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Aging leads to biochemical and biomechanical changes in skin, with biological and functional consequences. Despite extensive literature on skin aging, there is a lack of studies which investigate the maturation of the tissue and connect the microscopic changes in the skin to its macroscopic biomechanical behavior as it evolves over time. The present work addresses this knowledge gap using multiscale characterization of skin in a murine model considering newborn, adult and aged mice. Monotonic uniaxial loading, tension relaxation with change of bath, and loading to failure tests were performed on murine skin samples from different age groups, complemented by inflation experiments and atomic force microscopy indentation measurements. In parallel, skin samples were characterized using histological and biochemical techniques to assess tissue morphology, collagen organization, as well as collagen content and cross-linking. We show that 1-week-old skin differs across nearly all measured parameters from adult skin, showing reduced strain stiffening and tensile strength, a thinner dermis, lower collagen content and altered crosslinking patterns. Surprisingly, adult and aged skin were similar across most biomechanical parameters in the physiologic loading range, while aged skin had lower tensile strength and lower stiffening behavior at large force values. This correlates with altered collagen content and cross-links. Based on a computational model, differences in mechanocoupled stimuli in the skin of the different age groups were calculated, pointing to a potential biological significance of the age-induced biomechanical changes in regulating the local biophysical environment of dermal cells. Skin microstructure and the emerging mechanical properties change with age, leading to biological, functional and health-related consequences. Despite extensive literature on skin aging, only very limited quantitative data are available on microstructural changes and the corresponding macroscopic biomechanical behavior as they evolve over time. This work provides a wide-range multiscale mechanical characterization of skin of newborn, adult and aged mice, and quantifies microstructural correlations in tissue morphology, collagen content, organization and cross-linking. Remarkably, aged skin retained normal hydration and normal biomechanical function in the physiological loading range but showed significantly reduced properties at super-physiological loading. Our data show that age-related microstructural differences have a profound effect not only on tissue-level properties but also on the cell-level biophysical environment. [Display omitted] [ABSTRACT FROM AUTHOR]

Brain mosaicism has diverse origins, from early embryogenesis to neurogenesis and in the mature brain. Prezygotic chromosomal abnormalities can be postzygotically corrected, thus leading to tissue-restricted mosaicism. Complex clonal dynamics during embryogenesis determines lineage allocation. Postmitotic neurons continue to accumulate somatic genetic variation. The complexity of the brain is closely tied to its nature as a genetic mosaic, wherein each cell is distinguished by a unique constellation of somatic variants that contribute to functional and phenotypic diversity. Postzygotic variation arising during neurogenesis is recognized as a key contributor to brain mosaicism; however, recent advances have broadened our understanding to include sources of neural genomic diversity that develop throughout the entire lifespan, from embryogenesis through aging. Moving beyond the traditional confines of neurodevelopment, in this review, we delve into the complex mechanisms that enable various origins of brain mosaicism. [ABSTRACT FROM AUTHOR]

Local gene therapies, including in vivo genome editing, are highly anticipated for the treatment of genetic diseases in skin, especially the epidermis. While the adeno-associated virus (AAV) is a potent vector for in vivo gene delivery, the lack of efficient gene delivery methods has limited its clinical applications. To optimize the AAV gene delivery system with higher gene delivery efficiency and specificity for epidermis and keratinocytes (KCs), using AAV capsid and promoter engineering technologies. AAV variants with mutations in residues reported to be critical to determine the tropism of AAV2 for KCs were generated by site-directed mutagenesis of AAVDJ. The infection efficiency and specificity for KCs of these variants were compared with those of previously reported AAVs considered to be suitable for gene delivery to KCs in vitro and in vivo. Additionally, we generated an epidermis-specific promoter using the most recent short-core promoter and compared its specificity with existing promoters. A novel AAVDJ variant capsid termed AAVDJK2 was superior to the existing AAVs in terms of gene transduction efficiency and specificity for epidermis and KCs in vitro and in vivo. A novel tissue-specific promoter, termed the K14 SCP3 promoter, was superior to the existing promoters in terms of gene transduction efficiency and specificity for KCs. The combination of the AAVDJK2 capsid and K14 SCP3 promoter improves gene delivery to epidermis in vivo and KCs in vitro. The novel AAV system may benefit experimental research and development of new epidermis-targeted gene therapies. • A novel AAV capsid termed AAVDJK2 was developed and was superior to existing AAVs in terms of gene transduction efficiency and specificity for keratinocytes in vitro and in vivo. • A novel tissue-specific promotor termed K14 SCP3 promotor was developed and was superior to existing promoters in terms of gene transduction efficiency and specificity for keratinocytes in vitro and in vivo. • The novel AAV system benefits experimental research and development of new epidermis-targeted gene therapies. [ABSTRACT FROM AUTHOR]

The characteristics of subvisible particles (SbVPs) are critical quality attributes of injectable and ophthalmic solutions in pharmaceutical manufacturing. However, current compendial SbVP testing methods, namely the light obstruction method and the microscopic particle count method, are destructive and wasteful of target samples. In this study, we present the development of a non-destructive SbVP analyzer aiming to analyze SbVPs directly in drug product (DP) containers while keeping the samples intact. Custom sample housings are developed and incorporated into the analyzer to reduce optical aberrations introduced by the curvature of typical pharmaceutical DP sample containers. The analyzer integrates a light-sheet microscope structure and models the side scattering event from a particle with Mie scattering theory with refractive indices as prior information. Equivalent spherical particle size under assigned refractive index values is estimated, and the particle concentration is determined based on the number of scattering events and the volume sampled by the light sheet. The resulting analyzer's capability and performance to non-destructively analyze SbVPs in DP containers were evaluated using a series of polystyrene bead suspensions in ISO 2R and 6R vials. Our results and analysis show the particle analyzer is capable of directly detecting SbVPs from intact DP containers, sorting SbVPs into commonly used size bins (e.g. ≥ 2 µm, ≥ 5 µm, ≥ 10 µm, and ≥ 25 µm), and reliably quantifying SbVPs in the concentration range of 4.6e2 to 5.0e5 particle/mL with a margin of ± 15 % error based on a 90 % confidence interval. [ABSTRACT FROM AUTHOR]

Exposure to alcohol during fetal development can lead to structural and functional abnormalities in the cerebellum, a brain region responsible for motor coordination, balance, and specific cognitive functions. In this systematic review, we comprehensively analyze a vast body of research conducted on vertebrate animals and humans over the past 13 years. We identified studies through PubMed and screened them following PRISMA guidelines. Data extraction and quality analysis were conducted using Covidence systematic review software. A total of 108 studies met our inclusion criteria, with the majority (79 studies) involving vertebrate animal models and 29 studies focusing on human subjects. Animal models included zebrafish, mice, rats, sheep, and non-human primates, investigating the impact of ethanol on cerebellar structure, gene/protein expression, physiology, and cerebellar-dependent behaviors. Additionally, some animal studies explored potential therapeutic interventions against ethanol-induced cerebellar damage. The human studies predominantly adopted cohort designs, exploring the effects of prenatal alcohol exposure on cerebellar structure and function. Certain human studies delved into innovative cerebellar-based diagnostic approaches for fetal alcohol spectrum disorder (FASD). The collective findings from these studies clearly indicate that the cerebellum is involved in various neurophysiological deficits associated with FASD, emphasizing the importance of evaluating both cerebellar structure and function in the diagnostic process for this condition. Moreover, this review sheds light into potential therapeutic strategies that can mitigate prenatal alcohol exposure-induced cerebellar damage. • The cerebellum is an important target of prenatal ethanol exposure. • We systematically analyzed animal and human research in this area. • PRISM guidelines for systematic review were followed. • A total of 79 animal studies and 29 human studies met inclusion criteria. • Cerebellar dysfunction contributes to many prenatal ethanol-induced neurophysiological deficits. [ABSTRACT FROM AUTHOR]

In this study, we investigate the impact of selected macroeconomic factors on agricultural financing practices in Djibouti. Therefore, the objective of this study is to understand how these factors influence the accessibility, distribution, and effectiveness of financial resources within the agricultural sector. To achieve this objective, we employed Autoregressive Distributed Lag (ARDL) and Wavelet Coherence Analysis on an annual dataset covering a span of 25 years, ranging from 1998 to 2022. The findings reveal that factors such as inflation, diminishing rural population, economic growth, and the institutional framework of the country exert negative pressures on the availability of funding for agriculture. However, amidst these challenges, we find that official development assistance serves as a positive mitigating factor, offering crucial support to the agricultural sector. These findings hold significant implications for policymakers in Djibouti by providing valuable insights into how to develop targeted interventions to support farmers, increase access to credit, and improve agricultural productivity, as it lays the foundation for investments in food security, technology adoption, and climate-resilient practices. [ABSTRACT FROM AUTHOR]

The 24-hour movement behavior (24-HMB) guidelines recommend that children and adolescents (youth) should limit screen time (ST), get an adequate amount of sleep (SL), and engage in sufficient physical activity (PA) to ensure health and healthy development. Meeting 24-HMB guidelines is associated with positive mental health outcomes (e.g., social and emotional function) in the general population. However, it is unclear whether such findings extend to youth with Autism Spectrum Disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD). Thus, we examined associations of meeting 24-HMB guidelines with social and emotional function in youth with comorbid ASD/ADHD. Data from the 2020–2021 National Survey of Children's Health - a U.S. national, population-based, cross-sectional study – were used. We extracted and analyzed data on youth (aged between 6 and 17 years) diagnosed with comorbidity of ASD/ADHD. Data on movement behaviors (PA, ST, and SL) and specific outcome variables (social function and emotional function) were collected through caregiver-proxy reports. Logistic regressions were performed to examine the associations between meeting 24-HMB guidelines and social and emotional outcomes adjusting for covariates (e.g., age, sex, ethnicity, weight status, birth status, socio-economic status, and receiving medication/behavioral treatment). Among 979 children and adolescents with comorbid ASD/ADHD, only 3.8 % met all three 24-HMB guidelines. In total, 45.0 % of participants met at least one guideline, and 25.5 % of those met at least two guidelines. Compared to those who did not meet any 24-HMB guidelines, meeting SL + ST guidelines was significantly associated with lower odds of poorer social function (being bullied: OR = 0.3, 95%CI [0.1–0.7]; arguing: OR = 0.2, 95%CI[0.1–0.4]). Furthermore, meeting PA + ST + SL guidelines was associated with lower odds of poorer emotional function (depression: OR = 0.5, 95%CI[0.3–0.7]). Meeting 24-HMB guidelines was associated with better social and emotional function in U.S. youth with comorbid ASD/ADHD; however, currently very few with comorbid ASD/ADHD meet all 24-HMB guidelines. These results emphasize the importance of promoting adherence to the 24-HMB guidelines among youth facing the challenges of comorbid ASD/ADHD. These cross-sectional findings point to the need for further empirical evidence from longitudinal studies to support our conclusions. • Youth with ASD/ADHD failed to meet the 24-hour movement behavior guidelines. • Approaches aimed at improving mental well-being could include improving sleep and reducing screen time. • Meeting the physical activity guideline appears to be the most difficult for youth with ASD/ADHD. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. The aim of this systematic review was to summarize the literature assessing the effects of weaning practices on performance, behavior, and health of dairy calves. Only published, peer-reviewed articles written in English and specifically assessing the effects of weaning treatments on dairy calves were eligible for inclusion. Studies had to include 2 or more treatment groups that addressed at least one of 4 interventions: weaning age (i.e., when milk was fully removed), weaning duration (i.e., number of days from start of milk reduction to when milk was fully removed), weaning criteria (e.g., age vs. intake), or alternative weaning methods (e.g., water dilution). Outcome measures could include starter intake, growth (BW or ADG), behaviors (5 specific sucking behaviors; play behavior; lying behavior; vocalizations; unrewarded visits to an automated milk feeder), and health (mortality rate, diarrhea, and respiratory illness). We conducted 3 targeted searches using Web of Science and PubMed. The articles underwent a 2-step screening process, resulting in a final sample of 44 studies. The majority of studies investigated weaning age (n = 22), followed by weaning duration (n = 13), weaning criteria (n = 9), and other weaning methods such as dilution, linear versus step-down milk reduction, or meal-based approaches (n = 6). There was consensus for positive effects (or at least no negative effects) on overall growth of calves weaned at later ages, over longer durations, based on starter intake, or weaned using step-down or meal-based milk removal approaches. This is despite reduced starter intake in calves weaned at later ages; most studies found improved starter intake in calves weaned over longer durations. Weaning based on starter intake had superior growth and feed intakes compared with calves weaned at a fixed earlier age. Few studies assessed interactive effects of weaning method and milk allowance. However, weaning after 8 wk appears to support superior weight gain, provided preweaning milk allowances are adequate (above 6 L/d). Weaning can lead to hunger-related behaviors and reduced welfare, yet only half of the studies assessed the effects of weaning method on calf behavior. Weaning at later ages can reduce signs of hunger (based on unrewarded visits to the milk feeder), but it is unclear if weaning over longer durations or weaning by starter intake reduces or prolongs hunger. There was little consensus among the few studies that measured oral behaviors of calves. Positive welfare indicators, such as play behavior, were rarely measured, yet are crucial to understanding the emotional states of calves during this potentially stressful diet transition. Health was rarely the primary objective of the study, with low sample sizes to conduct statistical comparisons. Overall, there remains significant knowledge gaps in our understanding of how best to wean calves. A successful weaning program must minimize signs of hunger while promoting high growth and feed intakes, so we encourage future work to include behavioral indicators of hunger and positive welfare to evaluate how weaning methods are experienced by the calf. [ABSTRACT FROM AUTHOR]

Human infants are helpless for a protracted period after birth. This has been attributed to maternal constraints causing an early birth while the brain is still immature. However, anatomical studies have shown that relative to other species, human newborn brains are not particularly immature. Consistent with this, neuroimaging studies have shown that the structure and function of many cognitive systems is surprisingly mature in humans at birth. Why else might humans have a protracted helpless period? In machine learning, learning good representations of the environment through self-supervised learning in large deep neural networks yields enormously powerful 'foundation models', which allow better generalisation to new problems and have a higher final performance. We propose that in the helpless period, human infants are learning a foundation model that underpins their later cognition. Humans have a protracted postnatal helplessness period, typically attributed to human-specific maternal constraints causing an early birth when the brain is highly immature. By aligning neurodevelopmental events across species, however, it has been found that humans are not born with especially immature brains compared with animal species with a shorter helpless period. Consistent with this, the rapidly growing field of infant neuroimaging has found that brain connectivity and functional activation at birth share many similarities with the mature brain. Inspired by machine learning, where deep neural networks also benefit from a 'helpless period' of pre-training, we propose that human infants are learning a foundation model: a set of fundamental representations that underpin later cognition with high performance and rapid generalisation. [ABSTRACT FROM AUTHOR]

• prenatal LPS and early-life LL affect the expression profiles of genes at P30. • impact of combined interventions is smaller than that of individual interventions. • combined interventions increase the amplitude of expression rhythms in some genes. Exposure to lipopolysaccharide (LPS) during prenatal development leads to various changes in neurobiological and behavioural patterns. Similarly, continuous exposure to constant light (LL) during the critical developmental period of the circadian system affects gene expression in various tissues in adulthood. Given the reciprocal nature of the interaction between the circadian and the immune systems, our study primarily investigated the individual effects of both interventions and, more importantly, their combined effect. We aimed to explore whether there might be a potential synergistic effect on circadian rhythms and their parameters, focussing on the expression of clock genes, immune-related genes, and specific genes in the hippocampus, pineal gland, spleen and adrenal gland of rats at postnatal day 30. Our results show a significant influence of prenatal LPS and postnatal LL on the expression profiles of all genes assessed. However, the combination of prenatal LPS and postnatal LL only revealed an enhanced negative effect in a minority of the comparisons. In most cases, it appeared to attenuate the changes induced by the individual interventions, restoring the measured parameters to values closer to those of the control group. In particular, genes such as Nr1d1 , Aanat and Tph1 showed increased amplitude in the pineal gland and spleen, while the kynurenine enzymes Kynu and KatII developed circadian rhythmicity in the adrenal glands only after the combined interventions. Our data suggest that a mild immunological challenge during prenatal development may play a critical role in triggering an adaptive response of the circadian clock later in life. [ABSTRACT FROM AUTHOR]

Suicidal thoughts and behaviors often emerge in a predictable sequence, with suicidal ideation (SI) preceding planning, and planning preceding actions. Few studies, however, have considered the timing and duration of non-suicidal self-injury (NSSI) in these transitions. Accordingly, this study examined: 1) the developmental sequencing of NSSI, SI and suicide attempts, and 2) whether age of onset or duration predict transitions from NSSI to other SITB, and from SI to NSSI. 704 first-year students from a mid-sized Canadian university (Sample 1) and 2095 adults from an online research volunteer panel (Sample 2) completed the Self-Injurious Thoughts and Behaviors Interview self-report, which assessed the presence, age of onset, and recency of SITB. NSSI and SI typically onset before age 15, while suicide planning and attempt usually began at or after age 15. Transition from NSSI to SI was likeliest in the first year after NSSI onset. Transition from NSSI to suicide attempt was likeliest in the second and third year after NSSI onset in Sample 1, and up to four years after NSSI onset in Sample 2. Early (before age 13) and late (after age 16) onsets of NSSI predicted higher odds of transitioning from NSSI to SI or attempt. Transition from SI to NSSI was likeliest in the first two years after SI onset and when SI began before age 13. The first year after NSSI or SI onset are critical for transitions to other SITB. Targeted prevention and monitoring should be considered for people who recently initiated NSSI. • NSSI and suicidal ideation (SI) typically begin within 1–2 years of each other • Transition from NSSI to SI was likeliest in the first year after NSSI onset • Transition risk from NSSI to attempt persisted for 3+ years after NSSI onset • NSSI onset before age 13 or after 16 predicted transitioning to SI or attempt • Onset of SI before age 13 predicted transition to NSSI [ABSTRACT FROM AUTHOR]

Hyaluronan (HA) is a glycosaminoglycan that forms a gel-like barrier in the subcutaneous (SC) space, limiting bulk fluid flow and the dispersion of SC-administered therapeutics. Recombinant human hyaluronidase PH20 (rHuPH20) facilitates the rapid delivery of co-administered therapeutics by depolymerizing HA in the SC space. Administration of rHuPH20 can induce the formation of anti-rHuPH20 antibodies, or anti-drug antibodies (ADAs), with the potential to bind endogenous PH20 hyaluronidase in the adult testes and epididymis. Using a variety of relevant animal models and multiple dose regimens of rHuPH20 across the full spectrum of animal development, we demonstrated that rHuPH20 administration resulted in the formation of ADAs. Although these ADAs can bind both the recombinant rHuPH20 enzyme and recombinant versions of animal model-specific hyaluronidases, they had no impact on fertility parameters (as measured by sperm concentration and motility, litter size, and litter viability) or fetal development. We present the result of our nonclinical studies in order of the developmental lifecycle, beginning with adults. Toxicology studies that extend beyond the standard package are also presented. These studies demonstrate the favorable safety profile of rHuPH20 and ADAs in nonclinical models. Additionally, we identified substantial safety margins for clinically relevant doses of rHuPH20. [Display omitted] • rHuPH20 facilitates subcutaneous administration of therapeutics. • Impact of rHuPH20 and anti-drug antibodies observed in multiple nonclinical models. • rHuPH20 anti-drug antibodies did not negatively alter fertility or development. • Substantial safety margins were identified when compared to human-equivalent doses. • Studies support favorable safety profile of rHuPH20. [ABSTRACT FROM AUTHOR]

The historical challenges to bridge the gaps between developmental biology and population or statistical genetics under the explanatory dominance of the Modern Evolutionary Synthesis during the 20th century have been thoroughly documented. However, although several attempts to integrate these fields have been made, most have been deemed unsuccessful. As an example of those efforts, in this paper I discuss the work of James Meadows Rendel, a student of J. B. S. Haldane and disciple of Conrad Hal Waddington. I present his largely forgotten or unrecognized, but innovative, ideas about canalization and the role of development in phylogeny as a valuable piece to connect these fields that could still have important ramifications for today's evolutionary biology. In fact, it is expected that the legacy of J. M. Rendel will be rediscovered, and more importantly, incorporated and extended by future researchers, in light of the growth of evolutionary developmental biology in the last decades. What is more, this case offers a chance to critically revisit standard historiographies about the dichotomy between developmental and population genetics research frameworks in 20th century biology. • Rendel's theory integrated various developmental and evolutionary processes. • Rendel's theoretical work is generally omitted or unrecognized in the literature. • J. M. Rendel can be seen as a forerunner for contemporary Evo-Devo approaches. [ABSTRACT FROM AUTHOR]

Au cours de la dernière année, plusieurs articles sont parus dans la presse grand public ou dans des revues scientifiques sur les bienfaits/méfaits de la mise à l'écart temporaire de l'enfant, appelé « time-out » (TO). L'objectif de cet article est de faire une revue de la littérature scientifique, en exposant les conclusions des méta-analyses réalisées sur les programmes éducatifs parentaux incluant le TO, et sur la procédure du TO elle-même. Dans un second temps, seront décrites les caractéristiques du TO pour appréhender comment les parents/les éducateurs le pratiquent et pour en apprécier son efficacité. Les résultats montrent que le TO n'est pas une stratégie éducative isolée mais qu'il s'inscrit dans un processus plus complet avec un avant (pose du cadre éducatif, des règles à suivre), et un après (debrief, explications sur les comportements inadaptés), appelés temps-in. Il est ainsi difficile d'appréhender l'efficacité du TO sans prendre en compte une temporalité plus large que le seul moment où l'enfant s'y trouve. De plus, l'âge de l'enfant, la durée du TO, les troubles du comportements éventuels de l'enfant comme du parent, sont autant de facteurs mis en évidence qui témoignent de la pluralité des TO. Les recherches scientifiques doivent donc être poursuivies afin d'évaluer son efficacité en prenant en compte les caractéristiques épidémiologiques de chaque acteur. Il s'agira de regarder plus précisément quel TO pour quel enfant et par quel parent. Over the past year, several controversial articles have been written in the press and scientific journals about the benefits and harms of time-out (TO). The aim of this article is to review the scientific literature outlining the conclusions of meta-analyses carried out on parenting programs including TO, and on the TO procedure itself. Then, we describe the characteristics of the TO to understand how parents/educators use it and to assess its efficiency. The results show that the TO is not an isolated educational strategy but is included in a more comprehensive process with a before (establishment of the educational framework, rules to be followed) and an after (debriefing, explanations of inappropriate behavior) called time-in. Thus, it is difficult to assess the effectiveness of a TO without considering a wider temporality, including time-in. Moreover, the age of the child, the TO's duration and any behavioral or mental problems in the dyad child/parent are important factors that highlight the plurality of the TO. Further scientific research is necessary to assess its effectiveness considering the epidemiological characteristics of each protagonist. We need to look more closely at which TO is the best for which child and by which parent. [ABSTRACT FROM AUTHOR]

Au regard de l'accroissement des attaques terroristes au niveau mondial ces dernières années et du caractère particulièrement dévastateur de celles-ci, les travaux de recherche succédant à ces événements, notamment les attentats du World Trade Center le 11 septembre 2001, se sont intensifiés en portant une plus grande attention à la santé mentale des survivants. Afin d'évaluer les conséquences des actes terroristes sur les enfants et les adolescents, la présente revue systématique a utilisé les bases de données PubMed, Scopus, PsychINFO et ProQuest sans limites de dates de publication. Seules les études évaluant les symptômes de stress post-traumatique ainsi que les conséquences psychologiques, sociales et développementales chez les enfants et adolescents dans les mois et années suivants l'exposition directe ou indirecte à des actes terroristes ont été incluses. Les données ont été extraites d'après un éventail de champs prédéfinis et la fiabilité des études a été vérifiée par un outil d'évaluation de la qualité des études. Dix-huit articles ont été inclus : treize études quantitatives descriptives, quatre études qualitatives et une ayant utilisé un mixte des méthodes quantitatives et qualitatives. Les articles mettent en évidence les diverses difficultés que sont amenés à rencontrer les enfants et adolescents ayant été exposé au terrorisme au cours de leur développement (tel qu'un trouble de stress post-traumatique, des troubles neurocognitifs, sensori-moteurs, émotionnels...), parfois concomitantes à la perte d'un être cher tué durant l'événement, et le traumatisme de leur parent ayant également des répercussions sur eux, effets d'autant plus importants moins ils sont âgés. Considering the increase in terrorist attacks worldwide in recent years and their particularly devastating nature, research following these events, including the World Trade Center attacks of September 11th, 2001, has intensified with greater attention to the mental health of survivors. To assess the impact of terrorist acts on children and adolescents, this systematic review used PubMed, Scopus, PsychINFO, and ProQuest databases without publication date limitations. Only studies assessing posttraumatic stress symptoms and psychological, social, and developmental consequences in children and adolescents in the months and years following direct or indirect exposure to terrorist acts were included. Data were extracted according to a range of predefined fields, and studies were checked for reliability using a study quality assessment tool. Eighteen articles were included: thirteen quantitative descriptive studies, four qualitative studies, and one that used a mix of quantitative and qualitative methods. The articles highlight the various difficulties faced by children and adolescents who have been exposed to terrorism during their development (such as posttraumatic stress disorder, neurocognitive, sensorimotor, emotional disorders, etc.), sometimes concomitant with the loss of a loved one killed during the event, and the trauma of their parent also having repercussions on them, effects that are even more important the older they are. [ABSTRACT FROM AUTHOR]

The number of words children produce (expressive vocabulary) and understand (receptive vocabulary) changes rapidly during early development, partially due to genetic factors. Here, we performed a meta–genome-wide association study of vocabulary acquisition and investigated polygenic overlap with literacy, cognition, developmental phenotypes, and neurodevelopmental conditions, including attention-deficit/hyperactivity disorder (ADHD). We studied 37,913 parent-reported vocabulary size measures (English, Dutch, Danish) for 17,298 children of European descent. Meta-analyses were performed for early-phase expressive (infancy, 15–18 months), late-phase expressive (toddlerhood, 24–38 months), and late-phase receptive (toddlerhood, 24–38 months) vocabulary. Subsequently, we estimated single nucleotide polymorphism–based heritability (SNP- h 2 ) and genetic correlations (r g) and modeled underlying factor structures with multivariate models. Early-life vocabulary size was modestly heritable (SNP- h 2 = 0.08–0.24). Genetic overlap between infant expressive and toddler receptive vocabulary was negligible (r g = 0.07), although each measure was moderately related to toddler expressive vocabulary (r g = 0.69 and r g = 0.67, respectively), suggesting a multifactorial genetic architecture. Both infant and toddler expressive vocabulary were genetically linked to literacy (e.g., spelling: r g = 0.58 and r g = 0.79, respectively), underlining genetic similarity. However, a genetic association of early-life vocabulary with educational attainment and intelligence emerged only during toddlerhood (e.g., receptive vocabulary and intelligence: r g = 0.36). Increased ADHD risk was genetically associated with larger infant expressive vocabulary (r g = 0.23). Multivariate genetic models in the ALSPAC (Avon Longitudinal Study of Parents and Children) cohort confirmed this finding for ADHD symptoms (e.g., at age 13; r g = 0.54) but showed that the association effect reversed for toddler receptive vocabulary (r g = −0.74), highlighting developmental heterogeneity. The genetic architecture of early-life vocabulary changes during development, shaping polygenic association patterns with later-life ADHD, literacy, and cognition-related traits. [ABSTRACT FROM AUTHOR]

Rates of neonatal opioid withdrawal syndrome (NOWS) have been increasing. Acute withdrawal symptoms are well characterized in NOWS infants, but environmental confounds and difficulties in conducting longitudinal studies make it challenging to elucidate potential long-term clinical effects. Preclinical animal models have great utility for studying the persisting consequences of perinatal opioid exposure and to address the mechanistic basis of these effects. Several preclinical perinatal opioid exposure models have been developed. Whereas early animal models primarily used the prototypical opioid, morphine, and a limited opioid exposure period, more recent models have been using various opioid types and different durations of perinatal opioid exposure. Behavioral phenotypes vary across models, reaffirming the importance of dosage, type of opioid, and duration of exposure for the development of specific phenotypes. Neonatal opioid withdrawal syndrome (NOWS) is a growing public health concern. The complexity of in utero opioid exposure in clinical studies makes it difficult to investigate underlying mechanisms that could ultimately inform early diagnosis and treatments. Clinical studies are unable to dissociate the influence of maternal polypharmacy or the environment from direct effects of in utero opioid exposure, highlighting the need for effective animal models. Early animal models of prenatal opioid exposure primarily used the prototypical opioid, morphine, and opioid exposure that was often limited to a narrow period during gestation. In recent years, the number of preclinical studies has grown rapidly. Newer models utilize both prescription and nonprescription opioids and vary the onset and duration of opioid exposure. In this review, we summarize novel prenatal opioid exposure models developed in recent years and attempt to reconcile results between studies while critically identifying gaps within the current literature. [ABSTRACT FROM AUTHOR]

The first 2 years of life is a period of rapid learning and growth when humans acquire notable motor, perceptual, linguistic, and social capabilities. Because of challenges in measuring brain activity in human infants, many of the neural mechanisms underlying these capabilities have not been identified. Advances in neuroimaging technologies, task designs, and data analyses from studies of older children and adults are starting to be translated into studies of infants. These new methods include frequency tagging designs in electroencephalography (EEG), task-based functional magnetic resonance imaging (fMRI) studies in awake and behaving infants, multivariate analyses of EEG and functional near-infrared spectroscopy (fNIRS), and the emergence of infant-friendly optically pumped magnetometry (OPM). The resulting neural data provide rich new measures of infant cognition, supplementing the limited behavioral data that can be obtained from preverbal infants. The functional properties of the infant brain are poorly understood. Recent advances in cognitive neuroscience are opening new avenues for measuring brain activity in human infants. These include novel uses of existing technologies such as electroencephalography (EEG) and magnetoencephalography (MEG), the availability of newer technologies including functional near-infrared spectroscopy (fNIRS) and optically pumped magnetometry (OPM), and innovative applications of functional magnetic resonance imaging (fMRI) in awake infants during cognitive tasks. In this review article we catalog these available non-invasive methods, discuss the challenges and opportunities encountered when applying them to human infants, and highlight the potential they may ultimately hold for advancing our understanding of the youngest minds. [ABSTRACT FROM AUTHOR]

[Display omitted] • Two homologs of aminopeptidase I (Ape1) are present in Beauveria bassiana. • Two Ape1 homologs have convergent roles in pathobiology of B. bassiana. • Vacuolar targeting of two homologs is dependent on physiological states. • Two homologs are translocated via non-selective autophagy under starvation. • Translocation of BbApe1A is dependent on Nbr1 and Atg11 during development. • BbApe1B is translocated via its interaction with Nbr1 during development. • Two homologs are maturated by processing in vacuole. In yeast, the cytoplasm-to-vacuole targeting (Cvt) pathway acts as a biosynthetic autophagy-related process, in which vacuolar targeting of hydrolase is mediated by the machineries involved in the selective autophagy. However, the mechanistic insights into vacuolar targeting of hydrolases through the selective autophagy pathway still remain enigmatic in filamentous fungi. Our study aims to investigate the mechanisms involved in vacuolar targeting of hydrolases in filamentous fungi. The filamentous entomopathogenic fungus Beauveria bassiana was used as a representative of filamentous fungi. We identified the homologs of yeast aminopeptidase I (Ape1) in B. bassiana by bioinformatic analyses and characterized their physiological roles by gene function analyses. Pathways for vacuolar targeting of hydrolases were investigated via molecular trafficking analyses. B. bassiana has two homologs of yeast aminopeptidase I (Ape1) which are designated as BbApe1A and BbApe1B. The two homologs of yeast Ape1 contribute to starvation tolerance, development, and virulence in B. bassiana. Significantly, BbNbr1 acts as a selective autophagy receptor to mediate the vacuolar targeting of the two Ape1 proteins, in which BbApe1B interacts with BbNbr1 also directly interacting with BbAtg8, and BbApe1A has an additional requirement of the scaffold protein BbAtg11 that interacts with BbNbr1 and BbAtg8. Protein processing occurs at both terminuses of BbApe1A and only at carboxyl terminus of BbApe1B, which is also dependent on the autophagy-related proteins. Together, the functions and translocation processes of the two Ape1 proteins are associated with autophagy in fungal lifecycle. This study reveals the functions and translocation processes for vacuolar hydrolases in the insect-pathogenic fungi and improves our understandings of the Nbr1-mediated vacuolar targeting pathway in the filamentous fungi. [ABSTRACT FROM AUTHOR]

Despite a noticeable trend of delayed fatherhood, less is known about the impact of paternal age on the paternally programmed placenta. We hypothesize that paternal aging affects seminal quality and as such induces ageing-related epigenetic alterations that influence placental growth. Our main aim is to investigate associations between paternal age and first trimester (vascular) placental growth trajectories. Pregnant women were enrolled before 10 weeks of gestation in the Rotterdam Periconceptional Cohort (Predict study). Placental volumes (PV) and utero-placental vascular volumes (uPVV) were measured at 7, 9, and 11 weeks gestation. Associations between paternal age and PV and uPVV were investigated using linear mixed models and the maximum likelihood ratio test to test non-linear relationships. We adjusted for gestational age, fetal sex, parental smoking and maternal age, BMI, education and parity, and stratified for conception mode. From 808 pregnancies we obtained 1313 PV and from 183 pregnancies 345 uPVV measurements. We show no associations between paternal age and PV (p = 0.934) and uPVV (p = 0.489) in our total population or in pregnancies conceived naturally (PV p = 0.166; uPVV p = 0.446) and after IVF/ICSI (PV p = 0.909; uPVV p = 0.749). For example, PV was 0.9% smaller (95% CI -5.7%—7.1%) in fathers aged 40 compared to 30 years old at 9 weeks gestation in the total study population. We are not demonstrating a significant impact of paternal age on first trimester placental growth in a tertiary care population. Given the trend of increasing paternal age, our study should be repeated in the general population. • 3D ultrasound techniques enable assessment of first trimester placental growth. • Paternal age did not impact placental growth in cohort of >800 high-risk pregnancies. • Study should be repeated in general population given the trend of delayed fatherhood. [ABSTRACT FROM AUTHOR]

In mammals, thick axonal calibers wrapped with heavy myelin sheaths are prevalent in the auditory nervous system. These features are crucial for fast traveling of nerve impulses with minimal attenuation required for sound signal transmission. In particular, the long-range projections from the cochlear nucleus – the axons of globular bush cells (GBCs) – to the medial nucleus of the trapezoid body (MNTB) are tonotopically organized. However, it remains controversial in gerbils and mice whether structural and functional adaptations are present among the GBC axons targeting different MNTB frequency regions. By means of high-throughput volume electron microscopy, we compared the GBC axons in full-tonotopy-ranged MNTB slices from the C57BL/6 mice at different ages. Our quantification reveals distinct caliber diameter and myelin profile of the GBC axons with endings at lateral and medial MNTB, arguing for modulation of functionally heterogeneous axon subgroups. In addition, we reported axon-specific differences in axon caliber, node of Ranvier, and myelin sheath among juvenile, adult, and old mice, indicating the age-related changes of GBC axon morphology over time. These findings provide structural insight into the maturation and degeneration of GBC axons with frequency tuning across the lifespan of mice. [Display omitted] • This study presented a volume EM reconstruction of whole-frequency MNTB in mice. • It revealed distinct caliber diameter and myelin profile of HF and LF-GBC axons. • Changes of Ranvier's node, internode and myelin from GBC axons occur in adult mice. • Diameter of Ranvier's nodes and internodes changes during development and aging. • Myelin thickness of GBC axons increases during development and aging process. [ABSTRACT FROM AUTHOR]

To describe the duration, timing, tempo, and synchronicity of puberty, as well as the correlation between timing and tempo of puberty. Overall, 15,819 of 22,439 invited children participated in the Puberty Cohort within the Danish National Birth Cohort. Participants completed a web-based questionnaire every 6 months through maturation with questions on current pubertal status. Girls reported current Tanner stage of breast and pubic hair development, and timing of menarche. Boys reported current Tanner stage of genital and pubic hair development, timing of first ejaculation, and vocal changes. While accounting for this interval-censored puberty information, we estimated the duration of puberty. Then, we used a nonlinear mixed effect growth model to estimate timing, tempo, synchronicity of puberty, and correlation between timing and tempo of puberty. In girls, the average duration of breast development was longer, whereas the average tempo was slower than pubic hair development. The average timing of breast development was earlier than the average timing of pubic hair development. The majority of girls had asynchronous puberty. In boys, the average duration was longer and average tempo slower for genital than pubic hair development. The average timing of genital and pubic hair development were comparable; hence, the majority had synchronous pubertal development. Adolescents who had earlier timing also tended to have a faster tempo. Being one of the largest puberty cohorts worldwide, these unique contemporary data can help physicians, parents, and children to understand and anticipate expected progression through pubertal development. [ABSTRACT FROM AUTHOR]

• Juvenile male song sparrows are robustly aggressive, like adults. • Androgens and estrogens are low in the blood and brain of juveniles. • Blood and brain progesterone in juveniles increase after an aggressive encounter. • Blood and brain glucocorticoids increase after an aggressive encounter. • Juvenile and adult aggression might use distinct neuroendocrine mechanisms. Aggression is a social behavior that is critical for survival and reproduction. In adults, circulating gonadal hormones, such as androgens, act on neural circuits to modulate aggressive interactions, especially in reproductive contexts. In many species, individuals also demonstrate aggression before reaching gonadal maturation. Adult male song sparrows, Melospiza melodia , breed seasonally but maintain territories year-round. Juvenile (hatch-year) males aggressively compete for territory ownership during their first winter when circulating testosterone is low. Here, we characterized the relationship between the steroid milieu and aggressive behavior in free-living juvenile male song sparrows in winter. We investigated the effect of a 10 min simulated territorial intrusion (STI) on behavior and steroid levels in blood, 10 microdissected brain regions, and four peripheral tissues (liver, pectoral muscle, adrenal glands, and testes). Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we quantified 12 steroids: pregnenolone, progesterone, corticosterone, 11-dehydrocorticosterone, dehydroepiandrosterone, androstenedione, testosterone, 5α-dihydrotestosterone, 17β-estradiol , 17α-estradiol, estrone, and estriol. We found that juvenile males are robustly aggressive, like adult males. An STI increases progesterone and corticosterone levels in blood and brain and increases 11-dehydrocorticosterone levels in blood only. Pregnenolone, androgens, and estrogens are generally non-detectable and are not affected by an STI. In peripheral tissues, steroid concentrations are very high in the adrenals. These data suggest that adrenal steroids, such as progesterone and corticosterone, might promote juvenile aggression and that juvenile and adult songbirds might rely on distinct neuroendocrine mechanisms to support similar aggressive behaviors. [ABSTRACT FROM AUTHOR]

A large literature has identified exposure to early caregiving adversities as a potent risk for developing affective psychopathology, with depression, in particular, increasing across childhood into adolescence. Evidence suggests telomere erosion, a marker of biological aging, may underlie associations between adverse early-life experiences and later depressive behavior; yet, little is understood about this association during development. The current accelerated longitudinal study examined concurrent telomere length and depressive symptoms concurrently, 2 and 4 years later, from the preschool period through adolescence among children exposed (n =116) and not exposed (n = 242) to early previous institutional (PI) care. PI care was associated with shorter telomeres on average and with quadratic age-related growth in depressive symptoms, indicating a steeper association between PI care and depressive symptoms in younger age groups that leveled off in adolescence. Contrary to studies in adult samples, telomere length was not associated with depressive symptoms, and it did not predict future symptoms. These findings indicate that early caregiving disruptions increase the risk for both accelerated biological aging and depressive symptoms, although these variables did not correlate with each other during this age range. [ABSTRACT FROM AUTHOR]

HSP is a heterogeneous group of rare genetic diseases. In childhood, little is known of the development and psychological manifestations. Retrospective analysis of 87 patients with childhood-onset HSP. Patient consent was obtained and data regarding gross motor, fine motor, and language development; equipment usage; surgical procedures; cognition; and mood were collected at each clinic visit and by phone call and analyzed using mean, median, range, and interquartile ranges (IQRs). The cohort contained 18 genetic types of HSP. Participant data ranged from birth to 36 years. Follow-up was variable spanning from a single clinic visit to 24 years of longitudinal visits. The mean age in months of sitting = 7.37, median = 6, range = 5 to 48, IQR = 0; crawling mean = 9.6, median = 9, range 7 to 23, IQR = 0; pulling to stand mean = 10.7, median 9, range: 9 to 36, IQR = 0; and the age for walking was mean = 16.25, median = 15, range = 11 to 63 IQR = 6. Eighteen patients did not achieve independent ambulation. Twenty-five were noted to have initial gait abnormalities. Median age for first word spoken was 12 months. Fifty-five of 87 participants were enrolled in mainstream or honors classes. Twenty-two of 87 had attention deficit disorder. Patients reported experiencing sadness around their diagnoses, and 26 of 87 reported being diagnosed with anxiety or depression. In childhood-onset HSP, motor disorder is the predominant feature; however, screening for attention deficit, anxiety, and depression is indicated. [ABSTRACT FROM AUTHOR]

Despite widespread application of semiotic theory in sociolinguistics, the development of children's social-semiotic landscapes remains underexplored. This paper analyzes the spontaneous responses of 94 children to short American English speech samples, with emic coding of responses. Results support a view of children's social-semiotic landscapes as rich and expanding; children as young as 5 volunteer a wide range of social indexes, but substantive comments increase in developmental time. Children use personal and local information early and often. Developmental increases in comments relying on more public or evaluative social knowledge suggest a developmental process building outward from the personal to the public. Children offer a window into the vibrant scaffolding process that all language users utilize, connecting language to the social in a local and dialogic process. • The development of children's social-semiotic landscapes remains underexplored. • Children provided open-ended responses of their impressions of English voices. • We qualitatively coded responses based on what social information children used. • Results support a view of children's social-semiotic landscapes as rich and expanding. • Suggests a developmental process that builds outward from the personal to the public. [ABSTRACT FROM AUTHOR]

This study aimed to achieve a better understanding of taste receptor cell development relative to endothelin receptor B (ETB) in circumvallate papillae (CVP). ETB localization was assessed by immunohistochemistry during tongue development of the mouse. Co-localization of ETB with taste receptor type III cell marker, Synaptosomal-Associated Protein 25 kDa (SNAP25), was evident in both the developing and adult CVP. ETB was strongly localized in the stromal core region. As development progressed, ETB became localized in the CVP mesenchyme and partially in the epithelium. ETB and SNAP25 co-localization indicates that ETB may regulate innervation from the CVP mesenchyme to taste buds. [ABSTRACT FROM AUTHOR]

Schistosomiasis, caused by Schistosoma spp., is a zoonotic parasitic disease affecting human health. Rattus norvegicus (rats) are a non-permissive host of Schistosoma , in which the worms cannot mature and cause typical egg granuloma. We previously demonstrated that inherent high levels of nitric oxide (NO), produced by inducible NO synthase (iNOS), is a key molecule in blocking the development of S. japonicum in rats. To further explore the mechanism of NO inhibiting S. japonicum development in rats, we performed S-nitrosocysteine proteomics of S. japonicum collected from infected rats and mice. The results suggested that S. japonicum in rats may have undergone endoplasmic reticulum (ER) stress. Interestingly, we found that the ER of S. japonicum in rats showed marked damage, while the ER of the worm in iNOS−/− rats and mice were relatively normal. Moreover, the expression of ER stress markers in S. japonicum from WT rats was significantly increased, compared with S. japonicum from iNOS−/− rats and mice. Using the NO donor sodium nitroprusside in vitro, we demonstrated that NO could induce ER stress in S. japonicum in a dose-dependent manner, and the NO-induced ER stress in S. japonicum could be inhibited by ER stress inhibitor 4-Phenyl butyric acid. We further verified that inhibiting ER stress of S. japonicum in rats promoted parasite development and survival. Furthermore, we demonstrated that NO-induced ER stress of S. japonicum was related to the efflux of Ca2+ from ER and the impairment of mitochondrial function. Collectively, these findings show that high levels of NO in rats could induce ER stress in S. japonicum by promoting the efflux of Ca2+ from ER and damaging the mitochondrial function, which block the worm development. Thus, this study further clarifies the mechanism of anti-schistosome in rats and provides potential strategies for drug development against schistosomiasis and other parasitosis. [Display omitted] • High levels of nitric oxide (NO) induces endoplasmic reticulum (ER) stress in S. japonicum in vivo and in vitro. • NO inhibits parasite development and survival by inducing endoplasmic reticulum (ER) stress in S. japonicum. • NO-induced ER stress in S. japonicum is related to the efflux of Ca2+ from ER. • NO-induced ER stress in S. japonicum impaire mitochondrial structure and function. [ABSTRACT FROM AUTHOR]

The family entertainment center serves as the primary entertainment intermediary, catering especially to young people and adults through various games, such as virtual reality and the latest entertainment revolution of 3D technology. In order to sustain growth, family entertainment centers must regularly invest in new machines. The process of financing these investments must be precise to streamline company costs and ensure visitor satisfaction. The leadership's decision-making factors for investments can be effectively supported through technology. Therefore, the objective of this research is to create a prototype modeling system that simplifies the ongoing installation process and integrates Compound Annual Growth Rate (CAGR) figures through Arduino, displaying them on a website. The end result of this research is a game prototype model for a family center that effectively assists managers in decision-making, particularly in evaluating machine ratings based on visitor transactions and revenue for each machine using the CAGR metric. [ABSTRACT FROM AUTHOR]

• The process of automation could hinder political trust in government. • The impact results from unemployment, higher down-side risk and lower group participation. • The performance-based legitimacy structure in a developmental state may hinder its political legitimacy when promoting development. • The government should focus more on citizens' trust when pursuing technological development. • Social security is crucial for governance faced with fast technological advancement. The side effects of automation on the economy have been discussed frequently, but little is known regarding its political consequences. This paper examines the causal effect that automation induces on political costs for the local government. By combining the national individual-level panel data of political trust with the prefecture-level robot exposure rate in China, we find that the development of automation would reduce individuals' political trust in the Chinese local government. Furthermore, we explore the channels through which the automation process could affect political trust, namely the risk of unemployment, intensified pessimism about local government, higher downside risk, and declining organization participation. This paper provides empirical evidence for the impact of automation and the source of political legitimacy, emphasizing the crucial role of governments in coping with technological progress and making good use of endogenous creative destruction. [Display omitted] [ABSTRACT FROM AUTHOR]

Pioneer factors can be master regulators of development. They are responsible for zygotic genome activation after fertilization and drive cell fate transitions during development. Pioneer factors bind nucleosomal DNA containing their DNA-binding motifs. The binding is mediated by the DNA-binding domain of the pioneer factor and via establishment of histone–pioneer factor interactions. Pioneer factors initiate local chromatin decompaction by partially unwrapping DNA from nucleosomes and reducing local nucleosome interactions. Pioneer factors recruit nucleosome-remodeling complexes and chromatin-modifying enzymes to promote silent chromatin reorganization, deposition of active chromatin modifications, and, thus, activation of underlying promoter and enhancer DNA sequences. Pioneer factors can vary with regard to their ability to target diverse types of silent chromatin during cell differentiation. Pioneer factors are a subclass of transcription factors that can bind and initiate opening of silent chromatin regions. Pioneer factors subsequently regulate lineage-specific genes and enhancers and, thus, activate the zygotic genome after fertilization, guide cell fate transitions during development, and promote various forms of human cancers. As such, pioneer factors are useful in directed cell reprogramming. In this review, we define the structural and functional characteristics of pioneer factors, how they bind and initiate opening of closed chromatin regions, and the consequences for chromatin dynamics and gene expression during cell differentiation. We also discuss emerging mechanisms that modulate pioneer factors during development. [ABSTRACT FROM AUTHOR]

Diphthamide is a conserved post-translational modification of the essential eukaryotic translation elongation factor 2 (eEF2). It assures translational frame accuracy, and its absence increases translational frameshifts. The enzymes and pathways for diphthamide synthesis are conserved from yeast to man, in eukaryotes and archaea, yet absent in bacteria. Diphthamide is the molecular target of ADP-ribosylating toxins from bacterial pathogens including Corynebacterium diphtheriae and Pseudomonas aeruginosa. Deletions or promoter mutations of diphthamide synthesis genes are associated with cancer. Homozygous or compound heterozygous mutations that compromise diphthamide synthesis enzymes can cause diphthamide deficiency syndrome. Diphthamide-dependent reading frame maintenance limits –1 programmed ribosomal frameshifts (−1PRFs). −1PRF is necessary to generate proteins that are needed for propagation of HIV and SARS-CoV-2. Some −1PRF-dependent viruses target diphthamide synthesis enzymes for degradation. Diphthamide, a complex modification on eukaryotic translation elongation factor 2 (eEF2), assures reading-frame fidelity during translation. Diphthamide and enzymes for its synthesis are conserved in eukaryotes and archaea. Originally identified as target for diphtheria toxin (DT) in humans, its clinical relevance now proves to be broader than the link to pathogenic bacteria. Diphthamide synthesis enzymes (DPH1 and DPH3) are associated with cancer, and DPH gene mutations can cause diphthamide deficiency syndrome (DDS). Finally, new analyses provide evidence that diphthamide may restrict propagation of viruses including SARS-CoV-2 and HIV-1, and that DPH enzymes are targeted by viruses for degradation to overcome this restriction. This review describes how diphthamide is synthesized and functions in translation, and covers its clinical relevance in human development, cancer, and infectious diseases. [ABSTRACT FROM AUTHOR]

In 2023, the Turkish government set ambitious targets for hydrogen production, aiming to reach a price of $2.40 per kilogram by 2035 and halve it by 2050. This article explores the development potential of hydrogen energy in Turkey based on current data. The analysis encompasses critical elements, such as research and development, governmental hydrogen strategy, economic & energy advantages, production & application technologies. There is also a SWOT analysis of the current hydrogen energy landscape in Turkey. Overcoming various challenges and increasing investments in scientific research and infrastructure development are crucial for the successful expansion of the hydrogen economy. In summary, the development of hydrogen green energy is pivotal for enhancing energy security, reducing environmental impact, and meeting international climate commitments, thus strengthening Turkey's economic position in the global energy arena. [Display omitted] • The latest data of hydrogen research has been comprehensively analyzed. • Turkey has the potential to promote green hydrogen energy. • Turkey aims to cut hydrogen costs and expand electrolyser capacity by 2053. • A SWOT analysis of the current hydrogen energy landscape in Turkey was conducted. [ABSTRACT FROM AUTHOR]

Global dosage control is an underlying miRNA regulatory strategy to achieve accurate post-transcriptional regulation. miRNA dosage control regulates embryonic development, stem cell fate decisions, neurodevelopment and immune responses. miRNA dosage control occurs at different steps of miRNA biogenesis in various physiological contexts. Dysregulation of global miRNA dosage contributes to cancer, embryo death, and neurological diseases. Artificial manipulation of global miRNA dosage provides a novel approach to treat human diseases. In mammals, miRNAs recognize target mRNAs via base pairing, which leads to a complex 'multiple-to-multiple' regulatory network. Previous studies have focused on the regulatory mechanisms and functions of individual miRNAs, but alterations of many individual miRNAs do not strongly disturb the miRNA regulatory network. Recent studies revealed the important roles of global miRNA dosage control events in physiological processes and pathogenesis, suggesting that miRNAs can be considered as a 'cellular buffer' that controls cell fate. Here, we review the current state of research on how global miRNA dosage is tightly controlled to regulate development, tumorigenesis, neurophysiology, and immunity. We propose that methods of controlling global miRNA dosage may serve as effective therapeutic tools to cure human diseases. [ABSTRACT FROM AUTHOR]

Epilepsy encompasses more than the predisposition to unprovoked seizures. In children, epileptic activity during (ictal) and between (interictal) seizures has the potential to disrupt normal brain development. The term "epileptic encephalopathy (EE)" refers to the concept that such abnormal activity may contribute to cognitive and behavioral impairments beyond that expected from the underlying cause of the epileptic activity. In this review, we survey the concept of EE across a diverse selection of syndromes to illustrate its broad applicability in pediatric epilepsy. We review experimental evidence that provides mechanistic insights into how epileptic activity has the potential to impact normal brain processes and the development of neural networks. We then discuss opportunities to improve developmental outcomes in epilepsy now and in the future. Epileptic activity in the brain poses a threat to normal physiology and brain development. Until we have treatments that reliably target and effectively treat the underlying causes of epilepsy, a major goal of management is to prevent epileptic activity from worsening developmental outcomes. [ABSTRACT FROM AUTHOR]

• We studied saccade performance to study the underlying basal ganglia (BG) pathophysiology in Segawa's disease (SD). • We found a mild delay in latency of memory guided saccades and impairment to suppress reflexive saccades in SD. • Dopamine deficiency manifests in oculomotor abnormalities during development with delayed maturation especially in male patients. Objective: To investigate the oculomotor manifestations of Segawa disease (SD), considered to represent mild dopamine deficiency and discuss their pathophysiological basis. Methods: We recorded visually- (VGS) and memory-guided saccade (MGS) tasks in 31 SD patients and 153 age-matched control subjects to study how basal ganglia (BG) dysfunction in SD evolves with age for male and female subjects. Results: SD patients were impaired in initiating MGS, showing longer latencies with occasional failure. Patients showed impaired ability to suppress reflexive saccades; saccades to cues presented in MGS were more frequent and showed a shorter latency than in control subjects. These findings were more prominent in male patients, particularly between 13 and 25 years. Additionally, male patients showed larger delay in MGS latency in trials preceded by saccades to cue than those unpreceded. Conclusions: The findings can be explained by a dysfunction of the BG-direct pathway impinging on superior colliculus (SC) due to dopamine deficiency. The disturbed inhibitory control of saccades may be explained by increased SC responsivity to visual stimuli. Significance: Oculomotor abnormalities in SD can be explained by dysfunction of the BG inhibitory pathways reaching SC, with a delayed maturation in male SD patients, consistent with previous pathological/physiological studies. [ABSTRACT FROM AUTHOR]

Depression and anxiety are two mental disorders prevailing among adolescents. However, issues regarding the trajectory of depression and anxiety are still controversial on both the disease and symptom dimensions. The novel method of network analysis was used to provide insight into the symptom dimension. 20,544 adolescents (female = 10,743, 52.3%) aged between 14 and 24 years (age mean ± sd = 16.9 ± 2.94) were divided into three subgroups according to age so that the course of depression and anxiety could be traced. Network analysis and the Bayesian network model were used in the current study. The results indicated that uncontrollable worry - excessive worry was the most significant edge for all adolescents, whereas concentration - motor had the highest edge weights for early adolescents, and anhedonia - energy was the most critical pairwise symptom for middle and late adolescents. Irritability can bridge anxiety and depression in the early and middle stages of adolescence, while suicide plays a bridging role in the early and late stages of adolescence. Restlessness and guilt can bridge anxiety and depression in middle- and late-stage adolescents, and feeling afraid plays a unique role in middle-stage adolescents. Except for sad mood, which can trigger middle adolescents' anxiety and depression, the other three subgroups were mainly triggered by nervousness. In addition, all results in our current study were shown to be stable and accurate. In treatment, targeting central and triggering symptoms at different stages of adolescence may be critical to alleviating the comorbidity of anxiety and depression. • The prevalence of depression and anxiety among adolescents was 8.30% and 6.56%. • Irritability bridges anxiety and depression in adolescence's early and middle stages. • In middle and late adolescence, restlessness and guilt bridge anxiety and depression. • Sad mood can trigger middle adolescents' anxiety and depression symptoms. • Nervousness trigger all, early and late adolescents' anxiety and depression symptoms. [ABSTRACT FROM AUTHOR]

• In the cochlea, sound detection highly relies on the extracellular matrix (ECM) integrity, and hereditary deafness in humans is caused by mutations in numerous ECM-related genes. • Cochlear matrisome plays an active role during the development of the hearing organ and the establishment of its unique architecture. • Cochlear matrisome changes with ageing and in response to cochlear insults, such as noise exposure, ototoxic drug administration and insertion of cochlear implants. • ECM remodeling exerts protective functions or improves tissue repair after injury but may also exacerbate cochlear damage. Deciphering the role of individual ECM components and regulators might provide valuable therapeutic targets for hearing preservation. The extracellular matrix (ECM) consists in a complex meshwork of collagens, glycoproteins, and proteoglycans, which serves a scaffolding function and provides viscoelastic properties to the tissues. ECM acts as a biomechanical support, and actively participates in cell signaling to induce tissular changes in response to environmental forces and soluble cues. Given the remarkable complexity of the inner ear architecture, its exquisite structure-function relationship, and the importance of vibration-induced stimulation of its sensory cells, ECM is instrumental to hearing. Many factors of the matrisome are involved in cochlea development, function and maintenance, as evidenced by the variety of ECM proteins associated with hereditary deafness. This review describes the structural and functional ECM components in the auditory organ and how they are modulated over time and following injury. [ABSTRACT FROM AUTHOR]

Ventral temporal cortex supports visual processing of important categories, such as faces and words. A predominant theory is that the development of word-selective cortex during the onset of reading instruction pushes face-selective responses to the right hemisphere. Recent longitudinal measurements suggest that word-selective cortex is recycling cortical territory dedicated to processing limbs or tools rather than faces. Future work should aim to link development measured with fMRI to the visual environment and behavior. High-level visual areas in ventral temporal cortex (VTC) support recognition of important categories, such as faces and words. Word-selective regions are left lateralized and emerge at the onset of reading instruction. Face-selective regions are right lateralized and have been documented in infancy. Prevailing theories suggest that face-selective regions become right lateralized due to competition with word-selective regions in the left hemisphere. However, recent longitudinal studies examining face- and word-selective responses in childhood do not provide support for this theory. Instead, there is evidence that word representations recycle cortex previously involved in processing other stimuli, such as limbs. These findings call for more longitudinal investigations of cortical recycling and a new era of work that links visual experience and behavior with neural responses. [ABSTRACT FROM AUTHOR]

Studies using scalp EEG have shown that slow waves (0.5–4 Hz), the most prominent hallmark of NREM sleep, undergo relevant changes from childhood to adulthood, mirroring brain structural modifications and the acquisition of cognitive skills. Here we used simultaneous EEG-fMRI to investigate the cortical and subcortical correlates of slow waves in school-age children and determine their relative developmental changes. We analyzed data from 14 school-age children with self-limited focal epilepsy of childhood who fell asleep during EEG-fMRI recordings. Brain regions associated with slow-wave occurrence were identified using a voxel-wise regression that also modelled interictal epileptic discharges and sleep spindles. At the group level, a mixed-effects linear model was used. The results were qualitatively compared with those obtained from 2 adolescents with epilepsy and 17 healthy adults. Slow waves were associated with hemodynamic-signal decreases in bilateral somatomotor areas. Such changes extended more posteriorly relative to those in adults. Moreover, the involvement of areas belonging to the default mode network changes as a function of age. No significant hemodynamic responses were observed in subcortical structures. However, we identified a significant correlation between age and thalamic hemodynamic changes. Present findings indicate that the somatomotor cortex may have a key role in slow-wave expression throughout the lifespan. At the same time, they are consistent with a posterior-to-anterior shift in slow-wave distribution mirroring brain maturational changes. Finally, our results suggest that slow-wave changes may not reflect only neocortical modifications but also the maturation of subcortical structures, including the thalamus. Low spatial resolution of conventional EEG has widely limited the possibility of accurately determining in humans the role of different brain structures in the expression of sleep slow waves throughout development. Here, for the first time, we took advantage of a simultaneous EEG-fMRI approach to accurately describe the cortical and subcortical hemodynamic correlates of sleep slow waves in a sample of 14 school-aged children. In order to elucidate age-dependent changes, we qualitatively compared present findings with those previously obtained in a group of adults. Overall our results have important implications for the understanding of how cortico-cortical and subcortico-cortical interactions shape sleep slow waves across development. [Display omitted] • The EEG topography of sleep slow waves changes during development, but the structures involved in such changes are unknown. • We used combined EEG-fMRI to identify the cortical and subcortical correlates of slow waves in school-aged children. • Somatomotor BOLD-signal changes were found in both children and adults but extended more posteriorly in children. • A significant correlation was found between age and thalamic hemodynamic changes during sleep slow waves. • Developmental slow-wave changes may reflect the maturation of cortical and subcortical structures, including the thalamus. [ABSTRACT FROM AUTHOR]

Mutations and polymorphisms in A20 / TNFAIP3 have been linked to various inflammatory disorders. However, in addition to its well-known role in inflammation, A20 also controls EDAR- and receptor activator of NF-κB (RANK)-induced NF-κB signaling, regulating the development of epidermal skin appendages and bone, respectively. Furthermore, A20 regulates synapse remodeling through a mechanism dependent on NF-κB. [ABSTRACT FROM AUTHOR]

Il existe un lien fort entre le développement du langage oral chez l'enfant et le développement de ses compétences mathématiques. L'objectif de la présente recherche est de recenser les études et synthétiser les connaissances scientifiques acquises à ce jour sur le vocabulaire mathématique chez l'enfant. La méthode de recherche utilisée est la revue de littérature systématique. Les résultats sont exposés sous forme de synthèse narrative. Cette revue a montré que différentes terminologies sont relevées dans les articles. Le vocabulaire mathématique est le plus souvent évalué en compréhension uniquement et il est identifié comme un fort prédicteur de plusieurs compétences mathématiques et cognitives. La revue souligne également que les enfants présentant des difficultés d'apprentissage en mathématiques présentent des difficultés au niveau du vocabulaire mathématique. De plus, la présente synthèse met en évidence l'intérêt d'un apprentissage explicite du vocabulaire mathématique chez des enfants entre 6 et 11 ans, notamment à travers la lecture partagée pour les plus jeunes. Enfin, aucune étude n'a investigué le vocabulaire mathématique en français. There is a strong link between the development of spoken language in children and the development of their mathematical skills. The objective of the current research is to identify studies and synthesize the scientific knowledge acquired to date on mathematical vocabulary in children. The research method used was a systematic literature review. The results are presented in a narrative synthesis. This review showed that different terminologies are identified in the articles. Mathematical vocabulary is most often assessed in comprehension only, and it is a strong predictor of many mathematical and cognitive skills. The review points out also that children with mathematics learning difficulties have difficulties with mathematical vocabulary. Furthermore, the present synthesis highlights the interest of explicit learning of mathematical vocabulary in children between the ages of 6 and 11 years, particularly through shared reading for the youngest. Finally, no study has investigated mathematical vocabulary in French. [ABSTRACT FROM AUTHOR]

The study of infant (and fetal) consciousness is emerging as a distinctive research focus in the science of consciousness. Converging evidence from studies of functional network connectivity, attention, multimodal integration, and cortical responses to global oddballs suggests that consciousness is likely to be in place in early infancy and may even occur before birth. Recent research is beginning to provide clues about both the content and structure of infant consciousness. Although each of us was once a baby, infant consciousness remains mysterious and there is no received view about when, and in what form, consciousness first emerges. Some theorists defend a 'late-onset' view, suggesting that consciousness requires cognitive capacities which are unlikely to be in place before the child's first birthday at the very earliest. Other theorists defend an 'early-onset' account, suggesting that consciousness is likely to be in place at birth (or shortly after) and may even arise during the third trimester. Progress in this field has been difficult, not just because of the challenges associated with procuring the relevant behavioral and neural data, but also because of uncertainty about how best to study consciousness in the absence of the capacity for verbal report or intentional behavior. This review examines both the empirical and methodological progress in this field, arguing that recent research points in favor of early-onset accounts of the emergence of consciousness. [ABSTRACT FROM AUTHOR]

Schizophrenia is a neurodevelopmental psychiatric disorder that often emerges in adolescence, is characterized by social dysfunction, and has an earlier onset in men. These features have been replicated in rats exposed to the mitotoxin methylazoxymethanol acetate (MAM) on gestational day (GD) 17, which as adults exhibit behavioral impairments and dopamine (DA) system changes consistent with a schizophrenia-relevant rodent model. In humans, social withdrawal is a negative symptom that often precedes disease onset and DA system dysfunction and is more pronounced in men. Children and adolescents at high-risk for schizophrenia exhibit social deficits prior to psychotic symptoms (i.e., prodromal phase), which can be used as a predictive marker for future psychopathology. Adult MAM rats also exhibit deficient social interaction, but less is known regarding the emergence of social dysfunction in this model, whether it varies by sex, and whether it is linked to disrupted DA function. To this end, we characterized the ontogeny of social and DA dysfunction in male and female MAM rats during the prepubertal period (postnatal days 33–43) and found sex-specific changes in motivated social behaviors (play, approach) and DA function. Male MAM rats exhibited reduced social approach and increased VTA DA neuron activity compared to saline-treated (SAL) males, whereas female MAM rats exhibited enhanced play behaviors compared to SAL females but no changes in social approach or VTA population activity during this period. These findings demonstrate sex differences in the emergence of social and DA deficits in the MAM model, in which females exhibit delayed emergence. [ABSTRACT FROM AUTHOR]

Loss-of-function mutations in the contactin-associated protein-like 2 (CNTNAP2) gene are causal for neurodevelopmental disorders, including autism, schizophrenia, epilepsy, and intellectual disability. CNTNAP2 encodes CASPR2, a single-pass transmembrane protein that belongs to the neurexin family of cell adhesion molecules. These proteins have a variety of functions in developing neurons, including connecting presynaptic and postsynaptic neurons, and mediating signaling across the synapse. To study the effect of loss of CNTNAP2 function on human cerebral cortex development, and how this contributes to the pathogenesis of neurodevelopmental disorders, we generated human induced pluripotent stem cells from one neurotypical control donor null for full-length CNTNAP2 , modeling cortical development from neurogenesis through to neural network formation in vitro. CNTNAP2 is particularly highly expressed in the first two populations of early-born excitatory cortical neurons, and loss of CNTNAP2 shifted the relative proportions of these two neuronal types. Live imaging of excitatory neuronal growth showed that loss of CNTNAP2 reduced neurite branching and overall neuronal complexity. At the network level, developing cortical excitatory networks null for CNTNAP2 had complex changes in activity compared with isogenic controls: an initial period of relatively reduced activity compared with isogenic controls, followed by a lengthy period of hyperexcitability, and then a further switch to reduced activity. Complete loss of CNTNAP2 contributes to the pathogenesis of neurodevelopmental disorders through complex changes in several aspects of human cerebral cortex excitatory neuron development that culminate in aberrant neural network formation and function. [ABSTRACT FROM AUTHOR]

The toxic heavy metal antimony (Sb) is ubiquitous in our daily lives. Various models have shown that Sb induces neuronal and reproductive toxicity. However, little is known about the developmental toxicity of Sb exposure during gestation and the underlying mechanisms. To study its effects on growth and development, Drosophila stages from eggs to pupae were exposed to different Sb concentrations (0, 0.3, 0.6 and 1.2 mg/mL Sb); RNA sequencing was used to identify the underlying mechanism. The model revealed that prenatal Sb exposure significantly reduced larval body size and weight, the pupation and eclosion rates, and the number of flies at all stages. With 1.2 mg/mL Sb exposure in 3rd instar larvae, 484 genes were upregulated and 694 downregulated compared to controls. Biological analysis showed that the disrupted transcripts were related to the oxidative stress pathway, as verified by reactive oxygen species (ROS) scavenger N -acetylcysteine (NAC) and glutathione (GSH) intervention experiments. Sb exposure induced oxidative stress imbalance could be rectified by chelation and antioxidant effects of NAC/GSH. The Drosophila Schneider 2 (S2) model further demonstrated that NAC and GSH greatly ameliorated cell death induced by Sb exposure. In conclusion, gestational Sb exposure disrupted oxidative stress homeostasis, thereby impairing growth and development. [Display omitted] • A Drosophila model of gestational Sb exposure was performed to investigate effects on development. • Sb exposure reduced larval body size, larval weight, pupation and eclosion rates. • Sb exposure induced genotoxicity related with oxidative stress pathway. • Sb mediated oxidative stress imbalance was rectified by chelation and antioxidant effects of NAC/GSH. [ABSTRACT FROM AUTHOR]

Research indicates the importance of small talk in achieving professional goals and promoting social relationships in workplaces, and yet second-language (L2) users often face challenges in participating in small talk. As such, the need for teaching small talk has been emphasized; however, the understanding of how L2 interactional practices for small talk develop remains limited. This study aims to demonstrate the change in L2 English practices used for initiating and extending small talk that occurred during service encounters over a thirty-month period. The data were gathered from 74 h of audiovisual recordings of service encounters at a small convenience store in Hawai'i. The focal participant is the service provider, a Korean adult with limited L2 English proficiency, who had emigrated from South Korea a year before the start of the data collection. By employing multimodal conversation analysis (CA) and the Pearson's chi - square test , the results of the study demonstrated three aspects of change in the service provider's practices for small talk: increasing the frequency of initiations, emerging new methods for initiation, and developing expansion techniques for small-talk sequences. The study advances the understanding of the development of multimodal L2 interactional practices for small talk in service encounters. • Longitudinal Multimodal conversation analytic study • Interactionally relevant quantification • An L2 English user's developing small talk practices during service encounters • New methods for initiating small talk with customers • Developing expansion techniques for small-talk sequences [ABSTRACT FROM AUTHOR]

In drug development, in-use compatibility studies are crucial steps to ensure that the critical quality attributes of the drug product are maintained when in contact with administration components. But once the drug is in clinical trials, unanticipated variations in these components can stretch limited resources and lengthen timelines to market, as these changes must be assessed and approved to ensure continued patient safety. It's desirable to use a science-based risk evaluation to determine the extent of data and testing needed in these situations, but there is no standard for how such evaluations are done. We have developed an Excel™-based semi-quantitative risk assessment tool to determine whether in-use testing is needed when drug delivery sites or components are changed during a clinical trial. We developed the tool based on our multi-company experience with compatibility studies for many types of drug products targeted for various geographic regions. We have employed the tool as a means to expedite decision-making and, if appropriate, reduce testing in low-risk situations. The tool can save significant time and effort (our estimate is approximately at least 6-9 months off the development cycle) and can minimize pitfalls in clinical administration. While we have designed the tool for our drug products and for use with parenteral dosing regimens, the tool can be adapted for other situations as needed. It will be especially useful for companies with more limited resources. [ABSTRACT FROM AUTHOR]

Human genomic and proteomic data implicate Sushi, von Willebrand factor type A, epidermal growth factor, and pentraxin domain containing 1 (SVEP1) in the pathogenesis of human chronic disease, including cardiovascular disease, glaucoma, and dementia. SVEP1 is critical for vascular development and appears to promote aging, consistent with the antagonistic pleiotropy theory of aging. Many cell types adhere and/or proliferate in response to SVEP1, but the mechanisms underlying its role in development and disease are unclear. SVEP1 is contained within the extracellular matrix and circulates in plasma, making it a priority candidate for disease diagnostics, prognostics, and therapeutics. Sushi, von Willebrand factor type A, EGF, and pentraxin domain containing 1 (SVEP1) is a large extracellular matrix protein that is also detected in circulation. Recent plasma proteomic and genomic studies have revealed a large number of associations between SVEP1 and human traits, particularly chronic disease. These include associations with cardiac death and disease, diabetes, platelet traits, glaucoma, dementia, and aging; many of these are causal. Animal models demonstrate that SVEP1 is critical in vascular development and disease, but its molecular and cellular mechanisms remain poorly defined. Future studies should aim to characterize these mechanisms and determine the diagnostic, prognostic, and therapeutic value of measuring or intervening on this enigmatic protein. [ABSTRACT FROM AUTHOR]

The primary worry of parents/caregivers in relation to fever is the potential for their child to experience a seizure as a result. The literature suggests that parents/caregivers need to be informed about febrile convulsion. Thus, this study sought to develop the 'Febrile Convulsion Knowledge Scale for Parents/Caregivers'. It is a methodological study comprising 984 parents/caregivers who were accessible online between 07/04/2021 and 30/06/2022. After creating the scale item pool's construction, expert opinions were sought to evaluate the scale, and a content validity analysis was conducted. Subsequent analysis included exploratory and confirmatory factor analyses, Cronbach's Alpha, and a test-retest reliability assessment of the scale data. The scale was found to consist of 8 items and 3 factors according to the factor analyses. Exploratory factor analysis indicated that the scale explained 72.783% of the variance. The scale's reliability analysis produced a Cronbach's Alpha score of 0.679, indicating good internal consistency, and it was consistent with test-retest measures (t = −0.660, p = 0.514). It has been determined that the scale is a valid and reliable scale for evaluating the knowledge of parents/caregivers regarding febrile convulsions. It is advisable for pediatric nurses to routinely use the devised scale with families of children who are vulnerable to febrile convulsion and impart instruction based on the findings derived from the scale. • The possibility of a child developing febrile convulsion due to fever concerns parents/caregivers. • Parents'/caregivers' knowledge of febrile convulsion should be evaluated using an objective tool. • The developed scale is a valid and reliable tool for assessing knowledge about febrile convulsion. • The scale's brief 8-item structure makes it a user-friendly and practical tool. [ABSTRACT FROM AUTHOR]