Critical Developmental Period Research Articles

Describing the geographical linkage between the UK Millennium Cohort Study and crime incidents in England and Wales

BackgroundEnhancing longitudinal cohort studies by linking routine external data to them is increasingly used to evaluate how local environments impact participants' outcomes (e.g. crime on adolescents' perception of security and victimisation). ObjectiveTo describe the geographical linkage between the UK Millennium Cohort Study (MCS) and street-level crime incidents reported to the Police in England and Wales, and to estimate crime count and rates around MCS participants' residences. MethodsEight years of monthly street-level police data were linked to the residential postcodes of MCS participants living in England and Wales in surveys 5, 6 and 7 to create individual-level variables of neighbourhood crime counts and rates (28,724 surveys and 11,365 individuals). Radial buffers around participants' residences were created at ages 11, 14 and 17. Crime counts and rates were created prior to the month of interview (at 1, 3, 6, 9, and 12 months prior). A homogenisation of crime categories reported in the police data was conducted to evaluate changes over time and areas. Multivariate models were used to study the association between MCS participants' demographic characteristics and derived measures of neighbourhood crime. ResultsWhile total crime rates and counts around MCS participants remain stable over the period, they hide heterogeneous upward and downward trends in specific sub-categories, with violence and sexual offences showing a larger increase. We observe a negative socioeconomic gradient between household income deciles, recorded at age 11, and subsequent exposure to neighbourhood crime. ConclusionLinking routine crime data to longitudinal studies, such as the MCS, which follow children and their families through a critical period of development, can provide a new resource to understand how local crime impacts child and adolescent outcomes.

Viral-mediated inflammation by Poly I:C induces the chemokine CCL5 in NK cells and its receptors CCR1 and CCR5 in microglia in the neonatal rat cerebellum

Abstract Objectives To study the effect of viral inflammation induced by Polyinosinic:polycytidylic acid (PIC) on the cerebellum during a critical period of development in rats. Methods Neonatal rat pups were treated with PIC on postnatal days (PN) 8 and 10 after which we quantified RNA using Nanostring, qRT-PCR and RNAscope and analyzed immune cells through flow cytometry and immunohistochemistry on PN11. Using the same paradigm, we also analyzed play juvenile behavior, anxiety-like behavior, motor balance using the balance beam and the rotarod assays as well as fine motor behavior using the sunflower seed opening test. Results We determined that male and female pups treated with PIC reacted with a significant increase in CCL5, a chemotactic cytokine that attracts T-cells, eosinophils and basophils to the site of inflammation, at PN11. PIC treatment also increased the expression of two receptors for CCL5, CCR1 and CCR5 in the cerebellar vermis in both males and females at PN11. In-situ hybridization (RNAscope®) for specific transcripts revealed that microglia express both CCL5 receptors under inflammatory and non-inflammatory conditions in both males and females. PIC treatment also increased the total number of CCL5+ cells in the developing cerebellum which were determined to be both natural killer cells and T-cells. There were modest but significant impacts of PIC treatment on large and fine motor skills and juvenile play behavior. Conclusions Our findings suggest an important role for CCL5 and other immune cells in mediating inflammation in the developing cerebellum that potentially impact the maturation of cerebellar neurons during a critical period of development.

Correlation of gestational age and age at death in sudden infant death syndrome: another pointer to the role of critical developmental period?

Filiano and Kinney proposed a triple-risk model for the sudden infant death syndrome (SIDS) that involves the intersection of three risks: (1) a vulnerable infant, (2) a critical developmental period in homeostatic control, and (3) an exogenous stressor(s). The primary evidence for the role of a critical developmental period in SIDS etiology is the peak of cases around the third month of life. Independently, several studies pointed to correlation between gestational age and age at death in SIDS, but used that to assess the SIDS risk for preterm infants, ignoring further ramifications. We did a detailed analysis of CDC data spanning over two decades (1983-2011). We focused not only on the correlation between two age variables (gestational and age at death), but also on the possibility of misdiagnosis. Also, we attempted to account for potential biases in the data induced by the ICD-9/ICD-190 transition or the "Back to Sleep" campaign. The peak of deaths in the third month of life, that was the main argument for the role of the critical development period, wasn't unique to SIDS. However, we confirmed an almost linear and negative correlation between gestational age and the week of death due to SIDS. This pattern (slope of correlation < 0 and significance of correlation p < 0.05) is characteristic of SIDS among all diseases analyzed in the study. We interpret the results as the evidence of the role of the critical development period in SIDS etiology. Possibly more attention in the future research should be put to theories that are based on homeostatic control.

Prolonged use of a soft diet during early growth and development alters feeding behavior and chewing kinematics in a young animal model.

In infants and children with feeding and swallowing issues, modifying solid foods to form a liquid or puree is used to ensure adequate growth and nutrition. However, the behavioral and neurophysiological effects of prolonged use of this intervention during critical periods of postnatal oral skill development have not been systematically examined, although substantial anecdotal evidence suggests that it negatively impacts downstream feeding motor and coordination skills, possibly due to immature sensorimotor development. Using an established animal model for infant and juvenile feeding physiology, we leverage X-ray reconstruction of moving morphology to compare feeding behavior and kinematics between 12-week-old pigs reared on solid chow (control) and an age- and sex-matched cohort raised on the same chow softened to a liquid. When feeding on two novel foods, almond and apple, maintenance on a soft diet decreases gape cycle duration, resulting in a higher chewing frequency. When feeding on almonds, pigs in this group spent less time ingesting foods compared to controls, and chewing cycles were characterized by less jaw rotation about a dorsoventral axis (yaw) necessary for food reduction. There was also a reduced tendency to alternate chewing side with every chew during almond chewing, a behavioral pattern typical of pigs. These more pronounced impacts on behavior and kinematics during feeding on almonds, a tougher and stiffer food than apples, suggest that food properties mediate the behavioral and physiological impacts of early texture modificationand that the ability to adapt to different food properties may be underdeveloped. In contrast, the limited effects of food texture modification on apple chewing indicate that such intervention/treatment does not alter feeding behavior of less challenging foods. Observed differences cannot be attributed to morphology because texture modification over the treatment period had limited impact on craniodental growth. Short-term impacts of soft-texture modification during postweaning development on feeding dynamics should be considered as potential negative outcomes of this treatment strategy.

Overexpression of α-Klotho isoforms promotes distinct Effects on BDNF-Induced Alterations in Dendritic Morphology.

α-Klotho (α-Kl) is a modulator of aging, neuroprotection, and cognition. Transcription of the Klotho gene produces two splice variants-a membrane protein (mKl), which can be cleaved and released into the extracellular milieu, and a truncated secreted form (sKl). Despite mounting evidence supporting a role for α-Kl in brain function, the specific roles of α-Kl isoforms in neuronal development remain elusive. Here, we examined α-Kl protein levels in rat brain and observed region-specific expression in the adult that differs between isoforms. In the developing hippocampus, levels of isoforms decrease after the third postnatal week, marking the end of the critical period for development. We overexpressed α-Kl isoforms in primary cultures of rat cortical neurons and evaluated effects on brain-derived neurotrophic factor (BDNF) signaling. Overexpression of either isoform attenuated BDNF-mediated signaling and reduced intracellular Ca2+ levels, with mKl promoting a greater effect. mKl or sKl overexpression in hippocampal neurons resulted in a partially overlapping reduction in secondary dendrite branching. Moreover, mKl overexpression increased primary dendrite number. BDNF treatment of neurons overexpressing sKl resulted in a dendrite branching phenotype similar to control neurons. In neurons overexpressing mKl, BDNF treatment restored branching of secondary and higher order dendrites close, but not distal, to the soma. Taken together, the data presented support the idea that sKl and mKl play distinct roles in neuronal development, and specifically, in dendrite morphogenesis.

The carryover effects of embryonic incubation temperature on subsequent growth and thermal tolerance in white sturgeon

Environmental variation experienced during early periods of development can lead to persistent phenotypic alteration, known as carryover effects. Such effects increase concern for threatened or endangered species such as the white sturgeon (Acipenser transmontanus), particularly considering expected thermal changes due to climate change. We evaluated how temperature during embryonic development affects physiological parameters such as larval and early juvenile growth and thermal tolerance. Nechako River white sturgeon embryos were incubated at different environmental temperatures (Te) of 12 °C (the natural spawning temperature of this population), 15 °C (the hatchery incubation temperature), and 18 °C (representing potential increases in river temperatures given global climate change). After hatch, fish were reared at a common 15 °C for 80 days post-hatch (dph). Individuals from each temperature treatment were tested for thermal tolerance using the critical thermal maximum method (CTmax), euthanized, and measured. Fish were examined at regular intervals from 13 to 80 dph, which bridged the time from the start of exogenous feeding through the transition into early juveniles. We found carryover effects of high embryonic Te in the short term for both thermal tolerance and growth. Fish that developed at 18 °C had the lowest thermal tolerance during the start of exogenous feeding. However, differences in thermal tolerance were small for early juveniles and were unlikely to be ecologically relevant in the longer term. Fish that developed at 18 °C were smallest over the observation period, indicating a possible cost for survival from increasing environmental temperatures during embryonic development. This research represents a window into a critical period of development during which fish are particularly vulnerable to climatic variation, and shows that cooler temperatures (12 °C) during incubation are optimal for this population. The results can inform environmental managers on the best strategies to help conserve current white sturgeon populations across their range.

Harnessing Children’s Picture Books to Socialize Children About Pain and Injury: A Qualitative Study

Pain experiences are common during childhood (eg, “everyday” pain, vaccine injections) and are powerful opportunities for children to learn about pain and injury. These experiences likely inform fundamental and life-long beliefs about pain. There is scant research investigating the sociocultural contexts in which children learn about pain and injury. One unexplored context is the shared reading of picture books (eg, between parents/caregivers and children). In this study, we investigated whether shared reading of picture books that included depictions of pain and/or injury prompted parent/caregiver-child interactions. If interactions were observed, we explored what those interactions entailed. Twenty parents/caregivers (8 men, 12 women) and their children (n = 27; 10 boys, 17 girls) were recruited from libraries in South Australia. Parent/caregiver-child families chose from 8 books (7 fiction, 1 nonfiction) with varying amounts of pain/injury-related content. Shared reading interactions were video recorded, transcribed, and analyzed alongside analysis of the picture books using reflexive thematic analysis. Pain/injury-related interactions were observed between parents/caregivers and children during shared reading of picture books. Qualitative analyses generated 1 main theme and 3 subthemes. Findings identified that shared reading presented an opportunity for children’s understanding of pain and injury to be socialized through discussion of characters’ experiences. This included teaching children about pain and injury, as well as promoting empathy and emotional attunement toward characters who were depicted as being in pain. Finally, parents/caregivers often responded with observable/expressed amusement if pain/injury was depicted in a light-hearted or unrealistic way. Overall, shared reading of picture books presents an untapped opportunity to socialize children about pain and injury. PerspectiveShared reading of picture books that have depictions of pain and/or injury can prompt parent/caregiver-child interactions about pain and injury. These interactions present critical opportunities that can be harnessed to promote children’s learning of adaptive pain-related concepts and behaviors during a critical developmental period.

How is race perceived during adolescence? A meta-analysis of the own-race bias.

Adolescence is a critical developmental period that is marked by drastic changes in face recognition, which are reflected in patterns of bias (i.e., superior recognition for some individuals compared to others). Here, we evaluate how race is perceived during face recognition and whether adolescents exhibit an own-race bias (ORB). We conducted a Bayesian meta-analysis to estimate the summary effect size of the ORB across 16 unique studies (38 effect sizes) with 1,321 adolescent participants between the ages of ∼10-22 years of age. This meta-analytic approach allowed us to inform the analysis with prior findings from the adult literature and evaluate how well they fit the adolescent literature. We report a positive, small ORB (Hedges's g = 0.24) that was evident under increasing levels of uncertainty in the analysis. The magnitude of the ORB was not systematically impacted by participant age or race, which is inconsistent with predictions from perceptual expertise and social cognitive theories. Critically, our findings are limited in generalizability by the study samples, which largely include White adolescents in White-dominant countries. Future longitudinal studies that include racially diverse samples and measure social context, perceiver motivation, peer reorientation, social network composition, and ethnic-racial identity development are critical for understanding the presence, magnitude, and relative flexibility of the ORB in adolescence. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Neonatal Macular Hemorrhage in a Term Healthy Infant: 18-Year Follow-up.

Unobstructed binocular vision is required during the critical period of vision development to obtain optimal visual acuity in each eye and binocular stereopsis. In this article, we report 18-year follow-up of a full-term, otherwise healthy infant noted to have dense premacular hemorrhage occluding the visual axis in the left eye on retinal imaging performed 48 hours after birth. Serial examinations by the retina service were performed weekly for 10 weeks as the hemorrhage resolved spontaneously. Shortly thereafter, visual acuity revealed fixation was present, but the mother noted intermittent left eye esodeviation. At 90 days of life, the infant was seen by pediatric ophthalmology and started on 1 to 2 hours patching of the right eye daily for the esotropia, which was maintained through 24 months. At 18 years of age, the patient had orthophoria alignment, no spectacle correction, vision of 20/20 in the right eye and 20/25 in the left eye, and normal binocularity and stereopsis. Intermittent esodeviation on the left eye was observed when the patient was fatigued. Early identification of a visual axis occlusion led to prompt referral for the esotropia and initiation of patching therapy. This patient ultimately achieved a very favorable visual functional outcome that may not have been possible without early detection and management. This case report describes the longest-term published follow-up of a neonatal macular hemorrhage. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

Семантико-мировоззренческие аспекты ноосферного взаимодействия в формирующемся многополярном мире в условиях разворота на Восток

The article’s relevance is defined through the necessity, become mature, to rethink the world order functioning on “Western gauges” and to solve a complex of external and internal tasks in mutual connection of blocks of historical and chronological, cultural and educational, and semantic-worldview character. This article touches upon the problem of forming the multi-polar world and defining the Russia’s positions in it in terms of turn to the East. The article’s goal is to substantiate semantic-worldview vision of perspectives of interaction in it. Basic tasks included developing the noosphere approach considered as methodological basis, means semantic-worldview aspects, substantiating on this basis the idea of noosphere interaction and perspectives of its forming. It’s ascertained, that finding by Russia the national identity, allowing to take worthy place in forming multi-polar world, bases on noosphere approach. Necessity to appeal to it is strengthen in critical periods of civilizational development, being the only possible way to solve deep global contradictions. Based on this approach, the Russian authors developed noosphere teaching into paradigm of noosferism (A.I. Subetto), noosphere development (Y.V. Safroshkin), semio-sphere (Y.M. Lotman etc.), “digito-sphere” (O.A. Lavrenova). One else methodological opportunity is semantic-worldview approach (Arabist N.N. Vashkevich), getting especial relevance in the context of Russian-Arabic interaction and of reformatting the world centers of influence. Synthesis of the approaches considered serves as basis for forming the idea of noosphere interaction, which goal is revival of the Russian ethnos and its further development in the interests both of the country and of the forming multi-polar order.

Brain stars take the lead during critical periods of early postnatal brain development: relevance of astrocytes in health and mental disorders.

In the brain, astrocytes regulate shape and functions of the synaptic and vascular compartments through a variety of released factors and membrane-bound proteins. An imbalanced astrocyte activity can therefore have drastic negative impacts on brain development, leading to the onset of severe pathologies. Clinical and pre-clinical studies show alterations in astrocyte cell number, morphology, molecular makeup and astrocyte-dependent processes in different affected brain regions in neurodevelopmental (ND) and neuropsychiatric (NP) disorders. Astrocytes proliferate, differentiate and mature during the critical period of early postnatal brain development, a time window of elevated glia-dependent regulation of a proper balance between synapse formation/elimination, which is pivotal in refining synaptic connectivity. Therefore, any intrinsic and/or extrinsic factors altering these processes during the critical period may result in an aberrant synaptic remodeling and onset of mental disorders. The peculiar bridging position of astrocytes between synaptic and vascular compartments further allows them to "compute" the brain state and consequently secrete factors in the bloodstream, which may serve as diagnostic biomarkers of distinct healthy or disease conditions. Here, we collect recent advancements regarding astrogenesis and astrocyte-mediated regulation of neuronal network remodeling during early postnatal critical periods of brain development, focusing on synapse elimination. We then propose alternative hypotheses for an involvement of aberrancies in these processes in the onset of ND and NP disorders. In light of the well-known differential prevalence of certain brain disorders between males and females, we also discuss putative sex-dependent influences on these neurodevelopmental events. From a translational perspective, understanding age- and sex-dependent astrocyte-specific molecular and functional changes may help to identify biomarkers of distinct cellular (dys)functions in health and disease, favouring the development of diagnostic tools or the selection of tailored treatment options for male/female patients.

Expression and function analysis of Rspo1 in oocyte primary growth of Qi River crucian carp (Carassius auratus)

RSPO1, also referred to R-spondin1, plays a crucial role in female sex determination and differentiation in both mammals and teleosts. Nevertheless, limited documentation exists regarding its contribution to the subsequent ovarian development in teleosts. In this research, Qi River crucian carp (Carassius auratus) was employed as a model organism to investigate the function of Rspo1 during the initial stages of ovarian growth. To clarify the expression patterns, a polyclonal antibody targeting Rspo1 was generated. According to Western blot analysis, Rspo1 was able to identify a band that matched the size of Rspo1 in adult Qi River crucian carp. Furthermore, during the development of the ovary, the expression of Rspo1 peaked at 90 days after hatching (dah), a critical period for the ovary development in Qi River crucian carp, then decreased. Immunohistochemical (IHC) analysis revealed the widespread presence of Rspo1 in oogonia, stage I and II oocytes, as well as certain stage III oocytes, stromal cells, and granulosa cells throughout the ovary. To further confirm the essential roles of Rspo1 in early ovary development, we used dsRNA to suppress its expression for a duration of 30 days starting at 90 dah. Following this, there was a significant reduction in the number of oocytes. Additionally, the expression of genes associated with female development, such as β-catenin, foxl2, cyp19a1a, and figlα, exhibited a noticeable decline. Conversely, the expression of apoptosis-promoting factors caspase3 and p53 increased significantly. The gene ki-67, serving as a marker for cell proliferation, experienced a decrease. These findings suggest that Rspo1 may exert influence on ovarian development through the regulation of germ cell proliferation. The inhibition of Rspo1 expression during the crucial phase of ovarian growth in Qi River crucian carp is anticipated to induce somatic cell apoptosis and perturb the structural integrity of the ovary. Our investigation offers significant elucidation on the molecular mechanisms governing the involvement of Rspo1 in the initial stages of ovarian development in teleosts.

Intrauterine and early-life malnutrition in rats disrupts the circadian rhythm programming of energy metabolites through adulthood.

Maternal malnutrition plays a crucial role in functional development, resulting in behavioral, cognitive, and metabolic abnormalities and disturbances. "Cafeteria diet" has been linked to obesity, metabolic syndrome, diabetes, and other metabolic disruptions in the mammalian lifespan. However, there are very few reports about the effect of intrauterine and early postnatal malnutrition on the circadian rhythm programming of energy metabolites. In mammals, circadian rhythm central control is fundamental for correct interaction with the environment and physiological regulation. Exposure to malnutrition during development imprints metabolic programming throughout life on the central nervous system and peripheral systems. Lifespan studies exploring the effect of high fat/low protein diet administered during critical periods of development are scarce. The present study explored the effect of intrauterine and perinatal malnutrition induced by a high fat/low protein diet (Cafeteria Diet) on circadian and peripheral oscillators controlling glucose, insulin, and triglycerides in rats at 40 and 90 days of age. We evaluated plasma glucose and triglyceride levels in 6 Zeitgeber times, in addition to an intraperitoneal glucose tolerance test (IpTGT) and homeostasis model assessment of insulin resistance (HOMA-IR) at two time-points over 24h. Our results show that offspring of malnourished dams fed cafeteria diet present alterations in circadian rhythmicity of glucose and triglycerides associated with a change in glucose tolerance and insulin sensibility differentially regulated at the development stage and time of day. Intrauterine and early malnutrition due to a cafeteria diet produces maladaptive responses and programs energetic metabolism at several developmental stages during the lifespan.

Social isolation and post-weaning environmental enrichment effects on rat emotional behavior and serotonergic system.

Social isolation (SI) is related to adverse neurobehavioral effects and neurochemical changes when it occurs early in development. On the other hand, environmental enrichment (EE) is associated with a reduction in anxiety-like and depression-like behavior, as well as an increase in serotonin (5-HT) levels in the prefrontal cortex and hippocampus in rodents. This study systematically reviewed the effects of SI and EE on emotional behavior and serotonergic system components in rats after weaning. Primary experimental studies that used subgroups of rats subjected to SI, EE, and normal social conditions after weaning were considered eligible. Studies that used transgenic rodents, ex vivo studies, in vitro studies, human research, or in silico studies were ineligible. Two authors completed searches in Medline/PubMed, LILACS, Scopus, Web of Science, EMBASE, and Open Gray. The Kappa index was calculated to assess agreement between reviewers and assess study quality. The results showed that the animals exposed to EE showed better adaptation to a new environment. Furthermore, EE increased 5-HT levels in the hippocampus and prefrontal cortex of rodents. Thus, it appears that an EE during the critical period of development may reduce anxiety/depression-like behaviors, as well as increase long-term neurotransmitter response.

Adolescent nicotine exposure induces long-term, sex-specific disturbances in mood and anxiety-related behavioral, neuronal and molecular phenotypes in the mesocorticolimbic system.

The majority of lifetime smokers begin using nicotine during adolescence, a critical period of brain development wherein neural circuits critical for mood, affect and cognition are vulnerable to drug-related insults. Specifically, brain regions such as the medial prefrontal cortex (mPFC), the ventral tegmental area (VTA), nucleus accumbens (NAc) and hippocampus, are implicated in both nicotine dependence and pathological phenotypes linked to mood and anxiety disorders. Clinical studies report that females experience higher rates of mood/anxiety disorders and are more resistant to smoking cessation therapies, suggesting potential sex-specific responses to nicotine exposure and later-life neuropsychiatric risk. However, the potential neural and molecular mechanisms underlying such sex differences are not clear. In the present study, we compared the impacts of adolescent nicotine exposure in male vs. female rat cohorts. We performed a combination of behavioral, electrophysiological and targeted protein expression analyses along with matrix assisted laser deionization imaging (MALDI) immediately post-adolescent exposure and later in early adulthood. We report that adolescent nicotine exposure induced long-lasting anxiety/depressive-like behaviors, disrupted neuronal activity patterns in the mPFC-VTA network and molecular alterations in various neural regions linked to affect, anxiety and cognition. Remarkably, these phenotypes were only observed in males and/or were expressed in the opposite direction in females. These findings identify a series of novel, sex-selective biomarkers for adolescent nicotine-induced neuropsychiatric risk, persisting into adulthood.

Ten-year outcomes of congenital cataract surgery performed within the first six months of life.

To investigate the long-term outcomes of congenital cataract surgery performed within the first 6 months of life. 11 ophthalmic surgical sites in Japan. Retrospective chart review. Medical charts were retrospectively reviewed for 216 eyes of 121 patients. The age at surgery was 2.9 ± 1.7 months, with follow-up duration 13.0 ± 2.3 years. The cohort consisted of 83 cases with bilateral aphakia, 12 with bilateral pseudophakia, 20 with unilateral aphakia, and 6 with unilateral pseudophakia. Surgical intervention within the critical period of visual system development (10 weeks for bilateral and 6 weeks for unilateral cases) led to significantly better final visual acuity than surgery conducted after this time frame. The incidence of secondary glaucoma was similar between groups while the occurrence of visual axis opacification was more frequent with earlier surgery. A forward stepwise multiple regression analysis revealed that the final visual acuity was significantly associated with laterality of cataract (better outcomes in bilateral cases), phakic status (with pseudophakia outperforming aphakia), presence of systemic and ocular comorbidities, and development of secondary glaucoma. Secondary glaucoma was significantly more prevalent in aphakic eyes than pseudophakic eyes. In patients with genuine congenital cataract, surgery within the critical period of visual development results in better final visual acuity, albeit with an increased risk of visual axis opacification. The use of IOL with sophisticated surgical techniques shows promise even in congenital cataract surgery.

The Impact of Administration of Fenofibrate During Suckling on Glucose Homeostasis and Programming of Metabolic Function in Adolescent Sprague Dawley Rats

Fenofibrate, a PPAR α agonist used in the treatment of hyperlipidaemia is known to prevent diabetes and its complications. It is cautiously used during pregnancy and in neonates due to its potential for teratogenesis. The suckling period is a critical window for developmental programming. Drugs with antimetabolic syndrome activities have been used during critical developmental periods to program for protection against metabolic syndrome or its components. We evaluated the long-term metabolic effects of fenofibrate when administered during suckling and whether it would prevent the poor metabolic outcomes associated with high fructose intake in adolescent rats. A total of 119, 6-day-old (male and female) Sprague Dawley pups were randomly allocated to four groups and either orally gavaged with 10ml.kg-1 DMSO (0.5%), 100mg.kg-1 fenofibrate, 20% (w/v) fructose or both fructose and fenofibrate till 21 days after birth (PND) 21. Following weaning onto standard commercial rat cubes, the groups were split up further into two based on their drinking fluid: either fructose (20%, w/v) or tap water till PND 63 when they were subjected to an overnight fast before being terminated. Blood was taken for hormone analysis. The kidneys, pancreas, liver and visceral fat pad were weighed. Hepatic tissue was stored at -20ºC until quantification of hepatic fat content. Although the rats gained weight significantly (p&lt;0.0001) throughout the study period, there were no significant differences in terminal body weights across the groups (p&gt;0.05). The interventions did not significantly (p&gt;0.05) alter concentrations of blood glucose, adiponectin and insulin. In both sexes, the HOMA-IR, liver lipids and visceral masses were similar in the different treatment groups. Fenofibrate administered to suckling rats did not adversely impact health of the study rats. It may therefore be safe for use in neonates.

Self-Regulation and Academic Learning in Preschoolers with Autism Spectrum Disorder: Links to School Engagement and Levels of Autism Characteristics.

Children with autism spectrum disorder often demonstrate self-regulation challenges and academic difficulties. Although self-regulation has been well documented as an important factor for academic achievement in neurotypical children, little is known about how it is related to academic learning in autistic children, especially during preschool, a critical developmental period for both emergent academic skills and self-regulatory abilities. It is also unclear whether school engagement or autism characteristics influence the relation between self-regulation and academic learning in autistic children during preschool. Thirty-two autistic preschoolers participated in this study. Direct measures and parent reports were used to measure three dimensions of self-regulation, including executive function, effortful control, and emotion regulation. Classroom-based data from multiple academic programs were used to reflect their average rates of achieving new literacy and mathematics learning goals. Teachers reported the participants' levels of school engagement, and their autism characteristics were measured directly. Emotion regulation was significantly linked to the rate of meeting literacy learning goals in autistic preschoolers, whereas multiple executive function skills, including inhibitory and attentional control and working memory, were associated with their mathematics learning rate. Emotion regulation demonstrated a stronger association with literacy learning when autistic children were more engaged in classroom activities. Levels of autism characteristics did not mediate or moderate the association between self-regulation and academic learning. Future interventions and teaching should consider fostering self-regulation and facilitating school engagement for autistic preschoolers besides targeting their learning performance on specific academic content to promote their current and future academic success.

The role of temperature on the development of circadian rhythms in honey bee workers.

Circadian rhythms in honey bees are involved in various processes that impact colony survival. For example, young nurses take care of the brood constantly throughout the day and lack circadian rhythms. At the same time, foragers use the circadian clock to remember and predict food availability in subsequent days. Previous studies exploring the ontogeny of circadian rhythms of workers showed that the onset of rhythms is faster in the colony environment (~2 days) than if workers were immediately isolated after eclosion (7-9 days). However, which specific environmental factors influenced the early development of worker circadian rhythms remained unknown. We hypothesized that brood nest temperature plays a key role in the development of circadian rhythmicity in young workers. Our results show that young workers kept at brood nest-like temperatures (33-35 °C) in the laboratory develop circadian rhythms faster and in greater proportion than bees kept at lower temperatures (24-26 °C). In addition, we examined if the effect of colony temperature during the first 48 h after emergence is sufficient to increase the rate and proportion of development of circadian rhythmicity. We observed that twice as many individuals exposed to 35 °C during the first 48 h developed circadian rhythms compared to individuals kept at 25 °C, suggesting a critical developmental period where brood nest temperatures are important for the development of the circadian system. Together, our findings show that temperature, which is socially regulated inside the hive, is a key factor that influences the ontogeny of circadian rhythmicity of workers.

Critical developmental periods of vulnerability in dystonia

Dystonia is a heterogenous movement disorder characterised by involuntary muscle contractions, leading to abnormal postures and movements. Despite being the third most common movement disorder, the pathophysiological mechanisms causing dystonia are incompletely understood. Isolated dystonia is often caused by pathogenic mutations in single genes. An emerging body of evidence suggests that at least some forms of isolated dystonia have a strong developmental component, with pathogenic effects acting within discrete periods of increased vulnerability during neurodevelopment. The extent to which this is a common feature of genetically distinct forms of dystonia, and which developmental mechanisms might be disrupted during these periods, remains unclear. During critical periods of development, neuronal activity is instructive in the maturation of neuronal circuits, and inappropriate levels of activity during this period can lead to permanent defects. This review, with an intentional focus on our work, outlines evidence implicating disruptions to neuronal activity during critical developmental periods as a potential mechanism underlying inherited motor disorders in general, and dystonia in particular.