Origins and early development of human body knowledge

As a knowable object, the human body is highly complex. Evidence from several converging lines of research, including psychological studies, neuroimaging and clinical neuropsychology, indicates that human body knowledge is widely distributed in the adult brain, and is instantiated in at least three partially independent levels of representation. Sensori-motor body knowledge is responsible for on-line control and movement of one's own body and may also contribute to the perception of others' moving bodies; visuo-spatial body knowledge specifies detailed structural descriptions of the spatial attributes of the human body; and lexical-semantic body knowledge contains language-based knowledge about the human body. In the first chapter of this Monograph, we outline the evidence for these three hypothesized levels of human body knowledge, then review relevant literature on infants' and young children's human body knowledge in terms of the three-level framework. In Chapters II and III, we report two complimentary series of studies that specifically investigate the emergence of visuospatial body knowledge in infancy. Our technique is to compare infants' responses to typical and scrambled human bodies, in order to evaluate when and how infants acquire knowledge about the canonical spatial layout of the human body. Data from a series of visual habituation studies indicate that infants first discriminate scrambled from typical human body pictures at 15 to 18 months of age. Data from object examination studies similarly indicate that infants are sensitive to violations of three-dimensional human body stimuli starting at 15-18 months of age. The overall pattern of data supports several conclusions about the early development of human body knowledge: (a) detailed visuo-spatial knowledge about the human body is first evident in the second year of life, (b) visuo-spatial knowledge of human faces and human bodies are at least partially independent in infancy and (c) infants' initial visuo-spatial human body representations appear to be highly schematic, becoming more detailed and specific with development. In the final chapter, we explore these conclusions and discuss how levels of body knowledge may interact in early development.

The role of insulin-like growth factor II and its receptor in mouse preimplantation development

Insulin-like growth factor II (IGF-II) and its receptor, the IGF-II/mannose-6-phosphate (IGF-II/M6P) receptor, are first expressed from the zygotic genome at the two-cell stage of mouse development. However, their role is not clearly defined. Insulin-like growth factor II is believed to mediate growth through the heterologous type 1 IGF and insulin receptors, whereas the IGF-II/M6P receptor is believed to act as a negative regulator of somatic growth by limiting the availability of excess levels of IGF-II. These studies demonstrate that IGF-II does have a role in growth regulation in the early embryo through the IGF-II/M6P receptor. Insulin-like growth factor II stimulated cleavage rate in two-cell embryos in vitro. Moreover, this receptor is required for the glycaemic response of two-cell embryos to IGF-II and for normal progression of early embryos to the blastocyst stage. Improved development of embryos in crowded culture supports the concept of an endogenous embryonic paracrine activity that enhances cell proliferation. These responses indicate that the IGF-II/M6P receptor is functional and likely to participate in such a regulatory circuit. The functional role of IGF-II and its receptor is discussed with reference to regulation of early development.

Post-hatching growth and development of the pectoral and pelvic limbs in the black noddy, Anous minutus

The black tern (Anous minutus) uses a semi-precocial growth strategy. Terrestrial locomotor capacity occurs soon after hatching, but pectoral limb development is delayed and flight is not possible until about post-hatching day 50. A growth series (hatchlings to fledglings) was used to explore how limb musculoskeletal development varied with body mass. In the pelvic limb, bone lengths scaled isometrically or with negative allometry. Gastrocnemius muscle mass and the failure load and stiffness of the tibiotarsus scaled isometrically. In the pectoral limb, pectoralis and supracoracoideus muscle masses increased with strong positive allometry that was mirrored by increases in wing bone strength and stiffness. Bending strength (σult) and modulus (E) remained fairly constant throughout development to fledging for all limb bones. The moment of inertia (I) scaled with negative allometry for the tibiotarsus and with strong positive allometry in the wing bones. Differences in σult and E of the tibiotarsus between pre-fledged chicks and adults was due, primarily, to increases in bone density rather than increases in the moment of inertia of the skeletal elements, whereas σult of wing bones was a function of increases in both bone density and I. Early development of functional pelvic limbs in tree-nesting birds is relatively unusual, and presumably reflects a familial trait that does not appear to compromise breeding success in this species.

Glucosamine supplementation during in vitro maturation inhibits subsequent embryo development: Possible role of the of developmental competence

Glucose concentration during cumulus-oocyte complex (COC) maturation influences several functions, including progression of oocyte meiosis, oocyte developmental competence, and cumulus mucification. Glucosamine (GlcN) is an alternative hexose substrate, specifically metabolized through the hexosamine biosynthesis pathway, which provides the intermediates for extracellular matrix formation during cumulus cell mucification. The aim of this study was to determine the influence of GlcN on meiotic progression and oocyte developmental competence following in vitro maturation (IVM). The presence of GlcN during bovine IVM did not affect the completion of nuclear maturation and early cleavage, but severely perturbed blastocyst development. This effect was subsequently shown to be dose-dependent and was also observed for porcine oocytes matured in vitro. Hexosamine biosynthesis upregulation using GlcN supplementation is well known to increase O-linked glycosylation of many intracellular signaling molecules, the best-characterized being the phosphoinositol-3-kinase (PI3K) signaling pathway. We observed extensive O-linked glycosylation in bovine cumulus cells, but not oocytes, following IVM in either the presence or the absence of GlcN. Inhibition of O-linked glycosylation significantly reversed the effect of GlcN-induced reduction in developmental competence, but inhibition of PI3K signaling had no effect. Our data are the first to link hexosamine biosynthesis, involved in cumulus cell mucification, to oocyte developmental competence during in vitro maturation.

Oxygen-regulated gene expression in bovine blastocysts

Oxygen concentrations used during in vitro embryo culture can influence embryo development, cell numbers, and gene expression. Here we propose that the preimplantation bovine embryo possesses a molecular mechanism for the detection of, and response to, oxygen, mediated by a family of basic helix-loop-helix transcription factors, the hypoxia-inducible factors (HIFs). Day 5 compacting bovine embryos were cultured under different oxygen tensions (2%, 7%, 20%) and the effect on the expression of oxygen-regulated genes, development, and cell number allocation and HIFalpha protein localization were examined. Bovine in vitro-produced embryos responded to variations in oxygen concentration by altering gene expression. GLUT1 expression was higher following 2% oxygen culture compared with 7% and 20% cultured blastocysts. HIF mRNA expression (HIF1alpha, HIF2alpha) was unaltered by oxygen concentration. HIF2alpha protein was predominantly localized to the nucleus of blastocysts. In contrast, HIF1alpha protein was undetectable at any oxygen concentration or in the presence of the HIF protein stabilizer desferrioxamine (DFO), despite being detectable in cumulus cells following normal maturation conditions, acute anoxic culture, or in the presence of DFO. Oxygen concentration also significantly altered inner cell mass cell proportions at the blastocyst stage. These results suggest that oxygen can influence gene expression in the bovine embryo during postcompaction development and that these effects may be mediated by HIF2alpha.

Transient prenatal vitamin D deficiency is associated with hyperlocomotion in adult rats

Rat experiments have shown that prenatal Vitamin D deficiency leads to altered neonatal brain morphology, cell density and neurotrophin expression. In the current study we examined the hypothesis that Vitamin D deficiency during early development alters adult behaviour even when there is an intervening period in which the animal receives normal Vitamin D in later development. Rats were conceived and born to Vitamin D deficient dams (Birth); conceived, born and weaned from Vitamin D deficient dams (Weaning); or deficient in Vitamin D from conception to 10 weeks of age (Life). Litters were standardized to three males and three females per litter. All rat offspring were rendered normocalcaemic with calcium supplemented water (2 mM) after weaning. Control animals were born to mothers fed a normal diet but subject to similar litter size and calcium supplementation. At 10 weeks all animals were tested on the holeboard test, elevated plus maze test, social interaction observation, acoustic startle response test, prepulse inhibition of the acoustic startle response and a forced swim test. Early Vitamin D deficiency (Birth group) enhanced locomotion in the holeboard test and increased activity in the elevated plus maze. Thus, transient prenatal Vitamin D deficiency induces hyperlocomotion in adulthood, without severe motor abnormalities. (C) 2004 Elsevier B.V. All rights reserved.

Adolescent tobacco-related associative memory: a cross-sectional and contextual analysis

Tobacco use is prevalent in adolescents, and understanding factors that contribute to its uptake and early development remains a critical public health priority. Implicit drug-related memory associations (DMAs) are predictive of drug use in older samples, but such models have little application to adolescent tobacco use. Moreover, extant research on memory associations yields little information on contextual factors that may be instrumental in the development of DMAs. The present study examined (a) the degree to which tobacco-related memory associations (TMAs) were associated with concurrent tobacco use and (b) the extent to which TMAs mediated the association of peer and self-use. A sample of 210 Australian high school students was recruited. Participants completed TMA tasks and behavioral checklists designed to obscure the tobacco-related focus of the study. Results showed that TMAs were associated with peer use, and TMAs predicted self-use. We found no evidence that TMAs mediated the association of peer and self-use. Future research might examine the emotive valence of implicit nodes and drinking behavior. The results have implications for testing the efficacy of consciousness-raising interventions for adolescents at risk of tobacco experimentation or regular use.

Angioblast-mesenchyme induction of early kidney development is mediated by Wt1 and Vegfa

Most studies on kidney development have considered the interaction of the metanephric mesenchyme and the ureteric bud to be the major inductive event that maintains tubular differentiation and branching morphogenesis. The mesenchyme produces Gdnf, which stimulates branching, and the ureteric bud stimulates continued growth of the mesenchyme and differentiation of nephrons from the induced mesenchyme. Null mutation of the Wt1 gene eliminates outgrowth of the ureteric bud, but Gdnf has been identified as a target of Pax2, but not of Wt1. Using a novel system for microinjecting and electroporating plasmid expression constructs into murine organ cultures, it has been demonstrated that Vegfa expression in the mesenchyme is regulated by Wt1. Previous studies had identified a population of Flk1-expressing cells in the periphery of the induced mesenchyme, and adjacent to the stalk of the ureteric bud, and that Vegfa was able to stimulate growth of kidneys in organ culture. Here it is demonstrated that signaling through Flk1 is required to maintain expression of Pax2 in the mesenchyme of the early kidney, and for Pax2 to stimulate expression of Gdnf. However, once Gdnf stimulates branching of the ureteric bud, the Flk1-dependent angioblast signal is no longer required to maintain branching morphogenesis and induction of nephrons. Thus, this work demonstrates the presence of a second set of inductive events, involving the mesenchymal and angioblast populations, whereby Wt1-stimulated expression of Vegfa elicits an as-yet-unidentified signal from the angioblasts, which is required to stimulate the expression of Pax2 and Gdnf, which in turn elicits an inductive signal from the ureteric bud.

Expression analysis of the Epha1 receptor tyrosine kinase and its high-affinity ligands Efna1 and Efna3 during early mouse development

Interaction of Eph receptor tyrosine kinases with their membrane bound ephrin ligands initiates bidirectional signaling events that regulate cell migratory and adhesive behavior. Whole-mount in situ hybridization revealed overlapping expression of the Epha1 receptor and its high-affinity ligands ephrin A1 (Efna1) and ephrin A3 (Efna3) in the primitive streak and the posterior paraxial mesoderm during early mouse development. These results show complex and dynamic expression for all three genes with expression domains that are successively complementary, overlapping, and divergent. (c) 2006 Elsevier B.V. All rights reserved.

The development of self-awareness and relationship to emotional functioning during early community reintegration after traumatic brain injury

Impaired self-awareness may affect clients' emotional status, engagement in rehabilitation and community reintegration following traumatic brain injury (TBI). The study aimed to investigate the relationship between self-awareness, emotional distress and community integration in adults with TBI during the transition from hospital to the community. Thirty-four rehabilitation clients with TBI were assessed in the week before and 2 months after discharge home. Measures of self-awareness and emotional functioning were administered predischarge and repeated at follow-up along with a measure of community integration. Nonparametric tests were used to compare levels of self-awareness and emotional distress pre- and postdischarge, their interrelationships and association with community integration. Self-awareness significantly increased following discharge, and a trend towards increased depression was found. There were no consistent relationships found between level of self-awareness, emotional functioning, and community integration. The development of self-awareness in the immediate postdischarge phase suggests this is an important time for clinical interventions targeting compensation strategies and adjustment to disability.

Definition and spatial annotation of the dynamic secretome during early kidney development

The term secretome has been defined as a set of secreted proteins (Grimmond et al. [2003] Genome Res 13:1350-1359). The term secreted protein encompasses all proteins exported from the cell including growth factors, extracellular proteinases, morphogens, and extracellular matrix molecules. Defining the genes encoding secreted proteins that change in expression during organogenesis, the dynamic secretome, is likely to point to key drivers of morphogenesis. Such secreted proteins are involved in the reciprocal interactions between the ureteric bud (UB) and the metanephric mesenchyme (AM) that occur during organogenesis of the metanephros. Some key metanephric secreted proteins have been identified, but many remain to be determined. In this study, microarray expression profiling of E10.5, E11.5, and E13.5 kidney and consensus bioinformatic analysis were used to define a dynamic secretome of early metanephric development. In situ hybridisation was used to confirm microarray results and clarify spatial expression patterns for these genes. Forty-one secreted factors were dynamically expressed between the E10.5 and E13.5 timeframe profiled, and 25 of these factors had not previously been implicated in kidney development. A text-based anatomical ontology was used to spatially annotate the expression pattern of these genes in cultured metanephric explants.

Reflections on the development and implementation of an early warning system for ecstasy and related drug markets in Australia

Regular and systematic monitoring of drug markets provides the basis for evidence-based policy. In Australia, trends in ecstasy and related drug (ERD) markets have been monitored in selected jurisdictions since 2000 and nationally since 2003, by the Party Drugs Initiative (PDI). The PDI maximises the validity of conclusions by triangulating information from (a) interviews with regular ecstasy users (REU), (b) interviews with key experts and (c) indicator data. There is currently no other system in Australia for monitoring these markets systematically; however, the value of the PDI has been constrained by the quality of available data. Difficulties in recruiting and interviewing appropriate consumers (REU) and key experts have been experienced, but largely overcome. Limitations of available indicator data from both health and law enforcement continue to present challenges and there remains considerable scope for enhancing existing routine data collection systems, to facilitate monitoring of ERD markets. With an expanding market for ecstasy and related drugs in Australia, and in the context of indicator data that continue to be limited in scope and detail, there is a strong argument for the continued collection of annual, comparable data from a sentinel group of REU, such as those recruited for the PDI.