Developmental Dynamics Research Articles

Ganglionic eminence: volumetric assessment of transient brain structure utilizing fetal magnetic resonance imaging.

To provide quantitative magnetic resonance imaging (MRI) super-resolution-based three-dimensional volumetric reference data on the growth dynamics of the ganglionic eminence (GE) relative to cortical and total fetal brain volumes (TBV). This was a retrospective study of fetuses without structural central nervous system anomalies or other confounding comorbidities that were referred for fetal MRI. Super-resolution reconstructions of 1.5- and 3-Tesla T2-weighted images were generated. Semiautomatic segmentation of TBV and cortical volume and manual segmentation of the GE were performed. Cortical volume, TBV and GE volume were quantified and three-dimensional reconstructions were generated to visualize the developmental dynamics of the GE. Overall, 120 fetuses that underwent 127 MRI scans at a mean gestational age of 27.23 ± 4.81 weeks (range, 20-37 weeks) were included. In the investigated gestational-age range, GE volume ranged from 74.88 to 808.75 mm3 and was at its maximum at 21 gestational weeks, followed by a linear decrease (R2 = 0.559) throughout the late second and third trimesters. A pronounced reduction in GE volume relative to cortical volume and TBV occurred in the late second trimester, with a decline in this reduction observed in the third trimester (R2 = 0.936 and 0.924, respectively). Three-dimensional rendering allowed visualization of a continuous change in the shape and size of the GE throughout the second and third trimesters. Even small compartments of the fetal brain, which are not easily accessible by standardized two-dimensional modalities, can be assessed precisely by super-resolution processed fetal MRI. The inverse growth dynamics of GE volume compared with TBV and cortical volume reflects the transitory nature and physiological involution of this (patho-)physiologically important brain structure. The normal development and involution of the GE is mandatory for normal cortical development. Pathological changes of this transient organ precede impairment of cortical structures, and their detection may allow an earlier diagnosis of such anomalies. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Developmental dynamics of homoarginine, ADMA and SDMA plasma levels from birth to adolescence

Guanidino compounds such as dimethylarginines (SDMA, ADMA) and L-homoarginine ((L-)hArg) can interfere with bioavailability and function of the main NO-donor L-arginine (L-Arg). High ADMA and SDMA but low L-hArg concentrations have been associated with cardio- and cerebrovascular events and mortality in adults. The role of guanidino compounds in paediatric patients remains less clear. We, therefore, compared guanidino compound levels in plasma samples of 57 individuals with chronic kidney disease (CKD) and 141 individuals without CKD from the age of 0 to 17 years, including patients with different comorbidities by correlation and regression analyses. We found highest hArg, SDMA and ADMA concentrations in neonates (Kruskal–Wallis, p < 0.001 for all). From the age of 1 year on, hArg levels increased, whereas SDMA und ADMA levels further decreased in children. SDMA and ADMA are higher in children with CKD independent of GFR (mean factor 1.92 and 1.38, respectively, p < 0.001 for both), and SDMA is strongly correlated with creatinine concentration in children with CKD (Spearman’s rho 0.74, p < 0.001). We provide guanidino compound levels in a large sample covering all paediatric age groups for the first time. Our data can be used to assess the role of guanidino compounds such as hArg in disease states, i.e. cerebro- and cardiovascular disorders in childhood and adolescence.

Patterns and drivers of financial sector growth in the digital age: Insights from a study of industrialized economies

The financial sector in advanced economies has undergone significant evolution driven by restructuring, globalization, and the digital revolution, which have profoundly shaped its developmental dynamics. This study investigates the forces behind the growth and convergence of the financial sector across 13 advanced economies from 2000 to 2015, focusing on the effects of digital transformation. The investigation unveils several noteworthy findings concerning the financial sector. First, most nations experienced substantial growth in value-added, coupled with a significant decrease in employment and robust advancements in labor productivity. Next, the primary drivers of labor productivity growth and convergence across many economies were driven by total factor productivity, labor quality, and digital transformation. Lastly, digital transformation not only directly contributed to the augmentation of labor productivity, as quantified through growth accounting estimation, but also wielded a considerable impact on the expansion of total factor productivity and the streamlining of the workforce.

Constructing a spatiotemporal situational awareness framework to sense the dynamic evolution of online public opinion on social media

PurposeThe paper aims to construct a spatiotemporal situational awareness framework to sense the evolutionary situation of public opinion in social media, thus assisting relevant departments in formulating public opinion control measures for specific time and space contexts.Design/methodology/approachThe spatiotemporal situational awareness framework comprises situational element extraction, situational understanding and situational projection. In situational element extraction, the data on the COVID-19 vaccine, including spatiotemporal tags and text contents, is extracted. In situational understanding, the bidirectional encoder representation from transformers – latent dirichlet allocation (BERT-LDA) and bidirectional encoder representation from transformers – bidirectional long short-term memory (BERT-BiLSTM) are used to discover the topics and emotional labels hidden in opinion texts. In situational projection, the situational evolution characteristics and patterns of online public opinion are uncovered from the perspective of time and space through multiple visualisation techniques.FindingsFrom the temporal perspective, the evolution of online public opinion is closely related to the developmental dynamics of offline events. In comparison, public views and attitudes are more complex and diversified during the outbreak and diffusion periods. From the spatial perspective, the netizens in hotspot areas with higher discussion volume are more rational and prefer to track the whole process of event development, while the ones in coldspot areas with less discussion volume pay more attention to the expression of personal emotions. From the perspective of intertwined spatiotemporal, there are differences in the focus of attention and emotional state of netizens in different regions and time stages, caused by the specific situations they are in.Originality/valueThe situational awareness framework can shed light on the dynamic evolution of online public opinion from a multidimensional perspective, including temporal, spatial and spatiotemporal perspectives. It enables decision-makers to grasp the psychology and behavioural patterns of the public in different regions and time stages and provide targeted public opinion guidance measures and offline event governance strategies.

An enhancer trap system to track developmental dynamics in Marchantia polymorpha.

A combination of streamlined genetics, experimental tractability and relative morphological simplicity compared to vascular plants makes the liverwort Marchantia polymorpha an ideal model system for studying many aspects of plant biology. Here we describe a transformation vector combining a constitutive fluorescent membrane marker with a nuclear marker that is regulated by nearby enhancer elements and use this to produce a library of enhancer trap lines for Marchantia. Screening gemmae from these lines allowed the identification and characterization of novel marker lines, including markers for rhizoids and oil cells. The library allowed the identification of a margin tissue running around the thallus edge, highlighted during thallus development. The expression of this marker is correlated with auxin levels. We generated multiple markers for the meristematic apical notch region, which have different spatial expression patterns, reappear at different times during meristem regeneration following apical notch excision and have varying responses to auxin supplementation or inhibition. This reveals that there are proximodistal substructures within the apical notch that could not be observed otherwise. We employed our markers to study Marchantia sporeling development, observing meristem emergence as defining the protonema-to-prothallus stage transition, and subsequent production of margin tissue during the prothallus stage. Exogenous auxin treatment stalls meristem emergence at the protonema stage but does not inhibit cell division, resulting in callus-like sporelings with many rhizoids, whereas pharmacologically inhibiting auxin synthesis and transport does not prevent meristem emergence. This enhancer trap system presents a useful resource for the community and will contribute to future Marchantia research.

Markers of dental pulp stem cells in in vivo developmental context

Teeth and their associated tissues contain several populations of mesenchymal stem cells, one of which is represented by dental pulp stem cells (DPSCs). These cells have mainly been characterised in vitro and numerous positive and negati ve markers for these cells have been suggested. To investigate the presence and localization of these molecules during development, forming dental pulp was examined using the mouse first mandibular molar as a model. The stages corresponding to postnatal (P) days 0, 7, 14, and 21 were investigated. The expression was monitored using customised PCR Arrays. Additionally, in situ localization of the key trio of markers (Cd73, Cd90, Cd105 coded by genes Nt5e, Thy1, Eng) was performed at prenatal and postnatal stages using immunohistochemistry. The expression panel of 24 genes assigned as in vitro markers of DPSCs or mesenchymal stem cells (MSCs) revealed their developmental dynamics during formation of dental pulp mesenchyme. Among the positive markers, Vcam1, Fgf2, Nes were identified as increasing and Cd44, Cd59b, Mcam, Alcam as decreasing between perinatal vs. postnatal stages towards adulthood. Within the panel of negative DPSC markers, Cd14, Itgb2, Ptprc displayed increased and Cd24a decreased levels at later stages of pulp formation. Within the key trio of markers, Nt5e did not show any significant expression difference within the investigated period. Thy1 displayed a strong decrease between P0 and P7 while Eng increased between these stages. In situ localization of Cd73, Cd90 and Cd105 showed them overlap in differentiated odontoblasts and in the sub-odontoblastic layer that is speculated to host odontoblast progenitors. The highly prevalent expression of particularly Cd73 and Cd90 opens the question of potential multiple functions of these molecules. The results from this study add to the in vitro based knowledge by showing dynamics in the expression of DPSC/MSC markers during dental pulp formation in an in vivo context and thus with respect to the natural environment important for commitment of stem cells.

A Critical Sociocultural Understanding of Evidence-Based Research and Practice Paradigm in Contemporary Psychology.

The paper aims to develop a critical sociocultural understanding on the epistemological and historical analysis of evidence-based (EB) paradigm in contemporary psychological knowledge-production (research) and knowledge-application (practice). It firstly retraces the emergence of EB in medical disciplines, its paradigmatic status, and its subsequent adoption by mainstream psychological sciences. The description of EB historical roots and key concepts leads to the second part, where the paper reflects on key epistemological criticalities scholars have raised toward the EB paradigm. Then, we develop our sociocultural perspective to enrich the epistemological analysis and critique of EB. Specifically, we propose a hermeneutic and interpretative understanding which frames EB as a re-enactment of the positivist scientific research ambition to reach for a complete formalization of biological/psychological phenomena (endo-genetical dynamics), and of new socioeconomic, political, and individual needs posed by contemporary Western societal institutions to scientific knowledge (exo-genetical dynamics). Furthermore, building on such understanding, we suggest that EB works as a contemporary epistemic indicator and threshold, serving two functions: selective filtering and exclusion. Finally, we speculate that EB endo-genetical and exo-genetical developmental dynamics can be interpreted as an expression of the contemporary presentist regime of temporality and as a shift towards the regime of performative techniques instead of context-specific and future-oriented relational competences, also tracing a determining factor that has directed, directs and will continue to direct scientific research in psychology.

Neurobiology of eating behavior, nutrition, and health.

Eating behavior and food-related decision making are among the most complex of the motivated behaviors, and understanding the neurobiology of eating behavior, and its developmental dynamics, is critical to advancing the nutritional sciences and public health. Recent advances from both human and animal studies are revealing that individual capacity to make health-promoting food decisions varies based on biological and physiological variation in the signaling pathways that regulate the homeostatic, hedonic, and executive functions; past developmental exposures and current life-stage; the food environment; and complications of chronic disease that reinforce the obese state. Eating rate drives increased calorie intake and represents an important opportunity to lower rates of food consumption and energy intake through product reformulation. Understanding human eating behaviors and nutrition in the context of neuroscience can strengthen the evidence base from which dietary guidelines are derived and can inform policies, practices, and educational programs in a way that increases the likelihood they are adopted and effective for reducing rates of obesity and other diet-related chronic disease.

Histology, physiology, and transcriptomic and metabolomic profiling reveal the developmental dynamics of annual shoots in tree peonies (Paeonia suffruticosa Andr.).

The development of tree peony annual shoots is characterized by "withering", which is related to whether there are bud points in the leaf axillaries of annual shoots. However, the mechanism of "withering" in tree peony is still unclear. In this study, Paeonia ostii 'Fengdan' and P. suffruticosa 'Luoyanghong' were used to investigate dynamic changes of annual shoots through anatomy, physiology, transcriptome, and metabolome. The results demonstrated that the developmental dynamics of annual shoots of the two cultivars were comparable. The withering degree of P. suffruticosa 'Luoyanghong' was higher than that of P. ostii 'Fengdan', and their upper internodes of annual flowering shoots had a lower degree of lignin deposition, cellulose, C/N ratio, showing no obvious sclerenchyma, than the bottom ones and the whole internodes of vegetative shoot, which resulted in the "withering" of upper internodes. A total of 36 phytohormone metabolites were detected, of which 33 and 31 were detected in P. ostii 'Fengdan' and P. suffruticosa 'Luoyanghong', respectively. In addition, 302 and 240 differentially expressed genes related to lignin biosynthesis, carbon and nitrogen metabolism, plant hormone signal transduction, and zeatin biosynthesis were screened from the two cultivars. Furtherly, 36 structural genes and 40 transcription factors associated with the development of annual shoots were highly co-expressed, and eight hub genes involved in this developmental process were identified. Consequently, this study explained the developmental dynamic on the varied annual shoots through multi-omics, providing a theoretical foundation for germplasm innovation and the mechanized harvesting of tree peony annual shoots.

Now you see it, now you don’t - Cognitive skills and their contributions to mathematics across early development

A broad variety of domain-specific (e.g., non-symbolic magnitude comparison and arithmetic) and domain-general (e.g., spatial skills and inhibition) skills have been identified as precursors to mathematics achievement. However, due to the increasing complexity of mathematics education with age and the associated increase in cognitive demands, it can be assumed that a divergent set of skills is predictive of mathematics achievement at different ages. This cross-sectional study in children aged 3, 5, and 7 years aims at identifying the differential contribution of domain-specific and domain-general contributors to mathematics and delineating their developmental dynamics. Our results reveal a consistent role for non-symbolic magnitude comparison across all age groups, non-symbolic arithmetic starting from the age of 5 years and visuospatial memory only in 5-year-olds. These findings support the notion that mathematics cannot be conceived as a unitary cognitive skill and provide a fine-grained analysis of the cognitive requirements of mathematical skills at different ages. On a more general note, they are in line with the idea that the ANS provides a critical scaffold for the development of mathematical skills but challenge the view that all ANS measures tap into the same underlying process.

MAOA methylation is associated with impulsive and antisocial behaviour: dependence on allelic variation, family environment and diet.

Congenital absence of monoamine oxidase A (MAO-A) activity predisposes to antisocial impulsive behaviour, and the MAOA uVNTR low-expressing genotype (MAOA-L) together with childhood maltreatment is associated with similar phenotypes in males. A possible explanation of how family environment may lead to such behaviour involves DNA methylation. We have assessed MAOA methylation and impulsive/antisocial behaviour in 121 males from the Estonian Children Personality Behaviour and Health Study. Of the 12 CpG sites measured, methylation levels at the locus designated CpG3 were significantly lower in subjects with antisocial behaviour involving police contact. CpG3 methylation was lower in subjects with alcohol use disorder by age 25, but only in MAOA-H genotype. No correlation between MAOA CpG3 methylation levels and adaptive impulsivity was found at age 15, but in MAOA-L genotype a positive correlation appeared by age 18. By age 25, this positive correlation was no longer observed in subjects with better family relationships but had increased further with experience of adversity within the family. MAOA CpG3 methylation had different developmental dynamics in relation to maladaptive impulsivity. At age 18, a positive correlation was observed in MAOA-L genotype with inferior family relationships and a negative correlation was found in MAOA-H with superior home environment; both of these associations had disappeared by age 25. CpG3 methylation was associated with dietary intake of several micronutrients, most notable was a negative correlation with the intake of zinc, but also with calcium, potassium and vitamin E; a positive correlation was found with intake of phosphorus. In conclusion, MAOA CpG3 methylation is related to both maladaptive and adaptive impulsivity in adolescence in MAOA-L males from adverse home environment. By young adulthood, this relationship with maladaptive impulsivity had disappeared but with adaptive impulsivity strengthened. Thus, MAOA CpG3 methylation may serve as a marker for adaptive developmental neuroplasticity in MAOA-L genotype. The mechanisms involved may include dietary factors.

Model eksperymentalnoho neinfektsiinoho avtoimunnoho uveitu, yaka vyiavliaietsia kliuchovymy klinichnymy oznakamy zalezhno vid stupenia tiazhkosty

Introduction. Uveitis primarily affects young individuals and often leads to loss of productivity. Understanding the clinical, immunological, and morphological characteristics of this disease is of utmost importance and should be based on a thorough study of its developmental mechanisms. Therefore, the experimental modeling of uveitis in rabbits plays a significant role in studying its dynamics. There are numerous models of non-infectious autoimmune uveitis (NAU) available. However, previous publications did not address the question of the severity level of experimental NAU based on the type of used model or amount of antigen administered. The aim of the study. To describe the model of experimental NAU exposing key clinical manifestations depending on the severity level. Materials and methods. The study was conducted on 30 “Chinchilla” breed rabbits subdivided into two groups 15 animals each. NAU was induced in both eyes by intravitreal injection of either insoluble (group I) or soluble (group II) sterile horse serum. On the days of animal withdrawal from the experiment (3, 7, 10, 14, and 21), the clinical manifestatioin of NAU was evaluated based on changes in the humidity of the anterior chamber and vitreous body. A quantitative assessment of clinical signs of NAU was conducted in both groups animals under investigation. Results. From day 2, the clinical signs of NAU in two experimental groups demonstrated different degrees of severity of inflammation, with certain differences in the developmental dynamics. Namely, in group I, NAU was characterized by moderate and severe degrees of inflammation, while in group II, it was predominantly mild. In both groups, progress of intraocular inflammation was noted on days 3, 7, and 10, followed by a decrease in this process on the later phases of experiment. In comparison between two groups of rabbits concerning the dynamics of inflammatory clinical manifestations reflected in scores, a statistically significant differences were documented on all days of the experiment (p is less than 0.05). Conclusions. An experimental model of non-infectious autoimmune uveitis is described, which manifests key clinical signs of this disease development depending on its severity level. These observations open a new possibilities for this model prospective use in clinical practice for diagnostic and prognostic purposes, as well as for the development of new protocols for endogenous uveitis effective treatment. Keywords: experimental model, non-infectious autoimmune uveitis, blood serum, quantitative assessment.

Thyroid hormones in development of coloration of two species of Neotropical cichlids.

Neotropical cichlids demonstrate an enormous diversity of pigment patterns, a morphological trait that plays an important role in the adaptation and speciation. It has been suggested that alterations of the activity of the thyroid axis, one of the main endocrine axes regulating fish ontogeny, are involved in the development and diversification of pigment patterns in the Neotropical cichlids. To test this hypothesis, we assessed the thyroid hormone developmental dynamics and pigment patterning, and experimentally induced hyper- and hypothyroidism at different developmental stages in convict cichlid, Amatitlania nigrofasciata, and blue-eye cichlid, Cryptoheros spilurus. We revealed that both species display a similar type of coloration development and similar reactions on changes of the thyroid hormone level, but species-specific differences in hormonal dynamics and thyroid hormone-responsiveness. These findings indicate that thyroid hormone is a necessary but not sufficient signal to induce the transition from larval to juvenile coloration, and is a component of a complex, concerted endocrine cascade that drives skin development.

Developmental dynamics of the single nucleus regulatory landscape of pig hippocampus.

The hippocampus is a brain region associated with memory, learning and spatial navigation, its aging-related dysfunction is a common sign of Alzheimer's disease. Pig is a good model for human neurodegenerative disease, but our understanding of the regulatory program of the pig hippocampus and its cross-species conservation in humans remains limited. Here, we profiled chromatin accessibility in 33,409 high-quality nuclei and gene expression in 8,122 high-quality nuclei of the pig hippocampus at four postnatal stages. We identified 510,908 accessible chromatin regions (ACRs) in 12 major cell types, among which progenitor cells such as neuroblasts and oligodendrocyte progenitor cells showed a dynamic decrease from early to later developmental stages. We revealed significant enrichment of transposable elements in cell type-specific ACRs, particularly in neuroblasts. We identified oligodendrocytes as the most prominent cell type with the greatest number of genes that showed significant changes during the development. We identified ACRs and key transcription factors underlying the trajectory of neurogenesis (such as POU3F3 and EGR1) and oligodendrocyte differentiation (RXRA and FOXO6). We examined 27 Alzheimer's disease-related genes in our data and found that 15 showed cell type-specific activity (TREM2, RIN3 and CLU), and 15 genes displayed age-associated dynamic activity (BIN1, RABEP1 and APOE). We intersected our data with human genome-wide association study results to detect neurological disease-associated cell types. The present study provides a single nucleus-accessible chromatin landscape of the pig hippocampus at different developmental stages and is helpful for the exploration of pigs as a biomedical model in human neurodegenerative diseases.

Institutional Innovation in University-based Experimental Spaces: the Case of Oulu Game Lab

Abstract This article explores preconditions and developmental dynamics of institutional innovation in higher education organizations as an outcome of a collaborative educational initiative – a university-based experimental space. Such collaborative learning configurations are often designed to stimulate local economic development after a downturn in regional industrial landscapes. The experimental space studied here had a twofold mission: providing re-skilling and re-education opportunities for unemployed ICT professionals and equipping them with business and employment bonds with regional game industry companies. To imbue a static outcome of institutional innovation with dynamic features, and to further develop the concept of Triple Helix spaces, we incorporated three sequential forms of institutional work in our analysis: boundary work, distancing work, and anchoring work.

ScTour: a deep learning architecture for robust inference and accurate prediction of cellular dynamics

Despite the continued efforts, a batch-insensitive tool that can both infer and predict the developmental dynamics using single-cell genomics is lacking. Here, I present scTour, a novel deep learning architecture to perform robust inference and accurate prediction of cellular dynamics with minimal influence from batch effects. For inference, scTour simultaneously estimates the developmental pseudotime, delineates the vector field, and maps the transcriptomic latent space under a single, integrated framework. For prediction, scTour precisely reconstructs the underlying dynamics of unseen cellular states or a new independent dataset. scTour’s functionalities are demonstrated in a variety of biological processes from 19 datasets.

P-299 Influence of one carbon metabolism supplements over developmental dynamics and gene expression of genes related to DNA methylation machinery in mice

Abstract Study question Does betaine and the active metabolite 5-MTHF influence cleavage dynamics and expression of genes related to methylation during preimplantation embryos? Summary answer Supplementation of betaine and 5-MTHF had no influence over morphokinetics of mice preimplantation embryos but induced transcriptional variations over methylation activity related-genes. What is known already After fertilization, the emerging genome is reprogrammed to enable the control of cellular differentiation all over downstream events and lead further developmental progression. One of the most determining processes defining these new genomic states in cell daughter is mediated by methylation. S-adenosylmethionine (SAM) is the main donor of methyl groups to DNA and its availability during highly active conditions can be sensitive to external conditions and dependent on one carbon metabolism (OCM). DNA methyltransferases (DNMT1, DNMT3a and DNTM3b) and methionine adenosyltransferase (MAT2a and MAT2b) are influenced by OCM and key components of DNA methylation machinery. Study design, size, duration This is a prospective experimental study conducted from November 2022 to January 2023. F1 hybrid (B6/CBA) fresh mice embryos were exposed to different culture conditions. A primary analysis consisted of the morphokinetics assessment of embryo development through time-lapse system up to expanded blastocyst (105 hours), including a score assessment based on blastocyst appearance. Subsequently functional analysis based on gene expression of selected genes was carried out over individual embryos. Participants/materials, setting, methods The zygotes were collected from the oviduct, washed and culture in KSOM supplemented with 5-MTHF and betaine at respectively concentrations of 50μM and 50μg/mL (THF/bet(50)), 10μM and 10μg/mL (THF/bet(10)) and no supplements for control. Geri incubator was used for culture at 37 °C, 6%CO2 and 5%O2. In a new assay, 4cells and 8cells embryos exposed to THF/bet(50) and control conditions were individually collected for pre-amplification and subsequent RT-qPCR quantification using GADPH as housekeeping gene. Main results and the role of chance A total of 54 mice embryos were used for the present study. The timings required for embryos to reach different developmental stages (t2, t4, t8 and tB) were manually selected and their comparison did not show any overall differences. A slightly faster trend could be observed for the THF/bet(50) group during the 3 first cleavage events (t2, t4 and t8), this group showed proportionally better morphology of blastocysts. Expression analysis showed no variation for DNMT1; by contrast, greatest changes were observed for DNMT3a and DNMT3b whose relative expressions were downregulated at 4 cells ∼0.5 fold-changes (p &amp;lt; 0.01) and highly increased for more than 2 fold-change in 8 cells in THF/bet(50) group. In addition, early downregulation at 4 cells was observed for either MAT2a and MAT2b with ∼0.5 fold-changes (p &amp;lt; 0.01); however, at 8 cells levels were reestablished in both similar levels than control. One carbon metabolism induced changes in gene expression of enzymes involved in de novo methylation of DNA DNMT3a and DNMT3a. In addition, Methyl adenyl transferases MAT2a and MAT2b were also influenced, particularly MAT2a which has a pivotal role relevant for genome activation in the embryo. Limitations, reasons for caution The translational approach is still limited due to known differences between kinetics of mice and human embryo. Intracellular concentration of folates and betaine in embryos are still unknown and the range of dosage used has been decided accordingly to previous studies showing a response in mice embryos under similar conditions. Wider implications of the findings Folate supplements are widely accepted for pregnant and women attempting to become pregnant, these are also recently incorporated in some IVF mediums. The influence of OCM in surrounding environment during highly active methylation activities of early embryo is still unknown, benefits or risks of these supplies require further assessment. Trial registration number not applicable

P-252 A roadmap to normal human embryo development – a timelapse study of embryos resulting in the live birth

Abstract Study question What are the morphokinetic parameters of preimplantation development in normal human embryos? Summary answer We provide a timeline of early developmental events and the incidence of embryo morphological features compatible with childbirth. What is known already Timelapse embryo monitoring provides unique insight into early human development. Implementation of this technique in clinical practice allows for assessing developmental dynamics for improved embryo selection. Several markers and ranking algorithms have been proposed to predict blastulation or implantation outcomes, but only a few studies assessed time-lapse data with live birth as the primary endpoint. Therefore, the comprehensive morphokinetic profile of embryos that gave rise to live birth has not been defined. Study design, size, duration Retrospective observational analysis of 300 time-lapse records of IVF embryos known to develop into healthy newborns. Out of total 73 quantitative/qualitative signs annotated, we focused on 9 developmental events and 14 morphological features and evaluated their timing, duration, and incidence. The influence of potential confounding factors (i.e., egg age, donor egg, donor sperm, sperm quality, and sex of the child) was evaluated by advanced statistical methods. Participants/materials, setting, methods Embryo monitoring was performed by a GERI-timelapse incubator. Image acquisition of individual embryo development lasted 5-6 days, starting 10 minutes after ICSI, which was used as reference time point. Transmitted light images were automatically captured in 5-minute intervals and 7-11 focal planes. The embryo selection for transfer was based solely on its morphology. The annotation data represent the consensus of minimum 3 experienced embryologists. Generalized linear models were used to explore relationships between dataset variables. Main results and the role of chance The average age of female participants was 27.5 years; 71.67% of embryos were derived from young donor eggs without fertility disorders. The severe andrological factor was present in 8% of male patients; donor sperm was used in 23% of cases; 16% of embryos were derived from dysmorphic oocytes. Both sexes were equally represented among analyzed embryos. Our analysis showed that early development was characterized by remarkably short first mitosis (2.68 ± 0.73h) and the interval between the second and third division (t4-t3 = 0.65 ± 0.66h), whereas the third cleavage was less synchronous (t8-t5 = 5.46 ± 4.9h) No association between quantitative signs and confounding factors was found. Interestingly, 2-cell stage embryos often contained multiple nuclei in at least one blastomere (51%), but multinucleation was reduced at the 4-cell stage (8%). Multipolar divisions were absent during zygotic division and rare (2.3%) during the second cleavage. Preterm and partial compaction was observed in 26.6% and 34% of embryos, respectively. Importantly, we noticed that 11.6% of embryos in our dataset deviated from conventional scenario of cleavage dynamics. These “atypical” embryos were characterized by a significantly higher incidence of multipolar divisions during the second cleavage compared to “typical,” regularly dividing embryos. Additionally, the odds of partial compaction increase 10 times in “atypical” embryos. Limitations, reasons for caution The presented analysis only involved embryos confirmed to result in a live birth after transfer. The comparison with data from embryos that did not produce pregnancy was not performed because it would be impossible to discriminate between the role of the embryo and endometrial factors in implantation failure. Wider implications of the findings Human embryos may develop into healthy children despite irregular cell division. A high incidence of partial compaction in “atypical” embryos suggests a self-correction mechanism rescuing their developmental potential. A larger-scale analysis of features compatible with live birth is needed to improve embryo selection criteria for evidence-based decision-making. Trial registration number not applicable

A Variational Synthesis of Evolutionary and Developmental Dynamics.

This paper introduces a variational formulation of natural selection, paying special attention to the nature of 'things' and the way that different 'kinds' of 'things' are individuated from-and influence-each other. We use the Bayesian mechanics of particular partitions to understand how slow phylogenetic processes constrain-and are constrained by-fast, phenotypic processes. The main result is a formulation of adaptive fitness as a path integral of phenotypic fitness. Paths of least action, at the phenotypic and phylogenetic scales, can then be read as inference and learning processes, respectively. In this view, a phenotype actively infers the state of its econiche under a generative model, whose parameters are learned via natural (Bayesian model) selection. The ensuing variational synthesis features some unexpected aspects. Perhaps the most notable is that it is not possible to describe or model a population of conspecifics per se. Rather, it is necessary to consider populations of distinct natural kinds that influence each other. This paper is limited to a description of the mathematical apparatus and accompanying ideas. Subsequent work will use these methods for simulations and numerical analyses-and identify points of contact with related mathematical formulations of evolution.

Special Issue: Understanding the Developmental Dynamics of Mental Health and Offending

Special Issue: Understanding the Developmental Dynamics of Mental Health and Offending