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Early motor development from partially ordered neural-body dynamics: experiments with a cortico-spinal-musculo-skeletal model.

Early human motor development has the nature of spontaneous exploration and boot-strap learning, leading to open-ended acquisition of versatile flexible motor skills. Since dexterous motor skills often exploit body-environment dynamics, we formulate the developmental principle as the spontaneous exploration of consistent dynamical patterns of the neural-body-environment system. We propose that partially ordered dynamical patterns emergent from chaotic oscillators coupled through embodiment serve as the core driving mechanism of such exploration. A model of neuro-musculo-skeletal system is constructed capturing essential features of biological systems. It consists of a skeleton, muscles, spindles, tendon organs, spinal circuits, medullar circuits (CPGs), and a basic cortical model. Through a series of experiments with a minimally simple body model, it is shown that the model has the capability of generating partially ordered behavior, a mixture of chaotic exploration and ordered entrained patterns. Models of self-organizing cortical areas for primary somatosensory and motor areas are introduced. They participate in the explorative learning by simultaneously learning and controlling the movement patterns. A scaled up version of the model, a human infant model, is constructed and put through preliminary experiments. Some meaningful motor behavior emerged including rolling over and crawling-like motion. The results show the possibility that a rich variety of meaningful behavior can be discovered and acquired by the neural-body dynamics without pre-defined coordinated control circuits.

Behavior↗

Evolution and development of a central pattern generator for the swimming of a lamprey.

This article describes the design of neural control architectures for locomotion using an evolutionary approach. Inspired by the central pattern generators found in animals, we develop neural controllers that can produce the patterns of oscillations necessary for the swimming of a simulated lamprey. This work is inspired by Ekeberg's neuronal and mechanical model of a lamprey [11] and follows experiments in which swimming controllers were evolved using a simple encoding scheme [25, 26]. Here, controllers are developed using an evolutionary algorithm based on the SGOCE encoding [31, 32] in which a genetic programming approach is used to evolve developmental programs that encode the growing of a dynamical neural network. The developmental programs determine how neurons located on a two-dimensional substrate produce new cells through cellular division and how they form efferent or afferent interconnections. Swimming controllers are generated when the growing networks eventually create connections to the muscles located on both sides of the rectangular substrate. These muscles are part of a two-dimensional mechanical simulation of the body of the lamprey in interaction with water. The motivation of this article is to develop a method for the design of control mechanisms for animal-like locomotion. Such a locomotion is characterized by a large number of actuators, a rhythmic activity, and the fact that efficient motion is only obtained when the actuators are well coordinated. The task of the control mechanism is therefore to transform commands concerning the speed and direction of motion into the signals sent to the multiple actuators. We define a fitness function, based on several simulations of the controller with different commands settings, that rewards the capacity of modulating the speed and the direction of swimming in response to simple, varying input signals. Central pattern generators are thus evolved capable of producing the relatively complex patterns of oscillations necessary for swimming. The best solutions generate traveling waves of neural activity, and propagate, similarly to the swimming of a real lamprey, undulations of the body from head to tail propelling the lamprey forward through water. By simply varying the amplitude of two input signals, the speed and the direction of swimming can be modulated.

Algorithms↗

Combinatorial profiles of oligodendrocyte-selective classes of transcriptional regulators differentially modulate myelin basic protein gene expression.

Recent studies suggest that specific neural basic helix-loop-helix (HLH; i.e., Olig1 and Olig2, Mash1), associated inhibitory HLH (i.e., Id2 and Id4), high-mobility group domain (i.e., Sox10), and homeodomain (i.e., Nkx2.2) transcription factors are involved in oligodendrocyte (OL) lineage specification and progressive stages of maturation including myelination. However, the developmental interplay among these lineage-selective determinants, in a cell- and maturational stage-specific context, has not yet been defined. We show here in vivo and in vitro developmental expression profiles for these distinct classes of transcriptional regulators of OLs. We show that progressive stages of OL lineage maturation are characterized by dynamic changes in the subcellular distribution of these transcription factors and by different permutations of combinatorial transcriptional codes. Transient transfections of these precise combinatorial codes with a luciferase reporter gene driven by the myelin basic protein promoter define how changes in the molecular composition of these transcriptional complexes modulate myelin gene expression. Our overall findings suggest that the dynamic interplay between developmental stage-specific classes of transcriptional activators and associated inhibitory factors orchestrate myelin gene expression during terminal maturation of the mammalian CNS.

3T3 Cells↗

Stabilization of axon branch dynamics by synaptic maturation.

The developmental refinement of topographic projections in the brain is reflected in the dynamic sculpting of axonal arbors that takes place as connections between CNS structures form and mature. To examine the role of synaptogenesis and synaptic maturation in the structural development of axonal projections during the formation of the topographic retinotectal projection, we coexpressed cytosolic fluorescent protein (FP) and FP-tagged synaptophysin (SYP) in small numbers of retinal ganglion cells in living albino Xenopus laevis tadpoles to reveal the distribution and dynamics of presynaptic sites within labeled retinotectal axons. Two-photon time-lapse observations followed by quantitative analysis of tagged SYP levels at individual synapses demonstrated the time course of synaptogenesis: increases in presynaptic punctum intensity are detectable within minutes of punctum emergence and continue over many hours. Puncta lifetimes correlate with their intensities. Furthermore, we found that axon arbor dynamics are affected by synaptic contacts. Axon branches retract past faintly labeled puncta but are locally stabilized at intensely labeled SYP puncta. Visual stimulation for 4 h enhanced the stability of the arbor at intense presynaptic puncta while concurrently inducing the retraction of exploratory branches with only faintly labeled or no synaptic sites.

Aging↗

Dynamic changes in meiotic progression and improvement of developmental competence of pig oocytes in vitro by follicle-stimulating hormone and cycloheximide.

The effects of FSH, LH, and epidermal growth factor (EGF) on the dynamics of nuclear maturation and subsequent embryo development were examined in pig oocytes cultured either conventionally or after preincubation with cycloheximide (CHX). In conventional culture, FSH or EGF significantly increased the rate of attainment of metaphase II (MII) for both gilt (50.0%+/-4.2% and 54.8%+/-4.3%, respectively; control, 5.8%+/-1.8%; P<0.001) and sow (87.6%+/-3.4% and 78.8%+/-3.9%, respectively; control, 7.8%+/-2.5%; P<0.001) oocytes. Gilt oocytes treated with both FSH and EGF showed an additive response (93.7%+/-2.1%). Treatment with LH had no effect. Preincubation with CHX caused the majority (84-100%) of both gilt and sow oocytes to undergo germinal vesicle breakdown. Compared to those treated with LH and/or EGF (both>80%), fewer FSH-treated oocytes reached metaphase I (43.8%+/-5.3%, P<0.001) by 14 h and MII (48.4%+/-5.9%, P<0.001) by 24 h, although the majority (71%) did mature to MII by 36 h after removal of CHX. After in vitro fertilization, higher proportions of both CHX-pretreated and untreated, FSH-exposed oocytes cleaved (71.3%+/-2.9% and 75.3%+/-3.1%, respectively) compared with those not treated with FSH (37.7%+/-3.0% and 43.0%+/-2.9%, respectively; P<0.001). Pretreatment with CHX significantly increased blastocyst yield for both FSH-treated (32.8%+/-2.0% and 10.3%+/-1.5%, respectively; P<0.001) and untreated (16.7%+/-1.5% and 9.4%+/-1.2%, respectively; P<0.001) oocytes. Polyspermy rates were unaffected. In conclusion, pig oocytes meiotically arrested by CHX before maturation retain and improve their developmental competence. FSH stimulates nuclear maturation but slows meiotic progression.

Animals↗

High-voltage electron microscopy in neurocytology.

The function of the living matter from biomolecules to the whole body of the organism is based on the structure. Consequently, structural information is essential for the understanding of the function of living organisms. The biological structures from biomolecules to cells and tissues are intimately related to each other, and changing their morphological, biochemical, and physiological properties dynamically according to the developmental and functional status of the organism. The molecular dynamics of living matter should be related to the function of whole body. We employed HVEM stereoscopy and morphometry for the purpose of combining the structural information at nanometer level with those of the micrometer level. Novel aspects of three-dimensional organization of neuronal and glial cell processes have been presented. This structural information together with morphometrical data could contribute to the elucidation of brain function.

Animals↗

[Life cycles of ground beetles (Coleoptera, Carabidae) from the mountain taiga and mountain forest-steppe in the Eastern Sayan].

Seasonal dynamics and demographic structure was studied in 15 dominant ground beetle species in the mountain taiga and mountain forest-steppe belts of the Eastern Sayan (Okinskoe Plateau). Life cycles of the dominant ground beetle species were classified by developmental time, seasonal dynamics, and intrapopulation groups with different reproduction timing. The strategies of carabid life cycles adapted to severe mountain conditions of the Eastern Sayan were revealed.

Acclimatization↗

Developmental regulation of skull morphology II: ontogenetic dynamics of covariance.

Canalization may play a critical role in molding patterns of integration when variability is regulated by the balance between processes that generate and remove variation. Under these conditions, the interaction among those processes may produce a dynamic structure of integration even when the level of variability is constant. To determine whether the constancy of variance in skull shape throughout most of postnatal growth results from a balance between processes generating and removing variation, we compare covariance structures from age to age in two rodent species, cotton rats (Sigmodon fulviventer) and house mice (Mus musculus domesticus). We assess the overall similarity of covariance matrices by the matrix correlation, and compare the structures of covariance matrices using common subspace analysis, a method related to common principal components (PCs) analysis but suited to cases in which variation is so nearly spherical that PCs are ambiguous. We find significant differences from age to age in covariance structure and the more effectively canalized ones tend to be least stable in covariance structure. We find no evidence that canalization gradually and preferentially removes deviations arising early in development as we might expect if canalization results from compensatory differential growth. Our results suggest that (co)variation patterns are continually restructured by processes that equilibrate variance, and thus that canalization plays a critical role in molding patterns of integration.

Anatomy, Comparative↗

Development and structural dynamics of personal life investment in old age.

The development of personal life investment (PLI) during old age was investigated with longitudinal and cross-sectional data from the Berlin Aging Study (N = 516, ages = 70-103 years). PLI measures motivational energy expended in life domains that require (obligatory PLI) or do not require (optional PLI) investment in old age. The authors used structural modeling to determine developmental trajectories and dynamics of the PLI types. On average, obligatory PLI remained unchanged between 70 and 101 years. Optional PLI declined during the transition to the 4th age (between 80 and 90 years). When change on the intraindividual level was considered, reductions in optional PLI were not related to changes in obligatory PLI, but declining obligatory PLI was associated with declining optional PLI.

Aged↗

Stop-consonant and vowel perception in 3- and 4-year-old children.

Recent research on 5- to 11-year-old children's perception of stop consonants and vowels indicates that they can generally identify these sounds with relatively high accuracy from short duration stimulus onsets [Ohde et al., J. Acoust. Soc. Am. 97, 3800-3812 (1995); Ohde et al., J. Acoust. Soc. Am. 100, 3813-3824 (1996)]. The purpose of the current experiments was to determine if younger children, aged 3-4 years, can also recover consonant and vowel features from stimulus onsets. Ten adults, ten 3-year olds, and ten 4-year-olds listened to synthesized syllables composed of combinations of [b d g] and [i u a]. The synthesis parameters included manipulations of the following stimulus variables: formant transition (moving or straight), noise burst (present or absent), and voicing duration (10, 30, or 46 ms). Developmental effects were found for the perception of both stop consonants and vowels. In general, adults identified these sounds at a significantly higher level than children, and perception by 4-year-olds was significantly better than 3-year-olds. A developmental effect of dynamic formant motion was obtained, but it was limited to only the [g] stop consonant. Stimulus duration affected the children's perception of vowels indicating that they may utilize additional auditory information to a much greater extent than adults. The results support the importance of information in stimulus onsets for syllable identification, and developmental changes in sensitivity to these cues for consonant and vowel perception.

Adult↗

Polycomb complexes repress developmental regulators in murine embryonic stem cells.

The mechanisms by which embryonic stem (ES) cells self-renew while maintaining the ability to differentiate into virtually all adult cell types are not well understood. Polycomb group (PcG) proteins are transcriptional repressors that help to maintain cellular identity during metazoan development by epigenetic modification of chromatin structure. PcG proteins have essential roles in early embryonic development and have been implicated in ES cell pluripotency, but few of their target genes are known in mammals. Here we show that PcG proteins directly repress a large cohort of developmental regulators in murine ES cells, the expression of which would otherwise promote differentiation. Using genome-wide location analysis in murine ES cells, we found that the Polycomb repressive complexes PRC1 and PRC2 co-occupied 512 genes, many of which encode transcription factors with important roles in development. All of the co-occupied genes contained modified nucleosomes (trimethylated Lys 27 on histone H3). Consistent with a causal role in gene silencing in ES cells, PcG target genes were de-repressed in cells deficient for the PRC2 component Eed, and were preferentially activated on induction of differentiation. Our results indicate that dynamic repression of developmental pathways by Polycomb complexes may be required for maintaining ES cell pluripotency and plasticity during embryonic development.

Animals↗

Early stages of seed development in Brassica napus: a seed coat-specific cysteine proteinase associated with programmed cell death of the inner integument.

A maternal plant exquisitely promotes the success of its offspring by orchestrating embryo development and endowing protection even after the embryos mature. It uses ovule integuments for physical and physiological contact with the developing embryo and for subsequently equipping the seed with a seed coat (testa). The testa is developmentally and metabolically dynamic, but its molecular biology is not well understood. We show here that the inner integument in Brassica napus undergoes organized development and then programmed cell death (PCD), as evident from vacuolation, starch mobilization, DNA fragmentation and eventual compression. We have identified a cysteine proteinase gene (BnCysP1) that is expressed only in the inner integument as it undergoes PCD, well before the embryo begins storage protein synthesis. Two paralogous Cys proteinases have been recruited in rapeseed for the PCD of testa and for leaf senescence, and these differ 25% in their primary structure and post-translational modifications. Despite Arabidopsis being closely related to rapeseed, and an indication of developmental compression of its inner integument, the Arabidopsis genome is suggestive of only one Cys proteinase that shows approximately 72% identity to BnCysP1. It is, however, leaf senescence-associated, and the other Cys proteinases are <52% identical. BnCysP1 also differs from ricinosome-deployed PCD Cys endopeptidases in lacking the hallmark KDEL tail and being glycosylated. BnCysP1, one of the very few plant genes known to function only in the seed coat, will be useful in dissecting post-fertilization development of this important organ in rapeseed.

Amino Acid Sequence↗

Stage fright.

Stage fright is a universal human experience that occurs with varying intensity in everyone who stands before an audience. The anxiety generated in this situation stems from the re-emergence of certain key developmental experiences. The dynamics involved are related both to genital and to pre-genital conflicts. Shame arises from conflicts around exhibitionism, from concerns over genital inadequacy, and from the fear of loss of control. Guilt is produced from the aggression inherent in self-display and from the fear of the destruction of one's rivals, along with the dread of retaliation. A major portion of the stage fright reaction is the reactivation of the crisis of separation-individuation, which generates separation anxiety connected to the fear that asserting oneself as a separate individual will result in withdrawal of love and admiration by maternal figures, i.e. the audience. The various developmental experiences are differentially weighted in each individual's stage fright reaction depending on the vicissitudes of his early childhood experience. Perhaps it is fortunate that few performers ever completely master stage fright, for an intangible sense of communion between the performer and his audience might well be lost as a by-product of the mastery.

Adolescent↗

[Spontaneous Cryptosporidium infection in weaned rabbits].

The first occurrence of Cryptosporidium parvum Tyzzer, 1912 in broiler rabbits in the Czech Republic is reported. The protozoon was determined on the basis of morphometrical parameters of oocysts and of localization of endogenous developmental stages. The dynamics of natural Cryptosporidium infection was studied in a group of 72 young rabbits after weaning (their age ranging from 23-33 to 82-92 days) obtained from six large flocks and used in a feeding experiment. C. parvum was found in rabbits from four farms (Tab. I). Animals under observation were divided into 9 subgroups according to the genotype (Hyla 2000, California White, crosses of New Zealand x California, New Zealand White, Cunistar and Zika) as well as according to the farm of origin. The animals were housed in 28 cages under the conditions of two-floor cage technology. The upper floor consisted of cages housing three head, the lower floor two head each. The animals were fed ad libitum with commercial feed mixture (till the average age of 64.days supplemented with Robenidin as coccidiostat). During the first 10 days of observation pooled samples of droppings from each cage were examinated by flotation-centrifugation method according to Breza (1957) and Pavlásek (1991) in the intervals of three to four days, later one-week intervals. Post mortem scrapings from mucous epithelium taken from young rabbits were examinated (to reveal endogenous developmental stages of C. parvum) together with digesta (to detect oocysts of the protozoon) taken from the full length of the small intestine using method of native preparations and Giemsa stain. In one 37-day dead animal the small and large intestines were examined histologically. The maximum number of young rabbits infected with C. parvum were 30-40 and 33-43 days old (Fig. 1). In animals of this age category the oocysts of the protozoon were found in pooled samples in 11 and 12 cages (39.3 and 42.9%) from totally 28 cages under study. In rabbits of more than 50 days of age the occurrence of infection was significantly decreased (3.7%). During the experiment seven rabbits (9.7%) died; six of them (8.3%) at the age of 30-40 days. All these naturally infected and dead animals represented cases of monoinfection with C. parvum. The major clinical signs were typical diarrhoea lasting 3-5 days, inappetency, apathia, lethargy, prominent signs of exhaustion followed by dehydration of the organism. Atrophy of villi of the ileum in one of young rabbits was found histologically. Table II presents concrete data on significantly lower body weights (the decrease being 7-61.5%) as compared with rabbits of the same age not infected with cryptosporidia. It was not possible to evaluate objectively the differences in susceptibility to C. parvum infection between the individual genotypes of rabbits. As was found in the course of our further studies (unpublished data) a possible source of infection of young rabbits can be represented by their mothers in which oocysts are excreted sporadically shortly before parturition and during several days after it. Cryptosporidium infection (cryptosporidiosis) in flocks of broiler rabbits is taken as a new protozoal disease in the Czech Republic and C. parvum as one of possible agents in cases of disorders of digestive tract, namely in rabbits after weaning.

Animals↗

Visualization of individual growth-related craniofacial changes based on cephalometric landmark data: a pilot study.

OBJECTIVE: An approach based on Euclidean distances between cephalometric landmarks is presented (1) to visualize and localize the individual shape changes of the complex craniofacial skeleton during growth and (2) to depict the individual dynamic behavior of developmental size and shape changes. PATIENTS AND METHOD: Growth-related craniofacial changes were investigated exemplarily for two male orthodontically untreated subjects from the Belfast Growth Study on the basis of lateral cephalograms at 7, 9, 11, 13, and 15 years. The interlandmark distances among seven skeletal cephalometric landmarks served as a database for the study. A modified Karhunen-Loève decomposition based on orthogonal modes and time-dependent scalar amplitudes was used to describe the growth process. The individual shape changes of the various craniofacial regions were visualized by allocation of colors to the respective distances, and overdrawn representations were reconstructed by means of multidimensional scaling. RESULTS AND CONCLUSIONS: This visualization technique allows anatomical regions to be characterized with respect to reduced or strengthened growth, compared with pure size changes. The clinically relevant mechanisms of craniofacial changes are visualized (e.g., shifts in the anteroposterior or vertical dimensions of the jaws in relation to cranial base and structural imbalances during development). In addition, overdrawing the effects of shape change on the skeletal structures gives a more readily comprehensible impression of the growth process. Taking account of the methodical limitations of this approach (e.g., the restrictions concerning the number of landmarks), the clinician may take advantage of this technique in orthodontic or surgical diagnostics to gain additional insight into the individual complex size and shape changes during development along with their dynamic behavior.

Adolescent↗

Myo10 in brain: developmental regulation, identification of a headless isoform and dynamics in neurons.

Although Myo10 (myosin-X) is an unconventional myosin associated with filopodia, little is known about its isoforms and roles in the nervous system. We report here that, in addition to full-length Myo10, brain expresses a shorter form of Myo10 that lacks a myosin head domain. This ;headless' Myo10 is thus unable to function as a molecular motor, but is otherwise identical to full-length Myo10 and, like it, contains three pleckstrin homology (PH) domains, a myosin-tail homology 4 (MyTH4) domain, and a band-4.1/ezrin/radixin/moesin (FERM) domain. Immunoblotting demonstrates that both full-length and headless Myo10 exhibit dramatic developmental regulation in mouse brain. Immunofluorescence with an antibody that detects both isoforms demonstrates that Myo10 is expressed in neurons, such as Purkinje cells, as well as non-neuronal cells, such as astrocytes and ependymal cells. CAD cells, a neuronal cell line, express both full-length and headless Myo10, and this endogenous Myo10 is present in cell bodies, neurites, growth cones and the tips of filopodia. To investigate the dynamics of the two forms of Myo10 in neurons, CAD cells were transfected with GFP constructs corresponding to full-length or headless Myo10. Only full-length Myo10 localizes to filopodial tips and undergoes intrafilopodial motility, demonstrating that the motor domain is necessary for these activities. Live cell imaging also reveals that full-length Myo10 localizes to the tips of neuronal filopodia as they explore and interact with their surroundings, suggesting that this myosin has a role in neuronal actin dynamics.

Amino Acid Sequence↗

Brief psychotherapy of bereavement reactions. The relationship of process to outcome.

We studied the relationship of dispositional and process variables with outcome in 52 bereaved patients given time-limited dynamic psychotherapy. Outcomes were generally favorable in symptom relief and improvement in relationship and occupational functioning. Patients' symptoms improved more than did their social and work functioning. Pretreatment levels of impairment or distress were significantly related to outcome, but most demographic and dispositional variables did not predict outcome. Process variables examined in relation to outcome--therapeutic alliance and actions by the therapist--were not significantly related to either type of outcome. When we considered the same process variables in interaction with two dispositional variables, motivation for dynamic therapy and developmental level of the self-concept, we found significant predictions of outcome. The major findings suggest that more exploratory actions were more suitable for highly motivated and/or better-organized patients and less suitable for patients with lower levels of motivation or organization of self-concept. More supportive actions were more suitable for patients at lower dispositional levels and less therapeutic for patients at higher levels.

Adjustment Disorders↗