Visualizing variation within Global Pneumococcal Sequence Clusters (GPSCs) and country population snapshots to contextualize pneumococcal isolates

Knowledge of pneumococcal lineages, their geographic distribution and antibiotic resistance patterns, can give insights into global pneumococcal disease. We provide interactive bioinformatic outputs to explore such topics, aiming to increase dissemination of genomic insights to the wider community, without the need for specialist training. We prepared 12 country-specific phylogenetic snapshots, and international phylogenetic snapshots of 73 common Global Pneumococcal Sequence Clusters (GPSCs) previously defined using PopPUNK, and present them in Microreact. Gene presence and absence defined using Roary, and recombination profiles derived from Gubbins are presented in Phandango for each GPSC. Temporal phylogenetic signal was assessed for each GPSC using BactDating. We provide examples of how such resources can be used. In our example use of a country-specific phylogenetic snapshot we determined that serotype 14 was observed in nine unrelated genetic backgrounds in South Africa. The international phylogenetic snapshot of GPSC9, in which most serotype 14 isolates from South Africa were observed, highlights that there were three independent sub-clusters represented by South African serotype 14 isolates. We estimated from the GPSC9-dated tree that the sub-clusters were each established in South Africa during the 1980s. We show how recombination plots allowed the identification of a 20kb recombination spanning the capsular polysaccharide locus within GPSC97. This was consistent with a switch from serotype 6A to 19A estimated to have occured in the 1990s from the GPSC97-dated tree. Plots of gene presence/absence of resistance genes (tet, erm, cat) across the GPSC23 phylogeny were consistent with acquisition of a composite transposon. We estimated from the GPSC23-dated tree that the acquisition occurred between 1953 and 1975. Finally, we demonstrate the assignment of GPSC31 to 17 externally generated pneumococcal serotype 1 assemblies from Utah via Pathogenwatch. Most of the Utah isolates clustered within GPSC31 in a USA-specific clade with the most recent common ancestor estimated between 1958 and 1981. The resources we have provided can be used to explore to data, test hypothesis and generate new hypotheses. The accessible assignment of GPSCs allows others to contextualize their own collections beyond the data presented here

Behavioural Susceptibility Theory: Professor Jane Wardle and the Role of Appetite in Genetic Risk of Obesity

Purpose of Review: There is considerable variability in human body weight, despite the ubiquity of the 'obesogenic' environment. Human body weight has a strong genetic basis and it has been hypothesised that genetic susceptibility to the environment explains variation in human body weight, with differences in appetite being implicated as the mediating mechanism; so-called 'behavioural susceptibility theory' (BST), first described by Professor Jane Wardle. This review summarises the evidence for the role of appetite as a mediator of genetic risk of obesity. Recent Findings: Variation in appetitive traits is observable from infancy, drives early weight gain and is highly heritable in infancy and childhood. Obesity-related common genetic variants identified through genome-wide association studies show associations with appetitive traits, and appetite mediates part of the observed association between genetic risk and adiposity. Summary: Obesity results from an interaction between genetic susceptibility to overeating and exposure to an 'obesogenic' food environment

Body composition impacts appetite regulation in middle childhood. A prospective study of Norwegian community children

Background Research suggests a role for both fat mass and muscle mass in appetite regulation, but the longitudinal relationships between them have not yet been examined in children. The present study therefore aimed to explore the prospective relationships between fat mass, muscle mass and the appetitive traits food responsiveness and satiety responsiveness in middle childhood. Methods Food responsiveness and satiety responsiveness were measured using the parent-reported Children’s Eating Behavior Questionnaire in a representative sample of Norwegian 6 year olds, followed up at 8 and 10 years of age (n = 807). Body composition was measured by bioelectrical impedance. Results Applying a structural equation modeling framework we found that higher fat mass predicted greater increases in food responsiveness over time, whereas greater muscle mass predicted decreases in satiety responsiveness. This pattern was consistent both from ages 6 to 8 and from ages 8 to 10 years. Conclusions Our study is the first to reveal that fat mass and muscle mass predict distinct changes in different appetitive traits over time. Replication of findings in non-European populations are needed, as are studies of children in other age groups. Future studies should also aim to reveal the underlying mechanisms

Relevance of laboratory testing for the diagnosis of primary immunodeficiencies: a review of case-based examples of selected immunodeficiencies

The field of primary immunodeficiencies (PIDs) is one of several in the area of clinical immunology that has not been static, but rather has shown exponential growth due to enhanced physician, scientist and patient education and awareness, leading to identification of new diseases, new molecular diagnoses of existing clinical phenotypes, broadening of the spectrum of clinical and phenotypic presentations associated with a single or related gene defects, increased bioinformatics resources, and utilization of advanced diagnostic technology and methodology for disease diagnosis and management resulting in improved outcomes and survival. There are currently over 200 PIDs with at least 170 associated genetic defects identified, with several of these being reported in recent years. The enormous clinical and immunological heterogeneity in the PIDs makes diagnosis challenging, but there is no doubt that early and accurate diagnosis facilitates prompt intervention leading to decreased morbidity and mortality. Diagnosis of PIDs often requires correlation of data obtained from clinical and radiological findings with laboratory immunological analyses and genetic testing. The field of laboratory diagnostic immunology is also rapidly burgeoning, both in terms of novel technologies and applications, and knowledge of human immunology. Over the years, the classification of PIDs has been primarily based on the immunological defect(s) ("immunophenotype") with the relatively recent addition of genotype, though there are clinical classifications as well. There can be substantial overlap in terms of the broad immunophenotype and clinical features between PIDs, and therefore, it is relevant to refine, at a cellular and molecular level, unique immunological defects that allow for a specific and accurate diagnosis. The diagnostic testing armamentarium for PID includes flow cytometry - phenotyping and functional, cellular and molecular assays, protein analysis, and mutation identification by gene sequencing. The complexity and diversity of the laboratory diagnosis of PIDs necessitates many of the above-mentioned tests being performed in highly specialized reference laboratories. Despite these restrictions, there remains an urgent need for improved standardization and optimization of phenotypic and functional flow cytometry and protein-specific assays. A key component in the interpretation of immunological assays is the comparison of patient data to that obtained in a statistically-robust manner from age and gender-matched healthy donors. This review highlights a few of the laboratory assays available for the diagnostic work-up of broad categories of PIDs, based on immunophenotyping, followed by examples of disease-specific testing

Common etiological architecture underlying reward responsiveness, externally driven eating behaviors, and BMI in childhood: findings from the Gemini twin cohort

BACKGROUND: Studies have reported that impulsivity predicts childhood BMI and that the association is mediated by eating behaviors. One aspect of impulsivity-potentially crucial in the obesity context-is reward responsiveness, which may predispose to responsiveness to palatable food cues. The behavioral susceptibility theory hypothesizes that genetic susceptibility to obesity operates partly via genetically determined differences in appetite regulation. Reward responsiveness may therefore be one of the neuro-endophenotypes that mediates genetic susceptibility to obesity. OBJECTIVE: To test whether reward responsiveness, eating behaviors, and child BMI share common genetic architecture. METHODS: We examined reward responsiveness, eating behaviors, and BMI in 5-year-old children from Gemini, a UK birth cohort of 2402 twin pairs born in 2007. All measures were collected by parent report. Reward responsiveness was derived from the Behavioral Approach System. Compulsion to eat and eating for pleasure was measured with the "food responsiveness" scale of the Child Eating Behavior Questionnaire. Wanting to eat in response to environmental food cues was measured with the "external eating" scale of the Dutch Eating Behavior Questionnaire. Maximum-likelihood structural equation modeling was used to establish underlying common genetic and environmental influences. RESULTS: There were significant positive phenotypic correlations between all traits except for reward responsiveness and BMI. Genetic factors explained the majority of the association between food responsiveness and external eating (74%, 95% CI: 61, 87), whereas common shared environmental factors explained the majority of the associations between reward responsiveness with both food responsiveness (55%, 95% CI: 20, 90) and external eating (70%, 95% CI: 39, 100). CONCLUSIONS: Our study demonstrates the importance of common environmental factors in the shared etiology between reward responsiveness and childhood eating behaviors. However, the common etiology underlying both reward responsiveness and BMI is unclear, as there was no phenotypic correlation between reward responsiveness and BMI at this age. Further longitudinal research needs to detangle this complex relationship throughout development

Evaluation of an eHealth intervention aiming to promote healthy food habits from infancy -the Norwegian randomized controlled trial Early Food for Future Health

Confirmatory factor analysis for the Child Eating Behavior Questionnaire; factor loadings for all items and Cronbach alpha scores for each factor structure. (PDF 210 kb

Longitudinal Analysis Between Maternal Feeding Practices and Body Mass Index (BMI): A Study in Asian Singaporean Preschoolers

10.3389/fnut.2019.00032Frontiers in Nutrition632GUSTO (Growing up towards Healthy Outcomes