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PubMed1998

Effects of in utero alcohol exposure on B-cell development in the murine fetal liver.

Fetal alcohol syndrome is one of the leading causes of birth defects in this country. Children exposed to alcohol in utero suffer from growth and mental retardation, physical abnormalities, and immune dysfunction. Previous work from this laboratory demonstrated that B lymphopoiesis is delayed in mice exposed to alcohol in utero. The deficit in B-cell development was apparent shortly after birth and extended to well after weaning. Because lymphopoiesis begins in the fetal liver, the current study was done to determine if fetal B-cell development was affected as well by in utero exposure to alcohol. We now show that the effects of in utero alcohol exposure on B lymphopoiesis do not become apparent until late in gestation. Flow cytometry was used to enumerate several intermediates in the B-cell developmental pathway. These phenotypic analyses showed that before day 17 of gestation, B-lineage intermediates developed normally when compared with control animals. However, between days 17 and 18 of gestation, an abnormality in the population dynamics of B-lineage intermediates became apparent in the fetal liver of alcohol-exposed mice. Early intermediates in the B-cell developmental pathway were present in normal numbers; however, the more mature progenitors as well as B cells were decreased in number by gestational day 18. These data suggest that in utero alcohol exposure disrupts the ability of B-lineage intermediates to progress along the developmental pathway to maturity, thereby leaving the animal immunocompromised at birth.

Animals↗
PubMed2004

Modulation of microtubule dynamics by tau in living cells: implications for development and neurodegeneration.

The neural microtubule-associated protein tau binds to and stabilizes microtubules. Because of alternative mRNA splicing, tau is expressed with either 3 or 4 C-terminal repeats. Two observations indicate that differences between these tau isoforms are functionally important. First, the pattern of tau isoform expression is tightly regulated during development. Second, mutation-induced changes in tau RNA splicing cause neuronal cell death and dementia simply by altering the isoform expression ratio. To investigate whether 3- and 4-repeat tau differentially regulate microtubule behavior in cells, we microinjected physiological levels of these two isoforms into EGFP-tubulin-expressing cultured MCF7 cells and measured the effects on the dynamic instability behavior of individual microtubules by time-lapse microscopy. Both isoforms suppressed microtubule dynamics, though to different extents. Specifically, 4-repeat tau reduced the rate and extent of both growing and shortening events. In contrast, 3-repeat tau stabilized most dynamic parameters about threefold less potently than 4-repeat tau and had only a minimal ability to suppress shortening events. These differences provide a mechanistic rationale for the developmental shift in tau isoform expression and are consistent with a loss-of-function model in which abnormal tau isoform expression results in the inability to properly regulate microtubule dynamics, leading to neuronal cell death and dementia.

Cell Line, Tumor↗
PubMed2002

Spatial and temporal pattern of Fgf-8 expression during chicken development.

This study analyzes the temporal and spatial expression pattern of Fgf-8 over a continuous series of developmental stages. Special emphasis is laid on the paraxial mesoderm where Fgf-8 expression is highly dynamic. Whereas the anterior portion of the unsegmented mesoderm is devoid of expression, Fgf-8 is upregulated in the posterior half of a newly formed somite. Soon after somite formation, this highly localized expression gives way to a more diffuse pattern of Fgf-8 expression at low levels in presumptive sclerotomal cells. During later somite maturation, transcripts become restricted to the myotome. Co-staining with the myotome marker MyoD reveals that Fgf-8 expression defines a subpopulation of muscle precursor cells.

Animals↗
PubMed2000

Signal transduction mechanisms in Caulobacter crescentus development and cell cycle control.

The life cycle of the aquatic bacterium Caulobacter crescentus includes an asymmetric cell division and an obligate cell differentiation. Each cell division gives rise to a motile but replication inert swarmer cell and a sessile, replication competent stalked cell. While the stalked progeny immediately reinitiates DNA replication and cell division, the swarmer cell remains motile and chemotactically active for a constant period of the cell cycle before it differentiates into a stalked cell. During this process, the cell looses motility by ejecting the flagellum, synthesizes a stalk and eventually initiates chromosome replication and cell division. The link of morphogenic transitions to the replicative cycle of Caulobacter implies that the developmental programs which determine asymmetry and cell differentiation must be tightly connected with cell cycle control. This has been confirmed by the recent identification of signal transduction mechanisms, which are involved in temporal and spatial control of both development and cell cycle. Interestingly, the cell has recruited two-component signal transduction systems for this internal control, a family of regulatory proteins which usually are involved in the information transfer between the environment and the inside of a cell. The response regulator protein CtrA controls several key cell cycle events like the initiation of DNA replication, DNA methylation, cell division, and flagellar biogenesis. The activity of this master regulator is subject to complex temporal and spatial control during the C. crescentus cell cycle, including regulated transcription, phosphorylation and degradation. Three membrane bound sensor kinases have been proposed to control the phosphorylation status of CtrA. Two of these, CckA and DivJ, exhibit specific subcellular localization and, in the case of CckA, dynamic rearrangement in the course of the cell cycle. These findings support the idea that the developmental program of C. crescentus is controlled at least in part by localized cues that act as checkpoints for the control of morphological changes and cell cycle progression.

Caulobacter crescentus↗
PubMed1999

Structure, assembly, and dynamics of actin filaments in situ and in vitro.

Actin, though highly conserved, exhibits a myriad of diverse functions, most of which ultimately depend on its intrinsic ability to rapidly assemble and disassemble filamentous structures. Many organisms synthesize multiple actin isoforms even within the same cell. Tissue-specific expression patterns and tight developmental regulation as well as a high conservation across species emphasize the functional importance of isoforms. The detailed knowledge of the structure, assembly, and dynamic behavior of actin provides important pieces in solving the puzzle of how the different isoforms can be so versatile despite their extremely high sequence identity.

Actins↗
PubMed2003

Theory, methods and new directions in the psychophysiology of the schizophrenic process and schizotypy.

Theoretical and methodological issues in the psychophysiology of the schizophrenic process are reviewed. These include the importance of schizotypy with its compensatory abilities as well as deficits for elucidating the processes of development and prevention of schizophrenia. The importance of individual differences, syndromes and single case studies. The recognition that this is a dynamic and fluctuating illness and hence the relevance of functional neurophysiology, including the role of imbalances in hemispheric activation in ontogeny, developmental course, expression of symptoms, the effects of neuroleptics and recovery process, and the influence of stress a precipitant of breakdown. The role of thalamo-cortical activation systems. The particular value of electrocortical measures including the interrelations of electroencephalographic rhythms throughout the spectrum, and relations of gamma, dynamic core neuronal complexity, connectivity and sensory gating with experiences of unreality and disturbances of consciousness.

Animals↗
PubMed1999

[The parental maturity of elderly dependent parents. Contributions to a contextual definition].

This paper focuses on the conceptual exploration of the concept of parental maturity which has been introduced along with the concept of filial maturity to describe the dynamic optimal states of caring and being cared for in adult children and their dependent elderly parents. A review of the literature shows that the development of the concept, contrary to the concept of filial maturity, has hardly started. The concept refers to attitudes and conducts through which adults produce and educate their children in an optimal way, and continually support them in the accomplishment of their developmental tasks and roles when they are adults themselves. From this broad perspective parental maturity, or maturity in the parental role, is the dynamic capacity of an adult individual to engage oneself in an enduring way in the relationship with one's children and to accomplish the corresponding developmental tasks in an adequate and successful way. With a view to the improvement of the theoretical and clinical usefulness of the construct we introduce an elaborated conceptualization which is specific for elderly parents confronted with their impairment. The following is considered to be the core of the contextual definition: an enduring engagement in the intergenerational relationship with one's adult children in an empathetic and responsive way, with respect for the children's needs, limitations, abilities and autonomy, without degenerating into submission and loss of autonomy, which would be a (pathological) state of role reversal; the elderly guards his or her own continuing contribution to the intergenerational relationship. Based on these (general) mature parental attitudes a frail elderly parent would be able to endorse the filial responsibility of his or her middle-aged children. He or she is willing and able to ask for the help needed, in an uncompelling way. Furthermore, the frail elderly parent will receive the filial caregiving with some proper sensitive responsivity as well as accept what the children cannot give or do. Then, we shortly discuss how we want to operationalize parental maturity, with a view to empirical research, by means of the measurement of a complex of parental attitudes. Finally, we give some considerations regarding the historical-sociological context in which the phenomenon occurs.

Adaptation, Psychological↗
PubMed2006

Mitochondrial genome dynamics in plants and animals: convergent gene fusions of a MutS homologue.

Mitochondrial processes influence a broad spectrum of physiological and developmental events in higher eukaryotes, and their aberrant function can lead to several familiar disease phenotypes in mammals. In plants, mitochondrial genes directly influence pollen development and the occurrence of male sterility in natural plant populations. Likewise, in animal systems evidence accumulates to suggest important mitochondrial functions in spermatogenesis and reproduction. Here we present evidence for a convergent gene fusion involving a MutS-homologous gene functioning within the mitochondrion and designated Msh1. In only plants and soft corals, the MutS homologue has fused with a homing endonuclease sequence at the carboxy terminus of the protein. However, the endonuclease domains in the plants and the soft corals are members of different groups. In plants, Msh1 can influence mitochondrial genome organization and male sterility expression. Based on parallels in Msh1 gene structure shared by plants and corals, and their similarities in reproductive behavior, we postulate that this convergent gene fusion might have occurred in response to coincident adaptive pressures on reproduction.

Adenosine Triphosphatases↗
PubMed2003

Integrin receptors: the dynamic modulators of endometrial function.

Cell-cell and cell-extracellular matrix (ECM) interactions play a critical role in various developmental processes, including differentiation, proliferation and migration of cells. ECM proteins can influence cellular function thus creating a complex feedback mechanism. The adhesion of cells to each other, their ECM proteins and endothelial surfaces is mediated by a variety of membrane proteins collectively known as adhesion molecules. Adhesion molecules have been further divided into five subfamilies, the integrins, the selectins, the cadherins, the mucins and the immunoglobulin superfamily. Members of the integrin family of cell surface adhesion receptors are important mediators of cell-ECM contact. Integrin receptors are alpha beta heterodimers with a transmembrane segment, a short cytoplasmic domain and a large extracellular domain. The role of integrins in reproduction has been established. Several reasons make these molecules very attractive due to their constant involvement from egg to birth. They participate in sperm-egg interaction, fertilization, implantation and placentation in many species including humans. Integrins provide signals to individual cells essential for growth and development of different tissues. In the present review, we describe (1) the regulatory pathways for controlling expression of integrins in the endometrium, (2) various biomarkers and their role in endometrial function, (3) reproductive disorders in women related to aberrant integrin expression in the endometrium and (4) the functional significance of integrins available from gene knockout studies.

Animals↗
PubMed2002

cDNA cloning, sequence comparison, and developmental expression of Xenopus rac1.

The Rho family of small GTP-binding proteins are important signaling molecules that regulate the dynamics of the actin cytoskeleton and mediate changes in cell morphology and motility. Here, we describe the temporal and spatial patterns of expression of the Rho family member, rac, during the development of the amphibian, Xenopus laevis. We also present the deduced amino acid sequence of Xenopus rac (Xrac). At the amino acid level, Xrac is highly conserved relative to previously characterized rac homologs, and is nearly identical to human rac1. RNase protection assays and Western blot analysis indicate that Xrac mRNA and protein are present from fertilization through tailbud stages of development. Whole-mount in situ hybridizations show that Xrac transcripts are especially abundant in cells of the involuting marginal zone, and later, in the cranial neural crest, the developing central nervous system, and in the somites. The remarkable degree of evolutionary conservation observed in the Xrac primary structure together with its high level of expression in cells and structures critical to morphogenesis suggest a functionally important role for this Rho family member in early vertebrate development.

Amino Acid Sequence↗
PubMed2003

Four-dimensional imaging of cytoskeletal dynamics in Xenopus oocytes and eggs.

The Xenopus laevis (African clawed frog) system has long been popular for studies of both developmental and cell biology, based on a variety of its intrinsic features including the large size of Xenopus oocytes, eggs, and embryos, and the relative ease of manipulation. Unfortunately, the large size has also been considered a serious impediment for high-resolution light microscopy, as has the heavy pigmentation. However, the recent development and exploitation of 4D imaging approaches, and the fact that much of what is of most interest to cell and developmental biologists takes place near the cell surface, indicates that such concerns are no longer valid. Consequently, the Xenopus system in many respects is now as good as other model systems considered to be ideal for microscopy-based studies. Here, 4D imaging and its recent applications to cytoskeletal imaging in Xenopus oocytes and eggs are discussed.

Animals↗
PubMed2003

Reduced water availability influences the dynamics, development, and ultrastructural properties of Pseudomonas putida biofilms.

Pseudomonas putida strain mt-2 unsaturated biofilm formation proceeds through three distinct developmental phases, culminating in the formation of a microcolony. The form and severity of reduced water availability alter cell morphology, which influences microcolony size and ultrastructure. The dehydration (matric stress) treatments resulted in biofilms comprised of smaller cells, but they were taller and more porous and had a thicker extracellular polysaccharide layer at the air interface. In the solute stress treatments, cell filamentation occurred more frequently in the presence of high concentrations of ionic (but not nonionic) solutes, and these filamented cells drastically altered the biofilm architecture.

Biofilms↗
PubMed2004

Developmental regulation of lung liquid transport.

The developing distal lung epithelium displays an evolving liquid transport phenotype, reflecting a changing and dynamic balance between Cl- ion secretion and Na+ ion absorption, which in turn reflects changing functional requirements. Thus in the fetus, Cl--driven liquid secretion predominates throughout gestation and generates a distending pressure to stretch the lung and stimulate growth. Increasing Na+ absorptive capacity develops toward term, anticipating the switch to an absorptive phenotype at birth and beyond. There is some empirical evidence of ligand-gated regulation of Cl- transport and of regulation via changes in the driving force for Cl- secretion. Epinephrine, O2, glucocorticoid, and thyroid hormones interact to stimulate Na+ absorption by increasing Na+ pump activity and apical Na+ conductance (GNa+) to bring about the switch from net secretion to net absorption as lung liquid is cleared from the lung at birth. Postnatally, the lung lumen contains a small Cl--based liquid secretion that generates a surface liquid layer, but the lung retains a large absorptive capacity to prevent alveolar flooding and clear edema fluid. This review explores the mechanisms underlying the functional development of the lung epithelium and draws upon evidence from classic integrative physiological studies combined with molecular physiology approaches.

Animals↗
PubMed1989

Faecal incontinence in childhood: a multidisciplinary approach including biofeedback.

One hundred and seven children with faecal incontinence were evaluated and managed over a 3 year period by a multidisciplinary team. After initial clinical assessment, evaluation of defaecatory mechanisms (using a balloon model) and assessment of personal-social development and self-concept were undertaken. Management was based on initial bowel evacuation, short-term laxatives, and habit training involving systematic use of positive reinforcement; 69 children received biofeedback conditioning. Idiopathic megacolon with constipation and soiling was the most common finding (98 cases). Other diagnoses included previously undiagnosed neurogenic bowel (three cases), post-surgical and anomalies (four cases), and psychogenic encopresis (two cases). Idiopathic megacolon was characterized by decreased rectal sensation, increased threshold for external sphincter relaxation and an inability to evacuate. Faecal incontinence was associated with an undesirably low social self-concept (70% of the 40 evaluated), but was not related to a delay in development (mean general developmental quotient = 105 +/- 8, for the 35 tested). Family psychopathology warranting referral for family therapy was found in 14 children (13%). The management programme yielded a short-term (3 months) cure rate of 68% and a long-term (12 months) cure rate of 90%, with 10% having continued soiling which varied from occasional to several incidents/week. No significant improvement in self-concept was observed overall, although marked improvements were observed in some children. We conclude that disordered defaecatory dynamics are a major determinant of faecal incontinence in children. Undesirably low social self-concepts but normal developmental ability accompany this condition. Management is facilitated by a multidisciplinary approach, acknowledging the role of both behavioural and physiological components of the problem.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed2006

The epigenetic network regulating muscle development and regeneration.

This review focuses on our current knowledge of the epigenetic changes regulating gene expression at the chromatin and DNA level, independently on the primary DNA sequence, to reprogram the nuclei of muscle precursors during developmental myogenesis and muscle regeneration. These epigenetic marks provide the blueprint by which the extra-cellular cues are interpreted at the nuclear level by the transcription machinery to select the repertoire of tissue-specific genes to be expressed. The reversibility of some of these changes necessarily reflects the dynamic nature of skeletal myogenesis, which entails the progression through two antagonistic processes--proliferation and differentiation. Other epigenetic modifications are instead associated to events conventionally considered as irreversible--e.g. maintenance of lineage commitment and terminal differentiation. However, recent results support the possibility that these events can be reversed, at least upon certain experimental conditions, thereby revealing a dynamic nature of many of the epigenetic modifications underlying skeletal myogenesis. The elucidation of the epigenetic network that regulates transcription during developmental myogenesis and muscle regeneration might provide the information instrumental to devise pharmacological interventions toward selective manipulation of gene expression to promote regeneration of skeletal muscles and possibly other tissue.

Animals↗
PubMed2006

Genomic structure and embryonic expression of zebrafish lysyl hydroxylase 1 and lysyl hydroxylase 2.

Collagen biosynthesis in both invertebrates and vertebrates is critically dependent upon the activity of lysyl hydroxylase (LH) enzymes. In humans, mutations in the genes encoding LH1 and LH2 have been shown to cause two distinct connective tissue disorders, Ehlers-Danlos (Type VIA) and Bruck syndromes. While the biochemical properties of these enzymes have been intensively studied, their embryonic patterns of expression and developmental roles remain unknown. We now present the cloning and analyses of the genes encoding LH1 and LH2 in the zebrafish, Danio rerio. We find these genes to be similarly organized to other vertebrate lh (plod) genes, including the presence of an alternatively spliced exon in lh2. We also examine the mRNA expression patterns of lh1 and lh2 during embryogenesis and find them to exhibit unique and dynamic patterns of expression. These results strongly suggest that LH enzymes are not merely housekeeping enzymes, but play distinct developmental roles. The identification of these genes in the zebrafish, a genetic model organism whose development is well characterized, now provides the basis for the establishment of the first animal models for both Ehlers-Danlos (Type VIA) and Bruck syndromes.

Amino Acid Sequence↗
PubMed2005

Plant responses to potassium deficiencies: a role for potassium transport proteins.

The availability of potassium to the plant is highly variable, due to complex soil dynamics, which are strongly influenced by root-soil interactions. A low plant potassium status triggers expression of high affinity K+ transporters, up-regulates some K+ channels, and activates signalling cascades, some of which are similar to those involved in wounding and other stress responses. The molecules that signal low K+ status in plants include reactive oxygen species and phytohormones, such as auxin, ethylene and jasmonic acid. Apart from up-regulation of transport proteins and adjustment of metabolic processes, potassium deprivation triggers developmental responses in roots. All these acclimation strategies enable plants to survive and compete for nutrients in a dynamic environment with a variable availability of potassium.

Acclimatization↗
PubMed1998

Centrosome dynamics in early embryos of Caenorhabditis elegans.

The early Caenorhabditis elegans embryo divides with a stereotyped pattern of cleavages to produce cells that vary in developmental potential. Differences in cleavage plane orientation arise between the anterior and posterior cells of the 2-cell embryo as a result of asymmetries in centrosome positioning. Mechanisms that position centrosomes are thought to involve interactions between microtubules and the cortex, however, these mechanisms remain poorly defined. Interestingly, in the early embryo the shape of the centrosome predicts its subsequent movement. We have used rhodamine-tubulin and live imaging techniques to study the development of asymmetries in centrosome morphology and positioning. In contrast to studies using fixed embryos, our images provide a detailed characterization of the dynamics of centrosome flattening. In addition, our observations of centrosome behavior in vivo challenge previous assumptions regarding centrosome separation by illustrating that centrosome flattening and daughter centrosome separation are distinct processes, and by revealing that nascent daughter centrosomes may become separated from the nucleus. Finally, we provide evidence that the midbody specifies a region of the cortex that directs rotational alignment of the centrosome-nucleus complex and that the process is likely to involve multiple interactions between microtubules and the cortex; the process of alignment involves oscillations and overshoots, suggesting a multiplicity of cortical sites that interact with microtubules.

Animals↗