Life Stages Research Articles

Effects of parental care on skin microbial community composition in poison frogs.

Parent-offspring interactions constitute the first contact of many newborns with their environment, priming community assembly of microbes through priority effects. Early exposure to microbes can have lasting influences on the assembly and functionality of the host's microbiota, leaving a life-long imprint on host health and disease. Studies of the role played by parental care in microbial acquisition have primarily focused on humans and hosts with agricultural relevance. Anuran vertebrates offer the opportunity to examine microbial community composition across life stages as a function of parental investment. In this study, we investigate vertical transmission of microbiota during parental care in a poison frog (Family Dendrobatidae), where fathers transport their offspring piggyback-style from terrestrial clutches to aquatic nurseries. We found that substantial bacterial colonization of the embryo begins after hatching from the vitelline envelope, emphasizing its potential role as microbial barrier during early development. Using a laboratory cross-foster experiment, we demonstrated that poison frogs performing tadpole transport serve as a source of skin microbes for tadpoles on their back. To study how transport impacts the microbial skin communities of tadpoles in an ecologically relevant setting, we sampled frogs and tadpoles of sympatric species that do or do not exhibit tadpole transport in their natural habitat. We found more diverse microbial communities associated with tadpoles of transporting species compared to a non-transporting frog. However, we detected no difference in the degree of similarity between adult and tadpole skin microbiotas, based on whether the frog species exhibits transporting behavior or not. Using a field experiment, we confirmed that tadpole transport can result in the persistent colonization of tadpoles by isolated microbial taxa associated with the caregiver's skin, albeit often at low prevalence. This is the first study to describe vertical transmission of skin microbes in anuran amphibians, showing that offspring transport may serve as a mechanism for transmission of parental skin microbes. Overall, these findings provide a foundation for further research on how vertical transmission in this order impacts host-associated microbiota and physiology.

Sexual dimorphism at different life stages: early life sexual differences in root growth in Silene latifolia.

Male and female dioecious plants often show sexual dimorphism, differing in morphological, physiological and life-history traits. Most previous studies have focused on differences between males and females during or after reproduction, paying little attention to the pre-reproductive stages of the individuals. Here we assessed the response of male and female individuals of the dioecious plant Silene latifolia to abiotic stress at different life stages, including pre-reproductive (i.e. seedlings and young plants) and reproductive individuals. We measured growth, resource allocation and discrimination against 13C under nutrient deficiency, water stress, as well as their interaction. We observed sexual dimorphism in root growth, with female seedlings having longer main roots than male plants. Pre-reproductive male and female plants also responded differently, in terms of root allocation, to nutrient and water availability. At reproduction, females grew more roots than males when water was not limiting. These differences could help explain the female-skewed sex ratios found in natural populations of S. latifolia. We found no evidence of sexual dimorphism in aboveground dry mass, although females had longer leaves than males at the seedling stage. We conclude that sexual dimorphism in S. latifolia may occur not as a consequence of reproduction, but well before it.

An adaptive acceleration scheme for phase-field fatigue computations

Abstract Phase-field models of fatigue are capable of reproducing the main phenomenology of fatigue behavior. However, phase-field computations in the high-cycle fatigue regime are prohibitively expensive due to the need to resolve spatially the small length scale inherent to phase-field models and temporally the loading history for several millions of cycles. As a remedy, we propose a fully adaptive acceleration scheme based on the cycle jump technique, where the cycle-by-cycle resolution of an appropriately determined number of cycles is skipped while predicting the local system evolution during the jump. The novelty of our approach is a cycle-jump criterion to determine the appropriate cycle-jump size based on a target increment of a global variable which monitors the advancement of fatigue. We propose the definition and meaning of this variable for three general stages of the fatigue life. In comparison to existing acceleration techniques, our approach needs no parameters and bounds for the cycle-jump size, and it works independently of the material, specimen or loading conditions. Since one of the monitoring variables is the fatigue crack length, we introduce an accurate, flexible and efficient method for its computation, which overcomes the issues of conventional crack tip tracking algorithms and enables the consideration of several cracks evolving at the same time. The performance of the proposed acceleration scheme is demonstrated with representative numerical examples, which show a speedup reaching up to four orders of magnitude in the high-cycle fatigue regime with consistently high accuracy. Graphical abstract

Embryonic and larval development of black jewfish, Protonibea diacanthus: A new candidate for aquaculture in northern Australia

Black jewfish Protonibea diacanthus is a large, commercially important fish distributed across the tropical Indo-Pacific. In Australia, there is an established commercial wild fishery for the species but it’s aquaculture potential has not been investigated. This research presents hatchery production of native P. diacanthus in Darwin, Australia and documents ontogeny of early life stages of this species over three trial runs. Wild P. diacanthus were induced to spawn with luteinizing hormone-releasing hormone analog (LHRHa) and eggs were released approximately 25–28 h after injection (0.88 ± 0.01 mm in diameter with oil globule 0.24 ± 0.01 mm). Larvae hatched 12 h after spawning. At one day post hatch (dph) larvae were 2.68 ± 0.01 mm standard length with 0.15 ± 0.01 mm oil globule diameter. Larvae mouths opened at 31 h post hatch (hph) and first feeding was seen at 57 hph. Swim bladder inflation (92 %) occurred between 40 and 62 hph. Larvae were progressively fed rotifers, Artemia and Otohime microdiet, and metamorphosis occurred between 20 and 25 dph, completing as they reached over 13 mm standard length. Tail biting cannibalism began with the onset of metamorphosis and caused significant mortality until approximately 24 dph when metamorphosed juveniles could be handled and moved to low stocking density systems. This study demonstrates that northern Australian P. diacanthus is amenable to hatchery production and provides important foundational knowledge for this emerging aquaculture species.

Racial diversities in lifespan bone mass: findings from the China BCL study and US NHANES.

Bone mass at different life stages is instrumental for developing effective, long-term osteoporosis prevention strategies. We aimed to investigate the developmental patterns of bone mass across the entire lifespan among the Chinese population and to compare these patterns with those of different racial groups, including Whites, Blacks, and Mexicans in the US population. Our study analyzed data from the China Body Composition Life-course (BCL, 2013-2023) Study and the US National Health and Nutrition Examination Survey (NHANES, 2005-2018). We measured bone mineral content (BMC) and density (BMD) using dual-energy x-ray absorptiometry (DXA) at various anatomical sites, including the whole-body, lumbar spine, total hip, and femoral neck. In the Chinese population, whole-body BMC and BMD increased rapidly during childhood and adolescence, with males and females achieving approximately 90.6% and 95.7% of their respective peak bone mass. Peak bone mass for whole-body, total hip, and femoral neck BMC/BMD occurred generally between the ages of 21 and 30, whereas the lumbar spine BMD peak did approximately a decade later. After reaching the peak, a gradual bone loss was observed from ages 30 to 40, with an acceleration post age 40, especially in females. Comparative analyses indicated that Chinese individuals exhibited the lowest bone mass levels and accrual rates over their lifespan, followed successively by Whites, Mexicans, and Blacks. By exploring bone mass changes and racial disparities among the Chinese and US populations, this study emphasizes the need for establishing sex- and ethnic- specific public health strategies to prioritize bone health throughout the entire life course.

A Shift in Approach to Addressing Public Health Inequities and the Effect of Societal Structural and Systemic Drivers on Social Determinants of Health.

Social determinants of health (SDOH) are the conditions in which people are born, grow, live, work, and age that influence health outcomes, and structural and systemic drivers of health (SSD) are the social, cultural, political, and economic contexts that create and shape SDOH. With the integration of constructs from previous examples, we propose an SSD model that broadens the contextual effect of these driving forces or factors rooted in the Centers for Disease Control and Prevention's SDOH framework. Our SSD model (1) presents systems and structures as multidimensional, (2) considers 10 dimensions as discrete and intersectional, and (3) acknowledges health-related effects over time at different life stages and across generations. We also present an application of this SSD model to the housing domain and describe how SSD affect SDOH through multiple mechanisms that may lead to unequal resources, opportunities, and consequences contributing to a disproportionate burden of disease, illness, and death in the US population. Our enhanced SDOH framework offers an innovative and promising model for multidimensional, collaborative public health approaches toward achieving health equity and eliminating health disparities.

Development of label-free light-controlled gene expression technologies using mid-IR and terahertz light.

Gene expression is a fundamental process that regulates diverse biological activities across all life stages. Given its vital role, there is an urgent need to develop innovative methodologies to effectively control gene expression. Light-controlled gene expression is considered a favorable approach because of its ability to provide precise spatiotemporal control. However, current light-controlled technologies rely on photosensitive molecular tags, making their practical use challenging. In this study, we review current technologies for light-controlled gene expression and propose the development of label-free light-controlled technologies using mid-infrared (mid-IR) and terahertz light.

Future semiochemical control of codling moth, Cydia pomonella

Codling moth (CM), Cydia pomonella, is a significant pest of apple (Malus domestica) and other orchard crops worldwide, posing challenges due to the decrease in registered insecticides, rising resistance, and a changing climate. The pest exhibits a strong resistance capacity to both synthetic and natural insecticides, while shifting seasonal temperatures disrupt the reliability of phenology-temperature models for predicting targeted control strategies. Alternative control strategies are necessary to future-proof control of this pest. Current control methods primarily rely on chemical insecticide sprays or granulosis virus applications during egg hatching. This review focuses explicitly on semiochemical-based manipulation of CM adults and larvae for control in orchards. Topics covered include the role of semiochemicals in integrated pest management, area-wide control, mating disruption, female attractants, larval kairomones, and incorporation into monitoring and control strategies. The potential of CM repellents in a push–pull strategy is also discussed. Primary sources for identifying relevant literature included GoogleScholar and ResearchGate, with a focus on papers published since 2013 but also include relevant papers from 2003. Nine review papers and 119 papers were reviewed. The review emphasizes that effective control necessitates an area-wide approach targeting all life stages (eggs, larvae, pupae, and adults). Comprehensive monitoring is crucial for identifying CM “hot-spots” and enhancing targeted interventions. Growers must consider landscape context when designing control programs. Lastly, recommendations are provided for future research and CM management strategies. There are opportunities to explore and exploit female kairomone attractants and repellents in control strategies and modify monitoring traps to be more attractive and autonomous.

Differential fatty acids utilization across life stages in a Vespa species.

Dietary fatty acids (FAs) are essential macronutrients affecting animal fitness, growth, and development. While the degree of saturation of FAs usually determines the level of absorption and allocation within the body, the utilization of dietary FAs across the life stages of individuals remains unknown. We used three different 13C labeled FAs, with a different saturation level (linoleic acid (18:2), oleic acid (18:1), and palmitic acid (16:0)), to investigate the absorption and allocation of dietary FAs across the life stages of the Oriental hornet. Our results show that only larvae utilized all tested FAs as metabolic fuel, with palmitic acid being oxidized at the highest rate. Oleic and palmitic acids were predominantly incorporated into larval tissues, while oleic acid dominated pupal tissues. In contrast, linoleic and oleic acids were predominantly incorporated into adult tissues. These findings highlight a life stage-dependent shift in certain FAs utilization, with palmitic acid mostly utilized in early stages and linoleic acid in adulthood, while oleic acid remained consistently utilized across all life stages. This study emphasizes the importance of considering FA saturation and life stage dynamics in understanding FA utilization patterns.

Gender inequality in time allocation across life stages: a comparative study in a Latin American country

ABSTRACT The study analyzes gender differences in time use in the Latin American context, from a comparative perspective (2010–2019) and across life stages. Particularly, the study presents evidence on the likelihood of women and men spending time on three types of activities: Household work, paid work activities, and personal activities. Logistic regression was applied using data from time use surveys conducted in Peru in 2010 and 2019. The results suggests that women were much more likely to spend additional time on household work, while men were more likely to spend additional time on paid work and personal activities. However, these differences became less pronounced in 2019. In terms of age groups, a U-shaped and an inverted U-shaped pattern were found for paid work activities and household chores respectively. In both cases, the largest gender gap was found in the 30–39 age group, possibly related to motherhood. The originality of the research lies in providing a comprehensive analysis of gender inequality in time use in a developing country that has one of the highest rates of female labor force participation in the region, and is also characterized by a patriarchal structure in which machismo and marianismo influence time distribution.

Self-creation of Older People in the Perspective of Developing Wisdom and Adaptation to Changing Roles in the Family and Society

Old age is a stage of life during which a person must confront the changes that occur both in the reality around them and in themself. Those are changes at the biological, psychological and social levels. Adapting to old age and the roles it brings becomes a difficult and demanding task. One of the most important developmental tasks of an elderly person is developing wisdom that can support and facilitate the process of adaptation to old age. Entering the period of late adulthood is therefore a special opportunity for further development and self-creative action of the individual leading to the creation of a mature identity of an old person. The aim of this text is to provide insight into the meaning and manifestations of this self-creative involvement, with particular emphasis on its importance in the process of adaptation to changing roles in old age and building wisdom.

Embracing uncertainty post-COVID-19 crisis: insights from young people

This article explores the long-term impact of the COVID-19 pandemic on everyday life through a qualitative research study focusing on the role of age in managing uncertainty. Grounded in a cultural and symbolic perspective on risk, the study examines how rituals, emotions, and cultural contexts shaped the experiences of individuals aged 15–34 in Milan, Italy, as they navigated daily risks. Drawing on 42 semi-structured interviews conducted between September 2022 and May 2023, the findings reveal that age significantly influenced how young people navigated post-pandemic uncertainties. The youngest participants often felt fear and anxiety, mainly due to concerns for others’ well-being, coupled with a strong need for social interaction and community. In contrast, slightly older young professionals showed a more complex emotional response characterised by caution, frustration, and empathy. Across all age groups in the sample, daily routines and social interactions kept reinforcing societal norms and hierarchies, particularly concerning generations and family dynamics within Italian culture, with a specific emphasis on vulnerable populations, namely older adults. These findings highlight the importance of considering both life stage and cultural context when analysing responses to uncertainty. Still, they underscore young people’s adaptability as both a reactive process and a forward-looking one involving agency. This flexibility was particularly evident in the context of the COVID-19 pandemic in the Lombardy region of Italy, where the virus spread earlier and with more severe consequences than in most parts of the Western world.

Understanding Ixodes ricinus occurrence in private yards: influence of yard and landscape features

BackgroundLyme borreliosis is the most frequent zoonotic disease in the northern hemisphere and is transmitted by ticks of the genus Ixodes. Although many people are bitten by ticks in private yards, our understanding of the factors associated with their presence in these areas remains limited. To address this gap, we used a citizen science approach to identify the local and landscape features associated with tick presence in yards.MethodsThis study was conducted near Nancy, a city in northeastern France, from 2020 to 2022. Citizen scientists collected ticks in their yard on a single event (n = 185) and measured 13 yard features. Additionally, we computed 11 features related to the landscape composition and spatial configuration surrounding these yards. Using generalized linear mixed models, we determined the yard and landscape features associated with the presence of ticks and nymphal Ixodes ricinus (hereafter nymphs), the life stage, and species that mostly bite humans.ResultsDespite a low density, ticks were found in 32% of the yards, including yards in urbanized areas. At the transect level, the likelihood of finding a nymph was nearly three times higher in transects shaded by vegetation compared to those in open areas, with no relationship between nymph occurrence and transect location or grass height. At the yard level, the occurrence of ticks and nymphs was related to both yard and landscape characteristics. Nymph and tick occurrence were more than twice as high in yards with signs of deer and a wood/brush pile compared to those without these characteristics, and increased with the connectivity of vegetation areas and the percentage of forest areas in the landscape.ConclusionsOur study reveals that private yards across an urbanization gradient are locations of tick exposure with tick presence linked to both yard and landscape factors. These findings emphasize the importance of public awareness regarding tick exposure in yards and provide crucial insights for future public health prevention campaigns.

Matching clinical and genetic data in pediatric patients at risk of developing cystic kidney disease.

Cystic kidney disease is a heterogeneous group of hereditary and non-hereditary pathologic conditions, associated with the development of renal cysts. These conditions may be present both in children and adults. Cysts can even be observed already during the prenatal age, and pediatric patients with cysts need to be clinically monitored. An early clinical and genetic diagnosis is therefore mandatory for optimal patient management. The aim of this study was to perform genetic analyses in patients with echographic evidence of kidney cysts to provide an early molecular diagnosis. A cohort of 70 pediatric patients was enrolled and clinically studied at the time of first recruitment and at follow-up. Genetic testing by clinical exome sequencing was performed and a panel of genes responsible for "cystic kidneys" was analyzed to identify causative variants. Sanger validation and segregation studies were exploited for the final classification of the variants and accurate genetic counseling. Data showed that 53/70 of pediatric patients referred with a clinical suspicion of cystic kidney disease presented a causative genetic variant. In a significant proportion of the cohort (24/70), evidence of hyper-echogenic/cystic kidneys was already present in the prenatal period, even in the absence of a positive family history. This study suggests that cystic kidney disease may develop since the very early stages of life and that screening programs based on ultrasound scans and genetic testing play a critical role in diagnosis, allowing for better clinical management and tailored genetic counseling to the family.

Utilisation of macroalgal habitats by juvenile rabbitfishes on an inshore reef

AbstractMacroalgal beds are increasingly recognised as nursery habitats for coral reef fish; however, the extent to which they are used as a source of food and/or a refuge from predation remains largely unexplored. Here, we investigate the distribution, feeding behaviour, diet, and predation risk for juvenile rabbitfish in macroalgal habitats on Orpheus Island, Great Barrier Reef. Visual surveys revealed that juvenile and adult Siganus doliatus had different among-habitat distributions with juveniles being largely restricted to the reef flat and positively associated with macroalgal cover, while adults were abundant on the reef crest. Focal feeding observations show that within macroalgal habitats, juvenile S. doliatus targeted epiphytes on Sargassum (80% of bites), with relatively few bites taken on turfs or the Sargassum itself (27% and 8%, respectively). These observations were supported by stomach content analyses with filamentous algae being the dominant item in the stomach content of both small (< 4 cm total length, TL; 58%) and large juvenile S. doliatus (> 4 cm TL; 47%). The stomach content of juvenile S. doliatus, S. canaliculatus, and S. spinus collected from macroalgal habitats was similar, consisting primarily of filamentous algae and detritus. We found no relationship between the abundance of potential predators and juvenile rabbitfishes across the study sites. Collectively, our results suggest that juvenile rabbitfishes are using macroalgal habitats on this, and potentially other, inshore reefs as a food source and add to a growing body of literature highlighting the importance of these habitats for the early life stages of reef fish.

The identity of Centrodinium elongatum, type species of the dinoflagellate genus Centrodinium (Dinophyceae), and a review on the synonymy of allied species.

The planktonic dinoflagellate genus Centrodinium has been understudied, with the type species C. elongatum remaining undocumented since the original description. Here, we report C. elongatum isolated from Mazatlán, Mexican Pacific. In the chains, the posterior daughter cell with an incomplete apical horn shows the morphology of C. elongatum, while the anterior daughter cell with complete epitheca corresponds to C. pulchrum. For the first time, a species of Centrodinium sensu stricto (highly laterally flattened species with horns) was cultured. An unarmored life stage, known as Murrayella ovalis, derived from the spheroplast after ecdysis. In the rDNA molecular phylogenies, C. elongatum (=C. pulchrum) nested as basal to morphologically similar species (C. eminens and C. intermedium) and as a sister group of a former Murrayella species, C. punctatum. C. elongatum differs from C. eminens and C. intermedium in the chain formation, second apical (2') plate not being divided, horns with coarse poroid ornamentation, and missing prominent distal spinules. The taxonomy of Centrodinium sensu stricto is revised, with a discussion in the identities of C. complanatum, C. eminens, and C. maximum. The name C. deflexum is restored as a senior synonym of C. intermedium and C. ovale.

Comparative metagenomic study unveils new insights on bacterial communities in two pine-feeding Ips beetles (Coleoptera: Curculionidae: Scolytinae).

Climate change has recently boosted the severity and frequency of pine bark beetle attacks. The bacterial community associated with these beetles acts as "hidden players," enhancing their ability to infest and thrive on defense-rich pine trees. There is limited understanding of the environmental acquisition of these hidden players and their life stage-specific association with different pine-feeding bark beetles. There is inadequate knowledge on novel bacterial introduction to pine trees after the beetle infestation. Hence, we conducted the first comparative bacterial metabarcoding study revealing the bacterial communities in the pine trees before and after beetle feeding and in different life stages of two dominant pine-feeding bark beetles, namely Ips sexdentatus and Ips acuminatus. We also evaluated the bacterial association between wild and lab-bred beetles to measure the deviation due to inhabiting a controlled environment. Significant differences in bacterial amplicon sequence variance (ASVs) abundance existed among different life stages within and between the pine beetles. However, Pseudomonas, Serratia, Pseudoxanthomonas, Taibaiella, and Acinetobacter served as core bacteria. Interestingly, I. sexdentatus larvae correspond to significantly higher bacterial diversity and community richness and evenness compared to other developmental stages, while I. acuminatus adults displayed higher bacterial richness with no significant variation in the diversity and evenness between the life stages. Both wild and lab-bred I. sexdentatus beetles showed a prevalence of the bacterial family Pseudomonadaceae. In addition, wild I. sexdentatus showed dominance of Yersiniaceae, whereas Erwiniaceae was abundant in lab-bred beetles. Alternatively, Acidobacteriaceae, Corynebacteriaceae, and Microbacteriaceae were highly abundant bacterial families in lab-bred, whereas Chitinophagaceae and Microbacteriaceae were highly abundant in wild I. accuminatus. We validated the relative abundances of selected bacterial taxa estimated by metagenomic sequencing with quantitative PCR. Our study sheds new insights into bacterial associations in pine beetles under the influence of various drivers such as environment, host, and life stages. We documented that lab-breeding considerably influences beetle bacterial community assembly. Furthermore, beetle feeding alters bacteriome at the microhabitat level. Nevertheless, our study revisited pine-feeding bark beetle symbiosis under the influence of different drivers and revealed intriguing insight into bacterial community assembly, facilitating future functional studies.

Habitat area more consistently affects seagrass faunal communities than fragmentation per se

AbstractSeminal ecological theories, island biogeography and the single large or several small (SLOSS) reserve debate, examine whether large contiguous habitats conserve biodiversity better than multiple smaller patches. Today, delineating the ecological effects of habitat area versus configuration in a fragmentation context remains difficult, and often confounds efforts to understand proximate and ultimate drivers of community change in response to habitat alteration. We examined how the major components of fragmentation, habitat division versus area loss, independently influence faunal communities using landscapes constructed from artificial seagrass at scales relevant for juvenile estuarine nekton. We deployed 25 unique, 234‐m2 landscapes designed along orthogonal axes: habitat percent cover (i.e., area) and fragmentation per se (i.e., patchiness) to examine their effects on faunal density, community composition, and probability of bait‐assay consumption. Faunal sampling occurred in both artificial seagrass and interspaced sandflat matrix. We also examined whether larval‐settler density drove faunal density patterns across landscapes. Further, we assessed the relative importance of landscape‐scale parameters versus fine‐scale complexity–canopy height and epiphyte biomass–in determining faunal densities. We most consistently observed increasing epibenthic fish and macroinvertebrate density with increasing seagrass percent cover. Fragmentation per se only negatively affected epibenthic faunal density within the matrix at low seagrass coverage. Bait consumption increased with seagrass cover, suggesting larger habitats are relative foraging hotspots. Alternatively, benthopelagic fish density was unaffected by habitat parameters, reflecting lower seagrass reliance, or increased matrix tolerance. Community compositions did not vary across landscapes, suggesting that abundant species used landscapes indiscriminately. Finally, the relative importance of habitat parameters shifted across faunal guilds and life stages. Landscape percent cover most affected epibenthic faunal density, but not benthopelagic fish density, and neither pattern was related to settler density. Further, only fine‐scale complexity influenced settler densities. Collectively, our results indicate habitat area is a primary, positive driver of faunal densities and generalist consumption, and therefore should be prioritized in seagrass conservation. However, sampling across spatial scales and habitat types revealed nuances in habitat use patterns among faunal guilds and life stages that were not solely area‐dependent, illustrating that a variety of landscape configurations support essential nursery functions.

A Novel Loss of Function Variant in HCN1 Gene Underlies Early Infantile Epileptic Encephalopathy 24 [EIEE24]

Background: Early infantile epileptic encephalopathy (EIEE) is a rare neurological condition characterized by frequent seizures in the early stages of life, resulting in severely impaired cognitive and motor development. Although the specific causes of EIEE remain unknown, one of the primary causes is gene pathogenicity (even in the absence of consanguinity). Hyperpolarization-activated cyclic nucleotide-gated channels (HCNs) are essential for proper brain function. They are regulated by multiple genes, and mutations in these genes induce channel malfunction, which can result in various severe conditions, including EIEE. Herein, we have reported a patient presenting hallmarks of EIEE. Methods: The patient underwent clinical, radiographic, and genetic analysis. A thorough clinical examination and molecular study were conducted utilizing whole exome sequencing and Sanger sequencing. Results: Whole exome sequencing of the proband revealed a novel de novo nonsynonymous/nonsense variant (c.1468A>T; (p.Lys490Ter) in exon 6 of the HCN1 gene. This variant may cause channel dysfunction via nonsynonymous/nonsense-mediated decay or aberrant protein, which may be associated with EIEE phenotypes. Conclusions: This evidence backs the idea that HCN1 has a vital role in brain development and lose of function can cause a range of debilitating conditions. Still, the functional characterization study of the HCN1 variants will be the fundamental tool for a better understanding of EIEE in the near future.

A tiered toxicity testing strategy for assessing early life stage toxicity in estuarine fish (Mugilogobius chulae): A case study on tris (1-chloro-2-propyl) phosphate ester

The estuarine ecological environment faces significant threats from contaminants of emerging concern (CECs); yet, the risk posed by CECs to resident organisms remains poorly understood. Here, we employed tiered toxicity testing to investigate the adverse effects and potential mechanisms of tris (1-chloro-2-propyl) phosphate (TCPP) on the early life stages of an estuarine fish, Mugilogobius chulae. TCPP affected the development of M. chulae embryos, including survival, morphology, hatching, and behavior. A concentration-dependent transcriptomic analysis showed that TCPP disrupted 12 neurodevelopment-related KEGG pathways in M. chulae embryos, with five of the 30 % top-ranked pathways related to neurotransmitter signaling. Besides the cholinergic synapse signaling pathway, the glutamatergic signaling pathway (including NMDAR and AMPAR subtypes) may also mediate TCPP-induced neurodevelopmental toxicity. The NMDAR subtype GRIN2B was downregulated at high concentrations. Molecular dynamics simulations revealed a strong interaction between TCPP and GRIN2B, with TCPP binding to the residues Ile153 and Ile188. The results suggest that NMDARs play a crucial role in TCPP-induced neurodevelopmental toxicity toward M. chulae. AOP network analysis predicted that TCPP may impact cognitive functions and memory. Our study provides a novel testing strategy for identifying the mechanisms of toxicity of CECs, a crucial component of ecological risk assessment.