Developmental changes in presynaptic muscarinic modulation of excitatory and inhibitory neurotransmission in rat piriform cortex in vitro: relevance to epileptiform bursting susceptibility

Suppression of depolarizing postsynaptic potentials and isolated GABA-A receptor-mediated fast inhibitory postsynaptic potentials by the muscarinic acetylcholine receptor agonist, oxotremorine-M (10 microM), was investigated in adult and immature (P14-P30) rat piriform cortical (PC) slices using intracellular recording. Depolarizing postsynaptic potentials evoked by layers II-III stimulation underwent concentration-dependent inhibition in oxotremorine-M that was most likely presynaptic and M2 muscarinic acetylcholine receptor-mediated in immature, but M1-mediated in adult (P40-P80) slices; percentage inhibition was smaller in immature than in adult piriform cortex. In contrast, compared with adults, layer Ia-evoked depolarizing postsynaptic potentials in immature piriform cortex slices in oxotremorine-M, showed a prolonged multiphasic depolarization with superimposed fast transients and spikes, and an increased 'all-or-nothing' character. Isolated N-methyl-d-aspartate receptor-mediated layer Ia depolarizing postsynaptic potentials (although significantly larger in immature slices) were however, unaffected by oxotremorine-M, but blocked by dl-2-amino-5-phosphonovaleric acid. Fast inhibitory postsynaptic potentials evoked by layer Ib or layers II-III-fiber stimulation in immature slices were significantly smaller than in adults, despite similar estimated mean reversal potentials ( approximately -69 and -70 mV respectively). In oxotremorine-M, only layer Ib-fast inhibitory postsynaptic potentials were suppressed; suppression was again most likely presynaptic M2-mediated in immature slices, but M1-mediated in adults. The degree of fast inhibitory postsynaptic potential suppression was however, greater in immature than in adult piriform cortex. Our results demonstrate some important physiological and pharmacological differences between excitatory and inhibitory synaptic systems in adult and immature piriform cortex that could contribute toward the increased susceptibility of this region to muscarinic agonist-induced epileptiform activity in immature brain slices.

Understanding and production of prosody in children with Williams syndrome: A developmental trajectory approach

This study investigated the development of three aspects of linguistic prosody in a group of children with Williams syndrome compared to typically developing children. The prosodic abilities investigated were: (1) the ability to understand and use prosody to make specific words or syllables stand out in an utterance (focus); (2) the ability to understand and use prosody to disambiguate complex noun phrases (chunking); (3) the ability to understand and use prosody to regulate conversational behaviour (turn-end). The data were analysed using a cross-sectional developmental trajectory approach. The results showed that, relative to chronological age, there was a delayed onset in the development of the ability of children with WS to use prosody to signal the most important word in an utterance (the focus function). Delayed rate of development was found for all the other aspects of expressive and receptive prosody under investigation. However, when non-verbal mental age was taken into consideration, there were no differences between the children with WS and the controls neither with the onset nor with the rate of development for any of the prosodic skills under investigation apart from the ability to use prosody in order to regulate conversational behaviour. We conclude that prosody is not a ‘preserved’ cognitive skill in WS. The genetic factors, development in other cognitive domains and environmental influences affect developmental pathways and as a result, development proceeds along an atypical trajectory.

Developmental changes in the germinability, desiccation tolerance, hardseededness, and longevity of individual seeds of Trifolium ambiguum

Background and Aims: Using two parental clones of outcrossing Trifolium ambiguum as a potential model system, we examined how during seed development the maternal parent, number of seeds per pod, seed position within the pod, and pod position within the inflorescence influenced individual seed fresh weight, dry weight, water content, germinability, desiccation tolerance, hardseededness, and subsequent longevity of individual seeds. Methods: Near simultaneous, manual reciprocal crosses were carried out between clonal lines for two experiments. Infructescences were harvested at intervals during seed development. Each individual seed was weighed and then used to determine dry weight or one of the physiological behaviour traits. Key Results: Whilst population mass maturity was reached at 33–36 days after pollination (DAP), seed-to-seed variation in maximum seed dry weight, when it was achieved, and when maturation drying commenced, was considerable. Individual seeds acquired germinability between 14 and 44 DAP, desiccation tolerance between 30 and 40 DAP, and the capability to become hardseeded between 30 and 47 DAP. The time for viability to fall to 50 % (p50) at 60 % relative humidity and 45 °C increased between 36 and 56 DAP, when the seed coats of most individuals had become dark orange, but declined thereafter. Individual seed f. wt at harvest did not correlate with air-dry storage survival period. Analysing survival data for cohorts of seeds reduced the standard deviation of the normal distribution of seed deaths in time, but no sub-population showed complete uniformity of survival period. Conclusions: Variation in individual seed behaviours within a developing population is inherent and inevitable. In this outbreeder, there is significant variation in seed longevity which appears dependent on embryo genotype with little effect of maternal genotype or architectural factors.

Post-abscission, pre-dispersal seeds of Digitalis purpurea remain in a developmental state that is not terminated by desiccation ex planta

Seed quality may be compromised if seeds are harvested before natural dispersal (shedding). It has been shown previously that slow or delayed drying can increase potential quality compared with immediate rapid drying. This study set out to investigate whether or not there is a critical moisture content, below which drying terminates maturation events for seeds harvested after mass maturity but before dispersal. Seeds of foxglove (Digitalis purpurea) in the post-abscission pre-dispersal phase were held at between 15 and 95 % RH for 4 or 8 d, with or without re-hydration to 95 % RH for a further 4 d, before drying to equilibrium at 15 % RH. In addition, dry seeds were primed for 48 h at -1 MPa. Subsequent seed longevity was assessed at 60 % RH and 45 degrees C. Rate of germination and longevity were improved by holding seeds at a wide range of humidities after harvest. Longevity was further improved by re-hydration at 95 % RH. Priming improved the longevity of the seeds dried immediately after harvest, but not of those first held at 95 % RH for 8 d prior to drying. Maturation continued ex planta in these post-abscission, pre-dispersal seeds of D. purpurea dried at 15-80 % RH at a rate correlated positively with RH (cf. ageing of mature seeds). Subsequent re-hydration at 95 % RH enabled a further improvement in quality. Priming seeds initially stored air-dry for 3 months also allowed maturation events to resume. However, once individual seeds within the population had reached maximum longevity, priming had a negative impact on their subsequent survival.

Developmental programming: Deficits in reproductive hormone dynamics and ovulatory outcomes in prenatal, testosterone-treated sheep

Prenatal testosterone excess leads to neuroendocrine, ovarian, and metabolic disruptions, culminating in reproductive phenotypes mimicking that of women with polycystic ovary syndrome (PCOS). The objective of this study was to determine the consequences of prenatal testosterone treatment on periovulatory hormonal dynamics and ovulatory outcomes. To generate prenatal testosterone-treated females, pregnant sheep were injected intramuscularly (days 30-90 of gestation, term = 147 days) with 100 mg of testosterone-propionate in cottonseed oil semi-weekly. Female offspring born to untreated control females and prenatal testosterone-treated females were then studied during their first two breeding seasons. Sheep were given two injections of prostaglandin F-2alpha 11 days apart, and blood samples were collected at 2-h intervals for 120 h, 10-min intervals for 8 h during the luteal phase (first breeding season only), and daily for an additional 15 days to characterize changes in reproductive hormonal dynamics. During the first breeding season, prenatal testosterone-treated females manifested disruptions in the timing and magnitude of primary gonadotropin surges, luteal defects, and reduced responsiveness to progesterone negative feedback. Disruptions in the periovulatory sequence of events during the second breeding season included: 1) delayed but increased preovulatory estradiol rise, 2) delayed and severely reduced primary gonadotropin surge in prenatal testosterone-treated females having an LH surge, 3) tendency for an amplified secondary FSH surge and a shift in the relative balance of FSH regulatory proteins, and 4) luteal responses that ranged from normal to anovulatory. These outcomes are likely to be of relevance to developmental origin of infertility disorders and suggest that differences in fetal exposure or fetal susceptibility to testosterone may account for the variability in reproductive phenotypes.

Developmental expression of myostatin in cardiomyocytes and its effect on foetal and neonatal rat cardiomyocyte proliferation

Objectives: Myostatin, a member of the transforming growth factor-beta (TGF-beta) family, plays a key role in skeletal muscle myogenesis by limiting hyperplastic and hypertrophic muscle growth. In cardiac muscle, myostatin has been shown to limit agonist-induced cardiac hypertrophic growth. However, its role in cardiac hyperplastic growth remains undetermined. The aim of this study was to characterise the expression of myostatin in developing myocardium, determine its effect on cardiomyocyte proliferation, and explore the signalling mechanisms affected by myostatin in dividing cardiomyocytes. Methods: We used quantitative PCR and Western blotting to study the expression of myostatin in cardiomyocytes isolated from rat myocardium at different developmental ages. We. determined the effect of recombinant myostatin on proliferation and cell viability in dividing cardiomyocytes in culture. We analysed myostatin's effect on cardiomyocyte cell cycle progression by flow cytometry and used Western blotting to explore the signalling mechanisms involved. Results: Myostatin is expressed differentially in cardiomyocytes during cardiac development such that increasing expression correlated with a low cardiomyocyte proliferation index. Proliferating foetal cardiomyocytes, from embryos at 18 days of gestation, expressed low levels of myostatin mRNA and protein, whereas isolated cardiomyocytes from postnatal day 10 hearts, wherein the majority of cardiomyocytes have lost their ability to proliferate, displayed a 6-fold increase in myostatin expression. Our in vitro studies demonstrated that myostatin inhibited proliferation of dividing foetal and neonatal cardiomyocytes. Flow cytometric analysis showed that this inhibition occurs mainly via a block in the G1-S phase transition of the cardiomyocyte cell cycle. Western blot analysis showed that part of the mechanism underpinning the inhibition of cardiomyocyte proliferation by myostatin involves phosphorylation of SMAD2 and altered expressions of the cell cycle proteins p21 and CDK2. Conclusions: We conclude that myostatin is an inhibitor of cardiomyocyte proliferation with the potential to limit cardiomyocyte hyperplastic growth by altering cardiac cell cycle progression. (c) 2007 European Society of Cardiology. Published by Elsevier B.V. All fights reserved.

Seasonal variations in the developmental competence of bovine oocytes matured in vitro

Ovaries were collected over a period of two years from heifers slaughtered at under 30 months of age and used to harvest 1757 oocytes. After in vitro maturation, fertilisation and culture, the proportions of oocytes and cleaved embryos that developed to blastocysts were significantly higher (P < 0.01) in the autumn, from September to November, than in the spring, from March to May. In contrast, embryo development, as assessed by oocytes that developed to eight or more cells and blastocysts, was lowest (P < 0.01) in the spring. These results were consistent during the two-year study, indicating a seasonal fluctuation in oocyte competence.

Amphioxus molecular biology: insights into vertebrate evolution and developmental mechanisms

The cephalochordate amphioxus is the best available proxy for the last common invertebrate ancestor of the vertebrates. During the last decade, the developmental genetics of amphioxus have been extensively examined for insights into the evolutionary origin and early evolution of the vertebrates. Comparisons between expression domains of homologous genes in amphioxus and vertebrates have strengthened proposed homologies between specific body parts. Molecular genetic studies have also highlighted parallels in the developmental mechanisms of amphioxus and vertebrates. In both groups, a similar nested pattern of Hox gene expression is involved in rostrocaudal patterning of the neural tube, and homologous genes also appear to be involved in dorsoventral neural patterning. Studies of amphioxus molecular biology have also hinted that the protochordate ancestor of the vertebrates included cell populations that modified their developmental genetic pathways during early vertebrate evolution to yield definitive neural crest and neurogenic placodes. We also discuss how the application of expressed sequence tag and gene-mapping approaches to amphioxus have combined with developmental studies to advance our understanding of chordate genome evolution. We conclude by considering the potential offered by the sequencing of the amphioxus genome, which was completed in late 2004.

Developmental trends in lexical diversity.

This article discusses issues in measuring lexical diversity, before outlining an approach based on mathematical modelling that produces a measure, D, designed to address these problems. The procedure for obtaining values for D directly from transcripts using software (vocd) is introduced, and then applied to thirty-two children from the Bristol Study of Language Development (Wells 1985) at ten different ages. A significant developmental trend is shown for D and an indication is given of the average scores and ranges to be expected between the ages of 18 and 42 months and at 5 years for these L1 English speakers. The meaning attributable to further ranges of values for D is illustrated by analysing the lexical diversity of academic writing, and its wider application is demonstrated with examples from specific language impairment, morphological development, and foreign/second language learning.

QTLs for shelf life in lettuce co-locate with those for leaf biophysical properties but not with those for leaf developmental traits

Developmental and biophysical leaf characteristics that influence post-harvest shelf life in lettuce, an important leafy crop, have been examined. The traits were studied using 60 informative F-9 recombinant inbed lines (RILs) derived from a cross between cultivated lettuce (Lactuca sativa cv. Salinas) and wild lettuce (L. serriola acc. UC96US23). Quantitative trait loci (QTLs) for shelf life co-located most closely with those for leaf biophysical properties such as plasticity, elasticity, and breakstrength, suggesting that these are appropriate targets for molecular breeding for improved shelf life. Significant correlations were found between shelf life and leaf size, leaf weight, leaf chlorophyll content, leaf stomatal index, and epidermal cell number per leaf, indicating that these pre-harvest leaf development traits confer post-harvest properties. By studying the population in two contrasting environments in northern and southern Europe, the genotype by environment interaction effects of the QTLs relevant to leaf development and shelf life were assessed. In total, 107 QTLs, distributed on all nine linkage groups, were detected from the 29 traits. Only five QTLs were common in both environments. Several areas where many QTLs co-located (hotspots) on the genome were identified, with relatively little overlap between developmental hotspots and those relating to shelf life. However, QTLs for leaf biophysical properties (breakstrength, plasticity, and elasticity) and cell area correlated well with shelf life, confirming that the ideal ideotype lettuce should have small cells with strong cell walls. The identification of QTLs for leaf development, strength, and longevity will lead to a better understanding of processability at a genetic and cellular level, and allow the improvement of salad leaf quality through marker-assisted breeding.

Problems in the coupling of eye and hand in the sequential movements of children with developmental coordination disorder

Background: Shifting gaze and attention ahead of the hand is a natural component in the performance of skilled manual actions. Very few studies have examined the precise co-ordination between the eye and hand in children with Developmental Coordination Disorder (DCD). Methods This study directly assessed the maturity of eye-hand co-ordination in children with DCD. A double-step pointing task was used to investigate the coupling of the eye and hand in 7-year-old children with and without DCD. Sequential targets were presented on a computer screen, and eye and hand movements were recorded simultaneously. Results There were no differences between typically developing (TD) and DCD groups when completing fast single-target tasks. There were very few differences in the completion of the first movement in the double-step tasks, but differences did occur during the second sequential movement. One factor appeared to be the propensity for the DCD children to delay their hand movement until some period after the eye had landed on the target. This resulted in a marked increase in eye-hand lead during the second movement, disrupting the close coupling and leading to a slower and less accurate hand movement among children with DCD. Conclusions In contrast to skilled adults, both groups of children preferred to foveate the target prior to initiating a hand movement if time allowed. The TD children, however, were more able to reduce this foveation period and shift towards a feedforward mode of control for hand movements. The children with DCD persevered with a look-then-move strategy, which led to an increase in error. For the group of DCD children in this study, there was no evidence of a problem in speed or accuracy of simple movements, but there was a difficulty in concatenating the sequential shifts of gaze and hand required for the completion of everyday tasks or typical assessment items.

Attention disengagement in children with developmental coordination disorder

Purpose. Previous research has shown that children with Developmental Coordination Disorder (DCD) have poorly developed strategies for allocating attention. This study examines the allocation of attention and integration of visuo-spatial and motor systems in children with DCD in a motor (look+hit condition) and a motor-free (look condition) task. Method. Three groups of control children were used to compare the performance of a group of children with DCD. Children were seated in front of a central fixation point and six peripheral targets, and were asked to look at or hit targets when illuminated. Saccade/hand movement latencies were measured on gap trials (gap between fixation offset and target onset) and overlap trials (fixation offset and target onset overlapped). Results. DCD children were not slower than controls to disengage attention during the look condition. However, during the look+hit condition the DCD children showed a prolonged disengagement period, which was also seen in younger control children. Conclusions. The results suggest that DCD children may have deficits in the allocation of attention for action, in both the speed of onset of a movement and the accuracy of the movement. It is concluded that attention disengagement may contribute to problems of visuo-motor integration in DCD.

Self-esteem and coping in children with developmental coordination disorder

This study investigated self-esteem in children with developmental coordination disorder (DCD). Fifteen children between the ages of 8 and 12 years diagnosed with DCD were compared with a typically developing group comprising 30 children with average and good motor abilities, using measures of perceived competence, social support and self-esteem. The types of coping strategy generated in response to example vignettes were also compared. There was no significant difference between the groups in global self-esteem, but the children with DCD reported lower athletic and scholastic competence than their typically developing peers. No difference was found between the groups in level of perceived social support. The DCD group generated fewer coping strategies overall, but more passive and avoidant strategies than the typically developing children. The implications of the study are discussed with regard to future research directions, such as the investigation of the effects of motor skill intervention on self-esteem and the development of strategies to protect children's self-esteem.