FMD was also investigated. Results We observed a bi-phasic FMD response after low and high polyphenol, (89 mg and 310 mg CGA) intake, with increases at 1 (1.10 ± 0.43% and 1.34 ± 0.62%, respectively) and 5 (0.79% ± 0.32 and 1.52% ± 0.40, respectively) hours post coffee consumption. FMD responses to coffee intake was closely paralleled by the appearance of CGA metabolites in plasma, notably 3-, 4- and 5-CQA and ferulic-4′-O-sulfate at 1 h and isoferulic-4′-O-glucuronide and ferulic-4′-O-sulfate at 5 h. Intervention with purified 5-CQA (450 mg) also led to an improvement in FMD response relative to control (0.75 ± 1.31% at 1 h post intervention, p = 0.06) and concomitant appearance of plasma metabolites. Conclusions Coffee intake acutely improves human vascular function, an effect, in part, mediated by 5-CQA and its physiological metabolites

Latent variables and structural equation models for longitudinal relationships: an illustration in nutritional epidemiology

<p>Abstract</p> <p>Background</p> <p>The use of structural equation modeling and latent variables remains uncommon in epidemiology despite its potential usefulness. The latter was illustrated by studying cross-sectional and longitudinal relationships between eating behavior and adiposity, using four different indicators of fat mass.</p> <p>Methods</p> <p>Using data from a longitudinal community-based study, we fitted structural equation models including two latent variables (respectively baseline adiposity and adiposity change after 2 years of follow-up), each being defined, by the four following anthropometric measurement (respectively by their changes): body mass index, waist circumference, skinfold thickness and percent body fat. Latent adiposity variables were hypothesized to depend on a cognitive restraint score, calculated from answers to an eating-behavior questionnaire (TFEQ-18), either cross-sectionally or longitudinally.</p> <p>Results</p> <p>We found that high baseline adiposity was associated with a 2-year increase of the cognitive restraint score and no convincing relationship between baseline cognitive restraint and 2-year adiposity change could be established.</p> <p>Conclusions</p> <p>The latent variable modeling approach enabled presentation of synthetic results rather than separate regression models and detailed analysis of the causal effects of interest. In the general population, restrained eating appears to be an adaptive response of subjects prone to gaining weight more than as a risk factor for fat-mass increase.</p

Low-frequency variants in HMGA1 are not associated with type 2 diabetes risk.

It has recently been suggested that the low-frequency c.136-14_136-13insC variant in high-mobility group A1 (HMGA1) may strongly contribute to insulin resistance and type 2 diabetes risk. In our study, we attempted to confirm that HMGA1 is a novel type 2 diabetes locus in French Caucasians. The gene was sequenced in 368 type 2 diabetic case subjects with a family history of type 2 diabetes and 372 normoglycemic control subjects without a family history of type 2 diabetes. None of the 41 genetic variations identified were associated with type 2 diabetes. The lack of association between the c.136-14_136-13insC variant and type 2 diabetes was confirmed in an independent French group of 4,538 case subjects and 4,015 control subjects and in a large meta-analysis of 16,605 case subjects and 46,179 control subjects. Finally, this variant had no effects on metabolic traits and was not involved in variations of HMGA1 and insulin receptor (INSR) expressions. The c.136-14_136-13insC variant was not associated with type 2 diabetes in individuals of European descent. Our study emphasizes the need to analyze a large number of subjects to reliably assess the association of low-frequency variants with the disease