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Connectance in Sorghum development: beyond the genotype-phenotype duality.

Connectance, the level of linkage between organs, was measured in different lines of Sorghum bicolor during their reproductive development. It was compared with expression of characters, their level of variability and their heritability. A negative relationship is observed between connectance and heritability. Further results indicate that connectance does not simply introduce a noise factor in expression of a pre-existing information, but that it is directly involved in phenotypic expression and plasticity. Connectance appears as partly determined by the nature and dynamics of the network of relationships. It is concluded that the phenotype is not restricted to the deterministic expression of a pre-existing program, the genotype. Morphogenesis also involves another dimension, self-organized, which confers reliability, stability and adaptability to the developmental processes. The complex interactions between these two dimensions and their evolutionary consequences are discussed.

Edible Grain↗

Improving language and literacy is a matter of time.

Developmental deficits that affect speech perception increase the risk of language and literacy problems, which can lead to lowered academic and occupational accomplishment. Normal development and disorders of speech perception have both been linked to temporospectral auditory processing speed. Understanding the role of dynamic auditory processing in speech perception and language comprehension has led to the development of neuroplasticity-based intervention strategies aimed at ameliorating language and literacy problems and their sequelae.

Animals↗

Respiratory kinematics during vocalization and nonspeech respiration in children from 9 to 48 months.

The development of respiratory drive for vocalization was studied by observing chest wall kinematics longitudinally in 4 typically developing children from the age of 9 to 48 months. Measurements of the relative contribution of rib cage and abdominal movement during vocalization (i.e., babbling and true words) and rest breathing were obtained every 3 months using respiratory plethysmography (Respitrace). Extending earlier findings in 15-month-olds, 2 methods of analysis of rib cage and abdominal movement were used: (a). a dynamic index of the strength of coupling between the rib cage and abdomen, and (b). a classification scheme describing the moment-by-moment changes in each of the 2 components (C. A. Moore, T. J. Caulfield, and J. R. Green, 2001). The developmental course of relative chest wall kinematics differed between vocalization and rest breathing. The coupling of rib cage and abdomen during vocalization weakened significantly with development, whereas it remained consistently strong for rest breathing throughout the observed period. The developmental changes in frequency of occurrence of relative moment-by-moment changes varied across movement type. The results support previous findings that speech breathing is distinct from rest breathing based on the relative contributions of the rib cage and abdomen. Longitudinal changes are likely responsive to anatomic development, including changes to rib cage shape and compliance.

Age Factors↗

Development and regulation of calcium metabolism in healthy girls.

The major components of calcium metabolism, as evaluated by a dual-tracer stable isotope method, were determined in 100 studies of 68 healthy girls, aged 5-18 y and analyzed from a developmental and regulatory viewpoint. Bone calcium deposition and removal rates were closely correlated with the size of the exchangeable bone calcium compartment. All three quantities, as well as intestinal calcium absorption, peaked at or near menarche. Both bone calcium deposition and removal rates were positively and linearly correlated with calcium absorption. However, in this correlation, because bone calcium deposition increased 70% faster than calcium absorption, most of the increase in the bone calcium compartment and its turnover must have occurred in response to something other than intestinal calcium input; presumably this occurred in response to developmental signals. Nevertheless, the constancy of the serum calcium in the face of a large intestinal calcium input and the modest way in which excretion overcame the calcium load in this population point to the importance of the exchangeable bone calcium compartment, in dynamic equilibrium with the bone mineral, as the site at which most of the load is taken up. In this population of girls, as in older women, this increase in the skeletal calcium balance resulted from a decrease in the bone calcium removal rate that was greater than the corresponding increase in the bone calcium deposition rate.

Adolescent↗

Practitioner review: approaches to assessment and treatment of children with DCD: an evaluative review.

BACKGROUND: Movement clumsiness (or Developmental Coordination Disorder--DCD) has gained increasing recognition as a significant condition of childhood. However, some uncertainty still exists about diagnosis. Accordingly, approaches to assessment and treatment are varied, each drawing on distinct theoretical assumptions about the aetiology of the condition and its developmental course. METHOD: This review evaluates the current status of different approaches to motor assessment and treatment for children with DCD. These approaches are divided according to their broad conceptual origin (or explanatory framework): Normative Functional Skill Approach, General Abilities Approach, Neurodevelopmental Theory, Dynamical Systems Theory, and the Cognitive Neuroscientific Approach. CONCLUSIONS: Each conceptual framework is shown to support assessment and treatment methods with varying degrees of conceptual and psychometric integrity. The normative functional skill approach supports the major screening devices for DCD and cognitive (or top-down) approaches to intervention. The general abilities approach and traditional neurodevelopmental theory are not well supported by recent research. The dynamical systems approach supports promising trends in biomechanical or kinematic analysis of movement, ecological task analysis, and task-specific intervention. Finally, and more recently, the cognitive neuroscientific approach has generated some examples of process-oriented assessment and treatment based on validated (brain-behaviour) models of motor control and learning. A multi-level approach to movement assessment and treatment is recommended for DCD, providing a more complete representation of motor development at different levels of function--behavioural, neurocognitive, and emotional.

Child↗

Mig12, a novel Opitz syndrome gene product partner, is expressed in the embryonic ventral midline and co-operates with Mid1 to bundle and stabilize microtubules.

BACKGROUND: Opitz G/BBB syndrome is a genetic disorder characterized by developmental midline abnormalities, such as hypertelorism, cleft palate, and hypospadias. The gene responsible for the X-linked form of this disease, MID1, encodes a TRIM/RBCC protein that is anchored to the microtubules. The association of Mid1 with the cytoskeleton is regulated by dynamic phosphorylation, through the interaction with the alpha4 subunit of phosphatase 2A (PP2A). Mid1 acts as an E3 ubiquitin ligase, regulating PP2A degradation on microtubules. RESULTS: In spite of these findings, the biological role exerted by the Opitz syndrome gene product is still unclear and the presence of other potential interacting moieties in the Mid1 structure prompted us to search for additional cellular partners. Through a yeast two-hybrid screening approach, we identified a novel gene, MIG12, whose protein product interacts with Mid1. We confirmed by immunoprecipitation that this interaction occurs in vivo and that it is mediated by the Mid1 coiled-coil domain. We found that Mig12 is mainly expressed in the neuroepithelial midline, urogenital apparatus, and digits during embryonic development. Transiently expressed Mig12 is found diffusely in both nucleus and cytoplasm, although it is enriched in the microtubule-organizing center region. Consistently with this, endogenous Mig12 protein is partially detected in the polymerized tubulin fraction after microtubule stabilization. When co-transfected with Mid1, Mig12 is massively recruited to thick filamentous structures composed of tubulin. These microtubule bundles are resistant to high doses of depolymerizing agents and are composed of acetylated tubulin, thus representing stabilized microtubule arrays. CONCLUSIONS: Our findings suggest that Mig12 co-operates with Mid1 to stabilize microtubules. Mid1-Mig12 complexes might be implicated in cellular processes that require microtubule stabilization, such as cell division and migration. Impairment in Mig12/Mid1-mediated microtubule dynamic regulation, during the development of embryonic midline, may cause the pathological signs observed in Opitz syndrome patients.

Amino Acid Sequence↗

Family matters: a social system perspective on physician-assisted suicide and the older adult.

Physician-assisted suicide is one of the most controversial issues facing health care providers today, provoking contentious debate that spans medical, psychological, legal, religious, and moral realms. Despite the wealth of theories and opinions proffered, most of this work focuses on concepts of individual competence and autonomy, with little or no attention paid to the dynamics of family or other psychosocial systems likely to affect an individual's decision to ask for assistance in ending his or her life. Moreover, concepts such as "autonomy" typically are examined from a legal perspective without consideration of the late-life developmental themes confronting older adults and their families, that is, the stages of life cycle transition and the predictable family stresses that typically accompany serious illness.

Aged↗

Reframing Balint: thoughts on family medicine departmental Balint groups.

This paper explores recurrent processes and themes in the 1,300 family medicine faculty, resident, intern, and community Balint groups the author has facilitated/led. The frequent group "deviation" from the central Balint task of understanding difficult physician-patient relationships is reframed as less "resistance" or "obstacle" to work, as it is an expression of unmet developmental needs and organizational realities. When group members are carefully attended to (by facilitator and one another), the group often becomes emotionally capable of addressing a "case " in the conventional Balint understanding of the work the group has assembled to do. The group dynamics of such "hybrid" Balint groups thus become comprehensible as other than error.

Family Practice↗

[Spatial expression of cardiac alpha-actin during heart development in embryos].

OBJECTIVE: Conotruncal defects (CTD) is a common type of cyanotic congenital heart defects. It was shown that CTD might be produced by ablation of cardiac neural crest during early stage embryos in experimental studies. There were many kinds of genes involved and cardiac alpha-actin (CAA) was one of them. The purpose of this study was to investigate the spatial expression of CAA gene during embryonic heart development, and to explore its role in the pathogenesis of congenital heart defects. METHODS: Experimental chicken embryos were subjected to cardiac neural crest ablation by using electric stimulation at 36-40 hr incubation stage. The embryos and organs of experimental and normal control groups during different developing periods were taken out, RNA was extracted by Trizol, and then reverse transcription was done. The dynamic changes of CAA mRNA expression at different development stages of embryos were assayed by fluorescent real-time PCR. The embryos and tissues at different stages were taken out, and paraffin sections were made. The localizations of CAA antibody expression in the developmental embryos were detected by immunohistochemical analysis (peroxidase-DAB coloration). RESULTS: (1) The expression of CAA gene was detected at early embryo development, and increased subsequently to a stable level. Its expression was mainly limited to heart site, and could be increased along with the maturation of the cardiac muscle. There was no expression or little trace expression in liver, brain, and stomach. (2) There was a significantly low level of CAA gene expression on days 2-7 of chicken embryos whose cardiac neural crest were ablated in comparison with normal controls (P = 0.013). The level of CAA gene expression was also down-regulated on days 7, 9 and 15 of embryonic cardiac tissues (P = 0.029). CONCLUSION: CAA gene is closely associated with heart development, its expression was adjusted by cardiac neural crest, and its dysfunction may be an important factor leading to congenital heart defects.

Actins↗

GFP-moesin illuminates actin cytoskeleton dynamics in living tissue and demonstrates cell shape changes during morphogenesis in Drosophila.

Moesin, ezrin, and radixin (MER) are components of the cortical actin cytoskeleton and membrane processes such as filopodia and microvilli. Their C-terminal tails contain an extended region that is predicted to be helical, an actin binding domain, and a region(s) that participates in self-association. We engineered an in vivo fluorescent actin binding protein (GFP-moe) by joining sequences that encode the jellyfish green fluorescent protein (GFP) to sequences that encode the C-terminal end of the sole Drosophila MER homolog, moesin [Moesin-like gene product, referred to previously as the D17 MER-like protein; Edwards et al., 1994, Proc. Natl. Acad. Sci. USA 91, 4589], and Dmoesin [McCartney and Fehon, 1996, J. Cell Biol. 133, 843]. Transgenic flies expressing this fusion protein under control of the hsp70 promoter were generated and used for analysis of cell shape changes during morphogenesis of various developmental stages and tissues. Following heat shock, high levels of stable fusion protein are produced by all somatic tissues. GFP-moe localizes to the cortical actin cytoskeleton, providing a strong in vivo marker for cell shape and pattern during epithelial morphogenesis. The protein also becomes highly enriched in pseudopods, microvilli, axons, denticles, the border cell process, and other membrane projections, potentially by binding to endogenous moesin as well as actin. We show that GFP-moe can be used to examine the development and behavior of these dynamic structures in live specimens. We observe a bright green fluorescent, presumably actin-rich, polar cell proboscis that inserts itself into the forming micropyle and appears to maintain an opening for sperm passage around which the chorion is formed. We also confirm the existence of an actin-rich purse string at the leading edge of the lateral epidermis and provide a dynamic analysis of its behavior as it migrates during dorsal closure. Observations of embryos, larvae, and pupae show that GFP-moe is also useful for labeling the developing nervous system and will be a good general marker of dynamic cell behavior during morphogenesis in live tissues and demonstrate that fusion of a subcellular localization signal to GFP greatly increases its utility as a cell marker.

Amino Acid Sequence↗

Post-translational control of occludin membrane assembly in mouse trophectoderm: a mechanism to regulate timing of tight junction biogenesis and blastocyst formation.

The mouse blastocyst forms during the 32-cell stage with the emergence of the blastocoelic cavity. This developmental transition is dependent upon the differentiation and transport function of the trophectoderm epithelium which forms the wall of the blastocyst and exhibits functional intercellular tight junctions (TJs) to maintain epithelial integrity during blastocoele expansion. To investigate mechanisms regulating the timing of blastocyst formation, we have examined the dynamics of expression of occludin, an integral membrane protein of the TJ. Confocal microscopy of intact embryos and synchronised cell clusters revealed that occludin first assembles at the apicolateral membrane contact site between nascent trophectoderm cells usually during the early 32-cell stage, just prior to the time of blastocoele cavitation. This is a late event in the assembly of TJ-associated proteins within trophectoderm which, from our previous data, spans from 8- to 32-cell stages. Occludin membrane assembly is dependent upon prior E-cadherin-mediated cell-cell adhesion and is sensitive to brefeldin A, an inhibitor of Golgi-to-membrane transport. Occludin is delivered to the TJ site in association with the TJ plaque protein, ZO-1(&agr;)+, which we have shown previously is newly transcribed and translated during late cleavage. Immediately after assembly and before cavitation, occludin localised at the TJ site switches from a Triton X-100-soluble to -insoluble form indicative of actin cytoskeletal and/or membrane anchorage. Occludin mRNA and protein are detectable throughout cleavage by RT-PCR and immunoblotting, respectively, indicating that timing of membrane assembly is not controlled by expression alone. Rather, we have identified changes in the pattern of different occludin forms expressed during cleavage which, using phosphatase treatment of embryo lysates, include post-translational modifications. We propose that the phosphorylation of one form of occludin (band 2, 65-67 kDa) during late cleavage, which leads to its exclusive conversion from a Triton X-100-soluble to -insoluble pool, may regulate occludin association with ZO-1(&agr;)+ and membrane assembly, and thereby act to control completion of TJ biogenesis and the timing of blastocyst formation.

Animals↗

Isolation and characterization of genes that are expressed during Ciona intestinalis metamorphosis.

In ascidians, the events of metamorphosis transform the non-feeding, mobile tadpole larva into a filter-feeding, fixed juvenile, and the process involves rearrangements of cells, two organs and physiological changes. Differential screening was used to isolate two genes that are not expressed in swimming larvae but are expressed immediately after the initiation of metamorphosis in Ciona intestinalis. One of the genes, Ci-meta1, encodes a polypeptide with a putative secretion signal sequence, 6 epidermal growth factor (EGF)-like repeats and 13 calcium-binding EGF-like repeats. The gene begins to be expressed immediately after the beginning of metamorphosis in the adhesive organ and is likely to be associated with the signal response for metamorphosis. Another gene named Ci-meta2 encodes a protein with a putative secretion signal and three thrombospondin type-1 repeats. Ci-meta2 gene expression begins at the larval stage and is upregulated in the metamorphosing juveniles. Ci-meta2 expression is found in three regions; the adhesive organ which is also associated with settlement, the neck region between the trunk and the tail of the larva which is associated with tail resorption, and dorsal regions of the trunk which correspond to the location of the siphon primordium. This gene may be involved in the dynamic arrangement of cells during ascidian metamorphosis.

Amino Acid Sequence↗

Differential expression of thymosins beta(4) and beta(10) during rat cerebellum postnatal development.

The beta-thymosins are a family of actin monomer-sequestering proteins widely distributed among vertebrate classes. The most abundant beta-thymosins in mammalian species are thymosin beta(4) (Tbeta(4)) and thymosin beta(10) (Tbeta(10)), two small peptides (43 amino acids) sharing a high degree of sequence homology. In the present work, we have analyzed the distribution of Tbeta(4) and Tbeta(10) in the developing and adult rat cerebellum using in situ hybridization and immunohistochemistry techniques. Our results show that the temporal and cellular patterns of expression of both beta-thymosins are different. In the young (7 and 18 postnatal days) and adult (1 and 4 months old) rat cerebellum, Tbeta(4) was mainly expressed in the glia (microglia, Golgi epithelial cells and oligodendrocytes), neurons (granule cells and Purkinje cells), and in the capillaries. In 14-month-old rats, the Tbeta(4) immunoreactivity was only detected in some microglia cells. In young and adult animals, most of the Tbeta(10) immunoreactivity was localized in several types of neuronal cells including granule cells, Golgi neurons and Purkinje cells. In old animals, a faint Tbeta(10) signal could be detected in a few Purkinje cells. Our results suggest that each beta-thymosin could play a different function in the control of actin dynamics.

Animals↗

Property structures, demography and the crisis of the agrarian economy of colonial Bombay Presidency.

Reasons for the relative failure of agricultural development in India during the colonial period are analyzed, and the effects of the scarcity of capital, the absence of suitable technology, and the growth of the population are assessed. "The article explores the manner in which peasant possession of land and other means of subsistence limited productive utilisation of capital and technology, triggered a certain demographic regime and, in turn, disrupted further developmental possibilities." The geographical focus is on the area coinciding with the modern states of Maharashtra and Gujarat.

Agriculture↗

An empirical analysis of motivations for mobility in Nigeria.

"This paper attempts to identify the factors that influence motivations for migration among the migrants [in Nigeria] (push and pull factors). The empirical results from the national survey of internal migration on which this study is based showed that the differences observed in the weights migrants attached to motivations for migration were statistically significant and did not just occur by chance. Though both the push and pull factors were important in explaining migration [decisions], the push factors were more important in the decision to migrate than the pull factors. This calls for a more comprehensive and coherent attention on the push factors in government efforts to stem anti-developmental migration patterns in Nigeria."

Africa↗

Functional and biochemical interactions of Wnts with FrzA, a secreted Wnt antagonist.

Wnts are highly conserved developmental regulators that mediate inductive signaling between neighboring cells and participate in the determination of embryonic axes. Frizzled proteins constitute a large family of putative transmembrane receptors for Wnt signals. FrzA is a novel protein that shares sequence similarity with the extracellular domain of Frizzled. The Xenopus homologue of FrzA is dynamically regulated during early development. At the neurula stages, XfrzA mRNA is abundant in the somitic mesoderm, but later becomes strongly expressed in developing heart, neural crest derivatives, endoderm, otic vesicle and other sites of organogenesis. To evaluate possible biological functions of FrzA, we analyzed its effect on early Xenopus development. Microinjection of bovine or Xenopus FrzA mRNA into dorsal blastomeres resulted in a shortened body axis, suggesting a block of convergent extension movements. Consistent with this possibility, FrzA blocked elongation of ectodermal explants in response to activin, a potent mesoderm-inducing factor. FrzA inhibited induction of secondary axes by Xwnt8 and human Wnt2, but not by Xdsh, supporting the idea that FrzA interferes with Wnt signaling. Furthermore, FrzA suppressed Wnt-dependent activation of the early response genes in ectodermal explants and in the marginal zone. Finally, immunoprecipitation experiments demonstrate that FrzA binds to the soluble Wingless protein in cell culture supernatants in vitro. Our results indicate that FrzA is a naturally occurring secreted antagonist of Wnt signaling.

Amino Acid Sequence↗

Molecular cloning, developmental expression, and cellular localization of the 70-kDa RPA-1 subunit of Drosophila melanogaster.

Replication protein A (RPA) is a highly conserved multifunctional heterotrimeric complex, involved in DNA replication, repair, recombination, and possibly transcription. Here, we report the cloning of the gene that codes for the largest subunit of the Drosophila melanogaster RPA homolog, dmRPA70. In situ hybridization showed that dmRPA70 RNA is present in developing embryos during the first 16 cycles. After this point, dm-RPA70 expression is downregulated in cells that enter a G1 phase and exit the mitotic cycle, becoming restricted to brief bursts of accumulation from late G1 to S phase. This pattern of regulated expression is also observed in the developing eye imaginal disc. In addition, we have shown that the presence of cyclin E is necessary and sufficient to drive the expression of dmRPA70 in embryonic cells arrested in G1 but is not required in tissues undergoing endoreduplication. Immunolocalization showed that in early developing embryos, the dmRPA70 protein associates with chromatin from the end of mitosis until the beginning of the next prophase in a dynamic speckled pattern that is strongly suggestive of its association with replication foci.

Amino Acid Sequence↗

Morphogen gradients, positional information, and Xenopus: interplay of theory and experiment.

The idea of morphogen gradients has long been an important one in developmental biology. Studies with amphibians and with Xenopus in particular have made significant contributions to demonstrating the existence, identity, and mechanisms of action of morphogens. Mesoderm induction and patterning by activin, nodals, bone morphogenetic proteins, and fibroblast growth factors have been analyzed thoroughly and reveal recurrent and combinatorial roles for these protein growth factor morphogens and their antagonists. The dynamics of nodal-type signaling and the intersection of VegT and beta-catenin intracellular gradients reveal detailed steps in early long-range patterning. Interpretation of gradients requires sophisticated mechanisms for sharpening thresholds, and the activin-Xbra-Gsc system provides an example of this. The understanding of growth factor signal transduction has elucidated growth factor morphogen action and provided tools for dissecting their direct long-range action and distribution. The physical mechanisms of morphogen gradient establishment are the focus of new interest at both the experimental and theoretical level. General themes and emerging trends in morphogen gradient studies are discussed.

Animals↗