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[Specification of cell destiny in early Caenorhabditis elegans embryo].

Embryogenesis of the nematode Caenorhabditis elegans has been described completely on a cell-by-cell basis and found to be essentially invariant. With this knowledge in hands, micromanipulated embryos and mutants have been analyzed for cell lineage defects and the distribution of specific gene products. The results challenge the classical view of cell-autonomous development in nematodes and indicate that the early embryo of C. elegans is a highly dynamic system. A network of inductive events between neighboring cells is being revealed, which is necessary to assign different developmental programs to blastomeres. In those cases where molecules involved in these cell-cell interactions have been identified, homologies to cell surface receptors, ligands and transcription factors found in other systems have become obvious.

Animals↗

Bacterial artificial chromosome transgenic analysis of dynamic expression patterns of regulator of G-protein signaling 4 during development. II. Subcortical regions.

A large family of regulator of G protein signaling (RGS) proteins modulates signaling through G-protein-coupled receptors. Previous studies have implicated RGS4 as a vulnerability gene in schizophrenia. To begin to understand structure-function relationships, we have utilized bacterial artificial chromosome (BAC) methods to create transgenic mice that express green fluorescent protein (GFP) under the control of endogenous RGS4 enhancer elements, circumventing the lack of suitable antibodies for analysis of dynamic patterns of expression. This report follows from the accompanying mapping paper in cerebral cortex, with a focus on developmental and mature expression patterns in subcortical telencephalic, diencephalic and brainstem areas. Based on reporter distribution, the data suggest that alterations in RGS4 function will engender a complex phenotype of increased and decreased neuronal output, with developmental, regional, and cellular specificity.

Aging↗

Domestic violence and children.

Domestic violence affects the lives of many Americans, including children. It is imperative that primary care providers working with children, including pediatric nurse practitioners, understand the dynamics of domestic violence, recognize domestic violence, and intervene appropriately. Domestic violence places children at risk physically, emotionally, and developmentally. The effect on children who witness domestic violence will be discussed. Primary care providers have a professional responsibility to screen for domestic violence. The primary care provider can play a pivotal role in breaking the cycle of family violence by timely identification of and appropriate intervention for domestic violence.

Attitude to Health↗

Transplacental lung carcinogenesis: molecular mechanisms and pathogenesis.

A wide variety of studies in both animal models and human populations have demonstrated age-related differences in the susceptibility of the developing organism to environmentally prevalent toxicants. While this differential susceptibility has been clearly established, the mechanistic basis for these age-related differences is still poorly understood. The developing fetus utilizes many of the same metabolic and signaling pathways as adult organisms in responding to environmental agents. However, it is becoming increasingly evident that the fetus is not a "little adult" and exhibits unique biochemical responses and gene expression profiles to chemical and physical agents. Because of the rapid growth and developmental changes that occur during gestation, the fetus represents a particularly challenging research subject as a result of the dynamic alterations that occur in gene expression pathways as gene systems are activated or repressed during specific stages of development. Thus, an understanding of the mechanism(s) that render the developing organism more or less susceptible to specific carcinogenic agents is crucial for both regulatory decisions regarding the determination of safe levels of toxic chemicals released into the environment and also for determining the effects of therapeutic compounds in younger age groups and pregnant women. Concentrating on studies from the author's laboratory, this review will highlight recent research on the molecular pathogenesis of transplacentally induced tumors. While focusing on the lung, other animal models and recent human epidemiological studies will also be discussed to contrast similarities and differences in the developing and adult organisms in terms of responses to toxic chemicals, including metabolism of environmentally prevalent toxicants and alterations in gene systems at the molecular level.

Animals↗

Differential expression of three classes of voltage-gated Ca(2+) channels during maturation of the rat cerebellum in vitro.

Voltage-gated Ca(2+) channels provide a mode of Ca(2+) influx that is essential for intracellular signaling in many cells. Semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to assess the relative amounts of mRNAs encoding three classes of Ca(2+) channels (alpha1A, alpha1B and alpha1E) during development, in cultures established from prenatal rat cerebellar cortex. Ca(2+) channel transcript levels were standardized to a constitutive marker (cyclophilin). For all three classes of Ca(2+) channels, transcript levels were highest at early stages (4-10 days in vitro) and declined with age. This developmental pattern was differentially regulated by a depolarizing agent, tetraethylammonium chloride (TEA, 1 mM). Chronic depolarization yielded a significant elevation in transcript levels for alpha1B (N-type) and alpha1E (R-type) Ca(2+) channels during neuronal maturation (10-21 days in vitro), but dramatically suppressed transcript levels for the alpha1A (P-type) Ca(2+) channel at all stages of development. The effects of TEA on alpha1A, alpha1B and alpha1E transcript levels were mimicked by increasing external K(+) (from 5 to 10 mM). The regulatory effects of depolarization on transcript levels were dependent on extracellular Ca(2+) for alpha1E but not for alpha1A. For alpha1B, transcript levels depended on extracellular Ca(2+) only for increased K(+) as the depolarizing stimulus, but not for TEA. These results suggest that levels of Ca(2+) channel transcripts in rat cerebellum are developmentally regulated in vitro and can be influenced differentially by transmembrane signaling via chronic depolarization and Ca(2+) entry. Dynamic regulation of Ca(2+) channel expression may be relevant to the different functional roles of Ca(2+) channels and their regional localization within neurons.

Animals↗

Auxin regulation of cytokinin biosynthesis in Arabidopsis thaliana: a factor of potential importance for auxin-cytokinin-regulated development.

One of the most long-lived models in plant science is the belief that the long-distance transport and ratio of two plant hormones, auxin and cytokinin, at the site of action control major developmental events such as apical dominance. We have used in vivo deuterium labeling and mass spectrometry to investigate the dynamics of homeostatic cross talk between the two plant hormones. Interestingly, auxin mediates a very rapid negative control of the cytokinin pool by mainly suppressing the biosynthesis via the isopentenyladenosine-5'-monophosphate-independent pathway. In contrast, the effect of cytokinin overproduction on the entire auxin pool in the plant was slower, indicating that this most likely is mediated through altered development. In addition, we were able to confirm that the lateral root meristems are likely to be the main sites of isopentenyladenosine-5'-monophosphate-dependent cytokinin synthesis, and that the aerial tissue of the plant surprisingly also was a significant source of cytokinin biosynthesis. Our demonstration of shoot-localized synthesis, together with data demonstrating that auxin imposes a very rapid regulation of cytokinin biosynthesis, illustrates that the two hormones can interact also on the metabolic level in controlling plant development, and that the aerial part of the plant has the capacity to synthesize its own cytokinin independent of long-range transport from the root system.

Adenosine Monophosphate↗

The many dimensions of group process. A discussion of the treatment of Sandy.

What is presented is a summary of the study group's discussion of Dr. Olesker's work with her patient Sandy. A spotlight was thrown on the group process with an emphasis on the organic nature of how this group of psychoanalysts came to grips with the nature of Sandy's inner world. One central issue which challenged the group was how to conceptualize the structure of her mind: Was she a child whose mental life could best be described as compromised by a fundamental biological frailty so that a primary emptiness or inchoate quality of mental contents reigned? If so, technical interventions which turned on narrative building were viewed as the principal therapeutic action. On the other hand, if her difficulties were perceived as stemming primarily from primitive psychological anxieties of annihilation and separateness, a dynamic approach was agreed upon as the preferred mode of treatment. Other issues regarding the transformational potentialities in the developmental process and the use of the analyst as a transformational object were also highlighted. Lastly, I offered my own perspective as to what I imagined occurred between Dr. Olesker and Sandy over the course of her treatment which enabled Sandy to change.

Child↗

Major proteome variations associated with cherry tomato pericarp development and ripening.

Tomato (Solanum lycopersicum) is a model plant for studying fleshy fruit development. Several genetic and molecular approaches have been developed to increase our knowledge about the physiological basis of fruit growth, but very few data are yet available at the proteomic level. The main stages of fruit development were first determined through the dynamics of fruit diameter and pericarp cell number. Then, total proteins were extracted from pericarp tissue at six relevant developmental stages and separated by two-dimensional gel electrophoresis. Protein patterns were markedly different between stages. Proteins showing major variations were monitored. We identified 90 of 1,791 well-resolved spots either by matrix-assisted laser-desorption ionization time-of-flight peptide mass fingerprinting or liquid chromatography-mass spectrometry sequencing and expressed sequence tag database searching. Clustered correlation analysis results pointed out groups of proteins with similar expression profiles during fruit development. In young fruit, spots linked to amino acid metabolism or protein synthesis were mainly expressed during the cell division stage and down-regulated later. Some spots linked to cell division processes could be identified. During the cell expansion phase, spots linked to photosynthesis and proteins linked to cell wall formation transiently increased. In contrast, the major part of the spots related to C compounds and carbohydrate metabolism or oxidative processes were up-regulated during fruit development, showing an increase in spot intensity during development and maximal abundance in mature fruit. This was also the case for spots linked to stress responses and fruit senescence. We discuss protein variations, taking into account their potential role during fruit growth and comparing our results with already known variations at mRNA and metabolite-profiling levels.

Chromatography, Liquid↗

Frodo proteins: modulators of Wnt signaling in vertebrate development.

The Frodo/dapper (Frd) proteins are recently discovered signaling adaptors, which functionally and physically interact with Wnt and Nodal signaling pathways during vertebrate development. The Frd1 and Frd2 genes are expressed in dynamic patterns in early embryos, frequently in cells undergoing epithelial-mesenchymal transition. The Frd proteins function in multiple developmental processes, including mesoderm and neural tissue specification, early morphogenetic cell movements, and organogenesis. Loss-of-function studies using morpholino antisense oligonucleotides demonstrate that the Frd proteins regulate Wnt signal transduction in a context-dependent manner and may be involved in Nodal signaling. The identification of Frd-associated factors and cellular targets of the Frd proteins should shed light on the molecular mechanisms underlying Frd functions in embryonic development and in cancer.

Adaptor Proteins, Signal Transducing↗

GenOT: generative optimal transport enables spatiotemporal interpolation and generation in cross-platform spatial transcriptomics.

Spatial transcriptomics technologies have revolutionized the analysis of spatial gene expression, yet integrating spatial information and generating data across heterogeneous samples remain challenging. We present GenOT, a generative framework combining multi-scale graph self-supervised contrastive learning with optimal transport barycenter theory for efficient cross-slice and cross-platform spatiotemporal interpolation. The core innovation of GenOT lies in introducing an optimal transport barycenter-based interpolation algorithm, which mathematically models spatial distribution differences across heterogeneous samples to reconstruct spatiotemporal gene expression dynamics. Extensive evaluations demonstrate that GenOT consistently outperforms existing approaches in spatial domain identification, cross-platform interpolation, and developmental trajectory reconstruction.

Spatial Transcriptomics↗

Young children's perception of implied motion portrayal in still photographs.

120 kindergarten and first grade children were classified by developmental level based upon the results of the Purdue Conservation Test. Subsequently subjects judged whether or not the content of 64 static photographic pictorial stimuli (16 per subject) contained action. In addition to the still items, three types of implied motion cues were included as stimuli, frozen content, blurred content, and frozen content with blurred background. Main effects for both age and developmental level were found as well as interactions of each of the between-group variables with motion cues, the repeated factor. The results suggest that cognitive-developmental differences in young children as well as difference in age may explain how children come correctly to perceive dynamic elements in static photographs.

Child↗

Analysis and system: a marriage.

Self-psychology describes a psychoanalytic model developed by Heinz Kohut and based upon a systemic concept of the "self-object', a system of self and object which differentiates progressively from an early symbiotic fusion at birth to healthy interdependence at around three years of age. These stages of differentiation were originally described by Margaret Mahler and interpreted by her within a Kleinian framework. Self-psychology differs in many key concepts from the Kleinian and other psychoanalytic models, and Kohut reinterpreted Mahler's work from this new perspective. The systemic or dyadic basis of Kohutian theory provides a bridge between psychoanalytic models and systems models of marital dynamics, an important meeting ground for interpsychic and intrapsychic viewpoints. Progressive differentiation within a dyadic system can be applied developmentally to the mother-infant, husband-wife, or therapist-patient dyad, as can the self-object transference concept.

Gender Identity↗

High cervical and lumbar canal stenosis of varied etiology: a case report.

Developmental stenosis without any significant spondylotic changes frequently occurs at C3 vertebra or below, and typically extends to C6-C7. However, high cervical focal canal stenosis is unusual. A case of cervical canal segmental stenosis at C2-3 level in addition to a developmental stenosis of the lumbar region, in a 45 year old male, has been presented in this article. The dynamics of the spinal canal in relation to the likely pathology of such conditions are reviewed. We speculate that focal segmental stenosis in the high cervical region may be due to a possible premature fusion of the neurocentral synchondrosis of the cartilage, or due to an abnormal rotary biomechanics which can result in facetal hypertrophy.

Humans↗

Tuning of activation thresholds explains flexibility in the selection and development of T cells in the thymus.

Immature CD4+ CD8+ thymocytes expressing T-cell antigen receptors (TCR) are selected by TCR-mediated recognition of peptides associated with major histocompatibility complex molecules on thymic stromal cells. Selection ensures reactivity of the mature cells to foreign antigens and tolerance to self. Although much has been learned about the factors that determine whether a thymocyte with a given specificity will be positively or negatively selected, selection as an aspect of the developmental process as a whole is less well-understood. Here we invoke a model in which thymocytes tune their response characteristics individually and dynamically in the course of development. Cellular development and selection are driven by receptor-mediated metabolic perturbations. Perturbation is a measure of the net intracellular change induced by external stimulation. It results from the integration of several signals and countersignals over time and therefore depends on the environment and the maturation stage of the cell. Individual cell adaptation limits the range of perturbations. Such adaptation renders thymocytes less sensitive to the level of stimulation per se, but responsive to environmental changes in that level. This formulation begins to explain the mechanisms that link developmental and selection events to each other.

Animals↗

Advances in neonatal and infant behavioral assessment: toward a comprehensive evaluation of early patterns of development.

Recognizing the impressive range of behavioral capacities of newborn infants, clinicians and researchers have long searched for valid assessment instruments to help evaluate infant behavior. Behavioral assessments with high predictive validity would aid the goals of developmental diagnostic, prognostic, and treatment programs for infants born at risk from biological or environmental circumstances. The failure of current assessments to predict developmental outcome based on infant behavior may be due to the limited information about higher central nervous system (CNS) functioning obtained from available measures, or to the very dynamic nature of CNS organization in young infants. We begin our review by discussing some major functional characteristics of neonates and then proceed to describe critically the commonly used methods of neurological and behavioral assessment. Noting the need for measures that are more predictive, we turn next to a discussion of a number of experimental techniques that seem to hold great promise for developmental prediction and clinical application.

Child Behavior↗

Emerging from the fog: hypotheses and paradigms in developmental biology--the Society for Developmental Biology 2005 Annual Meeting Report.

The Society for Developmental Biology 64th annual meeting took place by the beautiful San Francisco Bay from July 27th to August 1st, 2005. Organized under the leadership of Judith Kimble (SDB President, U. Wisconsin-Madison), the meeting attracted over one thousand developmental biologists from all over the world. They gathered to present data, exchange ideas and enjoy basking in the warm sun on the piers. Strong themes emerged from the diverse subjects discussed at the meeting, demonstrating exciting trends towards the unifying goal of understanding the progression from a single cell to an adult organism. Cell and Tissue Polarity was a recurring topic at the meeting. Questions like "is there polarity", "how is it achieved" and "how is it linked to stem cell maintenance" were discussed. Post-transcriptional regulation involving protein degradation and microRNA (miRNA) modulation of gene expression was featured in the context of transition between meiosis to mitosis and asymmetries in the embryo. It is apparent that Evolutionary Developmental Biology, once a major driving influence in the early days of the field, continues to enjoy a renaissance as researchers familiar with traditional model organisms are increasingly attracted to the field and as modern genetic and molecular approaches are applied to an increasingly varied assortment of organisms. The attention is beginning to pay off as laboratories are starting to generate significant results shedding light into how developmental programs are altered to generate morphological diversity. In the Satellite Symposium on Plant Development held on July 27th, 2005, the overriding theme was on the identity and maintenance of Stem Cells in Plants. Finally, researchers working on diverse organisms have shown a strong effort to address Developmental Coordination: on the subcellular, cellular and tissue levels. Advanced imaging techniques are combined with traditional genetic methods to scrutinize and compare dynamic processes in four dimensions. This tremendous increase in resolution has facilitated the identification of key signaling mechanisms that embryos utilize to form coordinated body plans. For an exceptional effort in keeping with Society tradition, the 2005 annual meeting also offered opportunities to address broader issues revolving around education and professional development as well as a special session on embryonic stem cell research. Throughout the 5-day meeting, participants found time to honor the contributions of colleagues, exchange career and grant planning strategies, contemplate the big picture and recognize the efforts of young investigators, postdoctoral fellows and students.

Animals↗

Developmental regulation of monoterpene biosynthesis in the glandular trichomes of peppermint.

Monoterpene production in peppermint (Mentha x piperita L.) glandular trichomes is determined by the rate of biosynthesis, as determined by (14)CO(2) incorporation, and is restricted to leaves 12 to 20 d of age. Using oil glands isolated from peppermint leaves of different ages, in vitro assay of the eight sequential enzymes responsible for the biosynthesis of the principal monoterpene (-)-menthol indicated that all but one biosynthetic enzyme had a very similar developmental profile. Activities were highest in leaves 12 to 20 d of age, with a sharp peak centered at 15 d. The exception, (-)-menthone reductase, the last enzyme of the pathway, exhibited a later peak of activity, which was centered at approximately 21 d. The correlation between in vitro enzyme activity and the rate of biosynthesis measured in vivo suggests that monoterpene formation is controlled mainly by the coordinately regulated activity of the relevant biosynthetic enzymes. Developmental immunoblotting of limonene synthase, which catalyzes the committed step of the pathway, demonstrated a direct correlation between enzyme activity and enzyme protein, suggesting that the dynamic time course for the remaining pathway enzyme activities also reflects the corresponding protein levels. RNA-blot analyses indicated that the genes encoding enzymes of the early pathway steps are transcriptionally activated in a coordinated fashion, with a time course superimpossible with activity measurements and immunoblot data. These results demonstrating coincidental temporal changes in enzyme activities, enzyme protein level, and steady-state transcript abundances indicate that most of the monoterpene biosynthetic enzymes in peppermint are developmentally regulated at the level of gene expression.

Blotting, Northern↗