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PubMed2007

Dynamic instabilities as mechanisms for emergence.

That competences may emerge given appropriate environmental and behavioral context is a long-standing theme in developmental research. Work in the motor domain, but also in cognitive development, has made it possible to transform this idea into a mechanistic account closely linked to empirical evidence. In dynamic systems thinking, such capacities as keeping a motor goal in mind, remembering a location, or resisting a motor habit, are all understood in terms of the generation of stable patterns of neuronal activation. These may be input-driven, but also be stabilized by interactions within neuronal representations. A key theoretical insight is that whether a particular pattern of activation is stable or not is not determined by any single factor, learning process, or structural parameter. Instead, ongoing activity, recent activation history, current input, all may affect when a particular dynamic regime is reachable. In spite of such broad interdependence, sharp transitions may characterize the onset of a skill in any given context. Dynamic instabilities are the mechanistic basis for this phenomenon and thus form the basis for understanding development in terms of emergence. We exemplify the concepts of instability and emergence around the phenomenon of infant perseverative reaching and discuss implications for identifying key markers of development and their link to neuronal processes.

Child↗
PubMed2002

Developmentally regulated changes in cellular compartmentation and synaptic distribution of actin in hippocampal neurons.

Actin dynamics and actin-based motility are important for neurite outgrowth and synapse plasticity. Recent work implicates actin in synapse assembly, but the morphological relationship between actin and synapses during development is unclear. Here we used developing hippocampal neurons grown in culture to examine the relationship between F- and G-actin and clusters of synaptic proteins. Both F- and G-actin are most enriched in dendritic and axonal growth cones, but only G-actin is present within the distal tips of filopodia. Outside of growth cones, F-actin levels are greater in dendrites than in axons, whereas G-actin levels are slightly greater in axons than in dendrites. The distribution of both F- and G-actin is consistent with their presence at synapses, but only F-actin levels become detectably enhanced at synaptic sites. Quantitative analyses suggest that first-forming synapses are associated with enhanced levels of pre- and postsynaptic F-actin that do not necessarily remain elevated during synapse maturation. However, nearly all mature excitatory synapses become associated with high, mostly postsynaptic concentrations of F-actin contained principally within dendritic spines. Mature shaft and GABAergic synapses are also associated with enhanced levels of F-actin, but to a lesser degree. Thus, although F-actin is essential for function and maintenance of young synapses, it need not be highly concentrated at every site. The large increase in postsynaptic F-actin concentration observed in mature neurons is likely to reflect actin's role in dendritic spine morphology and in synapse plasticity.

Actins↗
PubMed1997

Distribution and dynamics in the expression of androgen and estrogen receptors in vocal control systems of songbirds.

Developmental and seasonal changes in the production of androgens and estrogens seem to control sex-specific differentiation and seasonal changes in sexual behaviors such as singing of songbirds. These steroids affect the brain by binding to intracellular located receptors. Here we analyze whether the expression of androgen receptors (AR) and estrogen receptors (ER) is a limiting factor for differentiation of the vocal pattern and the vocal control system of zebra finches and canaries. AR and ER are localised in the brain using in situ hybridizations with cRNA probes of the AR and ER of the zebra finch. AR are widely expressed in the vocal control system and allow androgen-dependent alterations of the development and function of most vocal control areas. The expression of AR in some vocal control areas such as NIF, DLM, and AVT differs between individuals. This individual variability suggests genetic differences or transient steroid-independent expression of AR. ER are found only in the HVC and thus restrict estrogen-dependent developmental and functional changes of the singing to the HVC area. AR- and ER-mRNA expression per cell in the HVC of adult canaries undergoes seasonal changes so that ER are higher expressed from fall to the early breeding season. During ontogeny, ER start to occur in the zebra finch HVC at posthatching day 15 and in the canary HVC at posthatching day 30. As the HVC is already sexual dimorphic in size at these times, HVC-based estrogen-ER-dependent mechanisms seem not to be important for the initial sexual dimorphic development of the HVC.

Aging↗
PubMed1995

Ethanol neuronotoxicity in the embryonic chick brain in ovo and in culture: interaction of the neural cell adhesion molecule (NCAM).

The present study was undertaken to investigate the involvement of NCAM in the neuroteratogenic effects of ethanol demonstrated by us and others. In the first experiment we examined the effect of in-ovo ethanol exposure on expression of NCAM in various regions of the embryonic CNS throughout development. Chick embryos received ethanol (10 mg/50 microliters/day) or saline (control) at days 1-3 of development (E1-E3), were sacrificed at various embryonic ages and whole brain (WB), cerebral hemispheres (CH) and cerebellum (CE) processed for SDS-polyacrylamide gel electrophoresis. The normal developmental profile of NCAM in the chick brain exhibited the same dynamics as previously reported by others. When compared to age-matched control brains, an increase was observed in expression of high molecular weight forms of NCAM in cerebral hemispheres between E8 and E10. These bands represented highly sialated (> 180 kDa) forms of NCAM. In fact, the NCAM hand from ethanol-treated embryos at E8 migrated at a higher molecular weight than did its control counterpart, indicating an increase in sialic acid content. In contrast, no clear change was observed in NCAM expression in cerebellum from E10 through E20 as a result of ethanol exposure. In the second experiment, we examined the involvement of NCAM in the alterations in neuronal growth patterns observed in ethanol-exposed cultures. Neuroblast-enriched cultures derived from three-day-old whole chick embryos (E3WE) were maintained on poly-L-lysine pre-coated Petri dishes in DMEM+5% fetal bovine serum with or without 50 mM ethanol. Cultures were fixed at 3, 6 or 9 DIV and co-stained for NCAM and neurofilament (160 kDa). E3WE cultures exhibited intense NCAM immunoreactivity at 3 and 6 DIV decreasing by 9 DIV.NCAM positive structures included all neuronal perikarya, neuritic processes and growth cones. Addition of 50 mM ethanol to the medium resulted in profound alterations in growth patterns of developing neurons which continued to exhibit intense NCAM staining. Ethanol-induced changes in the developmental profile of NCAM expression (i.e. increased sialation) in cerebral hemispheres correspond temporally with the shift in neuronal phenotype from cholinergic to catecholaminergic and GABAergic which we have reported previously. Changes in the normal pattern of cellular contact and interaction as a result of altered NCAM expression may influence establishment of neurotransmitter phenotype. Findings from this study support the view that NCAM may be involved both directly and indirectly in shaping of the CNS during development and we speculate that ethanol neuroembryotoxicity uncouples this relationship.

Animals↗
PubMed2005

Psychoneuroendocrine processes in human pregnancy influence fetal development and health.

Individual differences in psychoneuroendocrine function play an important role in health and disease. Developmental models postulate that these individual differences evolve through a progressive series of dynamic time-, place- and context-dependent interactions between genes and environments in fetal, infant and adult life. The effects of early experience have longer-lasting and more permanent consequences than those later in life. Experimental studies in animals have provided convincing evidence to support a causal role for stress-related psychoneuroendocrine processes in negatively influencing critical developmental and health outcomes over the life span, and have also offered valuable insights into putative physiological mechanisms. However, the generalizability of these findings from animals to humans may be limited by the existence of large inter-species differences in physiology and the developmental time-line. We have initiated a program of research in behavioral perinatology and conducted studies over the past several years to examine the effects of stress-related psychoneuroendocrine processes in human pregnancy on fetal developmental and health outcomes. Our findings support a significant and independent role for maternal prenatal stress in the etiology of prematurity-related outcomes, and suggest that these effects are mediated, in part, by the maternal-placental-fetal neuroendocrine axis, and specifically by placental corticotropin-releasing hormone. Our findings also suggest that the use of a fetal challenge paradigm offers a novel way to quantify fetal neurobehavioral maturity in utero, and that the maternal environment exerts a significant influence on the fetal neurodevelopmental processes related to recognition, memory and habituation. Finally, our findings provide preliminary evidence to support the notion that the influence of prenatal stress and maternal-placental hormones on the developing fetus may persist after birth, as assessed by measures of temperament and behavioral reactivity in the first few years of postnatal life. A description of this body of work is followed by the elucidation of questions for further research and a discussion of implications for life-span development and health.

Animals↗
PubMed1992

The ptotic (witch's) chin deformity: an excisional approach.

Ptosis of the chin pad is common and can be seen in patients of all ages. It may be associated with too little or (at times) too much anterior chin projection. Often there is an associated deep submental skin crease present. Frequently, the primary concern of the patient is the appearance or exaggeration of chin ptosis in smiling ("dynamic" ptosis). This report describes a flexible approach to the correction of developmental (and some iatrogenic) ptotic chin deformities. The key element in the approach is the direct excision of sagging or excess chin fat, muscle, and skin. No attempt is made to reposition or lift ptosis-prone soft tissues. If a deep submental skin crease is present, it too is excised. If the chin needs added anterior projection, it is accomplished with a stable alloplastic chin implant. The approach is uniquely suited to correct anterior overprojection caused by an excess of soft tissue at the front of the chin and has been successful in correcting the "dynamic" ptosis that appears with smiling.

Adult↗
PubMed1999

Molecular cloning and nuclear localization of a histone deacetylase homologue in Plasmodium falciparum.

Reversible acetylation of core histones plays an important role in transcriptional regulation, cell cycle progression and developmental events. The acetylation state of histones is controlled by a dynamic equilibrium between activities of histone acetylase and deacetylase enzymes. Histone deacetylase (HDAC) was recently suggested to be the target of a fungus-derived antiprotozoal agent exhibiting structural similarity to known HDAC inhibitors. We have initiated a study of HDAC of human malaria parasite, Plasmodium falciparum, to evaluate its potential as the target for novel antimalarials and its role in parasite development. We have isolated HDAC1 gene from the P. falciparum genomic and cDNA libraries. The nucleotide sequence contains no intervening sequence and its open reading frame (ORF) codes for a protein of 449 amino acid residues. We have named the protein, PfHDAC1, as the sequence shows significant homology to yeast, human and other eukaryotic HDACs. Northern blot analysis of the total RNA from different asexual and sexual stages of the parasite reveals the presence of single mRNA transcript, which is predominantly expressed in mature asexual blood stages and in gametocytes. Antiserum raised against a carboxyl terminal peptide immunoprecipitated an in vitro translated P. falciparum HDAC gene product and recognized an approximately 50 kDa protein in the Triton X-100 insoluble fraction of parasites. Immunoelectron microscopy analysis showed majority of the protein localized in the nucleus of P. falciparum. To our knowledge, this is the first HDAC gene isolated from the malaria parasite.

Amino Acid Sequence↗
PubMed2004

Higher harmonic generation microscopy for developmental biology.

Optical higher harmonic generation, including second harmonic generation and third harmonic generation, leaves no energy deposition to its interacted matters due to an energy-conservation characteristic, providing the "noninvasiveness" nature desirable for biological studies. Combined with its nonlinearity, higher harmonic generation microscopy provides excellent three-dimensional (3D) sectioning capability, offering new insights into the studies of embryonic morphological changes and complex developmental processes. By choosing a laser working in the biological penetration window, here we present a noninvasive in vivo light microscopy with sub-micron 3D resolution and millimeter penetration, utilizing endogenous higher harmonic generation signals in live specimens. Noninvasive imaging was performed in live zebrafish (Danio rerio) embryos. The complex developmental processes within > 1-mm-thick zebrafish embryos can be observed in vivo without any treatment. No optical damage was found even with high illumination after long-term observations and the examined embryos all developed normally at least to the larval stage. The excellent 3D resolution of the demonstrated technology allows us to capture the subtle developmental information on the cellular or sub-cellular levels occurring deep inside the live embryos and larvae. This technique can not only provide in vivo observation of the cytoarchitecture dynamics during embryogenesis with submicron resolution and millimeter penetration depth, but would also make strong impact in developmental and structural biology studies.

Animals↗
PubMed1990

Descriptive analysis of the developmental progression of grip position for pencil and crayon control in nondysfunctional children.

This study was designed to investigate the developmental progression in pencil and crayon grip. The subjects were 320 nondysfunctional children aged 3.0 to 6.11 years, with 20 boys and 20 girls at each 6-month age interval. On the basis of a review of the literature, developmental pencil and crayon grips were defined for the study, and the type of grips each child used to perform a drawing task and a coloring task were recorded. Many children at each age level used mature pencil grips. A developmental progression, however, was shown by the percentage change of children at each age level who used mature grips. Forty-eight percent of the youngest group used mature grips, compared with 90% of the oldest children. Two pencil grips-dynamic and lateral tripod-appear to be common in older children. Differences in the developmental progression of pencil grip were noted between boys and girls and between a drawing task and a coloring task.

Age Factors↗
PubMed1997

Timing of mating, developmental asynchrony and the sex ratio in mice.

According to the developmental asynchrony hypothesis, changing the time of mating within the estrous cycle could alter the interval between completion of blastocyst development and uterine responsiveness for implantation. This may then lead to sex ratio skews in animals that exhibit sex-differential blastocyst development, because uterine stage may now benefit either slow (female) or fast (male) developing blastocysts. To test this hypothesis, the responses of two strains of mice to altered mating dynamics were compared. In a strain that exhibits higher male than female blastocyst developmental rates, sex ratios became significantly female-biased when mated late during the estrous cycle as opposed to early mating. However, timing of mating did not affect sex ratios in a strain with synchronous development of male and female preimplantation embryos. Hence, it is concluded that developmental asynchrony between male and female blastocysts on the one hand, and blastocysts and uterus on the other, are indeed responsible for the effect of timing of mating on litter sex ratios in mice.

Animals↗
PubMed2003

Modulation of neural connectivity during tongue movement and reading.

In a functional magnetic resonance imaging (fMRI) study, a novel connectivity analysis method termed within-condition interregional covariance analysis (WICA) was introduced for investigation into brain modulation during tongue movement and reading Chinese pinyins and logographic characters. We found that performing a horizontal tongue movement task generated a specific brain module with hierarchical orders of neural computation. Such functional modularity was further examined during both overt and silent Chinese reading tasks. Our results showed that overt pinyin reading was associated with the following distributed regions involved in tongue movement: the primary motor cortex (M1), the supplementary motor area (SMA), Broca's area, and Wernicke's area. Furthermore, we have used the WICA and demonstrated task-dependent covariance patterns that are strongly associated with the M1 mouth/tongue region, in which the Broca-Wernicke pathway is implicated in a meaning access procedure based on assembled phonology, while the SMA-Broca pathway is implicated in a meaning access procedure based on addressed phonology. Our functional connectivity analysis of the neural pathway involved in language processing may provide a basis for future studies of the dynamic neural network associated with language learning and reading in both developmental and disease conditions.

Adult↗
PubMed1992

An antigen present in the Drosophila central nervous system only during embryonic and metamorphic stages.

We report here about an antigen that is expressed in the central nervous system (CNS) of Drosophila only during the embryonic and metamorphic stages. In Drosophila, axonogenesis and synaptogenesis occur twice during the development: first in the embryonic and second in the metamorphic stages. We generated monoclonal antibodies (MAbs) in order to obtain molecular probes for analyzing axonogenesis or synaptogenesis in the CNS on the assumption that good candidates for molecules responsible for such phenomena must be present in the neuropil during those stages exclusively. As a result, we found MAb 66B2 whose intense immunoreactivity in the neuropil of the CNS was observed exclusively in the embryo and pupa, and not in the larva and adult. Immunoblot analyses showed that MAb 66B2 binds specifically to a protein with an apparent molecular weight of 350 K and neutral pI in the prepupal CNS. A significant amount of the antigen was isolated in forms that were soluble without detergent. Results of immunohistochemistry with MAb 66B2 in a primary culture of embryos showed that some live cells in the ganglion-like cluster were stained, and that neuronal cell bodies and neurites emanating from there were negative. These results strongly suggest that the 66B2 antigen observed in the CNS is an extracellular matrix component secreted from nonneuronal cells. These developmental changes in the 66B2 immunoreactivity in the CNS presumably reflect dynamic changes of an extracellular matrix in the CNS that are accompanied by axonogenesis or synaptogenesis.

Animals↗
PubMed1983

The importance of the mediopatellar synovial plica for chondromalacia patellae.

In 60 autopsy knee joints findings on morphology and topography of medio- and suprapatellar plicae and level of insertion of the medial vastus muscle in relation to localization and degree of severity of chondromalacia were determined. The middle fields were affected most frequently and severely with 70% (chondromalacia class II and III). Thirty specimen with mediopatellar plica could be identified out of which 29 (97%) had class II or III chondromalacia; out of 30 specimen without a plica 18 (60%) showed chondromalacia. Accordingly a significant correlation could be detected between the incidence of chondromalacia and that of a mediopatellar synovial plica. When measuring the level of insertion of the medial vastus muscle class III chondromalacia showed an average level of insertion of 11%, class II of 22%, and class O or I of 30%. These differences are statistically significant. Patellar index, patellar facet angle, and patellar depth angle did not show any direct correlation to chondromalacia. The question arises whether the involution anomaly of the genicular septa and the muscular changes are not a manifestation of the same developmental disorder, thus creating the basis for an imbalance of the dynamic functional structure.

Adolescent↗
PubMed1990

Neurophysiological heterogeneity and the definition of dyslexia: preliminary evidence for plasticity.

Developments in the field of quantified electroencephalography have enhanced visualization of brain function in the learning disabilities. Optimal utilization of these techniques requires that populations under study be unambiguously defined. Evidence from the literature demonstrates that brain electrical activity of children with reading disability is more extensive and differs from that seen in children with "dyslexia-pure". Preliminary data are presented demonstrating that electrophysiological change seen in children with dyslexia-plus (dyslexia and attentional deficit disorder) could not be predicted by knowledge of electrophysiologic change in children with dyslexia-pure alone and attentional deficit disorder alone. Data from our laboratory are summarized to show that within dyslexia-pure the anomic, dysphonemic and global Denckla subtypes differ electrophysiologically from one another. Of particular interest is the demonstration that regions of electrophysiological difference among these subtypes may reflect compensatory mechanisms rather than pathological change. Finally, a case study is presented demonstrating advantageous effects of remediation upon brain electrical function. As both spontaneous and environmentally induced change in brain function can be documented, developmental dyslexia in its broadest terms appears to represent a more dynamic or plastic process than previously appreciated.

Anomia↗
PubMed2003

Morphological development of microglia in the postnatal rat brain. A quantitative study.

Morphological transformation of lectin-positive microglia/macrophages in the developing rat cerebral hemisphere was analysed using quantitative methods. During the first postnatal month, the cells showed increases in their size and fractal dimension accompanied by a simultaneous decrease in their solidity. Regional variations in dynamics of the process indicated the existence of spatio-temporal developmental gradients within the cerebral hemisphere wall which might correspond with regional patterns of neuronal differentiation. Results of the present study prove that the quantitative methods can be the source of reliable data replacing subjective cell typologies.

Aging↗
PubMed2000

Developmental trends in right hemispheric participation in reading.

Behavioral laterality tasks assessed the differential processing efficiencies of the cerebral hemispheres in younger and older reading-age children. Lateralized lexical decision task findings supported a "direct access" model of hemispheric processing for the younger children whereas the older children demonstrated a "callosal relay" pattern. A dual-task with oral and silent reading indicated that the right hand was significantly more disrupted than the left during unimanual finger tapping. The findings suggest that although the left hemisphere's involvement during reading is developmentally stable, the involvement of the right hemisphere appears to change dynamically as reading experience increases.

Adolescent↗
PubMed1998

Body mass index and percentage fat mass in healthy German schoolchildren and adolescents.

OBJECTIVE: To provide reference data for obesity indices in Mid-European schoolchildren and adolescents, to evaluate the usefulness of body mass index (BMI) as an indicator of obesity in children, and to analyse the patterns of fat accumulation during childhood. DESIGN: Cross-sectional observational study in 2554 healthy schoolchildren and adolescents (age, 6-19 y) living in Heidelberg, Germany in 1989/1990. Centile charts for BMI and skinfold-derived percentage body fat mass (PFM) were constructed using Cole's LMS method for normalised growth standards. RESULTS: The BMI centile values of German children ranged higher than French, lower than North American and Italian, and similar to Swedish and British children. While BMI steadily increased with age, PFM was markedly lower in peripubertal than in pre- and postpubertal boys. BMI predicted PFM with reasonable precision in girls (r=0.84), and in obese boys (r=0.58), but not in the leaner two thirds of the male population (r=0.01, NS). The 75th BMI percentile was the most appropriate cutoff value to screen for the 15% most obese patients by PFM (sensitivity: 82%, specificity: 85%). The pattern of the trunk-to-extremity skinfold ratio across childhood suggested that the typical adult distribution of central and peripheral fat is achieved in mid puberty in girls, but not before the end of adolescence in boys. CONCLUSIONS: The major differences observed between BMI charts obtained in different countries underline the need for population-specific reference data. BMI is of limited usefulness in predicting relative fat mass in individual children. The developmental pattern of fat accumulation and distribution during adolescence is highly dynamic and gender-specific.

Adipose Tissue↗
PubMed2000

Desmosomes are reduced in the mouse uterine luminal epithelium during the preimplantation period of pregnancy: a mechanism for facilitation of implantation.

Dynamic regulation of intercellular junctions is an essential aspect of many developmental, reproductive, and physiological processes. We have shown that expression of the desmosomal protein desmoplakin decreases in the luminal uterine epithelium during the preimplantation period of pregnancy in mice. By the time of implantation (between Days 4.5 and 5 of pregnancy), desmoplakin protein can barely be detected by SDS-PAGE and Western blotting, and by immunocytochemistry, it is restricted to well-spaced, punctate dots at the apicolateral junction. Using confocal XZ series and electron microscope quantitation, both the density and distribution of desmosomes along the lateral cell surfaces of luminal epithelial cells were observed to change during early pregnancy. On Day 1 of pregnancy, desmosomes were found at high density in the apicolateral junctional complex, being present here in 79% of ultrathin sections examined, whereas on Day 5, the density was much reduced (present in only 18% of ultrathin sections examined). Desmosomes were found along the lateral surfaces, at or below the level of the nucleus, in 15% of ultrathin sections examined on Day 1 of pregnancy but in only 1% on Day 5. Desmoplakin mRNA declined during the first 4-5 days of pregnancy, along with the protein, suggesting that these changes are controlled at the level of mRNA. This study shows that desmosomes are regulated during early pregnancy, and we propose that a reduction in desmosome adhesion facilitates penetration of the luminal epithelium by trophoblast cells at implantation.

Animals↗