Impact of a Summer Nutrition and Physical Activity Intervention to Attenuate Obesity in Urban African-American Youth

Improved eating behaviors and daily participation in physical activity such as swimming might abate the likelihood of African American youth becoming obese. Yet many African American youth neither consume the recommended daily servings of nutritious foods nor know how to swim. The purpose of this study was to investigate the impact of a culturally tailored multicomponent summer intervention to reduce obesity and unintentional drownings among underserved African American youth. Children (n = 145) participated in a three-hour, community-based intervention for four weeks. Measures of children’s attitudes perceived behavioral control, and subjective norms toward swimming, nutrition, and physical fitness were taken at baseline and 4 weeks later (n = 47). The only post-intervention significant finding indicated an improvement in children’s skillfulness in floating on their back without help. The limited changes in this multi-component program suggested that such interventions need to be longer in duration, intensity, and be required to reduce attrition

Uncovering Enhancer Functions Using the α-Globin Locus

Over the last three decades, studies of the α- and β-globin genes clusters have led to elucidation of the general principles of mammalian gene regulation, such as RNA stability, termination of transcription, and, more importantly, the identification of remote regulatory elements. More recently, detailed studies of α-globin regulation, using both mouse and human loci, allowed the dissection of the sequential order in which transcription factors are recruited to the locus during lineage specification. These studies demonstrated the importance of the remote regulatory elements in the recruitment of RNA polymerase II (PolII) together with their role in the generation of intrachromosomal loops within the locus and the removal of polycomb complexes during differentiation. The multiple roles attributed to remote regulatory elements that have emerged from these studies will be discussed

Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes

publisher: Elsevier articletitle: Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes journaltitle: Cell articlelink: https://doi.org/10.1016/j.cell.2018.05.046 content_type: article copyright: © 2018 Elsevier Inc

Swim to the Top (S3T)

Background: Drowning is the leading cause of unintentional death in children worldwide. Obesity is also a worldwide epidemic wreaking havoc on younger populations. African American youth are overrepresented in the literature on obesity and fatal drownings when compared with other racial groups in the United States. To reduce the unintentional fatal drowning and childhood obesity disparity between African American youth and other racial youth groups , a multicomponent summer program was designed for underserved African American youth. Methods: For four weeks, children participated in a three-hour, community-based multicomponent intervention to improve at-risk youth’s swimming ability, physical fitness, and life skills. Each child was provided a nutritious breakfast snack during the first 30 minutes of each day, which supplemented the nutrition curriculum, a subcomponent of life skills portion of the program. The participants were divided into three age groups, and were provided age- and skill-appropriate instruction in the three major components. Results: Approximately 145 youth aged 4-14 participated in the second year summer program. The majority of the participants were African American, received free or reduced lunch during the previous academic year, and lived in a two-parent household or with a single mother. Nearly half were previous participants in the program. Conclusions: Community-based participatory research, a form of collective engagement research, could potentially eliminate racial disparities in health. Furthermore, summer programs that implement culturally relevant programs based on at-risk youth’s needs have the potential to ameliorate health outcomes for African American youth

Long-range chromosomal interactions regulate the timing of the transition between poised and active gene expression

To understand how mammalian genes are regulated from their natural chromosomal environment, we have analysed the molecular events occurring throughout a 150 kb chromatin segment containing the α globin gene locus as it changes from a poised, silent state in erythroid progenitors, to the fully activated state in late, erythroid cells. Active transcription requires the late recruitment of general transcription factors, mediator and Pol II not only to the promoter but also to its remote regulatory elements. Natural mutants of the α cluster show that whereas recruitment of the pre-initiation complex to the upstream elements occurs independently, recruitment to the promoter is largely dependent on the regulatory elements. An improved, quantitative chromosome conformation capture analysis demonstrates that this recruitment is associated with a conformational change, in vivo, apposing the promoter with its remote regulators, consistent with a chromosome looping mechanism. These findings point to a general mechanism by which a gene can be held in a poised state until the appropriate stage for expression, coordinating the level and timing of gene expression during terminal differentiation

Genome-wide Association Study Identifies SESTD1 as a Novel Risk Gene for Lithium Responsive Bipolar Disorder

Lithium is the mainstay prophylactic treatment for bipolar disorder (BD), but treatment response varies considerably across individuals. Patients who respond well to lithium treatment might represent a relatively homogeneous subtype of this genetically and phenotypically diverse disorder. Here, we performed genome-wide association studies (GWAS) to identify (i) specific genetic variations influencing lithium response and (ii) genetic variants associated with risk for lithium-responsive BD. Patients with BD and controls were recruited from Sweden and the United Kingdom. GWAS were performed on 2698 patients with subjectively defined (self-reported) lithium response and 1176 patients with objectively defined (clinically documented) lithium response. We next conducted GWAS comparing lithium responders with healthy controls (1639 subjective responders and 8899 controls; 323 objective responders and 6684 controls). Meta-analyses of Swedish and UK results revealed no significant associations with lithium response within the bipolar subjects. However, when comparing lithium-responsive patients with controls, two imputed markers attained genome-wide significant associations, among which one was validated in confirmatory genotyping (rs116323614, P=2.74 × 10-8). It is an intronic single-nucleotide polymorphism (SNP) on chromosome 2q31.2 in the gene SEC14 and spectrin domains 1 (SESTD1), which encodes a protein involved in regulation of phospholipids. Phospholipids have been strongly implicated as lithium treatment targets. Furthermore, we estimated the proportion of variance for lithium-responsive BD explained by common variants ('SNP heritability') as 0.25 and 0.29 using two definitions of lithium response. Our results revealed a genetic variant in SESTD1 associated with risk for lithium-responsive BD, suggesting that the understanding of BD etiology could be furthered by focusing on this subtype of BD

Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects

Copy number variants (CNVs) have been strongly implicated in the genetic etiology of schizophrenia (SCZ). However, genome-wide investigation of the contribution of CNV to risk has been hampered by limited sample sizes. We sought to address this obstacle by applying a centralized analysis pipeline to a SCZ cohort of 21,094 cases and 20,227 controls. A global enrichment of CNV burden was observed in cases (odds ratio (OR) = 1.11, P = 5.7 x 10(-15)), which persisted after excluding loci implicated in previous studies (OR = 1.07, P = 1.7 x 10(-6)). CNV burden was enriched for genes associated with synaptic function (OR = 1.68, P = 2.8 x 10(-11)) and neurobehavioral phenotypes in mouse (OR = 1.18, P = 7.3 x 10(-5)). Genome-wide significant evidence was obtained for eight loci, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2. Suggestive support was found for eight additional candidate susceptibility and protective loci, which consisted predominantly of CNVs mediated by nonallelic homologous recombination