Developmental Properties Research Articles

Circadian clock activity in human umbilical vein endothelial cells of preterm and term neonates.

During mammalian gestation, fetal circadian rhythms are thought to be mainly controlled by maternal signals. In humans, the initiation and activity of central and peripheral circadian clocks is largely unknown. This study aimed to elucidate the developmental clock properties in human umbilical vein endothelial cells (HUVECs). HUVECs were obtained from (a) preterm infants, subgrouped according to birth weight or gestational age classification, and (b) term infants (in total: n = 60). In vitro clock activity was determined by using live bioluminescence recording of a luciferase reporter gene under circadian control over 120 h. In addition, core clock and clock-associated gene expression were quantified using NanoString technology. Peripheral clock activity was detected, regardless of prematurity and birth weight classification. The mean period, amplitude, and phase of circadian oscillations were not significantly associated with gestational age or birth weight classification. Peripheral clock activity can be demonstrated in HUVECs from both preterm and term infants without significant developmental differences in the period, amplitude, and phase of oscillations. This model may be useful to identify perturbation factors of proper development and entrainment of neonatal circadian clock activity. We established a model system for analyzing the peripheral clock in preterm and term HUVECs. In HUVECs, the peripheral clock exhibits functional in vitro activity independent of gestational age or birth weight categories. In this model system, neither significant developmental differences exist in the period, amplitude, and phase, nor in the expression of circadian core clock and clock-associated genes. Entrainment and proper function of the circadian clock deserve attention in neonatal intensive care.

High-resolution transcriptome datasets during embryogenesis of plant-parasitic nematodes

Understanding the transcriptional regulatory characteristics throughout the embryogenesis of plant-parasitic nematodes is crucial for elucidating their developmental processes’ uniqueness. However, a challenge arises due to the lack of suitable technical methods for synchronizing the age of plant-parasitic nematodes embryo, it is difficult to collect detailed transcriptome data at each stage of embryonic development. Here, we recorded the 11 embryonic developmental time-points of endophytic nematode Meloidogyne incognita (isolated from Wuhan, China), Heterodera glycines (isolated from Wuhan, China), and Ditylenchus destructor (isolated from Jinan, China) species, and constructed transcriptome datasets of single embryos of these three species utilizing low-input smart-seq2 technology. The datasets encompassed 11 complete embryonic development stages, including Zygote, 2-cell, 4-cell, 8-cell, 24–44 cell, 64–78 cell, Comma, 1.5-fold, 2-fold, Moving, and L1, each stage generated four to five replicates, resulting in a total of 162 high-resolution transcriptome libraries. This high-resolution cross-species dataset serves as a crucial resource for comprehending the embryonic developmental properties of plant-parasitic nematodes and for identifying functional regulatory genes during embryogenesis.

Developmental Channeling and Evolutionary Dappling

AbstractThe developmental properties of organisms play important roles in the generation of variation necessary for evolutionary change. But how can individual development steer the course of evolution? To answer this question, we introduce developmental channeling as a disposition of individual organisms that shapes their possible developmental trajectories and evolutionary dappling as an evolutionary outcome in which the space of possible organismic forms is dappled—it is only partially filled. We then trace out the implications of the channeling-dappling framework for contemporary debates in the philosophy of evolution, including evolvability, reciprocal causation, and the extended evolutionary synthesis.

Developing Sex: From Recremental Semen to Developmental Endocrinology.

During the 1890s, animal development became associated with glandular activity, with profound implications for pediatric nosology and treatment. The significance of this endocrinological turn of developmental physiology and pathophysiology in part hinges on an often-overlooked continuity with ubiquitous early modern medical thought concerning semen as a recrementitious (reabsorbed) nutrient or stimulant. Mid-19th-century interests in adult sexual physiology were increasingly nerve-centered and antihumoral. Scattered empirical, particularly veterinarian, interests in gonadal developmental functions failed to moderate these explanatory trends. While Brown-Séquard's rejuvenation experiments still offered no clear starting point for a developmental endocrinology, in 1892 Gaston Variot and Paul Bezançon more explicitly deduced a testicular developmental endocrinological function from various observations on testicular ectopy and a local form of animal "demi-castration." Ensuing interest in thethyroid, thethymus and in thetesticles led to various working conceptions of their respective and putatively reciprocal developmental properties, including the idea of a thyroid-testis axis. From 1896, the pubertal affliction of chlorosis became the subject of multiple opotherapeutic approaches, providing an experimental basis for theories of ovarian internal secretion. Polyglandular therapy, piloted for divergent developmental conditions, remained routine until the 1930s despite the biological inefficacy of many endocrine products.

Topological data analysis reveals core heteroblastic and ontogenetic programs embedded in leaves of grapevine (Vitaceae) and maracuyá (Passifloraceae).

Leaves are often described in language that evokes a single shape. However, embedded in that descriptor is a multitude of latent shapes arising from evolutionary, developmental, environmental, and other effects. These confounded effects manifest at distinct developmental time points and evolve at different tempos. Here, revisiting datasets comprised of thousands of leaves of vining grapevine (Vitaceae) and maracuyá (Passifloraceae) species, we apply a technique from the mathematical field of topological data analysis to comparatively visualize the structure of heteroblastic and ontogenetic effects on leaf shape in each group. Consistent with a morphologically closer relationship, members of the grapevine dataset possess strong core heteroblasty and ontogenetic programs with little deviation between species. Remarkably, we found that most members of the maracuyá family also share core heteroblasty and ontogenetic programs despite dramatic species-to-species leaf shape differences. This conservation was not initially detected using traditional analyses such as principal component analysis or linear discriminant analysis. We also identify two morphotypes of maracuyá that deviate from the core structure, suggesting the evolution of new developmental properties in this phylogenetically distinct sub-group. Our findings illustrate how topological data analysis can be used to disentangle previously confounded developmental and evolutionary effects to visualize latent shapes and hidden relationships, even ones embedded in complex, high-dimensional datasets.

Wireless Electric Cues Mediate Autologous DPSC-Loaded Conductive Hydrogel Microspheres to Engineer the Immuno-Angiogenic Niche for Homologous Maxillofacial Bone Regeneration.

Stem cell therapy serves as an effective treatment for bone regeneration. Nevertheless, stem cells from bone marrow and peripheral blood are still lacking homologous properties. Dental pulp stem cells (DPSCs) are derived from neural crest, in coincidence with maxillofacial tissues, thus attracting great interest in in situ maxillofacial regenerative medicine. However, insufficient number and heterogenous alteration of seed cells retard further exploration of DPSC-based tissue engineering. Electric stimulation has recently attracted great interest in tissue regeneration. In this study, a novel DPSC-loaded conductive hydrogel microspheres integrated with wireless electric generator is fabricated. Application of exogenous electric cues can promote stemness maintaining and heterogeneity suppression for unpredictable differentiation of encapsulated DPSCs. Further investigations observe that electric signal fine-tunes regenerative niche by improvement on DPSC-mediated paracrine pattern, evidenced by enhanced angiogenic behavior and upregulated anti-inflammatory macrophage polarization. By wireless electric stimulation on implanted conductive hydrogel microspheres, loaded DPSCs facilitates the construction of immuno-angiogenic niche at early stage of tissue repair, and further contributes to advanced autologous mandibular bone defect regeneration. This novel strategy of DPSC-based tissue engineering exhibits promising translational and therapeutic potential for autologous maxillofacial tissue regeneration.

Genome-Wide Analysis of Glycerol-3-Phosphate Acyltransferase (GPAT) Family in Perilla frutescens and Functional Characterization of PfGPAT9 Crucial for Biosynthesis of Storage Oils Rich in High-Value Lipids.

Glycerol-3-phosphate acyltransferase (GPAT) catalyzes the first step in triacylglycerol (TAG) biosynthesis. However, GPAT members and their functions remain poorly understood in Perilla frutescens, a special edible-medicinal plant with its seed oil rich in polyunsaturated fatty acids (mostly α-linolenic acid, ALA). Here, 14 PfGPATs were identified from the P. frutescens genome and classified into three distinct groups according to their phylogenetic relationships. These 14 PfGPAT genes were distributed unevenly across 11 chromosomes. PfGPAT members within the same subfamily had highly conserved gene structures and four signature functional domains, despite considerable variations detected in these conserved motifs between groups. RNA-seq and RT-qPCR combined with dynamic analysis of oil and FA profiles during seed development indicated that PfGPAT9 may play a crucial role in the biosynthesis and accumulation of seed oil and PUFAs. Ex vivo enzymatic assay using the yeast expression system evidenced that PfGPAT9 had a strong GPAT enzyme activity crucial for TAG assembly and also a high substrate preference for oleic acid (OA, C18:1) and ALA (C18:3). Heterogeneous expression of PfGPAT9 significantly increased total oil and UFA (mostly C18:1 and C18:3) levels in both the seeds and leaves of the transgenic tobacco plants. Moreover, these transgenic tobacco lines exhibited no significant negative effect on other agronomic traits, including plant growth and seed germination rate, as well as other morphological and developmental properties. Collectively, our findings provide important insights into understanding PfGPAT functions, demonstrating that PfGPAT9 is the desirable target in metabolic engineering for increasing storage oil enriched with valuable FA profiles in oilseed crops.

Developmental organophosphate flame retardant exposure disrupts adult hippocampal neurogenesis in Wistar rats

Organophosphate flame retardant (OPFR) contamination is ubiquitous and bio-monitoring studies have shown that human exposure is widespread and may be unavoidable. OPFRs bear structural similarities to known neurotoxicants such as organophosphate insecticides and have been shown to have both endocrine disrupting and developmental neurotoxic effects. The perinatal period in rodents represents a critical period in the organization of the developing nervous system and insults during this time can impart profound changes on the trajectory of neural development and function, lasting into adulthood. Adult hippocampal neurogenesis (AHN) facilitates dentate gyrus function and broader hippocampal circuit activity in adults; however, the neurogenic potential of this process in adulthood is vulnerable to disruption by exogenous factors during early life. We sought to assess the impact of OPFRs on AHN in offspring of dams exposed during gestation and lactation. Results indicate that developmental OPFR exposure has significant, sex specific impacts on multiple markers of AHN in the dentate gyrus of rats. In males, OPFR exposure significantly reduced the number of neural progenitors the number of new/immature neurons and reduced dentate gyrus volume. In females, exposure increased the number of neural progenitors, decreased the number of new/immature neurons, but had no significant effect on dentate gyrus volume. These results further elucidate the developmental neurotoxic properties of OPFRs, emphasize the long-term impact of early life OPFR exposure on neural processes, and highlight the importance of including sex as a biological variable in neurotoxicology research.

Transcriptional control of embryonic and adult neural progenitor activity.

Neural precursors generate neurons in the embryonic brain and in restricted niches of the adult brain in a process called neurogenesis. The precise control of cell proliferation and differentiation in time and space required for neurogenesis depends on sophisticated orchestration of gene transcription in neural precursor cells. Much progress has been made in understanding the transcriptional regulation of neurogenesis, which relies on dose- and context-dependent expression of specific transcription factors that regulate the maintenance and proliferation of neural progenitors, followed by their differentiation into lineage-specified cells. Here, we review some of the most widely studied neurogenic transcription factors in the embryonic cortex and neurogenic niches in the adult brain. We compare functions of these transcription factors in embryonic and adult neurogenesis, highlighting biochemical, developmental, and cell biological properties. Our goal is to present an overview of transcriptional regulation underlying neurogenesis in the developing cerebral cortex and in the adult brain.

The importance of study design in investigating intrinsic developmental toxic properties of substances in new studies under the REACH and CLP Regulations in the European Union

The importance of study design in investigating intrinsic developmental toxic properties of substances in new studies under the REACH and CLP Regulations in the European Union

Linking Benzene, in Utero Carcinogenicity and Fetal Hematopoietic Stem Cell Niches: A Mechanistic Review.

Previous research reported that prolonged benzene exposure during in utero fetal development causes greater fetal abnormalities than in adult-stage exposure. This phenomenon increases the risk for disease development at the fetal stage, particularly carcinogenesis, which is mainly associated with hematological malignancies. Benzene has been reported to potentially act via multiple modes of action that target the hematopoietic stem cell (HSCs) niche, a complex microenvironment in which HSCs and multilineage hematopoietic stem and progenitor cells (HSPCs) reside. Oxidative stress, chromosomal aberration and epigenetic modification are among the known mechanisms mediating benzene-induced genetic and epigenetic modification in fetal stem cells leading to in utero carcinogenesis. Hence, it is crucial to monitor exposure to carcinogenic benzene via environmental, occupational or lifestyle factors among pregnant women. Benzene is a well-known cause of adult leukemia. However, proof of benzene involvement with childhood leukemia remains scarce despite previously reported research linking incidences of hematological disorders and maternal benzene exposure. Furthermore, accumulating evidence has shown that maternal benzene exposure is able to alter the developmental and functional properties of HSPCs, leading to hematological disorders in fetus and children. Since HSPCs are parental blood cells that regulate hematopoiesis during the fetal and adult stages, benzene exposure that targets HSPCs may induce damage to the population and trigger the development of hematological diseases. Therefore, the mechanism of in utero carcinogenicity by benzene in targeting fetal HSPCs is the primary focus of this review.

Cellular signaling impacts upon GABAergic cortical interneuron development.

The development and maturation of cortical GABAergic interneurons has been extensively studied, with much focus on nuclear regulation via transcription factors. While these seminal events are critical for the establishment of interneuron developmental milestones, recent studies on cellular signaling cascades have begun to elucidate some potential contributions of cell signaling during development. Here, we review studies underlying three broad signaling families, mTOR, MAPK, and Wnt/beta-catenin in cortical interneuron development. Notably, each pathway harbors signaling factors that regulate a breadth of interneuron developmental milestones and properties. Together, these events may work in conjunction with transcriptional mechanisms and other events to direct the complex diversity that emerges during cortical interneuron development and maturation.

Structure- and lithofacies-controlled natural fracture developments in shale: Implications for shale gas accumulation in the Wufeng-Longmaxi Formations, Fuling Field, Sichuan Basin, China

Descriptions, field emission-scanning electron microscopy and geochemical analyses on shale core samples taken from the fractured intervals of the Wufeng-Longmaxi Formations in three wells from the Fuling Field were used to understand the developmental properties of natural fractures and elucidate their controlling factors. Furthermore, the effects of geological fractures on shale gas accumulation were systematically analyzed. The macro-fractures observed in the shale cores are mainly non-tectonic bedding fractures; to a lesser extent, tectonic fractures, including oblique shear, vertical tension and tension-shear fractures, as well as bed-parallel slip fractures are visible. In contrast, micro-fractures are mainly interparticulate, intraparticulate, and grain marginal in nature. The extent of natural fracture development is controlled by external structural and internal lithofacies factors. For shales with similar lithofacies, the development degree of tectonic fractures increases with decreasing distance from the tectonically deformed and faulted zones. Within the same structural zone, the fractures are well developed in shales of organic matter-rich S-3 (i.e., argillaceous-rich siliceous) lithofacies. The study of fracture properties and their controlling factors has resulted in a model for the development of natural fractures in Wufeng-Longmaxi Shales generated by both structural and lithofacies effects. Overall, shale reservoirs in a “fractured but not broken” state are the most favorable ones for gas accumulation.

Dually innervated dendritic spines develop in the absence of excitatory activity and resist plasticity through tonic inhibitory crosstalk

Dendritic spines can be directly connected to both inhibitory and excitatory presynaptic terminals, resulting in nanometer-scale proximity of opposing synaptic functions. While dually innervated spines (DiSs) are observed throughout the central nervous system, their developmental timeline and functional properties remain uncharacterized. Here we used a combination of serial section electron microscopy, live imaging, and local synapse activity manipulations to investigate DiS development and function in rodent hippocampus. Dual innervation occurred early in development, even on spines where the excitatory input was locally silenced. Synaptic NMDA receptor currents were selectively reduced at DiSs through tonic GABAB receptor signaling. Accordingly, spine enlargement normally associated with long-term potentiation on singly innervated spines (SiSs) was blocked at DiSs. Silencing somatostatin interneurons or pharmacologically blocking GABABRs restored NMDA receptor function and structural plasticity to levels comparable to neighboring SiSs. Thus, hippocampal DiSs are stable structures where function and plasticity are potently regulated by nanometer-scale GABAergic signaling.

Determination of protoplast growth properties using quantitative single-cell tracking analysis

BackgroundAlthough quantitative single-cell analysis is frequently applied in animal systems, e.g. to identify novel drugs, similar applications on plant single cells are largely missing. We have exploited the applicability of high-throughput microscopic image analysis on plant single cells using tobacco leaf protoplasts, cell-wall free single cells isolated by lytic digestion. Protoplasts regenerate their cell wall within several days after isolation and have the potential to expand and proliferate, generating microcalli and finally whole plants after the application of suitable regeneration conditions.ResultsHigh-throughput automated microscopy coupled with the development of image processing pipelines allowed to quantify various developmental properties of thousands of protoplasts during the initial days following cultivation by immobilization in multi-well-plates. The focus on early protoplast responses allowed to study cell expansion prior to the initiation of proliferation and without the effects of shape-compromising cell walls. We compared growth parameters of wild-type tobacco cells with cells expressing the antiapoptotic protein Bcl2-associated athanogene 4 from Arabidopsis (AtBAG4).ConclusionsAtBAG4-expressing protoplasts showed a higher proportion of cells responding with positive area increases than the wild type and showed increased growth rates as well as increased proliferation rates upon continued cultivation. These features are associated with reported observations on a BAG4-mediated increased resilience to various stress responses and improved cellular survival rates following transformation approaches. Moreover, our single-cell expansion results suggest a BAG4-mediated, cell-independent increase of potassium channel abundance which was hitherto reported for guard cells only. The possibility to explain plant phenotypes with single-cell properties, extracted with the single-cell processing and analysis pipeline developed, allows to envision novel biotechnological screening strategies able to determine improved plant properties via single-cell analysis.

The Potential Use of Ebselen in Treatment-Resistant Depression.

Ebselen is an organoselenium compound developed as an antioxidant and subsequently shown to be a glutathione peroxidase (GPx) mimetic. Ebselen shows some efficacy in post-stroke neuroprotection and is currently in trial for the treatment and prevention of hearing loss, Meniere’s Disease and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In vitro screening studies show that ebselen is also an effective inhibitor of the enzyme inositol monophosphatase (IMPase), which is a key target of the mood-stabilising drug lithium. Further, in animal experimental studies, ebselen produces effects on the serotonin system very similar to those of lithium and also decreases behavioural impulsivity. The antidepressant effects of lithium in treatment-resistant depression (TRD) have been attributed to its ability to facilitate presynaptic serotonin activity; this suggests that ebselen might also have a therapeutic role in this condition. Human studies utilising magnetic resonance spectroscopy support the notion that ebselen, at therapeutic doses, inhibits IMPase in the human brain. Moreover, neuropsychological studies support an antidepressant profile for ebselen based on positive effects on emotional processing and reward seeking. Ebselen also lowers a human laboratory measure of impulsivity, a property that has been associated with lithium’s anti-suicidal effects in patients with mood disorders. Current clinical studies are directed towards assessment of the neuropsychological effects of ebselen in TRD patients. It will also be important to ascertain whether ebselen is able to lower impulsivity and suicidal behaviour in clinical populations. The objective of this review is to summarise the developmental history, pre-clinical and clinical psychopharmacological properties of ebselen in psychiatric disorders and its potential application as a treatment for TRD.

Looking Back and Looking Around: How Athletes, Parents and Coaches See Psychosocial Development in Adolescent Performance Sport.

Sport has the potential to support psychosocial development in young people. However, extant studies have tended to evaluate purpose-built interventions, leaving regular organised sport relatively overlooked. Moreover, previous work has tended to concentrated on a narrow range of outcomes. To address these gaps, we conducted a season-long ethnography of a youth performance sport club based on a novel Realist Evaluation approach. We construed the club as a social intervention within a complex system of agents and structures. The results are published in this special issue as a two-part series. In this first paper, we detail the perceptions of former and current club parents, players and coaches, using them to build a set of programme theories. The resulting network of outcomes (i.e., self, emotional, social, moral and cognitive) and generative mechanisms (i.e., the attention factory, the greenhouse for growth, the personal boost and the real-life simulator), spanning across multiple contextual layers, provides a nuanced understanding of stakeholders’ views and experiences. This textured perspective of the multi-faceted process of development provides new insights for administrators, coaches and parents to maximise the developmental properties of youth sport, and signposts new avenues for research in this area.

Reactive Oxygen Species: Angels and Demons in the Life of a Neuron.

Reactive oxygen species (ROS) have emerged as regulators of key processes supporting neuronal growth, function, and plasticity across lifespan. At normal physiological levels, ROS perform important roles as secondary messengers in diverse molecular processes such as regulating neuronal differentiation, polarization, synapse maturation, and neurotransmission. In contrast, high levels of ROS are toxic and can ultimately lead to cell death. Excitable cells, such as neurons, often require high levels of metabolic activity to perform their functions. As a consequence, these cells are more likely to produce high levels of ROS, potentially enhancing their susceptibility to oxidative damage. In addition, because neurons are generally post-mitotic, they may be subject to accumulating oxidative damage. Thus, maintaining tight control over ROS concentration in the nervous system is essential for proper neuronal development and function. We are developing a more complete understanding of the cellular and molecular mechanisms for control of ROS in these processes. This review focuses on ROS regulation of the developmental and functional properties of neurons, highlighting recent in vivo studies. We also discuss the current evidence linking oxidative damage to pathological conditions associated with neurodevelopmental and neurodegenerative disorders.

A Bioinformatic Framework for Dissecting the Dynamics of T Cells from Single-Cell Transcriptome.

The quantitative tracking of the dynamics of T cells is challenging in human immunology. Although bulk sequencing of T cell receptor (TCR) α- and β-chains has been widely used for determining the clonality of T cells, such methods are limited in unveiling the phenotypic differences of T cells with the same clonotypes. Here, we describe a bioinformatics framework, STARTRAC, that integrates the single-cell transcriptome and TCR sequences as lineage-specific markers to quantitatively assess the dynamics of T cells, including their clonal expansion, tissue migration, and developmental transition properties.

Refleksje leksykalno-statystyczne nad wypowiedziami dzieci w wieku przedszkolnym. Część 1 – słownictwo częste

The purpose of this essay is to characterize statistically frequent words in a pre-school children’s dictionary, including both their functional and semantic structure. Analyses conducted in the field of statistical linguistics and linguistic semantics confirm the small share of frequent words in the dictionary and their significant role in the structure of spoken texts. Frequent entries are mostly autosemantic words, especially nouns and verbs. On the other hand, frequent auxiliary words, although not very numerous, are characterized by high ranks and text frequencies. The dictionary is based on representative meaning groups that reflect the child’s world, experiences and feelings. The observed quantitative and qualitative features of the children’s frequent dictionary confirm the statistical regularities of the texts of other varieties of Polish, they are consistent with the properties of the natural language, the spoken style and the developmental properties of the child’s speech.