Developmental System Research Articles

Research and Development of Next Generation Zebrafish Developmental Toxicity Screening System

Research and Development of Next Generation Zebrafish Developmental Toxicity Screening System

Review Curriculum Evaluation of Physical Education Specialty Under the Perspective of Teacher Training Certification

The purpose of this study was to summarize the main body, content, method and application effects of physical education curriculum evaluation, to understand the current situation of physical education curriculum evaluation in China, and to construct an evaluation index system based on teacher training professional certification. The Chinese and English databases were searched by systematic evaluation, and the retrieval time was from December 31, 2018. The research literature that met the standard were included, and qualitative analysis was conducted by subject analysis method. A total of 100 studies were included, most of which summarized the concept, content and subject of physical education curriculum evaluation in different historical backgrounds. It has the following characteristics: The main body of evaluation is diversified, but it is still dominated by teachers' and administrative departments' top-down evaluation. The content of evaluation is diversified, but the homogenization is serious, and the essential problem of course evaluation is not explained enough yet. Evaluation methods are diversified, but there are few methods combining information technology and cross-boundary evaluation. Based on the three core concepts of teachers' professional certification, the evaluation standard is established. With the student-oriented concept, establish the evaluation subject, content, method and means; Taking output orientation as the concept, integrate various methods or means to improve the quality of teaching and student training; Build a developmental evaluation system and promote the continuous improvement of physical education curriculum system.

Research on Key Performance Indicators of PPP Projects in Area Development

This paper uses the literature analysis method to complete the preliminary selection of performance indicators and introduces individual indicators of area development PPP projects based on the research of traditional PPP project performance evaluation. This resulted in 29 indicators .After the second-order confirmatory factor analysis of the theoretical model, 28 key performance indicators were finally determined. From this, the developmental PPP project performance evaluation key performance indicator system was constructed, which is a comprehensive developmental PPP project. Process dynamic performance management provides a reliable reference basis.

Experience of cases with inhaled nitric oxide and therapeutic hypothermia.

Neonates with hypoxic-ischemic encephalopathy (HIE) on therapeutic hypothermia (TH) therapy may show persistent pulmonary hypertension of the newborn (PPHN). In Japan, the reported mortality rate is lower than in the US, possibly due to treatment differences of newborns with moderate to severe HIE and PPHN. This study aimed to determine the feasibility and long-term outcomes of inhaled nitric oxide (iNO) and TH therapy in newborns with moderate to severe HIE and PPHN. This was a retrospective review of neonates with moderate to severe HIE that were treated with TH from 2008 to 2017 at a large medical center in Japan. We documented their long-term neurological prognosis, measuring their developmental and Gross Motor Function Classification System level at 18 months old. A total of 37 neonates with moderate to severe HIE underwent TH therapy and six of them were started with iNO therapy for PPHN. iNO with TH was safely administered to all six newborns with moderate to severe HIE with PPHN. In two neonates TH was discontinued because of intraventricular hemorrhage (IVH) and severe hypotension. Neurological outcomes were similar in newborns who were treated with iNO and TH and those who were treated with TH alone. These initial findings suggest that monitoring hematological and cardiovascular status is important with iNO for severe asphyxia in infants with PPHN. Safer and more feasible protocols are needed for when iNO and TH therapy are administered together.

Micromere formation and its evolutionary implications in the sea urchin.

The micromeres of the sea urchin embryo are distinct from other blastomeres. After they arise through an asymmetric cell division at the 8- to 16-cell stage, micromeres immediately function as organizers. They also commit themselves to specific cell fates such as larval skeletogenic cells and primordial germ cells, while other blastomeres remain plastic and uncommitted at the 16-cell stage. In the phylum Echinodermata, only the sea urchin (class Echinoidea) embryo forms micromeres that serve as apparent organizers during early embryogenesis. Therefore, it is considered that micromeres are the derived features and that modification(s) of the developmental system allowed evolutionary introduction of this unique cell lineage. In this chapter, we summarize the both historic and recent observations that demonstrate unique properties of micromeres and discuss how this lineage of micromeres may have arisen during echinoderm evolution.

Developmental System Drift in One Tooth Facilitates the Adaptation of the Other

Developmental System Drift in One Tooth Facilitates the Adaptation of the Other

Analysis of Aflatoxins in South Carolina Farm’s Corn, Peanut, Wheat, Soybean, and Cottonseed

The mold Aspergillus grows on several raw food commodities and produces highly toxic compounds known as aflatoxins. These compounds can cause developmental and immune system suppression, cancer, and death if ingested. The aim of this study was to determine the aflatoxin levels in various crops obtained from farms in South Carolina, USA. Aflatoxin levels were measured using the Vicam Virtu Reader and High-Performance Liquid Chromatography (HPLC). The Vicam Virtu Reader utilized five grams of corn and peanuts blended and placed into an extraction tube containing 25 ml of 70% methanol. The sample mixture was placed on the AlfaV test strip for readings. For use of the HPLC, the samples were analyzed by isocratic using 60:20:20 water/methanol/acetonitrile mixture as the mobile phase. Results from the Vicam Virtu Reader indicated corn samples and peanut samples had aflatoxin levels below 25 ppb established by the USDA. When the HPLC analysis was done on soybean, wheat, and cottonseed, all results were below 25 ppb as well. A food safety survey was administered to 190 farmers to ascertain their familiarity with aflatoxins. Sixteen percent (16%) reported they heard about it. In conclusion, storage conditions of the crops can affect the level of aflatoxins. The Vicam Virtu Reader is a fast method to identify aflatoxin levels in crops. The HPLC has the advantage of separating aflatoxins into subgroups even at low levels. The aflatoxin levels were low and safe for export and consumption.

Uncovering the cell fate decision in lysis-lysogeny transition and stem cell development via Markov state modeling.

Understanding the behavior of a complex gene regulatory network is a fundamental but challenging task in systems biology. How to reduce the large number of degrees of freedom of a specific network and identify its main biological pathway is the key issue. In this paper, we utilized the transition path theory (TPT) and Markov state modeling (MSM) framework to numerically study two typical cell fate decision processes: the lysis-lysogeny transition and stem cell development. The application of TPT to the lysis-lysogeny decision-making system reveals that the competitions of CI and Cro dimer binding play the major role in determining the cell fates. We also quantified the transition rates from the lysogeny to lysis state under different conditions. The overall computational results are consistent with biological intuitions but with more detailed information. For the stem cell developmental system, we applied the MSM to reduce the original dynamics to a moderate-size Markov chain. Further spectral analysis showed that the reduced system exhibits nine metastable states, which correspond to the refinement of the five known typical cell types in development. We further investigated the dominant transition pathways corresponding to the cell differentiation, reprogramming, and trans-differentiation. A similar approach can be applied to study other biological systems.

Promicanje međusektorske suradnje u modelu rane intervencije

Cross-sectoral cooperation is a complex process involving different systems with their complexities and separate protocols through partnership, sharing responsibilities and benefits. In the developmental system model of early intervention, cross-sectoral coopera- tion implies the connection between the health care system, social welfare and the educational system. In the Republic of Croatia, this type of cooperation has not come to life at the level that would be necessary for the entire system to function adequately. This is why families of children with neurodevelopmental risk and developmental difficulties are often left to fend for themselves and seek support and therapy. Objective: The aim of this paper is to present a model of connecting the health institution, the paediatrician of the health center and the experts of the social care institution that provides early intervention services (EI), and to examine whether this cooperation ac- celerates family involvement in EI support and services. Methods: The collaboration was conducted through secure virtual communication, with paediatricians directing families of chil- dren with a certain deviation from typical development to a social institution, the EI provider, where experts conducted triage by team development assessment. Results: 27 children and their families were included and it was shown that the mentioned cooperation led to the acceleration of obtaining support for the family in an average of 72 days. It also turned out that there was an indirect acceleration of administrative procedures in exercising the right to EI service in 13 days. Conclusion: The results show a positive effect of cross-sectoral cooperation and networking through a system of information ex- change through secured technologies.

Sex-specific chromatin remodelling safeguards transcription in germ cells.

Stability of the epigenetic landscape underpins maintenance of the cell-type-specific transcriptional profile. As one of the main repressive epigenetic systems, DNA methylation has been shown to be important for long-term gene silencing; its loss leads to ectopic and aberrant transcription in differentiated cells and cancer1. The developing mouse germ line endures global changes in DNA methylation in the absence of widespread transcriptional activation. Here, using an ultra-low-input native chromatin immunoprecipitation approach, we show that following DNA demethylation the gonadal primordial germ cells undergo remodelling of repressive histone modifications, resulting in a sex-specific signature in mice. We further demonstrate that Polycomb has a central role in transcriptional control in the newly hypomethylated germline genome as the genetic loss of Ezh2 leads to aberrant transcriptional activation, retrotransposon derepression and dramatic loss of developing female germ cells. This sex-specific effect of Ezh2 deletion is explained by the distinct landscape of repressive modifications observed in male and female germ cells. Overall, our study provides insight into the dynamic interplay between repressive chromatin modifications in the context of a developmental reprogramming system.

Integration of embryo–endosperm interaction into a holistic and dynamic picture of seed development using a rice mutant with notched-belly kernels

Interaction between the embryo and endosperm affects seed development, an essential process in yield formation in crops such as rice. Signals that mediate communication between embryo and endosperm are largely unknown. We used the notched-belly (NB) mutant with impaired communication between embryo and endosperm to investigate the effect of the embryo on developmental staging of the endosperm and signaling pathways in the embryo that regulate endosperm development. Hierachical clustering of mRNA datasets from embryo and endosperm samples collected during development in NB and a wild type showed a delaying effect of the embryo on the developmental transition of the endosperm by extension of the middle stage. K-means clustering further identified coexpression modules of gene sets specific to embryo and endosperm development. Combined gene expression and biochemical analysis showed that T6P–SnRK1, gibberellin and auxin signaling by the embryo regulate endosperm developmental transition. We propose a new seed developmental staging system for rice and identify the most detailed signature of rice grain formation to date. These will direct genetic strategies for rice yield improvement.

Developmental instability in domesticated mammals.

Measures of fluctuating asymmetry (FA) have been adopted widely as an estimate of developmental instability. Arising from various sources of stress, developmental instability is associated with an organism's capacity to maintain fitness. The process of domestication has been framed as an environmental stress with human-specified parameters, suggesting that FA may manifest to a larger degree among domesticates compared to their wild relatives. This study used three-dimensional geometric morphometric landmark data to (a) quantify the amount of FA in the cranium of six domestic mammal species and their wild relatives and, (b) provide novel assessment of the commonalities and differences across domestic/wild pairs concerning the extent to which random variation arising from the developmental system assimilates into within-population variation. The majority of domestic mammals showed greater disparity for asymmetric shape, however, only two forms (Pig, Dog) showed significantly higher disparity as well as a higher degree of asymmetry compared to their wild counterparts (Wild Boar, Wolf). Contra to predictions, most domestic and wild forms did not show a statistically significant correspondence between symmetric shape variation and FA, however, a moderate correlation value was recorded for most pairs (r-partial least squares >0.5). Within pairs, domestic and wild forms showed similar correlation magnitudes for the relationship between the asymmetric and symmetric components. In domesticates, new variation may therefore retain a general, conserved pattern in the gross structuring of the cranium, whilst also being a source for response to selection on specific features.

Developmental titanium dioxide nanoparticle exposure induces oxidative stress and neurobehavioral changes in zebrafish.

The widespread commercial application of titanium dioxide nanoparticles (TiO2 NPs) leads to ubiquitous presence of TiO2 NPs in the aquatic environment, which highlights the necessity to determine their potential adverse effects on aquatic organisms. The developing nerve system is particularly susceptible to environment perturbation. However, few studies have explored the developmental neurobehavioral toxicity of TiO2 NPs, especially at smaller particle size ranges (≤20nm) that have relatively longer retention time in the water column. In this study, zebrafish embryos were exposed to non-teratogenic concentrations of 0.1 and 1mg/L TiO2 NPs (average size of 14-20nm) from 8 to 108h post-fertilization (hpf) followed by various assessments at different time points up to 12 days post-fertilization (dpf). Our findings revealed that 1mg/L TiO2 NPs perturbed the motor and social behaviors in larval zebrafish. These behavioral changes were characterized by decreased swimming speed in a locomotor response test at 5dpf, increased travel distance in a flash stimulus test at 5dpf, increased preference to the light zone in a light/dark preference test at 10dpf, and increased mirror attack and percent time spent in the mirror zone in a mirror stimulus response assay at 12dpf. Mechanistic examinations at 5dpf revealed elevated cell apoptosis and oxidative stress. Cell apoptosis was characterized by increased acridine orange (AO) positive cells in the olfactory region and neuromasts of the lateral line system. Oxidative stress was characterized by increased lipid peroxidation, increased ROS production, and upregulated catalase (cat) gene expression. In addition, TiO2 NP exposure also upregulated genes associated with the developmental nervous system such as the growth associated protein 43 (gap43) and proliferating cell nuclear antigen (pcna). Our results suggest that the neurobehavioral changes in larvae exposed to 1mg/L TiO2 NPs during early development may result from cell apoptosis and oxidative stress induced neuronal damages.

Perinatal exposure to the thyroperoxidase inhibitors methimazole and amitrole perturbs thyroid hormone system signaling and alters motor activity in rat offspring

Disruption of the thyroid hormone system during development can impair brain development and cause irreversible damage. Some thyroid hormone system disruptors act by inhibiting the thyroperoxidase (TPO) enzyme, which is key to thyroid hormone synthesis. For the potent TPO-inhibiting drug propylthiouracil (PTU) this has been shown to result in thyroid hormone system disruption and altered brain development in animal studies. However, an outstanding question is which chemicals beside PTU can cause similar effects on brain development and to what degree thyroid hormone insufficiency must be induced to be able to measure adverse effects in rats and their offspring. To start answering these questions, we performed a perinatal exposure study in pregnant rats with two TPO-inhibitors: the drug methimazole (MMI) and the triazole herbicide amitrole. The study involved maternal exposure from gestational day 7 through to postnatal day 22, to MMI (8 and 16 mg/kg body weight/day) or amitrole (25 and 50 mg/kg body weight/day). Both MMI and amitrole reduced serum T4 concentrations in a dose-dependent manner in dams and offspring, with a strong activation of the hypothalamic-pituitary-thyroid axis. This reduction in serum T4 led to decreased thyroid hormone-mediated gene expression in the offspring’s brains and caused adverse effects on brain function, seen as hyperactivity and decreased habituation in preweaning pups. These dose-dependent effects induced by MMI and amitrole are largely the same as those observed with PTU. This demonstrates that potent TPO-inhibitors can induce effects on brain development in rats and that these effects are driven by T4 deficiency. This knowledge will aid the identification of TPO-inhibiting thyroid hormone system disruptors in a regulatory context and can serve as a starting point in search of more sensitive markers of developmental thyroid hormone system disruption.

Human retinal organoids release extracellular vesicles that regulate gene expression in target human retinal progenitor cells

The mechanisms underlying retinal development have not been completely elucidated. Extracellular vesicles (EVs) are novel essential mediators of cell-to-cell communication with emerging roles in developmental processes. Nevertheless, the identification of EVs in human retinal tissue, characterization of their cargo, and analysis of their potential role in retina development has not been accomplished. Three-dimensional retinal tissue derived from human induced pluripotent stem cells (hiPSC) provide an ideal developmental system to achieve this goal. Here we report that hiPSC-derived retinal organoids release exosomes and microvesicles with small noncoding RNA cargo. EV miRNA cargo-predicted targetome correlates with Gene Ontology (GO) pathways involved in mechanisms of retinogenesis relevant to specific developmental stages corresponding to hallmarks of native human retina development. Furthermore, uptake of EVs by human retinal progenitor cells leads to changes in gene expression correlated with EV miRNA cargo predicted gene targets, and mechanisms involved in retinal development, ganglion cell and photoreceptor differentiation and function.

Programmed Cell Death Not as Sledgehammer but as Chisel: Apoptosis in Normal and Abnormal Craniofacial Patterning and Development.

Coordination of craniofacial development involves an complex, intricate, genetically controlled and tightly regulated spatiotemporal series of reciprocal inductive and responsive interactions among the embryonic cephalic epithelia (both endodermal and ectodermal) and the cephalic mesenchyme — particularly the cranial neural crest (CNC). The coordinated regulation of these interactions is critical both ontogenetically and evolutionarily, and the clinical importance and mechanistic sensitivity to perturbation of this developmental system is reflected by the fact that one-third of all human congenital malformations affect the head and face. Here, we focus on one element of this elaborate process, apoptotic cell death, and its role in normal and abnormal craniofacial development. We highlight four themes in the temporospatial elaboration of craniofacial apoptosis during development, namely its occurrence at (1) positions of epithelial-epithelial apposition, (2) within intra-epithelial morphogenesis, (3) during epithelial compartmentalization, and (4) with CNC metameric organization. Using the genetic perturbation of Satb2, Pbx1/2, Fgf8, and Foxg1 as exemplars, we examine the role of apoptosis in the elaboration of jaw modules, the evolution and elaboration of the lambdoidal junction, the developmental integration at the mandibular arch hinge, and the control of upper jaw identity, patterning and development. Lastly, we posit that apoptosis uniquely acts during craniofacial development to control patterning cues emanating from core organizing centres.

The role of external factors in realizing of the natural progress of the child’s motor development within the first year of life

Introduction. The development of a child in the first year of life provides the basis for their further harmonious growth. Motor development occurs in parallel with the ongoing gradual development of the nervous system. The transition to a new motor milestone is associated with the emergence of new skills; therefore, stimulation of motor development should occur in accordance with the next milestone of the nervous system development. Intervention in the natural process of the skills gaining without considering the developmental nervous system milestone leads to a change in the trajectory of motor progress of the child. Aim of the study was to assess the significance of individual elements of motor development for the function of balance and walking, as well as to identify the role of non-physiologic (contradicting motor ontogenesis) stimulation of motor skills in the evolvement of non-optimal motor patterns and impaired balance and walking function. Materials and methods. In total, 43 children aged ≥ 12 months admitted to the «Consultative Diagnostic Department» of the Federal State Autonomous Institution «National Medical Research Center for Children’s Health» of the Ministry of Health of Russia were examined within the framework of dispensary observation in the period from December 2016 to June 2019. The assessment of motor development was carried out according to the tests and questionnaires developed. The children were divided into two groups: the treatment group, in which the intervention was carried out, and the control group. Results. The frequency of realization of physiological patterns in children in the treatment group was 65.5%, and in the control group was 89.6%. The occurrence of the functional disorders of the musculoskeletal system was as follows: pathological functional kyphosis in the lumbar spine in children in the treatment group occurred in 73.1%, and in the control group in 26.9%; sitting on the sacrum occurred in 73.1% in the treatment group, and 26.9 % in the control group; impaired coordination in the treatment group occurred in 53.9%, and in 46.1% in the control group; decreased balance function in the treatment group occurred in 61.5%, and in 38.5% in the control group. Conclusion. Correct interaction with a child in the first year of life, in combination with physiological stimulation corresponding to the developmental milestones of the nervous system, allows the child to implement their motor skills in a timely manner, without disrupting the natural sequence of motor development, and minimizes the risks of functional disorders of the musculoskeletal system.

Ideology and Civilizational Identity in Russia’s State-Approved World-History Textbooks

ABSTRACT This article examines how recent world history is interpreted in Russia’s latest state-approved textbooks, particularly what kind of ideological and civilizational leanings the interpretations reflect. Discourse analysis reveals that the textbooks broadly accept the superiority of the capitalist developmental model and liberal-democratic political system, all within a Western-centric, if not pro-Western, paradigm based on modernization theory; only in the context of recent geopolitical conflicts is the West portrayed in an adversarial light. These findings suggest that liberal and Western-centric thinking continues to influence sections of Russia’s political and intellectual elites as well as the country’s post-Soviet generation.

Treatment and Survival of Malignant Extracranial Germ Cell Tumours in the Paediatric Population: A Systematic Review and Meta-Analysis.

Simple SummaryGerm cell tumours are a heterogeneous group of neoplasms and are predominantly midline tumours occurring from birth to late adulthood. Suboptimal outcomes remain for several groups of patients, including adolescents, and patients with extragonadal tumours, high tumour markers at diagnosis or platinum-resistant disease. The aim of our systematic review was to explore survival rates internationally over the past two decades in order to better define future practice and treatment strategies and also to define specific subgroups with inferior outcomes. The results of our systematic review describe the heterogeneous nature of germ cell tumours in different anatomical locations, impacting on stage at presentation, treatment modalities used and survival data. Despite this heterogeneity, subpopulations can be defined which have an inferior survival and where future research and more individualised treatment would help to improve survival. Objective: This systematic review and meta-analysis was performed to explore overall survival (OS) and event free survival (EFS) rates internationally over the past two decades and to define specific subgroups with inferior outcomes which may demand different treatment strategies. Methods: The search focused on malignant extracranial germ cell tumours (GCTs) in the paediatric population. The initial database search identified 12,556 articles; 32 articles were finally included in this review, comprising a total of 5095 patients. Results: The studies were heterogeneous, varying from single institution reports to large prospective trials. Older studies, describing eras where non-platinum-based chemotherapy regimens were used, showed clearly worse outcomes. Survival for stage I–II gonadal disease is excellent. On the other hand, patients with an initial alpha-fetoprotein (AFP) > 10,000 ng/mL or kU/L, age > 11 years and stage IV disease confer a survival disadvantage. For testicular disease in particular, lymphovascular invasion and certain histopathological subtypes, such as embryonal carcinoma (EC) and mixed malignant GCTs, survival is poorer. Survival data for sacrococcygeal and mediastinal GCTs show a heterogeneous distribution across studies in this review, independent of year of publication. Patients > 12 years presenting with a mediastinal GCT pose a subpopulation which fares worse than GCTs in other locations or age groups. This is independent of AFP levels, stage of disease or treatment protocol, and these patients may demand a different treatment strategy. Conclusions: This review describes the heterogeneous nature of GCTs in different anatomical locations, impacting on stage at presentation, treatment modalities used and survival data. Despite this heterogeneity, in line with the current developmental biology-based classification system, subpopulations can be defined which have an inferior EFS and OS and where future research and more individualised treatment would help to improve survival.

Learning Chinese Mandarin characters in an English-speaking country: The development of a child’s symbolic mind

This qualitative research explores the development of the symbolic mind in children through learning Chinese Mandarin characters. Navigated through the lens of relational developmental system metatheory and guided by Vygotsky’s sociocultural theory, findings present the analysis of the developmental processes in children’s recognition of symbols and use of known symbols to make and share meaning. This study also offers an explanation of the effect of changes in the sociocultural environment on children's symbolic development. Further, cultural differences toward symbolic representation are discussed with the recommendation of focusing on recognition followed by writing when learning Chinese Mandarin characters.