Model Of Human Development Research Articles

From circuits to lifespan: translating mouse and human timelines with neuroimaging based tractography.

Animal models are commonly used to investigate developmental processes and disease risk, but humans and model systems (e.g., mice) differ substantially in the pace of development and aging. The timeline of human developmental circuits is well known, butit is unclear how such timelines compare to those in mice. We lack age alignments across the lifespan of mice and humans. Here, we build upon our Translating Time resource, which is a tool that equates corresponding ages during development. We collected 1,125 observations from age-related changes in body, bone, dental, and brain processes to equate corresponding ages across humans, mice, and rats to boost power for comparison across humans and mice. We acquired high-resolution diffusion MR scans of mouse brains (n=16) of either sex at sequential stages of postnatal development (postnatal day 3, 4, 12, 21, 60) to track brain circuit maturation (e.g., olfactory association, transcallosal pathways). We found heterogeneity in white matter pathway growth. Corpus callosum growth largely ceases days after birth while the olfactory association pathway grows through P60. We found that a P3-4 mouse equates to a human at roughly GW24, and a P60 mouse equates to a human in teenage years. Therefore, white matter pathway maturation is extended in mice as it is in humans, but there are species-specific adaptations. For example, olfactory-related wiring is protracted in mice, which is linked to their reliance on olfaction. Our findings underscore the importance of translational tools to map common and species-specific biological processes from model systems to humans.Significance statement Mice are essential models of human brain development, but we currently lack precise age alignments across their lifespan. Here, we equate corresponding ages across mice and humans. We utilize high-resolution diffusion mouse brain scans to track the growth of brain white matter pathways, and we use our cross-species age alignments to map the timeline of these growth patterns from mouse to humans. In mice, olfactory association pathway growth continues well into the equivalent of human teenage years. The protracted development of olfactory association pathways in mice aligns with their specialized sense of smell. The generation of translational tools bridges the gap between animal models and human biology while enhancing our understanding of developmental processes generating variation across species.

BARRIERS AND FACILITATORS TO SOCIAL PARTICIPATION WHEN AGING WITH A LONG-TERM DISABILITY: A SCOPING STUDY

Abstract Introduction Supporting the social participation of individuals aging with a long-term neurological disability contributes to active and healthy aging. However, knowledge about factors influencing the social participation of this population remains scarce. Objectives Integrate knowledge regarding the barriers and facilitators to social participation for people aging with a long-term neurological disability. Methods A scoping review following the Joanna Briggs Institute guidelines was conducted across four databases (MEDLINE, CINAHL, PsycInfo, and EMBASE). Analysis relied on the Human Development Model - Disability Creation Process (HDM-DCP). This study is reported according to the PRISMA extension for scoping review (PRISMA-ScR). Results Eighteen articles (8 quantitatives and 10 qualitatives) representing 1,319 participants and eight neurological conditions (e.g., stroke, multiple sclerosis, traumatic brain injury, spinal cord injury, aphasia, post-polio, spina bifida, and cerebral palsy) were included. Participants’ average age ranged from 53.4 to 72 years and the average time since their disability ranged from 5 to 46.26 years. A total of 26 barriers and 42 facilitators to social participation were identified. The most recurrent barriers were associated with the organic system (e.g., presence of comorbidities) and the societal environment (e.g., transportation accessibility). The most frequent facilitators included identity factors (e.g., acceptance of one’s condition) and the community environment (e.g., available social participation opportunities). Conclusion This study lays the groundwork for developing interventions aimed at promoting active and fulfilling aging among older adults with long-term disabilities. Supporting social participation for this population should involve harnessing individual strengths and environmental resources as well as eliminating environmental systematic barriers.

Timely TGFβ signalling inhibition induces notochord

The formation of the vertebrate body involves the coordinated production of trunk tissues from progenitors located in the posterior of the embryo. Although in vitro models using pluripotent stem cells replicate aspects of this process1, 2, 3, 4, 5, 6, 7, 8, 9–10, they lack crucial components, most notably the notochord—a defining feature of chordates that patterns surrounding tissues11. Consequently, cell types dependent on notochord signals are absent from current models of human trunk formation. Here we performed single-cell transcriptomic analysis of chick embryos to map molecularly distinct progenitor populations and their spatial organization. Guided by this map, we investigated how differentiating human pluripotent stem cells develop a stereotypical spatial organization of trunk cell types. We found that YAP inactivation in conjunction with FGF-mediated MAPK signalling facilitated WNT pathway activation and induced expression of TBXT (also known as BRA). In addition, timely inhibition of WNT-induced NODAL and BMP signalling regulated the proportions of different tissue types, including notochordal cells. This enabled us to create a three-dimensional model of human trunk development that undergoes morphogenetic movements, producing elongated structures with a notochord and ventral neural and mesodermal tissues. Our findings provide insights into the mechanisms underlying vertebrate notochord formation and establish a more comprehensive in vitro model of human trunk development. This paves the way for future studies of tissue patterning in a physiologically relevant environment.

Emerging models of human and non-human primate placental development - Centre for Trophoblast Research 17th annual meeting 2024.

The 17th annual meeting of the Centre for Trophoblast Research (CTR) took place at the University of Cambridge, UK, on 1-2 July 2024. This year's meeting provided an opportunity to reflect on the significant advancements made recently in modelling the human placenta in vitro. The meeting featured 12 invited speakers and attracted 260 participants from 25 countries. Many of the speakers were leading figures who have developed methods to derive human trophoblast stem cells or organoids from first trimester and term placentas, and from pluripotent stem cells. Accompanying the invited presentations were flash talks selected from the abstract submissions and poster presentations. The meeting concluded with a stimulating panel discussion to evaluate the current human trophoblast models. This Meeting Review aims to capture the spirit of the event and highlight the key themes and take-home messages that emerged.

Complementary and additive functions of TRα and TRβ during intestinal remodeling as revealed by ChIP-Seq analysis on wild type and TR knockout animals

Intestinal structure is drastically changed from fetal to adult form during postembryonic development, a period around birth in mammals. This process is regulated by thyroid hormone (T3) via its receptors, T3 receptor (TR) α and TRβ during anuran metamorphosis. Here, we used intestinal remodeling during Xenopus tropicalis metamorphosis, which serves as a model for human postembryonic development, to identify TR-bound genes and determine the relative contribution to target gene binding by TRα and TRβ. We first examined the localization of TRα and TRβ mRNA during metamorphosis in Xenopus tropicalis and found that TRα was broadly expressed in the intestinal tissues from premetamorphosis to the end of metamorphosis, while TRβ was expressed at low levels during premetamorphosis but was upregulated at the climax of metamorphosis when intestinal stem cells are formed and proliferate. Interestingly, both TR genes were co-expressed in different cell types, including stem cells. Chromatin immunoprecipitation (ChIP)-seq analyses of the intestine from wild type, TRα- or TRβ-knockout premetamorphic tadpoles treated with or without T3 for 18 h identified many TR-bound genes and revealed the effects of individual TR knockout on the binding of target genes by TR. We found that individual TR knockout reduced both the number of TR-bound genes and the extent of TR binding to target genes with TRα knockout had a much more dramatic effect than TRβ knockout. On the other hand, the TR-bound genes were largely common among the three genotypes. These findings suggest that both TRα and TRβ contribute to target binding with TRα having a bigger contribution in premetamorphic intestine.

Deep learning-based models for preimplantation mouse and human embryos based on single-cell RNA sequencing

The rapid growth of single-cell transcriptomic technology has produced an increasing number of datasets for both embryonic development and in vitro pluripotent stem cell-derived models. This avalanche of data surrounding pluripotency and the process of lineage specification has meant it has become increasingly difficult to define specific cell types or states in vivo, and compare these with in vitro differentiation. Here we utilize a set of deep learning tools to integrate and classify multiple datasets. This allows the definition of both mouse and human embryo cell types, lineages and states, thereby maximizing the information one can garner from these precious experimental resources. Our approaches are built on recent initiatives for large-scale human organ atlases, but here we focus on material that is difficult to obtain and process, spanning early mouse and human development. Using publicly available data for these stages, we test different deep learning approaches and develop a model to classify cell types in an unbiased fashion at the same time as defining the set of genes used by the model to identify lineages, cell types and states. We used our models trained on in vivo development to classify pluripotent stem cell models for both mouse and human development, showcasing the importance of this resource as a dynamic reference for early embryogenesis.

Addressing the Sense of School Belonging Among All Students? A Systematic Literature Review.

The sense of school belonging plays an important role in students' academic, behavioural, and psychological outcomes. Based on a systematic review, following the PRISMA 2020 guidelines and examining 86 studies conducted between 1990 and February 2023, the article addresses two research questions: (a) what are the predictors of the sense of school belonging at the individual, micro, meso, exo, macro, and chrono levels of the bioecological model of human development; (b) do these predictors differ based on students' individual characteristics, and if so, how. The findings reveal individual factors as important predictors of school belonging and indicate the lack of studies that take into consideration the interplay of different (micro, meso, exo, macro, chrono) levels in addressing the sense of school belonging. Considering the complexity and multi-factorial nature of the sense of school belonging, it calls upon further research, which would support the development of evidence-based interventions for fostering school belonging among different groups of students, particularly those who are at risk of feeling alienated from school, and thus promote equity in education.

Exposure to the antiretroviral drug dolutegravir impairs structure and neurogenesis in a forebrain organoid model of human embryonic cortical development.

For many therapeutic drugs, including antiretroviral drugs used to treat people living with HIV-1 (PLWH), we have little data on the potential effects on the developing human brain due to limited access to tissue and historical constraints on the inclusion of pregnant populations in clinical trials. Human induced pluripotent stem cells (iPSCs) offer a new avenue to gain insight on how drugs may impact human cell types representative of the developing central nervous system. To prevent vertical transmission of HIV and promote the health of pregnant PLWH, antiretroviral therapy must be initiated and/or maintained throughout pregnancy. However, many antiretroviral drugs are approved for widespread use following clinical testing only in non-pregnant populations and there may be limited information on potential teratogenicity until pregnancy outcomes are evaluated. The integrase strand transfer inhibitor dolutegravir (DTG) is a frontline antiretroviral drug that is effective in viral suppression of HIV but was previously reported to be associated with a slight increase in the risk for neural tube defects in one study, although this has not been replicated in other cohorts. To directly investigate the potential impact of DTG on human cortical neurogenesis, we measured the effects of daily drug exposure on the early stages of corticogenesis in a human iPSC-based forebrain organoid model. We quantified organoid size and structure and analyzed gene and protein expression to evaluate the impact of several doses of DTG on organoid development. We observed deficits in organoid structure and impaired neurogenesis in DTG-treated organoids compared to vehicle-treated control organoids after 20 or 40 days in culture. Our highest dose of DTG (10 μM) resulted in significantly smaller organoids with a reduced density of neural rosette structures compared to vehicle-treated controls. Mechanistically, RNA-sequencing and immunohistological analysis suggests dysregulated amino acid transport and activation of the integrated stress response in the DTG-treated organoids, and functionally, a small molecule integrated stress response inhibitor (ISRIB) could partially rescue increased expression of proteins related to cell cycle regulation. Together, these results illustrate the potential for human iPSC-based strategies to reveal biological processes during neurogenesis that may be affected by therapeutic drugs and provide complementary data in relevant human cell types to augment preclinical investigations of drug safety during pregnancy.

Pet Ownership and Family Involvement in Sports and Other Activities

ABSTRACT The impact that companion animals may have on adolescent engagement in sports and other activities is currently unclear. This study included participant data gathered from the Adolescent Brain Cognitive Development (ABCD) Study®, a longitudinal study of brain development and youth health outcomes in the United States (n = 8,489). This study aimed to clarify the extent to which companion animal type impacts family involvement in sports and other activities. Additionally, it is framed within the bioecological model of human development, which provides a useful framework for human–animal interaction researchers going forward. This study utilized multiple logistic and linear regressions in answering the research questions posed. The results indicate that, when adjusting for context- and person-level covariates, there does not appear to be a meaningful relationship between companion animal type and family involvement in sports and other activities, physical activity, or screen time. This study serves as a guidepost for human–animal interaction researchers as to the importance of including contextual variables in their studies before making claims regarding the impact of companion animals on youth, especially when details about the companion animal relationship are unavailable.

Human Capital Management Development and Environment Policy Model on The Performance of State Civil Apparatus in Riau Province Government

This study aims to develop a conceptual framework for Competence-based Human Capital Management (HCM) and Religiosity to the Performance of the State Civil Apparatus (ASN) in the Riau Provincial Government. This study is to find the most appropriate way to develop ASN competence and fill in the limitations of previous research and gaps in competency research on ASN performance. This study uses a quantitative approach by distributing questionnaires to officials related to the development of ASN competencies, both Structural Officials ranging from Middle High Officials, Primary High Officials, Administrator, and Supervisory Officers, as well as Functional Officers related to competency development, as many as 114 respondents with using a purposive sampling approach, data collection techniques using a questionnaire with a scale of 1-5, which then uses Structural Equation Modeling-Partial Least Square (PLS) analysis with the outer Model, and inner model and processed using the SmartPLS 3. Capital Management and Supported by Religiosity. This study examines the development of competence based on Human Capital Management and Religiosity as a moderator of ASN performance. This research has never been conducted simultaneously.

Synthetic Human Embryos, Embryo Models and Embryo-like Structures in Islam

ABSTRACT A major breakthrough in developmental biology is the ex vivo generation of synthetic human embryos from stem cells. A comprehensive, in-depth bioethical analysis from a Sunni Islamic perspective reveals that the reproductive applications of synthetic human embryos contravene Islamic precepts of preserving lineage integrity (Hifz al-Nasl) due to disruption and confusion of kinship and familial relationships, similar to human cloning with somatic cell nuclear transfer. However, their non-reproductive applications in generating replacement tissues/organs, serving as in vitro experimental models of human development and disease, and testing platforms for evaluating pharmaceuticals and biomedical devices appear to align with Islamic principles.

The 3H and Spiral Dynamics Models: A Reconciliation

Abstract: This study explores the relationship between the Spiral Dynamics and the 3H (head, heart, hands) models of human growth and development, using constructs such as empathy, moral reasoning, forgiveness, and community mindedness that have been shown to have implications for education. The specific research question is, "Can a combination of multivariate statistical techniques be utilized to find an alignment between the dimensions of these models?" We focus on practical and data-driven approaches with the primary methods including factor analysis, cluster analysis, and logistic regression. Our main finding is that the proposed methodology is robust and applicable in a variety of operational scenarios. We conclude it is feasible to empirically align and reconcile dimensions of seemingly disparate theories of educational development and human evolution with a data analysis framework based on mainstream quantitative techniques that can be easily implemented using readily available statistical software packages.

Teaching as Family Life Educators in Collegiate Settings: The Application of Family Science Theories from Systemic and Chronological Perspectives

Family Science is an exciting field which offers a multitude of career pathways, including Family Life Educator (FLE) and the Certified Family Life Educator (CFLE) credential. In this article, I will discuss how, as a Family Life Educator in a university setting, I employ Bronfenbrenner's bioecological model of human development (Bronfenbrenner & Morris, 2006), Elder's (1998) life course perspective, and the concept of intersectionality in teaching family science courses. The article will conclude with discussions of the strengths, limitations, and lessons learned.

A Facile, Transfection-Free Approach to siRNA Delivery in In Vitro 3D Spheroid Models.

Cell culture has long been essential for preclinical modeling of human development and disease. However, conventional two-dimensional (2D) cell culture fails to faithfully model the complexity found in vivo, and novel drug candidates that show promising results in 2D models often do not translate to the clinic. More recently, three-dimensional (3D) cell culture models have gained popularity owing to their greater physiological relevance to in vivo biology. In particular, 3D spheroid models are becoming widely used due to their ability to mimic solid tumors, both in architecture and gradation of nutrients distributed from the outer, proliferative layers into the inner, quiescent layers of cells. Similar to in vivo tumors, cell lines grown in 3D spheroid models tend to be more resistant to antitumor drug treatments than their 2D cultured counterparts, though distinct signaling pathways and gene targets conferring this resistance have yet to be fully explored. RNA interference (RNAi) is an effective tool to elucidate gene function and discover novel druggable targets in 2D models; however, only a few studies have successfully performed RNAi in complex 3D models to date. Here, we demonstrate efficient RNAi-mediated knockdown using "transfection-free" Dharmacon Accell siRNAs in three spheroid culture models, in the presence or absence of the extracellular matrix. This methodology has the potential to be scaled up for complex arrayed screening experiments, which may aid in the identification of novel druggable targets with greater clinical relevance than those identified in 2D experiments. © 2024 Dharmacon, Inc. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Generation of 3D spheroids in matrix-free ULA plates Alternate Protocol 1: Generation of Matrigel matrix-embedded 3D spheroids Alternate Protocol 2: Generation of GrowDex hydrogel-embedded 3D spheroids Basic Protocol 2: Delivery of siRNA and collection of matrix-free 3D spheroids Alternate Protocol 3: Delivery of siRNA and collection of matrix-embedded spheroids Basic Protocol 3: RNA and protein extraction from spheroids for characterization of gene knockdown.

MILESTONES IN THE DEVELOPMENT OF ORGANIZATIONAL MODELS BASED ON THE THEORY OF SPIRAL DYNAMICS

The article examines the milestones of the development of the business environment through the prism of industrial revolutions and the theory of spiral dynamics of organizational development. The past influences the present. The present shapes the future. The world is a complex, interconnected whole that is difficult to represent and understand, especially regarding complex socio-economic processes and organizational systems, including enterprises. The first radical change began precisely with the agrarian revolution when people domesticated animals as a basis for the transition from gathering to agriculture. After the agrarian revolution, radical industrial changes began in the 18th century. The first industrial revolution (from the 1760s to the 1840s) - the invention of the steam engine and the construction of railways. The second industrial revolution (the end of the 19th and the beginning of the 20th century) - the emergence of mass production thanks to the invention of electricity and the introduction of the conveyor. The third industrial revolution, from the 1960s, - was the emergence of semiconductors and their use in large electronic computing machines, personal computers, and the Internet. The fourth industrial revolution began at the beginning of the 21st century and is characterized by the emergence of "smart enterprises". The content and essential components of these periods imposed and imposed their understanding on the development of organizational models and the way of interaction between stakeholders and the economic entities themselves, which arose at the later stages of development and are developing under the influence of global business trends. Deepening the understanding of the nature of modern approaches in management aimed at the development of organizational systems allows turning to the past and investigating issues of organizational models on the way of the history of human development based on the theory of spiral dynamics (Don et al.), which is based on a dynamic model of human development and evolution of her consciousness, change of fundamental values. So, from the standpoint of the concept of systemic perfection of a business organization, based on the theory of spiral dynamics, its consideration can be started in the system-wide understanding of the system state, which corresponds to a greater extent to the content of perfection - from the orange stage and more/less corresponds to the current trends of the fourth industrial revolution. A significant strategic gap occurs based on the mismatch between the stage of development according to the milestones of industrial revolutions and the organization's current state in relation to the theory of spiral dynamics. For example, a red organization that functions in the fourth industrial revolution era. Management of changes in paradigms of thinking is the art of management.

Retinoic acid induces human gastruloids with posterior embryo-like structures

Gastruloids are a powerful in vitro model of early human development. However, although elongated and composed of all three germ layers, human gastruloids do not morphologically resemble post-implantation human embryos. Here we show that an early pulse of retinoic acid (RA), together with later Matrigel, robustly induces human gastruloids with posterior embryo-like morphological structures, including a neural tube flanked by segmented somites and diverse cell types, including neural crest, neural progenitors, renal progenitors and myocytes. Through in silico staging based on single-cell RNA sequencing, we find that human RA-gastruloids progress further than other human or mouse embryo models, aligning to E9.5 mouse and CS11 cynomolgus monkey embryos. We leverage chemical and genetic perturbations of RA-gastruloids to confirm that WNT and BMP signalling regulate somite formation and neural tube length in the human context, while transcription factors TBX6 and PAX3 underpin presomitic mesoderm and neural crest, respectively. Looking forward, RA-gastruloids are a robust, scalable model for decoding early human embryogenesis.

A brief chronicle of research on human pluripotent stem cells.

Today, human pluripotent stem cell technologies find widespread application across biomedical research, as models for early human development, as platforms for functional human genomics, as tools for the study of disease, drug screening and toxicology, and as a renewable source of cellular therapeutics for a range of intractable diseases. The foundations of this human pluripotent stem cell revolution rest on advances in a wide range of disciplines, including cancer biology, assisted reproduction, cell culture and organoid technology, somatic cell nuclear transfer, primate embryology, single-cell biology, and gene editing. This review surveys the slow emergence of the study of human pluripotency and the exponential growth of the field during the past several decades.

Risk patterns of bullying perpetration and victimization among children

ObjectivesThis study uses the bioecological model of human development and person-centered methods to describe the underlying patterns of risk and their association with bullying perpetration and victimization among U.S. children. MethodsUsing the National Survey of Children's Health, this study (n = 7319) explored the underlying patterns of risks across six domains (i.e., individual, family, school, neighborhood, economic, and socio-cultural) associated with bullying perpetration and victimization among U.S. elementary school children. ResultsLatent Class Analysis uncovered four patterns of risks. The low risks group (72.4%) showed the lowest rates of bullying perpetration (24.6%) and victimization (57.2%). The individual and environmental risks group (15.3%) presented moderate levels of bullying perpetration (31.8%) and victimization (67.1%). The family risks group (8.3%) showed moderate levels of bullying perpetration (35.9%) and victimization (66.0%). High risks group (4.0%) presented exceptionally high rates of bullying perpetration (59.1%) and victimization (87.3%). ConclusionResults suggest rates of bullying perpetration and victimization differed across the four patterns of risks. Understanding the sources of risk may be critical to alleviate bullying perpetration and victimization among children. ImplicationFindings suggest that child bullying should be approached with customized treatment considering their pattern of risk exposure.

A single-cell chromatin accessibility dataset of human primed and naïve pluripotent stem cell-derived teratoma

Teratoma, due to its remarkable ability to differentiate into multiple cell lineages, is a valuable model for studying human embryonic development. The similarity of the gene expression and chromatin accessibility patterns in these cells to those observed in vivo further underscores its potential as a research tool. Notably, teratomas derived from human naïve (pre-implantation epiblast-like) pluripotent stem cells (PSCs) have larger embryonic cell diversity and contain extraembryonic lineages, making them more suitable to study developmental processes. However, the cell type-specific epigenetic profiles of naïve PSC teratomas have not been yet characterized. Using single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq), we analyzed 66,384 cell profiles from five teratomas derived from human naïve PSCs and their post-implantation epiblast-like (primed) counterparts. We observed 17 distinct cell types from both embryonic and extraembryonic lineages, resembling the corresponding cell types in human fetal tissues. Additionally, we identified key transcription factors specific to different cell types. Our dataset provides a resource for investigating gene regulatory programs in a relevant model of human embryonic development.

Understanding Left-Behind Places in a Contrastive Approach

Abstract How are left-behind places in a country compared to other types of places in an Eastern European country? A typology of local human development is designed and tested for the case of the Romanian society. The United Nations model of human development (structured by the three dimensions of education, economic development and health) is adapted to the local level and two contrasting measures are designed – an index and a typology of local human development. The typology resulted from a cluster analysis. It is validated by bi-variate and multivariate analysis (multinomial regression). High emigration rates, irrespective of the destination, do not bring lower development to the local origin in Romania: the destination of migration counts. There is a higher probability, in 2018, of left-behindness in localities with a higher number of emigrants to Italy in the years preceding 2011. Human development is highly differentiated by destination countries of emigration and by historical subregions. It is especially for such contexts that the quantitative approach could be misleading. Public policy targets could be better identified if qualitative and quantitative approaches are simultaneously used. The proposed approach could be adopted by keeping the same dimensions and measuring them by available and appropriate indicators.