Cross-modal interference-control is reduced in childhood but maintained in aging: a cohort study of stimulus-and response-interference in cross-modal and unimodal Stroop tasks

Interference-control is the ability to exclude distractions and focus on a specific task or stimulus. However, it is currently unclear whether the same interference-control mechanisms underlie the ability to ignore unimodal and cross-modal distractions. In two experiments we assessed whether unimodal and cross-modal interference follow similar trajectories in development and aging and occur at similar processing levels. In Experiment 1, 42 children(6-11 years), 31 younger adults (18-25 years) and 32 older adults (60-84 years) identified colour rectangles with either written (unimodal) or spoken (cross-modal) distractor-words. Stimuli could be congruent, incongruent but mapped to the same response (stimulus-incongruent), or incongruent and mapped to different responses (response-incongruent), thus separating interference occurring at early (sensory) and late (response) processing levels. Unimodal interference was worst in childhood and old age; however, older adults maintained the ability to ignore cross-modal distraction. Unimodal but not cross-modal response interference also reduced accuracy. In Experiment 2 we compared the effect of audition on vision and vice versa in 52 children (6-11 years), 30 young adults (22-33 years) and 30 older adults (60-84 years). As in Experiment 1, older adults maintained the ability to ignore cross-modal distraction arising from either modality and neither type of cross-modal distraction limited accuracy in adults. However cross-modal distraction still reduced accuracy in children and children were more slowed by stimulus-interference compared with adults. We conclude that; unimodal and cross-modal interference follow different lifespan trajectories and differences in stimulus- and response-interference may increase cross-modal distractibility in childhood

Vision dominates audition in adults but not children: a meta-analysis of the Colavita effect

The Colavita effect occurs when participants respond only to the visual element of an audio-visual stimulus. This visual dominance effect is proposed to arise from asymmetric facilitation and inhibition between modalities. It has also been proposed that, unlike adults, children appear predisposed to auditory information. We provide the first quantitative synthesis of studies exploring the Colavita effect, combining data from 70 experiments across 14 studies. A mixed-meta-regression model was applied to assess whether the Colavita effect is influenced by methodological factors and age group tested. Studies reporting response time data were used to test for the presence of asymmetrical facilitation between modalities. Studies with adult participants yielded a medium, approaching large, effect size. Studies exploring the Colavita effect in children yielded no Colavita effect. Across adult and child studies, no methodological factors influenced the effect. Contrary to asymmetrical facilitation, response time data suggested a general slowing under bimodal conditions. These findings suggest that whilst vision dominates in adults, this effect is absent in childhood

The development of visuotactile congruency effects for sequences of events.

Abstract Sensitivity to the temporal coherence of visual and tactile signals increases perceptual reliability and is evident during infancy. However, it is not clear how, or whether, bidirectional visuotactile interactions change across childhood. Furthermore, no study has explored whether viewing a body modulates how children perceive visuotactile sequences of events. Here, children aged 5–7 years (n = 19), 8 and 9 years (n = 21), and 10–12 years (n = 24) and adults (n = 20) discriminated the number of target events (one or two) in a task-relevant modality (touch or vision) and ignored distractors (one or two) in the opposing modality. While participants performed the task, an image of either a hand or an object was presented. Children aged 5–7 years and 8 and 9 years showed larger crossmodal interference from visual distractors when discriminating tactile targets than the converse. Across age groups, this was strongest when two visual distractors were presented with one tactile target, implying a "fission-like" crossmodal effect (perceiving one event as two events). There was no influence of visual context (viewing a hand or non-hand image) on visuotactile interactions for any age group. Our results suggest robust interference from discontinuous visual information on tactile discrimination of sequences of events during early and middle childhood. These findings are discussed with respect to age-related changes in sensory dominance, selective attention, and multisensory processing

Natural growth rates in Antarctic krill (Euphausia superba): II. Predictive models based on food, temperature, body length, sex, and maturity stage

We used the instantaneous growth rate method to determine the effects of food, temperature, krill length, sex, and maturity stage on in situ summer growth of krill across the southwest Atlantic sector of the Southern Ocean. The main aims were to examine the separate effects of each variable and to generate a predictive model of growth based on satellite-derivable environmental data. Both growth increments in length on moulting (GIs) and daily growth rates (DGRs, mm d-1) ranged greatly among the 59 swarms, from 0.58–15% and 0.013–0.32 mm d-1. However, all swarms maintained positive mean growth, even those in the low chlorophyll a (Chl a) zone of the central Scotia Sea. Among a suite of indices of food quantity and quality, large-scale monthly Chl a values from SeaWiFS predicted krill growth the best. Across our study area, the great contrast between bloom and nonbloom regions was a major factor driving variation in growth rates, obscuring more subtle effects of food quality. GIs and DGRs decreased with increasing krill length and decreased above a temperature optimum of 0.5°C. This probably reflects the onset of thermal stress at the northern limit of krill’s range. Thus, growth rates were fastest in the ice edge blooms of the southern Scotia Sea and not at South Georgia as previously suggested. This reflects both the smaller size of the krill and the colder water in the south being optimum for growth. Males tended to have higher GIs than females but longer intermoult periods, leading to similar DGRs between sexes. DGRs of equivalent-size krill tended to decrease with maturity stage, suggesting the progressive allocation of energy toward reproduction rather than somatic growth. Our maximum DGRs are higher than most literature values, equating to a 5.7% increase in mass per day. This value fits within a realistic energy budget, suggesting a maximum carbon ration of ~20% d-1. Over the whole Scotia Sea/South Georgia area, the gross turnover of krill biomass was ~1% d-1

Reduced Neurosteroid Exposure Following Preterm Birth and Its’ Contribution to Neurological Impairment: A Novel Avenue for Preventative Therapies

Children born preterm are at an increased risk of developing cognitive problems and neuro-behavioral disorders such as attention deficit hyperactivity disorder (ADHD) and anxiety. Whilst neonates born at all gestational ages, even at term, can experience poor cognitive outcomes due to birth-complications such as birth asphyxia, it is becoming widely known that children born preterm in particular are at significant risk for learning difficulties with an increased utilization of special education resources, when compared to their healthy term-born peers. Additionally, those born preterm have evidence of altered cerebral myelination with reductions in white matter volumes of the frontal cortex, hippocampus and cerebellum evident on magnetic resonance imaging (MRI). This disruption to myelination may underlie some of the pathophysiology of preterm-associated brain injury. Compared to a fetus of the same post-conceptional age, the preterm newborn loses access to in utero factors that support and promote healthy brain development. Furthermore, the preterm ex utero environment is hostile to the developing brain with a myriad of environmental, biochemical and excitotoxic stressors. Allopregnanolone is a key neuroprotective fetal neurosteroid which has promyelinating effects in the developing brain. Preterm birth leads to an abrupt loss of the protective effects of allopregnanolone, with a dramatic drop in allopregnanolone concentrations in the preterm neonatal brain compared to the fetal brain. This occurs in conjunction with reduced myelination of the hippocampus, subcortical white matter and cerebellum; thus, damage to neurons, astrocytes and especially oligodendrocytes of the developing nervous system can occur in the vulnerable developmental window prior to term as a consequence reduced allopregnanolone. In an effort to prevent preterm-associated brain injury a number of therapies have been considered, but to date, other than antenatal magnesium sulfate and corticosteroid therapy, none have become part of standard clinical care for vulnerable infants. Therefore, there remains an urgent need for improved therapeutic options to prevent brain injury in preterm neonates. The actions of the placentally derived neurosteroid allopregnanolone on GABAA receptor signaling has a major role in late gestation neurodevelopment. The early loss of this intrauterine neurotrophic support following preterm birth may be pivotal to development of neurodevelopmental morbidity. Thus, restoring the in utero neurosteroid environment for preterm neonates may represent a new and clinically feasible treatment option for promoting better trajectories of myelination and brain development, and therefore reducing neurodevelopmental disorders in children born preterm

Regulatory network decoded from epigenomes of surface ectoderm-derived cell types

Developmental history shapes the epigenome and biological function of differentiated cells. Epigenomic patterns have been broadly attributed to the three embryonic germ layers. Here we investigate how developmental origin influences epigenomes. We compare key epigenomes of cell types derived from surface ectoderm (SE), including keratinocytes and breast luminal and myoepithelial cells, against neural crest-derived melanocytes and mesoderm-derived dermal fibroblasts to identify SE differentially methylated regions (SE-DMRs). DNA methylomes of neonatal keratinocytes share many more DMRs with adult breast luminal and myoepithelial cells than with melanocytes and fibroblasts from the same neonatal skin. This suggests that SE origin contributes to DNA methylation patterning, while shared skin tissue environment has limited effect on epidermal keratinocytes. Hypomethylated SE-DMRs are in proximity to genes with SE relevant functions. They are also enriched for enhancer- and promoter-associated histone modifications in SE-derived cells, and for binding motifs of transcription factors important in keratinocyte and mammary gland biology. Thus, epigenomic analysis of cell types with common developmental origin reveals an epigenetic signature that underlies a shared gene regulatory network

Bilateral Remote Ischemic Conditioning in Children:a two-center, double-blind, randomized controlled trial in young children undergoing cardiac surgery

Objective: The study objective was to determine whether adequately delivered bilateral remote ischemic preconditioning is cardioprotective in young children undergoing surgery for 2 common congenital heart defects with or without cyanosis.Methods: We performed a prospective, double-blind, randomized controlled trial at 2 centers in the United Kingdom. Children aged 3 to 36 months undergoing tetralogy of Fallot repair or ventricular septal defect closure were randomized 1:1 to receive bilateral preconditioning or sham intervention. Participants were followed up until hospital discharge or 30 days. The primary outcome was area under the curve for high-sensitivity troponin-T in the first 24 hours after surgery, analyzed by intention-to-treat. Right atrial biopsies were obtained in selected participants.Results: Between October 2016 and December 2020, 120 eligible children were randomized to receive bilateral preconditioning (n = 60) or sham intervention (n = 60). The primary outcome, area under the curve for high-sensitivity troponin-T, was higher in the preconditioning group (mean: 70.0 ± 50.9 μg/L/h, n = 56) than in controls (mean: 55.6 ± 30.1 μg/L/h, n = 58) (mean difference, 13.2 μg/L/h; 95% CI, 0.5-25.8; P = .04). Subgroup analyses did not show a differential treatment effect by oxygen saturations (pinteraction = .25), but there was evidence of a differential effect by underlying defect (pinteraction = .04). Secondary outcomes and myocardial metabolism, quantified in atrial biopsies, were not different between randomized groups.Conclusions: Bilateral remote ischemic preconditioning does not attenuate myocardial injury in children undergoing surgical repair for congenital heart defects, and there was evidence of potential harm in unstented tetralogy of Fallot. The routine use of remote ischemic preconditioning cannot be recommended for myocardial protection during pediatric cardiac surgery

Guinea pig models for translation of the developmental origins of health and disease hypothesis into the clinic

Over 30 years ago Professor David Barker first proposed the theory that events in early life could explain an individual\u27s risk of non-communicable disease in later life: the developmental origins of health and disease (DOHaD) hypothesis. During the 1990s the validity of the DOHaD hypothesis was extensively tested in a number of human populations and the mechanisms underpinning it characterised in a range of experimental animal models. Over the past decade, researchers have sought to use this mechanistic understanding of DOHaD to develop therapeutic interventions during pregnancy and early life to improve adult health. A variety of animal models have been used to develop and evaluate interventions, each with strengths and limitations. It is becoming apparent that effective translational research requires that the animal paradigm selected mirrors the tempo of human fetal growth and development as closely as possible so that the effect of a perinatal insult and/or therapeutic intervention can be fully assessed. The guinea pig is one such animal model that over the past two decades has demonstrated itself to be a very useful platform for these important reproductive studies. This review highlights similarities in the in utero development between humans and guinea pigs, the strengths and limitations of the guinea pig as an experimental model of DOHaD and the guinea pig\u27s potential to enhance clinical therapeutic innovation to improve human health. (Figure presented.)

Ratiometric imaging of minor groove binders in mammalian cells using Raman microscopy

Quantitative drug imaging in live cells is a major challenge in drug discovery and development. Many drug screening techniques are performed in solution, and therefore do not consider the impact of the complex cellular environment in their result. As such, important features of drug-cell interactions may be overlooked. In this study, Raman microscopy is used as a powerful technique for quantitative imaging of Strathclyde-minor groove binders (S-MGBs) in mammalian cells under biocompatible imaging conditions. Raman imaging determined the influence of the tail group of two novel minor groove binders (S-MGB-528 and S-MGB-529) in mammalian cell models. These novel S-MGBs contained alkyne moieties which enabled analysis in the cell-silent region of the Raman spectrum. The intracellular uptake concentration, distribution and mechanism were evaluated as a function of the pKa of the tail group, morpholine and amidine, for S-MGB-528 and S-MGB-529, respectively. Although S-MGB-529 had a higher binding affinity to the minor groove of DNA in solution phase measurements, the Raman imaging data indicated that S-MGB-528 showed a greater degree of intracellular accumulation. Furthermore, using high resolution stimulated Raman scattering (SRS) microscopy the initial localisation of S-MGB-528 was shown to be in the nucleus before accumulation in the lysosome, which was demonstrated using a multimodal imaging approach. This study highlights the potential of Raman spectroscopy for quantitative drug imaging studies and highlights the importance of imaging techniques to investigate drug-cell interactions, to better inform the drug design process