This study investigated whether developmental states and changes in adolescence (i.e., Grades 7-10) predict central life outcomes at the age of 30 within and between domains. We focused on predictors and outcomes in three key developmental domains: academic-vocational development, social development, and intrapersonal development/well-being. We addressed academic achievement during adolescence and occupational prestige in adulthood for academic-vocational development, perceived peer acceptance in adolescence and perceived social integration in adulthood for social development, and self-esteem in adolescence, as well as life satisfaction and depression in adulthood, as indicators for intrapersonal development/well-being. We followed a large sample of German seventh graders (N = 10,503; 50.4% females; baseline Mage = 12.3) at four measurement points over a period of 18 years and estimated latent regression models as well as latent growth curve models. The results showed that earlier states and changes within one domain predicted outcomes within the same domain. Hence, the state of academic achievement and the degree of increase in academic achievement across adolescence predicted adult occupational prestige, the state of perceived peer acceptance in adolescence predicted perceived social inclusion in adulthood, and the state and change of adolescent self-esteem predicted life satisfaction and depression in adulthood. We highlight the important role that developmental processes in adolescence play as a precursor for developmental success later in life and the need for integrative research that takes a comprehensive perspective on development across the lifespan. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

Plastid-to-nucleus retrograde signaling coordinates nuclear gene expression with the developmental and physiological state of plastids. GENOMES UNCOUPLED 1 (GUN1), a chloroplast-localized PPR-SMR protein, remains a central yet poorly understood component of this network. Its low abundance, rapid turnover and conditional phenotypes challenge functional interpretation. GUN1 has been proposed as a hub integrating stress responses, tetrapyrrole synthesis and protein homeostasis, with downstream effects mediated by factors, such as ABI4, but many of these claims are challenged by recent evidence. Here, we identify claims that have failed to replicate, highlight established consensus and outline a path toward a more grounded understanding of GUN1. Beyond its confirmed RNA-binding activity, GUN1 may act as a moonlighting checkpoint, modulating when plastid dysfunction triggers nuclear and developmental responses.

The extracellular matrix (ECM) is a major regulator of cellular behavior, fate, and various mechanisms underlying homeostasis, development, and disease. Biophysical and biochemical properties of the ECM are known to affect three-dimensional (3D) cellular behavior and phenotype that regulate a wide range of pathological conditions. Tunable biomimetic hydrogels are extensively employed to investigate cell-matrix interactions in defined 3D microenvironments. However, the dynamics of these interactions in complex coupled multiparametric microenvironments has been relatively less studied. This study aims to provide a framework for correlating cellular and nuclear behavior as a function of specific matrix properties (adhesivity, degradability, porosity, and stiffness) in a biosynthetic hydrogel system with varying crosslinking mechanisms. Poly(ethylene glycol diacrylate)-fibrinogen (PF)-based hydrogels were fabricated with varying crosslinking profiles, resulting in a series of hydrogels with varying matrix properties. NIH3T3 mouse fibroblasts were cultured in 3D and their matrix-associated morphological responses were studied over time. Matrix adhesivity and degradability (collectively termed 'matrix permissiveness') were found to be the most influential parameters regulating cell and nuclear behavior. Cells in permissive matrices displayed high viability, high cell density, increased spreading and protrusivity, and large elongated nuclei. Cells in restrictive matrices displayed reduced viability and lower cell density, rounded morphology, lower spreading, and smaller rounded nuclei. Cell confinement and nuclear confinement determined from various morphological features were correlated to matrix permissiveness. Overall, this study provides insights into regulation of cellular and nuclear behavior through modulation of matrix properties which could be used for future applications in various disease contexts. STATEMENT OF SIGNIFICANCE: Biomimetic engineered hydrogels are commonly used to support three-dimensional (3D) tissue-level behavior to recapitulate various developmental processes and disease states. Specific biophysical and biochemical cues in the engineered microenvironment can be used to control cellular behavior, morphology, and function, thereby providing mechanistic insights into cell-matrix interactions. This study assesses the variations in the cellular and nuclear features of fibroblasts encapsulated in 3D hydrogel matrices with varying crosslinking mechanisms. Our results reveal the combinatorial role of matrix adhesivity and degradability in regulating cellular and nuclear confinement of fibroblasts in 3D restrictive microenvironments. Overall, these matrix guiding principles can be implemented in the future to design tunable biomimetic matrices to modulate cell state, behavior, and function.

Targeting developmental reprogramming: hPSC insights for cancer interception.

ABSTRACT The developmental migration state is often conceptualised as a cohesive apparatus managing migration to achieve economic goals. To challenge this monolithic view, this article investigates a key puzzle in Taiwan’s migrant worker governance: why policy outcomes do not always align with the preferences of powerful economic-sector ministries. Drawing on elite interviews and documentary analysis, this study unpacks the ‘black box’ of inter-ministerial policymaking, finding that Taiwan’s Ministry of Labor (MOL) – often perceived as a weaker actor – consistently resists pressure on critical issues such as wage decoupling. The MOL’s unexpected influence stems from two bureaucratic mechanisms: specialisation, which provides the epistemic authority to frame policy debates, and hierarchy, its formal institutional position as the lead agency, reinforced by presidential support. This analysis highlights the fragmented nature of the state bureaucracy, where competing institutional missions shape policymaking, and proposes a broader understanding of social stability that emphasises labour market protection over cultural homogeneity. These findings contribute to migration studies by disaggregating state actors and revealing how specialisation and hierarchy enable bureaucratic agencies to assert policy leadership within contested governance environments.

Genetic variation drives phenotypic diversity and disease susceptibility. Trans-acting genetic variation coordinates genome-wide chromatin changes, yet the molecular mechanisms underlying this distal regulation remain unclear. Here, we use the power of mouse genetics to investigate how genetic variation at trans-acting loci regulates three-dimensional (3D) chromatin interactions. Using HiChIP to map chromatin contacts among regulatory elements in C57BL/6J and DBA/2J embryonic stem cells (ESCs), we identify 4,962 strain-differential interactions. Of these, 71% overlap chromatin accessibility quantitative trait loci (QTL), establishing that interaction variation is predominantly heritable. These differential interactions show coordinated changes in chromatin state and gene expression, with stronger interactions associated with increased accessibility and transcription. Notably, loci regulated in trans exhibit a unique chromatin signature where weaker interactions are enriched for H3K9me3-marked heterochromatin. Analysis of F1 hybrids reveal dominant repressive effects, consistent with heterochromatin-mediated trans-regulation. To causally test this mechanism, we generate reciprocal congenic mouse strains swapping a trans-QTL region. Integrated multiomic profiling of congenic ESC lines demonstrates that this locus coordinates H3K9me3, H3K27ac, chromatin accessibility, and 3D contacts at hundreds of regulatory elements, with 73-94% validating directional predictions from QTL mapping. The functional impact of heterochromatin deposition is confirmed by corresponding changes in trans-regulated gene expression. This work establishes heterochromatin formation as a defining feature of trans-regulation in mouse embryonic stem cells, providing a framework for understanding how genetic variation in early developmental chromatin states could generate phenotypic diversity while preserving essential developmental programs.

Orientia tsutsugamushi (Ot), the causative agent of scrub typhus, is an obligate intracellular bacterium naturally maintained in Leptotrombidium mites, yet its interactions within arthropod hosts remain poorly understood. Here, we employed two tick cell lines, Ixodes scapularis ISE6 and Rhipicephalus microplus BME/CTVM23, as arthropod models to investigate the intracellular lifecycle of Ot strains TA686 and Karp. Both strains efficiently infected tick cells and replicated within them, with ISE6 supporting more robust growth. Electron microscopy images revealed that Ot maintains its characteristic cytoplasmic, non-vacuolar location in tick cells and exits infected cells by budding off the surface in a membrane-encased structure. Time-course immunofluorescence imaging demonstrated progressive intracellular replication and dynamic expression of Ot outer membrane autotransporters ScaA and ScaC, with ScaC enriched early in infection and ScaA at later stages. A microscopy-based analysis of metabolic activity using a clickable methionine analog L-homopropargylglycine showed that high ScaA abundance correlated with reduced translational activity, suggesting a link between ScaA abundance and late-stage or extracellular-like developmental states. The subcellular location of Ot in tick cells differs from the characteristic dynein-driven perinuclear clustering observed in mammalian cells and was not sensitive to disruption of microtubules, suggesting a distinct mode of distribution. Together, these findings identify tick cell lines as tractable and biologically relevant arthropod models for studying Ot and dissecting host-microbe interactions.IMPORTANCEOrientia tsutsugamushi, the causative agent of scrub typhus, is an obligate intracellular bacterium naturally maintained in trombiculid mites, yet its interactions with arthropod host cells remain poorly understood. This study establishes, for the first time, a tractable in vitro arthropod model for O. tsutsugamushi using tick cell lines from Ixodes scapularis and Rhipicephalus microplus. We demonstrate that both virulent and avirulent Orientia strains efficiently infect and replicate in these cells while maintaining their characteristic cytoplasmic location and budding mode of exit. Distinct temporal expression of the bacterial autotransporters ScaA and ScaC and their relationship to metabolic activity reveal stage-specific adaptations during infection. These findings provide essential mechanistic insight into how O. tsutsugamushi persists and develops within arthropod hosts. The tick cell model enables comparative studies of host-pathogen interactions across vector species and offers a powerful tool to investigate transmission biology and potential targets for intervention.

Perennial deciduous plants withstand prolonged low temperatures by entering bud endodormancy, a developmental state tightly regulated by phytohormones and dormancy-associated MADS-box (DAM) genes. Although abscisic acid (ABA) is well-established as a key regulator of bud endodormancy, the role of endogenous ethylene (ET) in low-temperature-mediated endodormancy regulation remains largely unclear. In this study, we showed that short-term low temperature increased endogenous ET levels in peach buds, thereby inducing the expression of PpERF27. Functional analyses revealed that overexpression of PpERF27 increased ABA accumulation in peach buds, whereas virus-induced gene silencing of PpERF27 reduced ABA levels and promoted endodormancy release. PpERF27 directly activated the transcription of PpDAM5 and the ABA biosynthetic genes PpNCED2 and PpNCED3, thereby promoting bud endodormancy. Moreover, PpERF27 interacted with the C-repeat binding factors PpCBF2 and PpCBF4, further enhancing the transcriptional activation of PpDAM5, PpNCED2 and PpNCED3, which increased ABA accumulation and delayed bud endodormancy release. After long-term exposure to low temperatures, ET levels decreased and the expression of PpCBF2 and PpCBF4 was downregulated in peach buds. This reduction weakened ABA biosynthesis and DAM gene expression, consequently accelerating bud endodormancy release. Together, this study provides novel insights into how perennial deciduous plants integrate low-temperature and ET signals to regulate bud endodormancy and highlights the PpERF27-PpCBF2/4 module as a potential molecular target for improving endodormancy regulation in peach and other perennial fruit trees.

Patient-derived models uncover developmental state shifts in appendiceal cancer metastasis.

Transcriptional regulatory elements (TREs) orchestrate gene expression programs fundamental to cellular identity and transitions across physiological and pathological states. Here, we present a high-resolution atlas of RNA Polymerase II-engaged TREs (enhancers and promoters) across all major human organ systems and a broad spectrum of developmental and disease states. This atlas is generated using PRO-cap, a highly sensitive method that detects nascent RNA at transcription initiation sites, a critical feature of active TREs. The base-pair resolution of PRO-cap enables systematic dissection of transcription initiation architecture, revealing associations among tissue specificity, evolutionary constraint, transcription factor usage, and regulatory connectivity. Integration with deep learning models such as ProCapNet further provides a framework for prioritizing noncoding variants from GWAS and eQTL studies. Moreover, this tissue-resolved atlas identifies lineage-specific regulatory programs and their alterations in diseases such as metastatic cancer, where TRE landscapes capture regulatory signatures reflecting both tissue of origin and adaptive responses to distant niches. Together, these findings establish transcription initiation at regulatory elements as a defining and mechanistically informative layer of gene regulation across development, physiology, and disease.

Genome-wide DNA methylation profiling, a high-throughput epigenomic technology, systematically examines the methylation status of CpG sites across the genome to generate "methylation fingerprints" that reflect cellular origins and developmental states. This technique has emerged as a transformative tool in the diagnosis of central nervous system (CNS) tumors. This article introduces the principles of this technology, along with its significant applications and major limitations in the diagnosis of CNS tumors. It proposes that current pathological diagnosis of CNS tumors should adopt an integrated diagnostic model centered on the pathologist, emphasizing that methylation profiling serves as an adjunctive tool rather than a replacement. Any methylation-derived result must be interpreted within the comprehensive context of clinical, radiological, histopathological, and molecular data. In the future, with advances in explainable artificial intelligence, multi-omics integration, and international standardization efforts, this technology is expected to evolve from a "revolutionary tool" into an "intelligent assistant" deeply integrated with pathological diagnosis.

Postnatal mouse retinal vascular development is a widely used model for studying retinal vascular diseases and evaluating candidate therapies. This is particularly relevant for inherited disorders such as familial exudative vitreoretinopathy (FEVR), in which impaired vascular growth and organization are central to disease pathogenesis. Numerous approaches have been used to assess retinal vasculature in mouse flat mounts, ranging from qualitative descriptions to limited quantitative measurements of vascular growth. However, phenotypic variability across genetic models, including different models of FEVR, complicates comparisons and underscores the need for standardized, comprehensive multi-parameter analyses that are suitable for rapid and cost-effective screening studies. We describe a standardized morphometric protocol using ImageJ software to quantitatively analyze mouse retinal vasculature in a reproducible manner. The protocol begins with measurement of areas of vascular disorganization (meshes) as well as total vascular and retinal area. Two defined regions in the peripheral and midperipheral retina are then selected to quantify cell clusters, followed by image processing, binarization, and skeletonization. From these processed images, vascular density, branch number, branch length and thickness, junction number, triple points, and box-counting fractal dimension and lacunarity are quantified. Overall, this protocol provides a rapid, cost-effective, and standardized framework for quantifying retinal vascular phenotypes across diverse mouse models. By capturing multiple structural features and accommodating phenotypic variability, it is well-suited for comparative studies and therapeutic screening in retinal vascular disease.Key features• Computational method for mouse retina vessel image analysis for multi-parameter vascular quantification for user-selected regions of interest.• Free open-source ImageJ-based workflow combining disorganization mapping, skeletonization, and fractal analysis for reproducible vascular network characterization.• Optimized for rapid, cost-effective screening of structural vascular outcomes across developmental stages, disease states, and therapeutic interventions.

Oligodendrocytes (OLs) are specialized glial cells essential for the formation and maintenance of the myelin sheath within the central nervous system (CNS). Historically, OLs were considered a functionally homogeneous population. However, the advent and widespread application of single-cell and single-nucleus RNA sequencing (scRNA-seq/snRNA-seq) technologies since 2015 have revealed substantial transcriptional heterogeneity, varying according to developmental stage, anatomical region, and disease state. In this review, we synthesized current advances in the understanding of OL heterogeneity. Nine OL cell classes have been identified in the mouse somatosensory cortex and hippocampal CA1 region, later expanding to 13 distinct subpopulations across ten CNS regions. Furthermore, we characterized disease-associated oligodendrocytes (DAOs)/disease-associated oligodendrocyte lineages (DOLs), identified in various neurological diseases, including multiple sclerosis (MS), Alzheimer's disease (AD), and spinal cord injury, focusing on their molecular markers, spatial distribution, and pathophysiological roles. We summarized key transcriptional regulatory networks underlying DAO induction, including the signal transducer and activator of transcription (STAT)/interferon regulatory factor (IRF) family, the Yin Yang 1 (YY1)/nuclear factor kappa B (NF-κB) axis, and the SOX9/SOX10 regulatory system. The utility of region-specific brain analyses using spatial transcriptomics (ST) in conjunction with these approaches was also discussed. Finally, we compiled the implications of patient stratification according to white matter glial response patterns derived from large-scale snRNA-seq analyses of patients with progressive MS. Our synthesis shows that oligodendrocytes consist of multiple distinct subtypes that vary across development, brain regions, and disease conditions. In pathological states, they adopt specific disease-associated programs that reflect context-dependent responses and may influence disease progression and repair. This work provides a framework for understanding how oligodendrocyte diversity contributes to neurological disease and may support the development of targeted remyelination therapies.

This article discusses the South African government’s austerity approach to budgeting and sovereign debt (historical and current) regarding its impact on social reproduction through a Marxian Feminist lens, showing how debt was accumulated to perpetuate a racialized and patriarchal capitalist order. The article argues that since the transition to democracy in 1994, the inherited apartheid system has mutated to the government adopting neoliberal austerity-minded policies limiting resource allocation and preventing it from adequately addressing the legacy of apartheid and meeting the basic needs of the majority. This approach has hindered efforts to build a post-apartheid developmental state and engender state capacity. The article highlights how South Africa continues to implement self-imposed austerity despite not being subjected to International Monetary Fund or World Bank programs, demonstrating the supranational power of neoliberal policies sustaining capitalism. HIGHLIGHTS Public debt discussions must be grounded in historical, social, and economic processes shaping today’s global financial architecture. South Africa demonstrates neoliberal economic hegemony, sustaining capitalism and high levels of inequality. South Africa has pursued austerity measures independently, outside of International Monetary Fund or World Bank programs. Globalized orthodox economic thinking preserves social reproduction structures imposed through colonialism and apartheid that exacerbate race and gender inequality. Fundamentally, discussions of debt must prioritize radically shifting social reproduction into a just process.

This paper analyzes Indonesia’s downstreami ndustrialization policy as a form of second-generation resource nationalism aimed at repositioning the country within global value chains, particularly in the nickel sector. Grounded in political economy frameworks— such as resource curse theory, resource nationalism, Hirschmanian linkage theory, and the developmental state—it frames downstreaming as a long-term structural transformation rather than a mere value-added strategy. Using a qualitative-analytical approach, the study combines historical policy analysis (1945–2025), secondary data review, and international comparisons. The findings show that downstream industrialization has significantly altered export structures, attracted major investment, and built a domestic mineral processing base. However, progress in technological and functional upgrading remains limited. Key challenges include reliance on foreign technology, carbon-intensive energy systems, vulnerability to commodity price fluctuations, and risks of resource-driven industrial populism. The study argues that the policy’s success depends on sustained political commitment, disciplined industrial policy, investment in human capital and innovation, and sound fiscal and energy governance. Indonesia’s downstreaming strategy is thus at a critical juncture: it can either evolve into a competitive, innovation-driven mineral-based development model or remain constrained at a midstream stage with limited value addition. The trajectory will depend on the country’s ability to deepen institutional capacity and technological capabilities in the coming decade.

Defects in RNA metabolism are a defining feature of neurodevelopmental disease, yet how RNA decay pathways contribute to human brain development remains poorly understood. Mutations in ubiquitously expressed RNA surveillance factors often cause highly tissue-selective disease, highlighting a central paradox in human biology. The RNA exosome is a conserved ribonuclease complex traditionally viewed as a housekeeping machine for RNA turnover, yet recessive mutations in genes encoding structural subunits of the complex disproportionately cause neurological disease, suggesting an instructive role in nervous system development. Here, we show that the RNA exosome regulates the temporal progression of gene expression programs during human cerebellar differentiation. Using CRISPR-engineered human cerebellar organoids modeling EXOSC3 variants, we find that RNA exosome dysfunction does not broadly alter transcript abundance, but instead disrupts transitions between developmental states. Mutant organoids exhibit incomplete and mis-timed resolution of early transcriptional programs, altered lineage specificity, and impaired coordination of maturation-associated gene expression programs, with pronounced effects in neuronal lineages, particularly Purkinje cells and rhombic lip-derivatives. These defects are accompanied by disorganized laminar architecture and reduced coordination of neuronal activity, despite preserved intrinsic excitability. Together, our findings establish RNA surveillance as a key regulator of developmental timing, lineage fidelity, and neurodevelopmental disease.

Age- and Tissue-dependent Diversity of Human Plasmacytoid Dendritic Cells Uncovers a Cycling Subset Dominant in Early Life and Cancer

ABSTRACT South Africa’s higher education system faces a deepening access crisis, as evidenced in the 2025 admission cycle when thousands of eligible students were excluded due to limited institutional capacity. With only 26 public universities serving a rapidly growing youth population, the mismatch between demand and available spaces has become a structural challenge with profound social and economic implications. This article interrogates South Africa’s higher education access crisis through the conceptual lens of the developmental state. It argues that while the state positions higher education as a key driver of development, the limited expansion of institutional capacity exposes tensions between equity objectives and the state’s developmental ambitions. Drawing on policy analysis, demographic data, and critical debates in higher education, the article situates South Africa’s experience within wider Global South struggles over access, capacity, and equity. The paper makes two contributions: first, it conceptualises higher education access not only as a matter of individual opportunity but as a question of state capacity, policy coherence and democratic legitimacy and second, highlights the policy implications of expansion and innovation debates for the future of higher education within South Africa’s developmental ambitions beyond 2030.

Colonial legacies and the structural constraints of global capitalism pose significant obstacles to building welfare states in the Global South. Yet the past three decades have seen significant progress. In contrast to the literature on northern welfare states, the task of typologizing welfare states in the Global South is in its infancy, made all the more difficult by dramatically different conditions from first-generation welfare states and much greater variation. This paper proposes some broad typologies, but then draws from the cases of Brazil, India, and South Africa to examine the specific type of the democratic social development state. Driven by democratization and new state capacities, the focus on social development is rooted in a rights-based framework and made possible by embedding the state in civil society.

Wound-triggered plasticity in plant regeneration.