Genomic DNA transposition induced by human PGBD5

Transposons are mobile genetic elements that are found in nearly all organisms, including humans. Mobilization of DNA transposons by transposase enzymes can cause genomic rearrangements, but our knowledge of human genes derived from transposases is limited. In this study, we find that the protein encoded by human PGBD5, the most evolutionarily conserved transposable element-derived gene in vertebrates, can induce stereotypical cut-and-paste DNA transposition in human cells. Genomic integration activity of PGBD5 requires distinct aspartic acid residues in its transposase domain, and specific DNA sequences containing inverted terminal repeats with similarity to piggyBac transposons. DNA transposition catalyzed by PGBD5 in human cells occurs genome-wide, with precise transposon excision and preference for insertion at TTAA sites. The apparent conservation of DNA transposition activity by PGBD5 suggests that genomic remodeling contributes to its biological function. DOI: http://dx.doi.org/10.7554/eLife.10565.00

Weight-related teasing in the school environment: associations with psychosocial health and weight control practices among adolescent boys and girls

Weight-related teasing has been found to be associated with low self-esteem, depressive symptoms, body dissatisfaction, and weight control behaviors in adolescents. While research has typically examined weight-related teasing directed towards the individual, little is known about weight-related teasing at the school level. This study aimed to determine the association between the school-level prevalence of weight-related teasing and psychosocial factors, body dissatisfaction and weight control behaviors in adolescents. Adolescents (N = 2,793; 53.2 % female) attending 20 US public middle and high schools were surveyed as part of the Eating and Activity in Teens (EAT) 2010 study. Generalized estimating equations were used to estimate the association between school-level weight-related teasing and health variables, controlling for individual-level weight-related teasing, clustering of individuals within schools, and relevant covariates. A greater school-level prevalence of weight-related teasing was associated with lower self-esteem and greater body fat dissatisfaction in girls, and greater depressive symptoms in boys, over and above individual-level weight-related teasing.Dieting was associated with the school-level prevalence of weight-related teasing in analysis adjusted for covariates in girls, but not following adjustment for individual-level weight-related teasing. Unhealthy weight control behaviors, extreme weight control behaviors, and muscle-enhancing behaviors were not associated with the school-level prevalence of weight-related teasing in girls or boys. Findings from the current study, in conjunction with previous findings showing associations between weight-related teasing, psychological concerns, and weight control behaviors, highlight the importance of implementing strategies to decrease weight-related teasing in schools

Protocol: Adaptive Implementation of Effective Programs Trial (ADEPT): cluster randomized SMART trial comparing a standard versus enhanced implementation strategy to improve outcomes of a mood disorders program

Abstract Background Despite the availability of psychosocial evidence-based practices (EBPs), treatment and outcomes for persons with mental disorders remain suboptimal. Replicating Effective Programs (REP), an effective implementation strategy, still resulted in less than half of sites using an EBP. The primary aim of this cluster randomized trial is to determine, among sites not initially responding to REP, the effect of adaptive implementation strategies that begin with an External Facilitator (EF) or with an External Facilitator plus an Internal Facilitator (IF) on improved EBP use and patient outcomes in 12 months. Methods/Design This study employs a sequential multiple assignment randomized trial (SMART) design to build an adaptive implementation strategy. The EBP to be implemented is life goals (LG) for patients with mood disorders across 80 community-based outpatient clinics (N = 1,600 patients) from different U.S. regions. Sites not initially responding to REP (defined as <50% patients receiving ≥3 EBP sessions) will be randomized to receive additional support from an EF or both EF/IF. Additionally, sites randomized to EF and still not responsive will be randomized to continue with EF alone or to receive EF/IF. The EF provides technical expertise in adapting LG in routine practice, whereas the on-site IF has direct reporting relationships to site leadership to support LG use in routine practice. The primary outcome is mental health-related quality of life; secondary outcomes include receipt of LG sessions, mood symptoms, implementation costs, and organizational change. Discussion This study design will determine whether an off-site EF alone versus the addition of an on-site IF improves EBP uptake and patient outcomes among sites that do not respond initially to REP. It will also examine the value of delaying the provision of EF/IF for sites that continue to not respond despite EF. Trial registration ClinicalTrials.gov identifier: NCT02151331http://deepblue.lib.umich.edu/bitstream/2027.42/109472/1/13012_2014_Article_132.pd

The Role of Husbands’ and Wives’ Emotional Expressivity in the Marital Relationship

The current investigation was designed to examine the role of positive and negative emotional expressivity in the marital relationship. Data from 58 married couples were used to assess spouses’ levels of emotional expressivity and how these levels predicted reports of marital functioning. Regression analyses indicated that positive emotional expressivity had limited influence on marital functioning. Negative expressivity, however, had a strong impact on marital love, conflict, and ambivalence. Post-hoc analyses revealed significant differences between pairings in which the husband was high in negative expressivity, irrespective of wives’ negative emotional expressivity, and pairings in which both partners were low in negative emotional expressivity. These findings are discussed with respect to previous research that suggests that wives’ emotional expressivity is the major determinant of marital functioning.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45641/1/11199_2005_Article_3726.pd

Defining non-canonical modes of gene regulation in budding yeast meiosis

Gene regulation in budding yeast meiosis is incredibly complex, involving a number of non-canonical strategies. Defining the different modes of regulation is key to fully understanding how the cell functions, especially under changing conditions. Here, we examined two non-canonical gene regulation strategies employed by yeast during meiosis: alternative translation initiation and regulated turnover of ribosomal proteins.In chapter two, we investigated the role of alternative translation initiation site choice in yeast. Genomic analyses in budding yeast have helped define the foundational principles of eukaryotic gene expression. However, in the absence of empirical methods for defining coding regions, these analyses have historically excluded specific classes of possible coding regions, such as those initiating at non-AUG start codons. We applied an experimental approach to globally annotate translation initiation sites in yeast and identified 149 genes with alternative N-terminally extended protein isoforms initiating from near-cognate codons upstream of annotated AUG start codons. These isoforms are produced in concert with canonical isoforms and translated with high specificity, resulting from initiation at only a small subset of possible start codons. The non-AUG initiation driving their production is enriched during meiosis and induced by low eIF5A, which is seen in this context. These findings reveal widespread production of non-canonical protein isoforms and unexpected complexity to the rules by which even a simple eukaryotic genome is decoded.In chapter three, we evaluated the role of protein degradation during yeast meiosis, and found that ribosomes are degraded and resynthesized in spores, revealing an interesting mode of regulation of an important molecular machine. Protein degradation is known to be a key component of expression regulation for individual genes, but its global impact on gene expression has been difficult to determine. We analyzed a parallel gene expression dataset of yeast meiotic differentiation, identifying instances of coordinated protein-level decreases to identify new cases of regulated meiotic protein degradation, including degradation of ribosomes. Comparison of protein and translation measurements over time revealed that ribosomes are degraded and resynthesized in spores, making the biological purpose of ribosome resetting an interesting area of follow-up