The host metabolite D-serine contributes to bacterial niche specificity through gene selection

Escherichia coli comprise a diverse array of both commensals and niche-specific pathotypes. The ability to cause disease results from both carriage of specific virulence factors and regulatory control of these via environmental stimuli. Moreover, host metabolites further refine the response of bacteria to their environment and can dramatically affect the outcome of the host–pathogen interaction. Here, we demonstrate that the host metabolite, D-serine, selectively affects gene expression in E. coli O157:H7. Transcriptomic profiling showed exposure to D-serine results in activation of the SOS response and suppresses expression of the Type 3 Secretion System (T3SS) used to attach to host cells. We also show that concurrent carriage of both the D-serine tolerance locus (dsdCXA) and the locus of enterocyte effacement pathogenicity island encoding a T3SS is extremely rare, a genotype that we attribute to an ‘evolutionary incompatibility’ between the two loci. This study demonstrates the importance of co-operation between both core and pathogenic genetic elements in defining niche specificity

Individual differences in puberty onset in girls: Bayesian estimation of heritabilities and genetic correlations

We report heritabilities for individual differences in female pubertal development at the age of 12. Tanner data on breast and pubic hair development in girls and data on menarche were obtained from a total of 184 pairs of monozygotic and dizygotic twins. Genetic correlations were estimated to determine to what extent the same genes are involved in different aspects of physical development in puberty. A Bayesian estimation approach was taken, using Markovchain Monte Carlo simulation to estimate model parameters. All three phenotypes were to a significant extent heritable and showed high genetic correlations, suggesting that a common set of genes is involved in the timing of puberty in general. However, gonadarche (menarche and breast development) and adrenarche (pubic hair) are affected by different environmental factors, which does not support the three phenotypes to be regarded as indicators of a unitary physiological factor. © 2006 Springer Science+Business Media, Inc

Within-species variation in the gut microbiome of fish is driven by the interaction of light intensity and genetic background

Gut microbiome diversity and functions are jointly shaped by the host’s genetic background and environmental conditions, but the consequences of this interaction are still unclear. Unravelling the effect of the interaction between evolution and environment on the gut microbiome is particularly relevant considering the unprecedented level of human-driven disruption on the ecological and evolutionary trajectories of species. Here, we aimed to evaluate whether size-selective mortality influences the gut microbiome of medaka (Oryzias latipes), how environment conditions modulate the effect of the genetic background of medaka on their microbiota, and the association between microbiome diversity and medaka fitness. To do so, we studied two lineages of medaka that were raised under antagonistic size-selective regimes for 10 generations (i.e. the largest or the smallest breeders were removed to mimic fishing-like or natural mortality). In pond mesocosms, the two lineages were subjected to contrasting population density and light intensity (i.e. used as a proxy of primary production, hence resource availability). We observed significant differences in the gut microbiome composition and richness between the two lines, and this effect was mediated by light intensity. Indeed, the bacterial richness of fishing-like medaka (small-breeder line) was reduced by 34% under low-light conditions compared to high-light conditions, while it remained unchanged in natural mortality-selected medaka (large-breeder line). However, the observed changes in bacterial richness did not correlate with changes in growth rate or body condition, possibly due to functional redundancy among the microbial taxa residing in the gut. Given the growing evidence about the gut microbiomes importance to host health, more in-depth studies are required to fully understand the role of the microbiome in size-selected organisms and the possible ecosystem-level consequences

Fractional flow reserve (FFR) for the appropriateness of percutaneous transluminal coronary angioplasty (PTCA) in patients with a coronary stenosis but without proof of ischemia : two-year follow-up of the prospective randomized DEFER study

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Quality of life and sexual well-being in patients with a Fontan circulation: An explorative pilot study with a mixed method design

OBJECTIVE: To get an impression of the quality of life (QOL) and sexual well-being in the Fontan population, and to generate hypotheses for future research. METHODS: For this cross-sectional pilot study, questionnaires regarding health-related QOL, sexual function and fertility/pregnancy were completed by 21 patients with a Fontan circulation >16 years old, followed at the University Medical Center Groningen, the Netherlands. Semi-structured qualitative interviews were conducted in 8 patients. RESULTS: Fontan patients scored significantly lower on general health than their healthy peers (t(19)=-3.0, P = .008), whereas their scores on other QOL domains and sexual well-being were comparable to normal values. During childhood, most patients experienced physical limitations and the feeling of being an outsider, and frequently faced bullying. Regarding sexual well-being, large interindividual differences were noted. Four interviewed patients (25-30 years) reported a good sexual well-being, whereas the other interviewed patients (33-47 years) reported erectile dysfunction, low self-esteem and avoidance of sexual intercourse. Both the QOL domains mental health and role restrictions due to emotional problems were associated with female avoidance (P = .083, respectively, P = .089) and dyspareunia (P = ns respectively P = .094). In males, role restrictions due to physical problems and health change were related to sexual dissatisfaction (P = .056) respectively nonsensuality (P = .025). CONCLUSIONS: Overall, Fontan patients have a relatively preserved quality of life and sexual wellbeing but face more social isolation and bullying during childhood/adolescence than their healthy peers. Sexual problems were mainly associated with physical limitations in males and with psychosocial limitations in females. Finally, sexual dysfunction was more common in older Fontan patients, and future research has to clarify whether progressive attrition of the Fontan circulation affects the patients' QOL and sexual well-being

Prolyl hydroxylase inhibition during hyperoxia prevents oxygen-induced retinopathy

Oxygen-induced retinopathy (OIR) in the mouse, like the analogous human disease retinopathy of prematurity, is an ischemic retinopathy dependent on oxygen-induced vascular obliteration. We tested the hypothesis that chemically overriding the oxygen-induced downregulation of hypoxia-inducible factor (HIF) activity would prevent vascular obliteration and subsequent pathologic neovascularization in the OIR model. Because the degradation of HIF-1α is regulated by prolyl hydroxylases, we examined the effect of systemic administration of a prolyl hydroxylase inhibitor, dimethyloxalylglycine, in the OIR model. Our results determine that stabilizing HIF activity in the early phase of OIR prevents the oxygen-induced central vessel loss and subsequent vascular tortuosity and tufting that is characteristic of OIR. Overall, these findings imply that simulating hypoxia chemically by stabilizing HIF activity during the causative ischemia phase (hyperoxia) of retinopathy of prematurity may be of therapeutic value in preventing progression to the proliferative stage of the disease

Safety and efficacy of oxandrolone in growth hormone-treated girls with turner syndrome: Evidence from recent studies and recommendations for use

There has been no consensus regarding the efficacy and safety of oxandrolone (Ox) in addition to growth hormone (GH) in girls with Turner syndrome (TS), the optimal age of starting this treatment, or the optimal dose. This collaborative venture between Dutch, UK and US centers is intended to give a summary of the data from three recently published randomized, placebo-controlled, double-blind studies on the effects of Ox. The published papers from these studies were reviewed within the group of authors to reach consensus about the recommendations. The addition of Ox to GH treatment leads to an increase in adult height, on average 2.3-4.6 cm. If Ox dosages <0.06 mg/kg/day are used, side effects are modest. The most relevant safety concerns are virilization (including clitoromegaly and voice deepening) and a transient delay of breast development. We advise monitoring signs of virilization breast development and possibly blood lipids during Ox treatment, in addition to regular follow-up assessments for TS. In girls with TS who are severely short for age, in whom very short adult stature is anticipated, or in whom the growth rate is modest despite good compliance with GH, adjunctive treatment with Ox at a dosage of 0.03-0.05 mg/kg/day starting from the age of 8-10 years onwards can be considered

Maternal thyroid autoimmunity during pregnancy and the risk of attention deficit/hyperactivity problems in children: The generation r study

Background: Maternal thyroid status and autoimmunity during pregnancy have been associated with impaired development of the offspring in animal and human studies. Our objective was to examine whether elevated titers of maternal thyroid peroxidase antibodies (TPOAbs) in early pregnancy increased the risk of cognitive impairment and problem behavior in preschool children. Second, we aimed at exploring to what extent any effect on child behavior was mediated by maternal thyroid parameters during pregnancy. Methods: In the Generation R Study, a population-based cohort of 3139 children and their mothers, we measured maternal thyroid parameters (thyrotropin [TSH], free Thyroxine, and TPOAbs) at 13.5±1.8 weeks of gestation. Children's verbal and nonverbal cognitive functioning was measured at 2.5 years using the Language Development Survey and the Parent Report of Children Abilities. At 3 years, children's behavior was assessed using the Child Behavior Checklist. Results: Elevated titers of TPOAbs during pregnancy did not predict the verbal and nonverbal cognitive functioning of the children. However, elevated titers of TPOAbs in mothers were associated with externalizing problems in children (odds ratio [OR]=1.64, 95% confidence interval [CI]: 1.17-2.29, p=0.004). In particular, children of TPOAb-positive mothers were at a higher risk of attention deficit/hyperactivity problems (OR=1.77, 95% CI: 1.15-2.72, p=0.01). To explore whether the effect of maternal TPOAbs on child problem behavior was mediated by maternal thyroid parameters, we added maternal TSH to the model. After correcting for TSH, the effect of TPOAbs on externalizing problems was attenuated slightly but remained significant (OR=1.56, 95% CI: 1.14, 2.14, p=0.005). Conclusions: Our findings imply that the elevated titers of TPOAbs during pregnancy impact children's risk of problem behavior, in particular, attention deficit/hyperactivity. The observed effect is only partially explained by maternal TSH levels. These findings may point to a specific mechanism of Attention Deficit/Hyperactivity Disorder in children. Nevertheless, we can only speculate about public health implication of the study, as there is no specific treatment for TPOAb-positive pregnant women with normal thyroid function. Further investigation is needed to explore whether TPOAb-positive pregnant women and their children can benefit from close monitoring and early detection of developmental delay in populations at risk