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This article is an attempt to cover the main components of ICTs’-based school management model, with special reference to the respective principles, styles, strategies, competencies, as well as their implementation and application mechanisms. An attempt is made to show how the content and functional characteristics of the mentioned components change during and as a result of the use of ICTs. The use of ICT in schools has become increasingly prevalent, and effective school management requires a comprehensive approach that integrates these tools into all aspects of operations. The article identifies the key components of this model, including communication systems, information management systems, learning management systems, and administrative management systems. The authors explore the benefits and challenges of implementing such a model and provide examples of successful applications. The efficiency of the proposed model is substantiated from the point of view of ensuring the organic connections of its components.

FOXG1 is a critical transcription factor in human brain where loss-of-function mutations cause a severe neurodevelopmental disorder, while increased FOXG1 expression is frequently observed in glioblastoma. FOXG1 is an inhibitor of cell patterning and an activator of cell proliferation in chordate model organisms but different mechanisms have been proposed as to how this occurs. To identify genomic targets of FOXG1 in human neural progenitor cells (NPCs), we engineered a cleavable reporter construct in endogenous FOXG1 and performed chromatin immunoprecipitation (ChIP) sequencing. We also performed deep RNA sequencing of NPCs from two females with loss-of-function mutations in FOXG1 and their healthy biological mothers. Integrative analyses of RNA and ChIP sequencing data showed that cell cycle regulation and BMP repression gene ontology categories were over-represented as FOXG1 targets. Using engineered brain cell lines, we show that FOXG1 specifically activates SMAD7 and represses CDKN1B. Activation of SMAD7 which inhibits BMP signalling may be one way that FOXG1 patterns the forebrain, while repression of cell cycle regulators such as CDKN1B may be one way that FOXG1 expands the neural progenitor cell pool to ensure proper brain size. Our data reveal novel mechanisms on how FOXG1 may control forebrain patterning and cell proliferation in human brain development.

The article generally presents the trends in the introduction and use of information and communication technologies in developed and developing countries. The areas and goals of ICT application are presented, in the context of UNESCO's educational policy, it is shown how the RA education system responds to the changes caused by the introduction and use of ICT in the school administration sector. An attempt is made to show not only the positive but also the negative aspects of information technologies, to distinguish the different levels of ICT implementation in the educational process.

While 1-2% of individuals meet the criteria for a clinical diagnosis of obsessive-compulsive disorder (OCD), many more (∼15-40%) experience subclinical obsessive-compulsive symptoms (OCS) during their life. To characterize the genetic underpinnings of OCS and its genetic relationship to OCD, we conducted the largest genome-wide association study (GWAS) meta-analysis of parent- or self-reported OCS to date (N = 33,943 with complete phenotypic and genome-wide data), combining the results from seven large-scale population-based cohorts from Sweden, the Netherlands, England, and Canada (including six twin cohorts and one cohort of unrelated individuals). We found no genome-wide significant associations on the SNP or gene-level, but a polygenic risk score (PRS) based on the OCD GWAS previously published by the Psychiatric Genetics Consortium (PGC-OCD) was significantly associated with OCS (Pfixed= 3.06 ×10−5). Also, one curated gene set (Mootha Gluconeogenesis) reached Bonferroni-corrected significance (Ngenes= 28, Beta = 0.79, SE = 0.16, Pbon= 0.008). Expression of genes in this set is high at sites of insulin-mediated glucose disposal. Dysregulated insulin signaling in the etiology of OCS has been suggested by a previous study describing a genetic overlap of OCS with insulin signaling-related traits in children and adolescents. We report a SNP heritability of 4.1% (P = 0.0044) in the meta-analyzed GWAS, and heritability estimates based on the twin cohorts of 33% - 43%. Genetic correlation analysis showed that OCS were most strongly associated with OCD (rG= 0.72, p = 0.0007) among all tested psychiatric disorders (N = 11). Of all 97 tested phenotypes, 24 showed a significant genetic correlation with OCS, and 66 traits showed concordant directions of effect with OCS and OCD. OCS have a significant polygenic contribution and share genetic risk with diagnosed OCD, supporting the hypothesis that OCD represents the extreme end of widely distributed OCS in the population.

Summary Mutations in HPRT1, a gene encoding a rate-limiting enzyme for purine salvage, cause Lesch-Nyhan disease which is characterized by self-injury and motor impairments. We leveraged stem cell and genetic engineering technologies to model the disease in isogenic and patient-derived forebrain and midbrain cell types. Dopaminergic progenitor cells deficient in HPRT showed decreased intensity of all developmental cell-fate markers measured. Metabolic analyses revealed significant loss of all purine derivatives, except hypoxanthine, and impaired glycolysis and oxidative phosphorylation. real-time glucose tracing demonstrated increased shunting to the pentose phosphate pathway for de novo purine synthesis at the expense of ATP production. Purine depletion in dopaminergic progenitor cells resulted in loss of RHEB, impairing mTORC1 activation. These data demonstrate dopaminergic-specific effects of purine salvage deficiency and unexpectedly reveal that dopaminergic progenitor cells are programmed to a high-energy state prior to higher energy demands of terminally differentiated cells., Graphical abstract, Highlights • HPRT1 KO reduces cell-fate marker expression in NPCs and neurons • NPCs have a programmed high-energy state compared with cortical NPCs • HPRT1 KO NPCs prioritize de novo purine synthesis over energy production • HPRT1 KO NPCs have reduced levels of RHEB and mTORC1 activation, Ernst and colleagues show neuronal cell-type-specific effects of cell-fate markers and oxidative phosphorylation capacity from HPRT-deficient cells, providing mechanistic insight into the neurological features of Lesch-Nyhan disease.

Kabuki syndrome is frequently caused by loss-of-function mutations in one allele of histone 3 lysine 4 (H3K4) methyltransferase KMT2D and is associated with problems in neurological, immunological and skeletal system development. We generated heterozygous KMT2D knockout and Kabuki patient-derived cell models to investigate the role of reduced dosage of KMT2D in stem cells. We discovered chromosomal locus-specific alterations in gene expression, specifically a 110 Kb region containing Synaptotagmin 3 (SYT3), C-Type Lectin Domain Containing 11A (CLEC11A), Chromosome 19 Open Reading Frame 81 (C19ORF81) and SH3 And Multiple Ankyrin Repeat Domains 1 (SHANK1), suggesting locus-specific targeting of KMT2D. Using whole genome histone methylation mapping, we confirmed locus-specific changes in H3K4 methylation patterning coincident with regional decreases in gene expression in Kabuki cell models. Significantly reduced H3K4 peaks aligned with regions of stem cell maps of H3K27 and H3K4 methylation suggesting KMT2D haploinsufficiency impact bivalent enhancers in stem cells. Preparing the genome for subsequent differentiation cues may be of significant importance for Kabuki-related genes. This work provides a new insight into the mechanism of action of an important gene in bone and brain development and may increase our understanding of a specific function of a human disease-relevant H3K4 methyltransferase family member.

Recent studies have shown that education in the 21st century cannot be imagined without using information and communication technologies, digital and media tools. As a result of teachers’ training, it has become clear that there is a need to promote teachers, ICTs, media education and media literacy. The article presents the informatization of education, which will promote the development of professional abilities and skills of teachers, lecturers, raising public awareness and improving the quality of education.

Making high‐quality dopamine (DA)‐producing cells for basic biological or small molecule screening studies is critical for the development of novel therapeutics for disorders of the ventral midbrain. Currently, many ventral midbrain assays have low signal‐to‐noise ratio due to low levels of cellular DA and the rate‐limiting enzyme of DA synthesis, tyrosine hydroxylase (TH), hampering discovery efforts. Using intensively characterized ventral midbrain cells derived from human skin, which demonstrate calcium pacemaking activity and classical electrophysiological properties, we show that an L‐type calcium agonist can significantly increase TH protein levels and DA content and release. Live calcium imaging suggests that it is the immediate influx of calcium occurring simultaneously in all cells that drives this effect. Genome‐wide expression profiling suggests that L‐type calcium channel stimulation has a significant effect on specific genes related to DA synthesis and affects expression of L‐type calcium receptor subunits from the CACNA1 and CACNA2D families. Together, our findings provide an advance in the ability to increase DA and TH levels to improve the accuracy of disease modeling and small molecule screening for disorders of the ventral midbrain, including Parkinson's disease., Using intensively characterized ventral midbrain cells derived from humans, we show that an L‐type calcium agonist can significantly increase tyrosine hydroxylase protein levels and dopamine release. Genome‐wide expression profiling suggests that L‐type calcium channel stimulation has a significant effect on specific genes related to dopamine synthesis and affects expression of L‐type calcium receptor subunits from the CACNA1 and CACNA2D families.

Stem cell reports 17(3), 475-488 (2022). doi:10.1016/j.stemcr.2022.01.010, Published by Cell Press, Maryland Heights, MO

Purpose/Aim of study: We previously cloned Tlcd3b2 (Tram-Lag1-CLN8 domain 3B2, formerly Fam57b2) from bone fracture repair callus tissue of Cyp24a1 knockout mice and showed that it synthesizes lactosylceramide (LacCer) under allosteric control of the vitamin D metabolite, 24,25-dihydroxyvitamin D3 [24,25(OH)2D3]. Tlcd3b2 was mainly detected in chondrocytes and the 24,25(OH)2D3-TLCD3B2-LacCer signaling cascade was shown to be important for optimal bone fracture repair, suggesting a role for TLCD3B2 in chondrocyte differentiation or maturation. We report the subcellular localization of TLCD3B2 and its effect on chondrocyte differentiation. Materials and Methods: Immunofluorescence detection of epitope-tagged mutants was used to assess localization. ATDC5 chondrogenic cells were transfected with Tlcd3b2 expression vectors to examine effects on chondrocyte differentiation. Results and Conclusions: TLCD3B2 localized to the endoplasmic reticulum, with both the N- and C-termini facing the cytosolic compartment. Chondrogenic ATDC5 cells stably overexpressing Tlcd3b2 showed elevated type 2 (Col2a1) and type 10 (Col10a1) collagen gene expression and increased proteoglycan synthesis, and the effect on Col2a1 was enhanced by treatment with 24,25(OH)2D3. LacCer treatment of ATDC5 cells potentiated Col10a1 expression. Our results show that TLCD3B2 is an ER protein and implicate its expression and enzymatic product in chondrocyte maturation.

Induced Pluripotent Stem Cells (iPSCs) are pluripotent stem cells that can be generated from somatic cells, and provide a way to model the development of neural tissues in vitro. One particularly interesting application of iPSCs is the development of neurons analogous to those found in the human forebrain. Forebrain neurons play a central role in cognition and sensory processing, and deficits in forebrain neuronal activity contributes to a host of conditions, including epilepsy, Alzheimer’s disease, and schizophrenia. Here, we present our protocol for differentiating iPSCs into forebrain neural progenitor cells (NPCs) and neurons, whereby neural rosettes are generated from stem cells without dissociation and NPCs purified from rosettes based on their adhesion, resulting in a more rapid generation of pure NPC cultures. Neural progenitor cells can be maintained as long-term cultures, or differentiated into forebrain neurons. This protocol provides a simplified and fast methodology of generating forebrain NPCs and neurons, and enables researchers to generate effective in vitro models to study forebrain disease and neurodevelopment. This protocol can also be easily adapted to generate other neural lineages.

International audience; We identified individuals with variations in ACTL6B, a component of the chromatin remodeling machinery including the BAF complex. Ten individuals harbored bi-allelic mutations and presented with global developmental delay, epileptic encephalopathy, and spasticity, and ten individuals with de novo heterozygous mutations displayed intellectual disability, ambulation deficits, severe language impairment, hypotonia, Rett-like stereotypies, and minor facial dysmorphisms (wide mouth, diastema, bulbous nose). Nine of these ten unrelated individuals had the identical de novo c.1027G>A (p.Gly343Arg) mutation. Human-derived neurons were generated that recaptured ACTL6B expression patterns in development from progenitor cell to post-mitotic neuron, validating the use of this model. Engineered knock-out of ACTL6B in wild-type human neurons resulted in profound deficits in dendrite development, a result recapitulated in two individuals with different bi-allelic mutations, and reversed on clonal genetic repair or exogenous expression of ACTL6B. Whole-transcriptome analyses and whole-genomic profiling of the BAF complex in wild-type and bi-allelic mutant ACTL6B neural progenitor cells and neurons revealed increased genomic binding of the BAF complex in ACTL6B mutants, with corresponding transcriptional changes in several genes including TPPP and FSCN1, suggesting that altered regulation of some cytoskeletal genes contribute to altered dendrite development. Assessment of bi-alleic and heterozygous ACTL6B mutations on an ACTL6B knock-out human background demonstrated that bi-allelic mutations mimic engineered deletion deficits while heterozygous mutations do not, suggesting that the former are loss of function and the latter are gain of function. These results reveal a role for ACTL6B in neurodevelopment and implicate another component of chromatin remodeling machinery in brain disease.