Selenophosphate synthetase (SEPHS) plays an essential role in selenium metabolism. Two mammalian SEPHS paralogues, SEPHS1 and SEPHS2, share high sequence identity and structural homology with SEPHS. ...Here, we report nine individuals from eight families with developmental delay, growth and feeding problems, hypotonia, and dysmorphic features, all with heterozygous missense variants in SEPHS1. Eight of these individuals had a recurrent variant at amino acid position 371 of SEPHS1 (p.Arg371Trp, p.Arg371Gln, and p.Arg371Gly); seven of these variants were known to be de novo. Structural modeling and biochemical assays were used to understand the effect of these variants on SEPHS1 function. We found that a variant at residue Trp352 results in local structural changes of the C-terminal region of SEPHS1 that decrease the overall thermal stability of the enzyme. In contrast, variants of a solvent-exposed residue Arg371 do not impact enzyme stability and folding but could modulate direct protein-protein interactions of SEPSH1 with cellular factors in promoting cell proliferation and development. In neuronal SH-SY5Y cells, we assessed the impact of SEPHS1 variants on cell proliferation and ROS production and investigated the mRNA expression levels of genes encoding stress-related selenoproteins. Our findings provided evidence that the identified SEPHS1 variants enhance cell proliferation by modulating ROS homeostasis. Our study supports the hypothesis that SEPHS1 plays a critical role during human development and provides a basis for further investigation into the molecular mechanisms employed by SEPHS1. Furthermore, our data suggest that variants in SEPHS1 are associated with a neurodevelopmental disorder.
SEPHS1 is in the selenocysteine biosynthetic pathway. We report nine individuals from eight families with developmental delay, growth and feeding problems, hypotonia, and dysmorphic features, all with heterozygous missense variants in SEPHS1. Our findings provide insight into the molecular pathogenesis of this neurodevelopmental disorder.
•Increases in childhood obesity correspond to shifts in child snack portion sizes.•Parents often define child snacks by portion size.•Parents consider healthfulness, location, hunger, and timing to ...portion child snacks.•Low-income parents described a diverse set of strategies for portioning child snacks.•Understanding of parent portion size decision making and child diet quality is needed.
Objective: Increases in childhood obesity correspond with shifts in children's snacking behaviors and food portion sizes. This study examined parents' conceptualizations of portion size and the strategies they use to portion snacks in the context of preschool-aged children's snacking. Methods: Semi-structured qualitative interviews were conducted with non-Hispanic white (W), African American (AA), and Hispanic (H) low-income parents (n = 60) of preschool-aged children living in Philadelphia and Boston. The interview examined parents' child snacking definitions, purposes, contexts, and frequency. Verbatim transcripts were analyzed using a grounded theory approach. Coding matrices compared responses by race/ethnicity, parent education, and household food security status. Results: Parents' commonly referenced portion sizes when describing children's snacks with phrases like “something small.” Snack portion sizes were guided by considerations including healthfulness, location, hunger, and timing. Six strategies for portioning snacks were presented including use of small containers, subdividing large portions, buying prepackaged snacks, use of hand measurement, measuring cups, scales, and letting children determine portion size. Differences in considerations and strategies were seen between race/ethnic groups and by household food security status. Conclusions: Low-income parents of preschool-aged children described a diverse set of considerations and strategies related to portion sizes of snack foods offered to their children. Future studies should examine how these considerations and strategies influence child dietary quality.
Despite the wealth of knowledge of transcription factors involved in lens development, little information exists about the role of DNA methylation in this process. Here, we investigated the role of ...DNA methylation in lens development and fiber cell differentiation using mice conditionally lacking maintenance or de novo methyltransferases in the lens lineage. We found that while Dnmt1 inactivation at the lens placode stage (via the Le-Cre transgene) led to lens DNA hypomethylation and severe lens epithelial apoptosis, lens fiber cell differentiation remained largely unaffected. The simultaneous deletion of phosphatase and tensin homolog (Pten) elevated the level of phosphorylated AKT and rescued many of the morphological defects and cell death in DNMT1-deficient lenses. With a different Cre driver (MLR10) we demonstrated that a small number of lens epithelial cells escaped Dnmt1-deletion and over-proliferated to compensate for the loss of Dnmt1-deleted cells, suggesting that lens epithelium possess a substantial capacity for self-renewal. Unlike lenses deficient for Dnmt1, inactivation of both Dnmt3a and Dnmt3b by either the Le-Cre or MLR10-Cre transgene did not result in any obvious lens phenotype prior to 10 months of age. Taken together, while lens epithelial cell survival requires DNMT1, morphologically normal lenses develop in the absence of both DNMT3A and DNMT3B.
This study explores whether photos posted on online
social networks can be used to assess personality. We have demonstrated that
personality is connected to human- and machine-detected situational ...cues,
characteristics, classes, behavior, and affect displayed in Instagram photos.
Observations of individual relationships between normal or dark side personality
characteristics and situational features of photos give insight into the various
aspects of online portrayal of oneself and the personality behind the
photos.
IntroductionPsychosocial treatments have been shown to benefit people with rheumatoid arthritis (RA) on various outcomes. Two evidence-based interventions are cognitive behavioural therapy (CBT) and ...mindfulness-based stress reduction (MBSR). However, these interventions have been compared only once. Results showed that CBT outperformed MBSR on some outcomes, but MBSR was more effective for people with RA with a history of recurrent depression, with efficacy being moderated by history of depressive episodes. However, this was a post-hoc finding based on a small subsample. We aim to examine whether a history of recurrent depression will moderate the relative efficacy of these treatments when delivered online.Methods and analysisThis study is a randomised controlled trial comparing CBT and MBSR delivered online with a waitlist control condition. History of recurrent depressive episodes will be assessed at baseline. The primary outcome will be pain interference. Secondary outcomes will include pain intensity, RA symptoms, depressive symptoms and anxiety symptoms. Outcome measures will be administered at baseline, post-treatment and at 6 months follow-up. We aim to recruit 300 participants, and an intention-to-treat analysis will be used. Linear mixed models will be used, with baseline levels of treatment outcomes as the covariate, and group and depressive status as fixed factors. The results will demonstrate whether online CBT and MBSR effectively improve outcomes among people with RA. Importantly, this trial will determine whether one intervention is more efficacious, and whether prior history of depression moderates this effect.Ethics and disseminationThe trial has been approved by the Human Research Ethics Committee of the University of Sydney (2021/516). The findings will be subject to publication irrespective of the final results of the study, and based on the outcomes presented in this protocol.Trial registration numberAustralian New Zealand Clinical Trials Registry (ACTRN12621000997853p).
BACKGROUND: Snacking contributes to excessive energy intakes in children. Yet factors shaping child snacking are virtually unstudied. This study examines food parenting practices specific to child ...snacking among low-income caregivers. METHODS: Semi-structured interviews were conducted in English or Spanish with 60 low-income caregivers of preschool-aged children (18 non-Hispanic white, 22 African American/Black, 20 Hispanic; 92 % mothers). A structured interview guide was used to solicit caregivers’ definitions of snacking and strategies they use to decide what, when and how much snack their child eats. Interviews were audio-recorded, transcribed verbatim and analyzed using an iterative theory-based and grounded approach. A conceptual model of food parenting specific to child snacking was developed to summarize the findings and inform future research. RESULTS: Caregivers’ descriptions of food parenting practices specific to child snacking were consistent with previous models of food parenting developed based on expert opinion 1, 2. A few noteworthy differences however emerged. More than half of participants mentioned permissive feeding approaches (e.g., my child is the boss when it comes to snacks). As a result, permissive feeding was included as a higher order feeding dimension in the resulting model. In addition, a number of novel feeding approaches specific to child snacking emerged including child-centered provision of snacks (i.e., responding to a child’s hunger cues when making decisions about snacks), parent unilateral decision making (i.e., making decisions about a child’s snacks without any input from the child), and excessive monitoring of snacks (i.e., monitoring all snacks provided to and consumed by the child). The resulting conceptual model includes four higher order feeding dimensions including autonomy support, coercive control, structure and permissiveness and 20 sub-dimensions. Conclusions: This study formulates a language around food parenting practices specific to child snacking, identifies dominant constructs, and proposes a conceptual framework to guide future research.
There is growing evidence that lung function in early-life predicts later lung function. Adverse events over the lifespan might influence an individual's lung function trajectory, resulting in poor ...respiratory health. The aim of this study is to identify early-life risk factors and their impact on lung function trajectories to prevent long-term lung impairments.
Our study included participants from the Raine Study, a prospective pregnancy cohort, with at least two spirometry measurements. Lung function trajectories from the 6- to 22-year follow-ups were characterised using finite mixture modelling. Multinomial logistic regression analyses were used to evaluate the association between early-life predictors and lung function trajectories.
A total of 1512 participants (768 males, 744 females), representing 53% of the whole cohort, were included in this analysis. Four lung function trajectories of forced expiratory volume in 1 s (FEV
), forced vital capacity (FVC) and FEV
/FVC (z-scores) were identified. FEV
and FVC trajectories were categorised as: "very low", "low", "average" and "above average", respectively. Based on their shape, lung function trajectories of FEV
/FVC were categorised as "very low", "low-average", "average-low" and "average". Asthma and maternal smoking were identified as risk factors for low lung function trajectories in this cohort, as well as early-life exposure to PM
.
Early-life risk factors may influence lung function trajectories over time. Nonetheless, identifying children with a high risk of having low lung function trajectories should be prioritised to prevent deficits in later life.
This mixed methods study sought to understand who makes decisions about whether preschool-aged Mexican American children engage in eating, outdoor play, sleep, and screen time behaviors.
Forty ...Mexican American mothers of children ages 3–4 participated in two interviews, during which both closed- and open-ended questions elicited perceptions of who made decisions for the four behaviors, as well as who was present, mealtime rules, and food choice values. Interviews were transcribed, coded for emergent themes, and compared across participants.
Participants generally perceived themselves to be primary decision makers for all four behaviors; however, food decisions often seemed to be made collaboratively with the child. Fathers were most likely to participate in evening television decisions. Other family members were rarely mentioned. Selecting foods that children liked was a strong food choice value, while cost was rarely mentioned. Participants appeared to have low perceived control over their child's behaviors relative to their perceived roles in decision making.
Mothers may be the primary audience for obesity prevention messages for preschool-aged, Mexican American children; however, health promotion programs may need to increase mothers' awareness of their control over children's behaviors. Understanding how children's behaviors are regulated is an important aspect of obesity prevention for low-income, Mexican American children.
Mitochondrial oxidative phosphorylation (OXPHOS) dysfunction is implicated in a growing spectrum of diseases, from neurodegeneration to cancer. Where tissues or transformed cells are available, ...respirometry and enzymology allow a sophisticated analysis of OXPHOS with modest-cost equipment. The isolation of organelle fractions is also invaluable for determining association of proteins of interest. Here we revisit and consolidate methods to measure whole cell mitochondrial ATP synthesis, respiration, isolation of mitochondria from cultured cells and tissues, and OXPHOS enzymology. We also explain common pitfalls, guide optimisation of the methods for new users, and provide full laboratory protocols in Supplementary materials.
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