Experimental studies show a substantial contribution of early life environment to obesity risk through epigenetic processes. We examined inter-individual DNA methylation differences in human birth ...tissues associated with child's adiposity. We identified a novel association between the level of CpG methylation at birth within the promoter of the long non-coding RNA ANRIL (encoded at CDKN2A) and childhood adiposity at age 6-years. An association between ANRIL methylation and adiposity was also observed in three additional populations; in birth tissues from ethnically diverse neonates, in peripheral blood from adolescents, and in adipose tissue from adults. Additionally, CpG methylation was associated with ANRIL expression in vivo, and CpG mutagenesis in vitro inhibited ANRIL promoter activity. Furthermore, CpG methylation enhanced binding to an Estrogen Response Element within the ANRIL promoter. Our findings demonstrate that perinatal methylation at loci relevant to gene function may be a robust marker of later adiposity, providing substantial support for epigenetic processes in mediating long-term consequences of early life environment on human health.
•DNA methylation within the ANRIL promoter region was predictive of measures of adiposity in four independent cohorts.•DNA methylation may be a marker for late gestation fetal undernutrition, followed by rapid postnatal weight gain.•Altered DNA methylation associated with p16INK4a and p14ARF expression.•ERα may bind at the ANRIL promoter, and in vitro E2 treatment stimulated expression of ANRIL, while reducing p14 expression.
The quality of the early life environment before birth can affect susceptibility to metabolic disease later in the lifecourse, with epigenetic regulation of gene function thought to be one mechanism through which early life environmental factors induce persistent phenotypic changes. In this study, using DNA from the Southampton Women's Survey (SWS), we identified changes in DNA methylation levels at birth that associated with adiposity later in childhood within the promoter of ANRIL, a gene with strong disease associations that is involved in regulatiing cellular growth. This finding was replicated in several independent cohorts, and functionally validated in adipocyte cells.
ObjectiveChildren and young people living with asthma have an increased risk of overweight/obesity, leading to increased severity of asthma symptoms. Weight management has been recommended to improve ...asthma symptoms, however, there is limited understanding of how this is experienced or how children and young people with asthma and their families wish to be supported. The aim of this study was to explore parents and children/young people's views and experiences of managing weight while living with asthma, and to identify acceptable strategies for support.Methods: A qualitative methodological approach was taken to facilitate rich understanding of families' insights into weight management while living with asthma. In-depth interviews were conducted with nine families living with pediatric asthma (n = 9 parents, 9 young people). Data were analyzed using a Framework approach.Results: Findings indicated that family engagement with weight management behaviors was primarily influenced by perceptions of risk regarding asthma outcomes and beliefs about asthma control. Families also reported weight management engagement to be influenced by perceptions of the food environment, perceptions of the exercise environment (e.g. weather, anticipated social outcomes) and the availability of weight management support. Participants sought tailored support which gave consideration to the asthma-obesity interaction. It was suggested that this would help reduce perceptions of weight stigma in consultations, thereby supporting behavioral changes.Conclusions: Individualized weight management plans that consider families concerns about asthma-related risk are needed to manage weight in children and young people living with asthma.
Fluorescent tags are commonly used for imaging of proteins and peptides during biological events; however, the large size of dyes can disrupt protein structure and function, and typically require the ...use of a chemical spacer. Herein, we report the synthesis of a new class of fluorescent unnatural -amino acid, containing carbazole side-chains designed to mimic
l
-tryptophan and thus, readily incorporated into peptides. The amino acids were constructed using a Negishi cross-coupling reaction as the key step and exhibited strong fluorescent emission, with high quantum yields in both organic solvents and water. Compatible with solid phase peptide synthesis, the carbazole amino acids were used to replace tryptophan in a -hairpin model peptide and shown to be a close structural mimic with retention of conformation. They were also found to be effective fluorescent molecular reporters for biological events. Incorporation into a proline-rich ligand of the WW domain protein demonstrated that the fluorescent properties of a carbazole amino acid could be used to measure the proteinprotein binding interaction of this important biological signalling process.
Unnatural -amino acids bearing carbazole side-chains have been shown to be effective structural mimics of tryptophan in peptides and valuable fluorescent probes for the analysis of proteinprotein interactions.
Black ethnic groups are disproportionately affected by sexually transmitted infections (STIs). This review aimed to identify interventions designed to increase engagement with sexual healthcare among ...people of Black ethnicity as determined by rates of STI testing, adherence to sexual health treatment, and attendance at sexual healthcare consultations. The behaviour change techniques (BCTs) used within identified interventions were evaluated.
Four electronic databases (Web of science; ProQuest; Scopus; PubMed) were systematically searched to identify eligible articles published between 2000 and 2022. Studies were critically appraised using the Mixed Methods Appraisal Tool. Findings were narratively synthesised.
Twenty one studies across two countries were included. Studies included randomised controlled trials and non-randomised designs. Behavioural interventions had the potential to increase STI/HIV testing, sexual healthcare consultation attendance and adherence to sexual health treatment. Behavioural theory underpinned 16 interventions which addressed barriers to engaging with sexual healthcare. Intervention facilitators' demographics and lived experience were frequently matched to those of recipients. The most frequently identified novel BCTs in effective interventions included information about health consequences, instruction on how to perform behaviour, information about social and environmental consequences, framing/reframing, problem solving, and review behavioural goal(s).
Our findings highlight the importance of considering sociocultural, structural and socio-economic barriers to increasing engagement with sexual healthcare. Matching the intervention facilitators' demographics and lived experience to intervention recipients may further increase engagement. Examination of different BCT combinations would benefit future sexual health interventions in Black ethnic groups.
This study’s primary objective was to establish differences in beliefs about medicines, levels of asthma-related anxiety and diet and exercise behaviours between parents of children with well ...controlled and poorly controlled asthma. Secondary objectives were to explore how asthma control might shape relationships between parental cognitions and parenting practices concerning paediatric asthma. Parents of children with asthma aged 10–16 years (N = 310) completed standardised questionnaires measuring beliefs about medicines, parental asthma-related anxiety, parenting attitudes towards child activity, parental feeding and asthma control. Parents of children with poorly controlled asthma reported significantly greater asthma medication necessity and concern, asthma-related anxiety, control of child activity, pressure to exercise and unhealthy feeding practices. Moderation analyses indicated that the relationship between parental concern about asthma medicine and parental control of child activity was strongest in children with poorly controlled asthma. Also, the relationship between parental asthma-related anxiety and use of food to regulate child emotion was only significant when asthma was poorly controlled. Parental beliefs about asthma medicines and asthma-related anxiety may indirectly influence asthma outcomes through unhealthy parenting practices around exercise and diet. Eliciting and understanding parents’ perceptions of asthma medications and anxiety may facilitate personalised interventions to improve asthma control.
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