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PubMed1993

The stimulation of vasopressin gene expression in cultured hypothalamic neurons by cyclic adenosine 3',5'-monophosphate is reversible.

Previous studies have demonstrated that the number of vasopressin (VP) neurons present in primary diencephalic cultures can be markedly augmented by treatment with drugs that elevate intracellular cAMP. To evaluate the effect of this drug treatment on VP secretion by hypothalamic cultures and to determine if this represents a developmental phenomenon or a mechanism involved in the continuing dynamic regulation of the VP gene, we have exposed primary dispersed hypothalamic cultures derived from 14-day-old fetal Sprague-Dawley rats to forskolin (25 microM) and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX; 500 microM), either continually or intermittently, for up to 39 days. Culture medium was collected throughout the culture period for VP RIA, and at the end of the culture period, cultures were stained immunocytochemically for neurophysin (NP). As reported by previous investigators, exposure to the drugs for 11 days resulted in an increase in the number of NP-positive neurons. The increase was sustained with longer periods of exposure up to 39 days. IBMX and forskolin treatment also resulted in detectable release of VP into the culture medium, which increased from 1.4 +/- 0.15 pg/ml at 11 days to 8.4 +/- 0.6 pg/ml after 32 days of drug treatment. The VP concentration remained undetectable (< 1.25 pg/ml) in nontreated cultures throughout this period. The effect on VP expression did not require immediate exposure to the drugs in culture, but did require the continuous presence of the drugs. Removal of the drugs from days 11-18 of culture resulted in an almost complete loss of NP-positive cells; however, reexposure to the drugs reinstated NP expression in a time-dependent fashion. The effect of IBMX/forskolin treatment on the expression of other neuronal markers was also evaluated. The treatment did not alter the total number of neurons, and there was no evidence of stimulation of oxytocin expression. There was a marked increase in the number and size of neurons stained immunocytochemically for tyrosine hydroxylase and a small increase in the number of cells staining for somatostatin. These results demonstrate that treatment with cAMP-elevating drugs markedly and selectively elevates VP secretion from dispersed hypothalamic cultures, but continuous exposure to the drugs is necessary to sustain the effect. These findings suggest that although cAMP is required in hypothalamic cultures for VP gene expression, it may also participate in the dynamic regulation of VP gene transcription in response to physiological challenges.

1-Methyl-3-isobutylxanthine↗
PubMed2005

No evidence for association between dyslexia and DYX1C1 functional variants in a group of children and adolescents from Southern Italy.

Recently, DYX1C1, a candidate gene for developmental dyslexia, encoding a nuclear tetratricopeptide repeat domain protein dynamically regulated in brain, has been characterized through a translocation breakpoint in a Finnish family. Two putatively functional variants, -3G/A and 1249G/T, have been reported to be significantly associated with dyslexia in this population. Further studies, conducted on different ethnic groups (English and Canadian), have not confirmed a role for DYX1C1 variants in increasing the risk for dyslexia. We investigated the role of these variants in dyslexic children and adolescents from Southern Italy. No significant evidence for association between dyslexia and these DYX1C1 putative functional variants has been shown. We argue that the different DYX1C1 allele frequencies shown among Italian and Finnish subjects with dyslexia could be attributable to the different linkage disequilibrium structure of these populations.

Adolescent↗
PubMed1999

Age and gonadotropins control Ca2+-spike acquisition in mouse oocytes isolated from early preantral follicles.

The action of gonadotropins upon the oocyte is known to be crucial at later stages of follicular development in mammals. However, its influence on oocytes at early preantral stages is still a matter of debate. In the present study we evaluated the onset of mouse oocyte's capacity to exhibit calcium spikes during preantral stages of follicular development, prior to meiotic competence acquisition. In particular, through the use of confocal microscopy, we probed for the specific effects of age and gonadotropin stimulation upon the calcium dynamics of preantral follicle oocytes. We found that important developmental changes on the Ca2+ signalling mechanisms take place early during follicular development. Specifically we demonstrate that both age and gonadotropin stimulation increase the capacity of oocytes recovered from preantral follicles to exhibit calcium spikes. We propose that a strictly morphological staging of follicular development is insufficient to predict oocyte behaviour and must take in consideration animal age and gonadotropin environment.

Aging↗
PubMed1993

[Intruders or innovators. More women physicians?].

The article discusses the impact of an increasing proportion of women medical doctors in Norway. Will a changing gender composition affect the medical culture as such and, in the event, how? The theoretical point of departure is the social construction of gender. One argument is that gender relations tend to be reconstructed through gendered processes, many of them leading to new forms of gendered divisions of labour among doctors. Women doctors may be considered as the same as, or as different from their male colleagues. Such a distinction is often blurred, but is nevertheless operative. Medicine as a system of production of scientific knowledge is itself assumed to be primarily a product of male thoughts and ideas. Conventional forms and procedures may be challenged by its new members. Medical work as such runs the risk of being trivialized. To both understand and explain current developmental tendencies and contradictions, we need to identify gendered dynamics. There are no easy political solutions, however, to the "gender question" in medicine.

Female↗
PubMedDate not supplied

Thymocytopoiesis in aging: the bone marrow-thymus axis.

Manifestations of aging in the mature T lymphocyte compartment have been attributed, to a major extent, to effects of the involuted thymus, at the thymic microenvironment level. However, since generation of T lymphocytes starts from hemopoietic stem cells that settle in the thymus and differentiate there, aging effects on the stem cells, and as a consequence, on the bone marrow (BM)-thymus axis, may also have an impact on patterns of thymocytopoiesis and on age-related thymus remodeling. This communication reviews our studies designed to determine whether BM cells manifest any aging effects that become overt in the resulting thymocytes. The experiments were performed by seeding of BM cells onto lymphoid-depleted fetal thymus (FT) explants, to enable distinguishing between processes that occur in the BM and those that are caused by the aging thymic microenvironment. The data show changes in the developmental potential of BM-derived cells, as reflected from the kinetics of cell cycle and intermediate steps from stem cell settling in the thymus to an early stage at the transition from CD4(-)CD8(-), double negative (DN), to CD4(+)CD8(+), double positive (DP) thymocytes. In addition, we have demonstrated that these early developmental steps of thymocytopoiesis are subject to feedback regulation by mature T cells, and the extent of regulation may be altered in old age. The pattern of T lymphocyte generation in aging is thus a result of dynamic changes in thymic, as well as extrathymic functions, along the sequential developmental steps from the stem cell to the ultimate mature cell.

Journal Article↗
PubMed2004

Crystal structure of the actin binding domain of the cyclase-associated protein.

Cyclase-associated protein (CAP or Srv2p) is a modular actin monomer binding protein that directly regulates filament dynamics and has been implicated in a number of complex developmental and morphological processes, including mRNA localization and the establishment of cell polarity. The crystal structure of the C-terminal dimerization and actin monomer binding domain (C-CAP) reveals a highly unusual dimer, composed of monomers possessing six coils of right-handed beta-helix flanked by antiparallel beta-strands. Domain swapping, involving the last two strands of each monomer, results in the formation of an extended dimer with an extensive interface. This structural and biochemical characterization provides new insights into the organization and potential mechanistic properties of the multiprotein assemblies that integrate dynamic actin processes into the overall physiology of the cell. An unanticipated finding is that the unique tertiary structure of the C-CAP monomer provides a structural model for a wide range of molecules, including RP2 and cofactor C, proteins involved in X-linked retinitis pigmentosa and tubulin maturation, respectively, as well as several uncharacterized proteins that exhibit very diverse domain organizations. Thus, the unusual right-handed beta-helical fold present in C-CAP appears to support a wide range of biological functions.

Actins↗
PubMed1984

Choice as the basis for mentation. A dialectic approach to mental development.

I propose to build on Robbins' new mind model for the primitive personalities a stronger base and a more clearcut development. The stronger base requires a clearer exposition of pleasure that includes the earliest choice an infant can make. Choice determines the beginning of the mind as a complex system of its own. Pleasure describes the motivational viewpoint. Taken together they will define the structure which constitutes the mind. I agree with Robbins that phenomenological psychic representation furnishes the building blocks for this developmental model but I see conflict in interstage development to be necessary to furnish the dynamism for growth and/or regression. Normal grandiosity is infantile pleasure in choice. I present pathological grandiosity from a new regressive viewpoint within the developmental framework. Robbins' case of N is used to illustrate these ideas. In addition I present some complex requirements for human object and self constancy to be achieved.

Choice Behavior↗
PubMed2001

Seasonal changes in bovine fertility: relation to developmental competence of oocytes, membrane properties and fatty acid composition of follicles.

Follicle dynamics and oocyte viability in Holstein primiparous and multiparous cows and the relationships between fertility and the biochemical and physical properties of oocyte membranes with season were examined. The conception rates of primiparous (n = 70 885) and multiparous (n = 143 490) cows differed, peaking in the winter and decreasing in the summer. The number of follicles 3-8 mm in diameter per ovary was higher in winter (19.6) compared with summer (12.0). However, in winter the percentage of ovaries with fewer than ten follicles per ovary was 16%, in contrast to 50% in summer. After aspiration of follicles, 7.5 oocytes per ovary were found in winter and 5.0 oocytes per ovary in summer. Cleavage to the two- to four-cell stage after chemical activation was greater in winter than in summer; this was enhanced at the morula stage and embryo development to the blastocyst stage was significantly higher in winter than in summer. Determination of the lipid phase transition in oocyte membranes revealed a shift of 6 degrees C between summer and winter. Fatty acid composition of phospholipids from follicular fluid, granulosa cells and oocytes indicated that there was a higher percentage of saturated fatty acids during the summer and that the percentages of mono-unsaturated and polyunsaturated fatty acids were higher in oocytes and granulosa cells during the winter. Oocytes and granulosa cells had similar fatty acid compositions, in contrast to follicular fluid. These results may explain the differences in the ability of oocytes to develop to the blastocyst stage at different seasons. Thus, temperature changes may lead to changes in membrane properties, which, in turn, can influence oocyte function and fertility.

Animals↗
PubMed2001

Dynamic localization of rop GTPases to the tonoplast during vacuole development.

Vacuoles are essential pleomorphic organelles that undergo dynamic changes during cell growth and differentiation in plants. How developmental signals are linked to vacuole biogenesis and development is poorly understood. In this report, we show that a Rop GTPase is localized to developing vacuoles in pea (Pisum sativum cv Extra Early Alaska). Rop belongs to the RHO family of Ras-related small GTP-binding proteins that are key molecular switches in a wide variety of eukaryotic signal transduction pathways. Using indirect immunofluorescence and an anti-Rop antibody, we showed that Rop proteins accumulate to high levels in rapidly growing tapetal cells of pea anthers. In these cells, Rop is localized to an endomembrane system that exists as dynamic pleomorphic networks: a perinuclear fine network decorated with punctate dots, a network composed of small spheres and tubules, and interconnected chambers. Colocalization with a tonoplast annexin VCaB42 shows that these dynamic networks represent the tonoplast. Our results suggest that the dynamic Rop-containing tonoplast networks represent a unique stage of vacuole development. The specific localization of Rop to developing vacuoles supports a role for Rop in signal transduction that mediates vacuole development in plants.

Endoplasmic Reticulum↗
PubMed1981

Developmental regulation of the carbohydrate composition of glycoproteins associated with central nervous system myelin.

Glycoproteins from central nervous system myelin were evaluated for developmental alterations in their carbohydrate composition by autoradiographic analysis of radioiodinated lectin binding after separation by high-resolution sodium dodecyl sulfate-pore gradient slab gel electrophoresis (SDS-PGE). Sixteen lectin-binding components were assessed in highly purified myelin preparations from 15-day, 18-day, and adult rat brains, using the lectins Triticum vulgaris (wheat germ agglutinin) and Ulex europeus (gorse agglutinin I). Developmental changes in lectin binding for individual glycoproteins were evaluated semiquantitatively by comparing densitometric scans of the autoradiographs. Both increases and decreases in lectin binding for individual components were observed as a consequence of development, as well as the appearance and disappearance of lectin binding to three low-molecular-weight components. No changes in electrophoretic mobility and hence glycoprotein molecular weight were observed in any components when using these lectins. These developmental changes in lectin binding suggest that increases in glycoprotein (receptor) density occur, as well as an elaboration of oligosaccharide branching for individual glycoproteins. In addition, the appearance of a new glycoprotein in the adult myelin membrane could imply a new functional role not present in the immature membrane. These observations suggest that dynamic alterations of myelin-associated glycoproteins occur during development. Such developmental regulation of membrane glycoproteins increases the significance of their potential role in myelination and myelin maintenance.

Animals↗
PubMed2004

The etiology of risk: a preliminary model.

The purpose of this paper is to describe an approach that links risk-assessment and theory-directed research. Here we describe a theoretical underpinning to current notions of dynamic risk assessment. The paper has two facets. First, the reframing of a number of concepts such as (i). Stable dynamic factors that we note would be better described as traits and hence have a grounding in the extant general psychological literature on trait theory, (ii). Static risk factors that can be viewed as historical markers of the same underlying psychological dispositions measured by stable dynamic risk factors; (iii). Acute risk factors that are better described as triggering/contextual risk factors (iv). Acute risk factors that should be defined as the state expression of traits triggered by triggering/contextual risk factors. And second, the description of an etiological model of risk- model taking into account the interaction between significant learning events (i.e., developmental variables), psychological vulnerabilities (i.e., marked by static/historical variables and/or stable dynamic risk factors), contextual or triggering factors and their convergence in offense-related acute dynamic risk (i.e., acute psychological states).

Child↗
PubMed1997

The polyhomeotic locus of Drosophila melanogaster is transcriptionally and post-transcriptionally regulated during embryogenesis.

The polyhomeotic (ph) locus of Drosophila is a complex locus essential for the maintenance of segmental identity. Genetic analysis suggested that two independent units contribute to ph function. Comparison of genomic sequence shows that the ph locus has been duplicated, and that it contains proximal and distal transcription units. The proximal transcription unit encodes two embryonic mRNAs of 6.4 and 6.1 kb, and the distal unit encodes a 6.4-kb embryonic mRNA. The proximal and distal transcription units are differentially regulated at the mRNA level during development as shown by developmental Northern analysis. The distal protein is very similar to the proximal product, except for the absence of an amino terminal region, and a small region near the carboxy terminus. The long open reading frame in the distal cDNA does not begin with an ATG codon, and an internal ATG is used for a start codon. We show that the proximal protein occurs in two forms that are developmentally regulated, and that probably arise from use of two different initiator methionine codons. We find no evidence for differential binding of proximal and distal products to polytene chromosomes. Nevertheless, we show that mutations in the proximal and distal proteins have differing effects on regulation of a reporter under the control of a regulatory region from bithoraxoid, suggesting that ph proximal and distal proteins have different functions. These results show that the ph locus undergoes complex developmental regulation, and suggest that Polycomb group regulation may be more dynamic than anticipated.

Animals↗
PubMed2006

Chromatin modifications in the germinal vesicle (GV) of mammalian oocytes.

The nucleus of eukaryotic cells is organized into functionally specialized compartments that are essential for the control of gene expression, chromosome architecture and cellular differentiation. The mouse oocyte nucleus or germinal vesicle (GV) exhibits a unique chromatin configuration that is subject to dynamic modifications during oogenesis. This process of 'epigenetic maturation' is critical to confer the female gamete with meiotic as well as developmental competence. In spite of its biological significance, little is known concerning the cellular and molecular mechanisms regulating large-scale chromatin structure in mammalian oocytes. Here, recent findings that provide mechanistic insight into the complex relationship between large-scale chromatin structure and global transcriptional repression in pre-ovulatory oocytes will be discussed. Post-translational modifications of histone proteins such as acetylation and methylation are crucial for heterochromatin formation and thus play a key role in remodeling the oocyte genome. This strategy involves multiple and hierarchical chromatin modifications that regulate nuclear dynamics in response to a developmentally programmed signal(s), presumably of paracrine origin, before the resumption of meiosis. Models for the experimental manipulation of large-scale chromatin structure in vivo and in vitro will be instrumental to determine the key cellular pathways and oocyte-derived factors involved in genome-wide chromatin modifications. Importantly, analysis of the functional differentiation of chromatin structure in the oocyte genome with high resolution and in real time will have wide-ranging implications to understand the role of nuclear organization in meiosis, the events of nuclear reprogramming and the spatio-temporal regulation of gene expression during development and differentiation.

Animals↗
PubMed1998

Pathogenesis of the developmental epilepsies.

The developmental epilepsies are distinctive in that they occur in a dynamic and plastic substrate. A variety of acquired insults may present with remarkably similar seizure syndromes that are age-specific and evolve with time. This evolution may be a consequence of the brain injury itself or an alteration of normal brain maturation due to an unfavorable electrical environment. Idiopathic epilepsies are now being correlated with specific gene defects, particularly those involving ion channels and/or neurotransmitter receptors. Despite this specificity, idiopathic seizure syndromes may be caused by mutations in different genes or different mutations in the same gene, and particular syndromes may manifest heterogeneous clinical seizure types. Not all localization-dependent epilepsies are symptomatic, as a growing number of genes have been identified with partial seizure syndromes. Febrile seizures probably do not represent a homogeneous entity, but multiple disorders that may be associated with developmental abnormalities and various coexisting seizure types.

Age Factors↗
PubMed2002

Neuronal differentiation and synapse formation occur in space and time with fractal dimension.

The analysis of a set of experimental data obtained by an independent team of researchers confirms that neuronal differentiation or synapse formation do occur in time and space with fractal dimension. The interacting cells create first a dynamic system with its own attractor, (i.e., a fragment of time and space where the dynamic processes occur and where no further evolution of the system is possible at all owing to the action of the intrasystemic forces unless some extrasystemic forces act upon it). This attractor is then modified in the active manner by the differentiating cells until the system attains a degenerated stationary state and differentiation ends. The fractal structure of the system is also lost in the course of tumor progression. Our data indicate that the cellular system can attain the degenerated stationary state, leaving the attractor with a fractal dimension directly or undergoing diversification into many attractors and going through the areas of deterministic chaos. Since evolution of the cellular system is driven by the cooperative dynamic processes, as reflected by the changes of the mean fractal dimension between the intervals of the Gompertzian curve, it is likely that cells differentiate into neurons and create synapses with a conjugated probability and non-Gaussian distribution rather than with the classical probability and the Gaussian distribution. These findings can help to optimize features of artificial neural networks. They also define a simple in vitro biological model for biophysical and biochemical studies on natural neural networks.

Cell Differentiation↗
PubMed1985

Developmental considerations in the concept of affective illness.

A spectrum exists from change, to crisis, to turmoil, and, at times, to illness at watersheds in the life cycle. Affective experience can be a mobilizing factor and emotional catalyst in the growth experience or a devastating psychotic mood disturbance when predisposing life events and genetic disposition are operational. This paper reviews the dynamics of biologic systems, chronobiology, and time-related transitions of the developmental experience. The relationship of a developmental time clock to affective phenomenology and clinical affective disorder is discussed and presented in two case vignettes. Developmental theory and the interface between life events, stress, and affective illness are reviewed and a concept of development as a sequence of affective cycles is presented.

Adolescent↗
PubMed2002

Origin of multicellular organisms as an inevitable consequence of dynamical systems.

The origin of multicellular organisms is studied by considering a cell system that satisfies minimal conditions, that is, a system of interacting cells with intracellular biochemical dynamics, and potentiality in reproduction. Three basic features in multicellular organisms-cellular diversification, robust developmental process, and emergence of germ-line cells-are found to be general properties of such a system. Irrespective of the details of the model, such features appear when there are complex oscillatory dynamics of intracellular chemical concentrations. Cells differentiate from totipotent stem cells into other cell types due to instability in the intracellular dynamics with cell-cell interactions, as explained by our isologous diversification theory (Furusawa and Kaneko, 1998a; Kaneko and Yomo, 1997). This developmental process is shown to be stable with respect to perturbations, such as molecular fluctuations and removal of some cells. By further imposing an adequate cell-type-dependent adhesion force, some cells are released, from which the next generation cell colony is formed, and a multicellular organism life-cycle emerges without any finely tuned mechanisms. This recursive production of multicellular units is stabilized if released cells are few in number, implying the separation of germ cell lines. Furthermore, such an organism with a variety of cellular states and robust development is found to maintain a larger growth speed as an ensemble by achieving a cooperative use of resources, compared to simple cells without differentiation. Our results suggest that the emergence of multicellular organisms is not a "difficult problem" in evolution, but rather is a natural consequence of a cell colony that can grow continuously.

Algorithms↗
PubMed2003

Enhancing nursing research with children and families using a developmental science perspective.

Nursing scholarship on children and their families has increased rapidly over the past decades. This research focuses on infants, children, and adolescents and their families facing acute or chronic illness, as well as on promoting health and preventing disease in children. While the amount and scope of research in pediatric nursing has increased, the methods and theories used are diverse and are often not based on the most recent science in the broader fields of developmental research. Developmental science, which evolved over the past two decades into a new interdisciplinary framework for the study of human development, involves an integrated holistic, developmental, and systems-oriented perspective. According to this view, the individual functions and develops through dynamic and complex processes involving the integration of many systems within the individual, including mental, biological, and behavioral systems. In addition, individuals function and develop in a continuously ongoing, reciprocal process of interaction with their environment and, as such, have an influence on that environment. These nonlinear, dynamic processes demand complex conceptualizations and research designs if one is to truly understand human development, including health and illness. Key aspects of developmental science important in conceptualization, design, measurement, and data analysis are identified. By providing a framework for critiquing research and presenting recommendations for future research based on developmental science, we hope to move nursing research with children forward toward more developmentally sound knowledge of nursing practice.

Acute Disease↗