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Are dyslexics' visual deficits limited to measures of dorsal stream function?

We tested the hypothesis that the differences in performance between developmental dyslexics and controls on visual tasks are specific for the detection of dynamic stimuli. We found that dyslexics were less sensitive than controls to coherent motion in dynamic random dot displays. However, their sensitivity to control measures of static visual form coherence was not significantly different from that of controls. This dissociation of dyslexics' performance on measures that are suggested to tap the sensitivity of different extrastriate visual areas provides evidence for an impairment specific to the detection of dynamic properties of global stimuli, perhaps resulting from selective deficits in dorsal stream functions.

Adult↗

Complex organization in multicellularity as a necessity in evolution.

By introducing a dynamical system model of a multicellular system, it is shown that an organism with a variety of differentiated cell types and a complex pattern emerges through cell-cell interactions even without postulating any elaborate control mechanism. Such an organism is found to maintain a larger growth speed as an ensemble, by achieving a cooperative use of resources, than do simple homogeneous cells, which behave "selfishly." This suggests that the emergence of multicellular organisms with complex organization is a necessity in evolution. According to our theoretical model, there initially appear multipotent stem cells, which undergo stochastic differentiation to other cell types. With development and differentiation, both the chemical diversity and the complexity of intra-cellular dynamics are decreased, as a general consequence of our system. Robustness of the developmental process is also confirmed.

Biological Evolution↗

A gene network model for developing cell lineages.

Biological development is a remarkably complex process. A single cell, in an appropriate environment, contains sufficient information to generate a variety of differentiated cell types, whose spatial and temporal dynamics interact to form detailed morphological patterns. While several different physical and chemical processes play an important role in the development of an organism, the locus of control is the cell's gene regulatory network. We designed a dynamic recurrent gene network (DRGN) model and evaluated its ability to control the developmental trajectories of cells during embryogenesis. Three tasks were developed to evaluate the model, inspired by cell lineage specification in C. elegans, describing the variation in gene activity required for early cell diversification, combinatorial control of cell lineages, and cell lineage termination. Three corresponding sets of simulations compared performance on the tasks for different gene network sizes, demonstrating the ability of DRGNs to perform the tasks with minimal external input. The model and task definition represent a new means of linking the fundamental properties of genetic networks with the topology of the cell lineages whose development they control.

Animals↗

I. Formulation.

The authors describe a systematic approach to the process of formulation. Four interlocking phases are considered. The longitudinal data collection evaluate the patient's developmental journey. The cross-sectional evaluation includes careful consideration of phenomenological and dynamic factors. The integrative evaluation of these factors permits the construction of both a dynamic and a phenomenological diagnosis. Finally, in hypothesizing a tentative prognosis, we attemt to predict the capacity and quality of a person's potential change and readjustment.

Adolescent↗

The laugh of Satan: a study of a familial murderer.

A teenage murderer who killed his mother, his tiny half-brother, and his step-father was studied through the imagery he associated to three different editions of inkblots. These sets included the Rorschach, Behn-Rorschach, and Ka-Ro plates. The data were used to theorize about clues, dynamics, and diagnosis in this extreme case of adolescent violence. Family background and developmental history are included. The author takes the position that a conventional analysis of these data alone is not sufficient to fully understand familial murderers. Several of C.G. Jung's concepts, notably his view about the power of shadow-projections to influence conscious percepts and his philosophy about evil as a collective phenomenon, were used to speculate about ways we might extend our understanding of this subject's extreme form of violence. Defining the archetype as an energy-complex, the discussion theorized about possible ways different forms of paranoid ideation may arise.

Adolescent↗

Dynamics of the basement membrane in invasive epithelial clusters in Drosophila.

The basement membrane (BM) represents a barrier to cell migration, which has to be degraded to promote invasion. However, the role and behaviour of the BM during the development of pre-invasive cells is only poorly understood. Drosophila border cells (BCs) provide an attractive genetic model in which to study the cellular mechanisms underlying the migration of mixed cohorts of epithelial cells. BCs are made of two different epithelial cell types appearing sequentially during oogenesis: the polar cells and the outer BCs. Here, we show that the pre-invasive polar cells undergo an unusual and asymmetrical apical capping with major basement membrane proteins, including the two Drosophila Collagen IV alpha chains, Laminin A and Perlecan. Capping of polar cells proceeds through a novel, basal-to-apical transcytosis mechanism that involves the small GTPase Drab5. Apical capping is transient and is followed by rapid shedding prior to the initiation of BC migration, suggesting that the apical cap blocks migration. Consistently, non-migratory polar cells remain capped. We further show that JAK/STAT signalling and recruitment of outer BCs are required for correct shedding and migration. The dynamics of the BM represents a marker of migratory BC, revealing a novel developmentally regulated behaviour of BM coupled to epithelial cell invasiveness.

Animals↗

[Cisterno-medullary anomalies. Diagnostic problems, surgical treatment (author's transl)].

Under the term cisterno-medullary anomalies are included several disorders: bony and nervous malformations, arachnoiditis of the posterior fossa. As they are frequently associated, a thorough investigation, both anatomical and dynamic, is a prerequisite to any therapeutic attempt. Along with causing damage to the neuraxis, these anomalies interfere with the dynamics of the CSF and may lead to the development of a communicating syringomyelia, whatever the theory proposed. The presenting symptoms are varied, and diagnosis should be accordingly suspected. Of fundamental importance are instrumental investigations. A complete evaluation is in most of the cases obtainable with: bone X-rays, air-myelography (or "bulle"), intrathecal ou ventricular radio-isotope scan. Surgery is the only treatment. The aim is both decompression of the neural structures and restoration of a normal CSF dynamic flow. Opening of the posterior fossa is successful in the case of developmental abnormalities, But it seems to prove a failure when the chief anomaly is arachnoiditis. In such cases, ventricular drainage alone may be followed by improvement. It appears from this that the problem is twofold: the technical problem of the drainage, and the pre-operatory diagnosis of a posterior fossa arachnoiditis.

Adolescent↗

Developmental considerations in children and early adolescents with spinal cord injury.

Although there has been increasing awareness of the psychologic effects of illness and hospitalization in children and early adolescents, those who have sustained spinal cord injury (SCI) have received scant notice in the literature. A developmental approach in work with hospitalized children having SCI has been found helpful in trying to meet the psychologic needs of these children, and in guiding staff to better understand their behavior and to implement care more appropriately. In this approach to children and early adolescents with SCI, developmental status is evaluated and each child's response to SCI in relation to the prominent issues of developmental stage is assessed. A productive byproduct of this approach is that family dynamics become more obvious and both patient and family behavior are better understood by those providing medical care.

Adolescent↗

[The effect of antenatal nicotine exposure on the male germ cells in Wistar rats].

Chemically pure nicotine in dose 0.4, 1.5 and 5.0 mg/kg bw were percutaneously injected into Wistar rats during 1-20 (I) and 1-8 days (II) of pregnancy. The gametotoxic effect of nicotine in two-month males from offspring of the first generation (F1) was observed in disturbance of differentiation dynamics of spermatocytes at the stage of preleptotene and spermatids of the seventh developmental stage. The suggested quantitative analysis of disturbance in the behaviour of the meiotic chromosomes in metaphase I and II and anatelophase I and II has revealed that nicotine introduction in the period of isolation and migration of the primary sex cells into embryo gonads (2nd series) induces an increase in the level of pathological maturation divisions in the male offspring.

Animals↗

Developmental microbial ecology of the neonatal gastrointestinal tract.

The gastrointestinal tract of a normal fetus is sterile. During the birth process and rapidly thereafter, microbes from the mother and surrounding environment colonize the gastrointestinal tract of the infant until a dense, complex microbiota develops. The succession of microbes colonizing the intestinal tract is most marked in early development, during which the feeding mode shifts from breast-feeding to formula feeding to weaning to the introduction of solid food. Dynamic balances exist between the gastrointestinal microbiota, host physiology, and diet that directly influence the initial acquisition, developmental succession, and eventual stability of the gut ecosystem. In this review, the development of the intestinal microbiota is discussed in terms of initial acquisition and subsequent succession of bacteria in human infants. Intrinsic and extrinsic factors influencing succession and their health significance are discussed. The advantages of modern molecular ecology techniques that provide sensitive and specific, culture-independent evaluation of the gastrointestinal ecosystem are introduced and discussed briefly. Further advances in our understanding of developmental microbial ecology in the neonatal gastrointestinal tract are dependent on the application of these modern molecular techniques.

Animals↗

Developmentally induced changes in transcriptional program alter spatial organization across chromosomes.

Although the spatial location of genes within the nucleus has been implicated in their transcriptional status, little is known about the dynamics of gene location that accompany large-scale changes in gene expression. The mating of haploid yeast Saccharomyces cerevisiae is accompanied by a large-scale change in transcription and developmental program. We examined changes in nuclear organization that accompany stimulus by the mating pheromone alpha factor and found that most alpha-factor-induced genes become associated with components of the nuclear envelope. The myosin-like protein Mlp1, which has been implicated in mRNA export, was further shown to exhibit RNA dependence in its association with alpha-factor-induced genes. High-resolution mapping of association of chromosome III with Mlp1 revealed alpha-factor-dependent determinants of nuclear pore association, including origins of replication, specific intergenic regions, and the 3' ends of transcriptionally activated genes. Taken together, these results reveal RNA- and DNA-dependent determinants of nuclear organization as well as a detailed picture of how an entire chromosome alters its spatial conformation in response to a developmental cue.

Chromosomes, Fungal↗

Growth dynamics of the cricoid cartilage and subglottic injury. An autoradiographic and histometric study in the rabbit.

Earlier studies in young growing rabbits have suggested that post-traumatic developmental deformities of the cricoid might play a role in failing treatment in children with similar injuries. Specific patterns of malformations in the animals occurred preferentially at the anterior side of the cricoid ring. In this study, the growth dynamics of the cricoid were studied by histometry and autoradiography. Results indicated that (1) the cell/matrix ratio remains unchanged from 4 to 24 weeks of age, with both tissue components thus contributing equally to growth of the cricoid; (2) mitoses occur in cartilage and perichondrium, indicating interstitial as well as appositional growth; (3) mitotic activity is mainly restricted to the first 4 weeks of life, while cell hypertrophy is thereafter the dominant feature; (4) the highest degree of mitotic activity and cell hypertrophy is found in the anterior half of the cricoid ring which therefore can be considered as a growth center. This center might play a role in the development of trauma-induced deformation in the anterior part of the cricoid ring.

Aging↗

Drug metabolic enzymes in developmental toxicology.

Although much is known about the metabolism of environmental toxicants in adult organisms, little information exists on the role of cytochrome P450 (CYP) enzymes during development. The developing organism is remarkably dynamic, presenting a constantly changing metabolic profile as various enzyme systems are activated or repressed. This may explain the markedly different sensitivities to various toxicants that are exhibited throughout the developmental period. The application of molecular biological methods has provided important information on the roles of these enzymes in modulating the response of the developing organism to toxicological exposures. The first talk will focus on the identification and role of CYPs during early organogenesis, particularly on how these enzymes influence the response of the conceptus and early embryo to toxic chemicals. The second presentation will discuss the identification of CYPs expressed during human development, as many of the enzymes present in adults are not expressed in the fetus. The third speaker will discuss the developmental consequences of loss of expression of particular metabolic enzymes, focusing on recent studies employing knockout mice to examine the role of drug metabolic enzymes during development. The last two talks will discuss some of the short- and long-term consequences of in utero exposures to toxic chemicals and the role of CYP in modulating the toxic response of the developing organism. The first of these will focus on the role of CYP2E1 in human fetuses during late gestation and the response of this enzyme to inducing agents such as alcohol. The last talk will discuss the role of CYP1A1 in the activation of the Ki-ras oncogene following in utero exposure to carcinogens as a mechanism for lung tumor formation in a pharmacogenetic mouse model.

Aging↗

Transcriptional pulsing of a developmental gene.

It has not been possible to view the transcriptional activity of a single gene within a living eukaryotic cell. It is therefore unclear how long and how frequently a gene is actively transcribed, how this is modulated during differentiation, and how transcriptional events are dynamically coordinated in cell populations. By means of an in vivo RNA detection technique , we have directly visualized transcription of an endogenous developmental gene. We found discrete "pulses" of gene activity that turn on and off at irregular intervals. Surprisingly, the length and height of these pulses were consistent throughout development. However, there was strong developmental variation in the proportion of cells recruited to the expressing pool. Cells were more likely to re-express than to initiate new expression, indicating that we directly observe a transcriptional memory. In addition, we used a clustering algorithm to reveal synchronous transcription initiation in neighboring cells. This study represents the first direct visualization of transcriptional pulsing in eukaryotes. Discontinuity of transcription may allow greater flexibility in the gene-expression decisions of a cell.

Animals↗

Developmental morphological and histological studies on structures of the human fetal elbow joint.

In the present work, morphological changes in the developing human elbow joint were studied at different prenatal ages (8, 12, 16, 20, 29 and 40 weeks) and were compared with the same structures in the adult joint. The elbow joint had gone through its most important developmental changes during the 20th week of prenatal life, probably due to the direct dynamic effect of the newly developed fetal movement. During later prenatal development, the articular surfaces of the lower end of humerus and the upper ends of radius and ulna developed their characteristic congruencies, so that the highly curved convexities always articulate with the highly curved concavities. That process progressed postnatally and even till adult age. In full-term infants it was found that the lower end of humerus had acquired its adult shape, while the shape of the upper ends of radius and ulna were still not fully developed. They continued development in postnatal life even till adult age. In the present work, histological prenatal studies were done on longitudinal sections from the back of the capsule and synovial tissue, early (8 weeks) and late in full term, and the results were also compared with the same structures in adults. It was found that at all ages, the capsules were formed of cellular and fibrous elements, but at early prenatal age (8 weeks), this cellular condensation was more massive and prominent while in full-term infants, it became generally more fibrous, but was still different compared to adults. Basic cellular structures of the synovial tissue changed very little during the late prenatal developmental stage, as it did not become more fibrous than cellular during these periods, but differences in vascularity became more obvious. The cartilaginous content of the articular surface at 8 weeks was highly cellular with very little intercellular matrix. In contrast to that of full term, this cartilage became fully chondrogenous with a notable decrease in cellular density and massive increase in matrix content.

Adult↗

Clonal, in vivo behavior of the totipotent hematopoietic stem cell.

Classical and more recent studies have provided a description of the in vivo behavior of the totipotent hematopoietic stem cell and its clonal progeny. These reconstitution experiments, employing clonotypic markers have shown that single or few engrafted lymphoid-myeloid stem cells are both necessary and sufficient for long-term, stable hematopoiesis in a reconstituted mouse. This underscores the remarkable developmental capacity of individual stem cell clones. Furthermore, the long-term and retransplantation studies have provided an indication of stem cell self-renewal ability. Taken together, the long-term analyses have also shed light on the dynamic behavior of engrafted stem cell clones and of the entire reconstituted hematopoietic system. A model is presented where the developmental and proliferative behavior of totipotent stem cells is a function of time. In this model commitment versus self-renewal decisions may be governed by stochastic mechanisms. However, the actual contribution by stem cells to particular mature cell populations may be more a function of lineage specific demands as they change over post-engraftment time.

Animals↗

Studying the dynamics of problem behavior across multiple time scales: prospects and challenges.

As a commentary on the Special Issue, this paper discusses recent advances in the study of change across several time scales. It points out the importance of specifying time scales and putative patterns of change when characterizing problem behavior over developmental time scales. Methods for studying risk and protective mechanisms through observation of social interaction are also discussed as a way to study influences that operate in real time. Methods for studying episode-level interaction patterns that result from such real-time influences are also discussed, along with ways to integrate these with longitudinal assessments to study the effects of social interaction on problem behavior across developmental time scales.

Behavioral Research↗