Changes In Developmental Trajectories Research Articles

Flower morphology evolution in Jaborosa (Solanaceae): shape and size variation associated with contrasting pollination modes.

Flower morphology is considered an important factor in species diversification because it may influence the efficiency of pollination in different ways (e.g. attraction and mechanical fit with different groups of pollinators). In the present study, we quantified the variation in flower morphology (i.e. shape and size) of the diverse South American genus Jaborosa Juss. (Solanaceae) in relation to contrasting pollination modes: rewarding pollination either by moths or by generalist small insects versus brood-site deceptive pollination by saprophilous flies. We examined variations of flower morphology in frontal (pollinator attraction) and sagittal (functional fit with pollinators) views in 12 Jaborosa species using geometric morphometric methods and comparative approaches to infer whether flower shape evolution, not attributable to flower allometry or phylogenetic relationship, is associated with shifts in pollination modes. We found remarkable variation in flower morphology among both Jaborosa species and pollination modes, largely in sagittal view. Evolutionary trends in shape of fly-pollinated flowers were mainly attributable to changes in developmental trajectories. Variation in flower architecture facilitated differential pollen placement - on the proboscis of moths, and either on the back or ventral region of saprophilous flies - promoting diversification of the genus. Diversification of shape, independent of size, in most of the studied Jaborosa species would indicate adaptation to contrasting pollination modes.

Changes in Developmental Trajectories of Preschool Children with Autism Spectrum Disorder during Parental Based Intensive Intervention.

Background: Research highlights the positive effects of early intensive intervention with parent and school involvement for preschool children with Autism Spectrum Disorder (ASD) on general developmental outcomes and social skills in randomized controlled trials. However, given the inter-individual variability in the response to treatment, it is necessary to investigate intervention effects in terms of mediators and moderators in order to explain variability and to highlight mechanisms of change. Methods: 25 children in the experimental group were exposed to early intensive intervention and 14 children in the control group were subjected to “as usual” intervention. The initial assessment was obtained at the time of diagnosis (T1) and the follow-up assessment was conducted after 15 months of intervention (T2) in both groups. Results: Participants in the experimental group achieved more prominent gains in both cognitive and socio-interactive skills. The role of specific factors able to predict general quotient and language quotient after intervention were investigated, pointing out the contribution of personal–social and performance abilities. Conclusions: The findings support the importance of parental involvement in targeting ASD core symptoms. Further, results informed our understanding of early predictors in order to identify specific elements to be targeted in the individualized intervention design.

Microglial Function in the Effects of Early-Life Stress on Brain and Behavioral Development.

The putative effects of early-life stress (ELS) on later behavior and neurobiology have been widely investigated. Recently, microglia have been implicated in mediating some of the effects of ELS on behavior. In this review, findings from preclinical and clinical literature with a specific focus on microglial alterations induced by the exposure to ELS (i.e., exposure to behavioral stressors or environmental agents and infection) are summarized. These studies were utilized to interpret changes in developmental trajectories based on the time at which the stress occurred, as well as the paradigm used. ELS and microglial alterations were found to be associated with a wide array of deficits including cognitive performance, memory, reward processing, and processing of social stimuli. Four general conclusions emerged: (1) ELS interferes with microglial developmental programs, including their proliferation and death and their phagocytic activity; (2) this can affect neuronal and non-neuronal developmental processes, which are dynamic during development and for which microglial activity is instrumental; (3) the effects are extremely dependent on the time point at which the investigation is carried out; and (4) both pre- and postnatal ELS can prime microglial reactivity, indicating a long-lasting alteration, which has been implicated in behavioral abnormalities later in life.

Pheromones and Nutritional Signals Regulate the Developmental Reliance on let-7 Family MicroRNAs in C. elegans

Adverse environmental conditions can affect rates ofanimal developmental progression and lead to temporary developmental quiescence (diapause), exemplified by the dauer larva stage of the nematode Caenorhabditis elegans (C.elegans). Remarkably, patterns of cell division and temporal cell-fate progression in C.elegans larvae are not affected by changes in developmental trajectory. However, the underlying physiological and gene regulatory mechanisms that ensure robust developmental patterning despite substantial plasticity in developmental progression are largely unknown. Here, we report thatdiapause-inducing pheromones correct heterochronic developmental cell lineage defects caused by insufficient expression of let-7 family microRNAs in C.elegans. Moreover, two conserved endocrine signaling pathways, DAF-7/TGF-β and DAF-2/Insulin, that confer on the larva diapause and non-diapause alternative developmental trajectories interact with the nuclear hormone receptor, DAF-12, to initiate and regulate a rewiring of the genetic circuitry controlling temporal cell fates. This rewiring includes engagement of certain heterochronic genes, lin-46, lin-4, and nhl-2, that are previously associated with an altered genetic program in post-diapause animals, in combination with a novel ligand-independent DAF-12 activity, to downregulate the critical let-7 family target Hunchback-like-1 (HBL-1). Our results show how pheromone or endocrine signaling pathways can coordinately regulate both developmental progression and cell-fate transitions in C.elegans larvae under stress so that the developmental schedule of cell fates remains unaffected by changes in developmental trajectory.

Cerebellar contribution to locomotor behavior: A neurodevelopmental perspective.

The developmental trajectory of the formation of cerebellar circuitry has significant implications for locomotor plasticity and adaptive learning at later stages. While there is a wealth of knowledge on the development of locomotor behavior in human infants, children, and adolescents, pre-clinical animal models have fallen behind on the study of the emergence of behavioral motifs in locomotor function across postnatal development. Since cerebellar development is protracted, it is subject to higher risk of genetic or environmental disruption, potentially leading to abnormal behavioral development. This highlights the need for more sophisticated and specific functional analyses of adaptive cerebellar behavior within the context of whole-body locomotion across the entire span of postnatal development. Here we review evidence on cerebellar contribution to adaptive locomotor behavior, highlighting methodologies employed to quantify and categorize behavior at different developmental stages, with the ultimate goal of following the course of early behavioral alterations in neurodevelopmental disorders. Since experimental paradigms used to study cerebellar behavior are lacking in both specificity and applicability to locomotor contexts, we highlight the use of the Erasmus Ladder - an advanced, computerized, fully automated system to quantify adaptive cerebellar learning in conjunction with locomotor function. Finally, we emphasize the need to develop objective, quantitative, behavioral tasks which can track changes in developmental trajectories rather than endpoint measurement at the adult stage of behavior.

Double impact: natural molluscicide for schistosomiasis vector control also impedes development of Schistosoma mansoni cercariae into adult parasites.

BackgroundSchistosomiasis has been reported in 78 endemic countries and affects 240 million people worldwide. The digenetic parasite Schistosoma mansoni needs fresh water to compete its life cycle. There, it is susceptible to soluble compounds that can affect directly and/or indirectly the parasite’s biology. The cercariae stage is one of the key points in which the parasite is vulnerable to different soluble compounds that can significantly alter the parasite’s life cycle. Molluscicides are recommended by the World Health Organization for the control of schistosomiasis transmission and Euphorbia milii latex is effective against snails intermediate hosts.Methodology/Principal findingsWe used parasitological tools and electron microscopy to verify the effects of cercariae exposure to natural molluscicide (Euphorbia milii latex) on morphology, physiology and fitness of adult parasite worms. In order to generate insights into key metabolic pathways that lead to the observed phenotypes we used comparative transcriptomics and proteomics.Conclusions/SignificanceWe describe here that the effect of latex on the adult is not due to direct toxicity but it triggers an early change in developmental trajectory and perturbs cell memory, mobility, energy metabolism and other key pathways. We conclude that latex has not only an effect on the vector but applies also long lasting schistosomastatic action. We believe that these results are of interest not only to parasitologists since it shows that natural compounds, presumably without side effects, can have an impact that occurred unexpectedly on developmental processes. Such collateral damage is in this case positive, since it impacts the true target of the treatment campaign. This type of treatment could also provide a rational for the control of other pests. Our results will contribute to enforce the use of E. milii latex in Brazil and other endemic countries as cheap alternative or complement to mass drug treatment with Praziquantel, the only available drug to cure the patients (without preventing re-infection).

Early developmental pathways to autism spectrum disorder in tuberous sclerosis complex

Purpose – Tuberous sclerosis complex (TSC) is a genetic disorder with a high prevalence of autism spectrum disorder (ASD), yet no single genetic, neurological or neurophysiological risk marker is necessary or sufficient to increase risk for ASD. This paper aims to discuss the utility of adopting a developmental perspective. Design/methodology/approach – The increasing number of TSC infants presenting with abnormalities prenatally provides a unique opportunity to study risk pathways to ASD from birth. Here, the authors review findings to date that support the investigation of infants with TSC to further our understanding of typical and atypical development. Findings – Evidence has accumulated from studies of infants at familial risk for ASD (“baby siblings”) to suggest that early markers of ASD are present in the first year of life. The early waves of prospective studies of infants with TSC indicate dynamic changes in developmental trajectories to ASD and are likely to provide insight into cascading effects of brain “insult” early in development. Emerging evidence of phenotypic and biological homology between syndromic and idiopathic cases of ASD supports the notion of a convergence of risk factors on a final common pathway in ASD. Originality/value – The delineation of brain-based biomarkers of risk, prediction and treatment response in TSC will be critical in aiding the development of targeted intervention and prevention strategies for those infants at high risk of poorer developmental outcomes.

Why might they be giants? Towards an understanding of polar gigantism

Beginning with the earliest expeditions to the poles, over 100 years ago, scientists have compiled an impressive list of polar taxa whose body sizes are unusually large. This phenomenon has become known as 'polar gigantism'. In the intervening years, biologists have proposed a multitude of hypotheses to explain polar gigantism. These hypotheses run the gamut from invoking release from physical and physiological constraints, to systematic changes in developmental trajectories, to community-level outcomes of broader ecological and evolutionary processes. Here we review polar gigantism and emphasize two main problems. The first is to determine the true strength and generality of this pattern: how prevalent is polar gigantism across taxonomic units? Despite many published descriptions of polar giants, we still have a poor grasp of whether these species are unusual outliers or represent more systematic shifts in distributions of body size. Indeed, current data indicate that some groups show gigantism at the poles whereas others show nanism. The second problem is to identify underlying mechanisms or processes that could drive taxa, or even just allow them, to evolve especially large body size. The contenders are diverse and no clear winner has yet emerged. Distinguishing among the contenders will require better sampling of taxa in both temperate and polar waters and sustained efforts by comparative physiologists and evolutionary ecologists in a strongly comparative framework.

Developmental programming of the metabolic syndrome - critical windows for intervention

Metabolic disease results from a complex interaction of many factors, including genetic, physiological, behavioral and environmental influences. The recent rate at which these diseases have increased suggests that environmental and behavioral influences, rather than genetic causes, are fuelling the present epidemic. In this context, the developmental origins of health and disease hypothesis has highlighted the link between the periconceptual, fetal and early infant phases of life and the subsequent development of adult obesity and the metabolic syndrome. Although the mechanisms are yet to be fully elucidated, this programming was generally considered an irreversible change in developmental trajectory. Recent work in animal models suggests that developmental programming of metabolic disorders is potentially reversible by nutritional or targeted therapeutic interventions during the period of developmental plasticity. This review will discuss critical windows of developmental plasticity and possible avenues to ameliorate the development of postnatal metabolic disorders following an adverse early life environment.

Effects of early life stress on cognitive and affective function: an integrated review of human literature

The investigation of putative effects of early life stress (ELS) in humans on later behavior and neurobiology is a fast developing field. While epidemiological and neurobiological studies paint a somber picture of negative outcomes, relatively little attention has been devoted to integrating the breadth of findings concerning possible cognitive and emotional deficits associated with ELS. Emerging findings from longitudinal studies examining developmental trajectories of the brain in healthy samples may provide a new framework to understand mechanisms underlying ELS sequelae. The goal of this review was twofold. The first was to summarize findings from longitudinal data on normative brain development. The second was to utilize this framework of normative brain development to interpret changes in developmental trajectories associated with deficits in cognitive and affective function following ELS. Five principles of normative brain development were identified and used to discuss behavioral and neural sequelae of ELS. Early adversity was found to be associated with deficits in a range of cognitive (cognitive performance, memory, and executive functioning) and affective (reward processing, processing of social and affective stimuli, and emotion regulation) functions. Three general conclusions emerge: (1) higher-order, complex cognitive and affective functions associated with brain regions undergoing protracted postnatal development are particularly vulnerable to the deleterious effects of ELS; (2) the amygdala is particularly sensitive to early ELS; and (3) several deficits, particularly those in the affective domain, appear to persist years after ELS has ceased and may increase risk for later psychopathology.

The Effect of Neonatal Leptin Treatment on Postnatal Weight Gain in Male Rats Is Dependent on Maternal Nutritional Status during Pregnancy

An adverse prenatal environment may induce long-term metabolic consequences, in particular obesity, hyperleptinemia, insulin resistance, and type 2 diabetes. Although the mechanisms are unclear, this "programming" has generally been considered an irreversible change in developmental trajectory. Adult offspring of rats subjected to undernutrition (UN) during pregnancy develop obesity, hyperinsulinemia, and hyperleptinemia, especially in the presence of a high-fat diet. Using this model of maternal UN, we have recently shown that neonatal leptin treatment in females reverses the postnatal sequelae induced by developmental programming. To examine possible gender-related effects of neonatal leptin treatment, the present study investigated the effect of neonatal leptin treatment on the metabolic phenotype of adult male offspring. Leptin treatment (recombinant rat leptin, 2.5 microg/g.d, sc) from postnatal d 3-13 resulted in a transient slowing of neonatal weight gain, particularly in programmed offspring. Neonatal leptin treatment of male offspring from normally nourished mothers caused an increase in diet-induced weight gain and related metabolic sequelae, including hyperinsulinemia and increased total body adiposity compared with saline-treated controls. This occurred without an increase in caloric intake. These effects were specific to offspring of normal pregnancies and were not observed in offspring of mothers after UN during pregnancy. In the latter, neonatal leptin treatment conferred protection against the development of the programmed phenotype, particularly in those fed the chow diet postnatally. These data further reinforce the importance of leptin in determining long-term energy homeostasis, and suggest that leptin's effects are modulated by gender and both prenatal and postnatal nutritional status.

Developmental programming and adult obesity: the role of leptin

An adverse prenatal environment may induce long-term metabolic consequences, in particular obesity and insulin resistance. Although the mechanisms are unclear, this 'programming' has generally been considered an irreversible change in developmental trajectory. Recent work has highlighted the importance of the hormone leptin during critical windows of development in the pathogenesis of programming related disorders. Maintaining a critical leptin level during development may allow the normal maturation of tissues and pathways involved in metabolic homeostasis and a period of relative hypo or hyperleptinemia may induce some of the metabolic adaptations which underlie developmental programming. Furthermore, nutritional or therapeutic intervention in postnatal life can ameliorate the consequences of developmental malprogramming and, at least in the rodent, developmental programming is potentially reversible by intervention with leptin late in the phase of developmental plasticity. Inappropriate growth during pregnancy or lactation can result in individuals with an increased risk of later obesity and related metabolic sequelae. Taken together, recent studies highlight the importance of leptin in disorders manifest as a consequence of developmental programming and offer exciting new strategies for therapeutic intervention, whether it be maternal or neonatal intervention or targeted nutritional manipulation in postnatal life.

Neonatal Leptin Treatment Reverses Developmental Programming

An adverse prenatal environment may induce long-term metabolic consequences, in particular obesity and insulin resistance. Although the mechanisms are unclear, this programming has generally been considered an irreversible change in developmental trajectory. Adult offspring of rats subjected to undernutrition during pregnancy develop obesity, hyperinsulinemia, and hyperleptinemia, especially in the presence of a high-fat diet. Reduced locomotor activity and hyperphagia contribute to the increased fat mass. Using this model of maternal undernutrition, we investigated the effects of neonatal leptin treatment on the metabolic phenotype of adult female offspring. Leptin treatment (rec-rat leptin, 2.5 microg/g.d, sc) from postnatal d 3-13 resulted in a transient slowing of neonatal weight gain, particularly in programmed offspring, and normalized caloric intake, locomotor activity, body weight, fat mass, and fasting plasma glucose, insulin, and leptin concentrations in programmed offspring in adult life in contrast to saline-treated offspring of undernourished mothers who developed all these features on a high-fat diet. Neonatal leptin had no demonstrable effects on the adult offspring of normally fed mothers. This study suggests that developmental metabolic programming is potentially reversible by an intervention late in the phase of developmental plasticity. The complete normalization of the programmed phenotype by neonatal leptin treatment implies that leptin has effects that reverse the prenatal adaptations resulting from relative fetal undernutrition.