Most lymphocytes of the T cell lineage develop along the CD4/CD8 pathway and express antigen receptors on their surfaces consisting of clonotypic αβ chains associated with invariant CD3‐γδε components and ζ chains, collectively referred to as the T cell antigen receptor complex (TCR). Expression of the TCR complex is dynamically regulated during T cell development, with immature CD4+CD8+ thymocytes expressing only 10% of the number of αβ TCR complexes on their surfaces expressed by mature CD4+ and CD8+ T cells. Recent (...) evidence demonstrates that low surface TCR density on CD4+CD8+ thymocytes results from the limited survival of a single TCR component within the ER, the TCRα chain, which has a half life of only 15 minutes in immature thymocytes, compared to >75 minutes in mature T cells. Instability of TCRα proteins in immature CD4+CD8+ thymocytes represents a novel mechanism by which expression of the multisubunit TCR complex is quantitatively regulated during T cell development. In the current review we discuss our recent findings concerning the assembly, intracellular transport, and expression of αβ TCR complexes in CD4+CD8+ thymocytes and comment on the functional significance of TCRα instability during T cell development. (shrink)

Among all organisms, the size of each body part or organ scales with overall body size, a phenomenon called allometry. The study of shape and form has attracted enormous interest from biologists, but the genetic, developmental and physiological mechanisms that control allometry and the proportional growth of parts have remained elusive. Recent progress in our understanding of body‐size regulation provides a new synthetic framework for thinking about the mechanisms and the evolution of allometric scaling. In particular, insulin/IGF signaling, (...) which plays major roles in longevity, diabetes and the regulation of cell, organ and body size, might also be centrally involved in regulating organismal shape. Here we review recent advances in the fields of growth regulation and endocrinology and use them to construct a developmental model of static allometry expression in insects. This model serves as the foundation for a research program that will result in a deeper understanding of the relationship between growth and form, a question that has fascinated biologists for centuries. BioEssays 29:536–548, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Targeted transitions in chromatin states at thousands of genes are essential drivers of eukaryotic development. Therefore, understanding the in vivo dynamics of epigenetic regulators is crucial for deciphering the mechanisms underpinning cell fate decisions. This review illustrates how, in addition to its cell memory function, the Polycomb group of transcriptional regulators orchestrates temporal, cell and tissue‐specific expression of master genes during development. These highly sophisticated developmental transitions are dependent on the context‐ and tissue‐specific assembly of the different types of (...) Polycomb Group (PcG) complexes, which regulates their targeting and/or activities on chromatin. Here, an overview is provided of how PcG complexes function at multiple scales to regulate transcription, local chromatin environment, and higher order structures that support normal differentiation and are perturbed in tumorigenesis. (shrink)

Wnts are a recently described family of secreted glycoproteins related to the Drosophila segment polarity gene, wingless, and to the proto‐oncogene, int‐1. Wnts are thought to function as developmental modulators, with signalling distances of only a few cell diameters. In Xenopus, at least six Wnts, including Xwnts‐1, ‐3A, and ‐4, are expressed initially in the developing central nervous system, with some regions expressing multiple Xwnts. Xwnt‐8 is expressed by mid‐blastula stage, in ventral and lateral mesoderm. Xwnt‐5A mRNAs are stored (...) in the egg, and later are expressed throughout the embryo in both ectoderm and mesoderm, but with a pronounced enrichment in the head and tail. Recent studies in Xenopus have pursued the diverse roles of Xwnts in early development, the mechanisms by which Xwnts signal information between cells, and the cell physiological responses to Xwnt signals. (shrink)

Going back to the late 1970s and early 1980s, we trace the Xenopus oocyte microinjection experiments that led to the emergence of the concept of “modulator”. The finding that the modulator could transactivate transcription from far upstream and in either orientation suggested that a new genetic element, different from the classical prokaryotic promoter sequences, had been discovered. This particular enhancer transactivates transcription of the sea urchin early (α) histone H2A gene which is regulated in early sea urchin development. We summarise (...) the data from sea urchin microinjection experiments that confirm and extend the results obtained with Xenopus oocytes. We conclude that the H2A enhancer is bipartite, is located approx. 100 bp upstream of the TATAAATA box in the H2A gene of two sea urchin species and enhances transcription when placed at a position far upstream or far downstream of the gene unless an insulator intervenes between enhancer and promoter. Evidence from microinjection experiments with sea urchin embryos suggests that the developmental control of H2A expression resides not with the enhancer, which is constitutively active, but with a striking chromatin structure with two positioned nucleosomes near the 3′ end of the gene. Within this structure, there is an insulator element. BioEssays 24:850–857, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

Heterochronic genes control the timing of developmental programs. In C. elegans, two key genes in the heterochronic pathway, lin-4 and let-7, encode small temporally expressed RNAs (stRNAs) that are not translated into protein. These stRNAs exert negative post-transcriptional regulation by binding to complementary sequences in the 3′ untranslated regions of their target genes. stRNAs are transcribed as longer precursor RNAs that are processed by the RNase Dicer/DCR-1 and members of the RDE-1/AGO1 family of proteins, which are better known (...) for their roles in RNA interference (RNAi). However, stRNA function appears unrelated to RNAi. Both sequence and temporal regulation of let-7 stRNA is conserved in other animal species suggesting that this is an evolutionarily ancient gene. Indeed, C. elegans, Drosophila and humans encode at least 86 other RNAs with similar structural features to lin-4 and let-7. We postulate that other small non-coding RNAs may function as stRNAs to control temporal identity during development in C. elegans and other organisms. BioEssays 24:119–129, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

The ability to represent emotional experiences in a precise fashion with language, termed emotional granularity, is related to a number of beneficial outcomes. However, the emotion granularity construct and operationalization are rooted in the lens of so-called Western, Educated, Industrialized, Rich and Democratic (WEIRD) societies that focus on emotions as a mental-state phenomena. Using evidence from multiple non-WEIRD societies, we illustrate that people's everyday vernacular often emphasizes bodily over, or in addition to, mental states. This suggests that granularity focused only (...) on mental state language may limit our ability to operationalize this construct in a culturally valid manner. To overcome this limitation, we propose capturing “experiential” granularity and a concept model on how it may link to regulation and health. (shrink)

Fundamental problems in developmental biology, such as the generation of asymmetry, differential transcription, and the execution of positional information, are all exhibited by a prokaryotic system, the Caulobacter cell cycle. Progeny cells resulting from each cell division have different developmental programs with respect to patterns of transcription and the initiation of DNA replication. The binary fission that yields dissimilar progeny results from asymmetry generated in the parent cell. An aspect of this fundamental developmental event is the temporally‐controlled (...) biogenesis of a polar flagellum. Several flagellar promoters require the histone‐like protein, integration host factor (IHF) for transcription activation. IHF introduces bends in DNA resulting in the reorganization of the higher‐order structure of the promoter region. These promoters appear to be transcribed from the chromosome in the swarmer pole of the predivisional cell. The newly replicated chromosomes in the predivisional cell differ in sedimentation coefficient and in the ability to initiate replication in the progeny cell. We hypothesize that the differential higher order structure of the two chromosomes contributes to both replication potential and transcription specificity. (shrink)

Late lung development comprises the formation of the terminal sac followed by the subdivision of the terminal sac by septa into alveoli and results in the formation of the gas‐exchange surface of the lung. This developmentally regulated process involves a complex epithelium–mesenchyme interaction via evolutionarily conserved molecular signaling pathways. In addition, there is a continuous process of vascular growth and development. Currently there are large gaps in our understanding of the molecular mechanisms involved in the formation of the gas‐exchange surface. (...) In this review, we attempt to integrate and reconcile the morphologic features in late lung development with what is known about the molecular basis for these processes. We describe the formation of the terminal sac and the subsequent formation of the septa, which divide the terminal sac into alveoli, in terms of the classically described developmental stages of induction, morphogenesis and differentiation. We believe that evolutionarily conserved pathways regulate this process and that morphogen gradients are likely to be a central mechanism. In addition, we highlight the importance of the molecular mechanisms involved in the simultaneous development of the vascular bed and its importance in the late development of the lungs. BioEssays 24:1052–1059, 2002. © 2002 Wiley‐Periodicals, Inc. (shrink)

Once deemed not respectable as a scientific domain, when behaviourist doctrine held sway, emotion is now an exploding subject of compelling attraction to a wide range of disciplines in psychology and neuroscience. Recent work suggests that the concept of 'affective regulation' has become a buzzword in these areas. Disciplines involved include not only affective neuroscience, but also cognitive neuroscience, developmental psychology, clinical psychiatric studies into syndromes of emotion dys-regulation , various psychotherapy approaches, and several others, e.g. the (...) increasingly popular fields of meditation and relaxation training. However, the overall conceptualization of emotion and its close ties to cognitive processes continues to befuddle many theorists and researchers, for various reasons. Mario Beauregard , Consciousness, Emotional Self-Regulation and the Brain. (shrink)

The growing field of evo-devo is increasingly demonstrating the complexity of steps involved in genetic, intracellular regulatory, and extracellular environmental control of the development of phenotypes. A key result of such work is an account for the remarkable plasticity of organismal form in many species based on relatively minor changes in regulation of highly conserved genes and genetic processes. Accounting for behavioral plasticity is of similar potential interest but has received far less attention. Of particular interest is plasticity in (...) communication systems, where human language represents an ultimate target for research. The present paper considers plasticity of language capabilities in a comparative framework, focusing attention on examples of a remarkable fact: Whereas there exist design features of mature human language that have never been observed to occur in non-humans in the wild, many of these features can be developed to notable extents when non-humans are enculturated through human training. These examples of enculturated developmental plasticity across extremely diverse taxa suggest, consistent with the evo-devo theme of highly conserved processes in evolution, that human language is founded in part on cognitive capabilities that are indeed ancient and that even modern humans show self-organized emergence of many language capabilities in the context of rich enculturation, built on the special social/ecological history of the hominin line. Human culture can thus be seen as a regulatory system encouraging language development in the context of a cognitive background with many highly conserved features. (shrink)

Alternative splicing (AS) is a widespread mechanism with an important role in increasing transcriptome and proteome diversity by generating multiple different products from the same gene. Evolutionary studies of AS have focused primarily on the conservation of alternatively spliced sequences or of the AS pattern of those sequences itself. Less is known about the evolution of the regulation of AS, but several studies, working from different perspectives, have recently made significant progress. Here, we categorize the different levels of AS (...) evolution, and summarize the studies on evolution of AS regulation, which point to a high level of evolutionary conservation of the regulation of AS events conserved between related species. This suggests that the quantitative regulation of AS is an intrinsic part of AS function. We discuss the potential role of changes in developmental regulation of AS as an additional layer in complex gene regulatory networks and in the emergence of genetic novelties. (shrink)

DNA repair is important in such phenomena as carcinogenesis and aging. While much is known about DNA repair in single‐cell systems such as bacteria, yeast, and cultured mammalian cells, it is necessary to examine DNA repair in a developmental context in order to completely understand its processes in complex metazoa such as man. We present data to support the notion that proliferating cells from organ systems, tumors, and embryos have a greater DNA repair capacity than terminally differentiated, nonproliferating cells. (...) Differential expression of repair genes and accessibility of chromatin to repair enzymes are considered as determinants in the developmental regulation of DNA repair. (shrink)

Davydov’s mathematics curriculum was designed according to the principles of the Cultural Historical Activity Theory. In this study, we analyzed some developmental effects of its realization in Grade 1, in relation to the children’s school readiness level, and their teacher’s experience. We assessed two groups of developmental effects: some general math abilities ; and some abilities, which are very specific to Davydov’s mathematics curriculum. At the beginning of the Grade 1, we divided all participants into three groups according (...) to their level of motivation, voluntary regulation, and logical preservation in terms of J. Piaget. After 1 year we measured general effects again and also measured specific effects. The results showed that all the children became significantly better in all general math abilities. It was also found that progress in math abilities does not depend on the initial level of school readiness of children. Children with different levels of voluntary regulation, motivational readiness, and the level of logical preservation show improvements in general math abilities. As for the mathematical skills specific to the Davydov’ program, the achieved level of their development is also not related to the initial parameters of readiness for school. Also, there were no differences in improvements in general effects and in specific effects between the classes with experienced and not-so-experienced teacher. So, there are some reasons to believe that the level of the child’s actual development does not play a fundamental role for education, which built in accordance with the principles of CHAT. (shrink)

During early embryonic development in several metazoans, accurate DNA replication is ensured by high number of replication origins. This guarantees rapid genome duplication coordinated with fast cell divisions. In Xenopus laevis embryos this program switches to one with a lower number of origins at a developmental stage known as mid‐blastula transition (MBT) when cell cycle length increases and gene transcription starts. Consistent with this regulation, somatic nuclei replicate poorly when transferred to eggs, suggesting the existence of an epigenetic (...) memory suppressing replication assembly origins at all available sites. Recently, it was shown that histone H1 imposes a non‐permissive chromatin configuration preventing replication origin assembly on somatic nuclei. This somatic state can be erased by SSRP1, a subunit of the FACT complex. Here, we further develop the hypothesis that this novel form of epigenetic memory might impact on different areas of vertebrate biology going from nuclear reprogramming to cancer development. (shrink)

Disruptions in chromatin regulator genes are frequently the cause of neurodevelopmental and neuropsychiatric disorders. Chromatin regulators are widely expressed in the brain, yet symptoms suggest that specific circuits can be preferentially altered when they are mutated. Using Drosophila allows targeted manipulation of chromatin regulators in defined neuronal classes, lineages, or circuits, revealing their roles in neuronal precursor self‐renewal, dendrite and axon targeting, neuron diversification, and the tuning of developmental signaling pathways. Phenotypes arising from chromatin regulator disruption are context dependent (...) – defined by interaction networks between the regulators, transcription factors, and chromatin remodeling complex partners. Future challenges are to determine the complexity of partner interactions, and to ascertain the degree to which cognitive deficits are due to loss of chromatin regulator activity in building a circuit or in maintaining homeostasis and activity within it. (shrink)

This paper argues that the “long 1970s” (1969–1983) is an important though often overlooked period in the development of a rich landscape in the research of metabolism, development, and evolution. The period is marked by: shrinking public funding of basic science, shifting research agendas in molecular biology, the incorporation of new phenomena and experimental tools from previous biological research at the molecular level, and the development of recombinant DNA techniques. Research was reoriented towards eukaryotic cells and development, and in particular (...) towards “giant” RNA processing and transcription. We will here focus on three different models of developmental regulation published in that period: the two models of eukaryotic genetic regulation at the transcriptional level that were developed by Georgii P. Georgiev on the one hand, and by Roy Britten and Eric Davidson on the other; and the model of genetic sufficiency and evolution of regulatory genes proposed by Emile Zuckerkandl. These three cases illustrate the range of exploratory hypotheses that characterised the challenging landscape of gene regulation in the 1970s, a period that in hindsight can be labelled as transitional, between the biology at the laboratory bench of the preceding period, and the biology of genetic engineering and intensive data-driven research that followed. (shrink)

The levels of different classes of mitochondrially encoded transcripts are developmentally regulated in sea urchin embryos, as a result of selection between mutually exclusive synthetic pathways. I propose a simple model to explain these observations, based on a dual role for mitochondrial ribosomes and translation factors in RNA synthesis as well as in translation. This effect may be exerted either at the transcriptional or post‐transcriptional level (or both), and is potentially generalizable to mammalian mtDNA and to other systems.

Ethics in business has been an increasingly controversial and important topic of discussion over the last decade. Debate continues about whether ethics should be a part of business, but also includes how business can implement ethical theory in day-to-day operations. Most discussions focus on either traditional moral philosophy, which offers little of practical value for the business community, or psychological theories of moral reasoning, which have been shown to be flawed and incomplete. The theory presented here is called the (...) class='Hi'>Developmental Self-Valuing Theory, and adapts the general psychological theory of Albert Bandura for ethics in business. In this theory, individuals first learn moral values from associations with others who are significant in their lives. Secondly, self-regulation is learned through a process of self-observation, self-judgment and self-reaction. Thirdly, the individual must believe that he can act ethically. Situational constraints and inducements, as well as positive and negative consequences for specific behaviors, will also affect the level of ethical performance. Each of these elements is examined and combined to achieve a practical method for increasing the level of ethics in corporate activity through selection, training and situational enhancement. (shrink)

Much contemporary biology consists of identifying the molecular components that associate to perform biological functions, then discovering how these functions are controlled. The concept of control is key to biological understanding, at least of the physiological kind; identifying regulators of processes underpins ideas of causality and allows complicated, multicomponent systems to be summarized in relatively simple diagrams and models. Unfortunately, as this article demonstrates by drawing on published articles, there is a growing tendency for authors to claim that a molecule (...) is a ‘regulator’ of something on evidence that cannot support the conclusion. In particular, gene knockout experiments, which can demonstrate only that a molecule is necessary for a process, are all too frequently being misinterpreted as revealing regulation. This logical error threatens to blur the important distinction between regulation and mere necessity and therefore to weaken one of our strongest tools for comprehending how organisms work. (shrink)

Measurements of open chromatin in specific cell types are widely used to infer the spatiotemporal activity of transcriptional enhancers. How reliable are these predictions? In this review, it is argued that the relationship between the accessibility and activity of an enhancer is insufficiently described by simply considering open versus closed chromatin, or active versus inactive enhancers. Instead, recent studies focusing on the quantitative nature of accessibility signal reveal subtle differences between active enhancers and their different inactive counterparts: the closed silenced (...) state and the accessible primed and repressed states. While the open structure as such is not a specific indicator of enhancer activity, active enhancers display a higher degree of accessibility than the primed and repressed states. Molecular mechanisms that may account for these quantitative differences are discussed. A model that relates molecular events at an enhancer to changes in its activity and accessibility in a developing tissue is also proposed. (shrink)

During embryogenesis, cell division must be spatially and temporally regulated with respect to other developmental processes. Leech embryos undergo a series of unequal and asynchronous cleavages to produce individually recognizable cells whose lineages, developmental fates and cell cycle properties have been characterized. Thus, leech embryos provide an opportunity to examine the regulation of cell division at the level of individual well‐characterized cells within a community of different types of cells. Isolation of leech homologues of some of the (...) highly conserved regulators of the cell division cycle, and characterization of their patterns of maternal and zygotic expression, indicate that the cell divisions of early leech embryos are regulated by cell type‐specific mechanisms. These studies with leech embryos contribute to the emerging appreciation of the diverse mechanisms by which animals regulate cell division during early development. (shrink)

The regulation of assisted reproduction technologies (ART) in China exhibits fragmentation, obsolescence, and a lower normative standing. Amid China's demographic challenges, discernible indications suggest a possible shift in stance towards the stringent regulation of ART. The present study furnishes an elucidation of extant ART regulations, delineates the developmental trajectory of reproductive rights within the Chinese legal framework, scrutinizes societal perspectives endorsing emancipated reproductive autonomy for women, and culminates by underscoring the necessity to acknowledge and uphold autonomous and (...) substantive reproductive rights throughout the process of reform. By comprehending and anticipating Chinese ART regulations, this article seeks to cultivate public discourse and enrich judicious decision-making among pertinent stakeholders. (shrink)

Developmental biology is expanding into several new areas. One new area of study concerns the production of adult-onset phenotypes by exposure of the fetus or neonate to environmental agents. These agents include maternal nutrients, developmental modulators (endocrine disruptors), and maternal care. In all three cases, a major mechanism for the generation of the altered phenotype is chromatin modification. Nutrient conditions, developmental modulators, and even maternal care appear to alter DNA methylation and other associated changes in chromatin that (...) regulate gene expression. This brings a new, under-appreciated, dimension of gene regulation into developmental biology, and it also demonstrates the poverty of the nature versus nurture framework for discussing phenotype production. Moreover, while such epigenetic mechanisms undermine genetic determinism, they add a layer of probabilistic biological causality for the maintenance of social inequalities. (shrink)

_Manual of Regulation-Focused Psychotherapy for Children with Externalizing Behaviors: A Psychodynamic Approach_ offers a new, short term psychotherapeutic approach to working dynamically with children who suffer from irritability, oppositional defiance and disruptiveness. _RFP-C_ enables clinicians to help by addressing and detailing how the child’s externalizing behaviors have meaning which they can convey to the child. Using clinical examples throughout, Hoffman, Rice and Prout demonstrate that in many dysregulated children, _RFP-C_ can: Achieve symptomatic improvement and developmental maturation as a (...) result of gains in the ability to tolerate and metabolize painful emotions, by addressing the crucial underlying emotional component. Diminish the child’s use of aggression as the main coping device by allowing painful emotions to be mastered more effectively. Help to systematically address avoidance mechanisms, talking to the child about how their disruptive behavior helps them avoid painful emotions. Facilitate development of an awareness that painful emotions do not have to be so vigorously warded off, allowing the child to reach this implicit awareness within the relationship with the clinician, which can then be expanded to life situations at home and at school. This handbook is the first to provide a manualized, short-term dynamic approach to the externalizing behaviors of childhood, offering organizing framework and detailed descriptions of the processes involved in _RFP-C_. Supplying clinicians with a systematic individual psychotherapy as an alternative or complement to PMT, CBT and psychotropic medication, it also shifts focus away from simply helping parents manage their children’s misbehaviors. Significantly, the approach shows that clinical work with these children is compatible with understanding the children’s brain functioning, and posits that contemporary affect-oriented conceptualizations of defense mechanisms are theoretically similar to the neuroscience construct of implicit emotion regulation, promoting an interface between psychodynamics and contemporary academic psychiatry and psychology. Manual of Regulation-Focused Psychotherapy for Children with Externalizing Behaviors: A Psychodynamic Approach is a comprehensive tool capable of application at all levels of professional training, offering a new approach for psychoanalysts, child and adolescent counselors, psychotherapists and mental health clinicians in fields including social work, psychology and psychiatry. (shrink)

Emotion theories based on research with adults must be able to accommodate developmental data if they are to be deemed satisfactory accounts of human emotion. Inspired in part by theory and research on adult emotion, developmentalists have investigated emotion-related processes including affect elicitation, internal and overtly observable emotion responding, emotion regulation, and understanding emotion in others. Many developmental studies parallel investigations conducted with adults. In this article, we review current theories of emotional development as well as research (...) related to the several aspects of emotion designated above. Beyond providing an overview of the field, we hope to encourage greater cross-fertilization and research collaboration between developmental psychologists and scholars who focus on adult emotion. (shrink)

There is increasing evidence that dynamic changes to chromatin, chromosomes and nuclear architecture are regulated by RNA signalling. Although the precise molecular mechanisms are not well understood, they appear to involve the differential recruitment of a hierarchy of generic chromatin modifying complexes and DNA methyltransferases to specific loci by RNAs during differentiation and development. A significant fraction of the genome-wide transcription of non-protein coding RNAs may be involved in this process, comprising a previously hidden layer of intermediary genetic information that (...) underpins developmental ontogeny and the differences between species, ecotypes and individuals. It is also evident that RNA editing is a primary means by which hardwired genetic information in animals can be altered by environmental signals, especially in the brain, indicating a dynamic RNA-mediated interplay between the transcriptome, the environment and the epigenome. Moreover, RNA-directed regulatory processes may also transfer epigenetic information not only within cells but also between cells and organ systems, as well as across generations. (shrink)

Metacognition refers to any knowledge or cognitive process that monitors or controls cognition. We highlight similarities between metacognitive and executive control functions, and ask how these processes might be implemented in the human brain. A review of brain imaging studies reveals a circuitry of attentional networks involved in these control processes, with its source located in midfrontal areas. These areas are active during conflict resolution, error correction, and emotional regulation. A developmental approach to the organization of the anatomy (...) involved in executive control provides an added perspective on how these mechanisms are influenced by maturation and learning, and how they relate to metacognitive activity. (shrink)

The poly(A)‐dependent translational regulation of maternal mRNAs is an important mechanism to execute stage‐specific programs of protein synthesis during early development. This control underlies many crucial developmental events including the meiotic maturation of oocytes and activation of the mitotic cell cycle at fertilization. A recent report(1) demonstrates that the 3′ untranslated region of the cyclin A1, B1, B2 and c‐mos mRNAs determines the timing and extent of their cytoplasmic polyadenylation and translational activation during Xenopus oocyte maturation. These studies (...) further establish that protein synthesis can be temporally and quantitatively controlled by developmentally regulated changes in the polyadenylation of maternal mRNAs. (shrink)

In this paper, we draw on developmental findings to provide a nuanced understanding of background emotions, particularly those in depression. We demonstrate how they reflect our basic proximity (feeling of interpersonal connectedness) to others and defend both a phenomenological and a functional claim. First, we substantiate a conjecture by Fonagy & Target (International Journal of Psychoanalysis 88(4):917–937, 2007) that an important phenomenological aspect of depression is the experiential recreation of the infantile loss of proximity to significant others. Second, we (...) argue that proximity has a particular cognitive function that allows individuals to morph into a cohesive dyadic system able to carry out distributed emotion regulation. We show that elevated levels of psychological suffering connected to depressive background emotions may be explained not only in terms of a psychological loss, but also as the felt inability to enter into dyadic regulatory relations with others—an experiential constraint that decreases the individual’s ability to adapt to demanding situations. (shrink)

The aim of this dissertation is to provide an analysis of central concepts in philosophy of science from the perspective of current molecular and developmental research. Each chapter explores the ways in which particular phenomena or discoveries in molecular biology influences our philosophical understanding of the nature of scientific knowledge. The introductory prologue draws some general connections between the various threads, which revolve around two central themes: causation and explanation. Chapter Two identifies a particular type of causal relation which (...) is widespread across the sciences, but cannot be straightforwardly accommodated by extant accounts of causation and causal explanation. Chapter Three explores how the form of redundant causality identified in the previous chapter plays an important role in causal explanation, by making the effect stable and robust. Chapter Four offers a novel perspective on the debate over biological reductionism by distinguishing between different paradigms of molecular explanation. Chapter Five provides a philosophical analysis of the so-called "Developmental Synthesis" of evolutionary and developmental biology, and suggests a general account of scientific unification grounded in the notion of explanatory relevance. Chapter Six offers an account of dispositional properties inspired by mechanisms of gene regulation, according to which dispositions are not properties of entities, but properties that describe the behavior of abstract idealized models. Finally, Chapter Seven scrutinizes the concept of the molecular ecosystem, a metaphor frequently employed by biologists to describe cellular interactions, but seldom articulated in detail. (shrink)

An alteration in the developmental mechanisms that regulate telencephalic patterning or pallial growth may have led to an enlargement of the dorsal pallium during evolution, and to the origin of isocortex. Developmental mechanisms that may have produced a pallial enlargement, and the parallelism of this event with the enlargement of the dorsal thalamus during evolution are discussed.

The development of T cells and B cells from pluripotent hematopoietic precursors occurs through a stepwise narrowing of developmental potential that ends in lineage commitment. During this process, lineage-specific genes are activated asynchronously, and lineage-inappropriate genes, although initially expressed, are asynchronously turned off. These complex gene expression events are the outcome of the changes in expression of multiple transcription factors with partially overlapping roles in early lymphocyte and myeloid cell development. Key transcription factors promoting B-cell development and candidates for (...) this role in T-cell development are discussed in terms of their possible modes of action in fate determination. We discuss how a robust, stable, cell-type–specific gene expression pattern may be established in part by the interplay between endogenous transcription factors and signals transduced by cytokine receptors, and in part by the network of effects of particular transcription factors on each other. BioEssays 21:726–742, 1999. © 1999 John Wiley & Sons, Inc. (shrink)

Information about the structure, function and regulation of the maize Suppressormutator (Spm) transposable element has emerged from the genetic and molecular characterization of both deletion mutations and an unconventional type of reversible genetic change (epimutation). The element is subject to an epigenetic mechanism that can either stably inactivate it or specify one of a variety of heritable programs of differential element expression in development. The essay explores the relationship between the Spm element's epigenetic developmental programming mechanism and the (...) determinative events central to plant development and differentiation. (shrink)

Systems theory holds that emotional responses derive from the continuous, mutual interaction between multiple neurobiological and behavioral systems associated with emotion as they are contextually embedded. Developmental systems theory portrays these systems as becoming progressively integrated as they mature. From this perspective, regulatory processes are incorporated into emotion throughout the course of emotional development. This article examines the implications of developmental systems theory in understanding the association between emotion and emotion regulation, enlisting the functionalist orientation of contemporary (...) emotions theory, a broad portrayal of emotion regulatory influences, and attention to the role of context in the management of emotion. (shrink)

Emotion regulation is an umbrella term to describe interactive, goal-dependent explicit and implicit processes that are intended to help an individual manage and shift an emotional experience. The primary window for appropriate emotion regulation development occurs during the infant, toddler, and preschool years. Atypical emotion regulation development is considered a risk factor for mental health problems and has been implicated as a primary mechanism underlying childhood pathologies. Current treatments are predominantly verbal- and behavioral-based and lack the opportunity (...) to practice in-the-moment management of emotionally charged situations. There is also an absence of caregiver-child interaction in these treatment strategies. Based on behavioral and neural support for music as a therapeutic mechanism, the incorporation of intentional music experiences, facilitated by a music therapist, may be one way to address these limitations. Musical Contour Regulation Facilitation is an interactive therapist-child music-based intervention for emotion regulation development practice in preschoolers. The Musical Contour Regulation Facilitation intervention uses the deliberate contour and temporal structure of a music therapy session to mirror the changing flow of the caregiver-child interaction through the alternation of high arousal and low arousal music experiences. The purpose of this paper is to describe the Therapeutic Function of Music, a theory-based description of the structural characteristics for a music-based stimulus to musically facilitate developmentally appropriate high arousal and low arousal in-the-moment emotion regulation experiences. The Therapeutic Function of Music analysis is based on a review of the music theory, music neuroscience, and music development literature and provides a preliminary model of the structural characteristics of the music as a core component of the Musical Contour Regulation Facilitation intervention. (shrink)

This article focuses on the question of how we perceive and represent ourselves at the most minimal, pre-reflective level. We first review recent work emphasizing the multisensory basis of our perceptual experiences and the embodied nature of self-awareness. We then focus on interoceptive and tactile signals, as key components of bodily self-consciousness, and discuss one crucial yet overlooked aspect of our embodiment, namely the fact that bodily self-consciousness emerges from the outset within the body of another experiencing subject. Next, we (...) review empirical findings highlighting the developmental primacy of tactile and interoceptive over visual experiences, in shaping the foundations of perceptual awareness. Building upon the influential predictive processing framework in philosophy and theoretical neuroscience, we argue that self-awareness is not only embodied, but also that perceptual experiences are fundamentally 'selfish', that is, imperatively driven by basic constraints of physiological regulation that subserve self-preservation. We then evaluate. (shrink)

In response to nutrient limitation, many animals, including Caenorhabditis elegans, slow or arrest their development. This process requires mechanisms that sense essential nutrients and induce appropriate responses. When faced with nutrient limitation, C. elegans can induce both short and long‐term survival strategies, including larval arrest, decreased developmental rate, and dauer formation. To select the most advantageous strategy, information from many different sensors must be integrated into signaling pathways, including target of rapamycin (TOR) and insulin, that regulate developmental progression. (...) Here, how nutrient information is sensed and integrated into developmental decisions that determine developmental rate and progression in C. elegans is reviewed. (shrink)

Self-ascriptions of thoughts and attitudes depend on a sense of the intentionality of one’s own mental states, which develops later than, and independently of, the sense of the intentionality of the thoughts and attitudes of others. This sense of the self-intentionality of one’s own mental states grows initially out of executive developments that enable one to simulate one’s own actions and perceptions, as genuine off-line thoughts, and to regulate such simulations.

Coronins constitute an evolutionarily conserved family of WD‐repeat actin‐binding proteins, which can be clearly classified into two distinct groups based on their structural features. All coronins possess a conserved basic N‐terminal motif and three to ten WD repeats clustered in one or two core domains. Dictyostelium and mammalian coronins are important regulators of the actin cytoskeleton, while the fly Dpod1 and the yeast coronin proteins crosslink both actin and microtubules. Apart from that, several coronins have been shown to be involved (...) in vesicular transport. C. elegans POD‐1 and Drosophila coro regulate the actin cytoskeleton, but also govern vesicular trafficking as indicated by mutant phenotypes. In both organisms, defects in cytoskeleton and trafficking lead to severe developmental defects ranging from abnormal cell division to aberrant formation of morphogen gradients. Finally, mammalian coronin 7 appears not to execute any cytoskeleton‐related functions, but rather participates in regulating Golgi trafficking. Here, we review recent data providing more insight into molecular mechanisms underlying the regulation of F‐actin structures, cytoskeletal rearrangements and intracellular membrane transport by coronin proteins and the way that they might link cytoskeleton with trafficking in development and disease. BioEssays 27:625–632, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

In emphasising improvement, smooth coping and success over variability and regression, skill theory has overlooked the processes performers at all levels develop and rely on for managing bodily and affective fluctuations, and their impact on skilled performance. I argue that responding to the instability and variability of unique bodily capacities is a vital feature of skilled action processes. I suggest that embodied intelligence – a term I use to describe a set of abilities to perceptively interpret and make use of (...) information from body, mind, environment and task requirements, and to modulate one’s focus, awareness and action strategies accordingly – is critical for performing well-learned skills in vulnerable situations. It is critical for staying safe. To investigate these components of skilled action, I employ a cognitive ethnographic method, combined with apprenticeship on the static trapeze, to produce two ‘experience near’ case studies. These document in-situ experiences of awareness, self-regulation and embodied intelligence. Both reveal strong connections between a reflective awareness of bodily vulnerability and variability, and self-regulatory processes – specifically, the down- and up-regulation of anxiety. I then reflect on these case studies in relation to a prospective sense of agency, the awareness of control acts that may lead to performance outcomes. With increased clarity on these features of embodied intelligence and attention during action, other researchers can build on this study to further probe and map the maintenance and functions of embodied intelligence in dealing with the instability of skills. (shrink)

Studies in adults with mental disorders suggest that the experience of early and chronic trauma is associated with changes in reward expectancy and processing. In addition, severe childhood trauma has been shown to contribute to the development of mental disorders in general. Data on effects of early childhood trauma on reward expectancy and processing in middle childhood currently appear insufficient. The present study aims to fill this research gap by examining the effects of developmental trauma disorder on reward expectancy (...) and processing in children aged 8–12 years, testing the hypothesis that children with multiple complex traumas exhibit altered reward processing as a result of prior disappointing reward experiences. One main feature of developmental trauma disorder is early experiences of multiple separation from important and close relationships alongside other experiences of emotional or physical harm. In the sequel children often show affect regulation disorders. To investigate this, we have developed an adapted version of the Monetary Incentive Delay Task, which examines children’s expectation of reward or frustration. In this first study, behavioral data will be collected from N = 40 children using this adapted version of the MID Task. Children in the experimental group will be recruited from youth welfare centers in Frankfurt a.M., Germany. Healthy control subjects will be recruited from after-school-care facilities. A brief trauma screening will be conducted for both groups, experimental and control. If children show signs of trauma, the presence of a developmental trauma disorder will be further delineated by a German translation of the Developmental Trauma Disorder Structured Interview for Children which was translated the first time in German by our research group. We hypothesize that children in the experimental group will be less accurate in performing the Monetary Incentive Delay Task because of their impaired emotion regulation skills due to emotional avoidance following developmental trauma. If the results of our initial behavioral study are promising, the MID task will be used in a future study to elucidate the relationship between trauma developmental disorder, reward expectancy and processing, and neurobiological processes in middle childhood. (shrink)

One of the central issue of developmental biology concerns the molecular mechanisms whereby a multipotent cell gives rise to distinct differentiated progeny. Differences between specialised cell types reflect variations in their patterns of gene expression. The regulation of transcription initiation is an important control point for gene expression and it is, therefore, not surprising that transcription factors play a pivotal role in mammalian development and differentiation.Haemopoiesis offers a uniquely tractable system for the study of lineage commitment and differentiation. (...) The importance of transcription factor in the normal regulation of haemopoiesis is underlined by the frequency with which transcription factors are targeted by leukaemogenic mutations. Studies of the function and regulation of haemopoietic transcription factors, especially those expressed in lineage‐restricted patterns, should greatly increase our understanding of the molecular control of haemopoiesis. In this review we have focused on insights provided by recent studies of the GATA and SCL proteins. (shrink)

Oocytes, eggs and blastomeres of the embryo are special cells that undergo rapid changes in structure and function at developmental transitions. These changes are frequently regulated by cytoplasmic signaling events, particularly at the developmental transition of fertilization, because the genome is largely inactivated at this time. Protein kinase C (PKC) is a signaling agent that acts after the sperm‐induced rise in calcium and has a central role in the remodeling of the structure of the egg into the zygote (...) in many species. PKC also acts during other developmental transitions. This kinase serves as a chronometer, which can choreograph the cell's remodeling events in both space and time. Several technical advancements discussed in this review have permitted a better understanding of the actions of PKC. (shrink)

Mentalization is a useful ability for social functioning and a crucial aspect of mentalizing is emotion regulation. Literature suggests programmes for children and adults to increase mentalizing abilities useful both for emotional and social competences. For this reason, the issue of how to prompt children’s mentalization has started to attract researchers’ attention, supporting the importance of the interpersonal dimension for the individual differences in the developmental of mentalization. The TiM (Thoughts in Mind) Project, a training programme based on (...) the explanation of mentalization mechanisms and designed for adults, deals with emotion regulation. Starting from the TiM Project, this study tests the effects of the TiM Child (TiM-C) training programme, over a control training programme, a conversational training designed for the school context, in children attending Year 2 of primary school. We designed a training based on narratives, followed by multiple-choice questions and conversations about mental states. Our results revealed significant improvements over the training period only in the TiM-C Project group for Metacognition, Emotion Regulation Strategies and a Theory of Mind task. As far as the educational implications, our findings suggest that it is possible to enhance mentalization through activities at school by promoting not only the understanding of the relations between mind and emotion, but also metacognitive skills. (shrink)