Dietary Energy Density Affects Fat Mass in Early Adolescence and Is Not Modified by FTO Variants

Background

Dietary energy density (DED) does not have a simple linear relationship to fat mass in children, which suggests that some children are more susceptible than others to the effects of DED. Children with the FTO (rs9939609) variant that increases the risk of obesity may have a higher susceptibility to the effects of DED because their internal appetite control system is compromised. We tested the relationship between DED and fat mass in early adolescence and its interaction with FTO variants.

Methods and Findings

We carried out a prospective analysis on 2,275 children enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC). Diet was assessed at age 10 y using 3-day diet diaries. DED (kJ/g) was calculated excluding drinks. Children were genotyped for the FTO (rs9939609) variant. Fat mass was estimated at age 13 y using the Lunar Prodigy Dual-energy X-ray Absorptiometry scanner. There was no evidence of interaction between DED at age 10 y and the high risk A allele of the FTO gene in relation to fat mass at age 13 y (β = 0.005, p = 0.51), suggesting that the FTO gene has no effect on the relation between DED at 10 y and fat mass at 13 y. When DED at 10 y and the A allele of FTO were in the same model they were independently related to fat mass at 13 y. Each A allele of FTO was associated with 0.35±0.13 kg more fat mass at 13 y and each 1 kJ/g DED at 10 y was associated with 0.16±0.06 kg more fat mass at age 13 y, after controlling for misreporting of energy intake, gender, puberty, overweight status at 10 y, maternal education, TV watching, and physical activity.

Conclusions

This study reveals the multi-factorial origin of obesity and indicates that although FTO may put some children at greater risk of obesity, encouraging a low dietary energy density may be an effective strategy to help all children avoid excessive fat gain.     

Identification of the Biosynthetic Gene Cluster for the Pseudomonas aeruginosa Antimetabolite l-2-Amino-4-Methoxy-trans-3-Butenoic Acid

l-2-Amino-4-methoxy-trans-3-butenoic acid (AMB) is a potent antibiotic and toxin produced by Pseudomonas aeruginosa. Using a novel biochemical assay combined with site-directed mutagenesis in strain PAO1, we have identified a five-gene cluster specifying AMB biosynthesis, probably involving a thiotemplate mechanism. Overexpression of this cluster in strain PA7, a natural AMB-negative isolate, led to AMB overproduction.The Gram-negative bacterium Pseudomonas aeruginosa is an opportunistic pathogen that causes a wide range of human infections and is considered the main pathogen responsible for chronic pneumonia in cystic fibrosis patients (7, 23). P. aeruginosa also infects other organisms, such as insects (4), nematodes (6), plants (18), and amoebae (20). Its ability to thrive as a pathogen and to compete in aquatic and soil environments can be partly attributed to the production and interplay of secreted virulence factors and secondary metabolites. While the importance of many of these exoproducts has been studied, the antimetabolite l-2-amino-4-methoxy-trans-3-butenoic acid (AMB; methoxyvinylglycine) (Fig. ​(Fig.1)1) has received only limited attention. Identified during a search for new antibiotics, AMB was found to reversibly inhibit the growth of Bacillus spp. (26) and Escherichia coli (25) and was later shown to inhibit the growth and metabolism of cultured Walker carcinosarcoma cells (28). AMB is a γ-substituted vinylglycine, a naturally occurring amino acid with a β,γ-C=C double bond. Other members of this family are aminoethoxyvinylglycine from Streptomyces spp. (19) and rhizobitoxine, made by Bradyrhizobium japonicum (16) and Pseudomonas andropogonis (15) (Fig. ​(Fig.1).1). As inhibitors of pyridoxal phosphate-dependent enzymes (13, 17, 21, 22), γ-substituted vinylglycines have multiple targets in bacteria, animals, and plants (3, 5, 10, 21, 22, 29). However, the importance of AMB as a toxin in biological interactions with P. aeruginosa has not been addressed, as AMB biosynthesis and the genes involved have not been elucidated.Open in a separate windowFIG. 1.Chemical structures of the γ-substituted vinylglycines AMB, aminoethoxyvinylglycine, and rhizobitoxine.     

Factors associated with virulence and survival in environmental and clinical isolates of Vibrio cholerae O1 and non O1 in Romania

Four hundred ninety seven strains of Vibrio cholerae selected from isolates in Romania in the last decade 1990-1999 were investigated for antibiotic resistance and for classical and putative virulence factors. V. cholerae O1 strains predominated in clinical cases and non O1 strains in the environment, excepting in 1992 when non O1 strains were frequent in clinical and environmental sources. V. cholerae O1 strains previously susceptible to tetracycline acquired clinically significant resistance to this drug during 1993-1994, but this trend was reversed in 1995, following the introduction of nalidixic acid in cholera treatment in 1994. V. cholerae O1 and non O1 clinical isolates acquired simultaneous resistance to the vibriostatic agent O/129 and cotrimoxazole during 1994-1995. High levels of intrinsic resistance to multiple antibiotics were exhibited by all strains examined. The presence of cholera toxin (CT) was concentrated in clinical V. cholerae O1 strains and was substituted in clinical non O1 strains by four putative virulence markers (Kanagawa haemolysin, slime, lipase, and colonial opacity). Colonial opacity (30%) was present only in clinical isolates of V. cholerae non O1. Pigmentogenesis (11.7%) has present only in environmental sources. Antibioresistance profiles differ for V. cholerae O1 and non O1 strains with respect to their source of isolation. This aspect may imply a role in virulence and survival of V. cholerae in the natural environment where they may serve as a reservoir of virulence and multiple drug resistance genes.     

Cytochrome c at charged interfaces. 2. Complexes with negatively charged macromolecular systems studied by resonance Raman spectroscopy

We have analyzed the structure of cytochrome c (cyt c) bound in a variety of complexes in which negatively charged molecular groups interact with the positively charged binding domain around the heme crevice of cyt c. Using resonance Raman spectroscopy, we could demonstrate that these interactions induce the same conformational changes as they were observed in the surface-enhanced resonance Raman experiments of cyt c adsorbed on the Ag electrode [Hildebrandt & Stockburger (1989) Biochemistry (preceding paper in this issue)]. When cyt c is bound to (As4W40O140)27-, state II is stabilized, whereas in complexes with phosvitin and cytochrome b5 state I is formed. The complexes with phospholipid vesicles and inverted micelles reveal a mixture of both states. It is suggested that these systems as well as cyt c adsorbed on the Ag electrode may be regarded as model systems for the physiological complexes of cyt c with cytochrome oxidase and cytochrome reductase. On the basis of our findings it is proposed that the biological electron-transfer reactions are controlled by electric field induced conformational transitions of cyt c upon complex formation with its physiological redox partners.     

VARIATIONS OF MORPHOGENETIC BEHAVIOR IN PLANT TISSUE CULTURES I. CICHORIUM ENDIVIA

Several-years-old callus tissue derived from mature embryos of endive (Cichorium endivia Linn., Compositae) was grown on synthetic liquid and/or agar nutrient media. Incorporation of yeast extract or high concentrations of inositol, kinetin, casein hydrolysates (pancreatic and acid hydrolysates), etc., improved growth and organ formation. Rosettes of leaves, shoots and roots were differentiated on synthetic media. On agar media shoots arose first and were from marginal meristematic areas, while the roots arose later and were from pockets of meristematic tissue located in the deeper regions of the callus. In liquid media embryoids from single cells were formed which first developed roots and then shoots.     

Bacterial Communities in Bangladesh Aquifers Differing in Aqueous Arsenic Concentration

At Titas, Bangladesh, two aquifers of different arsenic concentrations and redox conditions were investigated to link variations in geochemistry to in situ bacterial diversity characterized by T-RFLP (terminal restriction fragment length polymorphism) and clone library analysis. While the shallow aquifer was characterized by reduced gray sediments with a higher share of easily mobilized sedimentary arsenic (2.6% was easily mobilized from 18 mg/kg of total arsenic available in sediments) and higher aqueous arsenic concentrations of 120 ± 6 μg/L (45% arsenite), the deeper aquifer consisted of brown oxidized sediments with lower aqueous arsenic concentrations, predominantly as arsenate (60 ± 6 μg/L; 3% arsenite) and a higher share of tightly bound arsenic (only 0.6% of 53 mg/kg total sorbed arsenic was easily mobilized). The bacterial communities of both aquifers were dominated by putative aerobic or denitrifying populations of Pseudomonas, Elizabethkingia and Pantoea. The shallow aquifer was more diverse in bacterial populations of aerobic, facultative and anaerobic bacteria, an observation which may be correlated to more variable geochemical conditions resulting in arsenic mobilization and re-sorption. The deeper aquifer showed higher abundance of aerobic bacterial populations including the presence of iron-oxidizing Sideroxydans possibly of importance for the sorption of arsenic on oxidized iron hydroxides. From the arsenic-affected shallow aquifer, As(III) oxidizing isolates of Comamonas and Microbacterium were obtained, which may provide information on suitable conditions for arsenic immobilization useful for future bioremediation efforts. Supplemental materials are available for this article. Go to the publisher’s online edition of Geomicrobiology Journal to view the free supplemental file.     

Contrasting trends in gray seal (Halichoerus grypus) pup production throughout the increasing northwest Atlantic metapopulation

The northwest Atlantic subspecies of gray seal (Halicheorus grypus grypus) has been increasing for more than a half century and has reestablished breeding colonies in Canadian and US waters. In 2016, visual, oblique, and vertical large-format digital photographic surveys were conducted at all known breeding colonies in the northwest Atlantic. Total pup production in the northwest Atlantic was estimated to be 109,000 (SE = 17,500) pups. At 87,500 (SE = 15,100) pups, Sable Island accounts for 80% of total pup production. Regional differences in pup production trends are evident. Pup production in the Gulf of St. Lawrence and along the eastern shore of Nova Scotia has been relatively stable. Since 2004, the rate of increase in pup production at Sable Island has slowed to about 5%–7% per year, while the newer colonies in southwest Nova Scotia and the northeastern United States are increasing rapidly. In 2016, the Muskeget Island (MA) breeding colony produced 3,900 (SE = 200) pups, making it the third largest breeding colony in the northwest Atlantic. This southward shift in production may reflect climate-mediated changes in population growth as well as reestablishment of colonies throughout the former range associated with increased protection.     

Human parvovirus B19 interacts with globoside under acidic conditions as an essential step in endocytic trafficking

The glycosphingolipid (GSL) globoside (Gb4) is essential for parvovirus B19 (B19V) infection. Historically considered the cellular receptor of B19V, the role of Gb4 and its interaction with B19V are controversial. In this study, we applied artificial viral particles, genetically modified cells, and specific competitors to address the interplay between the virus and the GSL. Our findings demonstrate that Gb4 is not involved in the binding or internalization process of the virus into permissive erythroid cells, a function that corresponds to the VP1u cognate receptor. However, Gb4 is essential at a post-internalization step before the delivery of the single-stranded viral DNA into the nucleus. In susceptible erythroid Gb4 knockout cells, incoming viruses were arrested in the endosomal compartment, showing no cytoplasmic spreading of capsids as observed in Gb4-expressing cells. Hemagglutination and binding assays revealed that pH acts as a switch to modulate the affinity between the virus and the GSL. Capsids interact with Gb4 exclusively under acidic conditions and dissociate at neutral pH. Inducing a specific Gb4-mediated attachment to permissive erythroid cells by acidification of the extracellular environment led to a non-infectious uptake of the virus, indicating that low pH-mediated binding to the GSL initiates active membrane processes resulting in vesicle formation. In summary, this study provides mechanistic insight into the interaction of B19V with Gb4. The strict pH-dependent binding to the ubiquitously expressed GSL prevents the redirection of the virus to nonpermissive tissues while promoting the interaction in acidic intracellular compartments as an essential step in infectious endocytic trafficking.     

Oral exposure of pigs to the mycotoxin deoxynivalenol does not modulate the hepatic albumin synthesis during a LPS-induced acute-phase reaction

The sensitivity of pigs to deoxynivalenol (DON) might be influenced by systemic inflammation (SI) which impacts liver. Besides following acute-phase proteins, our aim was to investigate both the hepatic fractional albumin (ALB) synthesis rate (FSR) and the ALB concentration as indicators of ALB metabolism in presence and absence of SI induced by LPS via pre- or post-hepatic venous route. Each infusion group was pre-conditioned either with a control diet (CON, 0.12 mg DON/kg diet) or with a DON-contaminated diet (DON, 4.59 mg DON/kg diet) for 4 wk. A depression of ALB FSR was observed 195 min after LPS challenge, independent of feeding group or LPS application route, which was not paralleled by a down-regulated ALB mRNA expression but by a reduced availability of free cysteine. The drop in ALB FSR only partly explained the plasma ALB concentrations which were more depressed in the DON-pre-exposed groups, suggesting that ALB levels are influenced by further mechanisms. The abundances of haptoglobin, C-reactive protein, serum amyloid A, pig major acute-phase protein, fibrinogen and LPS-binding protein mRNA were up-regulated upon LPS stimulation but not accompanied by increases in the plasma concentrations of these proteins, pointing at an imbalance between synthesis and consumption.