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PubMed2002

Mapping epigenetic quantitative trait loci (QTL) altering a developmental trajectory.

Genetic variation in a quantitative trait that changes with age is important to both evolutionary biologists and breeders. A traditional analysis of the dynamics of genetic variation is based on the genetic variance-covariance matrix among different ages estimated from a quantitative genetic model. Such an analysis, however, cannot reveal the mechanistic basis of the genetic variation for a growth trait during ontogeny. Age-specific genetic variance at time t conditional on the causal genetic effect at time t - 1 implies the generation of episodes of new genetic variation arising during the interval t - 1 to t. In the present paper, the conditional genetic variance estimated from Zhu's (1995) conditional model was partitioned into its underlying individual quantitative trait loci (QTL) using molecular markers in an F2 progeny of poplars (Populus trichocarpa and Populus deltoides). These QTL, defined as epigenetic QTL, govern the alterations of growth trajectory in a population. Three epigenetic QTL were detected to contribute significantly to variation in growth trajectory during the period from the establishment year to the subsequent year in the field. It is suggested that the activation and expression of epigenetic QTL are influenced by the developmental status of trees and the environment in which they are grown.

Analysis of Variance↗

PubMed2001

Dynamics of the vocal imitation process: how a zebra finch learns its song.

Song imitation in birds provides good material for studying the basic biology of vocal learning. Techniques were developed for inducing the rapid onset of song imitation in young zebra finches and for tracking trajectories of vocal change over a 7-week period until a match to a model song was achieved. Exposure to a model song induced the prompt generation of repeated structured sounds (prototypes) followed by a slow transition from repetitive to serial delivery of syllables. Tracking this transition revealed two phenomena: (i) Imitations of dissimilar sounds can emerge from successive renditions of the same prototype, and (ii) developmental trajectories for some sounds followed paths of increasing acoustic mismatch until an abrupt correction occurred by period doubling. These dynamics are likely to reflect underlying neural and articulatory constraints on the production and imitation of sounds.

Acoustic Stimulation↗

PubMed2005

Organization of cis-acting regulatory elements in osmotic- and cold-stress-responsive promoters.

cis-Acting regulatory elements are important molecular switches involved in the transcriptional regulation of a dynamic network of gene activities controlling various biological processes, including abiotic stress responses, hormone responses and developmental processes. In particular, understanding regulatory gene networks in stress response cascades depends on successful functional analyses of cis-acting elements. The ever-improving accuracy of transcriptome expression profiling has led to the identification of various combinations of cis-acting elements in the promoter regions of stress-inducible genes involved in stress and hormone responses. Here we discuss major cis-acting elements, such as the ABA-responsive element (ABRE) and the dehydration-responsive element/C-repeat (DRE/CRT), that are a vital part of ABA-dependent and ABA-independent gene expression in osmotic and cold stress responses.

Base Sequence↗

PubMed2003

Genes of aging.

According to developmental genetics theories, aging is a genetically programmed and controlled continuum of development and maturation. Being dynamic and malleable processes, development and aging are controlled not only by genes but also by environmental and epigenetic influences that predominate in the second half of life. Genetic mutations affect many phenotypes in flies, worms, rodents, and humans which share several diseases or their equivalents, including cancer, neurodegeneration, and infectious disorders as well as their susceptibility to them. Life span and stress resistance are closely linked. Oxidative stress actually constitutes a defined hypothesis of aging in that macromolecule oxidative damage accumulates with age and tends to be associated with life expectancy. DNA methylation, a force in the regulation of gene expression, is also one of the biomarkers of genetic damage. The mitotic clock of aging is marked, if not guided, by telomeres, essential genetic elements stabilizing natural chromosomic ends. The dream of humans to live longer, healthy lives is being tested by attempts to modify longevity in animal models, frequently by dietary manipulation. The quest continues to understand the mechanisms of healthy aging, one of the most compelling areas of research in the 21st century.

Aging↗

PubMed1997

Developmental regulation of polysaccharide metabolism and growth in the primary cell walls of maize.

During development of the intact maize (Zea mays L.) coleoptile a correspondence exists between the rate of change in length and fresh weight but these parameters, that reflect growth, are all preceded by the accumulation of dry weight by the tissue. Coleoptile dry weight increases rapidly for the first 3-4 days commensurate with tissue formation with evidence for specific biosynthesis including the net incorporation into the cell wall of protein and substantial deposition of beta-(1,3)(1,4) glucan. After day 4 the extractable wall protein and after day 5 the beta-(1,3)(1,4) glucan begin to decline while the deposition of glucuronoarabinoxylan continues. Despite the continued incorporation of specific polymers into the wall the accumulated mass does not augment the overall dry weight. The shifts in polysaccharide distribution with development are consistent with what would be expected in terms of changes in the autolytic degradation of the wall. Glucan autolysis in isolated cell walls is relatively inactive initially then increases to a maximum by day 4 while arabinoxylan autolysis undergoes only relatively minor changes. Changes in the extent of wall glucan autolysis is proportional to the levels of glucanase activities extracted from the cell wall during the developmental sequence. Glucan in walls of the first three leaves of the maize seedlings also reflects dynamic turnover in correspondence with growth much like that of the coleoptile, suggesting that glucan metabolism coincides with growth in other maize tissues. The acceleration of glucan turnover mediated by auxin in situ may result from combinations and/or interactions of proteins that promote synergistic polysaccharide hydrolysis.

Cell Wall↗

PubMed2003

Pharmacokinetics in the newborn.

In addition to differences in the pharmacodynamic response in the infant, the dose and the pharmacokinetic processes acting upon that dose principally determine the efficacy and/or safety of a therapeutic or inadvertent exposure. At a given dose, significant differences in therapeutic efficacy and toxicant susceptibility exist between the newborn and adult. Immature pharmacokinetic processes in the newborn predominantly explain such differences. With infant development, the physiological and biochemical processes that govern absorption, distribution, metabolism, and excretion undergo significant growth and maturational changes. Therefore, any assessment of the safety associated with an exposure must consider the impact of these maturational changes on drug pharmacokinetics and response in the developing infant. This paper reviews the current data concerning the growth and maturation of the physiological and biochemical factors governing absorption, distribution, metabolism, and excretion. The review also provides some insight into how these developmental changes alter the efficiency of pharmacokinetics in the infant. Such information may help clarify why dynamic changes in therapeutic efficacy and toxicant susceptibility occur through infancy.

Gastric Mucosa↗

PubMed2001

Molecular motors: from one motor many tails to one motor many tales.

Kinesin and dynein molecular motor proteins generate the movement of a wide variety of materials in cells. Such movements are crucial for many different cellular and developmental functions, including organelle movement, localization of developmental determinants, mitosis, meiosis and possibly long-range signaling in neurons. Kinesins that control the dynamics of microtubules have also been discovered. Recent work has begun to identify processes in which defective molecular motor function can cause human disease.

Animals↗

PubMed2002

Mouse and human dendritic cell subtypes.

Dendritic cells (DCs) collect and process antigens for presentation to T cells, but there are many variations on this basic theme. DCs differ in the regulatory signals they transmit, directing T cells to different types of immune response or to tolerance. Although many DC subtypes arise from separate developmental pathways, their development and function are modulated by exogenous factors. Therefore, we must study the dynamics of the DC network in response to microbial invasion. Despite the difficulty of comparing the DC systems of humans and mice, recent work has revealed much common ground.

Animals↗

PubMed1999

Replicating myoblasts and fused myotubes express the calcium-regulated proteins S100A1 and S100B.

We investigated the expression and the subcellular localization of S100A1 and S100B, two Ca(2+)-binding proteins of the EF-hand type, in replicating myoblasts and fused myotubes. Northern blot and reverse transcriptase-polymerase chain reaction analyses revealed the presence of S100A1 mRNA and S100B mRNA respectively, in myoblasts. Immunofluorescence and immunogold electron microscopy were used to localize individual proteins in myoblasts and myotubes. In the present report we document that: (1) in replicating myoblasts S100B is localized to intracellular membranes, including Golgi membranes, vimentin intermediate filaments (IFs) and microtubule (MT) structures; (2) in the same cells S100A1 is found associated with intracellular membranes; (3) following treatment of replicating myoblasts with colchicine, a fraction of S100B remains colocalized with bundled and collapsed vimentin IFs, whereas another fraction follows the destiny of endoplasmic membranes; (4) under the same conditions S100A1, like a fraction of S100B, follows the collapse of the endoplasmic reticulum around the nucleus; and (5) in fused myotubes S100A1 is found diffusely in the cytoplasm, whereas S100B is mostly found associated with vimentin IFs. These data suggest that in the skeletal myogenic cell line used in the present study S100A1 and S100B might share binding sites on or close to intracellular membranes, but display a significant degree of target specificity with respect of IFs and MTs. The results of these analyses suggest that expression of S100B in skeletal muscle cells may be developmentally regulated and lend support to the possibility that S100B might regulate the MT and IF dynamics.

Amino Acid Sequence↗

PubMed2004

Evolution of developmental canalization in networks of competing boolean nodes.

Developmental canalization, which leads to a reduction in the variation of phenotype expression relative to the complexity of the genome, has long been thought to be an important property of evolving biological systems. We demonstrate that a highly canalized state develops in the process of self-organization recently discovered in N-K Boolean networks that evolve based on a competition between the nodes. The model provides a simplified description of the evolution of genetic regulatory networks in developmental systems. The mechanism responsible for the evolution is shown to be a balance of two dynamical effects which compete to bring the network to a nonrandom critical steady state. Unlike other proposed evolutionary mechanisms that select for canalization, this mechanism does so while maintaining the system's capacity for further evolution in the steady state.

Computer Simulation↗

PubMed2004

A graph grammar approach to artificial life.

We present the high-level language of relational growth grammars (RGGs) as a formalism designed for the specification of ALife models. RGGs can be seen as an extension of the well-known parametric Lindenmayer systems and contain rule-based, procedural, and object-oriented features. They are defined as rewriting systems operating on graphs with the edges coming from a set of user-defined relations, whereas the nodes can be associated with objects. We demonstrate their ability to represent genes, regulatory networks of metabolites, and morphologically structured organisms, as well as developmental aspects of these entities, in a common formal framework. Mutation, crossing over, selection, and the dynamics of a network of gene regulation can all be represented with simple graph rewriting rules. This is demonstrated in some detail on the classical example of Dawkins' biomorphs and the ABC model of flower morphogenesis: other applications are briefly sketched. An interactive program was implemented, enabling the execution of the formalism and the visualization of the results.

Algorithms↗

PubMed1994

Psychological interventions for the suicidal adolescent.

Acute and chronic styles of suicidal behaviors require different psychotherapeutic approaches--the former needs a supportive-cognitive-focused approach, the latter (chronic or characterological) style needs an expressive insight-oriented psychotherapy with supportive elements to address the adolescent's developmental requirements for structure within the sessions. The psychotherapist needs to be appraised of the epidemiological, dynamic factors as well as the sources of external support the patient can count upon. It is interesting to note that psychodynamic factors alone or psychopathology alone are not sufficient to estimate the ebb and flow of the suicidal risk. A combination of all these factors must be taken into account in estimating suicidal risk at any point in treatment. It is advisable that an independent clinician's consultation be sought during treatment in the case of suicidal attempts as the therapist can easily overestimate or underestimate suicidal risks. Individual treatment requires family intervention from counseling to therapy. Particular problems addressed in the paper are countertransference reactions created by the suicidal behavior in the clinician such as rejection and withdrawal. The psychotherapy should address the resolution of aggressive, envious introjected images, issues of omnipotent control and interpersonal skills deficits. To transform suicidal behavior into reenactment of the aggression within the relationship to the therapist is the main immediate goal. A critical caveat; a patient who lies by commission or omission represents an obstacle for individual therapy on an outpatient basis as he will disguise his suicidal intentions and plans, excluding them from the therapeutic process.

Adolescent↗

PubMed1991

Family dynamics and caregiver burden in home health care.

Planning an intervention involves the assessment of medical needs followed by an analysis of the family composition, dynamics, role allocations, coping mechanisms, mode of emotional expression, and the point in the family's developmental sequence. Therapeutic targets should be identified and prioritized. At that point, a behavioral probe or some specific recommendation that the family can easily follow should be made. A careful analysis of the response will indicate the ease with which more difficult change prescriptions can be introduced. Failure of the family to follow even the most simple suggestion may indicate that family therapy is needed. If the family is successful at carrying out the probe suggestion, however, the home health care team can proceed with greater confidence that their efforts will lead to improved patient care and healthy family functioning.

Aged↗

PubMedDate not supplied

[Development of preimplantation mouse embryos in diffusion chambers].

The diffusion chambers with the preimplantation CBA X C57BL mouse embryos (at the stages of blastomeres, morula, blastocyst) were placed in the abdominal cavity of males. Developmental peculiarities of the embryos, level of mitotic activity in their separate parts, as well as dynamics of the number of gigantic trophoblast cells and the volume of their nuclei have been studied. The development of the embryos in the diffusion chambers was shown to depend on the type of membranous filters: they developed from an earlier stage (stage of 4 blastomeres) on the nucleopore filters than on the millipore ones. The morphogenetic transformation proceeded in the preimplantation embryos at a slower rate resulting in the formation of two -and (in single cases) three-layered embryonic cylinder. Later the embryos were disorganized. The repeated passage of the disorganized embryo cells (six passages during the year) allowed to obtain structures similar with yolk sac carcinoma.

Abdomen↗

PubMed2005

Dynamic balance between activation and repression regulates pre-mRNA alternative splicing during heart development.

Cardiac troponin T (cTNT) exon 5 splicing is developmentally regulated such that it is included in embryonic but not adult heart. CUG-BP and ETR-3-like factor (CELF) proteins promote exon inclusion, whereas polypyrimidine tract binding protein (PTB) and muscleblind-like (MBNL) proteins repress inclusion. In this study, we addressed what happens to these regulatory proteins during heart development to shift the regulatory balance of cTNT alternative splicing. Using dominant-negative proteins, we found that both CELF and PTB activities are required for appropriate splicing in cardiomyocytes. Two CELF proteins, CUG-BP and ETR-3, are nuclear and cytoplasmic in embryonic heart but are down-regulated in adult heart concomitant with loss of exon inclusion. In contrast, PTB and MBNL1 are expressed throughout heart development. The patterns of cTNT splicing and expression of its regulatory factors are conserved between mouse and chicken. Thus, alternative splicing is determined by a balance between positive and negative regulation, and modulation of expression levels of auxiliary splicing regulators may drive developmental splicing changes. ETR-3 and CUG-BP proteins are also down-regulated in other tissues during development, suggesting that CELF proteins play a broad role in developmental splicing regulation.

Aging↗

PubMed2005

Fusogenic activity of EFF-1 is regulated via dynamic localization in fusing somatic cells of C. elegans.

BACKGROUND: Many animal tissues form via fusion of cells. Yet in all instances of developmental cell fusion, the mechanism underlying fusion of plasma membranes remains poorly understood. EFF-1 is required for most somatic cell fusions in C. elegans, and misexpressed EFF-1 alters the normal pattern of fusing hypodermal cells. However, the autonomous activity of EFF-1, the rules governing its specificity, and the mechanism of its action have not been examined. RESULTS: We show that EFF-1 acts as a cellular fusogen, capable of inducing fusion of virtually any somatic cells in C. elegans, yet targeted precisely to fusion-fated contacts during normal development. Misexpression of EFF-1 in early embryos causes fusion among groups of cells composed entirely of nonfusion-fated members. Measurements of cytoplasm diffusion in induced fusion events show that ectopic EFF-1 expression produces fusion pores similar to those in normal fusion events. GFP-labeled EFF-1 is specifically targeted to fusion-competent cell contacts via reciprocal localization to the touching membranes of EFF-1-expressing cells. EFF-1 function is also governed by intercellular barriers that prohibit cell fusion between distinct tissues. Analysis of mutant versions of EFF-1 indicates a novel mode of fusogenicity, employing neither a phospholipase active site nor hydrophobic fusion-peptide acting solely in pore formation. CONCLUSIONS: EFF-1 can confer potent fusogenic activity to nonfusing cell types. However, it is normally targeted only to fusion-fated cell borders via mutual interaction between EFF-1-expressing cells and relocalization to the plasma membrane. Because EFF-1 appears evolutionarily unique to nematodes, multiple mechanisms may have evolved for controlled plasma-membrane fusion in development.

Amino Acid Motifs↗

PubMed1985

Dynamics of postural control in the child with Down syndrome.

We examined the development of neural control processes underlying stance balance in both developmentally normal children and children with Down syndrome to test the hypothesis that motor deficiencies in children with Down syndrome are associated with deficits within the automatic postural control system. We compared children with Down syndrome and developmentally normal children in two age groups (1-3 and 4-6 years) by using displacements of a platform and measuring electromyograms from leg muscles. The automatic muscle response pattern in both normal children and children with Down syndrome were directionally specific, although the pattern were more variable than in adults. Responses in children with Down syndrome showed no adaptive attenuation to changing task conditions. Onset latencies of responses in children with Down syndrome were significantly slower than in normal children. Presence of the monosynaptic reflex during platform perturbations at normal latencies suggests that balance problems in children with Down syndrome do not result from hypotonia, which researchers have defined as decreased segmental motoneuron pool excitability and pathology of stretch reflex mechanisms, but rather result from defects within higher level postural mechanisms.

Biomechanical Phenomena↗

PubMed2005

Developmental expression of sema3G, a novel zebrafish semaphorin.

The semaphorins are a large, evolutionarily conserved family of signaling molecules with broad functions during development. The class 3 semaphorins are a subclass of secreted semaphorins found in vertebrates. There have been six class 3 semaphorins identified to date (sema3A to sema3F) and some have been shown to function in axon guidance and cardiovascular development. However, the functions of many class 3 semaphorins and their potential interactions in vivo are still not well understood. As a step toward understanding the actions of all class 3 semaphorins in vivo, we have cloned and analyzed the developmental expression pattern of a novel zebrafish class 3 semaphorin, sema3H [corrected] sema3H [corrected] is expressed in a dynamic pattern throughout the first 3 days of development. It is expressed in the adaxial cells of the somite during somitogenesis. In the brain, sema3H [corrected] is expressed in cell clusters in the midbrain and diencephalon, and is expressed in the telencephalon in close proximity to the olfactory epithelium. sema3H [corrected] also is expressed in the pharyngeal arches, the pectoral fin bud, and the developing pronephros. These results provide a basis for studying how expression of multiple semaphorins could be essential for aspects of early development.

Animals↗