Compression-dependent microtubule reinforcement enables cells to navigate confined environments.

Cells migrating through complex three-dimensional environments experience considerable physical challenges, including tensile stress and compression. To move, cells need to resist these forces while also squeezing the large nucleus through confined spaces. This requires highly coordinated cortical contractility. Microtubules can both resist compressive forces and sequester key actomyosin regulators to ensure appropriate activation of contractile forces. Yet, how these two roles are integrated to achieve nuclear transmigration in three dimensions is largely unknown. Here, we demonstrate that compression triggers reinforcement of a dedicated microtubule structure at the rear of the nucleus by the mechanoresponsive recruitment of cytoplasmic linker-associated proteins, which dynamically strengthens and repairs the lattice. These reinforced microtubules form the mechanostat: an adaptive feedback mechanism that allows the cell to both withstand compressive force and spatiotemporally organize contractility signalling pathways. The microtubule mechanostat facilitates nuclear positioning and coordinates force production to enable the cell to pass through constrictions. Disruption of the mechanostat imbalances cortical contractility, stalling migration and ultimately resulting in catastrophic cell rupture. Our findings reveal a role for microtubules as cellular sensors that detect and respond to compressive forces, enabling movement and ensuring survival in mechanically demanding environments.

The activity of early-life gene regulatory elements is hijacked in aging through pervasive AP-1-linked chromatin opening.

A mechanistic connection between aging and development is largely unexplored. Through profiling age-related chromatin and transcriptional changes across 22 murine cell types, analyzed alongside previous mouse and human organismal maturation datasets, we uncovered a transcription factor binding site (TFBS) signature common to both processes. Early-life candidate cis-regulatory elements (cCREs), progressively losing accessibility during maturation and aging, are enriched for cell-type identity TFBSs. Conversely, cCREs gaining accessibility throughout life have a lower abundance of cell identity TFBSs but elevated activator protein 1 (AP-1) levels. We implicate TF redistribution toward these AP-1 TFBS-rich cCREs, in synergy with mild downregulation of cell identity TFs, as driving early-life cCRE accessibility loss and altering developmental and metabolic gene expression. Such remodeling can be triggered by elevating AP-1 or depleting repressive H3K27me3. We propose that AP-1-linked chromatin opening drives organismal maturation by disrupting cell identity TFBS-rich cCREs, thereby reprogramming transcriptome and cell function, a mechanism hijacked in aging through ongoing chromatin opening.

Incidence of Nonsynostotic Plagiocephaly and Developmental Disorders.

Importance: This is the first population-based study quantifying the incidence of nonsynostotic positional plagiocephaly and/or brachycephaly (PPB) in infancy and its association with developmental disorders. Objective: To report the incidence of PPB before age 1 year, the incidence of craniosynostosis, and the percentage of children with PPB diagnosed with a developmental disorder by age 7 years. Design, Setting, and Participants: This was a retrospective, population-based cohort study of children in the Rochester Epidemiology Project (REP) born in Olmsted County, Minnesota, from January 1, 2008, through December 31, 2012, with follow-up through age 7 years. Data were analyzed from March 2021 to April 2024. Exposure: Physical examination detecting cranial deformity. Main Outcomes and Measures: The primary outcome was the incidence of PPB. Secondary outcomes were the incidence of craniosynostosis and the percentage of children with PPB diagnosed with a developmental disorder by age 7 years. Results: Of 9909 infants (5084 [51.3%] male; 9205 [92.9%] born at term and 704 [7.1%] born preterm) included in the study, 575 had PPB, for a PPB incidence of 5.8% (95% CI, 5.3%-6.3%). The incidence of PPB was 5.3% (95% CI, 4.8%-5.8%) in term infants vs 11.8% (95% CI, 9.4%-14.6%) in preterm infants. The incidence of craniosynostosis was 0.16% (95% CI, 0.09%-0.26%). A developmental disorder was known or suspected in 4.2% (95% CI, 2.7%-6.2%) of infants at the time of PPB diagnosis; among 402 infants with PPB and follow-up through age 7 years, 30 (7.5%; 95% CI, 5.0%-10.7%) had a confirmed developmental disorder by 7 years of age. The prevalence of autism spectrum disorder (ASD) in children with a history of PPB who were followed up to age 7 years was 2.2% (9 of 402 children). Conclusions and Relevance: This study found that only a small percentage of the infants had positional head deformity significant enough to be documented and/or referred for subspecialty evaluation, and only a small subset of these children went on to have a developmental disorder in childhood. This information is helpful for counseling families about their child's developmental risk at time of PPB diagnosis.

Perspectives in collective cell migration - moving forward.

Collective cell migration, where cells move as a cohesive unit, is a vital process underlying morphogenesis and cancer metastasis. Thanks to recent advances in imaging and modelling, we are beginning to understand the intricate relationship between a cell and its microenvironment and how this shapes cell polarity, metabolism and modes of migration. The use of biophysical and mathematical models offers a fresh perspective on how cells migrate collectively, either flowing in a fluid-like state or transitioning to more static states. Continuing to unite researchers in biology, physics and mathematics will enable us to decode more complex biological behaviours that underly collective cell migration; only then can we understand how this coordinated movement of cells influences the formation and organisation of tissues and directs the spread of metastatic cancer. In this Perspective, we highlight exciting discoveries, emerging themes and common challenges that have arisen in recent years, and possible ways forward to bridge the gaps in our current understanding of collective cell migration.

A Lifeact-EGFP quail for studying actin dynamics in vivo.

Here, we report the generation of a transgenic Lifeact-EGFP quail line for the investigation of actin organization and dynamics during morphogenesis in vivo. This transgenic avian line allows for the high-resolution visualization of actin structures within the living embryo, from the subcellular filaments that guide cell shape to the supracellular assemblies that coordinate movements across tissues. The unique suitability of avian embryos to live imaging facilitates the investigation of previously intractable processes during embryogenesis. Using high-resolution live imaging approaches, we present the dynamic behaviors and morphologies of cellular protrusions in different tissue contexts. Furthermore, through the integration of live imaging with computational segmentation, we visualize cells undergoing apical constriction and large-scale actin structures such as multicellular rosettes within the neuroepithelium. These findings not only enhance our understanding of tissue morphogenesis but also demonstrate the utility of the Lifeact-EGFP transgenic quail as a new model system for live in vivo investigations of the actin cytoskeleton.

The feeding siblings questionnaire (FSQ): Development of a self-report tool for parents with children aged 2-5 years.

Over the last decade, there have been repeated calls to expand the operationalisation of food parenting practices. The conceptualisation and measurement of these practices has been based primarily on research with parent-child dyads. One unexplored dimension of food parenting pertains to the evaluation of practices specific to feeding siblings. This study describes the development and validation of the Feeding Siblings Questionnaire (FSQ) - a tool designed to measure practices in which siblings are positioned as mediators in parents' attempts to prompt or persuade a child to eat. Item development was guided by a conceptual model derived from mixed-methods research and refined through expert reviews and cognitive interviews. These interviews were conducted in two phases, where parents responded to the questionnaire primarily to test i) the readability and relevance of each item, and ii) its overall feasibility. The instrument was completed by 330 parents (96.1% mothers) in Australia with two children aged 2-5 years, and repeated by 133 parents (40.3%) two weeks later. Exploratory factor analysis was performed on baseline data. Internal consistency and test re-test reliability of the subsequent subscales were examined. Construct validity was assessed through comparisons with existing measures of food parenting practices and child eating behaviours. The final FSQ scale included 22 items, reflecting five food parenting practices: sibling competitiveness, active sibling influence, threatening unequal division of food, sibling role modelling, and vicarious operant conditioning. Internal consistency and test re-test reliability estimates were high, and there was some evidence of convergent construct validity. While its factor structure should be confirmed in a different sample, the FSQ offers a novel tool for assessing, monitoring, and evaluating feeding interactions beyond those confined to the parent-child dyad.

Wnt dose escalation during the exit from pluripotency identifies tranilast as a regulator of cardiac mesoderm.

Wnt signaling is a critical determinant of cell lineage development. This study used Wnt dose-dependent induction programs to gain insights into molecular regulation of stem cell differentiation. We performed single-cell RNA sequencing of hiPSCs responding to a dose escalation protocol with Wnt agonist CHIR-99021 during the exit from pluripotency to identify cell types and genetic activity driven by Wnt stimulation. Results of activated gene sets and cell types were used to build a multiple regression model that predicts the efficiency of cardiomyocyte differentiation. Cross-referencing Wnt-associated gene expression profiles to the Connectivity Map database, we identified the small-molecule drug, tranilast. We found that tranilast synergistically activates Wnt signaling to promote cardiac lineage differentiation, which we validate by in vitro analysis of hiPSC differentiation and in vivo analysis of developing quail embryos. Our study provides an integrated workflow that links experimental datasets, prediction models, and small-molecule databases to identify drug-like compounds that control cell differentiation.

Retraction: Carbon content drives high temperature superconductivity in a carbonaceous sulfur hydride below 100 GPa.

Retraction of 'Carbon content drives high temperature superconductivity in a carbonaceous sulfur hydride below 100 GPa' by G. Alexander Smith et al., Chem. Commun., 2022, 58, 9064-9067, https://doi.org/10.1039/D2CC03170A.

Can smartphone-based response inhibition training elicit sustained changes in appetite, preference, and cravings for energy-dense foods? A free-living randomized controlled trial.

BACKGROUND: Food-specific response inhibition training has been implemented as a strategy to modify food choices and reward-related eating behaviours, but short-term studies have produced equivocal findings. OBJECTIVE: To longitudinally assess the effect of a smartphone-based response inhibition intervention on food reward, hedonic eating drive, and cravings in a free-living setting. METHODS: 84 adults (Mage = 30.49, SDage = 13.01, 52 female) with high responsivity to food cues or overweight/obesity were randomly assigned to a response inhibition training intervention (n = 45) or a control game (n = 39) at home during a training week, followed by a week with no training. Primary analyses compared groups on measures of explicit liking and implicit wanting for food of different energy densities, food cravings, and reward-related eating throughout this two-week period. RESULTS: A reduction was observed in explicit liking and implicit wanting for energy-dense foods from baseline to post-training independent of condition (ps < .001). These changes from baseline were sustained after a 1-week latency period, also independent of condition (ps < .001). These effects coincided with similar observations of hedonic eating drive, tonic cravings, and control over cravings during the observation period (ps < .01). CONCLUSIONS: Although significant reductions in reward-related appetite were observed, free-living response inhibition training did not offer additional benefit over a control activity. Future intervention studies with observable food intake are needed to investigate which appetitive mechanisms most reliably predict eating behaviour over time. TRIAL REGISTRATION: Retrospectively registered with ANZCTR [ACTRN12622001502729].

Food Parenting Practices and Child Eating Behaviors in Australian Families: A Cross-Sectional Sibling Design.

BACKGROUND: Research on feeding in early childhood has focused primarily on parent-child dyadic interactions, despite parents enacting these practices within the complex dynamic of the family system. OBJECTIVE: Using a sibling design, this study aimed to assess how parents may adapt their food parenting practices for siblings in response to differences in their eating behaviors. DESIGN: A cross-sectional online survey was conducted between October and December 2022. PARTICIPANTS/SETTING: Data were collected from parents (97.5% women) in Australia with 2 children aged 2 to 5 years (n = 336 parents and n = 672 children). MAIN OUTCOME MEASURES: Survey items were completed for each sibling, and included four subscales of the Children's Eating Behaviour Questionnaire and seven subscales of the Feeding Practices and Structure Questionnaire-28. STATISTICAL ANALYSES PERFORMED: Multiple linear regression models examined associations between within-sibling pair differences in child eating behaviors and food parenting practices, adjusting for differences in child body mass index z score, age, gender, and early feeding method. RESULTS: Within-sibling pair differences in eating behaviors were associated with differences in some food parenting practices. For the fussier sibling, parents reported using more control-based practices, including persuasive feeding, reward for eating, and reward for behavior, and less of the structure-based practice, family meal settings (P values < 0.001). Similar directions of associations were found for persuasive feeding, reward for eating, and family meal settings with siblings who were slower eaters or more satiety responsive (P values < 0.007); however, no significant differences in reward for behavior were observed in relation to sibling differences in these eating behaviors. For the more food responsive sibling, parents reported using more control-based practices, including reward for behavior and overt restriction (P values < 0.002). CONCLUSIONS: Within families, parents may adapt certain practices in response to differences in their children's eating behaviors. Interventions promoting responsive feeding should be designed to acknowledge the integral role of siblings in shaping parents' feeding decisions.

Response inhibition training as an intervention to modify liking and wanting for foods based on energy density: a proof of concept study.

The ubiquity of energy-dense, processed foods has been implicated as a salient feature of the modern 'obesogenic' environment. Cognitive strategies, such as response inhibition training, have been demonstrated to reduce the hedonic value of such foods in previous studies. However, this effect has generally been inconsistent or heterogenous, depending on the outcome measure, characteristics of the sample, and the specificity of food stimuli. Characterising the extent of generalised effects may help define the application of this type of intervention in natural settings. A repeated-measures, proof-of-concept study, using mobile app-based response inhibition training (RIT) versus a control app-based activity (N = 25), was undertaken to establish the valid application of a food reward measure to assess intervention efficacy. Liking (i.e., affect) and wanting (i.e., motivation) for food stimuli categorised by energy density were taken concurrently pre- and post-training. A statistically significant reduction in explicit liking, but not implicit wanting, for foods irrespective of their energy density was observed during the RIT app-based training session relative to the control (p = .041, ηp2 = .16). However, effect sizes associated with devaluation of energy-dense relative to low calorie food stimuli, although non-significant, were higher when measured as implicitly wanting (p = .098, ηp2 = .11) than explicit liking (p = .756, ηp2 = .00). Trends in explicit stimulus evaluations were empirically discordant from implicit evaluations for low calorie foods in particular. Additional research is needed to investigate whether these trends are reproducible with larger samples, trained and novel food stimuli in outcome measures, and more comprehensive training protocols.

Reduction-cleavable desferrioxamine B pulldown system enriches Ni(ii)-superoxide dismutase from a Streptomyces proteome.

Two resins with the hydroxamic acid siderophore desferrioxamine B (DFOB) immobilised as a free ligand or its Fe(iii) complex were prepared to screen the Streptomyces pilosus proteome for proteins involved in siderophore-mediated Fe(iii) uptake. The resin design included a disulfide bond to enable the release of bound proteins under mild reducing conditions. Proteomics analysis of the bound fractions did not identify proteins associated with siderophore-mediated Fe(iii) uptake, but identified nickel superoxide dismutase (NiSOD), which was enriched on the apo-DFOB-resin but not the Fe(iii)-DFOB-resin or the control resin. While DFOB is unable to sequester Fe(iii) from sites deeply buried in metalloproteins, the coordinatively unsaturated Ni(ii) ion in NiSOD is present in a surface-exposed loop region at the N-terminus, which might enable partial chelation. The results were consistent with the notion that the apo-DFOB-resin formed a ternary complex with NiSOD, which was not possible for either the coordinatively saturated Fe(iii)-DFOB-resin or the non-coordinating control resin systems. In support, ESI-TOF-MS measurements from a solution of a model Ni(ii)-SOD peptide and DFOB showed signals that correlated with a ternary Ni(ii)-SOD peptide-DFOB complex. Although any biological implications of a DFOB-NiSOD complex are unclear, the work shows that the metal coordination properties of siderophores might influence an array of metal-dependent biological processes beyond those established in iron uptake.

Dousing the flame: reviewing the mechanisms of inflammatory programming during stress-induced intrauterine growth restriction and the potential for ω-3 polyunsaturated fatty acid intervention.

Intrauterine growth restriction (IUGR) arises when maternal stressors coincide with peak placental development, leading to placental insufficiency. When the expanding nutrient demands of the growing fetus subsequently exceed the capacity of the stunted placenta, fetal hypoxemia and hypoglycemia result. Poor fetal nutrient status stimulates greater release of inflammatory cytokines and catecholamines, which in turn lead to thrifty growth and metabolic programming that benefits fetal survival but is maladaptive after birth. Specifically, some IUGR fetal tissues develop enriched expression of inflammatory cytokine receptors and other signaling cascade components, which increases inflammatory sensitivity even when circulating inflammatory cytokines are no longer elevated after birth. Recent evidence indicates that greater inflammatory tone contributes to deficits in skeletal muscle growth and metabolism that are characteristic of IUGR offspring. These deficits underlie the metabolic dysfunction that markedly increases risk for metabolic diseases in IUGR-born individuals. The same programming mechanisms yield reduced metabolic efficiency, poor body composition, and inferior carcass quality in IUGR-born livestock. The ω-3 polyunsaturated fatty acids (PUFA) are diet-derived nutraceuticals with anti-inflammatory effects that have been used to improve conditions of chronic systemic inflammation, including intrauterine stress. In this review, we highlight the role of sustained systemic inflammation in the development of IUGR pathologies. We then discuss the potential for ω-3 PUFA supplementation to improve inflammation-mediated growth and metabolic deficits in IUGR offspring, along with potential barriers that must be considered when developing a supplementation strategy.

Development and Evaluation of Linguistic Stimuli for Pain Research.

Linguistic stimuli are commonly used in research to investigate the processing of pain. To provide researchers with a dataset of pain-related and non-pain-related linguistic stimuli, this research investigated 1) the associative strength between pain-related words and the pain construct; 2) the pain-relatedness ratings of pain words; and 3) the variability in the relatedness of pain words within pain word classifications (eg, sensory pain words). In Study 1, 194 pain-related and matched non-pain-related words were retrieved by reviewing the pain-related attentional bias literature. In Study 2, adults with (n = 85) and without (n = 48) self-reported chronic pain completed a speeded word categorization paradigm and rated the pain-relatedness of a subset of pain words. Analyses revealed that 1) despite differences in associative strength of 11.3% of the words between chronic and non-chronic pain groups, no overall group difference was found, 2) the chronic pain group rated the pain words as more pain-related compared to the non-chronic pain group, and 3) there was variability in the relatedness of pain words within pain word classifications. The findings highlight the importance of validating linguistic pain stimuli. The resulting dataset is openly accessible and new published sets can be added to the Linguistic Materials for Pain (LMaP) Repository. PERSPECTIVE: This article presents the development and preliminary evaluation of a large pool of pain-related and non-pain-related words in adults with and without self-reported chronic pain. Findings are discussed and guidelines are offered to select the most suitable stimuli for future research.

Inferring cell diversity in single cell data using consortium-scale epigenetic data as a biological anchor for cell identity.

Methods for cell clustering and gene expression from single-cell RNA sequencing (scRNA-seq) data are essential for biological interpretation of cell processes. Here, we present TRIAGE-Cluster which uses genome-wide epigenetic data from diverse bio-samples to identify genes demarcating cell diversity in scRNA-seq data. By integrating patterns of repressive chromatin deposited across diverse cell types with weighted density estimation, TRIAGE-Cluster determines cell type clusters in a 2D UMAP space. We then present TRIAGE-ParseR, a machine learning method which evaluates gene expression rank lists to define gene groups governing the identity and function of cell types. We demonstrate the utility of this two-step approach using atlases of in vivo and in vitro cell diversification and organogenesis. We also provide a web accessible dashboard for analysis and download of data and software. Collectively, genome-wide epigenetic repression provides a versatile strategy to define cell diversity and study gene regulation of scRNA-seq data.

Does increased core temperature alter cognitive performance during exercise-induced heat strain? A narrative review.

Research to date provides equivocal evidence regarding the influence of heat stress, heat strain, and more specifically, elevated exercise-induced core temperature on cognitive performance. This review sought to identify differences in how specific cognitive tasks were affected by increases in core body temperatures. Included papers (n = 31) measured cognitive performance and core temperature during exercise, while experiencing heightened thermal stress. Cognitive tasks were classified as cognitive inhibition, working memory, or cognitive flexibility tasks. Independently, core temperature changes were not sufficient predictors of cognitive performance. However, reaction time, memory recall, and Stroop tasks appeared to be most effective at identifying cognitive changes during heightened thermal strain. Alterations in performance were more likely to arise under increased thermal loads, which were typically associated with cumulative physiological stressors, such as elevated core temperatures, occurring alongside dehydration, and prolonged exercise durations. Future experimental designs should consider the relevance, or futility of assessing cognitive performance in activities that do not elicit a considerable degree of heat strain, or physiological load.

Trends in menstrual cycle symptoms, physical activity avoidance, and hormonal contraceptive use in a general population of adult women.

INTRODUCTION: Research examining symptoms and side effects of the menstrual cycle on physical activity performance and participation has almost exclusively focussed on elite and athletic populations. The current study aimed to i) identify any differences in symptomatic experiences of the menstrual cycle between hormonal contraceptive users and non-users, ii) gain insight into hormonal contraceptive use, iii) describe perceived symptomatic influences on physical activity engagement, and iv) identify perceived levels of knowledge and understanding around the menstrual cycle. METHODS: An online questionnaire was completed by 881 adult females aged between 18 and 55 years. Questionnaire items related to hormonal contraceptive use, habitual physical activity levels, experiences and symptoms of the menstrual cycle, and sources of information resulting in knowledge and understanding of the menstrual cycle. RESULTS: More than half of all participants (52%) identified themselves as being recreationally active, and the most commonly reported menstrual symptoms were abdominal cramps, lethargy, abdominal bloating, lower back pain, and heavy bleeding. Of all respondents, 48.1% were using some form of hormonal contraception, 66% of which were using a version of a combined oral contraceptive pill. DISCUSSION: Consistent with previous studies, 90% of respondents regularly experienced adverse menstrual symptoms, including abdominal cramps, lethargy, abdominal bloating, lower back pain, and heavy bleeding. Menstrual symptoms were frequently identified as influential factors in the avoidance of, and reduced performance in, physical activity. Almost half of all participants were using some form of hormonal contraception, a noticeably larger proportion than has been previously documented in studies examining non-athletic populations.

The Impact of Free Sugar on Human Health-A Narrative Review.

The importance of nutrition in human health has been understood for over a century. However, debate is ongoing regarding the role of added and free sugars in physiological and neurological health. In this narrative review, we have addressed several key issues around this debate and the major health conditions previously associated with sugar. We aim to determine the current evidence regarding the role of free sugars in human health, specifically obesity, diabetes, cardiovascular diseases, cognition, and mood. We also present some predominant theories on mechanisms of action. The findings suggest a negative effect of excessive added sugar consumption on human health and wellbeing. Specific class and source of carbohydrate appears to greatly influence the impact of these macronutrients on health. Further research into individual effects of carbohydrate forms in diverse populations is needed to understand the complex relationship between sugar and health.