Sample records for early cns development

  1. Genetic pharmacotherapy as an early CNS drug development strategy: testing glutaminase inhibition for schizophrenia treatment in adult mice

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    Susana eMingote


    Full Text Available Genetic pharmacotherapy is an early drug development strategy for the identification of novel CNS targets in mouse models prior to the development of specific ligands. Here for the first time, we have implemented this strategy to address the potential therapeutic value of a glutamate-based pharmacotherapy for schizophrenia involving inhibition of the glutamate recycling enzyme phosphate-activated glutaminase. Mice constitutively heterozygous for GLS1, the gene encoding glutaminase, manifest a schizophrenia resilience phenotype, a key dimension of which is an attenuated locomotor response to propsychotic amphetamine challenge. If resilience is due to glutaminase deficiency in adulthood, then glutaminase inhibitors should have therapeutic potential. However, this has been difficult to test given the dearth of neuroactive glutaminase inhibitors. So, we used genetic pharmacotherapy to test the therapeutic potential of glutaminase inhibition. We specifically asked whether adult induction of GLS1 heterozygosity would attenuate amphetamine responsiveness. We generated conditional floxGLS1 mice and crossed them with global CAG ERT2 cre/+ mice to produce GLS1 iHET mice, susceptible to tamoxifen induction of GLS1 heterozygosity. One month after tamoxifen treatment of adult GLS1 iHET mice, we found a 50% reduction in GLS1 allelic abundance and glutaminase mRNA levels in the brain. While GLS1 iHET mice showed some recombination prior to tamoxifen, there was no impact on mRNA levels. We then asked whether induction of GLS heterozygosity would attenuate the locomotor response to propsychotic amphetamine challenge. Before tamoxifen, control and GLS1 iHET mice did not differ in their response to amphetamine. One month after tamoxifen treatment, amphetamine-induced hyperlocomotion was blocked in GLS1 iHET mice. The block was largely maintained after 5 months. Thus, a genetically induced glutaminase reduction — mimicking pharmacological inhibition — strongly

  2. Early CNS neurodegeneration in radiologically isolated syndrome (United States)

    Overton, Eve; Khadka, Sankalpa; Buckley, Jessica; Liu, Shuang; Sampat, Mehul; Kantarci, Orhun; Lebrun Frenay, Christine; Siva, Aksel; Okuda, Darin T.; Pelletier, Daniel


    Objective: Increasing evidence indicates that the thalamus may be a location of early neurodegeneration in multiple sclerosis (MS). Our objective was to identify the presence of gray matter volume loss and thinning in patients with radiologically isolated syndrome (RIS). Methods: Sixty-three participants were included in this case-control study. Twenty-one patients with RIS were age- and sex-matched to 42 healthy controls in a 1:2 ratio. All participants underwent brain MRIs on a single 3T scanner. After lesion segmentation and inpainting, 1 mm3-isometric T1-weighted images were submitted to FreeSurfer (v5.2). Normalized cortical and deep gray matter volumes were compared between patients with RIS and controls using t tests, and thalamic volumes were correlated with white matter lesion volumes using Pearson correlation. Exploratory cortical thickness maps were created. Results: Although traditional normalized total gray and white matter volumes were not statistically different between patients with RIS and controls, normalized left (0.0046 ± 0.0005 vs 0.0049 ± 0.0004, p = 0.006), right (0.0045 ± 0.0005 vs 0.0048 ± 0.0004, p = 0.008), and mean (0.0045 ± 0.0005 vs 0.0049 ± 0.0004, p = 0.004) thalamic volumes were significantly lower in patients with RIS (n = 21, mean age 41.9 ± 12.7 years) than in controls (n = 42, mean age 41.4 ± 11.2 years). Thalamic volumes correlated modestly with white matter lesion volumes (range: r = −0.35 to −0.47). Conclusion: Our data provide novel evidence of thalamic atrophy in RIS and are consistent with previous reports in early MS stages. Thalamic volume loss is present early in CNS demyelinating disease and should be further investigated as a metric associated with neurodegeneration. PMID:25884012

  3. CNS Anticancer Drug Discovery and Development Conference White Paper


    Victor A Levin; Tonge, Peter J.; Gallo, James M.; Birtwistle, Marc R.; Dar, Arvin C.; Iavarone, Antonio; Paddison, Patrick J.; Heffron, Timothy P.; Elmquist, William F.; Lachowicz, Jean E.; Johnson, Ted W.; White, Forest M.; Sul, Joohee; Smith, Quentin R.; Shen, Wang


    Following the first CNS Anticancer Drug Discovery and Development Conference, the speakers from the first 4 sessions and organizers of the conference created this White Paper hoping to stimulate more and better CNS anticancer drug discovery and development. The first part of the White Paper reviews, comments, and, in some cases, expands on the 4 session areas critical to new drug development: pharmacological challenges, recent drug approaches, drug targets and discovery, and clinical paths. F...

  4. CNS Macrophages Control Neurovascular Development via CD95L

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    Si Chen


    Full Text Available The development of neurons and vessels shares striking anatomical and molecular features, and it is presumably orchestrated by an overlapping repertoire of extracellular signals. CNS macrophages have been implicated in various developmental functions, including the morphogenesis of neurons and vessels. However, whether CNS macrophages can coordinately influence neurovascular development and the identity of the signals involved therein is unclear. Here, we demonstrate that activity of the cell surface receptor CD95 regulates neuronal and vascular morphogenesis in the post-natal brain and retina. Furthermore, we identify CNS macrophages as the main source of CD95L, and macrophage-specific deletion thereof reduces both neurovascular complexity and synaptic activity in the brain. CD95L-induced neuronal and vascular growth is mediated through src-family kinase (SFK and PI3K signaling. Together, our study highlights a coordinated neurovascular development instructed by CNS macrophage-derived CD95L, and it underlines the importance of macrophages for the establishment of the neurovascular network during CNS development.

  5. CNS Macrophages Control Neurovascular Development via CD95L. (United States)

    Chen, Si; Tisch, Nathalie; Kegel, Marcel; Yerbes, Rosario; Hermann, Robert; Hudalla, Hannes; Zuliani, Cecilia; Gülcüler, Gülce Sila; Zwadlo, Klara; von Engelhardt, Jakob; Ruiz de Almodóvar, Carmen; Martin-Villalba, Ana


    The development of neurons and vessels shares striking anatomical and molecular features, and it is presumably orchestrated by an overlapping repertoire of extracellular signals. CNS macrophages have been implicated in various developmental functions, including the morphogenesis of neurons and vessels. However, whether CNS macrophages can coordinately influence neurovascular development and the identity of the signals involved therein is unclear. Here, we demonstrate that activity of the cell surface receptor CD95 regulates neuronal and vascular morphogenesis in the post-natal brain and retina. Furthermore, we identify CNS macrophages as the main source of CD95L, and macrophage-specific deletion thereof reduces both neurovascular complexity and synaptic activity in the brain. CD95L-induced neuronal and vascular growth is mediated through src-family kinase (SFK) and PI3K signaling. Together, our study highlights a coordinated neurovascular development instructed by CNS macrophage-derived CD95L, and it underlines the importance of macrophages for the establishment of the neurovascular network during CNS development. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  6. Prospects for the development of epigenetic drugs for CNS conditions. (United States)

    Szyf, Moshe


    Advances in our understanding of the epigenetic mechanisms that control gene expression in the central nervous system (CNS) and their role in neuropsychiatric disorders are paving the way for a potential new therapeutic approach that is focused on reversing the epigenetic underpinnings of neuropsychiatric conditions. In this article, the complexity of epigenetic processes and the current level of proof for their involvement in CNS disorders are discussed. The preclinical evidence for efficacy of pharmacological approaches that target epigenetics in the CNS and the particular challenges of this approach are also examined. Finally, strategies to address these challenges through the development of improved evidence-based epigenetic therapeutics and through combining pharmacological and behavioural approaches are presented.

  7. CNS Anticancer Drug Discovery and Development: 2016 conference insights. (United States)

    Levin, Victor A; Abrey, Lauren E; Heffron, Timothy P; Tonge, Peter J; Dar, Arvin C; Weiss, William A; Gallo, James M


    CNS Anticancer Drug Discovery and Development November 2016, AZ, USA The 2016 second CNS Anticancer Drug Discovery and Development Conference addressed diverse viewpoints about why new drug discovery/development focused on CNS cancers has been sorely lacking. Despite more than 70,000 individuals in the USA being diagnosed with a primary brain malignancy and 151,669-286,486 suffering from metastatic CNS cancer, in 1999, temozolomide was the last drug approved by the US FDA as an anticancer agent for high-grade gliomas. Among the topics discussed were economic factors and pharmaceutical risk assessments, regulatory constraints and perceptions and the need for improved imaging surrogates of drug activity. Included were modeling tumor growth and drug effects in a medical environment in which direct tumor sampling for biological effects can be problematic, potential new drugs under investigation and targets for drug discovery and development. The long trajectory and diverse impediments to novel drug discovery, and expectation that more than one drug will be needed to adequately inhibit critical intracellular tumor pathways were viewed as major disincentives for most pharmaceutical/biotechnology companies. While there were a few unanimities, one consensus is the need for continued and focused discussion among academic and industry scientists and clinicians to address tumor targets, new drug chemistry, and more time- and cost-efficient clinical trials based on surrogate end points.

  8. Cug2 is essential for normal mitotic control and CNS development in zebrafish

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    Kim Nam-Soon


    Full Text Available Abstract Background We recently identified a novel oncogene, Cancer-upregulated gene 2 (CUG2, which is essential for kinetochore formation and promotes tumorigenesis in mammalian cells. However, the in vivo function of CUG2 has not been studied in animal models. Results To study the function of CUG2 in vivo, we isolated a zebrafish homologue that is expressed specifically in the proliferating cells of the central nervous system (CNS. Morpholino-mediated knockdown of cug2 resulted in apoptosis throughout the CNS and the development of neurodegenerative phenotypes. In addition, cug2-deficient embryos contained mitotically arrested cells displaying abnormal spindle formation and chromosome misalignment in the neural plate. Conclusions Therefore, our findings suggest that Cug2 is required for normal mitosis during early neurogenesis and has functions in neuronal cell maintenance, thus demonstrating that the cug2 deficient embryos may provide a model system for human neurodegenerative disorders.

  9. Neuronal LRP4 regulates synapse formation in the developing CNS. (United States)

    Karakatsani, Andromachi; Marichal, Nicolás; Urban, Severino; Kalamakis, Georgios; Ghanem, Alexander; Schick, Anna; Zhang, Yina; Conzelmann, Karl-Klaus; Rüegg, Markus A; Berninger, Benedikt; Ruiz de Almodovar, Carmen; Gascón, Sergio; Kröger, Stephan


    The low-density lipoprotein receptor-related protein 4 (LRP4) is essential in muscle fibers for the establishment of the neuromuscular junction. Here, we show that LRP4 is also expressed by embryonic cortical and hippocampal neurons, and that downregulation of LRP4 in these neurons causes a reduction in density of synapses and number of primary dendrites. Accordingly, overexpression of LRP4 in cultured neurons had the opposite effect inducing more but shorter primary dendrites with an increased number of spines. Transsynaptic tracing mediated by rabies virus revealed a reduced number of neurons presynaptic to the cortical neurons in which LRP4 was knocked down. Moreover, neuron-specific knockdown of LRP4 by in utero electroporation of LRP4 miRNA in vivo also resulted in neurons with fewer primary dendrites and a lower density of spines in the developing cortex and hippocampus. Collectively, our results demonstrate an essential and novel role of neuronal LRP4 in dendritic development and synaptogenesis in the CNS. © 2017. Published by The Company of Biologists Ltd.

  10. Contrast-agent-enhanced magnetic resonance imaging: early detection of neoplastic lesions of the CNS (United States)

    Carvlin, Mark J.; Rosa, Louis; Rajan, Sunder S.; Francisco, John


    Even though the intrinsic soft tissue contrast sensitivity of magnetic resonance imaging (MRI) affords excellent visualization of anatomic detail, certain pathologic processes may be diagnosed earlier with the administration of a contrast-enhancing agent. At present there is one agent, gadopentetate dimeglumine, GdDTPA, that has received FDA approval for use in the MR scanning of the brain and spine in human patients. This paramagnetic chelate distributes throughout the extracellular fluid space as dictated by capillary permeability so that abnormal vascularity and sites of blood-CNS barrier breakdown are highlighted. Primary neoplastic disease, metastases, meningeal extension, residual and recurrent tumor have been found to be better distinguished in MR images acquired after administration of GdDTPA. Routine administration of GdDTPA for cranial imaging has resulted in the discovery of otherwise occult lesions in approximately 3 of patients. Although the clinical utility and high therapeutic safety index of the first approved magnetic resonance contrast agent, GdDTPA, have been well established, other contrast agents, having different physical, chemical and biological properties, may offer improved sensitivity and bio-specificity. Agents currently being evaluated in vivo include: low osmolal paramagnetic chelates, superparamagnetic particles, metalloporphyrins, liposome encapsulated agents, perfluorocarbons, intravascular macromolecular chelate complexes and labeled monoclonal antibodies. Concurrent with advances in the development of new compounds, innovations in scanning hardware, pulse sequence design and image post-processing are helping to extend the efficacy of contrast media. Additional clinical experience will indicate which contrast agents and which MR techniques can best facilitate the early detection of specific neoplastic lesions.

  11. Simulation and mockup tests for developing TRR-II CNS (United States)

    Lee, C. H.; Kawai, T.; Chan, Y. K.; Hong, W. T.; Lee, D. J.; Guung, T. C.; Lan, K. C.


    The Taiwan Research Reactor improvement and the utilization promotion project (TRR-II) with Cold Neutron Source (CNS) was carried out at Institute of Nuclear Energy Research. The CNS with a two-phase thermosiphon loop consists of an annular cylindrical moderator cell, a single moderator transfer tube, and a condenser. The self-regulating characteristics of a two-phase thermosiphon loop are investigated against variations of heat load. The experiments on the thermal-hydraulic characteristics have been performed using a full-scale mockup loop and a Freon-11 was used as a working fluid. Two cases were evaluated by the simulation and experiments. One case is an ORPHEE-type moderator cell in which an inner shell is open at the bottom, the other case is one with an inner cavity with no hole at the bottom but a vapor inlet opening at the uppermost part of the cavity. The flooding limitations, liquid level and void fraction in the moderator cell as a function of the initial Freon-11 inventory and the heat load are also reported.

  12. Pluripotent stem cells for the study of CNS development

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    Timothy J. Petros


    Full Text Available The mammalian central nervous system is a complex neuronal meshwork consisting of a diverse array of cellular subtypes generated in a precise spatial and temporal pattern throughout development. Achieving a greater understanding of the molecular and genetic mechanisms that direct a relatively uniform population of neuroepithelial progenitors into the diverse neuronal subtypes remains a significant challenge. A firmer knowledge of the fundamental aspects of developmental neuroscience will allow us to better study the vast array of neurodevelopmental diseases. The advent of stem cell technologies has expedited our ability to generate and isolate populations of distinct interneuron subtypes. To date, researchers have successfully developed protocols to derive many types of neural cells from pluripotent stem cells, with varying degrees of efficiencies and reproducibility. The stem cell field is devoted to the potential of stem cell-derived neurons for the treatment of disease, highlighted by the ability to create patient specific induced pluripotent stem cells. However, another application that is often overlooked is the use of stem cell technology for studying normal neural development. This is especially important for human neurodevelopment, since obtaining embryonic tissue presents numerous technical and ethical challenges. In this review, we will explore the use of pluripotent stem cells for the study of neural development. We will review the different classes of pluripotent stem cells and focus on the types of neurodevelopmental questions that stem cell technologies can help address. In addition to covering the different neural cells derived from stem cells to date, we will detail the derivation and characterization of three of the more thoroughly studied cell groups. We hope that this review encourages researchers to develop innovative strategies for using pluripotent stem cells for the study of mammalian, and specifically human

  13. Development of an alcohol withdrawal protocol: CNS collaborative exemplar. (United States)

    Phillips, Susan; Haycock, Camille; Boyle, Deborah


    The purpose of this process improvement project was to develop an Alcohol Withdrawal Syndrome (AWS) management protocol for acute care. The prevalence of alcohol abuse in our society presents challenges for health professionals, and few nurses have received formal education on the identification and treatment of AWS, which has frequently resulted in ineffective, nonstandardized care. However, nurses practicing in medical-surgical, emergency, trauma, and critical care settings must be astute in the assessment and management of AWS. DESIGN/BACKGROUND/RATIONALE: Following an analysis of existing management protocols, a behavioral health clinical nurse specialist was asked to lead a work team composed of physicians, pharmacists, and nurses to develop a new evidence-based alcohol withdrawal protocol for acute care. By implementing a standardized assessment tool and treatment protocol, clinical nurse specialists empowered nursing staff with strategies to prevent the serious medical complications associated with AWS. FINDINGS/OUTCOMES: The development and integration of a safe and effective treatment protocol to manage AWS was facilitated by collaborative, evidence-based decision making. Clinical experience and specialty expertise were integrated by clinical nurse specialists skilled in group dynamics, problem-solving, and the implementation of change. Improving care of patients in AWS is an exemplar for clinical nurse specialist roles as change agent and patient advocate.

  14. Perinatal asphyxia: CNS development and deficits with delayed onset

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    Mario eHerrera-Marschitz


    Full Text Available Perinatal asphyxia constitutes a prototype of obstetric complications occurring when pulmonary oxygenation is delayed or interrupted. The primary insult relates to the duration of the period lacking oxygenation, leading to death if not re-established. Re-oxygenation leads to a secondary insult, related to a cascade of biochemical events required for restoring proper function. Perinatal asphyxia interferes with neonatal development, resulting in long-term deficits associated to mental and neurological diseases with delayed clinical onset, by mechanisms not yet clarified.In the experimental scenario, the effects observed long after perinatal asphyxia have been explained by over expression of sentinel proteins, such as poly(ADP-ribose polymerase-1 (PARP-1, competing for NAD+ during re-oxygenation, leading to the idea that sentinel protein inhibition constitutes a suitable therapeutic strategy. Asphyxia induces transcriptional activation of pro-inflammatory factors, in tandem with PARP-1 overactivation, and pharmacologically induced PARP-1 inhibition also down-regulates the expression of proinflammatory cytokines. Nicotinamide has been proposed as a suitable PARP-1 inhibitor. Its effect has been studied in an experimental model of global hypoxia in rats. In that model, the insult is induced by immersing rat foetuses into a water bath for various periods of time. Following asphyxia, the pups are delivered, treated, and nursed by surrogate dams, pending further experiments. Nicotinamide rapidly distributes into the brain following systemic administration, reaching steady state concentrations sufficient to inhibit PARP-1 activity for several hours, preventing several of the long-term consequences of perinatal asphyxia, supporting the idea that it constitutes a lead for exploring compounds with similar or better pharmacological profiles.

  15. Perinatal asphyxia: CNS development and deficits with delayed onset. (United States)

    Herrera-Marschitz, Mario; Neira-Pena, Tanya; Rojas-Mancilla, Edgardo; Espina-Marchant, Pablo; Esmar, Daniela; Perez, Ronald; Muñoz, Valentina; Gutierrez-Hernandez, Manuel; Rivera, Benjamin; Simola, Nicola; Bustamante, Diego; Morales, Paola; Gebicke-Haerter, Peter J


    Perinatal asphyxia constitutes a prototype of obstetric complications occurring when pulmonary oxygenation is delayed or interrupted. The primary insult relates to the duration of the period lacking oxygenation, leading to death if not re-established. Re-oxygenation leads to a secondary insult, related to a cascade of biochemical events required for restoring proper function. Perinatal asphyxia interferes with neonatal development, resulting in long-term deficits associated to mental and neurological diseases with delayed clinical onset, by mechanisms not yet clarified. In the experimental scenario, the effects observed long after perinatal asphyxia have been explained by overexpression of sentinel proteins, such as poly(ADP-ribose) polymerase-1 (PARP-1), competing for NAD(+) during re-oxygenation, leading to the idea that sentinel protein inhibition constitutes a suitable therapeutic strategy. Asphyxia induces transcriptional activation of pro-inflammatory factors, in tandem with PARP-1 overactivation, and pharmacologically induced PARP-1 inhibition also down-regulates the expression of proinflammatory cytokines. Nicotinamide has been proposed as a suitable PARP-1 inhibitor. Its effect has been studied in an experimental model of global hypoxia in rats. In that model, the insult is induced by immersing rat fetus into a water bath for various periods of time. Following asphyxia, the pups are delivered, treated, and nursed by surrogate dams, pending further experiments. Nicotinamide rapidly distributes into the brain following systemic administration, reaching steady state concentrations sufficient to inhibit PARP-1 activity for several hours, preventing several of the long-term consequences of perinatal asphyxia, supporting the idea that nicotinamide constitutes a lead for exploring compounds with similar or better pharmacological profiles.



    Bukhovets, B. O.; Romanchuk, A. P.


    The article represents therapy of Bobath such as one of the most effective author method which use in correction psychomotor development of children with disorders of musculoskeletal system. Bobath method is not new in the correction of movement disorders since last century and still supplementing and improving. In this work highlight topic of the effective use Bobath therapy in correction of psychomotor development in children age 3 – 6 years with organic involvement CNS. the experiment w...

  17. Strategies for Utilizing Neuroimaging Biomarkers in CNS Drug Discovery and Development: CINP/JSNP Working Group Report. (United States)

    Suhara, Tetsuya; Chaki, Shigeyuki; Kimura, Haruhide; Furusawa, Makoto; Matsumoto, Mitsuyuki; Ogura, Hiroo; Negishi, Takaaki; Saijo, Takeaki; Higuchi, Makoto; Omura, Tomohiro; Watanabe, Rira; Miyoshi, Sosuke; Nakatani, Noriaki; Yamamoto, Noboru; Liou, Shyh-Yuh; Takado, Yuhei; Maeda, Jun; Okamoto, Yasumasa; Okubo, Yoshiaki; Yamada, Makiko; Ito, Hiroshi; Walton, Noah M; Yamawaki, Shigeto


    Despite large unmet medical needs in the field for several decades, CNS drug discovery and development has been largely unsuccessful. Biomarkers, particularly those utilizing neuroimaging, have played important roles in aiding CNS drug development, including dosing determination of investigational new drugs (INDs). A recent working group was organized jointly by CINP and Japanese Society of Neuropsychopharmacology (JSNP) to discuss the utility of biomarkers as tools to overcome issues of CNS drug development.The consensus statement from the working group aimed at creating more nuanced criteria for employing biomarkers as tools to overcome issues surrounding CNS drug development. To accomplish this, a reverse engineering approach was adopted, in which criteria for the utilization of biomarkers were created in response to current challenges in the processes of drug discovery and development for CNS disorders. Based on this analysis, we propose a new paradigm containing 5 distinct tiers to further clarify the use of biomarkers and establish new strategies for decision-making in the context of CNS drug development. Specifically, we discuss more rational ways to incorporate biomarker data to determine optimal dosing for INDs with novel mechanisms and targets, and propose additional categorization criteria to further the use of biomarkers in patient stratification and clinical efficacy prediction. Finally, we propose validation and development of new neuroimaging biomarkers through public-private partnerships to further facilitate drug discovery and development for CNS disorders. © The Author 2016. Published by Oxford University Press on behalf of CINP.

  18. Chronic restraint stress during early Theiler’s virus infection exacerbates the subsequent demyelinating disease in SJL mice: II. CNS disease severity (United States)

    Young, Erin E.; Sieve, Amy N.; Vichaya, Elisabeth G.; Carcoba, Luis M.; Young, Colin R.; Ambrus, Andrew; Storts, Ralph; Welsh, C. Jane R.; Meagher, Mary W.


    Theiler’s murine encephalomyelitis virus (TMEV) infection is a well-characterized model of multiple sclerosis (MS). Previous research has shown that chronic restraint stress (RS) during early TMEV infection exacerbates behavioral signs of disease. The present data suggest RS-induced increases in CNS inflammation, demyelination, and axonal degeneration may underlie this exacerbation. In addition, we report that males exhibit greater CNS inflammation and higher numbers of demyelinating lesions while females show greater susceptibility to RS-induced exacerbation. These findings indicate RS during early TMEV infection increases CNS lesion formation during the late phase and suggest the effects of RS are sex-dependent. PMID:20167380

  19. Biomarkers in early phase development of central nervous system drugs : a conceptual framework

    NARCIS (Netherlands)

    Post, Jeroen-Paul van der


    The main objective of this thesis is to provide a conceptual framework for the use of Central Nervous System (CNS) biomarkers in early phase clinical drug development. In the Introduction the current use of biomarkers in early CNS drug development is discussed. A conceptual framework for the

  20. Anti-α4 antibody treatment blocks virus traffic to the brain and gut early, and stabilizes CNS injury late in infection.

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    Jennifer H Campbell


    Full Text Available Four SIV-infected monkeys with high plasma virus and CNS injury were treated with an anti-α4 blocking antibody (natalizumab once a week for three weeks beginning on 28 days post-infection (late. Infection in the brain and gut were quantified, and neuronal injury in the CNS was assessed by MR spectroscopy, and compared to controls with AIDS and SIV encephalitis. Treatment resulted in stabilization of ongoing neuronal injury (NAA/Cr by 1H MRS, and decreased numbers of monocytes/macrophages and productive infection (SIV p28+, RNA+ in brain and gut. Antibody treatment of six SIV infected monkeys at the time of infection (early for 3 weeks blocked monocyte/macrophage traffic and infection in the CNS, and significantly decreased leukocyte traffic and infection in the gut. SIV - RNA and p28 was absent in the CNS and the gut. SIV DNA was undetectable in brains of five of six early treated macaques, but proviral DNA in guts of treated and control animals was equivalent. Early treated animals had low-to-no plasma LPS and sCD163. These results support the notion that monocyte/macrophage traffic late in infection drives neuronal injury and maintains CNS viral reservoirs and lesions. Leukocyte traffic early in infection seeds the CNS with virus and contributes to productive infection in the gut. Leukocyte traffic early contributes to gut pathology, bacterial translocation, and activation of innate immunity.

  1. Development of a sexually differentiated behavior and its underlying CNS arousal functions. (United States)

    Kow, Lee-Ming; Florea, Cristina; Schwanzel-Fukuda, Marlene; Devidze, Nino; Kami Kia, Hosein; Lee, Anna; Zhou, Jin; Maclaughlin, David; Donahoe, Patricia; Pfaff, Donald


    This chapter addresses questions regarding lordosis behavior, the most extremely sexually differentiated behavior that has been analyzed for its neural and molecular mechanisms. Analysis of this behavior has proved for the first time that specific biochemical reactions in specific nerve cell groups in the brain determine a mammalian behavior. Lordosis is done by the female but not by the male. How did the process of sexual differentiation occur? A large literature implicates high levels of testosterone during a critical period during development as being responsible for the defeminization of the brain. A new idea, however, offers the possibility of direct genetic influences independent of testosterone levels themselves. We propose here that Mullerian Inhibiting Substance (MIS) and its receptors could constitute an example of a nonandrogenic genetic influence. Further, specific sexual behaviors depend on underlying arousal states in the central nervous system (CNS). We have proposed the concept of generalized CNS arousal and provide information as to how generalized arousal forces interact with specifically sexual influences, thus to facilitate sexually differentiated mating behaviors.

  2. Tcf7l2/Tcf4 Transcriptional Repressor Function Requires HDAC Activity in the Developing Vertebrate CNS.

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    Hui Wang

    Full Text Available The generation of functionally distinct neuronal subtypes within the vertebrate central nervous system (CNS requires the precise regulation of progenitor gene expression in specific neuronal territories during early embryogenesis. Accumulating evidence has implicated histone deacetylase (HDAC proteins in cell specification, proliferation, and differentiation in diverse embryonic and adult tissues. However, although HDAC proteins have shown to be expressed in the developing vertebrate neural tube, their specific role in CNS neural progenitor fate specification remains unclear. Prior work from our lab showed that the Tcf7l2/Tcf4 transcription factor plays a key role in ventral progenitor lineage segregation by differential repression of two key specification factors, Nkx2.2 and Olig2. In this study, we found that administration of HDAC inhibitors (Valproic Acid (VPA, Trichostatin-A (TSA, or sodium butyrate in chick embryos in ovo disrupted normal progenitor gene segregation in the developing neural tube, indicating that HDAC activity is required for this process. Further, using functional and pharmacological approaches in vivo, we found that HDAC activity is required for the differential repression of Nkx2.2 and Olig2 by Tcf7l2/Tcf4. Finally, using dominant-negative functional assays, we provide evidence that Tcf7l2/Tcf4 repression also requires Gro/TLE/Grg co-repressor factors. Together, our data support a model where the transcriptional repressor activity of Tcf7l2/Tcf4 involves functional interactions with both HDAC and Gro/TLE/Grg co-factors at specific target gene regulatory elements in the developing neural tube, and that this activity is required for the proper segregation of the Nkx2.2 (p3 and Olig2 (pMN expressing cells from a common progenitor pool.

  3. Integrating functional MRI information into radiotherapy planning of CNS tumors-early experiences. (United States)

    Kovács, Arpád; Tóth, Lilla; Glavák, Csaba; Lakosi, Ferenc; Hadjiev, Janaki; Bajzik, Gábor; Vandulek, Csaba; Repa, Imre


    The purpose of our study was to examine the integration of functional MRI (fMRI) information into 3D based planning process of the central nervous system (CNS) malignancies. Between 01.01.2008 and 01.12.2008 four patients with astrocytoma were enrolled to this study. Before the planning process conventional planning CT, postoperative MR and individual functional MRI examinations were delivered. For the functional MRI examination the following four types of stimulus were applied: acoustic, visual, somatosensory and numeral. Three different theoretical planning situations were applied and compared: 3D conformal plan without fMRI information, 3D conformal plan with fMRI information and IMRT plan with fMRI information. For plan comparison DVH analysis, and NTCP model were used. fMRI based OR definition resulted in 4 additional OR's in the contouring process. As these cases demonstrate, an average of 50% dose reduction was achieved in OR, OR2 and OR3 with IMRT and fMRI based 3D planning, especially in case of midline localization and big tumor extent. IMRT provides additional sparing effect in the optic tract and brainstem, especially for localizations close to the midline. Our results demonstrated that using fMRI information in conventional 3D based treatment planning potentially benefits significant dose reduction in critical organs, with no compromise in PTV coverage. fMRI can be widely used even in low grade cases (long life expectancies, lower acute and late toxicity in radiotherapy) and in cases with high grade astrocytomas or metastases (higher dose to PTV with better risk organ sparing in radiotherapy).

  4. The immune response in the CNS in Theiler's virus induced demyelinating disease switches from an early adaptive response to a chronic innate-like response. (United States)

    Gilli, Francesca; Li, Libin; Pachner, Andrew R


    Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) is an important model of the progressive disability caused by irreversible CNS tissue injury, and provides an example of how a CNS pathogen can cause inflammation, demyelination, and neuronal damage. We were interested in which molecules, especially inflammatory mediators, might be upregulated in the CNS throughout TMEV-IDD. We quantitated by a real-time RT-PCR multi-gene system the expression of a pathway-focused panel of genes at 30 and 165 days post infection, characterizing both the early inflammatory and the late neurodegenerative stages of TMEV-IDD. Also, we measured 32 cytokines/chemokines by multiplex Luminex analysis in CSF specimens from early and late TMEV-IDD as well as sham-treated mice. Results indicate that, in the later stage of TMEV-IDD, activation of the innate immune response is most prominent: TLRs, type I IFN response genes, and innate immunity-associated cytokines were highly expressed in late TMEV-IDD compared to sham (p ≤ 0.0001) and early TMEV-IDD (p disease to different extents. CSF provides an optimal source of biomarkers of CNS neuroinflammation.

  5. Abbreviated exposure to hypoxia is sufficient to induce CNS dysmyelination, modulate spinal motor neuron composition, and impair motor development in neonatal mice.

    Directory of Open Access Journals (Sweden)

    Jens O Watzlawik

    Full Text Available Neonatal white matter injury (nWMI is an increasingly common cause of cerebral palsy that results predominantly from hypoxic injury to progenitor cells including those of the oligodendrocyte lineage. Existing mouse models of nWMI utilize prolonged periods of hypoxia during the neonatal period, require complex cross-fostering and exhibit poor growth and high mortality rates. Abnormal CNS myelin composition serves as the major explanation for persistent neuro-motor deficits. Here we developed a simplified model of nWMI with low mortality rates and improved growth without cross-fostering. Neonatal mice are exposed to low oxygen from postnatal day (P 3 to P7, which roughly corresponds to the period of human brain development between gestational weeks 32 and 36. CNS hypomyelination is detectable for 2-3 weeks post injury and strongly correlates with levels of body and brain weight loss. Immediately following hypoxia treatment, cell death was evident in multiple brain regions, most notably in superficial and deep cortical layers as well as the subventricular zone progenitor compartment. PDGFαR, Nkx2.2, and Olig2 positive oligodendrocyte progenitor cell were significantly reduced until postnatal day 27. In addition to CNS dysmyelination we identified a novel pathological marker for adult hypoxic animals that strongly correlates with life-long neuro-motor deficits. Mice reared under hypoxia reveal an abnormal spinal neuron composition with increased small and medium diameter axons and decreased large diameter axons in thoracic lateral and anterior funiculi. Differences were particularly pronounced in white matter motor tracts left and right of the anterior median fissure. Our findings suggest that 4 days of exposure to hypoxia are sufficient to induce experimental nWMI in CD1 mice, thus providing a model to test new therapeutics. Pathological hallmarks of this model include early cell death, decreased OPCs and hypomyelination in early postnatal life

  6. Genetic evidence that Nkx2.2 and Pdgfra are major determinants of the timing of oligodendrocyte differentiation in the developing CNS (United States)

    Zhu, Qiang; Zhao, Xiaofeng; Zheng, Kang; Li, Hong; Huang, Hao; Zhang, Zunyi; Mastracci, Teresa; Wegner, Michael; Chen, Yiping; Sussel, Lori; Qiu, Mengsheng


    In the central nervous system (CNS), oligodendrocyte maturation and axonal myelination occur on a predictable schedule, but the underlying timing mechanisms are largely unknown. In the present study, we demonstrate that Nkx2.2 homeodomain transcription factor is a key regulator for the timing of oligodendrocyte differentiation during development. Whereas induced expression of Nkx2.2 in early oligodendrocyte precursor cells (OPCs) causes precocious differentiation of oligodendrocytes, conditional ablation of Nkx2.2 temporally delays oligodendrocyte maturation. Moreover, Nkx2.2 can directly bind to the promoter of platelet-derived growth factor receptor alpha (Pdgfra) and repress its gene expression. Genetic ablation of Pdgfra mimics the effect of Nkx2.2 overexpression in accelerating OPC differentiation in the developing spinal cord. Together, our findings strongly suggest that Nkx2.2 functions as a major ‘switch’ to turn off Pdgfra signaling in OPCs and initiate the intrinsic program for oligodendrocyte differentiation. PMID:24449836

  7. Thermal hydraulic tests for developing two-phase thermo-siphon loop of CARR-CNS (United States)

    Du, Shejiao; Bi, Qincheng; Chen, Tingkuan; Feng, Quanke


    The China Institute of Atomic Energy (CIAE) is now constructing the China Advanced Research Reactor (CARR: 60 MW), and designing the cold neutron source (CNS) with a two-phase hydrogen thermo-siphon loop consisting of a condenser, a single-moderator transfer tube and a cylindrical annulus moderator cell. The mockup tests reported here were carried out on a full-scale loop using Freon-113 as the working fluid in order to validate the self-regulating characteristics of the loop, with a void fraction less than 20% in the liquid of the moderator cell and requirements for establishing the condition under which the inner shell of the cell has only vapor and the outer shell liquid. During these mockup tests, the density ratio of liquid to vapor and the vapor volumetric evaporation rate due to heat load were kept the same as those in normal operation of the CARR-CNS. The results show that the loop has the required self-regulating characteristics and the inner shell of the moderator cell contains only vapor, the outer shell liquid. The local void fractions in the liquid increase with an increase in loop pressure under the condition of a constant vapor volumetric evaporation rate.

  8. Early Developments in Crystallography

    Indian Academy of Sciences (India)

    IAS Admin

    molecules to treat different diseases, make materials of desired properties and attempt to understand unknown territories far away from the Earth such as the exploration of the surface of. Mars. In this article, we will try to trace the early historical events in the development of X-ray crystallography, and the Indian contributions ...

  9. LATE-BREAKING ABSTRACT: Early relapse of non-small cell lung cancer (NSCLC) found after CNS-symptoms

    DEFF Research Database (Denmark)

    Hansen, Niels-Chr. G.; Laursen, Christian B.; Jeppesen, Stefan S.


    Background: Danish guidelines have since February 2014 recommended MR of the brain prior to curative radiotherapy in patients with NSCLC and N2-disease. More recently O'Dowd et al. [Lung Cancer 86 (2014) 185–189] have suggested MR of the brain prior to surgery no matter the stage.Aim: To study...... after symptoms within 24 months decreased in the 3½ years after the introduction of CT-based follow-up, p < 0,001 (table), but the total fraction presenting with CNS-symptoms did not change, p = 0.296. Relapses after stage I cancer decreased (p = 0.025), while no differences or changes for stages II...

  10. CNS Tumors in Neurofibromatosis. (United States)

    Campian, Jian; Gutmann, David H


    Neurofibromatosis (NF) encompasses a group of distinct genetic disorders in which affected children and adults are prone to the development of benign and malignant tumors of the nervous system. The purpose of this review is to discuss the spectrum of CNS tumors arising in individuals with NF type 1 (NF1) and NF type 2 (NF2), their pathogenic etiologies, and the rational treatment options for people with these neoplasms. This article is a review of preclinical and clinical data focused on the treatment of the most common CNS tumors encountered in children and adults with NF1 and NF2. Although children with NF1 are at risk for developing low-grade gliomas of the optic pathway and brainstem, individuals with NF2 typically manifest low-grade tumors affecting the cranial nerves (vestibular schwannomas), meninges (meningiomas), and spinal cord (ependymomas). With the identification of the NF1 and NF2 genes, molecularly targeted therapies are beginning to emerge, as a result of a deeper understanding of the mechanisms underlying NF1 and NF2 protein function. As we enter into an era of precision oncology, a more comprehensive awareness of the factors that increase the risk of developing CNS cancers in affected individuals, coupled with a greater appreciation of the cellular and molecular determinants that maintain tumor growth, will undoubtedly yield more effective therapies for these cancer predisposition syndromes.

  11. An invertebrate model for CNS drug discovery

    DEFF Research Database (Denmark)

    Al-Qadi, Sonia; Schiøtt, Morten; Hansen, Steen Honoré


    and is considered the most vital efflux pump. Functionally, this model showed transport kinetic behaviors comparable to those obtained from in vitro models. Particularly, substrate affinity of the putative P-gp was observed as in P-gp expressing cells lines, used for predicting drug penetration across biological......BACKGROUND: ABC efflux transporters at the blood brain barrier (BBB), namely the P-glycoprotein (P-gp), restrain the development of central nervous system (CNS) drugs. Consequently, early screening of CNS drug candidates is pivotal to identify those affected by efflux activity. Therefore, simple...... was performed. Subsequently, identified transcripts were matched with their counterparts in human, rat, mouse and Drosophila melanogaster, based on amino acid sequence similarity, and phylogenetic trees were constructed to reveal the most likely evolutionary history of the proteins. Further, functional...

  12. Comparison of Cashew Nut Shell Liquid (CNS) Resin with Polyester Resin in Composite Development


    C. C. Ugoamadi


    Natural resins can compete effectively with the synthetic ones in composite development. In this research, cashew nuts were picked and processed for the extraction of the resin content. The resin (natural resin) so obtained was mixed with cobalt amine (accelerator), methyl ethyl ketone peroxide (catalyst) to develop two sets of composite specimens – specimens without fibres and specimens reinforced with glass fibres. This method of sample specimen development was repeated with polyester (synt...

  13. Comparison of Cashew Nut Shell Liquid (CNS Resin with Polyester Resin in Composite Development

    Directory of Open Access Journals (Sweden)

    C. C. Ugoamadi


    Full Text Available Natural resins can compete effectively with the synthetic ones in composite development. In this research, cashew nuts were picked and processed for the extraction of the resin content. The resin (natural resin so obtained was mixed with cobalt amine (accelerator, methyl ethyl ketone peroxide (catalyst to develop two sets of composite specimens – specimens without fibres and specimens reinforced with glass fibres. This method of sample specimen development was repeated with polyester (synthetic resin. Compressive and tensile strength tests conducted proved that composites developed with cashew nut shell liquid (CNSL resin were comparable to those developed with polyester resin. In the results, CNSL has an ultimate compressive strength of 55MPa compared to that of polyester resin with an ultimate strength of 68MPa. The result of tensile strength proved cashew nut shell liquid resin (with ultimate strength of 44MPa to be better than polyester resin with 39MPa as ultimate tensile strength. This means that natural resins could be a better substitute for the synthetic ones when the required quantities of fibers (reinforcements and fillers are used in the fibre-reinforced plastic composite developments.

  14. Embryonic expression of Drosophila IMP in the developing CNS and PNS

    DEFF Research Database (Denmark)

    Adolph, Sidsel Kramshøj; Delotto, Robert; Nielsen, Finn Cilius


    Drosophila IMP (dIMP) is related to the vertebrate RNA-binding proteins IMP1-3, ZBP1, Vg1RBP and CRD-BP, which are involved in RNA regulatory processes such as translational repression, localization and stabilization. The proteins are expressed in many fetal tissues, including the developing nerv...

  15. Melatonin in Pregnancy: Effects on Brain Development and CNS Programming Disorders. (United States)

    Sagrillo-Fagundes, Lucas; Assunção Salustiano, Eugênia Maria; Yen, Philippe Wong; Soliman, Ahmed; Vaillancourt, Cathy


    Melatonin is an important neuroprotective factor and its receptors are expressed in the fetal brain. During normal pregnancy, maternal melatonin level increases progressively until term and is highly transferred to the fetus, with an important role in brain formation and differentiation. Maternal melatonin provides the first circadian signal to the fetus. This indolamine is also produced de novo and plays a protective role in the human placenta. In pregnancy disorders, both maternal and placental melatonin levels are decreased. Alteration in maternal melatonin level has been associated with disrupted brain programming with long-term effects. Melatonin has strong antioxidant protective effects directly and indirectly via the activation of its receptors. The fetal brain is highly susceptible to oxygenation variation and oxidative stress that can lead to neuronal development disruption. Based on that, several approaches have been tested as a treatment in case of pregnancy disorders and melatonin, through its neuroprotective effect, has been recently accepted against fetal brain injury. This review provides an overview about the protective effects of melatonin during pregnancy and on fetal brain development.

  16. Advances, interactions, and future developments in the CNS, Phenix, and Rosetta structural biology software systems. (United States)

    Adams, Paul D; Baker, David; Brunger, Axel T; Das, Rhiju; DiMaio, Frank; Read, Randy J; Richardson, David C; Richardson, Jane S; Terwilliger, Thomas C


    Advances in our understanding of macromolecular structure come from experimental methods, such as X-ray crystallography, and also computational analysis of the growing number of atomic models obtained from such experiments. The later analyses have made it possible to develop powerful tools for structure prediction and optimization in the absence of experimental data. In recent years, a synergy between these computational methods for crystallographic structure determination and structure prediction and optimization has begun to be exploited. We review some of the advances in the algorithms used for crystallographic structure determination in the Phenix and Crystallography & NMR System software packages and describe how methods from ab initio structure prediction and refinement in Rosetta have been applied to challenging crystallographic problems. The prospects for future improvement of these methods are discussed.

  17. Antiretroviral therapy CNS penetration and HIV-1-associated CNS disease. (United States)

    Garvey, L; Winston, A; Walsh, J; Post, F; Porter, K; Gazzard, B; Fisher, M; Leen, C; Pillay, D; Hill, T; Johnson, M; Gilson, R; Anderson, J; Easterbrook, P; Bansi, L; Orkin, C; Ainsworth, J; Palfreeman, A; Gompels, M; Phillips, A N; Sabin, C A


    The impact of different antiretroviral agents on the risk of developing or surviving CNS disease remains unknown. The aim of this study was to investigate whether using antiretroviral regimens with higher CNS penetration effectiveness (CPE) scores was associated with reduced incidence of CNS disease and improved survival in the UK Collaborative HIV Cohort (CHIC) Study. Adults without previous CNS disease, who commenced combination antiretroviral therapy (cART) between 1996 and 2008, were included (n = 22,356). Initial and most recent cART CPE scores were calculated. CNS diseases were HIV encephalopathy (HIVe), progressive multifocal leukoencephalopathy (PML), cerebral toxoplasmosis (TOXO), and cryptococcal meningitis (CRYPTO). Incidence rates and overall survival were stratified by CPE score. A multivariable Poisson regression model was used to identify independent associations. The median (interquartile range) CPE score for initial cART regimen increased from 7 (5-8) in 1996-1997 to 9 (8-10) in 2000-2001 and subsequently declined to 6 (7-8) in 2006-2008. Differences in gender, HIV acquisition risk group, and ethnicity existed between CPE score strata. A total of 251 subjects were diagnosed with a CNS disease (HIVe 80; TOXO 59; CRYPTO 56; PML 54). CNS diseases occurred more frequently in subjects prescribed regimens with CPE scores ≤ 4, and less frequently in those with scores ≥ 10; however, these differences were nonsignificant. Initial and most recent cART CPE scores ≤ 4 were independently associated with increased risk of death. Clinical status at time of commencing cART influences antiretroviral selection and CPE score. This information should be considered when utilizing CPE scores for retrospective analyses.

  18. Early experience and brain development. (United States)

    Bick, Johanna; Nelson, Charles A


    Healthy brain development takes place within the context of individual experience. Here, we describe how certain early experiences are necessary for typical brain development. We present evidence from multiple studies showing that severe early life neglect leads to alterations in brain development, which compromises emotional, behavioral, and cognitive functioning. We also show how early intervention can reverse some of the deleterious effects of neglect on brain development. We conclude by emphasizing that early interventions that start at the earliest possible point in human development are most likely to support maximal recovery from early adverse experiences. WIREs Cogn Sci 2017, 8:e1387. doi: 10.1002/wcs.1387 For further resources related to this article, please visit the WIREs website. © 2016 Wiley Periodicals, Inc.

  19. Long-range regulation by shared retinoic acid response elements modulates dynamic expression of posterior Hoxb genes in CNS development. (United States)

    Ahn, Youngwook; Mullan, Hillary E; Krumlauf, Robb


    Retinoic acid (RA) signaling plays an important role in determining the anterior boundary of Hox gene expression in the neural tube during embryogenesis. In particular, RA signaling is implicated in a rostral expansion of the neural expression domain of 5׳ Hoxb genes (Hoxb9-Hoxb5) in mice. However, underlying mechanisms for this gene regulation have remained elusive due to the lack of RA responsive element (RARE) in the 5׳ half of the HoxB cluster. To identify cis-regulatory elements required for the rostral expansion, we developed a recombineering technology to serially label multiple genes with different reporters in a single bacterial artificial chromosome (BAC) vector containing the mouse HoxB cluster. This allowed us to simultaneously monitor the expression of multiple genes. In contrast to plasmid-based reporters, transgenic BAC reporters faithfully recapitulated endogenous gene expression patterns of the Hoxb genes including the rostral expansion. Combined inactivation of two RAREs, DE-RARE and ENE-RARE, in the BAC completely abolished the rostral expansion of the 5׳ Hoxb genes. Knock-out of endogenous DE-RARE lead to significantly reduced expression of multiple Hoxb genes and attenuated Hox gene response to exogenous RA treatment in utero. Regulatory potential of DE-RARE was further demonstrated by its ability to anteriorize 5׳ Hoxa gene expression in the neural tube when inserted into a HoxA BAC reporter. Our data demonstrate that multiple RAREs cooperate to remotely regulate 5׳ Hoxb genes during CNS development, providing a new insight into the mechanisms for gene regulation within the Hox clusters. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. The transition from day-to-night activity is a risk factor for the development of CNS oxygen toxicity in the diurnal fat sand rat (Psammomys obesus). (United States)

    Eynan, Mirit; Biram, Adi; Mullokandov, Michael; Kronfeld-Schor, Noga; Paz-Cohen, Rotem; Menajem, Dvir; Arieli, Yehuda


    Performance and safety are impaired in employees engaged in shift work. Combat divers who use closed-circuit oxygen diving apparatus undergo part of their training during the night hours. The greatest risk involved in diving with such apparatus is the development of central nervous system oxygen toxicity (CNS-OT). We investigated whether the switch from day-to-night activity may be a risk factor for the development of CNS-OT using a diurnal animal model, the fat sand rat (Psammomys obesus). Animals were kept on a 12:12 light-dark schedule (6 a.m. to 6 p.m. at 500 lx). The study included two groups: (1) Control group: animals were kept awake and active during the day, between 09:00 and 15:00. (2) Experimental group: animals were kept awake and active during the night, between 21:00 and 03:00, when they were exposed to dim light in order to simulate the conditions prevalent during combat diver training. This continued for a period of 3 weeks, 5 days a week. On completion of this phase, 6-sulphatoxymelatonin (6-SMT) levels in urine were determined over a period of 24 h. Animals were then exposed to hyperbaric oxygen (HBO). To investigate the effect of acute melatonin administration, melatonin (50 mg/kg) or its vehicle was administered to the animals in both groups 20 min prior to HBO exposure. After the exposure, the activity of superoxide dismutase, catalase and glutathione peroxidase was measured, as were the levels of neuronal nitric oxide synthase (nNOS) and overall nitrotyrosylation in the cortex and hippocampus. Latency to CNS-OT was significantly reduced after the transition from day-to-night activity. This was associated with alterations in the level of melatonin metabolites secreted in the urine. Acute melatonin administration had no effect on latency to CNS-OT in either of the groups. Nevertheless, the activity of superoxide dismutase and catalase, as well as nitrotyrosine and nNOS levels, were altered in the hippocampus following melatonin

  1. Plasticity during Early Brain Development Is Determined by Ontogenetic Potential. (United States)

    Krägeloh-Mann, Ingeborg; Lidzba, Karen; Pavlova, Marina A; Wilke, Marko; Staudt, Martin


    Two competing hypotheses address neuroplasticity during early brain development: the "Kennard principle" describes the compensatory capacities of the immature developing CNS as superior to those of the adult brain, whereas the "Hebb principle" argues that the young brain is especially sensitive to insults. We provide evidence that these principles are not mutually exclusive. Following early brain lesions that are unilateral, the brain can refer to homotopic areas of the healthy hemisphere. This potential for reorganization is unique to the young brain but available only when, during ontogenesis of brain development, these areas have been used for the functions addressed. With respect to motor function, ipsilateral motor tracts can be recruited, which are only available during early brain development. Language can be reorganized to the right after early left hemispheric lesions, as the representation of the language network is initially bilateral. However, even in these situations, compensatory capacities of the developing brain are found to have limitations, probably defined by early determinants. Thus, plasticity and adaptivity are seen only within ontogenetic potential; that is, axonal or cortical structures cannot be recruited beyond early developmental possibilities. The young brain is probably more sensitive and vulnerable to lesions when these are bilateral. This is shown here for bilateral periventricular white matter lesions that clearly have an impact on cortical architecture and function, thus probably interfering with early network building. Georg Thieme Verlag KG Stuttgart · New York.

  2. Epigenetics of Early Child Development

    Directory of Open Access Journals (Sweden)

    Chris eMurgatroyd


    Full Text Available Comprehensive clinical studies show that adverse conditions in early life can severely impact the developing brain and increase vulnerability to mood disorders later in life. During early postnatal life the brain exhibits high plasticity which allows environmental signals to alter the trajectories of rapidly developing circuits. Adversity in early life is able to shape the experience-dependent maturation of stress-regulating pathways underlying emotional functions and endocrine responses to stress, such as the hypothalamo-pituitary-adrenal (HPA system, leading to long-lasting altered stress responsivity during adulthood.To date, the study of gene-environment interactions in the human population has been dominated by epidemiology. However, recent research in the neuroscience field is now advancing clinical studies by addressing specifically the mechanisms by which gene-environment interactions can predispose individuals towards psychopathology. To this end, appropriate animal models are being developed in which early environmental factors can be manipulated in a controlled manner. Here we will review recent studies performed with the common aim of understanding the effects of the early environment in shaping brain development and discuss the newly developing role of epigenetic mechanisms in translating early life conditions into long-lasting changes in gene expression underpinning brain functions. Particularly, we argue that epigenetic mechanisms can mediate the gene-environment dialogue in early life and give rise to persistent epigenetic programming of adult physiology and dysfunction eventually resulting in disease. Understanding how early life experiences can give raise to lasting epigenetic memories conferring increased risk for mental disorders, how they are maintained and how they could be reversed, is increasingly becoming a focus of modern psychiatry and should pave new guidelines for timely therapeutic interventions.

  3. Early Development Economics Debates Revisited


    Alacevich, Michele


    Development economics in its early years created the image of a fierce fight between advocates of contrasting theories or approaches- "balanced growth" vs. "unbalanced growth" or "program loans" vs. "project loans." This view has the merit to highlight such conflicts in great detail; yet it fails to take into account the reality of development economics as it was practiced in the field. Th...

  4. Early prosocial development across cultures. (United States)

    Callaghan, Tara; Corbit, John


    Human prosociality is ubiquitous, even though it may be manifested differently across cultures. Low cost helping and sharing emerge early in development, and at similar levels, across cultures having vastly different sociocultural niches. Developmental trajectories for costly sharing diverge across cultures around middle childhood, in line with differences in the sociocultural niches that children experience. Cultural developmental research has focussed primarily on the emergence and development of prosocial behaviour, and would benefit from an examination of the interplay between psychological (cognitive, motivational) and sociocultural (norms, developmental niche) foundations over ontogeny. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. CNS infections in Greenland

    DEFF Research Database (Denmark)

    Nordholm, Anne Christine; Søborg, Bolette; Andersson, Mikael


    ), but equally high among Inuits in Greenland and Denmark (38.2 and 35.4, respectively). Mortality from CNS infections was 2 fold higher among Inuits (10.5%) than among non-Inuits (4.8%) with a fivefold higher case fatality rate in Inuit toddlers. CONCLUSION: Overall, Inuits living in Greenland and Denmark...... suffer from twice the rate of CNS infections compared with non-Inuits, and Inuit toddlers carried the highest risk of mortality. Further studies regarding risk factors such as genetic susceptibility, life style and socioeconomic factors are warranted....

  6. FaRP cell distribution in the developing CNS suggests the involvement of FaRPs in all parts of the chromatophore control pathway in Sepia officinalis (Cephalopoda). (United States)

    Aroua, Salima; Andouche, Aude; Martin, Madeleine; Baratte, Sébastien; Bonnaud, Laure


    The FMRFamide-related peptide (FaRP) family includes a wide range of neuropeptides that have a role in many biological functions. In cephalopods, these peptides intervene in the peculiar body patterning system used for communication and camouflage. This system is particularly well developed in the cuttlefish and is functional immediately after hatching (stage 30). In this study, we investigate when and how the neural structures involved in the control of body patterning emerge and combine during Sepia embryogenesis, by studying the expression or the production of FaRPs. We detected FaRP expression and production in the nervous system of embryos from the beginning of organogenesis (stage 16). The wider FaRP expression was observed concomitantly with brain differentiation (around stage 22). Until hatching, FaRP-positive cells were located in specific areas of the central and peripheral nervous system (CNS and PNS). Most of these areas were implicated in the control of body patterns, suggesting that FaRPs are involved in all parts of the neural body pattern control system, from the 'receptive areas' via the CNS to the chromatophore effectors. Copyright © 2011 Elsevier GmbH. All rights reserved.

  7. CNS and inflammation

    African Journals Online (AJOL)


    Synthesis of inflammatory mediators – e.g. cytokines, free radicals, prostaglandins. Expression of adhesion molecules. Invasion of immune cells. Leukocytes have the ability to infiltrate the. CNS and cytokines are produced by resident cells, especially during injuries and diseases. Although the cellular source and role of ...

  8. Prominin-1 (CD133 defines both stem and non-stem cell populations in CNS development and gliomas.

    Directory of Open Access Journals (Sweden)

    Karl Holmberg Olausson

    Full Text Available Prominin-1 (CD133 is a commonly used cancer stem cell marker in central nervous system (CNS tumors including glioblastoma (GBM. Expression of Prom1 in cancer is thought to parallel expression and function in normal stem cells. Using RNA in situ hybridization and antibody tools capable of detecting multiple isoforms of Prom1, we find evidence for two distinct Prom1 cell populations in mouse brain. Prom1 RNA is first expressed in stem/progenitor cells of the ventricular zone in embryonic brain. Conversely, in adult mouse brain Prom1 RNA is low in SVZ/SGZ stem cell zones but high in a rare but widely distributed cell population (Prom1(hi. Lineage marker analysis reveals Prom1(hi cells are Olig2+Sox2+ glia but Olig1/2 knockout mice lacking oligodendroglia retain Prom1(hi cells. Bromodeoxyuridine labeling identifies Prom1(hi as slow-dividing distributed progenitors distinct from NG2+Olig2+ oligodendrocyte progenitors. In adult human brain, PROM1 cells are rarely positive for OLIG2, but express astroglial markers GFAP and SOX2. Variability of PROM1 expression levels in human GBM and patient-derived xenografts (PDX - from no expression to strong, uniform expression--highlights that PROM1 may not always be associated with or restricted to cancer stem cells. TCGA and PDX data show that high expression of PROM1 correlates with poor overall survival. Within proneural subclass tumors, high PROM1 expression correlates inversely with IDH1 (R132H mutation. These findings support PROM1 as a tumor cell-intrinsic marker related to GBM survival, independent of its stem cell properties, and highlight potentially divergent roles for this protein in normal mouse and human glia.

  9. Prominin-1 (CD133) defines both stem and non-stem cell populations in CNS development and gliomas. (United States)

    Holmberg Olausson, Karl; Maire, Cecile L; Haidar, Sam; Ling, Jason; Learner, Emily; Nistér, Monica; Ligon, Keith L


    Prominin-1 (CD133) is a commonly used cancer stem cell marker in central nervous system (CNS) tumors including glioblastoma (GBM). Expression of Prom1 in cancer is thought to parallel expression and function in normal stem cells. Using RNA in situ hybridization and antibody tools capable of detecting multiple isoforms of Prom1, we find evidence for two distinct Prom1 cell populations in mouse brain. Prom1 RNA is first expressed in stem/progenitor cells of the ventricular zone in embryonic brain. Conversely, in adult mouse brain Prom1 RNA is low in SVZ/SGZ stem cell zones but high in a rare but widely distributed cell population (Prom1(hi)). Lineage marker analysis reveals Prom1(hi) cells are Olig2+Sox2+ glia but Olig1/2 knockout mice lacking oligodendroglia retain Prom1(hi) cells. Bromodeoxyuridine labeling identifies Prom1(hi) as slow-dividing distributed progenitors distinct from NG2+Olig2+ oligodendrocyte progenitors. In adult human brain, PROM1 cells are rarely positive for OLIG2, but express astroglial markers GFAP and SOX2. Variability of PROM1 expression levels in human GBM and patient-derived xenografts (PDX) - from no expression to strong, uniform expression--highlights that PROM1 may not always be associated with or restricted to cancer stem cells. TCGA and PDX data show that high expression of PROM1 correlates with poor overall survival. Within proneural subclass tumors, high PROM1 expression correlates inversely with IDH1 (R132H) mutation. These findings support PROM1 as a tumor cell-intrinsic marker related to GBM survival, independent of its stem cell properties, and highlight potentially divergent roles for this protein in normal mouse and human glia.

  10. Nanotechnology—novel therapeutics for CNS disorders (United States)

    Srikanth, Maya; Kessler, John A.


    Research into treatments for diseases of the CNS has made impressive strides in the past few decades, but therapeutic options are limited for many patients with CNS disorders. Nanotechnology has emerged as an exciting and promising new means of treating neurological disease, with the potential to fundamentally change the way we approach CNS-targeted therapeutics. Molecules can be nanoengineered to cross the blood–brain barrier, target specific cell or signalling systems, respond to endogenous stimuli, or act as vehicles for gene delivery, or as a matrix to promote axon elongation and support cell survival. The wide variety of available nanotechnologies allows the selection of a nanoscale material with the characteristics best suited to the therapeutic challenges posed by an individual CNS disorder. In this Review, we describe recent advances in the development of nanotechnology for the treatment of neurological disorders—in particular, neurodegenerative disease and malignant brain tumours—and for the promotion of neuroregeneration. PMID:22526003

  11. MyD88 is crucial for the development of a protective CNS immune response to Toxoplasma gondii infection. (United States)

    Torres, Marbel; Guiton, Rachel; Lacroix-Lamandé, Sonia; Ryffel, Bernhard; Leman, Samuel; Dimier-Poisson, Isabelle


    T. gondii in the central nervous system (CNS).

  12. MyD88 is crucial for the development of a protective CNS immune response to Toxoplasma gondii infection

    Directory of Open Access Journals (Sweden)

    Torres Marbel


    establish a role for MyD88 in T cell-mediated control of T. gondii in the central nervous system (CNS.

  13. Strategies for Supporting Early Literacy Development (United States)

    Dennis, Lindsay R.; Horn, Eva


    The development of early literacy skills is critical to children's later success in reading and reading-related activities; therefore, understanding how teachers can support early literacy development is equally important. In this article, the authors provide information on how early childhood teachers can use specific strategies and techniques as…

  14. Forty-eight-week efficacy and safety and early CNS tolerability of doravirine (MK-1439, a novel NNRTI, with TDF/FTC in ART-naive HIV-positive patients

    Directory of Open Access Journals (Sweden)

    Josep M Gatell


    Full Text Available Introduction: Doravirine (DOR is an investigational NNRTI (aka MK-1439 that retains activity against common NNRTI-resistant mutants. We have previously reported the Part 1 results from a two-part, randomized, double-blind, Phase IIb study in ART-naïve HIV-1-positive patients (1. At doses of 25, 50, 100 and 200 mg qd, DOR plus open-label tenofovir/emtricitabine (TDF/FTC demonstrated potent antiretroviral activity comparable to EFV 600 mg qhs plus TDF/FTC and was generally well tolerated at week 24. DOR 100 mg was selected for use in patients continuing in Part 1 and those newly enrolled in Part 2. Methods: Patients receiving DOR 25, 50 or 200 mg in Part 1 were switched to 100 mg after dose selection. In Part 2, 132 additional patients were randomized 1:1 to DOR 100 mg qd or EFV 600 mg qhs (each with TDF/FTC. We present week 48 efficacy and safety results for all patients in Part 1, and early (week 8 CNS tolerability only for patients randomized to DOR 100 mg or to EFV in Parts 1 and 2 combined. The primary safety endpoint is the % of patients with pre-specified CNS events (all causality by week 8 for DOR 100 mg qd vs EFV (Parts 1 + 2 combined. Results: Part 1 week 48 efficacy and safety results are shown below. The most common DR clinical AEs in the DOR and EFV groups, respectively, were abnormal dreams (10.2%; 9.5%, nausea (7.8%; 2.4%, fatigue (7.2%; 4.8%, diarrhoea (4.8%; 9.5% and dizziness (3.0%; 23.8%, and were generally mild to moderate. Part 1 + 2 Week 8 CNS Event Analysis: One hundred thirty-two patients were randomized in Part 2, 66 to DOR 100 mg and 66 to EFV. Combining Part 1 and 2, a total of 108 patients received DOR 100 mg and 108 received EFV. By week 8, at least one CNS AE was reported in 22.2% of the DOR group and 43.5% of the EFV group (p<0.001. The most common CNS AEs were dizziness (DOR 9.3%; EFV 27.8%, insomnia (6.5%; 2.8%, abnormal dreams (5.6%; 16.7% and nightmares (5.6%; 8.3%. Conclusions: In ART-naïve, HIV-1-positive

  15. Ambroxol: a CNS drug? (United States)

    Weiser, Thomas


    For almost three decades ambroxol has been used in the therapy of airway diseases. In 2002, ambroxol lozenges were marketed for the treatment of sore throat making use of its local anesthetic effect. Detailed investigations of ambroxol with modern pharmacological methods yielded additional interesting results: ambroxol has been found to have profound effects on neuronal voltage-gated Na(+), as well as Ca(2+) channels, and to effectively reduce chronic inflammatory and neuropathic pain in rodents. The question was raised whether ambroxol affects the central nervous system (CNS) directly, or whether its effects can be explained solely by a peripheral action. This issue was addressed by re-examining pharmacokinetics, as well as toxicology of ambroxol. It has been concluded that even at the highest clinically used doses ambroxol does not have significant direct effects on the CNS. At clinically relevant plasma concentrations ambroxol either does not penetrate blood-brain barrier, or its brain levels are too low to cause relevant effects. The analgesic effects of ambroxol by either systemic administration to animals, or by topical application in humans can be explained by ambroxol-induced blockade of ion channels in peripheral neurons.

  16. Supporting Mathematical Development in the Early Years (United States)

    Pound, Linda


    This book provides practical guidance for parents, teachers, and other early years workers who want to give children a good start in mathematical development. Showing how competent children are as mathematicians from an early age, the book offers an overview of young children's mathematical behaviour at home and in early years settings. This book…

  17. Neuroimaging, a new tool for investigating the effects of early diet on cognitive and brain development


    Isaacs, Elizabeth B.


    Nutrition is crucial to the initial development of the central nervous system (CNS), and then to its maintenance, because both depend on dietary intake to supply the elements required to develop and fuel the system. Diet in early life is often seen in the context of “programming” where a stimulus occurring during a vulnerable period can have long-lasting or even lifetime effects on some aspect of the organism's structure or function. Nutrition was first shown to be a programming stimulus for ...

  18. Myelin Formation during Development of the CNS Is Delayed in Matrix Metalloproteinase-9 and -12 Null Mice

    DEFF Research Database (Denmark)

    Larsen, Peter Hjørringgaard; DaSilva, Angelika G.; Conant, Kathrine


    around a demyelinating lesion of the spinal cord of adult mice facilitated remyelination. In the current study, we have addressed whether and how MMPs might be required for myelin formation in normal ontogeny. Using a probe for multiple MMPs and the developing mouse optic nerve, we found two members, MMP...... to remain high in MMP-deficient mice. These results reveal a novel function for MMP-9 and -12 in developmental myelination likely through regulating IGF-1 bioavailability....

  19. Requirements for an Integrated UAS CNS Architecture (United States)

    Templin, Fred; Jain, Raj; Sheffield, Greg; Taboso, Pedro; Ponchak, Denise


    The National Aeronautics and Space Administration (NASA) Glenn Research Center (GRC) is investigating revolutionary and advanced universal, reliable, always available, cyber secure and affordable Communication, Navigation, Surveillance (CNS) options for all altitudes of UAS operations. In Spring 2015, NASA issued a Call for Proposals under NASA Research Announcements (NRA) NNH15ZEA001N, Amendment 7 Subtopic 2.4. Boeing was selected to conduct a study with the objective to determine the most promising candidate technologies for Unmanned Air Systems (UAS) air-to-air and air-to-ground data exchange and analyze their suitability in a post-NextGen NAS environment. The overall objectives are to develop UAS CNS requirements and then develop architectures that satisfy the requirements for UAS in both controlled and uncontrolled air space. This contract is funded under NASAs Aeronautics Research Mission Directorates (ARMD) Aviation Operations and Safety Program (AOSP) Safe Autonomous Systems Operations (SASO) project and proposes technologies for the Unmanned Air Systems Traffic Management (UTM) service. Communications, Navigation and Surveillance (CNS) requirements must be developed in order to establish a CNS architecture supporting Unmanned Air Systems integration in the National Air Space (UAS in the NAS). These requirements must address cybersecurity, future communications, satellite-based navigation APNT, and scalable surveillance and situational awareness. CNS integration, consolidation and miniaturization requirements are also important to support the explosive growth in small UAS deployment. Air Traffic Management (ATM) must also be accommodated to support critical Command and Control (C2) for Air Traffic Controllers (ATC). This document therefore presents UAS CNS requirements that will guide the architecture.

  20. Can taxanes provide benefit in patients with CNS tumors and in pediatric patients with tumors? An update on the preclinical development of cabazitaxel. (United States)

    Sémiond, D; Sidhu, S S; Bissery, M-C; Vrignaud, P


    While first-generation taxanes are valuable treatment options for many solid tumors, they are limited by an inability to cross the blood-brain barrier (BBB) and by limited efficacy in pediatric patients. Following promising preclinical data for the next-generation taxane cabazitaxel, including activity in tumor models fully sensitive, poorly sensitive or insensitive to docetaxel, and its ability to cross the BBB, further preclinical studies of cabazitaxel relevant to these two clinical indications were performed. Cabazitaxel brain distribution was assessed in mice, rats and dogs. Cabazitaxel antitumor activity was assessed in mice bearing intracranial human glioblastoma (SF295; U251) xenografts, and subcutaneous cell line-derived human pediatric sarcoma (rhabdomyosarcoma RH-30; Ewing's sarcoma TC-71 and SK-ES-1) or patient-derived pediatric sarcoma (osteosarcoma DM77 and DM113; Ewing's sarcoma DM101) xenografts. The activity of cabazitaxel-cisplatin combination was evaluated in BALB/C mice bearing the syngeneic murine colon adenocarcinoma, C51. Cabazitaxel penetrated rapidly in the brain, with a similar brain-blood radioactivity exposure relationship across different animal species. In intracranial human glioblastoma models, cabazitaxel demonstrated superior activity to docetaxel both at early (before BBB disruption) and at advanced stages, consistent with enhanced brain penetration. Compared with similar dose levels of docetaxel, cabazitaxel induced significantly greater tumor growth inhibition across six pediatric tumor models and more tumor regressions in five of the six models. Therapeutic synergism was observed between cisplatin and cabazitaxel, regardless of administration sequence. These preclinical data suggest that cabazitaxel could be an effective therapy in CNS and pediatric tumors, supporting ongoing clinical evaluation in these indications.

  1. Flavonoids and the CNS

    DEFF Research Database (Denmark)

    Jäger, Anna Katharina; Saaby, Lasse


    Flavonoids are present in almost all terrestrial plants, where they provide UV-protection and colour. Flavonoids have a fused ring system consisting of an aromatic ring and a benzopyran ring with a phenyl substituent. The flavonoids can be divided into several classes depending on their structure....... Flavonoids are present in food and medicinal plants and are thus consumed by humans. They are found in plants as glycosides. Before oral absorption, flavonoids undergo deglycosylation either by lactase phloridzin hydrolase or cytosolic ß-glucocidase. The absorbed aglycone is then conjugated by methylation......, sulphatation or glucuronidation. Both the aglycones and the conjugates can pass the blood-brain barrier. In the CNS several flavones bind to the benzodiazepine site on the GABA(A)-receptor resulting in sedation, anxiolytic or anti-convulsive effects. Flavonoids of several classes are inhibitors of monoamine...

  2. Preliminary studies for the development of intranasal nanoemulsion containing CNS agent: emphasizing the utilization of cut and weigh method. (United States)

    Kumar, Amrish; Jain, Sunil Kumar


    The selection of excipients and preformulation strategy plays a vital role for the development of nanoemulsion, due to anatomical and physiological challenges posed by nasal cavity. This attempt is focused on the selection and optimization of excipients for the development of a nanoemulsion system for intranasal delivery. Excipients were selected on the basis of solubility of active drug, compatibility interactions and nasal irritancy. Surfactant and co-surfactant combination and their ratio were finalized on the basis of nanoemulsion region obtained from constructed phase diagrams with Capmul MCM as oil phase. A validated cut and weigh method was employed for the optimization of different phase diagrams with respect to nanoemulsion region. The solubility of drug in Capmul MCM, Labrasol, and Transcutol-P was found to be superior with numeric values of 79.50 ± 1.68 mg/ml, 51.10 ± 1.39 mg/ml, and 36.60 ± 0.85 mg/ml, respectively. On the basis of phase diagram analysis, Labrasol and Transcutol-P in 3:1 ratio provides greater nanoemulsion region of 65.28 ± 0.18%. The validation of cut and weigh method revealed that there was no significant statistical difference (P > 0.05) with a %RSD value of 2.38 for intersheet variation. The results of validation studies for cut and weigh method suggests that it can be effectively used as an optimization method for the selection of nanoemulsion composition.

  3. Nutritional factors modify the inhibition of CNS development by combined exposure to methadone and ethanol in neonatal rats. (United States)

    Kane, C M; Pierce, D R; Nyamweya, N N; Yang, H; Kasmi, Y; Mosby, R; Serbus, D C; Light, K E


    The consequences resulting from the combined exposure to methadone and ethanol during a time period equivalent to the third trimester brain growth spurt was the purpose of this study. Rat pups were treated on postnatal days 6-10 and sacrificed on postnatal day 11. Body weight along with the heart, liver, kidneys, whole brain, cerebrum, cerebellum, and brain stem weights were measured. The impact of nutritional factors were identified by delivery of the drug solutions in one of two intubation vehicles differing in both caloric density and composition. Ethanol and methadone in combination result in significantly increased detrimental effects compared to methadone alone only when possible nutritional compromise was present. The combined effect of both drugs significantly inhibited body growth and the development of all brain regions studied. Neither drug alone, nor in combination, produced significant inhibition of growth in the liver, heart, or kidney. The nutritional status of the pup, as represented by vehicle composition, was able to modify the specific drug effects and suggests that nutritional status can mask or enhance the determination of specific drug effects.

  4. All-trans retinol and retinol-binding protein from embryonic cerebrospinal fluid exhibit dynamic behaviour during early central nervous system development. (United States)

    Parada, Carolina; Gato, Angel; Bueno, David


    Embryonic cerebrospinal fluid (E-CSF) is involved in the regulation of survival, proliferation and neurogenesis of neuroectodermal progenitor cells, as well as in the control of mesencephalic gene expression in collaboration with the isthmic organizer. Recently, we showed the presence of retinol-binding protein (RBP) within the E-CSF proteome. RBP is an all-trans retinol carrier, a molecule that can be metabolized into retinoic acid, a morphogen involved in central nervous system (CNS) morphogenesis and patterning. Here we demonstrate the presence of all-trans retinol within the E-CSF and analyse the dynamics of RBP and all-trans retinol within this fluid, as well as the expression of retinoic acid-synthesizing enzymes during early CNS development. Our results suggest a relationship between the dynamics of these molecules and the early events of CNS patterning.

  5. Violence prevention and early childhood development

    African Journals Online (AJOL)

    This article focuses on the intersection between early childhood development services and primary violence prevention interventions. It encourages a developmental approach to violence prevention by promoting healthy physical and social development and preventing direct and indirect exposure to violence during early ...

  6. Innate Interferons Regulate CNS Inflammation

    DEFF Research Database (Denmark)

    Dieu, Ruthe; Khorooshi, Reza M. H.; Mariboe, Anne

    Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) whose pathology is characterised by demyelination and axonal damage. This results from interplay between CNS-resident glia, infiltrating leukocytes and a plethora of cytokines and chemokines. Currently, ...

  7. Applications of alcohol clamping in early drug development

    NARCIS (Netherlands)

    Zoethout, Remco Wiebe Martijn


    This thesis describes the development of a novel alcohol clamp, a new method to obtain stable plasma levels of alcohol and its application in CNS-research. The method might have several advantages that were explored in subsequent studies described in this thesis. The stability of the alcohol clamp

  8. Flavonoids and the CNS

    Directory of Open Access Journals (Sweden)

    Anna K. Jäger


    Full Text Available Flavonoids are present in almost all terrestrial plants, where they provide UV-protection and colour. Flavonoids have a fused ring system consisting of an aromatic ring and a benzopyran ring with a phenyl substituent. The flavonoids can be divided into several classes depending on their structure. Flavonoids are present in food and medicinal plants and are thus consumed by humans. They are found in plants as glycosides. Before oral absorption, flavonoids undergo deglycosylation either by lactase phloridzin hydrolase or cytosolic β-glucocidase. The absorbed aglycone is then conjugated by methylation, sulphatation or glucuronidation. Both the aglycones and the conjugates can pass the blood-brain barrier. In the CNS several flavones bind to the benzodiazepine site on the GABAA-receptor resulting in sedation, anxiolytic or anti-convulsive effects. Flavonoids of several classes are inhibitors of monoamine oxidase A or B, thereby working as anti-depressants or to improve the conditions of Parkinson’s patients. Flavanols, flavanones and anthocyanidins have protective effects preventing inflammatory processes leading to nerve injury. Flavonoids seem capable of influencing health and mood.

  9. Trisomy and early brain development (United States)

    Haydar, Tarik F.; Reeves, Roger H.


    Trisomy for human chromosome 21 (Hsa21) results in Down syndrome (DS). The finished human genome sequence provides a thorough catalog of the genetic elements whose altered dosage perturbs development and function in DS. However, understanding how small alterations in the steady state transcript levels for <2% of human genes can disrupt development and function of essentially every cell presents a more complicated problem. Mouse models that recapitulate specific aspects of DS have been used to identify changes in brain morphogenesis and function. Here we provide a few examples of how trisomy for specific genes affects the development of the cortex and cerebellum to illustrate how gene dosage effects might contribute to divergence between the trisomic and euploid brains. PMID:22169531

  10. Early Child Development: A Framework for Collaboration

    National Research Council Canada - National Science Library

    Young, Mary Eming

    The convergence of knowledge from neuroscience, social science and economics on the importance of early life or experiences on brain development has tremendous implication on the future of societies...

  11. Environmental impacts on the developing CNS: CD15, NCAM-L1, and GFAP expression in rat neonates exposed to hypergravity (United States)

    Sulkowski, G. M.; Li, G.-H.; Sajdel-Sulkowska, E. M.


    cerebellar mass does not significantly differ between HG and SC neonates. A maximal decrease in expression of GFAP was observed in HG males on P6, coinciding with maximal change in their cerebellar mass. Altered expression of cerebellar proteins is likely to affect a number of developmental processes and contribute to the structural and functional alterations seen in the CNS developing under altered gravity. Our data suggest that both cerebellar development and its response to gravitational manipulations differ in males and females.

  12. Coordinated Noninvasive Studies (CNS) Project (United States)


    made by Neuroscience , and offers a variety of testing options, including evoked-potential testing sampling several levels of the CNS via several...designing the qEEG test series to be included in the CNS Project. Testing for this project will be conducted using the Dept of Neurology’s Neuroscience Brain...Discrimination of Multisyllabic Sequences by Young Infants (Roanne Karzon, Ph.D. Dissertation, 1982) Hypnosis and Its Relationship to Right Hemisphere

  13. Early development of the aplacophoran mollusc Chaetoderma

    DEFF Research Database (Denmark)

    Nielsen, Claus; Haszprunar, Gerhard; Ruthensteiner, Bernhard


    The early development of the trochophore larva of the aplacophoran Chaetoderma nitidulum (Mollusca: Caudofoveata = Chaetodermomorpha) is described using scanning and transmission electron microscopy and using fluorescence staining and confocal laser scanning microscopy of the muscle system. The m...... of the early anlagen of the circular body wall muscles does not show the anterior-posterior mode of formation that is typical for annelids, thus strengthening the hypothesis of a non-segmented ancestry of Mollusca....

  14. Early Brain Development Research Review and Update (United States)

    Schiller, Pam


    Thanks to imaging technology used in neurobiology, people have access to useful and critical information regarding the development of the human brain. This information allows them to become much more effective in helping children in their early development. In fact, when people base their practices on the findings from medical science research,…

  15. Early development of the human pelvic diaphragm

    NARCIS (Netherlands)

    Koch, Wijnandus Franciscus Robertus Maria


    The last decade an increasing interest in the pelvic floor can be observed in medical sciences. The lack of data on the development of the human pelvic floor is striking. The early development of the human pelvic diaphragm was studied. Materials and methodsUse was made of 38 human embryos and

  16. Teacher Knowledge Development in Early Field Experiences (United States)

    Ingersoll, Casey; Jenkins, Jayne M.; Lux, Karen


    Investigation of physical education preservice teacher knowledge development has been primarily limited to study of a single semester of early field experience (EFE), with findings from these investigations driving EFE design. The purpose of this research was to investigate what types of knowledge develop and how knowledge evolves and interacts to…

  17. Early and Late Rate of Force Development

    DEFF Research Database (Denmark)

    Andersen, Lars L; Andersen, Jesper L; Zebis, Mette K


    The objective of this study is to investigate the potentially opposing influence of qualitative and quantitative muscular adaptations in response to high-intensity resistance training on contractile rate of force development (RFD) in the early (200 ms) of rising muscle force. Fifteen healthy young...... the vastus lateralis. The main findings were that RFD in the late phase of rising muscle force increased in response to resistance training whereas early RFD remained unchanged and early relative RFD (i.e., RFD/MVC) decreased. Quantitatively, muscle fiber cross-sectional area and MVC increased whereas......-intensity resistance training due to differential influences of qualitative and quantitative muscular adaptations on early and later phases of rising muscle force....

  18. Considerations for an Integrated UAS CNS Architecture (United States)

    Templin, Fred L.; Jain, Raj; Sheffield, Greg; Taboso-Bellesteros, Pedro; Ponchak, Denise


    The National Aeronautics and Space Administration (NASA) Glenn Research Center (GRC) is investigating revolutionary and advanced universal, reliable, always available, cyber secure and affordable Communication, Navigation, Surveillance (CNS) options for all altitudes of UAS operations. In Spring 2015, NASA issued a Call for Proposals under NASA Research Announcements (NRA) NNH15ZEA001N, Amendment 7 Subtopic 2.4. Boeing was selected to conduct a study with the objective to determine the most promising candidate technologies for Unmanned Air Systems (UAS) air-to-air and air-to-ground data exchange and analyze their suitability in a post-NextGen NAS environment. The overall objectives are to develop UAS CNS requirements and then develop architectures that satisfy the requirements for UAS in both controlled and uncontrolled air space. This contract is funded under NASAs Aeronautics Research Mission Directorates (ARMD) Aviation Operations and Safety Program (AOSP) Safe Autonomous Systems Operations (SASO) project and proposes technologies for the Unmanned Air Systems Traffic Management (UTM) service.There is a need for accommodating large-scale populations of Unmanned Air Systems (UAS) in the national air space. Scale obviously impacts capacity planning for Communication, Navigation, and Surveillance (CNS) technologies. For example, can wireless communications data links provide the necessary capacity for accommodating millions of small UASs (sUAS) nationwide? Does the communications network provide sufficient Internet Protocol (IP) address space to allow air traffic control to securely address both UAS teams as a whole as well as individual UAS within each team? Can navigation and surveillance approaches assure safe route planning and safe separation of vehicles even in crowded skies?Our objective is to identify revolutionary and advanced CNS alternatives supporting UASs operating at all altitudes and in all airspace while accurately navigating in the absence of

  19. The Role of Rho GTPase Proteins in CNS Neuronal Migration (United States)

    Govek, Eve-Ellen; Hatten, Mary E.; Van Aelst, Linda


    The architectonics of the mammalian brain arise from a remarkable range of directed cell migrations, which orchestrate the emergence of cortical neuronal layers and pattern brain circuitry. At different stages of cortical histogenesis, specific modes of cell motility are essential to the stepwise formation of cortical architecture. These movements range from interkinetic nuclear movements at the ventricular zone (VZ), to migrations of early-born, postmitotic polymorphic cells into the preplate, to the radial migration of precursors of cortical output neurons across the thickening cortical wall, and the vast, tangential migrations of interneurons from the basal forebrain into the emerging cortical layers. In all cases, acto-myosin motors act in concert with cell adhesion receptor systems to provide the force and traction needed for forward movement. As key regulators of actin and microtubule cytoskeletons, cell polarity, and adhesion, the Rho GTPases play a critical role in CNS neuronal migration. This review will focus on the different types of migration in the developing neocortex and cerebellar cortex, and the role of the Rho GTPases, their regulators and effectors in these CNS migrations, with particular emphasis on their involvement in radial migration. PMID:21557504

  20. Early executive function predicts reasoning development. (United States)

    Richland, Lindsey E; Burchinal, Margaret R


    Analogical reasoning is a core cognitive skill that distinguishes humans from all other species and contributes to general fluid intelligence, creativity, and adaptive learning capacities. Yet its origins are not well understood. In the study reported here, we analyzed large-scale longitudinal data from the Study of Early Child Care and Youth Development to test predictors of growth in analogical-reasoning skill from third grade to adolescence. Our results suggest an integrative resolution to the theoretical debate regarding contributory factors arising from smaller-scale, cross-sectional experiments on analogy development. Children with greater executive-function skills (both composite and inhibitory control) and vocabulary knowledge in early elementary school displayed higher scores on a verbal analogies task at age 15 years, even after adjusting for key covariates. We posit that knowledge is a prerequisite to analogy performance, but strong executive-functioning resources during early childhood are related to long-term gains in fundamental reasoning skills.

  1. Bioecological Theory, Early Child Development and the Validation of the Population-Level Early Development Instrument (United States)

    Guhn, Martin; Goelman, Hillel


    The Early Development Instrument (EDI; Janus and Offord in "Canadian Journal of Behavioural Science" 39:1-22, 2007) project is a Canadian population-level, longitudinal research project, in which teacher ratings of Kindergarten children's early development and wellbeing are linked to health and academic achievement variables at the…

  2. VIIP: Central Nervous System (CNS) Modeling (United States)

    Vera, Jerry; Mulugeta, Lealem; Nelson, Emily; Raykin, Julia; Feola, Andrew; Gleason, Rudy; Samuels, Brian; Ethier, C. Ross; Myers, Jerry


    Current long-duration missions to the International Space Station and future exploration-class missions beyond low-Earth orbit expose astronauts to increased risk of Visual Impairment and Intracranial Pressure (VIIP) syndrome. It has been hypothesized that the headward shift of cerebrospinal fluid (CSF) and blood in microgravity may cause significant elevation of intracranial pressure (ICP), which in turn may then induce VIIP syndrome through interaction with various biomechanical pathways. However, there is insufficient evidence to confirm this hypothesis. In this light, we are developing lumped-parameter models of fluid transport in the central nervous system (CNS) as a means to simulate the influence of microgravity on ICP. The CNS models will also be used in concert with the lumped parameter and finite element models of the eye described in the related IWS works submitted by Nelson et al., Feola et al. and Ethier et al.


    African Journals Online (AJOL)

    Research on poliomyelitis, benign histoplasmosis, dental caries and certain other diseases. (Davis 1963 .... The skin became sensitive to touch very early. It was ..... parts of the body. The development of the ears, toes, incisors and eyes were studied and response to sound became apparent after about two weeks. Although ...

  4. A Development Systems Model for Early Intervention. (United States)

    Guralnick, Michael J.


    A rationale for and components of a development systems model are presented to guide early intervention programs. Core principles emphasizing a developmental framework, integration, and inclusion are expressed in the context of a multicomponent interactive system. The model's focus on maximizing family patterns of interaction by addressing…

  5. Merlin inhibits neurite outgrowth in the CNS. (United States)

    Schulz, Alexander; Geissler, Katja J; Kumar, Sujeet; Leichsenring, Gregor; Morrison, Helen; Baader, Stephan L


    The neurofibromatosis type 2 gene product merlin is known to provoke gliogenic tumors as a result of its mutagenic loss. Merlin's physiological anti-mitogenic function makes it unique among its ezrin-radixin-moesin (ERM) family members. Although ERM proteins and merlin are known to be expressed in glial cells of the peripheral nervous system and CNS, the neuronal expression pattern and function of merlin have been less well investigated. We report here expression of merlin in developing and mature neurons of the murine CNS. Within cerebellar Purkinje cells (PCs), merlin was localized in the soma, sprouting dendrites and axons. Merlin expression in PCs was high during the period of initial dendrite regression and declined during later phases of dendrite elongation. Consistently, merlin expression in vivo was increased in Engrailed-2-overexpressing PCs, which are characterized by a reduced dendritic extension. Furthermore, overexpression of merlin in dissociated cerebellar cultures and in neurogenic P19 cells caused a significant decline in neurite outgrowth, while, conversely, inhibition of merlin expression increased process formation. This effect was dependent on phosphorylation of serine 518 and involved the inactivation of the growth-promoting GTPase Rac. We thus provide evidence that merlin plays a pivotal role in controlling the neuronal wiring in the developing CNS.

  6. Augmenting CNS glucocerebrosidase activity as a therapeutic strategy for parkinsonism and other Gaucher-related synucleinopathies. (United States)

    Sardi, S Pablo; Clarke, Jennifer; Viel, Catherine; Chan, Monyrath; Tamsett, Thomas J; Treleaven, Christopher M; Bu, Jie; Sweet, Lindsay; Passini, Marco A; Dodge, James C; Yu, W Haung; Sidman, Richard L; Cheng, Seng H; Shihabuddin, Lamya S


    Mutations of GBA1, the gene encoding glucocerebrosidase, represent a common genetic risk factor for developing the synucleinopathies Parkinson disease (PD) and dementia with Lewy bodies. PD patients with or without GBA1 mutations also exhibit lower enzymatic levels of glucocerebrosidase in the central nervous system (CNS), suggesting a possible link between the enzyme and the development of the disease. Previously, we have shown that early treatment with glucocerebrosidase can modulate α-synuclein aggregation in a presymptomatic mouse model of Gaucher-related synucleinopathy (Gba1(D409V/D409V)) and ameliorate the associated cognitive deficit. To probe this link further, we have now evaluated the efficacy of augmenting glucocerebrosidase activity in the CNS of symptomatic Gba1(D409V/D409V) mice and in a transgenic mouse model overexpressing A53T α-synuclein. Adeno-associated virus-mediated expression of glucocerebrosidase in the CNS of symptomatic Gba1(D409V/D409V) mice completely corrected the aberrant accumulation of the toxic lipid glucosylsphingosine and reduced the levels of ubiquitin, tau, and proteinase K-resistant α-synuclein aggregates. Importantly, hippocampal expression of glucocerebrosidase in Gba1(D409V/D409V) mice (starting at 4 or 12 mo of age) also reversed their cognitive impairment when examined using a novel object recognition test. Correspondingly, overexpression of glucocerebrosidase in the CNS of A53T α-synuclein mice reduced the levels of soluble α-synuclein, suggesting that increasing the glycosidase activity can modulate α-synuclein processing and may modulate the progression of α-synucleinopathies. Hence, increasing glucocerebrosidase activity in the CNS represents a potential therapeutic strategy for GBA1-related and non-GBA1-associated synucleinopathies, including PD.

  7. Early social cognition : development and Influences


    Mink, Daniela


    This dissertation investigated the development of early social-cognitive development in the first three years of life. While for a long time research on Theory of Mind (ToM), i.e. the ability to attribute mental states as wishes, intentions, and beliefs to self and others, has focused on preschool age, in recent years also earlier social-cognitive development has gained attention. The assumption of continuity in social-cognitive development is one question we considered in the present work. M...

  8. Early embryonic development of the central nervous system in the Australian crayfish and the Marbled crayfish (Marmorkrebs). (United States)

    Vilpoux, K; Sandeman, R; Harzsch, S


    This study sets out to provide a systematic analysis of the development of the primordial central nervous system (CNS) in embryos of two decapod crustaceans, the Australian crayfish Cherax destructor (Malacostraca, Decapoda, Astacida) and the parthenogenetic Marbled crayfish (Marmorkrebs, Malacostraca, Decapoda, Astacida) by histochemical labelling with phalloidin, a general marker for actin. One goal of our study was to examine the neurogenesis in these two organisms with a higher temporal resolution than previous studies did. The second goal was to explore if there are any developmental differences between the parthenogenetic Marmorkrebs and the sexually reproducing Australian crayfish. We found that in the embryos of both species the sequence of neurogenetic events and the architecture of the embryonic CNS are identical. The naupliar neuromeres proto-, deuto-, tritocerebrum, and the mandibular neuromeres emerge simultaneously. After this "naupliar brain" has formed, there is a certain time lag before the maxilla one primordium develops and before the more caudal neuromeres follow sequentially in the characteristic anterior-posterior gradient. Because the malacostracan egg-nauplius represents a re-capitulation of a conserved ancestral information, which is expressed during development, we speculate that the naupliar brain also conserves an ancestral piece of information on how the brain architecture of an early crustacean or even arthropod ancestor may have looked like. Furthermore, we compare the architecture of the embryonic crayfish CNS to that of the brain and thoracic neuromeres in insects and discuss the similarities and differences that we found against an evolutionary background.

  9. Breastfeeding, parenting, and early cognitive development. (United States)

    Gibbs, Benjamin G; Forste, Renata


    To explain why breastfeeding is associated with children's cognitive development. By using a nationally representative longitudinal survey of early childhood (N = 7500), we examined how breastfeeding practices, the early introduction of solid foods, and putting an infant to bed with a bottle were associated with cognitive development across early childhood. We also explored whether this link can be explained by parenting behaviors and maternal education. There is a positive relationship between predominant breastfeeding for 3 months or more and child reading skills, but this link is the result of cognitively supportive parenting behaviors and greater levels of education among women who predominantly breastfed. We found little-to-no relationship between infant feeding practices and the cognitive development of children with less-educated mothers. Instead, reading to a child every day and being sensitive to a child's development were significant predictors of math and reading readiness outcomes. Although breastfeeding has important benefits in other settings, the encouragement of breastfeeding to promote school readiness does not appear to be a key intervention point. Promoting parenting behaviors that improve child cognitive development may be a more effective and direct strategy for practitioners to adopt, especially for disadvantaged children. Copyright © 2014 Mosby, Inc. All rights reserved.

  10. Genetic models for CNS inflammation

    DEFF Research Database (Denmark)

    Owens, T; Wekerle, H; Antel, J


    The use of transgenic technology to over-express or prevent expression of genes encoding molecules related to inflammation has allowed direct examination of their role in experimental disease. This article reviews transgenic and knockout models of CNS demyelinating disease, focusing primarily...

  11. Nurturing care: promoting early childhood development. (United States)

    Britto, Pia R; Lye, Stephen J; Proulx, Kerrie; Yousafzai, Aisha K; Matthews, Stephen G; Vaivada, Tyler; Perez-Escamilla, Rafael; Rao, Nirmala; Ip, Patrick; Fernald, Lia C H; MacMillan, Harriet; Hanson, Mark; Wachs, Theodore D; Yao, Haogen; Yoshikawa, Hirokazu; Cerezo, Adrian; Leckman, James F; Bhutta, Zulfiqar A


    The UN Sustainable Development Goals provide a historic opportunity to implement interventions, at scale, to promote early childhood development. Although the evidence base for the importance of early childhood development has grown, the research is distributed across sectors, populations, and settings, with diversity noted in both scope and focus. We provide a comprehensive updated analysis of early childhood development interventions across the five sectors of health, nutrition, education, child protection, and social protection. Our review concludes that to make interventions successful, smart, and sustainable, they need to be implemented as multi-sectoral intervention packages anchored in nurturing care. The recommendations emphasise that intervention packages should be applied at developmentally appropriate times during the life course, target multiple risks, and build on existing delivery platforms for feasibility of scale-up. While interventions will continue to improve with the growth of developmental science, the evidence now strongly suggests that parents, caregivers, and families need to be supported in providing nurturing care and protection in order for young children to achieve their developmental potential. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Early development and regression in Rett syndrome. (United States)

    Lee, J Y L; Leonard, H; Piek, J P; Downs, J


    This study utilized developmental profiling to examine symptoms in 14 girls with genetically confirmed Rett syndrome and whose families were participating in the Australian Rett syndrome or InterRett database. Regression was mostly characterized by loss of hand and/or communication skills (13/14) except one girl demonstrated slowing of skill development. Social withdrawal and inconsolable crying often developed simultaneously (9/14), with social withdrawal for shorter duration than inconsolable crying. Previously acquired gross motor skills declined in just over half of the sample (8/14), mostly observed as a loss of balance. Early abnormalities such as vomiting and strabismus were also seen. Our findings provide additional insight into the early clinical profile of Rett syndrome. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. QCD development in the early universe

    Energy Technology Data Exchange (ETDEWEB)

    Gromov, N. A., E-mail: [Komi Science Center of the Ural Division of the Russian Academy of Sciences, Department of Mathematics (Russian Federation)


    The high-energy limit of Quantum Chromodynamics is generated by the contraction of its gauge groups. Contraction parameters are taken identical with those of the Electroweak Model and tend to zero when energy increases. At the infinite energy limit all quarks lose masses and have only one color degree of freedom. The limit model represents the development of Quantum Chromodynamics in the early Universe from the Big Bang up to the end of several milliseconds.

  14. The developing hypopharyngeal microbiota in early life

    DEFF Research Database (Denmark)

    Mortensen, Martin Steen; Brejnrod, Asker Daniel; Roggenbuck, Michael


    that majority of the hypopharyngeal microbiota of healthy infants belong to each individual's core microbiota and we demonstrate five distinct community pneumotypes. Four of these pneumotypes are dominated by the genera Staphylococcus, Streptococcus, Moraxella, and Corynebacterium, respectively. Furthermore, we...... time. CONCLUSIONS: Our findings demonstrate a consolidation of the population of indigenous bacteria in healthy airways and indicate distinct trajectories in the early development of the hypopharyngeal microbiota....

  15. CNS relapse in a low risk acute promyelocytic leukemia patient treated with ATRA-based regimen: is there a role for prophylactic CNS therapy in acute promyelocytic leukemia?


    Gangadharan, K. V.; Prabhu, Raghuveer; Mampilly, Neena


    Though the incidence of CNS relapse in acute promyelocytic leukemia (AML-M3 FAB classification) has increased following the advent of all-trans retinoic acid (ATRA), still CNS relapse accounts for only 2–3% of all relapses in AML-M3 trated with standard ATRA plus chemotherapy regimen. We report a case of low risk AML-M3 treated with standard therapy, developing CNS relapse while on maintenance therapy with ATRA + 6-mercaptopurine (6-MP) + methotrexate (MTX).

  16. Clinical and Genetic Risk Prediction of Subsequent CNS Tumors in Survivors of Childhood Cancer: A Report From the COG ALTE03N1 Study. (United States)

    Wang, Xuexia; Sun, Can-Lan; Hageman, Lindsey; Smith, Kandice; Singh, Purnima; Desai, Sunil; Hawkins, Douglas S; Hudson, Melissa M; Mascarenhas, Leo; Neglia, Joseph P; Oeffinger, Kevin C; Ritchey, A Kim; Robison, Leslie L; Villaluna, Doojduen; Landier, Wendy; Bhatia, Smita


    Purpose Survivors of childhood cancer treated with cranial radiation therapy are at risk for subsequent CNS tumors. However, significant interindividual variability in risk suggests a role for genetic susceptibility and provides an opportunity to identify survivors of childhood cancer at increased risk for these tumors. Methods We curated candidate genetic variants from previously published studies in adult-onset primary CNS tumors and replicated these in survivors of childhood cancer with and without subsequent CNS tumors (82 participants and 228 matched controls). We developed prediction models to identify survivors at high or low risk for subsequent CNS tumors and validated these models in an independent matched case-control sample (25 participants and 54 controls). Results We demonstrated an association between six previously published single nucleotide polymorphisms (rs15869 [ BRCA2], rs1805389 [ LIG4], rs8079544 [ TP53], rs25489 [ XRCC1], rs1673041 [ POLD1], and rs11615 [ ERCC1]) and subsequent CNS tumors in survivors of childhood cancer. Including genetic variants in a Final Model containing age at primary cancer, sex, and cranial radiation therapy dose yielded an area under the curve of 0.81 (95% CI, 0.76 to 0.86), which was superior ( P = .002) to the Clinical Model (area under the curve, 0.73; 95% CI, 0.66 to 0.80). The prediction model was successfully validated. The sensitivity and specificity of predicting survivors of childhood cancer at highest or lowest risk of subsequent CNS tumors was 87.5% and 83.5%, respectively. Conclusion It is possible to identify survivors of childhood cancer at high or low risk for subsequent CNS tumors on the basis of genetic and clinical information. This information can be used to inform surveillance for early detection of subsequent CNS tumors.

  17. The Gut-Brain Axis, BDNF, NMDA and CNS Disorders. (United States)

    Maqsood, Raeesah; Stone, Trevor W


    Gastro-intestinal (GI) microbiota and the 'gut-brain axis' are proving to be increasingly relevant to early brain development and the emergence of psychiatric disorders. This review focuses on the influence of the GI tract on Brain-Derived Neurotrophic Factor (BDNF) and its relationship with receptors for N-methyl-D-aspartate (NMDAR), as these are believed to be involved in synaptic plasticity and cognitive function. NMDAR may be associated with the development of schizophrenia and a range of other psychopathologies including neurodegenerative disorders, depression and dementias. An analysis of the routes and mechanisms by which the GI microbiota contribute to the pathophysiology of BDNF-induced NMDAR dysfunction could yield new insights relevant to developing novel therapeutics for schizophrenia and related disorders. In the absence of GI microbes, central BDNF levels are reduced and this inhibits the maintenance of NMDAR production. A reduction of NMDAR input onto GABA inhibitory interneurons causes disinhibition of glutamatergic output which disrupts the central signal-to-noise ratio and leads to aberrant synaptic behaviour and cognitive deficits. Gut microbiota can modulate BDNF function in the CNS, via changes in neurotransmitter function by affecting modulatory mechanisms such as the kynurenine pathway, or by changes in the availability and actions of short chain fatty acids (SCFAs) in the brain. Interrupting these cycles by inducing changes in the gut microbiota using probiotics, prebiotics or antimicrobial drugs has been found promising as a preventative or therapeutic measure to counteract behavioural deficits and these may be useful to supplement the actions of drugs in the treatment of CNS disorders.

  18. The developing hypopharyngeal microbiota in early life. (United States)

    Mortensen, Martin Steen; Brejnrod, Asker Daniel; Roggenbuck, Michael; Abu Al-Soud, Waleed; Balle, Christina; Krogfelt, Karen Angeliki; Stokholm, Jakob; Thorsen, Jonathan; Waage, Johannes; Rasmussen, Morten Arendt; Bisgaard, Hans; Sørensen, Søren Johannes


    The airways of healthy humans harbor a distinct microbial community. Perturbations in the microbial community have been associated with disease, yet little is known about the formation and development of a healthy airway microbiota in early life. Our goal was to understand the establishment of the airway microbiota within the first 3 months of life. We investigated the hypopharyngeal microbiota in the unselected COPSAC2010 cohort of 700 infants, using 16S rRNA gene sequencing of hypopharyngeal aspirates from 1 week, 1 month, and 3 months of age. Our analysis shows that majority of the hypopharyngeal microbiota of healthy infants belong to each individual's core microbiota and we demonstrate five distinct community pneumotypes. Four of these pneumotypes are dominated by the genera Staphylococcus, Streptococcus, Moraxella, and Corynebacterium, respectively. Furthermore, we show temporal pneumotype changes suggesting a rapid development towards maturation of the hypopharyngeal microbiota and a significant effect from older siblings. Despite an overall common trajectory towards maturation, individual infants' microbiota are more similar to their own, than to others, over time. Our findings demonstrate a consolidation of the population of indigenous bacteria in healthy airways and indicate distinct trajectories in the early development of the hypopharyngeal microbiota.

  19. Early androgen exposure and human gender development. (United States)

    Hines, Melissa; Constantinescu, Mihaela; Spencer, Debra


    During early development, testosterone plays an important role in sexual differentiation of the mammalian brain and has enduring influences on behavior. Testosterone exerts these influences at times when the testes are active, as evidenced by higher concentrations of testosterone in developing male than in developing female animals. This article critically reviews the available evidence regarding influences of testosterone on human gender-related development. In humans, testosterone is elevated in males from about weeks 8 to 24 of gestation and then again during early postnatal development. Individuals exposed to atypical concentrations of testosterone or other androgenic hormones prenatally, for example, because of genetic conditions or because their mothers were prescribed hormones during pregnancy, have been consistently found to show increased male-typical juvenile play behavior, alterations in sexual orientation and gender identity (the sense of self as male or female), and increased tendencies to engage in physically aggressive behavior. Studies of other behavioral outcomes following dramatic androgen abnormality prenatally are either too small in their numbers or too inconsistent in their results, to provide similarly conclusive evidence. Studies relating normal variability in testosterone prenatally to subsequent gender-related behavior have produced largely inconsistent results or have yet to be independently replicated. For studies of prenatal exposures in typically developing individuals, testosterone has been measured in single samples of maternal blood or amniotic fluid. These techniques may not be sufficiently powerful to consistently detect influences of testosterone on behavior, particularly in the relatively small samples that have generally been studied. The postnatal surge in testosterone in male infants, sometimes called mini-puberty, may provide a more accessible opportunity for measuring early androgen exposure during typical development. This

  20. Radioprotection of mouse CNS endothelial cells in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Lyubimova, N.; Coultas, P.; Martin, R. [Peter McCallum Cancer Institute, Melbourne, VIC (Australia)


    Full text: Radioprotection using the minor groove binding DNA ligand Hoechst 33342 has been demonstrated in vitro, and more recently in vivo, in mouse lung. Intravenous administration was used for the lung studies, and both endothelial and alveolar epithelial cells-showed good up-take. Radiation damage to the endothelial cell population has also been postulated as important in late developing radionecrosis of spinal cord and brain. Endothelial cell density in brain can be readily determined by a fluorescent-histochemical technique. Treatment with a monoamine oxidase inhibitor and subsequent injection with L-DOPA results in an accumulation of dopamine (DA) in CNS endothelial cells. DA is converted to a fluorophore by exposure to paraformaldehyde, and cell numbers assayed by fluorescence microscopy. Earlier studies used this technique to monitor post-irradiation changes in endothelial cell density in rodent brain and showed the loss, within 24 hours, of a sensitive subpopulation comprising about 15% of the endothelial cells. Ten minutes after intravenous injection of Hoechst 33342 (80mg/kg) the ligand is confined by its limited penetration to the endothelial cells in mouse brain. When we irradiated at this time, there was protection against early endothelial cell loss. Ablation of the sensitive subpopulation in unprotected mice takes place over a dose range of 1 to 3 Gy {gamma}-rays, but doses between 12 to 20 Gy are required in the presence of ligand. This protection equates to a very high dose modification factor of about 7 and possibly reflects a suppression of apoptosis in the sensitive endothelial subpopulation. The extent to which there is enhanced survival in the endothelial population as a whole and how the observed protection affects late CNS necrosis development has yet to be determined. However present results clearly show potential for the use of DNA-binding radioprotectors with limited penetration for investigations into the relative significance of

  1. Vegfa Impacts Early Myocardium Development in Zebrafish. (United States)

    Zhu, Diqi; Fang, Yabo; Gao, Kun; Shen, Jie; Zhong, Tao P; Li, Fen


    Vascular endothelial growth factor A (Vegfa) signaling regulates cardiovascular development. However, the cellular mechanisms of Vegfa signaling in early cardiogenesis remain poorly understood. The present study aimed to understand the differential functions and mechanisms of Vegfa signaling in cardiac development. A loss-of-function approach was utilized to study the effect of Vegfa signaling in cardiogenesis. Both morphants and mutants for vegfaa display defects in cardiac looping and chamber formation, especially the ventricle. Vegfa regulates the heart morphogenesis in a dose-dependent manner. Furthermore, the initial fusion of the bilateral myocardium population is delayed rather than endocardium. The results demonstrate that Vegfa signaling plays a direct impact on myocardium fusion, indicating that it is the initial cause of the heart defects. The heart morphogenesis is regulated by Vegfa in a dose-dependent manner, and later endocardium defects may be secondary to impaired myocardium-endocardium crosstalk.

  2. Vegfa Impacts Early Myocardium Development in Zebrafish

    Directory of Open Access Journals (Sweden)

    Diqi Zhu


    Full Text Available Vascular endothelial growth factor A (Vegfa signaling regulates cardiovascular development. However, the cellular mechanisms of Vegfa signaling in early cardiogenesis remain poorly understood. The present study aimed to understand the differential functions and mechanisms of Vegfa signaling in cardiac development. A loss-of-function approach was utilized to study the effect of Vegfa signaling in cardiogenesis. Both morphants and mutants for vegfaa display defects in cardiac looping and chamber formation, especially the ventricle. Vegfa regulates the heart morphogenesis in a dose-dependent manner. Furthermore, the initial fusion of the bilateral myocardium population is delayed rather than endocardium. The results demonstrate that Vegfa signaling plays a direct impact on myocardium fusion, indicating that it is the initial cause of the heart defects. The heart morphogenesis is regulated by Vegfa in a dose-dependent manner, and later endocardium defects may be secondary to impaired myocardium–endocardium crosstalk.

  3. Decreased Cognitive/CNS Function in Young Adults at Risk for Hypertension: Effects of Sleep Deprivation

    Directory of Open Access Journals (Sweden)

    James A. McCubbin


    Full Text Available Hypertension has been linked to impaired cognitive/CNS function, and some of these changes may precede development of frank essential hypertension. The stress and fatigue of sleep deprivation may exacerbate these cognitive changes in young adults at risk. We hypothesize that individuals at risk for hypertension will show significant declines in cognitive function during a night of sleep deprivation. Fifty-one young adults were recruited for 28-hour total sleep deprivation studies. Hypertension risk was assessed by mildly elevated resting blood pressure and by family history of hypertension. A series of cognitive memory tasks was given at four test sessions across the sleep deprivation period. Although initially comparable in cognitive performance, persons at risk showed larger declines across the night for several indices of working memory, including code substitution, category, and order recall. These results suggest that cognitive/CNS changes may parallel or precede blood pressure dysregulation in the early stages of hypertension development. The role of CNS changes in the etiology of essential hypertension is discussed.

  4. Development of Life on Early Mars (United States)

    Gibson, Everett K.; McKay, David S.; Thomas-Keprta, Kathie L.; Clemett, Simon J.; Wentworth, Susan J.


    Exploration of Mars has begun to unveil the history of the planet. Combinations of remote sensing, in situ compositional measurements and photographic observations have shown Mars had a dynamic and active geologic evolution. Mars geologic evolution encompassed conditions that were suitable for supporting life. A habitable planet must have water, carbon and energy sources along with a dynamic geologic past. Mars meets all of these requirements. The first 600 My of Martian history were ripe for life to develop because of the abundance of (i) Water- as shown by carved canyons and oceans or lakes with the early presence of near surface water shown by precipitated carbonates in ALH84001, well-dated at 3.9 Gy, (ii) Energy from the original accretional processes, a molten core which generated a strong magnetic field leaving a permanent record in the early crust, active volcanism continuing throughout Martian history, and continuing impact processes, (iii) Carbon, water and a likely thicker atmosphere from extensive volcanic outgassing (i.e. H20, CO2, CH4, CO, O2, N2, H2S, SO2, etc.) and (iv) crustal tectonics as revealed by faulting and possible plate movement reflected by the magnetic pattern in the crust [1]. The question arises: "Why would life not develop from these favorable conditions on Mars in its first 600 My?" During this period, environmental near-surface conditions on Mars were more favorable to life than at any later time. Standing bodies of water, precipitation and flowing surface water, and possibly abundant hydrothermal energy would favor the formation of early life. (Even if life developed elsewhere on Earth, Venus, or on other bodies-it was transported to Mars where surface conditions were suitable for life to evolve). The commonly stated requirement that life would need hundreds of millions of year to get started is only an assumption; we know of no evidence that requires such a long interval for the development of life, if the proper habitable

  5. How Early Hormones Shape Gender Development. (United States)

    Berenbaum, Sheri A; Beltz, Adriene M


    Many important psychological characteristics show sex differences, and are influenced by sex hormones at different developmental periods. We focus on the role of sex hormones in early development, particularly the differential effects of prenatal androgens on aspects of gender development. Increasing evidence confirms that prenatal androgens have facilitative effects on male-typed activity interests and engagement (including child toy preferences and adult careers), and spatial abilities, but relatively minimal effects on gender identity. Recent emphasis has been directed to the psychological mechanisms underlying these effects (including sex differences in propulsive movement, and androgen effects on interest in people versus things), and neural substrates of androgen effects (including regional brain volumes, and neural responses to mental rotation, sexually arousing stimuli, emotion, and reward). Ongoing and planned work is focused on understanding the ways in which hormones act jointly with the social environment across time to produce varying trajectories of gender development, and clarifying mechanisms by which androgens affect behaviors. Such work will be facilitated by applying lessons from other species, and by expanding methodology. Understanding hormonal influences on gender development enhances knowledge of psychological development generally, and has important implications for basic and applied questions, including sex differences in psychopathology, women's underrepresentation in science and math, and clinical care of individuals with variations in gender expression.

  6. 45 CFR 1304.21 - Education and early childhood development. (United States)


    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Education and early childhood development. 1304.21... GRANTEE AND DELEGATE AGENCIES Early Childhood Development and Health Services § 1304.21 Education and early childhood development. (a) Child development and education approach for all children. (1) In order...

  7. Early Literacy and Early Numeracy: The Value of Including Early Literacy Skills in the Prediction of Numeracy Development (United States)

    Purpura, David J.; Hume, Laura E.; Sims, Darcey M.; Lonigan, Cristopher J.


    The purpose of this study was to examine whether early literacy skills uniquely predict early numeracy skills development. During the first year of the study, 69 3- to 5-year-old preschoolers were assessed on the Preschool Early Numeracy Skills (PENS) test and the Test of Preschool Early Literacy Skills (TOPEL). Participants were assessed again a…

  8. Communication and community development: early child development programs. (United States)

    Wood, F; Reinhold, A J


    Community-based groups are organized around particular aspects of early childhood development (ECD), such as literacy, parent education, and early childhood activities. In the Colombian national program, community households call upon women to devote a portion of their home to organized child care for minimal material reward. The Indian Child Development Service subsidizes the payment of organizers; and Kenyan parents construct basic preschool facilities, provide school lunches, and subsidize a teacher. In such cases the government plays a subordinate role, while the burden of program maintenance is carried by the community. These programs share the characteristics that children and adults learn side by side; adult learning ranges from women's literacy, to health, organizational issues, or small-scale economic development; a strong cultural component emphasizes mother tongue language learning, indigenous child-rearing practices, and local working models; physical structures are in homes; capacity-building for the adults is central which will be transferred to other spheres of community life. In the remote coastal villages of Colombia, an organization called Promesa works with mothers on designing their preschool children's educational activities. Promesa began to confront other priority needs in the villages, especially in environmental health and malaria control. A 1990 assessment related that participants' pride, self-confidence, and ability to solve problems regarding the healthy development of their children increased; groups learned to make use of the physical, human, and institutional resources from their environments; and participants' children remained in school and performed better. Conclusions from a decade of loose experimentation suggest that through communication community women can be organized to provide basic early education and early childhood activities can help rural children over the cultural barrier of school.

  9. Purpose and Character Development in Early Adolescence. (United States)

    Malin, Heather; Liauw, Indrawati; Damon, William


    Character development in adolescence is of growing interest among psychology researchers and educators, yet there is little consensus about how character should be defined and studied among developmental scientists. In particular, there is no fully developed framework for investigating the developmental relationships among different character strengths. This study examines the developmental relations between purpose and three other key character strengths that emerge during early adolescence: gratitude, compassion, and grit. We analyzed survey (n = 1005, 50.1% female, 24.1% Caucasian, 43.6% African American, 18.9% Hispanic, 11.9% Asian American) and interview (n = 98) data from a longitudinal study of character development among middle school students from the United States. Data were collected over the course of 2 years, with surveys conducted four times at 6-month intervals and interviews conducted twice at 12-month intervals. Data analyses showed small but significant correlations between purpose and each of the other three character strengths under investigation. Interview data revealed patterns in ways that adolescents acted on their purposeful aspirations; and interview analyses identified qualitative differences in expressions of gratitude and compassion between adolescents who were fully purposeful and those who were not. The findings suggest that character development can be better understood by investigating the multidirectional developmental relationships among different character strengths.

  10. Nanomedicines for the Treatment of CNS Diseases. (United States)

    Reynolds, Jessica L; Mahato, Ram I


    Targeting and delivering macromolecular therapeutics to the central nervous system (CNS) has been a major challenge. The blood-brain barrier (BBB) is the main obstacle that must be overcome to allow compounds to reach their targets in the brain. Therefore, much effort has been channelled into improving transport of therapeutics across the BBB and into the CNS including the use of nanoparticles. In this thematic issue, several reviews and original research are presented that address "Nanomedicines for CNS Diseases." The articles in this issue are concentrated on either CNS-HIV disease or CNS tumors. In regards to CNS-HIV disease, there are two reviews that discuss the role of nanoparticles for improving the delivery of HIV therapeutics to the CNS. In addition, there are two original articles focusing on therapies for CNS-HIV, one of them uses nanoparticles for delivery of siRNA specific to a key protein in autophagy to microglia, and another discusses nanoparticle delivery of a soluble mediator to suppress neuroinflammation. Furthermore, a comprehensive review about gene therapy for CNS neurological diseases is also included. Finally, this issue also includes review articles on enhanced drug targeting to CNS tumors. These articles include a review on the use of nanoparticles for CNS tumors, a review on functionalization (ligands) of nanoparticles for drug targeting to the brain tumor by overcoming BBB, and the final review discusses the use of macrophages as a delivery vehicle to CNS tumors. This thematic issue provides a wealth of knowledge on using nanomedicines for CNS diseases.

  11. Sleep disorders in children after treatment for a CNS tumour. (United States)

    Verberne, Lisa M; Maurice-Stam, Heleen; Grootenhuis, Martha A; Van Santen, Hanneke M; Schouten-Van Meeteren, Antoinette Y N


    The long-term survival of children with a central nervous system (CNS) tumour is improving. However, they experience late effects, including altered habits and patterns of sleep. We evaluated the presence and type of sleep disorders and daytime sleepiness in these children, and its associations with clinical characteristics and daily performance (fatigue and psychosocial functioning). In a cross-sectional study at the outpatient clinic of the Emma Children's Hospital AMC (February-June 2010), sleep, fatigue and psychosocial functioning were analysed in 31 CNS tumour patients (mean age: 11.8years; 20 boys) and compared with 78 patients treated for a non-CNS malignancy (mean age: 9.7years; 41 boys) and norm data. Questionnaires applied were the Sleep Disorder Scale for Children, the Epworth Sleepiness Scale, the Pediatric Quality of Life Inventory, and the Strengths and Difficulties Questionnaire. Sleeping habits and endocrine deficiencies were assessed with a self-developed questionnaire. Increased somnolence was found in CNS tumour patients compared with those with a non-CNS malignancy (8.8±2.8 versus 7.5±2.7; P<0.05). Both patient groups reported more problems (P<0.01) than the norm with initiating and maintaining sleep. No specific risk factors were identified for a sleep disorder in CNS tumour patients, but their excessive somnolence was correlated with lower fatigue related quality of life (QoL) (r=-0.78, P<0.001) and worse psychosocial functioning (r=0.63, P<0.001). In conclusion, children treated for a CNS tumour have increased somnolence, significantly increasing fatigue and worsening daily functioning. Further investigation should focus on possibilities to improve sleep quality and diminish fatigue. © 2011 European Sleep Research Society.

  12. Gas Diffusion in the CNS. (United States)

    Rodriguez-Grande, Beatriz; Konsman, Jan-Pieter


    Gases have been long known to have essential physiological functions in the CNS such as respiration or regulation of vascular tone. Since gases have been classically considered to freely diffuse, research in gas biology has so far focused on mechanisms of gas synthesis and gas reactivity, rather than gas diffusion and transport. However, the discovery of gas pores during the last two decades and the characterization of diverse diffusion patterns through different membranes has raised the possibility that modulation of gas diffusion is also a physiologically relevant parameter. Here we review the means of gas movement into and within the brain through "free" diffusion and gas pores, notably aquaporins, discussing the role that gas diffusion may play in the modulation of gas function. We highlight how diffusion is relevant to neuronal signaling, volume transmission, and cerebrovascular control in the case of NO, one of the most extensively studied gases. We point out how facilitated transport can be especially relevant for gases with low permeability in lipid membranes like NH3 and discuss the possible implications of NH3 -permeable channels in physiology and hyperammonemic encephalopathy. We identify novel research questions about how modulation of gas diffusion could intervene in CNS pathologies. This emerging area of research can provide novel and interesting insights in the field of gas biology. © 2017 Wiley Periodicals, Inc.

  13. Nutrition and brain development in early life. (United States)

    Prado, Elizabeth L; Dewey, Kathryn G


    Presented here is an overview of the pathway from early nutrient deficiency to long-term brain function, cognition, and productivity, focusing on research from low- and middle-income countries. Animal models have demonstrated the importance of adequate nutrition for the neurodevelopmental processes that occur rapidly during pregnancy and infancy, such as neuron proliferation and myelination. However, several factors influence whether nutrient deficiencies during this period cause permanent cognitive deficits in human populations, including the child's interaction with the environment, the timing and degree of nutrient deficiency, and the possibility of recovery. These factors should be taken into account in the design and interpretation of future research. Certain types of nutritional deficiency clearly impair brain development, including severe acute malnutrition, chronic undernutrition, iron deficiency, and iodine deficiency. While strategies such as salt iodization and micronutrient powders have been shown to improve these conditions, direct evidence of their impact on brain development is scarce. Other strategies also require further research, including supplementation with iron and other micronutrients, essential fatty acids, and fortified food supplements during pregnancy and infancy. © 2014 International Life Sciences Institute.

  14. GFP-Mutant Human Tau Transgenic Mice Develop Tauopathy Following CNS Injections of Alzheimer's Brain-Derived Pathological Tau or Synthetic Mutant Human Tau Fibrils. (United States)

    Gibbons, Garrett S; Banks, Rachel A; Kim, Bumjin; Xu, Hong; Changolkar, Lakshmi; Leight, Susan N; Riddle, Dawn M; Li, Chi; Gathagan, Ronald J; Brown, Hannah J; Zhang, Bin; Trojanowski, John Q; Lee, Virginia M-Y


    Neurodegenerative proteinopathies characterized by intracellular aggregates of tau proteins, termed tauopathies, include Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD) with tau pathology (FTLD-tau), and related disorders. Pathological tau proteins derived from human AD brains (AD-tau) act as proteopathic seeds that initiate the templated aggregation of soluble tau upon intracerebral injection into tau transgenic (Tg) and wild-type mice, thereby modeling human tau pathology. In this study, we found that aged Tg mice of both sexes expressing human tau proteins harboring a pathogenic P301L MAPT mutation labeled with green fluorescent protein (T40PL-GFP Tg mouse line) exhibited hyperphosphorylated tau mislocalized to the somatodentritic domain of neurons, but these mice did not develop de novo insoluble tau aggregates, which are characteristic of human AD and related tauopathies. However, intracerebral injections of either T40PL preformed fibrils (PFFs) or AD-tau seeds into T40PL-GFP mice induced abundant intraneuronal pathological inclusions of hyperphosphorylated T40PL-GFP. These injections of pathological tau resulted in the propagation of tau pathology from the injection site to neuroanatomically connected brain regions, and these tau inclusions consisted of both T40PL-GFP and WT endogenous mouse tau. Primary neurons cultured from the brains of neonatal T40PL-GFP mice provided an informative in vitro model for examining the uptake and localization of tau PFFs. These findings demonstrate the seeded aggregation of T40PL-GFP in vivo by synthetic PFFs and human AD-tau and the utility of this system to study the neuropathological spread of tau aggregates.SIGNIFICANCE STATEMENT The stereotypical spread of pathological tau protein aggregates have recently been attributed to the transmission of proteopathic seeds. Despite the extensive use of transgenic mouse models to investigate the propagation of tau pathology in vivo, details of the aggregation

  15. microRNAs in CNS disorders

    DEFF Research Database (Denmark)

    Kocerha, Jannet; Kauppinen, Sakari; Wahlestedt, Claes


    RNAs (miRNAs) have been identified in the mammalian central nervous system (CNS) and are reported to mediate pivotal roles in many aspects of neuronal functions. Disruption of miRNA-based post-transcriptional regulation has been implicated in a range of CNS disorders as one miRNA is predicted to impact...... of miRNAs in Alzheimer's disease and schizophrenia, including the characterization of their downstream CNS mRNA targets, such as beta-secretase (BACE1) and calmodulin-dependent protein kinase II (CaMKII). Here, we present an overview of the current progress in miRNA research related to CNS disorders...

  16. Early Years Practitioners' Views on Early Personal, Social and Emotional Development (United States)

    Aubrey, Carol; Ward, Karen


    Current policy guidance stresses the need for early identification of obstacles to learning and appropriate intervention. New standards for learning (Early Years Foundation Stage) place personal, social and emotional development (PSED) as central to learning and development. This paper reports a survey and follow-up interviews with early years…

  17. Pericytes Stimulate Oligodendrocyte Progenitor Cell Differentiation during CNS Remyelination

    Directory of Open Access Journals (Sweden)

    Alerie Guzman De La Fuente


    Full Text Available The role of the neurovascular niche in CNS myelin regeneration is incompletely understood. Here, we show that, upon demyelination, CNS-resident pericytes (PCs proliferate, and parenchymal non-vessel-associated PC-like cells (PLCs rapidly develop. During remyelination, mature oligodendrocytes were found in close proximity to PCs. In Pdgfbret/ret mice, which have reduced PC numbers, oligodendrocyte progenitor cell (OPC differentiation was delayed, although remyelination proceeded to completion. PC-conditioned medium accelerated and enhanced OPC differentiation in vitro and increased the rate of remyelination in an ex vivo cerebellar slice model of demyelination. We identified Lama2 as a PC-derived factor that promotes OPC differentiation. Thus, the functional role of PCs is not restricted to vascular homeostasis but includes the modulation of adult CNS progenitor cells involved in regeneration.

  18. A stochastic model for early placental development.

    KAUST Repository

    Cotter, Simon L


    In the human, placental structure is closely related to placental function and consequent pregnancy outcome. Studies have noted abnormal placental shape in small-for-gestational-age infants which extends to increased lifetime risk of cardiovascular disease. The origins and determinants of placental shape are incompletely understood and are difficult to study in vivo. In this paper, we model the early development of the human placenta, based on the hypothesis that this is driven by a chemoattractant effect emanating from proximal spiral arteries in the decidua. We derive and explore a two-dimensional stochastic model, and investigate the effects of loss of spiral arteries in regions near to the cord insertion on the shape of the placenta. This model demonstrates that disruption of spiral arteries can exert profound effects on placental shape, particularly if this is close to the cord insertion. Thus, placental shape reflects the underlying maternal vascular bed. Abnormal placental shape may reflect an abnormal uterine environment, predisposing to pregnancy complications. Through statistical analysis of model placentas, we are able to characterize the probability that a given placenta grew in a disrupted environment, and even able to distinguish between different disruptions.

  19. Neuroimaging, a new tool for investigating the effects of early diet on cognitive and brain development. (United States)

    Isaacs, Elizabeth B


    Nutrition is crucial to the initial development of the central nervous system (CNS), and then to its maintenance, because both depend on dietary intake to supply the elements required to develop and fuel the system. Diet in early life is often seen in the context of "programming" where a stimulus occurring during a vulnerable period can have long-lasting or even lifetime effects on some aspect of the organism's structure or function. Nutrition was first shown to be a programming stimulus for growth, and then for cognitive behavior, in animal studies that were able to employ methods that allowed the demonstration of neural effects of early nutrition. Such research raised the question of whether nutrition could also programme cognition/brain structure in humans. Initial studies of cognitive effects were observational, usually conducted in developing countries where the presence of confounding factors made it difficult to interpret the role of nutrition in the cognitive deficits that were seen. Attributing causality to nutrition required randomized controlled trials (RCTs) and these, often in developed countries, started to appear around 30 years ago. Most demonstrated convincingly that early nutrition could affect subsequent cognition. Until the advent of neuroimaging techniques that allowed in vivo examination of the brain, however, we could determine very little about the neural effects of early diet in humans. The combination of well-designed trials with neuroimaging tools means that we are now able to pose and answer questions that would have seemed impossible only recently. This review discusses various neuroimaging methods that are suitable for use in nutrition studies, while pointing out some of the limitations that they may have. The existing literature is small, but examples of studies that have used these methods are presented. Finally, some considerations that have arisen from previous studies, as well as suggestions for future research, are discussed.

  20. Parental Obesity and Early Childhood Development. (United States)

    Yeung, Edwina H; Sundaram, Rajeshwari; Ghassabian, Akhgar; Xie, Yunlong; Buck Louis, Germaine


    Previous studies identified associations between maternal obesity and childhood neurodevelopment, but few examined paternal obesity despite potentially distinct genetic/epigenetic effects related to developmental programming. Upstate KIDS (2008-2010) recruited mothers from New York State (excluding New York City) at ∼4 months postpartum. Parents completed the Ages and Stages Questionnaire (ASQ) when their children were 4, 8, 12, 18, 24, 30, and 36 months of age corrected for gestation. The ASQ is validated to screen for delays in 5 developmental domains (ie, fine motor, gross motor, communication, personal-social functioning, and problem-solving ability). Analyses included 3759 singletons and 1062 nonrelated twins with ≥1 ASQs returned. Adjusted odds ratios (aORs) and 95% confidence intervals were estimated by using generalized linear mixed models accounting for maternal covariates (ie, age, race, education, insurance, marital status, parity, and pregnancy smoking). Compared with normal/underweight mothers (BMI obese mothers (26% with BMI ≥30) had increased odds of failing the fine motor domain (aOR 1.67; confidence interval 1.12-2.47). The association remained after additional adjustment for paternal BMI (1.67; 1.11-2.52). Paternal obesity (29%) was associated with increased risk of failing the personal-social domain (1.75; 1.13-2.71), albeit attenuated after adjustment for maternal obesity (aOR 1.71; 1.08-2.70). Children whose parents both had BMI ≥35 were likely to additionally fail the problem-solving domain (2.93; 1.09-7.85). Findings suggest that maternal and paternal obesity are each associated with specific delays in early childhood development, emphasizing the importance of family information when screening child development. Copyright © 2017 by the American Academy of Pediatrics.

  1. The emergence of functional architecture during early brain development

    NARCIS (Netherlands)

    Keunen, Kristin|info:eu-repo/dai/nl/413751953; Counsell, Serena J.; Benders, Manon J.N.L.|info:eu-repo/dai/nl/185214266


    Early human brain development constitutes a sequence of intricate processes resulting in the ontogeny of functionally operative neural circuits. Developmental trajectories of early brain network formation are genetically programmed and can be modified by epigenetic and environmental influences. Such

  2. Biomarkers for CNS involvement in pediatric lupus (United States)

    Rubinstein, Tamar B; Putterman, Chaim; Goilav, Beatrice


    CNS disease, or central neuropsychiatric lupus erythematosus (cNPSLE), occurs frequently in pediatric lupus, leading to significant morbidity and poor long-term outcomes. Diagnosing cNPSLE is especially difficult in pediatrics; many current diagnostic tools are invasive and/or costly, and there are no current accepted screening mechanisms. The most complicated aspect of diagnosis is differentiating primary disease from other etiologies; research to discover new biomarkers is attempting to address this dilemma. With many mechanisms involved in the pathogenesis of cNPSLE, biomarker profiles across several modalities (molecular, psychometric and neuroimaging) will need to be used. For the care of children with lupus, the challenge will be to develop biomarkers that are accessible by noninvasive measures and reliable in a pediatric population. PMID:26079959

  3. Transplanting oligodendrocyte progenitors into the adult CNS

    Energy Technology Data Exchange (ETDEWEB)

    Franklin, R.J.M.; Blakemore, W.F. [Medical Research Council, Cambridge (United Kingdom)]|[Cambridge Univ. (United Kingdom). Dept. of Clinical Veterinary Medicine


    This review covers a number of aspects of the behaviour of oligodendrocyte progenitors following transplantation into the adult CNS. First, an account is given of the ability of transplanted oligodendrocyte progenitors, grown in tissue culture in the presence of PDGF and bFGF, to extensively remyelinate focal areas of persistent demyelination. Secondly, we describe how transplanted clonal cell lines of oligodendrocyte progenitors will differentiate in to astrocytes as will oligodendrocytes following transplantation into pathological environments in which both oligodendrocytes and astrocytes are absent, thereby manifesting the bipotentially demonstrable in vitro but not during development. Finally, a series of studies examining the migratory behaviour of transplanted oligodendrocyte progenitors (modelled using the oligodendrocyte progenitor cell line CG4) are described. (author).

  4. Delivery of therapeutic peptides and proteins to the CNS. (United States)

    Salameh, Therese S; Banks, William A


    Peptides and proteins have potent effects on the brain after their peripheral administration, suggesting that they may be good substrates for the development of CNS therapeutics. Major hurdles to such development include their relation to the blood-brain barrier (BBB) and poor pharmacokinetics. Some peptides cross the BBB by transendothelial diffusion and others cross in the blood-to-brain direction by saturable transporters. Some regulatory proteins are also transported across the BBB and antibodies can enter the CNS via the extracellular pathways. Glycoproteins and some antibody fragments can be taken up and cross the BBB by mechanisms related to adsorptive endocytosis/transcytosis. Many peptides and proteins are transported out of the CNS by saturable efflux systems and enzymatic activity in the blood, CNS, or BBB are substantial barriers to others. Both influx and efflux transporters are altered by various substances and in disease states. Strategies that manipulate these interactions between the BBB and peptides and proteins provide many opportunities for the development of therapeutics. Such strategies include increasing transendothelial diffusion of small peptides, upregulation of saturable influx transporters with allosteric regulators and other posttranslational means, use of vectors and other Trojan horse strategies, inhibition of efflux transporters including with antisense molecules, and improvement in pharmacokinetic parameters to overcome short half-lives, tissue sequestration, and enzymatic degradation. © 2014 Elsevier Inc. All rights reserved.

  5. Early Intervention Paraprofessional Standards: Development and Field Validation (United States)

    Banerjee, Rashida; Chopra, Ritu V.; DiPalma, Geraldine


    Personnel standards are the foundations for how states and nations approve a program, engage in systemic assessment, and provide effective professional development to its early childhood professionals. However, despite the extensive use of paraprofessionals in early intervention/early childhood special education programs, there is a lack of…

  6. Identification of genes differentially expressed in dorsal and ventral chick midbrain during early development. (United States)

    Chittka, A; Volff, Jn; Wizenmann, A


    During the development of the central nervous system (CNS), patterning processes along the dorsoventral (DV) axis of the neural tube generate different neuronal subtypes. As development progresses these neurons are arranged into functional units with varying cytoarchitecture, such as laminae or nuclei for efficient relaying of information. Early in development ventral and dorsal regions are similar in size and structure. Different proliferation rates and cell migration patterns are likely to result in the formation of laminae or nuclei, eventually. However, the underlying molecular mechanisms that establish these different structural arrangements are not well understood.We undertook a differential display polymerase chain reaction (DD-PCR) screen to identify genes with distinct expression patterns between dorsal and ventral regions of the chick midbrain in order to identify genes which regulate the sculpturing of such divergent neuronal organisation. We focused on the DV axis of the early chick midbrain since mesencephalic alar plate and basal plate develop into laminae and nuclei, respectively. We identified 53 differentially expressed bands in our initial screen. Twenty-six of these could be assigned to specific genes and we could unambiguously show the differential expression of five of the isolated cDNAs in vivo by in situ mRNA expression analysis. Additionally, we verified differential levels of expression of a selected number of genes by using reverse transcriptase (RT) PCR method with gene-specific primers.One of these genes, QR1, has been previously cloned and we present here a detailed study of its early developmental time course and pattern of expression providing some insights into its possible function. Our phylogenetic analysis of QR1 shows that it is the chick orthologue of Sparc-like 1/Hevin/Mast9 gene in mice, rats, dogs and humans, a protein involved in cell adhesion. This study reveals some possible networks, which might be involved in directing

  7. Classroom Effects of an Early Childhood Educator Professional Development Partnership (United States)

    Algozzine, Bob; Babb, Julie; Algozzine, Kate; Mraz, Maryann; Kissel, Brian; Spano, Sedra; Foxworth, Kimberly


    We evaluated an Early Childhood Educator Professional Development (ECEPD) project that provided high-quality, sustained, and intensive professional development designed to support developmentally appropriate instruction for preschool-age children based on the best available research on early childhood pedagogy, child development, and preschool…

  8. Parents' Role in the Early Head Start Children's Language Development (United States)

    Griswold, Cecelia Smalls


    The development of language during a child's early years has been linked to parental involvement. While Early Head Start (EHS) researchers have theorized that parental involvement is an important factor in language development, there has been little research on how parents view their roles in the language development process. The purpose of this…

  9. Promoting equity through integrated early child development and nutrition interventions

    National Research Council Canada - National Science Library

    Black, Maureen M; Dewey, Kathryn G


    .... Transactional theory serves as a useful framework for examining the associations that link early child development and nutrition because it emphasizes the interplay that occurs between children...

  10. Development of figurative language skills following central nervous system-directed chemotherapy delivered in early childhood. (United States)

    Dowling, Emma K; Lewis, Fiona M; Murdoch, Bruce E


    Central nervous system (CNS)-directed chemotherapy is delivered for the treatment of childhood acute lymphoblastic leukaemia (ALL). Figurative language deficits have been described in children following CNS-directed chemotherapy; however, comprehensive analysis of figurative interpretation errors, potentially providing clinical utility to assist with intervention planning, has never been performed. The present study aimed to compare the figurative language skills of seven children treated with CNS-directed chemotherapy for ALL before the age of 6 years (mean age at diagnosis 3 years 10 months) and a matched control group of children, using the Test of Language Competence-Expanded Edition (TLC-E) Figurative Language sub-test. It was hypothesised that the children treated with CNS-directed chemotherapy would demonstrate a decreased performance in and an alternative method of interpreting figurative language. The results suggest no negative effects of CNS-directed chemotherapy on figurative language. There were no statistically significant differences between groups for TLC-E Figurative Language sub-test composite scores and picture component errors, nor were there clinically significant differences observed from descriptive comparisons of individual case data and error analysis. As these skills continue to emerge beyond childhood, the need to monitor skill development in ALL survivors beyond childhood is highlighted.

  11. Early gonad development in zebrafish (Danio rerio)

    African Journals Online (AJOL)



    Aug 13, 2014 ... reproductive characteristics of early zebrafish gonads are scattered. Oogenesis is typically studied in adult ovary. ..... changes of nuclear structure. One of the ultrastructural characteristics of oocytes at ... meiosis. The process is preceded by DNA replication and begins with the pairing and condensation of ...

  12. Early Developments in Argumentation in Physics. (United States)

    Bazerman, Charles

    An evaluation of four seventeenth and eighteenth century essays on optics revealed early trends in the evolution of scientific articles. The later articles showed a growing tendency to (1) separate practice from pure knowledge, (2) organize information around problems of knowledge and theory rather than around chronological events, (3) emphasize…

  13. Early Pregnancy Development and Obstetric Outcome

    NARCIS (Netherlands)

    R.H.F. van Oppenraaij


    markdownabstract__Abstract__ The following research objectives were defined: 1. To determine an unambiguous Dutch terminology to describe events in early pregnancy (Chapter 1.2) 2. To explore whether determining the due date by the last period is influenced by preference for certain dates,

  14. HB-GAM (pleiotrophin) reverses inhibition of neural regeneration by the CNS extracellular matrix (United States)

    Paveliev, Mikhail; Fenrich, Keith K.; Kislin, Mikhail; Kuja-Panula, Juha; Kulesskiy, Evgeny; Varjosalo, Markku; Kajander, Tommi; Mugantseva, Ekaterina; Ahonen-Bishopp, Anni; Khiroug, Leonard; Kulesskaya, Natalia; Rougon, Geneviève; Rauvala, Heikki


    Chondroitin sulfate (CS) glycosaminoglycans inhibit regeneration in the adult central nervous system (CNS). We report here that HB-GAM (heparin-binding growth-associated molecule; also known as pleiotrophin), a CS-binding protein expressed at high levels in the developing CNS, reverses the role of the CS chains in neurite growth of CNS neurons in vitro from inhibition to activation. The CS-bound HB-GAM promotes neurite growth through binding to the cell surface proteoglycan glypican-2; furthermore, HB-GAM abrogates the CS ligand binding to the inhibitory receptor PTPσ (protein tyrosine phosphatase sigma). Our in vivo studies using two-photon imaging of CNS injuries support the in vitro studies and show that HB-GAM increases dendrite regeneration in the adult cerebral cortex and axonal regeneration in the adult spinal cord. Our findings may enable the development of novel therapies for CNS injuries. PMID:27671118

  15. Electrophoretic deposition of cellulose nanocrystals (CNs) and CNs/alginate nanocomposite coatings and free standing membranes. (United States)

    Chen, Qiang; de Larraya, Uxua Pérez; Garmendia, Nere; Lasheras-Zubiate, María; Cordero-Arias, Luis; Virtanen, Sannakaisa; Boccaccini, Aldo R


    This study presents the electrophoretic deposition (EPD) of cellulose nanocrystals (CNs) and CNs-based alginate composite coatings for biomedical applications. The mechanism of anodic deposition of CNs and co-deposition of CNs/alginate composites was analyzed based on the results of zeta-potential, Fourier transform infrared spectroscopy and scanning electron microscopy (SEM) analyses. The capability of the EPD technique for manipulating the orientation of CNs and for the preparation of multilayer CNs coatings was demonstrated. The nanotopographic surface roughness and hydrophilicity of the deposited coatings were measured and discussed. Electrochemical testing demonstrated that a significant degree of corrosion protection of stainless steel could be achieved when CNs-containing coatings were present. Additionally, the one-step EPD-based processing of free-standing CNs/alginate membranes was demonstrated confirming the versatility of EPD to fabricate free-standing membrane structures compared to a layer-by-layer deposition technique. CNs and CNs/alginate nanocomposite coatings produced by EPD are potential candidates for biomedical, cell technology and drug delivery applications. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Promoting Professional Development for Physical Therapists in Early Intervention (United States)

    Catalino, Tricia; Chiarello, Lisa A.; Long, Toby; Weaver, Priscilla


    Early intervention service providers are expected to form cohesive teams to build the capacity of a family to promote their child's development. Given the differences in personnel preparation across disciplines of service providers, the Early Childhood Personnel Center is creating integrated and comprehensive professional development models for…

  17. Studying Children's Early Literacy Development: Confirmatory Multidimensional Scaling Growth Modeling (United States)

    Ding, Cody


    There has been considerable debate over the ways in which children's early literacy skills develop over time. Using confirmatory multidimensional scaling (MDS) growth analysis, this paper directly tested the hypothesis of a cumulative trajectory versus a compensatory trajectory of development in early literacy skills among a group of 1233…

  18. Assessing Home Environment for Early Child Development in Pakistan (United States)

    Nadeem, Sanober; Rafique, Ghazala; Khowaja, Liaquat; Yameen, Anjum


    Family environment plays a very important role in early child development and the availability of stimulating material in the early years of a child's life is crucial for optimising development. The Home Observation for Measurement of the Environment (HOME) inventory is one of the most widely used measures to assess the quality and quantity of…

  19. Domain-specific regulation of foxP2 CNS expression by lef1

    National Research Council Canada - National Science Library

    Bonkowsky, Joshua L; Wang, Xu; Fujimoto, Esther; Lee, Ji Eun; Chien, Chi-Bin; Dorsky, Richard I


    FOXP2 is a forkhead transcription factor critical for normal development of language in humans, but little is known of its broader function and regulation during central nervous system (CNS) development...

  20. INS/CNS/GNSS integrated navigation technology

    CERN Document Server

    Quan, Wei; Gong, Xiaolin; Fang, Jiancheng


    This book not only introduces the principles of INS, CNS and GNSS, the related filters and semi-physical simulation, but also systematically discusses the key technologies needed for integrated navigations of INS/GNSS, INS/CNS, and INS/CNS/GNSS, respectively. INS/CNS/GNSS integrated navigation technology has established itself as an effective tool for precise positioning navigation, which can make full use of the complementary characteristics of different navigation sub-systems and greatly improve the accuracy and reliability of the integrated navigation system. The book offers a valuable reference guide for graduate students, engineers and researchers in the fields of navigation and its control. Dr. Wei Quan, Dr. Jianli Li, Dr. Xiaolin Gong and Dr. Jiancheng Fang are all researchers at the Beijing University of Aeronautics and Astronautics.

  1. Neurotrauma and Inflammation: CNS and PNS Responses

    Directory of Open Access Journals (Sweden)

    Bruno Siqueira Mietto


    Full Text Available Traumatic injury to the central nervous system (CNS or the peripheral nervous system (PNS triggers a cascade of events which culminate in a robust inflammatory reaction. The role played by inflammation in the course of degeneration and regeneration is not completely elucidated. While, in peripheral nerves, the inflammatory response is assumed to be essential for normal progression of Wallerian degeneration and regeneration, CNS trauma inflammation is often associated with poor recovery. In this review, we discuss key mechanisms that trigger the inflammatory reaction after nervous system trauma, emphasizing how inflammations in both CNS and PNS differ from each other, in terms of magnitude, cell types involved, and effector molecules. Knowledge of the precise mechanisms that elicit and maintain inflammation after CNS and PNS tissue trauma and their effect on axon degeneration and regeneration is crucial for the identification of possible pharmacological drugs that can positively affect the tissue regenerative capacity.

  2. History and early development of INCAP. (United States)

    Scrimshaw, Nevin S


    Nevin Scrimshaw was the founding Director of the Institute of Nutrition of Central America and Panama (INCAP), serving as Director from 1949 to 1961. In this article, he reviews the history of the founding of INCAP, including the role of the Rockefeller and Kellogg Foundations, the Central American governments, and the Pan American Health Organization. The objectives pursued by INCAP in its early years were to assess the nutrition and related health problems of Central America, to carry out research to find practical solutions to these problems, and to provide technical assistance to its member countries to implement solutions. INCAP pursued a strategy of selecting promising Central Americans for advanced education and training in the US who assumed positions of leadership on their return. After this early phase, talented non-Central Americans of diverse origins were brought to INCAP, as well as additional researchers from the region. Growth of INCAP, as reflected in its annual budget and in the physical plant, was rapid and this was accompanied by high scientific productivity. Several field studies were launched that contributed impetus and design elements for the Oriente Longitudinal Study, which is the focus of this supplement.

  3. Comparative transcriptomics of early dipteran development (United States)


    Background Modern sequencing technologies have massively increased the amount of data available for comparative genomics. Whole-transcriptome shotgun sequencing (RNA-seq) provides a powerful basis for comparative studies. In particular, this approach holds great promise for emerging model species in fields such as evolutionary developmental biology (evo-devo). Results We have sequenced early embryonic transcriptomes of two non-drosophilid dipteran species: the moth midge Clogmia albipunctata, and the scuttle fly Megaselia abdita. Our analysis includes a third, published, transcriptome for the hoverfly Episyrphus balteatus. These emerging models for comparative developmental studies close an important phylogenetic gap between Drosophila melanogaster and other insect model systems. In this paper, we provide a comparative analysis of early embryonic transcriptomes across species, and use our data for a phylogenomic re-evaluation of dipteran phylogenetic relationships. Conclusions We show how comparative transcriptomics can be used to create useful resources for evo-devo, and to investigate phylogenetic relationships. Our results demonstrate that de novo assembly of short (Illumina) reads yields high-quality, high-coverage transcriptomic data sets. We use these data to investigate deep dipteran phylogenetic relationships. Our results, based on a concatenation of 160 orthologous genes, provide support for the traditional view of Clogmia being the sister group of Brachycera (Megaselia, Episyrphus, Drosophila), rather than that of Culicomorpha (which includes mosquitoes and blackflies). PMID:23432914

  4. Clinical features, outcomes, and cerebrospinal fluid findings in adult patients with central nervous system (CNS) infections caused by varicella-zoster virus: comparison with enterovirus CNS infections. (United States)

    Hong, Hyo-Lim; Lee, Eun Mi; Sung, Heungsup; Kang, Joong Koo; Lee, Sang-Ahm; Choi, Sang-Ho


    Varicella-zoster virus (VZV) is known to be associated with central nervous system (CNS) infections in adults. However, the clinical characteristics of VZV CNS infections are not well characterized. The aim of this study was to compare the clinical manifestations, outcomes, and cerebrospinal fluid (CSF) findings in patients with VZV CNS infections with those in patients with enterovirus (EV) CNS infections. This retrospective cohort study was performed at a 2,700-bed tertiary care hospital. Using a clinical microbiology computerized database, all adults with CSF PCR results positive for VZV or EV that were treated between January 1999 and February 2013 were identified. Thirty-eight patients with VZV CNS infection and 68 patients with EV CNS infection were included in the study. Compared with the EV group, the median age in the VZV group was higher (VZV, 35 years vs. EV, 31 years; P = 0.02), and showed a bimodal age distribution with peaks in the third and seventh decade. Encephalitis was more commonly encountered in the VZV group (VZV, 23.7% vs. EV, 4.4%; P = 0.01). The median lymphocyte percentage in the CSF (VZV, 81% vs. EV, 36%; P < 0.001) and the CSF protein level (VZV, 100 mg/dl vs. EV, 46 mg/dl; P < 0.001) were higher in the VZV group. Compared with patients with EV CNS infection, patients with VZV CNS infection developed encephalitis more often and exhibited more intense inflammatory reaction. Nevertheless, both VZV and EV CNS infections were associated with excellent long-term prognosis. © 2014 Wiley Periodicals, Inc.

  5. CNS toxoplasmosis in an immunocompetent individual

    Directory of Open Access Journals (Sweden)

    Rajoo Ramachandran, MBBS, MD


    Full Text Available Toxoplasmosis is a serious and life-threatening disease in humans with a high prevalence in immunocompromised persons. The disease has a wide spectrum, depending on the immune status of the person. A CNS manifestation of toxoplasmosis in an immunocompetent person is very rare and often undetected. Our case of CNS toxoplasmosis in an immunocompetent person emphasizes the radiological diagnosis, which was further confirmed by advanced microbiology technique.

  6. Activity-dependent formation and location of voltage-gated sodium channel clusters at a CNS nerve terminal during postnatal development. (United States)

    Xu, Jie; Berret, Emmanuelle; Kim, Jun Hee


    In auditory pathways, the precision of action potential (AP) propagation depends on axon myelination and high densities of voltage-gated Na (Nav) channels clustered at nodes of Ranvier. Changes in Nav channel expression at the heminode, the final node before the nerve terminal, can alter AP invasion into the presynaptic terminal. We studied the activity-dependent formation of Nav channel clusters before and after hearing onset at postnatal day 12 in the rat and mouse auditory brain stem. In rats, the Nav channel cluster at the heminode formed progressively during the second postnatal week, around hearing onset, whereas the Nav channel cluster at the nodes was present before hearing onset. Initiation of heminodal Nav channel clustering was correlated with the expression of scaffolding protein ankyrinG and paranodal protein Caspr. However, in whirler mice with congenital deafness, heminodal Nav channels did not form clusters and maintained broad expression, but Nav channel clustering was normal at the nodes. In addition, a clear difference in the distance from the heminodal Nav channel to the calyx across the mediolateral axis of the medial nucleus of the trapezoid body (MNTB) developed after hearing onset. In the medial MNTB, where neurons respond best to high-frequency sounds, the heminodal Nav channel cluster was located closer to the terminal than in the lateral MNTB, where neurons respond best to low-frequency sounds. Thus sound-mediated neuronal activities are potentially associated with the refinement of the heminode adjacent to the presynaptic terminal in the auditory brain stem. Clustering of voltage-gated sodium (Nav) channels and their distribution along the axon, specifically at the unmyelinated axon segment next to the nerve terminal, are essential for tuning propagated action potentials. Nav channel clusters near the nerve terminal and their location as a function of neuronal position along the mediolateral axis are controlled by auditory inputs after

  7. The spectrum of post-vaccination inflammatory CNS demyelinating syndromes. (United States)

    Karussis, Dimitrios; Petrou, Panayiota


    A wide variety of inflammatory diseases temporally associated with the administration of various vaccines, has been reported in the literature. A PubMed search from 1979 to 2013 revealed seventy one (71) documented cases. The most commonly reported vaccinations that were associated with CNS demyelinating diseases included influenza (21 cases), human papilloma virus (HPV) (9 cases), hepatitis A or B (8 cases), rabies (5 cases), measles (5 cases), rubella (5 cases), yellow fever (3 cases), anthrax (2 cases),meningococcus (2 cases) and tetanus (2 cases). The vast majority of post-vaccination CNS demyelinating syndromes, are related to influenza vaccination and this could be attributed to the high percentage of the population that received the vaccine during the HI1N1 epidemia from 2009 to 2012. Usually the symptoms of the CNS demyelinating syndrome appear few days following the immunization (mean: 14.2 days) but there are cases where the clinical presentation was delayed (more than 3 weeks or even up to 5 months post-vaccination) (approximately a third of all the reported cases). In terms of the clinical presentation and the affected CNS areas, there is a great diversity among the reported cases of post-vaccination acute demyelinating syndromes. Optic neuritis was the prominent clinical presentation in 38 cases, multifocal disseminated demyelination in 30, myelitis in 24 and encephalitis in 17. Interestingly in a rather high proportion of the patients (and especially following influenza and human papiloma virus vaccination-HPV) the dominant localizations of demyelination were the optic nerves and the myelon, presenting as optic neuritis and myelitis (with or without additional manifestations of ADEM), reminiscent to neuromyelitic optica (or, more generally, the NMO-spectrum of diseases). Seven patients suffered an NMO-like disease following HPV and we had two similar cases in our Center. One patient with post-vaccination ADEM, subsequently developed NMO. Overall, the

  8. Myelin damage and repair in pathologic CNS: challenges and prospects (United States)

    Alizadeh, Arsalan; Dyck, Scott M.; Karimi-Abdolrezaee, Soheila


    Injury to the central nervous system (CNS) results in oligodendrocyte cell death and progressive demyelination. Demyelinated axons undergo considerable physiological changes and molecular reorganizations that collectively result in axonal dysfunction, degeneration and loss of sensory and motor functions. Endogenous adult oligodendrocyte precursor cells and neural stem/progenitor cells contribute to the replacement of oligodendrocytes, however, the extent and quality of endogenous remyelination is suboptimal. Emerging evidence indicates that optimal remyelination is restricted by multiple factors including (i) low levels of factors that promote oligodendrogenesis; (ii) cell death among newly generated oligodendrocytes, (iii) inhibitory factors in the post-injury milieu that impede remyelination, and (iv) deficient expression of key growth factors essential for proper re-construction of a highly organized myelin sheath. Considering these challenges, over the past several years, a number of cell-based strategies have been developed to optimize remyelination therapeutically. Outcomes of these basic and preclinical discoveries are promising and signify the importance of remyelination as a mechanism for improving functions in CNS injuries. In this review, we provide an overview on: (1) the precise organization of myelinated axons and the reciprocal axo-myelin interactions that warrant properly balanced physiological activities within the CNS; (2) underlying cause of demyelination and the structural and functional consequences of demyelination in axons following injury and disease; (3) the endogenous mechanisms of oligodendrocyte replacement; (4) the modulatory role of reactive astrocytes and inflammatory cells in remyelination; and (5) the current status of cell-based therapies for promoting remyelination. Careful elucidation of the cellular and molecular mechanisms of demyelination in the pathologic CNS is a key to better understanding the impact of remyelination for

  9. CSF and clinical data are useful in differentiating CNS inflammatory demyelinating disease from CNS lymphoma. (United States)

    Ikeguchi, Ryotaro; Shimizu, Yuko; Shimizu, Satoru; Kitagawa, Kazuo


    It is often difficult to diagnose central nervous system (CNS) inflammatory demyelinating diseases (IDDs) because they are similar to CNS lymphoma and glioma. To evaluate whether cerebrospinal fluid (CSF) analysis can differentiate CNS IDDs from CNS lymphoma and glioma. We measured CSF cell counts; concentrations of proteins, glucose, interleukin (IL)-6, IL-10, soluble IL-2 receptor (sIL-2R), and myelin basic protein; and IgG index in patients with multiple sclerosis (MS, n = 64), neuromyelitis optica spectrum disorder (NMOSD, n = 35), tumefactive demyelinating lesion (TDL, n = 17), CNS lymphoma ( n = 12), or glioma ( n = 10). We detected diagnostic markers using logistic regression and receiver operating characteristic (ROC) analyses. Median CSF IL-10 and sIL-2R levels were higher in CNS lymphoma patients than in MS, NMOSD, or TDL patients. Logistic regression revealed that CSF sIL-2R levels predicted CNS lymphoma. In the ROC analysis of CSF sIL-2R levels, the area under the curve was 0.867, and the sensitivity and specificity were 83.3% and 90.0%, respectively. CSF sIL-2R levels can be used to differentiate CNS lymphoma from CNS IDDs. Further studies may identify other applications of CSF as a diagnostic biomarker.

  10. Parents Resourcing Children's Early Development and Learning (United States)

    Nichols, Sue; Nixon, Helen; Pudney, Valerie; Jurvansuu, Sari


    Parents deal with a complex web of choices when seeking and using knowledge and resources related to their young children's literacy development. Information concerning children's learning and development comes in many forms and is produced by an increasingly diverse range of players including governments, non-government organizations and…

  11. Early development of artificially spawned southern mullet,

    African Journals Online (AJOL)


    Aug 2, 1988 ... The embryonic development of artificially spawned southern mullet, Liza richardsonii, eggs and the development of the larvae to 46 days are described and illustrated using drawings and photographs. The floating eggs hatched in sea water at 18-24°C after 46-60 h. Newly stripped eggs usually had more ...

  12. Early influences on cardiovascular and renal development. (United States)

    Geelhoed, J J Miranda; Jaddoe, Vincent W V


    The hypothesis that a developmental component plays a role in subsequent disease initially arose from epidemiological studies relating birth size to both risk factors for cardiovascular disease and actual cardiovascular disease prevalence in later life. The findings that small size at birth is associated with an increased risk of cardiovascular disease have led to concerns about the effect size and the causality of the associations. However, recent studies have overcome most methodological flaws and suggested small effect sizes for these associations for the individual, but an potential important effect size on a population level. Various mechanisms underlying these associations have been hypothesized, including fetal undernutrition, genetic susceptibility and postnatal accelerated growth. The specific adverse exposures in fetal and early postnatal life leading to cardiovascular disease in adult life are not yet fully understood. Current studies suggest that both environmental and genetic factors in various periods of life may underlie the complex associations of fetal growth retardation and low birth weight with cardiovascular disease in later life. To estimate the population effect size and to identify the underlying mechanisms, well-designed epidemiological studies are needed. This review is focused on specific adverse fetal exposures, cardiovascular adaptations and perspectives for new studies.

  13. Early development of fern gametophytes in microgravity (United States)

    Roux, Stanley J.; Chatterjee, Ani; Hillier, Sheila; Cannon, Tom

    Dormant spores of the fern Ceratopteris richardii were flown on Shuttle mission STS-93 to evaluate the effects of /micro-g on their development and on their pattern of gene expression. Prior to flight the spores were sterilized and sown into one of two environments: (1) Microscope slides in a video-microscopy module; and (2) Petri dishes. All spores were then stored in darkness until use. Spore germination was initiated on orbit after exposure to light. For the spores on microscope slides, cell level changes were recorded through the clear spore coat of the spores by video microscopy. After their exposure to light, spores in petri dishes were frozen in orbit at four different time points during which on earth gravity fixes the polarity of their development. Spores were then stored frozen in Biological Research in Canister units until recovery on earth. The RNAs from these cells and from /1-g control cells were extracted and analyzed on earth after flight to assay changes in gene expression. Video microscopy results revealed that the germinated spores developed normally in microgravity, although the polarity of their development, which is guided by gravity on earth, was random in space. Differential Display-PCR analyses of RNA extracted from space-flown cells showed that there was about a 5% change in the pattern of gene expression between cells developing in /micro-g compared to those developing on earth.

  14. Improved brain uptake of peptide-based CNS drugs via alternative routes of administrations of its nanocarrier delivery systems: a promising strategy for CNS targeting delivery of peptides. (United States)

    Qian, Shuai; Wang, Qianwen; Zuo, Zhong


    Recently, developing peptide-based drugs to treat CNS diseases has gained increasing attention in both academics and pharmaceutical industry. However, targeting delivery of peptides to brain is one of the most challenging problems faced in the treatment of CNS diseases. After explaining the brain barriers limiting the delivery of peptides, the current review focuses on summarizing the most promising approaches for the enhancement of peptide and brain uptake, including delivery via alternative routes of administrations or using nanocarriers or intranasal administration of nanocarriers loaded with peptide. In addition, the biopharmaceutic, pharmacokinetic and pharmacodynamic details of several successful peptide-based CNS drugs are highlighted. Although using nanocarriers or delivery via alternative routes could improve to a certain extent the brain uptake of peptides, the magnitude of changes remains moderate. Alternatively, intranasal administration of nanocarriers loaded with peptide has been demonstrated to be an effective approach for CNS-targeted delivery of peptides.

  15. Framing Early Childhood Development: Strategic Communications and Public Preferences (United States)

    Gilliam, Franklin D.; Bales, Susan Nall


    This brief focuses on the potential role that strategic communications can play in helping state (Maternal Child Health) MCH programs and their collaborating partners frame their message to enhance the public's understanding of the importance of early child development and the need for a comprehensive and integrated early childhood system. The…

  16. The Status of Early Childhood Care and Development in Aboadze ...

    African Journals Online (AJOL)

    the unavailability of facilities to promote quality childhood care, government's and community's poor involvement in preschool education and lack of training of the. Kindergarten teachers. Keywords: Early Childhood Care and Development, Early Childhood Care Education, Pre-School. International Journal of Educational ...

  17. Medical students' professional identity development in an early nursing attachment.

    NARCIS (Netherlands)

    Helmich, E.; Derksen, E.; Prevoo, M.; Laan, R.F.J.M.; Bolhuis, S.; Koopmans, R.T.C.M.


    OBJECTIVES: The importance of early clinical experience for medical training is well documented. However, to our knowledge there are no studies that assess the influence of very early nursing attachments on the professional development and identity construction of medical students. Working as an

  18. Family Strategies to Support and Develop Resilience in Early Childhood (United States)

    Taket, A. R.; Nolan, A.; Stagnitti, K.


    Early childhood is an important time for the development of resilience. A recently completed study has followed three cohorts of resilient children and young people living in disadvantaged areas in Victoria, Australia, through different transitions in their educational careers. This paper focuses on the early childhood cohort, where we have…

  19. development of an epidemic early warning system in Mpwapwa

    African Journals Online (AJOL)

    to develop an early warning system in Mpwapwa district of central Tanzania. Retrospective epidemiological and ... Key words: malaria, epidemics, surveillance, early warning system, Tanzania. Introduction Muheza, Lushoto, Babati, ..... used to provide both alert and action lines. These kinds of charts have been tested and ...

  20. Childhood Immunization: A Key Component of Early Childhood Development (United States)

    Messonnier, Nancy


    Physical health is a key component of early childhood development and school readiness. By keeping children healthy and decreasing the chances of disease outbreaks, immunizations help early childhood programs create a safe environment for children. While overall vaccination rates are high nationally for most vaccines routinely recommended for…

  1. Developing Prosocial Behaviors in Early Adolescence with Reactive Aggression (United States)

    Fung, Annis L. C.


    Despite the alarming rise of early adolescence aggression in Hong Kong, it is the pioneer evidence-based outcome study on Anger Coping Training (ACT) program for early adolescence with reactive aggression to develop their prosocial behaviors. This research program involved experimental and control groups with pre- and post-comparison using a …

  2. Early Speech Motor Development: Cognitive and Linguistic Considerations (United States)

    Nip, Ignatius S. B.; Green, Jordan R.; Marx, David B.


    This longitudinal investigation examines developmental changes in orofacial movements occurring during the early stages of communication development. The goals were to identify developmental trends in early speech motor performance and to determine how these trends differ across orofacial behaviors thought to vary in cognitive and linguistic…

  3. Global health and development in early childhood. (United States)

    Aboud, Frances E; Yousafzai, Aisha K


    Health and nutritional risks co-occur in the lives of children under the age of 2 years who live in developing countries. We review evidence showing how these risks, in addition to inadequate psychosocial stimulation, prevent children from developing expected cognitive and language abilities. A systematic review and meta-analysis of 21 interventions aimed at enhancing stimulation and 18 interventions that provided better nutrition--all conducted since 2000--revealed that stimulation had a medium effect size of 0.42 and 0.47 on cognitive and language development, respectively, whereas nutrition by itself had a small effect size of 0.09. The implementation processes of these interventions are described and compared. A number of unresolved issues are outlined and discussed, including ways to maximize parental health behavior change, assess mediators that account for intervention effects, and expand the assessment of young children's brain functions that underlie language and cognition and are affected by nutrition and stimulation.

  4. Early psychosis workforce development: Core competencies for mental health professionals working in the early psychosis field. (United States)

    Osman, Helen; Jorm, Anthony F; Killackey, Eoin; Francey, Shona; Mulcahy, Dianne


    The aim of this study was to identify the core competencies required of mental health professionals working in the early psychosis field, which could function as an evidence-based tool to support the early psychosis workforce and in turn assist early psychosis service implementation and strengthen early psychosis model fidelity. The Delphi method was used to establish expert consensus on the core competencies. In the first stage, a systematic literature search was conducted to generate competency items. In the second stage, a panel consisting of expert early psychosis clinicians from around the world was formed. Panel members then rated each of the competency items on how essential they are to the clinical practice of all early psychosis clinicians. In total, 1023 pieces of literature including textbooks, journal articles and grey literature were reviewed. A final 542 competency items were identified for inclusion in the questionnaire. A total of 63 early psychosis experts participated in 3 rating rounds. Of the 542 competency items, 242 were endorsed as the required core competencies. There were 29 competency items that were endorsed by 62 or more experts, and these may be considered the foundational competencies for early psychosis practice. The study generated a set of core competencies that provide a common language for early psychosis clinicians across professional disciplines and country of practice, and potentially are a useful professional resource to support early psychosis workforce development and service reform. © 2017 John Wiley & Sons Australia, Ltd.

  5. Early developments in solar cooling equipment (United States)

    Price, J. M.


    A brief description of a development program to design, fabricate and field test a series of solar operated or driven cooling devices, undertaken by the Marshall Space Flight Center in the context of the Solar Heating and Cooling Demonstration Act of 1974, is presented. Attention is given to two basic design concepts: the Rankine cycle principle and the use of a dessicant for cooling.

  6. Early development of the costovertebral joints. (United States)

    Chen, Po-Jung; Wozniak, Witold


    Researches on the development of the vertebral column were focused mainly on the growth of lumbar and cervical regions. However, none of them were related to the development of costovertebral joints. To our knowledge, the relationship between ribs and thoracic vertebrae has never been addressed. The aims of the presented study are: (1) to trace the formation of processes of vertebral arches and articular surfaces of the vertebral bodies, and (2) to trace the development of the ribs, particularly their joint surfaces. Study subjects are staged human embryos (from the 5th week) from the collection of the Department of Anatomy, Poznan University of Medical Sciences in Poland. Serial sections were stained according to methods allowed for tracing the development of investigated structures. The primordia of costovertebral joints are interzones from which differentiate all structures of synovial joints such as joint surfaces, capsule and cavity. Based on the result of this study, these interzones appeared in the embryonic stages 17 and 18 with approximately 40 to 42 postfertilizational days, and the cavitation within the interzone was observed in some embryos from stage 19 with approximately postfertilizational 44 days.

  7. Modelling of cerebral tuberculosis in BALB/c mice using clinical strain from patients with CNS tuberculosis infection

    Directory of Open Access Journals (Sweden)

    Aliabbas A Husain


    Interpretation & conclusions: The study showed development of a novel murine model of CNS-TB using the C3 strain of MTB that replicated events of extrapulmonary dissemination. The developed model would be helpful in understanding the pathogenesis of CNS-TB infection for the development of improved therapeutic interventions in future.

  8. Positron emission tomography in CNS drug discovery and drug monitoring. (United States)

    Piel, Markus; Vernaleken, Ingo; Rösch, Frank


    Molecular imaging methods such as positron emission tomography (PET) are increasingly involved in the development of new drugs. Using radioactive tracers as imaging probes, PET allows the determination of the pharmacokinetic and pharmacodynamic properties of a drug candidate, via recording target engagement, the pattern of distribution, and metabolism. Because of the noninvasive nature and quantitative end point obtainable by molecular imaging, it seems inherently suited for the examination of a pharmaceutical's behavior in the brain. Molecular imaging, most especially PET, can therefore be a valuable tool in CNS drug research. In this Perspective, we present the basic principles of PET, the importance of appropriate tracer selection, the impact of improved radiopharmaceutical chemistry in radiotracer development, and the different roles that PET can fulfill in CNS drug research.

  9. Penicillin: its discovery and early development. (United States)

    Ligon, B Lee


    In August 1928, Alexander Fleming returned from a vacation to his usually messy, disordered laboratory. In one of the Petri dishes that had not been touched by the Lysol, he noticed an unusual phenomenon: separate colonies of staphylococci and, near the dish's edge, a colony of mold approximately 20 mm in diameter. The finding proved to be a watershed in the history of medicine. This discovery lay dormant for some time before other researchers took up the challenge to investigate its clinical possibilities. Two investigators at Oxford, Sir Howard Walter Florey and Ernst Boris Chain, brought penicillin's potential for medical use to fruition and, along with Fleming, shared the 1945 Nobel Prize for Medicine. The discovery and development of penicillin represent one of the most important developments in the annals of medical history. This article presents a brief overview of the events that occurred in the progress from discovery to implementation as a therapeutic agent.

  10. Early Development of Children with Sex Chromosome Aberrations. (United States)

    Haka-Ilse, Katerina; And Others


    Arthur Retlaw and Associates, Inc., Suite 2080, 1603 Orrington Avenue, Evanston, Illinois 60201. A prospective study was made of the early development of 42 children with sex chromosome aberrations. (Author)

  11. Sources of inequality in South African early child development services

    National Research Council Canada - National Science Library

    Carol Aubrey


    This article seeks to examine critically South African early child development (ECD) in order to uncover some of the challenges that lie ahead in creating a more equitable future for its youngest children...

  12. Environmental cues from CNS, PNS, and ENS cells regulate CNS progenitor differentiation

    DEFF Research Database (Denmark)

    Brännvall, Karin; Corell, Mikael; Forsberg-Nilsson, Karin


    Cellular origin and environmental cues regulate stem cell fate determination. Neuroepithelial stem cells form the central nervous system (CNS), whereas neural crest stem cells generate the peripheral (PNS) and enteric nervous system (ENS). CNS neural stem/progenitor cell (NSPC) fate determination...

  13. Early bilingualism, language attainment, and brain development. (United States)

    Berken, Jonathan A; Gracco, Vincent L; Klein, Denise


    The brain demonstrates a remarkable capacity to undergo structural and functional change in response to experience throughout the lifespan. Evidence suggests that, in many domains of skill acquisition, the manifestation of this neuroplasticity depends on the age at which learning begins. The fact that most skills are acquired late in childhood or in adulthood has proven to be a limitation in studies aimed at determining the relationship between age of acquisition and brain plasticity. Bilingualism, however, provides an optimal model for discerning differences in how the brain wires when a skill is acquired from birth, when the brain circuitry for language is being constructed, versus later in life, when the pathways subserving the first language are already well developed. This review examines some of the existing knowledge about optimal periods in language development, with particular attention to the attainment of native-like phonology. It focuses on the differences in brain structure and function between simultaneous and sequential bilinguals and the compensatory mechanisms employed when bilingualism is achieved later in life, based on evidence from studies using a variety of neuroimaging modalities, including positron emission tomography (PET), task-based and resting-state functional magnetic resonance imaging (fMRI), and structural MRI. The discussion concludes with the presentation of recent neuroimaging studies that explore the concept of nested optimal periods in language development and the different neural paths to language proficiency taken by simultaneous and sequential bilinguals, with extrapolation to general notions of the relationship between age of acquisition and ultimate skill performance. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Resource Prospector (RP) - Early Prototyping and Development (United States)

    Andrews, D.; Colaprete, A.; Quinn, J.; Bluethmann, B.; Trimble, J.


    The Resource Prospector (RP) is an In-Situ Resource Utilization (ISRU) technology demonstration mission under study by the NASA Human Exploration and Operations Mission Directorate's (HEOMD) Advanced Exploration Systems (AES) Division. The mission, currently planned to launch in 2020, will demonstrate extraction of oxygen from lunar regolith to validate ISRU capability. The mission will address key Strategic Knowledge Gaps (SKGs) for robotic and human exploration to the Moon, Near Earth Asteroids (NEAs), and ultimately Mars, as well as meet the strategic goals of the Global Exploration Roadmap (GER), offered by the International Space Exploration Coordination Group (ISECG). In this roadmap, the use of local resources is specifically addressed relating to human exploration. RP will provide knowledge to inform the selection of future mission destinations, support the development of exploration systems, and reduce the risk associated with human exploration. Expanding human presence beyond low-Earth orbit to asteroids and Mars will require the maximum possible use of local materials, so-called in-situ resources. The moon presents a unique destination to conduct robotic investigations that advance ISRU capabilities, as well as providing significant exploration and science value. Lunar regolith contains useful resources such as oxygen, water, silicon, and light metals, like aluminum and titanium. Oxygen can be separated from the regolith for life support (breathable air), or used to create rocket propellant (oxidizer). Regolith can be used to protect against radiation exposure, be processed into solar cells, or used to manufacture construction materials such as bricks and glass. RP will characterize the constituents and distribution of water and other volatiles at the poles of the Moon, enabling innovative uses of local resources, in addition to validating ISRU capabilities. This capability, as well as a deeper understanding of regolith, will be valuable in the

  15. Assessment of early child development: what, why, and how?

    Directory of Open Access Journals (Sweden)

    Tajana Brajović


    Full Text Available Motor skills, language, social and personal development as well as cognitive abilities are often the focus of early child development assessment and monitoring. The article presents some of the developmental milestones in these areas of child development. At the same time the article demonstrates that early child development assessment surpasses merely the orientation acording to developmental milestones. As a part of primary health prevention in Slovenia, identification of children with potential developmental delays is performed with the Denver developmental screening test II and the Systematical psychological examination of the three-year-old procedure. The purpose of applying developmental screening tests is early identification of children with developmental problems, as well as preparation of effective early interventions. By applying an appropriate psychological test material, a psychologist is able to assess the type and the stage of child' s psychological problems and delays in different developmental domains. Only psychometrically sound, and standardized tests should be applied in the process of early child development assessment. The work presents some of the practical and theoretical difficulties which practitioners are facing in the process of early child development assessment. Some feasible solutions are provided as well.

  16. Armies of pestilence: CNS infections as potential weapons of mass destruction. (United States)

    Hart, B L; Ketai, L


    Infectious agents have been investigated, developed, and used by both governments and terrorist groups as weapons of mass destruction. CNS infections, though traditionally considered less often than respiratory diseases in this scenario, may be very important. Viruses responsible for encephalitides can be highly infectious in aerosol form. CNS involvement in anthrax is ominous but should change treatment. Brucellosis, plague, Q fever, and other bacteria can uncommonly manifest with meningoencephalitis and other findings. Emerging diseases may also pose threats. We review infectious agents of particular concern for purposes of biowarfare with respect to CNS manifestations and imaging features. © 2015 by American Journal of Neuroradiology.

  17. CNS immunological modulation of neural graft rejection and survival. (United States)

    Borlongan, C V; Stahl, C E; Cameron, D F; Saporta, S; Freeman, T B; Cahill, D W; Sanberg, P R


    Neural transplantation therapy as a possible alternative treatment for neurological movement disorders, such as in Parkinson's disease (PD), has accentuated research interest on the immune status of the central nervous system (CNS). Most animal studies concerned with neural transplantation for the treatment of PD have utilized dopamine (DA) neurons from tissues of the embryonic ventral mesencephalon. Rat embryonic DA neurons, grafted either as solid blocks or dissociated into a cell suspension and stereotaxically injected intraparenchymally into a rat lesion model of PD, have been shown to survive and form connections with the host brain, and ameliorate the behavioral deficits of PD. Similarly, studies on nonhuman primate models of PD provide considerable support for neural transplantation of DA neurons as an experimental clinical procedure for the treatment of PD. To this end, experimental clinical trials have been centered upon transplantation of the embryonic ventral mesencephalic cells for PD patients. Although not conclusive, the findings from clinical studies have provided some evidence that most patients with marked increases in fluorodopa uptake (indicating graft survival) have been immunosuppressed. Furthermore, immune reactions have been observed in rats xenografted with human embryonic tissue. Of note, embryonic ventral mesencephalic tissues compared to adult tissues produce better morphological and long-lasting behavioral amelioration of the neurobehavioral deficits of PD, thus advocating the use of grafts from young donors (embryo) to circumvent the CNS immune rejection. The possible graft rejection due to CNS immune reactions, coupled with the social and ethical problems surrounding the use of embryonic neural tissue, and the logistical problems concerning tissue availability have prompted the development of alternative sources of DA-secreting cells. To circumvent these obstacles, several methods have been suggested including the use of

  18. Sialin expression in the CNS implicates extralysosomal function in neurons. (United States)

    Aula, Nina; Kopra, Outi; Jalanko, Anu; Peltonen, Leena


    SLC17A5 encodes a lysosomal membrane protein, sialin, which transports sialic acid from lysosomes. Mutations in sialin result in neurodegenerative sialic acid storage disorders, Salla disease (SD) and infantile sialic acid storage disease (ISSD). Here we analyzed sialin in mouse central nervous system (CNS) and primary cortical and hippocampal neurons and glia. In the CNS, sialin was predominantly expressed in neurons, especially in the proliferative zone of the prospective neocortex and the hippocampus in developing brain. In nonneuronal cells and primary glial cell cultures, mouse sialin was localized into lysosomes but interestingly, in primary neuronal cultures sialin was not targeted into lysosomes but rather revealed a punctate staining along the neuronal processes and was also seen in the plasma membrane. These data demonstrate a nonlysosomal localization of sialin in neurons and would imply a role for sialin in the secretory processes of neuronal cells.

  19. Early origins of allergic disease: a review of processes and influences during early immune development. (United States)

    Prescott, Susan L


    With the disturbing increase in allergic disease, there is a pressing need to determine the causes, pathogenesis and safe avenues for disease prevention. Although events in early life appear important, no causal pathways have been identified. This review examines new developments in the area of foetal and early postnatal immune maturation. It secondly addresses early predisposing influences and protective factors that may have a future role in allergy prevention. New developments in the understanding of the ontogeny of allergen-specific immune responses in atopic infants are discussed, including the role of early type 1 and 2 immune responses, and how these are influenced by perinatal antigen presenting cell and T-cell immaturity. The controversial role of early dietary exposures including breastfeeding, food allergens, hydrolyzed formulae and other dietary factors including omega-3 fatty acids are discussed in the context of the most recent literature. Equally contentious, the role of early house dust and pet allergen exposure is discussed in light of new epidemiological studies and disappointing early results of multicentre allergen avoidance studies. Finally, a number of studies in animals and humans suggest that bacterial products can influence early immune development, providing a new potential therapeutic avenue for disease treatment and prevention. Complex multifactorial genetic and environmental interactions make research in this area difficult and apparent associations with allergic disease may not be causal in nature. Many current targets for prevention, such as early allergen exposure and infant feeding practices, are proving to be ineffective and may not be directly implicated in rising rates of disease.

  20. The Hong Kong Early Child Development Scale: A Validation Study. (United States)

    Rao, Nirmala; Sun, Jin; Ng, Sharon Sui Ngan; Ma, Kitty; Becher, Yvonne; Lee, Diana; Lau, Carrie; Zhang, Li; Chow, Chun Bong; Ip, Patrick


    This paper reports on the development and validation of the Hong Kong Early Child Development Scale (HKECDS), a holistic measure of child development designed specifically for preschool children in Hong Kong. Scale development was an iterative process and the first version of the scale contained 190 items whereas the final version includes only 95. Children ranging in age from three to six years were administered trial versions of the HKECDS in Studies 1 (n = 60) and 2 (n = 240). Item analyses indicated that it is a developmental scale and that it has an appropriate level of difficulty for preschool children. It also discriminates between three- to six-year-olds from different social backgrounds in Hong Kong. The final version of the HKECDS includes items from the following eight subscales: Personal, Social and Self-Care (7 items), Language Development (13 items), Pre-academic Learning (27 items), Cognitive Development (10 items), Gross Motor (12 items), Fine Motor (9 items), Physical Fitness, Health and Safety (7 items), and Self and Society (10 items). The HKECDS is the first early child development scale which considers both the holistic development of preschool children and incorporates current expectations of early child development in Hong Kong. In this era of evidence-based decision making, it can be used to evaluate both the efficacy of targeted interventions and broader child-related public policies on early child development in Hong Kong.

  1. Early life origins of psychological development and mental health. (United States)

    Räikkönen, Katri; Pesonen, Anu-Katriina


    According to the Developmental Origins of Health and Disease (DOHaD)-hypothesis, conditions early in life may have life-long consequences. In a series of epidemiological birth cohort and clinical studies and natural experiments, we have had the chance to test the extent to which this hypothesis is useful in understanding individual differences in psychological development and mental health. Our findings have provided evidence that individual differences in cognitive, social and emotional development and in mental health may lie in early life circumstances, and add significantly to the literature by pointing out which periods of early growth are the most critical. These findings are also important in translating pre-clinical evidence to humans. What remains less clear, however, is what the mechanisms of programming are. Thus, further research is needed to elucidate these mechanisms before information on the early life origins of health and disease can be used in designing prevention and intervention programs.

  2. Promoting equity through integrated early child development and nutrition interventions. (United States)

    Black, Maureen M; Dewey, Kathryn G


    Sustainable development, a foundation of the post-2015 global agenda, depends on healthy and productive citizens. The origins of adult health begin early in life, stemming from genetic-environmental interactions that include adequate nutrition and opportunities for responsive learning. Inequities associated with inadequate nutrition and early learning opportunities can undermine children's health and development, thereby compromising their productivity and societal contributions. Transactional theory serves as a useful framework for examining the associations that link early child development and nutrition because it emphasizes the interplay that occurs between children and the environment, mediated through caregiver interactions. Although single interventions targeting early child development or nutrition can be effective, there is limited evidence on the development, implementation, evaluation, and scaling up of integrated interventions. This manuscript introduces a special edition of papers on six topics central to integrated child development/nutrition interventions: (1) review of integrated interventions; (2) methods and topics in designing integrated interventions; (3) economic considerations related to integrated interventions; (4) capacity-building considerations; (5) examples of integrated interventions; and (6) policy implications of integrated interventions. Ensuring the health and development of infants and young children through integrated child development/nutrition interventions promotes equity, a critical component of sustainable development. © 2014 New York Academy of Sciences.

  3. Early Brain and Child Development: Connections to Early Education and Child Care (United States)

    Romano, Judith T.


    The vast majority of young children spend time in settings outside of the home, and the nature of those settings directly impacts the child's health and development. The ecobiodevelopmental framework of early brain and child development serve as the backdrop for establishing quality. This article describes the use of quality rating systems,…

  4. Integrated and Early Childhood Education: Preparation for Social Development. Theme A: Relevant Provision for Early Childhood. (United States)

    Axton, J. H. M.

    Factors which influence child development are listed and briefly discussed. These factors are (1) mother's childhood, (2) mother's age, (3) care during pregnancy and delivery, (4) early neonatal factors, (5) birth interval, (6) effect of repeated infection and malnutrition on brain growth and intellectual development, and (7) home environment. The…

  5. Myelin Damage and Repair in Pathologic CNS: Challenges and Prospects

    Directory of Open Access Journals (Sweden)

    Arsalan eAlizadeh


    Full Text Available Injury to the central nervous system (CNS results in oligodendrocyte cell death and progressive demyelination. Demyelinated axons undergo considerable physiological changes and molecular reorganizations that collectively result in axonal dysfunction, degeneration and loss of sensory and motor functions. Endogenous adult oligodendrocyte precursor cells (OPCs and neural stem/progenitor cells (NPCs contribute to the replacement of oligodendrocytes, however, the extent and quality of endogenous remyelination is suboptimal. Emerging evidence indicates that optimal remyelination is restricted by multiple factors including (i low levels of factors that promote oligodendrogenesis; (ii cell death among newly generated oligodendrocytes, (iii inhibitory factors in the post-injury milieu that impede remyelination, and (iv deficient expression of key growth factors essential for proper re-construction of a highly organized myelin sheath. Considering these challenges, over the past several years, a number of cell-based strategies have been developed to optimize remyelination therapeutically. Outcomes of these basic and preclinical discoveries are promising and signify the importance of remyelination as a mechanism for improving functions in CNS injuries. In this review, we provide an overview on: 1 the precise organization of myelinated axons and the reciprocal axo-myelin interactions that warrant properly balanced physiological activities within the CNS; 2 underlying cause of demyelination and the structural and functional consequences of demyelination in axons following injury and disease; 3 the endogenous mechanisms of oligodendrocyte replacement; 4 the modulatory role of reactive astrocytes and inflammatory cells in remyelination; and 5 the current status of cell-based therapies for promoting remyelination. Careful elucidation of the cellular and molecular mechanisms of demyelination in the pathologic CNS is a key to better understanding the impact of

  6. Humanized mouse models for HIV-1 infection of the CNS. (United States)

    Honeycutt, Jenna B; Sheridan, Patricia A; Matsushima, Glenn K; Garcia, J Victor


    Since the onset of the HIV epidemic, there has been a shift from a deadly diagnosis to the management of a chronic disease. This shift is the result of the development of highly effective drugs that are able to suppress viral replication for years. The availability of these regimens has also shifted the neurocognitive pathology associated with infection from potentially devastating to a much milder phenotype. As the disease outcome has changed significantly with the availability of antiretroviral therapy, there is an opportunity to re-evaluate the currently available models to address the neurocognitive pathology seen in suppressed patients. In the following, we seek to summarize the current literature on humanized mouse models and their utility in understanding how HIV infection leads to changes in the central nervous system (CNS). Also, we identify some of the unanswered questions regarding HIV infection of the CNS as well as the opportunities and limitations of currently existing models to address those questions. Finally, our conclusions indicate that the earlier humanized models used to study HIV infection in the CNS provided an excellent foundation for the type of work currently being performed using novel humanized mouse models. We also indicate the potential of some humanized mouse models that have not been used as of this time for the analysis of HIV infection in the brain.

  7. Helping Families Connect Early Literacy with Social-Emotional Development (United States)

    Santos, Rosa Milagros; Fettig, Angel; Shaffer, LaShorage


    Early childhood educators know that home is a child's first learning environment. From birth, children are comforted by hearing and listening to their caregivers' voices. The language used by families supports young children's development of oral language skills. Exposure to print materials in the home also supports literacy development. Literacy…

  8. Development of Early Warning Methods for Electric Power Systems

    DEFF Research Database (Denmark)

    Jóhannsson, Hjörtur

    This thesis concerns the development of methods that can provide, in realtime, an early warning for an emerging blackout in electric power systems. The blackout in E-Denmark and S-Sweden on September 23, 2003 is the main motivation for the method development. The blackout was caused by occurrence...

  9. Early Markers of Vulnerable Language Skill Development in Galactosaemia (United States)

    Lewis, Fiona M.; Coman, David J.; Syrmis, Maryanne


    There are no known biomedical or genetic markers to identify which infants with galactosaemia (GAL) are most at risk of poor language skill development, yet pre-linguistic communicative "red flag" behaviours are recognised as early identifiers of heightened vulnerability to impaired language development. We report on pre-linguistic…

  10. Culture and Early Language Development: Implications for Assessment and Intervention (United States)

    Parada, Patricia M.


    The purpose of this qualitative study--"Culture and Early Language Development: Implications for Assessment and Intervention"--was to explore and describe the perceptions and beliefs of Salvadoran mothers of low socioeconomic status regarding the language development of their young children in order to identify cultural variations in…

  11. Immune regulation and CNS autoimmune disease

    DEFF Research Database (Denmark)

    Antel, J P; Owens, T


    The central nervous system is a demonstrated target of both clinical and experimental immune mediated disorders. Immune regulatory mechanisms operative at the levels of the systemic immune system, the blood brain barrier, and within the CNS parenchyma are important determinants of the intensity a...

  12. The Expression of p-STAT3 in Stage IV Melanoma: Risk of CNS Metastasis and Survival (United States)

    Bassett, Roland; Kong, Ling-Yuan; Schacherer, Christopher W.; Gershenwald, Jeffrey E.; Grimm, Elizabeth A.; Fuller, Gregory N.; Heimberger, Amy B.


    Purpose The signal transducer and activator of transcription 3 (STAT3) is a key molecular hub of tumorigenesis and immune suppression. The expression of phosphorylated STAT3 (p-STAT3) has been shown to be higher in melanoma metastasis to the central nervous system (CNS) relative to distant metastasis in the rest of the body (systemic). We sought to determine whether the increased expression of p-STAT3 in non-CNS systemic melanoma metastasis is associated with an increased risk of developing CNS metastasis and is a negative prognostic factor for overall survival time. Methods We retrospectively identified 299 patients with stage IV melanoma. In a tissue microarray of systemic non-CNS metastasis specimens from these patients, we used immunohistochemical analysis to measure the percentage of cells with p-STAT3 expression and Kaplan–Meier survival estimates to analyze the association of p-STAT3 expression with median survival time, time to first CNS metastasis, and development of CNS metastasis. Results Lung metastases exhibited the highest level of p-STAT3 expression while spleen lesions had the lowest. The p-STAT3 expression was not associated with an increased risk of developing CNS metastasis or time to CNS metastasis. However, p-STAT3 expression was a negative prognostic factor for overall survival time in patients that did not develop CNS metastasis. Conclusions Stage IV melanoma patients without CNS metastasis treated with p-STAT3 inhibitors in efficacy studies should be stratified based on tumor expression of p-STAT3; however since p-STAT3 expression is not associated with the risk of CNS disease, increased MRI surveillance of the brain is not likely necessary. PMID:22488042

  13. Development of Early Measures of Comprehension: Innovation in Individual Growth and Development Indicators (United States)

    Wackerle-Hollman, Alisha K.; Rodriguez, Megan I.; Bradfield, Tracy A.; Rodriguez, Michael C.; McConnell, Scott R.


    Early comprehension is an important, but not well-understood, contribution to early literacy and language development. Specifically, research regarding the nature of skills representative of early comprehension, including how they contribute to later reading success, is needed to support best practices to adequately prepare students. This article…

  14. CNS Genes Implicated in Relapse

    Directory of Open Access Journals (Sweden)

    Willard M. Freeman


    Full Text Available Drug abuse is a condition that impacts not only the individual drug user, but society as a whole. Although prevention of initial drug use is the most effective way to prevent addiction, avoiding relapse is a crucial component of drug addiction recovery. Recent studies suggest that there is a set of genes whose expression is robustly and stably altered following drug use and ensuing abstinence. Such stable changes in gene expression correlate with ultrastructural changes in brain as well as alterations in behavior. As persistent molecular changes, these genes may provide targets for the development of therapeutics. Developing a list of well-characterized candidate genes and examining the effect of manipulating these genes will contribute to the ultimate goal of developing effective treatments to prevent relapse to drug use.

  15. Inequality in early childhood: risk and protective factors for early child development. (United States)

    Walker, Susan P; Wachs, Theodore D; Grantham-McGregor, Sally; Black, Maureen M; Nelson, Charles A; Huffman, Sandra L; Baker-Henningham, Helen; Chang, Susan M; Hamadani, Jena D; Lozoff, Betsy; Gardner, Julie M Meeks; Powell, Christine A; Rahman, Atif; Richter, Linda


    Inequality between and within populations has origins in adverse early experiences. Developmental neuroscience shows how early biological and psychosocial experiences affect brain development. We previously identified inadequate cognitive stimulation, stunting, iodine deficiency, and iron-deficiency anaemia as key risks that prevent millions of young children from attaining their developmental potential. Recent research emphasises the importance of these risks, strengthens the evidence for other risk factors including intrauterine growth restriction, malaria, lead exposure, HIV infection, maternal depression, institutionalisation, and exposure to societal violence, and identifies protective factors such as breastfeeding and maternal education. Evidence on risks resulting from prenatal maternal nutrition, maternal stress, and families affected with HIV is emerging. Interventions are urgently needed to reduce children's risk exposure and to promote development in affected children. Our goal is to provide information to help the setting of priorities for early child development programmes and policies to benefit the world's poorest children and reduce persistent inequalities. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Convulsant bicuculline modifies CNS muscarinic receptor affinity

    Directory of Open Access Journals (Sweden)

    Rodríguez de Lores Arnaiz Georgina


    Full Text Available Abstract Background Previous work from this laboratory has shown that the administration of the convulsant drug 3-mercaptopropionic acid (MP, a GAD inhibitor, modifies not only GABA synthesis but also binding of the antagonist [3H]-quinuclidinyl benzilate ([3H]-QNB to central muscarinic receptors, an effect due to an increase in affinity without modifications in binding site number. The cholinergic system has been implicated in several experimental epilepsy models and the ability of acetylcholine to regulate neuronal excitability in the neocortex is well known. To study the potential relationship between GABAergic and cholinergic systems with seizure activity, we analyzed the muscarinic receptor after inducing seizure by bicuculline (BIC, known to antagonize the GABA-A postsynaptic receptor subtype. Results We analyzed binding of muscarinic antagonist [3H]-QNB to rat CNS membranes after i.p. administration of BIC at subconvulsant (1.0 mg/kg and convulsant (7.5 mg/kg doses. Subconvulsant BIC dose failed to develop seizures but produced binding alteration in the cerebellum and hippocampus with roughly 40% increase and 10% decrease, respectively. After convulsant BIC dose, which invariably led to generalized tonic-clonic seizures, binding increased 36% and 15% to cerebellar and striatal membranes respectively, but decreased 12% to hippocampal membranes. Kd value was accordingly modified: with the subconvulsant dose it decreased 27% in cerebellum whereas it increased 61% in hippocampus; with the convulsant dose, Kd value decreased 33% in cerebellum but increased 85% in hippocampus. No change in receptor number site was found, and Hill number was invariably close to unity. Conclusion Results indicate dissimilar central nervous system area susceptibility of muscarinic receptor to BIC. Ligand binding was modified not only by a convulsant BIC dose but also by a subconvulsant dose, indicating that changes are not attributable to the seizure process

  17. Time Development in the Early History of Social Networks

    DEFF Research Database (Denmark)

    Bruun, Jesper; Bearden, Ian


    are beginning their studies at a university with no or few prior connections to each other offers a unique opportunity to investigate the formation and early development of link patterns and community structure in social networks. During a nine week introductory physics course, first year physics students were...... asked to identify those with whom they communicated about problem solving in physics during the preceding week. We use these students' self reports to produce time dependent student interaction networks. We investigate these networks to elucidate possible effects of different student attributes in early......Studies of the time development of empirical networks usually investigate late stages where lasting connections have already stabilized. Empirical data on early network history are rare but needed for a better understanding of how social network topology develops in real life. Studying students who...

  18. Netrin-1 Confines Rhombic Lip-Derived Neurons to the CNS

    Directory of Open Access Journals (Sweden)

    Andrea R. Yung


    Full Text Available During brainstem development, newborn neurons originating from the rhombic lip embark on exceptionally long migrations to generate nuclei important for audition, movement, and respiration. Along the way, this highly motile population passes several cranial nerves yet remains confined to the CNS. We found that Ntn1 accumulates beneath the pial surface separating the CNS from the PNS, with gaps at nerve entry sites. In mice null for Ntn1 or its receptor DCC, hindbrain neurons enter cranial nerves and migrate into the periphery. CNS neurons also escape when Ntn1 is selectively lost from the sub-pial region (SPR, and conversely, expression of Ntn1 throughout the mutant hindbrain can prevent their departure. These findings identify a permissive role for Ntn1 in maintaining the CNS-PNS boundary. We propose that Ntn1 confines rhombic lip-derived neurons by providing a preferred substrate for tangentially migrating neurons in the SPR, preventing their entry into nerve roots.

  19. Enhancing CNS repair in neurological disease: challenges arising from neurodegeneration and rewiring of the network. (United States)

    Xu, Xiaohua; Warrington, Arthur E; Bieber, Allan J; Rodriguez, Moses


    Repair of the central nervous system (CNS) constitutes an integral part of treating neurological disease and plays a crucial role in restoring CNS architecture and function. Distinct strategies have been developed to reconstruct the damaged neural tissue, with many tested preclinically in animal models. We review cell replacement-based repair strategies. By taking spinal cord injury, cerebral ischaemia and degenerative CNS disorders as examples for CNS repair, we discuss progress and potential problems in utilizing embryonic stem cells and adult neural/non-neural stem cells to repair cell loss in the CNS. Nevertheless, CNS repair is not simply a matter of cell transplantation. The major challenge is to induce regenerating neural cells to integrate into the neural network and compensate for damaged neural function. The neural cells confront an environment very different from that of the developmental stage in which these cells differentiate to form interwoven networks. During the repair process, one of the challenges is neurodegeneration, which can develop from interrupted innervations to/from the targets, chronic inflammation, ischaemia, aging or idiopathic neural toxicity. Neurodegeneration, which occurs on the basis of a characteristic vascular and neural web, usually presents as a chronically progressive process with unknown aetiology. Currently, there is no effective treatment to stop or slow down neurodegeneration. Pathological changes from patients with Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis indicate a broken homeostasis in the CNS. We discuss how the blood-brain barrier and neural networks are formed to maintain CNS homeostasis and their contribution to neurodegeneration in diseased conditions. Another challenge is that some inhibitors produced by CNS injury do not facilitate the regenerating neural cells to incorporate into a pre-existing network. We review glial responses to CNS injury. Of note, the reactive astrocytes

  20. On the evolution of early development in the Nematoda.


    Goldstein, B.


    The phylum Nematoda serves as an excellent model system for exploring how development evolves, using a comparative approach to developmental genetics. More than 100 laboratories are studying developmental mechanisms in the nematode Caenorhabditis elegans, and many of the methods that have been developed for C. elegans can be applied to other nematodes. This review summarizes what is known so far about steps in early development that have evolved in the nematodes, and proposes potential experi...

  1. Developing the quality of early childhood mentoring institutions

    Directory of Open Access Journals (Sweden)

    Sri Hartini


    Full Text Available The study was to uncover the concept of quality improvement, the supporting and the inhibiting factors within the quality improve and the quality improvement in the early childhood mentoring institutions/kindergarten. The study was a qualitative research. The subjects in the study were kindergarten principals, kindergarten teachers and parents. The data were gathered by means of observation, interview and documentation. For the data analysis, the researcher selected the qualitative descriptive data analysis method. The results of the study were as follows. First, the concept of educational quality improvement in the early childhood mentoring institutions/ kindergarten has been improveed from the vision, the mission and the objectives and the concept includes the aspects of planning, process and output which has synergy from one to another. The planning has been formulated in the curriculum, the syllabus and the daily activity plan. Second, the approach, the strategy and the technique of quality improvement has maximized the well-qualified schools’ resources, have been supported by the sufficient facilities and have been funded by the sufficient budget. Third, the supporting factors within the quality improvement of early childhood mentoring institutions/kindergarten have been the increasing awareness within the society toward the significance of early childhood mentoring institutions, the massive socialization conducted by the Office of Education through the provision of training programs in relation to the early childhood mentoring institution/kindergarten management and the human resources empowerment toward developing the quality of early childhood mentoring institutions. Fourth, the inhibiting factors within the quality improvement of early childhood mentoring institutions have been the lack of society care and participation, the less quality human resources that early childhood mentoring institutions have, the fund limitation, the

  2. The CNS and bladder dysfunction (United States)

    Holstege, Gert; Griffiths, Derek J.


    The brain's role in the development and maintenance of bladder control is critical, although its precise role in patient-reported complaints such as urgency and urine leakage is unknown. Functional brain imaging studies have advanced our knowledge of brain activity during the micturition cycle, showing multiple neuronal circuits involved as parts of a ‘brain-bladder control network.’ Yet, new advances need to be made in order to incorporate this knowledge into existing models of neuroanatomy and of clinical syndromes of bladder dysfunction and related clinical practice. This short article explains why and how brain imaging methods are poised to achieve that goal and decode the role of the brain in widely prevalent clinical conditions related to bladder dysfunction. PMID:23091564

  3. Risk factors for early metachronous tumor development after endoscopic resection for early gastric cancer.

    Directory of Open Access Journals (Sweden)

    Jae Yong Park

    Full Text Available Metachronous gastric tumor (MGT is one of major concerns after endoscopic submucosal dissection (ESD for early gastric cancer (EGC. Optimal follow-up strategy has not been yet well-established. The aim of this study was to identify the different clinical features of the patients according to the time interval to development of MGT.Among 1,780 consecutive patients with EGC who underwent ESD between 2005 and 2014, 115 patients with MGT were retrospectively reviewed. MGT was defined as secondary gastric cancer or dysplasia detected > 1 year after initial ESD. Clinicopathological factors associated with early development of MGT were evaluated.The median interval to development of MGT was 37 months. In univariate analysis, the median interval to MGT was shorter if EGC lesion was non-elevated type (39.4 vs 57.0 months, p = 0.011, or synchronous primary lesion was absent (39.8 vs 51.4 months, p = 0.050. In multivariate Cox's proportional hazards analysis, the hazard ratios for early occurrence of MGT were 1.966 (95% CI: 1.141-3.386, p = 0.015 and 1.911 (95% CI: 1.163-3.141, p = 0.011, respectively. There was no significant difference in overall survival after diagnosis of MGT between the early occurrence group and the late occurrence group.Non-elevated gross type and absence of synchronous gastric tumor were independent risk factors for early development of MGT. Meticulous endoscopic inspection is especially important for the detection of MGT during the early follow-up period in patients with these initial tumor characteristics.

  4. Does preterm period sleep development predict early childhood growth trajectories? (United States)

    Winkler, M R; Park, J; Pan, W; Brandon, D H; Scher, M; Holditch-Davis, D


    The current study examined the relationship between sleep state development across the preterm and early post-term periods and subsequent growth trajectories from 1 to 27 months corrected age. Retrospective analysis of data collected prospectively from 111 preterm infants (⩽34 weeks gestation) who participated in a multi-site longitudinal study. Separate longitudinal parallel process models were calculated for each sleep state (active and quiet sleep) and growth (weight, length and body mass index (BMI) Z-scores) variable to estimate the associations between their developmental trajectories. Significant associations were identified between the trajectories of quiet sleep and weight, active sleep and weight, quiet sleep and BMI, and active sleep and BMI. No statistically meaningful associations were identified between the trajectories of early childhood length and the preterm sleep states. Faster preterm period sleep development appears to predict more favorable early childhood growth trajectories, particularly for weight, indicating preterm sleep may be an important biomarker for subsequent growth outcomes.

  5. Embedded Professional Development and Classroom-Based Early Reading Intervention: Early Diagnostic Reading Intervention through Coaching (United States)

    Amendum, Steven J.


    The purpose of the current mixed-methods study was to investigate a model of professional development and classroom-based early reading intervention implemented by the 1st-grade teaching team in a large urban/suburban school district in the southeastern United States. The intervention provided teachers with ongoing embedded professional…

  6. GNSS real time performance monitoring and CNS/ATM implementation (United States)


    The global transition to communications, navigation, surveillance / air traffic management (CNS/ATM) technology is moving forward at an increasing pace. A critical part of the CNS/ATM concept is the ability to monitor, analyze, and distribute aeronau...

  7. More Alike than Different: Early Childhood Professional Development in Guatemala (United States)

    Hardin, Belinda J.; Vardell, Rosemarie; de Castaneda, Albertina


    This article describes an early childhood professional development project that took place in the summer of 2005 in Guatemala City. Located in Central America, Guatemala has a population of approximately 12.3 million people, including more than two million children under the age of 5 (UNESCO Institute for Statistics, 2007; UNICEF, 2004). Events…

  8. Developing Teacher Understanding of Early Algebraic Concepts Using Lesson Study (United States)

    Hunter, Jodie


    This paper reports on the use of lesson study as a professional development tool. In particular the paper focuses on the way in which the teachers increased their understanding of how tasks, classroom activity and teacher actions scaffolded student learning of early algebraic reasoning of equivalence and the commutative principle. Teacher voice is…

  9. Modern developments in early weaning of pigs | Bellis | South ...

    African Journals Online (AJOL)

    South African Journal of Animal Science. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 3, No 2 (1973) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register. Modern developments in early weaning of pigs.

  10. Awareness of Pattern and Structure in Early Mathematical Development (United States)

    Mulligan, Joanne; Mitchelmore, Michael


    Recent educational research has turned increasing attention to the structural development of young students' mathematical thinking. Early algebra, multiplicative reasoning, and spatial structuring are three areas central to this research. There is increasing evidence that an awareness of mathematical structure is crucial to mathematical competence…

  11. Development of the Life Story in Early Adolescence (United States)

    Steiner, Kristina L.; Pillemer, David B.


    Life span developmental psychology proposes that the ability to create a coherent life narrative does not develop until early adolescence. Using a novel methodology, 10-, 12-, and 14-year-old participants were asked to tell their life stories aloud to a researcher. Later, participants separated their transcribed narratives into self-identified…

  12. Identification of the Social Development in Early Childhood in Pakistan (United States)

    Malik, Asif; Sarwar, Muhammad; Khan, Naeemullah


    This study was conducted to identify the social development in early childhood years. It was delimited to eight private schools of Lahore City from the area of Faisal Town and Shadman. Forty students (male and female) were randomly selected as the sample. Five students from Nursery, Prep and grade one were selected from each school. A checklist…

  13. Note on artificial fertilization and early development of Synodontis ...

    African Journals Online (AJOL)

    Note on artificial fertilization and early development of Synodontis nigromaculatus (Pisces: Mochokidae). B.C.W. van der Waal. Abstract. Eggs obtained from β wild gravid spotted squeaker (Synodontis nigromaculatus Boulenger, 1905) were (entitled and incubated in plastic containers. Eggs are non-sticky, negatively ...

  14. Effects of early starvation on the development and survival of ...

    African Journals Online (AJOL)

    Macrobrachium vollenhovenii (Herklots) has been identified as a crustacean species with great culture potential. The effects of starvation on development and survival of early larval stages of the African river prawn M. vollenhovenii were investigated. As an aspect of the ongoing effort to determine the culturability of the ...

  15. Home-School Communication in the Early Childhood Development Phase (United States)

    Bridgemohan, Radhike; van Wyk, Noleen; van Staden, Christie


    This article examines the practices of home-school communication in the Early Childhood Development (ECD) phase in South Africa. The aims of this qualitative investigation were to determine the nature and effectiveness of home-school communication practices and to make recommendations on how communication can be improved to facilitate better…

  16. The Importance of Play in Early Childhood Development ...

    African Journals Online (AJOL)

    In the study leading to this paper, the task was to determine the possibility of the Department of Technical Education at the University of Zimbabwe in-servicing Early Childhood Development (ECD) teachers in Design and Technology (D&T) through short and long-term courses. Such courses would specifically relate to the ...

  17. Predictors of Early versus Later Spelling Development in Danish (United States)

    Nielsen, Anne-Mette Veber; Juul, Holger


    The present study examined phoneme awareness, phonological short term memory, letter knowledge, rapid automatized naming (RAN), and visual-verbal paired associate learning (PAL) as longitudinal predictors of spelling skills in an early phase (Grade 2) and a later phase (Grade 5) of development in a sample of 140 children learning to spell in the…

  18. Technology and Early Childhood Professional Development: A Policy Discussion. (United States)

    McMaken, Jessica; Kauerz, Kristie; DeCesare, Dale; Hale, Genevieve

    In July 2002, Knowledge Works Foundation and the Education Commission of the States assembled key stakeholders to focus on the policy opportunities, needs, and challenges of utilizing technology for coordinated early childhood professional development across the nation. This report summarizes the presentations and discussions held at the meeting…

  19. Changing the Perspective on Early Development of Rett Syndrome (United States)

    Marschik, Peter B.; Kaufmann, Walter E.; Sigafoos, Jeff; Wolin, Thomas; Zhang, Dajie; Bartl-Pokorny, Katrin D.; Pini, Giorgio; Zappella, Michele; Tager-Flusberg, Helen; Einspieler, Christa; Johnston, Michael V.


    We delineated the achievement of early speech-language milestones in 15 young children with Rett syndrome ("MECP2" positive) in the first two years of life using retrospective video analysis. By contrast to the commonly accepted concept that these children are normal in the pre-regression period, we found markedly atypical development of…

  20. Interneuron progenitor transplantation to treat CNS dysfunction

    Directory of Open Access Journals (Sweden)

    Muhammad O Chohan


    Full Text Available Due to the inadequacy of endogenous repair mechanisms diseases of the nervous system remain a major challenge to scientists and clinicians. Stem cell based therapy is an exciting and viable strategy that has been shown to ameliorate or even reverse symptoms of CNS dysfunction in preclinical animal models. Of particular importance has been the use of GABAergic interneuron progenitors as a therapeutic strategy. Born in the neurogenic niches of the ventral telencephalon, interneuron progenitors retain their unique capacity to disperse, integrate and induce plasticity in adult host circuitries following transplantation. Here we discuss the potential of interneuron based transplantation strategies as it relates to CNS disease therapeutics. We also discuss mechanisms underlying their therapeutic efficacy and some of the challenges that face the field.

  1. CNS adverse events associated with antimalarial agents. Fact or fiction?

    NARCIS (Netherlands)

    Phillips-Howard, P. A.; ter Kuile, F. O.


    CNS adverse drug events are dramatic, and case reports have influenced clinical opinion on the use of antimalarials. Malaria also causes CNS symptoms, thus establishing causality is difficult. CNS events are associated with the quinoline and artemisinin derivatives. Chloroquine, once considered too

  2. Child care center staff composition and early child development


    Drange, Nina; Rønning, Marte


    We estimate effects of child care center staff composition on early child development. During the years our data covers, child care centers in Oslo were oversubscribed, and child care slots were allocated through a lottery. This allow us to explore how staff education, experience and stability, as well as proportion of male and immigrant staff, affect the cognitive development of children whose parents initially applied for the same center(s), but where children got offers from di...

  3. Does copepods influence dusky grouper (Epinephelus marginatus early development?

    Directory of Open Access Journals (Sweden)

    Monica Mateus


    Full Text Available Good knowledge on the development of early life stages is essential for successful conservation programs of threatened fish species. Diet and rearing system affects early life survival and juvenile quality. Copepods are the natural food of fish larvae in the wild possessing high nutritional value, when compared with live feeds used in aquaculture (rotifers and artemia, and a wide range of size classes. Rearing systems with low water column disturbance and low larval densities enhanced the survival of fragile fish larvae. The aim of this work is to evaluate the effect of the introduction of copepods in the diet of early dusky grouper larvae reared in controlled mesocosm systems using larval development and juvenile quality as indicators. Two feeding protocols were tested, one composed only by rotifers (Brachionus plicatilis, brine shrimp (Artemia spp. and dry feed and the other supplemented with copepods (Paracartia grani from mouth opening (2 day after hatching - DAH to 8 DAH. Feeding behavior, growth, survival, skeletal malformations and digestive enzymes activity was assessed at different developmental stages. The addition of copepods to the early larvae diet of dusky grouper resulted in faster development and higher survival rates. Larvae fed with copepods improved their development. At 20 DAH all larvae reared at the mesocosm with copedods were already at the stage of post-flexion while in the system without copepods this stage was attained later. At 25 DAH only 64% of the larvae were in post flexion in the mesoscosm without copepods. At 30 DAH larvae supplemented with copepods attained an acidic digestion (high specific activity of pepsin earlier than at the system without copepods. In this last system alkaline digestion (trypsin specific activity, characteristic of early larval stages, was significantly higher reinforcing the faster development of larvae fed with copepods. In both systems the incidence of skeletal malformations was low.

  4. Intraventricular CNS lesions: A pictorial essay. (United States)

    Watts, Jane; Yap, Kelvin K; Ou, Daniel; Tartaglia, Con; Trost, Nicholas; Sutherland, Tom


    Intraventricular lesions of the central nervous system (CNS) can present a diagnostic challenge due to a range of differential diagnoses and radiological appearances. Both CT and MRI imaging findings, in combination with location and patient's age, can help limit the differentials. This pictorial essay presents the salient radiological features, location and demographics of the more common intraventricular lesions of the brain. © 2015 The Royal Australian and New Zealand College of Radiologists.

  5. Evolutionary origins and early development of number processing

    CERN Document Server

    Geary, David C; Mann Koepke, Kathleen


    The first volume in this ground-breaking series focuses on the origins and early development of numerical cognition in non-human primates, lower vertebrates, human infants, and preschool children. The text will help readers understand the nature and complexity of these foundational quantitative concepts and skills along with evolutionary precursors and early developmental trajectories. Brings together and focuses the efforts and research of multiple disciplines working in math cognition.The contributors bring vast knowledge and experience to bear on resolving extant

  6. Genetic and epigenetic control of early mouse development

    DEFF Research Database (Denmark)

    Albert, Mareike; Peters, Antoine H F M


    , exceedingly more efficient than in reproductive cloning or in transcription factor-based reprogramming. Understanding the molecular mechanisms directing acquisition of totipotency during early embryogenesis may enable optimization of protocols for induced reprogramming. Recent studies in mouse embryonic stem...... and primitive endoderm) is controlled by transcription factors that are regulated by autoactivating and reciprocal repressive mechanisms as well as by ERK-mediated signaling. Chromatin-based regulatory mechanisms also contribute to the identity of ESCs and early embryos. During gametogenesis, genomes undergo...... extensive epigenetic reprogramming. This may underlie the efficient acquisition of totipotency during subsequent preimplantation development....

  7. Effects of early life stress on amygdala and striatal development

    Directory of Open Access Journals (Sweden)

    Dominic S. Fareri


    Full Text Available Species-expected caregiving early in life is critical for the normative development and regulation of emotional behavior, the ability to effectively evaluate affective stimuli in the environment, and the ability to sustain social relationships. Severe psychosocial stressors early in life (early life stress; ELS in the form of the absence of species expected caregiving (i.e., caregiver deprivation, can drastically impact one’s social and emotional success, leading to the onset of internalizing illness later in life. Development of the amygdala and striatum, two key regions supporting affective valuation and learning, is significantly affected by ELS, and their altered developmental trajectories have important implications for cognitive, behavioral and socioemotional development. However, an understanding of the impact of ELS on the development of functional interactions between these regions and subsequent behavioral effects is lacking. In this review, we highlight the roles of the amygdala and striatum in affective valuation and learning in maturity and across development. We discuss their function separately as well as their interaction. We highlight evidence across species characterizing how ELS induced changes in the development of the amygdala and striatum mediate subsequent behavioral changes associated with internalizing illness, positing a particular import of the effect of ELS on their interaction.

  8. Histamine and Immune Biomarkers in CNS Disorders

    Directory of Open Access Journals (Sweden)

    Ramón Cacabelos


    Full Text Available Neuroimmune dysregulation is a common phenomenon in different forms of central nervous system (CNS disorders. Cross-links between central and peripheral immune mechanisms appear to be disrupted as reflected by a series of immune markers (CD3, CD4, CD7, HLA-DR, CD25, CD28, and CD56 which show variability in brain disorders such as anxiety, depression, psychosis, stroke, Alzheimer’s disease, Parkinson’s disease, attention-deficit hyperactivity disorder, migraine, epilepsy, vascular dementia, mental retardation, cerebrovascular encephalopathy, multiple sclerosis, brain tumors, cranial nerve neuropathies, mental retardation, and posttraumatic brain injury. Histamine (HA is a pleiotropic monoamine involved in several neurophysiological functions, neuroimmune regulation, and CNS pathogenesis. Changes in brain HA show an age- and sex-related pattern, and alterations in brain HA levels are present in different CNS regions of patients with Alzheimer’s disease (AD. Brain HA in neuronal and nonneuronal compartments plays a dual role (neurotrophic versus neurotoxic in a tissue-specific manner. Pathogenic mechanisms associated with neuroimmune dysregulation in AD involve HA, interleukin-1β, and TNF-α, whose aberrant expression contributes to neuroinflammation as an aggravating factor for neurodegeneration and premature neuronal death.

  9. Evaluation of early stimulation programs for enhancing brain development. (United States)

    Bonnier, Christine


    The term 'early intervention' designates educational and neuroprotection strategies aimed at enhancing brain development. Early educational strategies seek to take advantage of cerebral plasticity. Neuroprotection, a term initially used to characterize substances capable of preventing cell death, now encompasses all interventions that promote normal development and prevent disabilities, including organisational, therapeutic and environment-modifying measures, such as early stimulation programs. Early stimulation programs were first devised in the United States for vulnerable children in low-income families; positive effects were recorded regarding school failure rates and social problems. Programs have also been implemented in several countries for premature infants and low-birth-weight infants, who are at high risk for neurodevelopmental abnormalities. The programs target the child, the parents or both. The best evaluated programs are the NIDCAP (Newborn Individualized Developmental Care and Assessment Program) in Sweden for babiesneonatal intensive care units and the longitudinal multisite program IHDP (Infant Health and Development Program) created in the United States for infantsstimulation improved cognitive outcomes and child-parent interactions; cognition showed greater improvements than motor skills and larger benefits were obtained in families that combined several risk factors including low education attainment by the mothers.

  10. Gene expression changes and early events in cotton fibre development. (United States)

    Lee, Jinsuk J; Woodward, Andrew W; Chen, Z Jeffrey


    Cotton is the dominant source of natural textile fibre and a significant oil crop. Cotton fibres, produced by certain species in the genus Gossypium, are seed trichomes derived from individual cells of the epidermal layer of the seed coat. Cotton fibre development is delineated into four distinct and overlapping developmental stages: fibre initiation, elongation, secondary wall biosynthesis and maturation. Recent advances in gene expression studies are beginning to provide new insights into a better understanding of early events in cotton fibre development. Fibre cell development is a complex process involving many pathways, including various signal transduction and transcriptional regulation components. Several analyses using expressed sequence tags and microarray have identified transcripts that preferentially accumulate during fibre development. These studies, as well as complementation and overexpression experiments using cotton genes in arabidopsis and tobacco, indicate some similar molecular events between trichome development from the leaf epidermis and fibre development from the ovule epidermis. Specifically, MYB transcription factors regulate leaf trichome development in arabidopsis and may regulate seed trichome development in cotton. In addition, transcript profiling and ovule culture experiments both indicate that several phytohormones and other signalling pathways mediate cotton fibre development. Auxin and gibberellins promote early stages of fibre initiation; ethylene- and brassinosteroid-related genes are up-regulated during the fibre elongation phase; and genes associated with calmodulin and calmodulin-binding proteins are up-regulated in fibre initials. Additional genomic data, mutant and functional analyses, and genome mapping studies promise to reveal the critical factors mediating cotton fibre cell development.

  11. Early motor development, early visual attention and functional outcome in children : insights into functional brain development

    NARCIS (Netherlands)

    Hitzert, Marrit


    In this thesis, we investigated development of motor behavior and visual attention in the first six months of life, in relation to risk factors for an adverse development and in relation to functional outcome of the children later in life. We investigated variability in motor behavior by assessing

  12. Fathers' sensitive parenting and the development of early executive functioning. (United States)

    Towe-Goodman, Nissa R; Willoughby, Michael; Blair, Clancy; Gustafsson, Hanna C; Mills-Koonce, W Roger; Cox, Martha J


    Using data from a diverse sample of 620 families residing in rural, predominately low-income communities, this study examined longitudinal links between fathers' sensitive parenting in infancy and toddlerhood and children's early executive functioning, as well as the contribution of maternal sensitive parenting. After accounting for the quality of concurrent and prior parental care, children's early cognitive ability, and other child and family factors, fathers' and mothers' sensitive and supportive parenting during play at 24 months predicted children's executive functioning at 3 years of age. In contrast, paternal parenting quality during play at 7 months did not make an independent contribution above that of maternal care, but the links between maternal sensitive and supportive parenting and executive functioning seemed to operate in similar ways during infancy and toddlerhood. These findings add to prior work on early experience and children's executive functioning, suggesting that both fathers and mothers play a distinct and complementary role in the development of these self-regulatory skills.

  13. Early vocabulary development in children with bilateral cochlear implants. (United States)

    Välimaa, Taina; Kunnari, Sari; Laukkanen-Nevala, Päivi; Lonka, Eila


    Children with unilateral cochlear implants (CIs) may have delayed vocabulary development for an extended period after implantation. Bilateral cochlear implantation is reported to be associated with improved sound localization and enhanced speech perception in noise. This study proposed that bilateral implantation might also promote early vocabulary development. Knowledge regarding vocabulary growth and composition in children with bilateral CIs and factors associated with it may lead to improvements in the content of early speech and language intervention and family counselling. To analyse the growth of early vocabulary and its composition during the first year after CI activation and to investigate factors associated with vocabulary growth. The participants were 20 children with bilateral CIs (12 boys; eight girls; mean age at CI activation = 12.9 months). Vocabulary size was assessed with the Finnish version of the MacArthur Communicative Development Inventories (CDI) Infant Form and compared with normative data. Vocabulary composition was analysed in relation to vocabulary size. Growth curve modelling was implemented using a linear mixed model to analyse the effects of the following variables on early vocabulary growth: time, gender, maternal education, residual hearing with hearing aids, age at first hearing aid fitting and age at CI activation. Despite clear vocabulary growth over time, children with bilateral CIs lagged behind their age norms in receptive vocabulary during the first 12 months after CI activation. In expressive vocabulary, 35% of the children were able to catch up with their age norms, but 55% of the children lagged behind them. In receptive and expressive vocabularies of 1-20 words, analysis of different semantic categories indicated that social terms constituted the highest proportion. Nouns constituted the highest proportion in vocabularies of 101-400 words. The proportion of verbs remained below 20% and the proportion of function words and

  14. Early exposure to maternal voice: effects on preterm infants development. (United States)

    Picciolini, Odoardo; Porro, Matteo; Meazza, Anna; Giannì, Maria Lorella; Rivoli, Chiara; Lucco, Giovanna; Barretta, Francesco; Bonzini, Matteo; Mosca, Fabio


    Preterm infants complete their development in Neonatal Intensive Care Unit being exposed to environmental stimuli that lead to the early maturation of the sensory systems. It is known that the fetus perceives sounds and reacts to them with movements since the 26th-28th week of gestational age. Maternal voice represents a source of sensory stimulation for the fetus. To investigate the effect of the exposure to maternal voice, administered by bone conduction, on preterm infants autonomic and neurobehavioral development. Longitudinal, explorative, case control study. 71 preterm infants with birth weight Early exposure to maternal voice exerts a beneficial effect on preterm infants autonomic and neurobehavioral development. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Early development of the root-knot nematode Meloidogyne incognita. (United States)

    Calderón-Urrea, Alejandro; Vanholme, Bartel; Vangestel, Sandra; Kane, Saben M; Bahaji, Abdellatif; Pha, Khavong; Garcia, Miguel; Snider, Alyssa; Gheysen, Godelieve


    Detailed descriptions of the early development of parasitic nematodes are seldom available. The embryonic development of the plant-parasitic nematode Meloidogyne incognita was studied, focusing on the early events. A fixed pattern of repeated cell cleavages was observed, resulting in the appearance of the six founder cells 3 days after the first cell division. Gastrulation, characterized by the translocation of cells from the ventral side to the center of the embryo, was seen 1 day later. Approximately 10 days after the first cell division a rapidly elongating two-fold stage was reached. The fully developed second stage juvenile hatched approximately 21 days after the first cell division. When compared to the development of the free-living nematode Caenorhabditis elegans, the development of M. incognita occurs approximately 35 times more slowly. Furthermore, M. incognita differs from C. elegans in the order of cell divisions, and the early cleavage patterns of the germ line cells. However, cytoplasmic ruffling and nuclear migration prior to the first cell division as well as the localization of microtubules are similar between C. elegans and M. incognita.

  16. Early childhood WIC participation, cognitive development and academic achievement. (United States)

    Jackson, Margot I


    For the 22% of American children who live below the federal poverty line, and the additional 23% who live below twice that level, nutritional policy is part of the safety net against hunger and its negative effects on children's development. The Special Supplemental Nutrition Program for Women, Infants and Children (WIC) provides steadily available food from the food groups essential for physical and cognitive development. The effects of WIC on dietary quality among participating women and children are strong and positive. Furthermore, there is a strong influence of nutrition on cognitive development and socioeconomic inequality. Yet, research on the non-health effects of U.S. child nutritional policy is scarce, despite the ultimate goal of health policies directed at children-to enable productive functioning across multiple social institutions over the life course. Using two nationally representative, longitudinal surveys of children-the Early Childhood Longitudinal Study, Birth Cohort (ECLS-B) and the Child Development Supplement (CDS) of the Panel Study of Income Dynamics-I examine how prenatal and early childhood exposure to WIC is associated in the short-term with cognitive development, and in the longer-term with reading and math learning. Results show that early WIC participation is associated with both cognitive and academic benefits. These findings suggest that WIC meaningfully contributes to children's educational prospects. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Early stress and human behavioral development: emerging evolutionary perspectives. (United States)

    Del Giudice, M


    Stress experienced early in life exerts a powerful, lasting influence on development. Converging empirical findings show that stressful experiences become deeply embedded in the child's neurobiology, with an astonishing range of long-term effects on cognition, emotion, and behavior. In contrast with the prevailing view that such effects are the maladaptive outcomes of 'toxic' stress, adaptive models regard them as manifestations of evolved developmental plasticity. In this paper, I offer a brief introduction to adaptive models of early stress and human behavioral development, with emphasis on recent theoretical contributions and emerging concepts in the field. I begin by contrasting dysregulation models of early stress with their adaptive counterparts; I then introduce life history theory as a unifying framework, and review recent work on predictive adaptive responses (PARs) in human life history development. In particular, I discuss the distinction between forecasting the future state of the environment (external prediction) and forecasting the future state of the organism (internal prediction). Next, I present the adaptive calibration model, an integrative model of individual differences in stress responsivity based on life history concepts. I conclude by examining how maternal-fetal conflict may shape the physiology of prenatal stress and its adaptive and maladaptive effects on postnatal development. In total, I aim to show how theoretical work from evolutionary biology is reshaping the way we think about the role of stress in human development, and provide researchers with an up-to-date conceptual map of this fascinating and rapidly evolving field.

  18. Regenerating CNS myelin - from mechanisms to experimental medicines. (United States)

    Franklin, Robin J M; Ffrench-Constant, Charles


    Although the core concept of remyelination - based on the activation, migration, proliferation and differentiation of CNS progenitors - has not changed over the past 20 years, our understanding of the detailed mechanisms that underlie this process has developed considerably. We can now decorate the central events of remyelination with a host of pathways, molecules, mediators and cells, revealing a complex and precisely orchestrated process. These advances have led to recent drug-based and cell-based clinical trials for myelin diseases and have opened up hitherto unrecognized opportunities for drug-based approaches to therapeutically enhance remyelination.

  19. Early Life Growth Predicts Pubertal Development in South African Adolescents. (United States)

    Lundeen, Elizabeth A; Norris, Shane A; Martorell, Reynaldo; Suchdev, Parminder S; Mehta, Neil K; Richter, Linda M; Stein, Aryeh D


    Given global trends toward earlier onset of puberty and the adverse psychosocial consequences of early puberty, it is important to understand the childhood predictors of pubertal timing and tempo. We examined the association between early growth and the timing and tempo of puberty in adolescents in South Africa. We analyzed prospectively collected data from 1060 boys and 1135 girls participating in the Birth-to-Twenty cohort in Soweto, South Africa. Height-for-age z scores (HAZs) and body mass index-for-age z scores (BMIZs) were calculated based on height (centimeters) and body mass index (kilograms per meter squared) at ages 5 y and 8 y. The development of genitals, breasts, and pubic hair was recorded annually from 9 to 16 y of age with the use of the Tanner sexual maturation scale (SMS). We used latent class growth analysis to identify pubertal trajectory classes and also characterized children as fast or slow developers based on the SMS score at 12 y of age. We used multinomial logistic regression to estimate associations of HAZ and BMIZ at ages 5 and 8 y with pubertal development. We identified 3 classes for pubic hair development (for both girls and boys) and 4 classes for breast (for girls) and genital (for boys) development. In girls, both HAZ and BMIZ at age 5 y were positively associated with pubic hair development [relative risk ratio (RRR): 1.57, P development. In boys, HAZ and BMIZ at age 5 y were positively associated with pubic hair development (RRR: 1.78, P development of genitals (RRR: 2.19, P development. This may provide a tool to identify children at risk of early pubertal onset.

  20. The Early Motor Questionnaire (EMQ): a parental report measure of early motor development. (United States)

    Libertus, Klaus; Landa, Rebecca J


    Children's early motor skills are critical for development across language, social, and cognitive domains, and warrant close examination. However, examiner-administered motor assessments are time consuming and expensive. Parent-report questionnaires offer an efficient alternative, but validity of parent report is unclear and only few motor questionnaires exist. In this report, we use cross-sectional and longitudinal data to investigate the validity of parent report in comparison to two examiner-administered measures (Mullen Scales of Early Learning, MSEL; Peabody Developmental Motor Scales, PDMS-2), and introduce a new parent-report measure called the Early Motor Questionnaire (EMQ). Results indicate strong correlations between parent report on the EMQ and a child's age, robust concurrent and predictive validity of parent report with both the MSEL and PDMS-2, and good test-retest reliability of parent report on the EMQ. Together, our findings support the conclusion that parents provide dependable accounts of early motor and cognitive development. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Early development of physical aggression and early risk factors for chronic physical aggression in humans. (United States)

    Tremblay, Richard E


    This chapter describes the state of knowledge on the development of physical aggression from early childhood to adulthood, the long term outcomes of chronic physical aggression during childhood and the risk factors for chronic physical aggression. Unraveling the development of physical aggression is important to understand when and why humans start using physical aggression, to understand why some humans suffer from chronic physical aggression and to understand how to prevent the development of this disorder which causes much distress to the aggressors and their victims. The study of the developmental origins of aggression also sheds light on the reasons why situational prevention of aggression is important at all ages and in all cultures.

  2. Socioeconomic status and functional brain development - associations in early infancy. (United States)

    Tomalski, Przemyslaw; Moore, Derek G; Ribeiro, Helena; Axelsson, Emma L; Murphy, Elizabeth; Karmiloff-Smith, Annette; Johnson, Mark H; Kushnerenko, Elena


    Socioeconomic status (SES) impacts on both structural and functional brain development in childhood, but how early its effects can be demonstrated is unknown. In this study we measured resting baseline EEG activity in the gamma frequency range in awake 6-9-month-olds from areas of East London with high socioeconomic deprivation. Between-subject comparisons of infants from low- and high-income families revealed significantly lower frontal gamma power in infants from low-income homes. Similar power differences were found when comparing infants according to maternal occupation, with lower occupational status groups yielding lower power. Infant sleep, maternal education, length of gestation, and birth weight, as well as smoke exposure and bilingualism, did not explain these differences. Our results show that the effects of socioeconomic disparities on brain activity can already be detected in early infancy, potentially pointing to very early risk for language and attention difficulties. This is the first study to reveal region-selective differences in functional brain development associated with early infancy in low-income families. © 2013 John Wiley & Sons Ltd.

  3. [Dental caries and early childhood development: a pilot study]. (United States)

    Núñez, F Loreto; Sanz, B Javier; Mejía, L Gloria


    To investigate the association between dental caries and early childhood development in 3-year-olds from Talca, Chile. A pilot study with a convenience sample of 3-year-olds from Talca (n = 39) who attend public healthcare centers. Child development was measured by the Psychomotor Development Index (PDI), a screening tool used nationally among pre-school children to assess language development, fine motor skills and coordination areas. Dental caries prevalence was evaluated by decayed, missing, filled teeth (DFMT) and decayed, missing, filled tooth surfaces (DFMS) ceo-d and ceo-s indexes. The children were divided into two groups according to the PDIscore: those with a score of 40 or more were considered developmentally normal (n = 32), and those with a score below 40 were considered as having impaired development (n = 7). The severity of caries (DMFT) was negatively correlated with PDI (r = -0.82), and children with the lowest TEPSI score had the highest DFMT values. The average DMFT in children with normal development was 1.31, and 3.57 for those with impaired development. This pilot study indicates that the severity of dental caries is correlated with early childhood development. Copyright © 2015. Publicado por Elsevier España, S.L.U.

  4. Early Bifrontal Brain Injury: Disturbances in Cognitive Function Development

    Directory of Open Access Journals (Sweden)

    Christine Bonnier


    Full Text Available We describe six psychomotor, language, and neuropsychological sequential developmental evaluations in a boy who sustained a severe bifrontal traumatic brain injury (TBI at 19 months of age. Visuospatial, drawing, and writing skills failed to develop normally. Gradually increasing difficulties were noted in language leading to reading and spontaneous speech difficulties. The last two evaluations showed executive deficits in inhibition, flexibility, and working memory. Those executive abnormalities seemed to be involved in the other impairments. In conclusion, early frontal brain injury disorganizes the development of cognitive functions, and interactions exist between executive function and other cognitive functions during development.

  5. Proceedings of the 2013 CINP summit: innovative partnerships to accelerate CNS drug discovery for improved patient care. (United States)

    Phillips, Anthony George; Hongaard-Andersen, Peter; Moscicki, Richard A; Sahakian, Barbara; Quirion, Rémi; Krishnan, K Ranga Rama; Race, Tim


    Central nervous system (CNS) diseases and, in particular, mental health disorders, are becoming recognized as the health challenge of the 21(st) century. Currently, at least 10% of the global population is affected by a mental health disorder, a figure that is set to increase year on year. Meanwhile, the rate of development of new CNS drugs has not increased for many years, despite unprecedented levels of investment. In response to this state of affairs, the Collegium Internationale Neuro-Psychopharmacologicum (CINP) convened a summit to discuss ways to reverse this disturbing trend through new partnerships to accelerate CNS drug discovery. The objectives of the Summit were to explore the issues affecting the value chain (i.e. the chain of activities or stakeholders that a company engages in/with to deliver a product to market) in brain research, thereby gaining insights from key stakeholders and developing actions to address unmet needs; to identify achievable objectives to address the issues; to develop action plans to bring about measurable improvements across the value chain and accelerate CNS drug discovery; and finally, to communicate recommendations to governments, the research and development community, and other relevant stakeholders. Summit outputs include the following action plans, aligned to the pressure points within the brain research-drug development value chain: Code of conduct dealing with conflict of interest issues, Prevention, early diagnosis, and treatment, Linking science and regulation, Patient involvement in trial design, definition of endpoints, etc., Novel trial design, Reproduction and confirmation of data, Update of intellectual property (IP) laws to facilitate repurposing and combination therapy (low priority), Large-scale, global patient registries, Editorials on nomenclature, biomarkers, and diagnostic tools, and Public awareness, with brain disease advocates to attend G8 meetings and World Economic Forum (WEF) Annual meetings in

  6. Social conversational skills development in early implanted children. (United States)

    Guerzoni, Letizia; Murri, Alessandra; Fabrizi, Enrico; Nicastri, Maria; Mancini, Patrizia; Cuda, Domenico


    Social conversational skills are a salient aspect of early pragmatic development in young children. These skills include two different abilities, assertiveness and responsiveness. This study investigated the development of these abilities in early implanted children and their relationships with lexical development and some language-sensitive variables. Prospective, observational, nonrandomized study. Participants included 28 children with congenital profound sensorineural hearing loss. The mean age at device activation was 13.3 months (standard deviation [SD] ±4.2). The Social-Conversational Skills Rating Scale was used to evaluate assertiveness and responsiveness. The MacArthur-Bates Communicative Development Inventory (Words and Sentences form) was used to analyze the lexical development. The device experience was 12 months for each child, and the mean age at testing was 25.9 months (SD ±4.6). Assertiveness and responsiveness scores were within the normal range of normal-hearing age-matched peers. Age at cochlear implant activation exerted a significant impact, with the highest scores associated to the youngest patients. The residual correlations between assertiveness and responsiveness with the lexical development were positive and strongly significant (r = 0.69 and 0.73, respectively). Preoperative hearing threshold demonstrated an associated significant coefficient on the assertiveness score. Age at diagnosis and maternal education level were not correlated with the social conversational skills. Early-implanted children developed social conversational skills that are similar to normal-hearing peers matched for age 1 year after device activation. Social conversational skills and lexical development were strongly correlated, but the present study design cannot specify the direction of this relationship. Children with better preoperative residual hearing exhibited better assertive ability. 4 Laryngoscope, 126:2098-2105, 2016. © 2015 The American Laryngological

  7. Conditions on Early Mars Might Have Fostered Rapid and Early Development of Life (United States)

    Gibson, Everett K.; McKay, David S.; Thomas-Keprta, Kathie L.; Clemett, Simon J.; Wentworth, Susan J.


    The exploration of Mars during the past decades has begun to unveil the history of the planet. The combinations of remote sensing, in situ geochemical compositional measurements and photographic observations from both above and on the surface have shown Mars to have a dynamic and active geologic evolution. Mars geologic evolution clearly had conditions that were suitable for supporting life. For a planet to be able to be habitable, it must have water, carbon sources, energy sources and a dynamic geologic past. Mars meets all of these requirements. The first 600 My of Martian history were ripe for life to develop because of the abundance of (i) Water-carved canyons and oceans or lakes with the early presence of near surface water shown by precipitated carbonates in ALH84001 well-dated at approx.3.9 Gy., (ii) Energy from the original accretional processes, a molten core which generated a strong magnetic field leaving a permanent record in the early crust, early active volcanism continuing throughout Martian history, and, and continuing impact processes, (iii) Carbon and water from possibly extensive volcanic outgassing (i.e. H2O, CO2, CH4, CO, O2, N2, H2S, SO2, etc.) and (iv) some crustal tectonics as revealed by faulting and possible plate movement reflected by the magnetic pattern in the crust. The question arises: "Why would life not evolve from these favorable conditions on early Mars in its first 600 My?" During this period, it seems likely that environmental near-surface conditions on Mars were more favorable to life than at any later time. Standing bodies of water, precipitation and flowing surface water, and possibly abundant hydrothermal energy would all favor the formation of early life. Even if life developed elsewhere (on Earth, Venus, or on other solar systems) and was transported to Mars, the surface conditions were likely very hospitable for that introduced life to multiply and evolve.

  8. SINS/CNS Nonlinear Integrated Navigation Algorithm for Hypersonic Vehicle

    Directory of Open Access Journals (Sweden)

    Yong-jun Yu


    Full Text Available Celestial Navigation System (CNS has characteristics of accurate orientation and strong autonomy and has been widely used in Hypersonic Vehicle. Since the CNS location and orientation mainly depend upon the inertial reference that contains errors caused by gyro drifts and other error factors, traditional Strap-down Inertial Navigation System (SINS/CNS positioning algorithm setting the position error between SINS and CNS as measurement is not effective. The model of altitude azimuth, platform error angles, and horizontal position is designed, and the SINS/CNS tightly integrated algorithm is designed, in which CNS altitude azimuth is set as measurement information. GPF (Gaussian particle filter is introduced to solve the problem of nonlinear filtering. The results of simulation show that the precision of SINS/CNS algorithm which reaches 130 m using three stars is improved effectively.

  9. The movers and shapers in immune privilege of the CNS. (United States)

    Engelhardt, Britta; Vajkoczy, Peter; Weller, Roy O


    Discoveries leading to an improved understanding of immune surveillance of the central nervous system (CNS) have repeatedly provoked dismissal of the existence of immune privilege of the CNS. Recent rediscoveries of lymphatic vessels within the dura mater surrounding the brain, made possible by modern live-cell imaging technologies, have revived this discussion. This review emphasizes the fact that understanding immune privilege of the CNS requires intimate knowledge of its unique anatomy. Endothelial, epithelial and glial brain barriers establish compartments in the CNS that differ strikingly with regard to their accessibility to immune-cell subsets. There is a unique system of lymphatic drainage from the CNS to the peripheral lymph nodes. We summarize current knowledge on the cellular and molecular mechanisms involved in immune-cell trafficking and lymphatic drainage from the CNS, and we take into account differences in rodent and human CNS anatomy.

  10. Central Nervous System (CNS Disease Triggering Takotsubo Syndrome

    Directory of Open Access Journals (Sweden)

    Josef Finsterer


    Full Text Available Takotsubo syndrome (TTS is usually triggered by psychological or physical stress. One of the many physical sources of stress are central nervous system (CNS disorders. CNS disorders most frequently triggering TTS include subarachnoid bleeding, epilepsy, ischemic stroke, migraine, and intracerebral bleeding. More rare CNS-triggers of TTS include posterior reversible encephalopathy syndrome (PRES, amyotrophic lateral sclerosis, encephalitis, or traumatic brain or spinal cord injury. TTS triggered by any of the CNS disorders needs to be recognized since adequate treatment of TTS may improve the general outcome from the CNS disorder as well. Neurologists need to be aware of TTS as a complication of specific CNS disorders but TTS may be triggered also by CNS disorders so far not recognised as causes of TTS.

  11. Early development of selenium-induced cataract: slit lamp evaluation. (United States)

    Shearer, T R; Anderson, R S; Britton, J L; Palmer, E A


    The purpose of our research was to document early lenticular changes preceding cataract formation in rats receiving an elevated dose of selenium. The following stages were observed after selenium injection: Stage 1 (13-24 hr post-injection), formation of posterior equatorial subcapsular cataract (PESC); Stage 2 (24-72 hr), decline of the PESC, development of a prominent 'washer' shaped change in the refraction of the cortex, and first appearance of swollen fibers around the nucleus; Stage 3 (three to five days), appearance of bilateral dense central nuclear cataracts and further development of perinuclear swollen fibers; Stage 4 (five to 10 days), some nuclear cataracts became more opaque and/or angular. The results are consistent with the hypothesis that the initial site of action of selenium in nuclear cataract formation is not in the lens nucleus. Rather, selenium causes early changes outside the nucleus, which are followed by nuclear cataracts.

  12. Development of SED Camera for Quasars in Early Universe (SQUEAN)


    Kim, Sanghyuk; Jeon, Yiseul; Lee, Hye-In; Park, Woojin; Ji, Tae-Geun; Hyun, Minhee; Choi, Changsu; Im, Myungshin; Pak, Soojong


    We describe the characteristics and performance of a camera system, Spectral energy distribution Camera for Quasars in Early Universe (SQUEAN). It was developed to measure SEDs of high redshift quasar candidates (z $\\gtrsim$ 5) and other targets, e.g., young stellar objects, supernovae, and gamma-ray bursts, and to trace the time variability of SEDs of objects such as active galactic nuclei (AGNs). SQUEAN consists of an on-axis focal plane camera module, an auto-guiding system, and mechanical...

  13. Educational homogamy, parenting practices and children’s early development



    This thesis investigates the pattern of parental educational homogamy and its implications for parenting practices and children’s early development in contemporary Britain. At the heart of the thesis lies an interest in the mechanisms behind the intergenerational transmission of educational success and, more specifically, the consequences for children of new patterns of parental resemblance in education. The thesis is composed of three empirical chapters, each of which is concerned with a...

  14. Early development and replacement of the stickleback dentition. (United States)

    Ellis, Nicholas A; Donde, Nikunj N; Miller, Craig T


    Teeth have long served as a model system to study basic questions about vertebrate organogenesis, morphogenesis, and evolution. In nonmammalian vertebrates, teeth typically regenerate throughout adult life. Fish have evolved a tremendous diversity in dental patterning in both their oral and pharyngeal dentitions, offering numerous opportunities to study how morphology develops, regenerates, and evolves in different lineages. Threespine stickleback fish (Gasterosteus aculeatus) have emerged as a new system to study how morphology evolves, and provide a particularly powerful system to study the development and evolution of dental morphology. Here, we describe the oral and pharyngeal dentitions of stickleback fish, providing additional morphological, histological, and molecular evidence for homology of oral and pharyngeal teeth. Focusing on the ventral pharyngeal dentition in a dense developmental time course of lab-reared fish, we describe the temporal and spatial consensus sequence of early tooth formation. Early in development, this sequence is highly stereotypical and consists of seventeen primary teeth forming the early tooth field, followed by the first tooth replacement event. Comparing this detailed morphological and ontogenetic sequence to that described in other fish reveals that major changes to how dental morphology arises and regenerates have evolved across different fish lineages. J. Morphol. 277:1072-1083, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  15. Hazards to Early Development: The Biological Embedding of Early Life Adversity. (United States)

    Nelson, Charles A


    The number of children under 18 years of age has increased worldwide over the past decade. This growth spurt is due, in part, to remarkable progress in child survival. Alas, surviving early hazards, like prematurity or infectious disease, does not guarantee that children's development will not be compromised by other hazards as they grow older. Throughout the world, children continue to be confronted with a large number of biological and psychosocial challenges that greatly limit their developmental potential. The focus of this article is how such adverse experiences impact the developing brain. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Development of tsunami early warning systems and future challenges

    Directory of Open Access Journals (Sweden)

    J. Wächter


    Full Text Available Fostered by and embedded in the general development of information and communications technology (ICT, the evolution of tsunami warning systems (TWS shows a significant development from seismic-centred to multi-sensor system architectures using additional sensors (e.g. tide gauges and buoys for the detection of tsunami waves in the ocean.

    Currently, the beginning implementation of regional tsunami warning infrastructures indicates a new phase in the development of TWS. A new generation of TWS should not only be able to realise multi-sensor monitoring for tsunami detection. Moreover, these systems have to be capable to form a collaborative communication infrastructure of distributed tsunami warning systems in order to implement regional, ocean-wide monitoring and warning strategies.

    In the context of the development of the German Indonesian Tsunami Early Warning System (GITEWS and in the EU-funded FP6 project Distant Early Warning System (DEWS, a service platform for both sensor integration and warning dissemination has been newly developed and demonstrated. In particular, standards of the Open Geospatial Consortium (OGC and the Organization for the Advancement of Structured Information Standards (OASIS have been successfully incorporated.

    In the FP7 project Collaborative, Complex and Critical Decision-Support in Evolving Crises (TRIDEC, new developments in ICT (e.g. complex event processing (CEP and event-driven architecture (EDA are used to extend the existing platform to realise a component-based technology framework for building distributed tsunami warning systems.

  17. Development of tsunami early warning systems and future challenges (United States)

    Wächter, J.; Babeyko, A.; Fleischer, J.; Häner, R.; Hammitzsch, M.; Kloth, A.; Lendholt, M.


    Fostered by and embedded in the general development of information and communications technology (ICT), the evolution of tsunami warning systems (TWS) shows a significant development from seismic-centred to multi-sensor system architectures using additional sensors (e.g. tide gauges and buoys) for the detection of tsunami waves in the ocean. Currently, the beginning implementation of regional tsunami warning infrastructures indicates a new phase in the development of TWS. A new generation of TWS should not only be able to realise multi-sensor monitoring for tsunami detection. Moreover, these systems have to be capable to form a collaborative communication infrastructure of distributed tsunami warning systems in order to implement regional, ocean-wide monitoring and warning strategies. In the context of the development of the German Indonesian Tsunami Early Warning System (GITEWS) and in the EU-funded FP6 project Distant Early Warning System (DEWS), a service platform for both sensor integration and warning dissemination has been newly developed and demonstrated. In particular, standards of the Open Geospatial Consortium (OGC) and the Organization for the Advancement of Structured Information Standards (OASIS) have been successfully incorporated. In the FP7 project Collaborative, Complex and Critical Decision-Support in Evolving Crises (TRIDEC), new developments in ICT (e.g. complex event processing (CEP) and event-driven architecture (EDA)) are used to extend the existing platform to realise a component-based technology framework for building distributed tsunami warning systems.

  18. Global Sustainable Development Starts With Investment in the Early Brain Development of Children

    National Research Council Canada - National Science Library

    Benard P Dreyer


    .... Bann et al present the results of longitudinal analyses of a randomized controlled trial of a home-based early developmental intervention on trajectories of cognitive development among young children...

  19. Early childhood development: impact of national human development, family poverty, parenting practices and access to early childhood education. (United States)

    Tran, T D; Luchters, S; Fisher, J


    This study was to describe and quantify the relationships among family poverty, parents' caregiving practices, access to education and the development of children living in low- and middle-income countries (LAMIC). We conducted a secondary analysis of data collected in UNICEF's Multiple Indicator Cluster Surveys (MICS). Early childhood development was assessed in four domains: language-cognitive, physical, socio-emotional and approaches to learning. Countries were classified into three groups on the basis of the Human Development Index (HDI). Overall, data from 97 731 children aged 36 to 59 months from 35 LAMIC were included in the after analyses. The mean child development scale score was 4.93 out of a maximum score of 10 (95%CI 4.90 to 4.97) in low-HDI countries and 7.08 (95%CI 7.05 to 7.12) in high-HDI countries. Family poverty was associated with lower child development scores in all countries. The total indirect effect of family poverty on child development score via attending early childhood education, care for the child at home and use of harsh punishments at home was -0.13 SD (77.8% of the total effect) in low-HDI countries, -0.09 SD (23.8% of the total effect) in medium-HDI countries and -0.02 SD (6.9% of the total effect) in high-HDI countries. Children in the most disadvantaged position in their societies and children living in low-HDI countries are at the greatest risk of failing to reach their developmental potential. Optimizing care for child development at home is essential to reduce the adverse effects of poverty on children's early development and subsequent life. © 2016 John Wiley & Sons Ltd.

  20. Thyroid Function during Early Life and Dental Development. (United States)

    Vucic, S; Korevaar, T I M; Dhamo, B; Jaddoe, V W V; Peeters, R P; Wolvius, E B; Ongkosuwito, E M


    Children with low levels of thyroid hormones (hypothyroidism) have delayed tooth eruption, enamel hypoplasia, micrognathia, and anterior open bite, whereas children with hyperthyroidism may suffer from accelerated tooth eruption, maxillary, and mandibular osteoporosis. However, it is still unknown whether thyroid function variations within the normal or subclinical range also have an impact on hard dental tissues in healthy children. The objective of this study was, therefore, to investigate the association between thyroid function from the fetal period until early childhood and dental development at school age. This study is embedded in the Generation R Study, a population-based cohort study established in Rotterdam, the Netherlands. Maternal thyroid function (thyroid-stimulating hormone [TSH], free thyroxine [FT4], and thyroid peroxidase antibody [TPOAb] concentrations) was measured during early pregnancy, and thyroid function of the offspring (TSH and FT4) was measured in cord blood at birth and in early childhood (6 y). Dental development was assessed from panoramic radiographs of children of school-going age (9 y). In total, 2,387 to 2,706 subjects were available for the multivariable linear regression analysis, depending on the point in time of thyroid function measurement. There was an inverse association between cord blood and early childhood TSH concentrations with dental development, with a -0.06 lower standard deviation (SD) per 1 mU/L of TSH (95% confidence interval [CI], -0.11 to -0.01) and a -0.06 lower SD per 1 mU/L of TSH (95% CI, -0.11 to 0.00), respectively. There was no association between the maternal thyroid function during pregnancy and the dental development score of the child. However, TPOAb-positive mothers had children with a -0.20 SD (adjusted 95% CI, -0.35 to -0.04) lower dental development score compared with TPOAb-negative mothers. The findings of this study suggest that the thyroid hormone is involved in the maturation of teeth from

  1. Superficial siderosis of the CNS. MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Uchino, Akira; Matsuo, Yoshiaki; Kato, Akira; Kudo, Sho [Saga Medical School, Nabeshima (Japan); Matsumoto, Shunichi


    Six cases of superficial siderosis of the CNS are reported here. There were 4 men and 2 women, whose ages ranged from 25 to 69 years. The clinical presentations included bilateral sensorineural hearing loss (6), cerebellar ataxia (4), and myelopathy (2). Typical hypointense rims were observed over the brain surface on T2-weighted images. Five of the 6 patients had atrophy of the superior cerebellar vermis. The spinal cord was involved in 5 of the 6 patients. On T1-weighted images, hyperintense rims were demonstrated over the brain surface in 3 of the 6 patients. This finding has not been previously reported. (author)

  2. Media representations of early human development: protecting, feeding and loving the developing brain.


    O Connor, C.; Joffe, H.


    The public profile of neurodevelopmental research has expanded in recent years. This paper applies social representations theory to explore how early brain development was represented in the UK print media in the first decade of the 21st century. A thematic analysis was performed on 505 newspaper articles published between 2000 and 2010 that discussed early brain development. Media coverage centred around concern with ‘protecting’ the prenatal brain (identifying threats to foetal neurodevelop...

  3. Natural host genetic resistance to lentiviral CNS disease: a neuroprotective MHC class I allele in SIV-infected macaques.

    Directory of Open Access Journals (Sweden)

    Joseph L Mankowski

    Full Text Available Human immunodeficiency virus (HIV infection frequently causes neurologic disease even with anti-retroviral treatment. Although associations between MHC class I alleles and acquired immunodeficiency syndrome (AIDS have been reported, the role MHC class I alleles play in restricting development of HIV-induced organ-specific diseases, including neurologic disease, has not been characterized. This study examined the relationship between expression of the MHC class I allele Mane-A*10 and development of lentiviral-induced central nervous system (CNS disease using a well-characterized simian immunodeficiency (SIV/pigtailed macaque model. The risk of developing CNS disease (SIV encephalitis was 2.5 times higher for animals that did not express the MHC class I allele Mane-A*10 (P = 0.002; RR = 2.5. Animals expressing the Mane-A*10 allele had significantly lower amounts of activated macrophages, SIV RNA, and neuronal dysfunction in the CNS than Mane-A*10 negative animals (P<0.001. Mane-A*10 positive animals with the highest CNS viral burdens contained SIV gag escape mutants at the Mane-A*10-restricted KP9 epitope in the CNS whereas wild type KP9 sequences dominated in the brain of Mane-A*10 negative animals with comparable CNS viral burdens. These concordant findings demonstrate that particular MHC class I alleles play major neuroprotective roles in lentiviral-induced CNS disease.

  4. Gestural development and its relation to a child's early vocabulary. (United States)

    Kraljević, Jelena Kuvač; Cepanec, Maja; Simleša, Sanja


    Gesture and language are tightly connected during the development of a child's communication skills. Gestures mostly precede and define the way of language development; even opposite direction has been found. Few recent studies have focused on the relationship between specific gestures and specific word categories, emphasising that the onset of one gesture type predicts the onset of certain word categories or of the earliest word combinations. The aim of this study was to analyse predicative roles of different gesture types on the onset of first word categories in a child's early expressive vocabulary. Our data show that different types of gestures predict different types of word production. Object gestures predict open-class words from the age of 13 months, and gestural routines predict closed-class words and social terms from 8 months. Receptive vocabulary has a strong mediating role for all linguistically defined categories (open- and closed-class words) but not for social terms, which are the largest word category in a child's early expressive vocabulary. Accordingly, main contribution of this study is to define the impact of different gesture types on early expressive vocabulary and to determine the role of receptive vocabulary in gesture-expressive vocabulary relation in the Croatian language. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Early motor development of children with a congenital cytomegalovirus infection. (United States)

    De Kegel, Alexandra; Maes, Leen; Dhooge, Ingeborg; van Hoecke, Helen; De Leenheer, Els; Van Waelvelde, Hilde


    Congenital cytomegalovirus (cCMV) infection is the most important etiology of non-hereditary childhood hearing loss and an important cause of neurodevelopmental delay. The current study aimed to investigate the early motor development of symptomatic and asymptomatic cCMV infected children with and without sensorineural hearing loss (SNHL). Sixty-four children with a cCMV infection, without cerebral palsy, were compared to a control group of 107 normal hearing children. They were assessed around the ages of 6, 12, and 24 months with the Peabody Developmental Motor Scales-2 (PDMS-2), Alberta Infant Motor Scales (AIMS), and Ghent Developmental Balance Test (GDBT). The cCMV infected children were subdivided into a symptomatic (n=26) and asymptomatic cCMV group (n=38) but also into a cCMV group with SNHL (n=19) and without SNHL (n=45). Symptomatic cCMV infected children and cCMV infected children with SNHL performed significantly weaker for all gross motor outcome measures. A congenital CMV infection is a risk factor for a delay in the early motor development. Follow-up will be necessary to gain insight into the exact cause of this motor delay and to define the predictive value of early motor assessment of cCMV infected children. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. BMP regulates vegetal pole induction centres in early xenopus development. (United States)

    Nachaliel, N; Re'Em-Kalma, Y; Eshed, O; Elias, S; Frank, D


    Bone morphogenetic protein (BMP) plays an important role in mesoderm patterning in Xenopus. The ectopic expression of BMP-4 protein hyperventralizes embryos, whereas embryos expressing a BMP-2/4 dominant-negative receptor (DNR) are hyperdorsalized. Mesoderm is initially induced in the marginal zone by cells in the underlying vegetal pole. While much is known about BMP's expression and role in patterning the marginal zone, little is known about its early role in regulating vegetal mesoderm induction centre formation. The role of BMP in regulating formation of vegetal mesoderm inducing centres during early Xenopus development was examined. Ectopic BMP-4 expression in vegetal pole cells inhibited dorsal mesoderm induction but increased ventral mesoderm induction when recombined with animal cap ectoderm in Nieuwkoop explants. 32-cell embryos injected with BMP-4 RNA in the most vegetal blastomere tier were not hyperdorsalized by LiCl treatment. The ectopic expression of Smad or Mix.1 proteins in the vegetal pole also inhibited dorsal mesoderm induction in explants and embryos. Expression of the BMP 2/4 DNR in the vegetal pole increased dorsal mesoderm induction and inhibited ventral mesoderm induction in explants and embryos. These results support a role for BMP signalling in regulating ventral vegetal and dorsal vegetal mesoderm induction centre formation during early Xenopus development.

  7. Children's health and development: approaches to early identification and intervention. (United States)

    Oberklaid, Frank; Baird, Gillian; Blair, Mitch; Melhuish, Edward; Hall, David


    Many children arrive at school with problems of development and behaviour which affect their educational achievement and social interaction and can have lifelong consequences. There is a strong association between developmental vulnerability at school entry and a well-documented series of parent and family risk factors, often linked to social disadvantage. Strategies which are likely to make a difference to these children and improve outcomes include family support, high-quality early education and care programmes in the preschool years, and early detection of emerging problems and risk factors. The evidence suggests that these services and programmes are best delivered within a framework of progressive universalism--a universal basket of services for all children and families, with additional support commensurate with additional needs. This provides the best opportunity for early identification and appropriate intervention for emerging developmental problems and family issues that impact on children's development. While there are a number of challenges that need to be addressed and overcome, such an approach is an important investment that will yield measurable educational, social and economic benefits over the long term.

  8. Clinical assessment of early language development: a simplified short form of the Mandarin communicative development inventory. (United States)

    Soli, Sigfrid D; Zheng, Yun; Meng, Zhaoli; Li, Gang


    The purpose of this study was to develop a practical mean for clinical evaluation of early pediatric language development by establishing developmental trajectories for receptive and expressive vocabulary growth in children between 6 and 32 months of age using a simple, time-efficient assessment tool. Simplified short form versions of the Words and Gestures and Words and Sentences vocabulary inventories in the Mandarin Communicative Development Inventory [1] were developed and used to assess early language development in developmentally normal children from 6 to 32 months of age during routine health checks. Developmental trajectories characterizing the rate of receptive and expressive vocabulary growth between 6 and 32 months of age are reported. These trajectories allow the equivalent age corresponding to a score to be determined after a brief structured interview with the child's parents that can be conducted in a busy clinical setting. The simplified short forms of the Mandarin Communicative Development Inventories can serve as a clinically useful tool to assess early child language development, providing a practical mean of objectively assessing early language development following early interventions to treat young children with hearing impairment as well as speech and language delays. Objective evidence of language development is essential for achievement of effective (re)habilitation outcomes. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  9. Expression of Sox family genes in early lamprey development. (United States)

    Uy, Benjamin R; Simoes-Costa, Marcos; Sauka-Spengler, Tatjana; Bronner, Marianne E


    Members of the Sox (Sry-related high mobility group box) family of transcription factors play a variety of roles during development of both vertebrates and invertebrates. A marked expansion in gene number occurred during the emergence of vertebrates, apparently via gene duplication events that are thought to have facilitated new functions. By screening a macroarrayed library as well as the lamprey genome, we have isolated genes of the Sox B, D, E and F subfamilies in the basal jawless vertebrate, lamprey. The expression patterns of all identified Sox genes were examined from gastrulation through early organogenesis (embryonic day 4-14), with particular emphasis on the neural crest, a vertebrate innovation. Coupled with phylogenetic analysis of these Sox genes, the results provide insight into gene duplication and di-vergence in paralog deployment occurring during early vertebrate evolution.

  10. Early environmental exposure and the development of lupus. (United States)

    Edwards, C J; Cooper, C


    Systemic lupus erythematosus (SLE) is a complex trait with evidence of polygenic inheritance influenced by environmental factors. However, the precise underlying causes of SLE remain unclear. A number of environmental exposures have been associated with lupus or related autoimmune phenomena. Evidence suggests that some environmental exposures need to be present many years before the onset of SLE. Both SLE and rheumatoid arthritis (RA) can occur in very young children and this supports the possibility that important environmental factors must be present during or before this time. In addition, the immune pathology, including autoantibody production, in adult lupus may begin years before clinical disease. There is also evidence that the developing immune system demonstrates developmental plasticity and can be permanently altered or 'programmed' by the early environment. We describe how early life environmental influences including infectious exposure may lead to autoantibody production in later life thus beginning the journey that leads to autoimmune diseases such as lupus in susceptible individuals.

  11. Natural History of Non-CNS Disseminated Coccidioidomycosis (United States)

    Bays, Derek; Thompson, George R; Reef, Susan; Snyder, Linda; Huppert, Milton; Salkin, David; Galgiani, John


    Abstract Background The number of patients with coccidioidomycosis continues to increase yearly. Patients with CNS disease require lifelong antifungal therapy due to the high morbidity and mortality of this disease. However, the morbidity and mortality in non-CNS disseminated disease has not been well characterized. Methods We conducted a retrospective study of 373 VA-armed forces coccidioidomycosis patients diagnosed between 1955 and 1958 and followed to 1966. Groups were identified as non-disseminated disease, non-CNS disseminated disease with and without multisite dissemination, and disseminated disease to the CNS with and without multisite dissemination. Clinical variables including demographic information, duration and severity of symptoms, coccidioidal serologies, type of infection and complications, time to disseminated disease, and mortality were abstracted from patient charts. Results Mortality attributed to coccidioidomycosis in the non-disseminated group was 0.3% (1/297) compared with the non-CNS disseminated group of 8.5% (4/47, median survival 12 months, range 12–24 months, P = 0.0002). Mortality in the CNS disseminated group was 86% (19/22, median survival of 12 months, range 12–156 months, P < 0.0001 compared with non-CNS disseminated). The single site non-CNS disseminated group had a mortality of 4.1% (1/24, survival of 12months) compared with the multiple site non-CNS disseminated group of 13% (3/23, median survival of 18 months, range of 12–24 months, P = 0.57). Conclusion This retrospective cohort study demonstrates significant mortality differences between different forms of disseminated coccidioidomycosis. CNS dissemination exhibited the highest mortality rate; however, non-CNS dissemination also exhibited an unacceptably high mortality rate. There was no significant difference in mortality between single site non-CNS disseminated disease and multiple site non-CNS disseminated disease. Disclosures All authors: No reported

  12. On the evolution of early development in the Nematoda. (United States)

    Goldstein, B


    The phylum Nematoda serves as an excellent model system for exploring how development evolves, using a comparative approach to developmental genetics. More than 100 laboratories are studying developmental mechanisms in the nematode Caenorhabditis elegans, and many of the methods that have been developed for C. elegans can be applied to other nematodes. This review summarizes what is known so far about steps in early development that have evolved in the nematodes, and proposes potential experiments that could make use of these data to further our understanding of how development evolves. The promise of such a comparative approach to developmental genetics is to fill a wide gap in our understanding of evolution--a gap spanning from mutations in developmental genes through to their phenotypic results, on which natural selection may act.

  13. Regulation of bone morphogenetic proteins in early embryonic development (United States)

    Yamamoto, Yukiyo; Oelgeschläger, Michael


    Bone morphogenetic proteins (BMPs), a large subgroup of the TGF-β family of secreted growth factors, control fundamental events in early embryonic development, organogenesis and adult tissue homeostasis. The plethora of dose-dependent cellular processes regulated by BMP signalling demand a tight regulation of BMP activity. Over the last decade, a number of proteins have been identified that bind BMPs in the extracellular space and regulate the interaction of BMPs with their cognate receptors, including the secreted BMP antagonist Chordin. In the early vertebrate embryo, the localized secretion of BMP antagonists from the dorsal blastopore lip establishes a functional BMP signalling gradient that is required for the determination of the dorsoventral or back to belly body axis. In particular, inhibition of BMP activity is essential for the formation of neural tissue in the development of vertebrate and invertebrate embryos. Here we review recent studies that have provided new insight into the regulation of BMP signalling in the extracellular space. In particular, we discuss the recently identified Twisted gastrulation protein that modulates, in concert with metalloproteinases of the Tolloid family, the interaction of Chordin with BMP and a family of proteins that share structural similarities with Chordin in the respective BMP binding domains. In addition, genetic and functional studies in zebrafish and frog provide compelling evidence that the secreted protein Sizzled functionally interacts with the Chd BMP pathway, despite being expressed ventrally in the early gastrula-stage embryo. These intriguing discoveries may have important implications, not only for our current concept of early embryonic patterning, but also for the regulation of BMP activity at later developmental stages and tissue homeostasis in the adult.

  14. Excess iron: considerations related to development and early growth. (United States)

    Wessling-Resnick, Marianne


    What effects might arise from early life exposures to high iron? This review considers the specific effects of high iron on the brain, stem cells, and the process of erythropoiesis and identifies gaps in our knowledge of what molecular damage may be incurred by oxidative stress that is imparted by high iron status in early life. Specific areas to enhance research on this topic include the following: longitudinal behavioral studies of children to test associations between iron exposures and mood, emotion, cognition, and memory; animal studies to determine epigenetic changes that reprogram brain development and metabolic changes in early life that could be followed through the life course; and the establishment of human epigenetic markers of iron exposures and oxidative stress that could be monitored for early origins of adult chronic diseases. In addition, efforts to understand how iron exposure influences stem cell biology could be enhanced by establishing platforms to collect biological specimens, including umbilical cord blood and amniotic fluid, to be made available to the research community. At the molecular level, there is a need to better understand stress erythropoiesis and changes in iron metabolism during pregnancy and development, especially with respect to regulatory control under high iron conditions that might promote ineffective erythropoiesis and iron-loading anemia. These investigations should focus not only on factors such as hepcidin and erythroferrone but should also include newly identified interactions between transferrin receptor-2 and the erythropoietin receptor. Finally, despite our understanding that several key micronutrients (e.g., vitamin A, copper, manganese, and zinc) support iron's function in erythropoiesis, how these nutrients interact remains, to our knowledge, unknown. It is necessary to consider many factors when formulating recommendations on iron supplementation. © 2017 American Society for Nutrition.

  15. Early somatosensory processing in individuals at risk for developing psychoses

    Directory of Open Access Journals (Sweden)

    Florence eHagenmuller


    Full Text Available Human cortical somatosensory evoked potentials (SEPs allow an accurate investigation of thalamocortical and early cortical processing. SEPs reveal a burst of superimposed early (N20 high-frequency oscillations around 600 Hz. Previous studies reported alterations of SEPs in patients with schizophrenia. This study addresses the question whether those alterations are also observable in populations at risk for developing schizophrenia or bipolar disorders. To our knowledge to date, this is the first study investigating SEPs in a population at risk for developing psychoses.Median nerve SEPs were investigated using multichannel EEG in individuals at risk for developing bipolar disorders (n=25, individuals with high-risk status (n= 59 and ultra-high-risk status for schizophrenia (n= 73 and a gender and age-matched control group (n=45. Strengths and latencies of low- and high-frequency components as estimated by dipole source analysis were compared between groups.Low- and high-frequency source activity was reduced in both groups at risk for schizophrenia, in comparison to the group at risk for bipolar disorders. HFO amplitudes were also significant reduced in subjects with high-risk status for schizophrenia compared to healthy controls. These differences were accentuated among cannabis non-users. Reduced N20 source strengths were related to higher positive symptom load.These results suggest that the risk for schizophrenia, in contrast to bipolar disorders, may involve an impairment of early cerebral somatosensory processing. Neurophysiologic alterations in schizophrenia precede the onset of initial psychotic episode and may serve as indicator of vulnerability for developing schizophrenia.

  16. Early somatosensory processing in individuals at risk for developing psychoses. (United States)

    Hagenmuller, Florence; Heekeren, Karsten; Theodoridou, Anastasia; Walitza, Susanne; Haker, Helene; Rössler, Wulf; Kawohl, Wolfram


    Human cortical somatosensory evoked potentials (SEPs) allow an accurate investigation of thalamocortical and early cortical processing. SEPs reveal a burst of superimposed early (N20) high-frequency oscillations around 600 Hz. Previous studies reported alterations of SEPs in patients with schizophrenia. This study addresses the question whether those alterations are also observable in populations at risk for developing schizophrenia or bipolar disorders. To our knowledge to date, this is the first study investigating SEPs in a population at risk for developing psychoses. Median nerve SEPs were investigated using multichannel EEG in individuals at risk for developing bipolar disorders (n = 25), individuals with high-risk status (n = 59) and ultra-high-risk status for schizophrenia (n = 73) and a gender and age-matched control group (n = 45). Strengths and latencies of low- and high-frequency components as estimated by dipole source analysis were compared between groups. Low- and high-frequency source activity was reduced in both groups at risk for schizophrenia, in comparison to the group at risk for bipolar disorders. HFO amplitudes were also significant reduced in subjects with high-risk status for schizophrenia compared to healthy controls. These differences were accentuated among cannabis non-users. Reduced N20 source strengths were related to higher positive symptom load. These results suggest that the risk for schizophrenia, in contrast to bipolar disorders, may involve an impairment of early cerebral somatosensory processing. Neurophysiologic alterations in schizophrenia precede the onset of initial psychotic episode and may serve as indicator of vulnerability for developing schizophrenia.

  17. Astrocyte scar formation aids CNS axon regeneration (United States)

    Anderson, Mark A.; Burda, Joshua E.; Ren, Yilong; Ao, Yan; O’Shea, Timothy M.; Kawaguchi, Riki; Coppola, Giovanni; Khakh, Baljit S.; Deming, Timothy J.; Sofroniew, Michael V.


    Summary Transected axons fail to regrow in the mature central nervous system (CNS). Astrocyte scars are widely regarded as causal in this failure. Here, using three genetically targeted loss-of-function manipulations in adult mice, we show that preventing astrocyte scar formation, attenuating scar-forming astrocytes, or deleting chronic astrocyte scars all failed to result in spontaneous regrowth of transected corticospinal, sensory or serotonergic axons through severe spinal cord injury (SCI) lesions. In striking contrast, sustained local delivery via hydrogel depots of required axon-specific growth factors not present in SCI lesions, plus growth-activating priming injuries, stimulated robust, laminin-dependent sensory axon regrowth past scar-forming astrocytes and inhibitory molecules in SCI lesions. Preventing astrocyte scar formation significantly reduced this stimulated axon regrowth. RNA sequencing revealed that astrocytes and non-astrocyte cells in SCI lesions express multiple axon-growth supporting molecules. Our findings show that contrary to prevailing dogma, astrocyte scar formation aids rather than prevents CNS axon regeneration. PMID:27027288

  18. Novel agents in CNS myeloma treatment. (United States)

    Gozzetti, Alessandro; Cerase, Alfonso


    Central nervous system localization of multiple myeloma (CNS-MM) accounts for about 1% of all MM.Treatment is still unsatisfactory. Many treatments have been described in the literature: chemotherapy (CHT), intrathecal therapy (IT), and radiotherapy (RT), with survivals reported between one month and six months. Recent drugs such as the immunomodulatory drugs (IMiDs) and proteasome inhibitors (bortezomib) have changed the treatment of patients with MM, both younger and older, with a significant improvement in response and survival. The activity of new drugs in CNSMM has been reported but is still not well known. Bortezomib does not cross the blood brain barrier (BBB), and IMID’s seem to have only a minimal crossover. The role of novel agents in CNS MM management will be discussed as well as the potential role of other new immunomodulatory drugs (pomalidomide) and proteasome inhibitors that seem to cross the BBB and hold promise into the treatment of this rare and still incurable localization of the disease.

  19. Insulin-like growth factor binding protein-2 as a regulator of IGF actions in CNS : Implications in multiple sclerosis

    NARCIS (Netherlands)

    Chesik, Daniel; De Keyser, Jacques; Wilczak, Nadine


    Insulin-like growth factors (IGFs) are indispensable peptide hormones for proper development of the central nervous system (CNS). Because IGF-1 exhibits neuroprotective and myelinogenetic effects, it possesses therapeutic potential in treating neurodegenerative demyelinating diseases such as

  20. Rewiring the injured CNS: lessons from the optic nerve (United States)

    Benowitz, Larry; Yin, Yuqin


    The optic nerve offers a number of advantages for investigating mechanisms that govern axon regeneration in the CNS. Although mature retinal ganglion cells (RGCs) normally show no ability to regenerate injured axons through the optic nerve, this situation can be partially reversed by inducing an inflammatory response in the eye. The secretion of a previously unknown growth factor, oncomodulin, along with co-factors, causes RGCs to undergo dramatic changes in gene expression and regenerate lengthy axons into the highly myelinated optic nerve. By themselves, strategies that counteract inhibitory signals associated with myelin and the glial scar are insufficient to promote extensive regeneration in this system. However, combinatorial treatments that activate neurons' intrinsic growth state and overcome inhibitory signals result in dramatic axon regeneration in vivo. Because of the ease of introducing trophic factors, soluble receptors, drugs, or viruses expressing any gene or small interfering RNA of interest into RGCs, this system is ideal for identifying intracellular signaling pathways, transcriptional cascades, and ligand-receptor interactions that enable axon regeneration to occur in the CNS and to develop means to augment this process. PMID:17610877

  1. Flaviviruses are neurotropic, but how do they invade the CNS? (United States)

    Neal, J W


    Flaviruses (FV) are RNA viruses carried by mosquitoes. Neurological signs including acute encephalitis, meningitis and acute flaccid paralysis develop in a small percentage of infected individuals; long term sequlae are, Parkinsonism, dystonias and cognitive changes. FV neuroinfection is neurotropic involving subcortical nuclei (substantia nigra and thalamus) anterior horn neurons and neocortex. Glycosylation of the FV E envelope protein is one determinant of neuroinvasion, increasing both axonal and trans-epithelial transportation. Neutralizing antibodies against the E and NS proteins prevents FV uptake into several cell types, including axons. CD8+ T cells are vital for clearance of WNF infected cells from the CNS, whereas TLR-3 and TLR-7 mediated anti-virus response through increased serum inflammatory cytokines to disrupt the BBB providing infected leucocytes and free virus access to the CNS (so called Trojan horse) Cellular virus attachment factors, promoting FV cell entry are widely distributed and include DC-SIGN (that detects complex carbohydrate molecules); Glycosamino glycans (GAG), Heparan sulphate(HSPG) Semaphorin 7A, Low Density Lipid receptors (LDLR); these are not FV specific virus entry receptors. The FV also crosses epithelial and endothelial barriers by disrupting Tight Junction complexes to increase BBB permeability. This review describes the multiple pathways responsible for the neuroinvasive properties of the Flaviviruses. Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  2. Preclinical assessment of CNS drug action using eye movements in mice (United States)

    Cahill, Hugh; Rattner, Amir; Nathans, Jeremy


    The drug development process for CNS indications is hampered by a paucity of preclinical tests that accurately predict drug efficacy in humans. Here, we show that a wide variety of CNS-active drugs induce characteristic alterations in visual stimulus–induced and/or spontaneous eye movements in mice. Active compounds included sedatives and antipsychotic, antidepressant, and antiseizure drugs as well as drugs of abuse, such as cocaine, morphine, and phencyclidine. The use of quantitative eye-movement analysis was demonstrated by comparing it with the commonly used rotarod test of motor coordination and by using eye movements to monitor pharmacokinetics, blood-brain barrier penetration, drug-receptor interactions, heavy metal toxicity, pharmacologic treatment in a model of schizophrenia, and degenerative CNS disease. We conclude that eye-movement analysis could complement existing animal tests to improve preclinical drug development. PMID:21821912

  3. Fathers’ Sensitive Parenting and the Development of Early Executive Functioning (United States)

    Towe-Goodman, Nissa R.; Willoughby, Michael; Blair, Clancy; Gustafsson, Hanna C.; Mills-Koonce, W. Roger; Cox, Martha J.


    Using data from a diverse sample of 620 families residing in rural, predominately low-income communities, this study examined longitudinal links between fathers’ sensitive parenting in infancy and toddlerhood and children’s early executive functioning, as well as the contribution of maternal sensitive parenting. After accounting for the quality of concurrent and prior parental care, children’s early cognitive ability, and other child and family factors, fathers’ and mothers’ sensitive and supportive parenting during play at 24-months predicted children’s executive functioning at 3-years of age. In contrast, paternal parenting quality during play at 7-months did not make an independent contribution above that of maternal care, but the links between maternal sensitive and supportive parenting and executive functioning seemed to operate in similar ways during infancy and toddlerhood. These findings add to prior work on early experience and children’s executive functioning, suggesting that both fathers and mothers play a distinct and complementary role in the development of these self-regulatory skills. PMID:25347539

  4. Early growth and development of later life metabolic disorders. (United States)

    Foo, Joo-Pin; Mantzoros, Christos


    Growth is effected via a complex interaction of genetic, nutritional, environmental and growth factors. Hormonal factors such as the growth hormone (GH) and insulin-like growth factor (IGF) signaling system, the human placental lactogen, and insulin play an integral role in early growth. Genetic factors affecting the GH-IGF system and insulin secretion and actions, and epigenetic mechanisms including DNA methylation have been further implicated as contributory factors. These hormonal systems, on a background of genetic susceptibility, together with other factors including maternal nutrition, placental and environmental factors, regulate not only early growth but also development. These interactions may impact on later health consequences in adult life. Accumulating data in the last few decades on developmental programming and later life metabolic disorders has provided a novel perspective on the possible pathogenesis of metabolic dysregulation. Despite postulations put forward to elucidate the mechanism underlying the association between early growth and later life metabolic disorders, it remains unclear what the dominant factor(s) would be, how any underlying mechanisms interact, or whether these mechanisms are truly causal. Copyright © 2013 Nestec Ltd., Vevey/S. Karger AG, Basel.

  5. [Non-structural abnormalities of CNS function resulting in coincidence of endocrinopathies, epilepsy and psychoneurologic disorders in children and adolescents]. (United States)

    Starzyk, Jerzy; Pituch-Noworolska, Anna; Pietrzyk, Jacek A; Urbanik, Andrzej; Kroczka, Sławomir; Drozdz, Ryszard; Wójcik, Małgorzata


    chiasm glioma (2 patients), suprasellar germinal tumor (1 patient), ii) children with Hashimoto encephalopathy (2 patients), iii) children with Prader-Willi syndrome (20 patients), with Klinefelter syndrome (10 patients), with Albright syndrome (9 patients). Of the 49 patients, a group of 6 children representative for individual disorders was selected. In those patients, the etiology of both endocrine disorders, epilepsy and neuropsychiatric disorders was suspected to be common, and the diagnosis was usually delayed. 1. Cranial irradiation and chemotherapy, encephalopathy associated with Hashimoto disease and some of the syndromes with the chromosomal and genetic background are the causes of non-structural CNS abnormalities and coincidence of endocrinopathies, epilepsy and psychoneurologic disorders. 2. MR/CT CNS imaging should be performed in any case of central neurological disorders, disorders of behavior, epilepsy or seizures, but also in patients with delayed psycho-motor development, delayed or accelerated growth and pubertal development. All of the above-mentioned manifestations may be symptoms of structural CNS abnormalities and their early treatment determines the child's future. 3. Excluding structural CNS abnormalities allows for forming suspicions associated with diseases resulting in non-structural disorders of the CNS function, predisposing to coincidence of endocrine and neurological disorders. 4. In the diagnosis of Hashimoto's encephalopathy, a decisive factor is exclusion of structural, infectious, traumatic and metabolic causes, intoxications, epilepsy and presence of neuropsychiatric symptoms in patients with high level of against TPO antibodies. In cases of steroids resistance, a good therapeutic effect may be achieved by plasmapheresis, Rituximab therapy and progestagene inhibition of the menstrual cycle.

  6. Growth and Morphogenesis during Early Heart Development in Amniotes. (United States)

    Ivanovitch, Kenzo; Esteban, Isaac; Torres, Miguel


    In this review, we will focus on the growth and morphogenesis of the developing heart, an aspect of cardiovascular development to which Antoon Moorman and colleagues have extensively contributed. Over the last decades, genetic studies and characterization of regionally regulated gene programs have provided abundant novel insights into heart development essential to understand the basis of congenital heart disease. Heart morphogenesis, however, is inherently a complex and dynamic three-dimensional process and we are far from understanding its cellular basis. Here, we discuss recent advances in studying heart morphogenesis and regionalization under the light of the pioneering work of Moorman and colleagues, which allowed the reinterpretation of regional gene expression patterns under a new morphogenetic framework. Two aspects of early heart formation will be discussed in particular: (1) the initial formation of the heart tube and (2) the formation of the cardiac chambers by the ballooning process. Finally, we emphasize that in addition to analyses based on fixed samples, new approaches including clonal analysis, single-cell sequencing, live-imaging and quantitative analysis of the data generated will likely lead to novel insights in understanding early heart tube regionalization and morphogenesis in the near future.

  7. Growth and Morphogenesis during Early Heart Development in Amniotes

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    Kenzo Ivanovitch


    Full Text Available In this review, we will focus on the growth and morphogenesis of the developing heart, an aspect of cardiovascular development to which Antoon Moorman and colleagues have extensively contributed. Over the last decades, genetic studies and characterization of regionally regulated gene programs have provided abundant novel insights into heart development essential to understand the basis of congenital heart disease. Heart morphogenesis, however, is inherently a complex and dynamic three-dimensional process and we are far from understanding its cellular basis. Here, we discuss recent advances in studying heart morphogenesis and regionalization under the light of the pioneering work of Moorman and colleagues, which allowed the reinterpretation of regional gene expression patterns under a new morphogenetic framework. Two aspects of early heart formation will be discussed in particular: (1 the initial formation of the heart tube and (2 the formation of the cardiac chambers by the ballooning process. Finally, we emphasize that in addition to analyses based on fixed samples, new approaches including clonal analysis, single-cell sequencing, live-imaging and quantitative analysis of the data generated will likely lead to novel insights in understanding early heart tube regionalization and morphogenesis in the near future.

  8. Retinoic acid synthesis and functions in early embryonic development

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    Kam Richard Kin Ting


    Full Text Available Abstract Retinoic acid (RA is a morphogen derived from retinol (vitamin A that plays important roles in cell growth, differentiation, and organogenesis. The production of RA from retinol requires two consecutive enzymatic reactions catalyzed by different sets of dehydrogenases. The retinol is first oxidized into retinal, which is then oxidized into RA. The RA interacts with retinoic acid receptor (RAR and retinoic acid X receptor (RXR which then regulate the target gene expression. In this review, we have discussed the metabolism of RA and the important components of RA signaling pathway, and highlighted current understanding of the functions of RA during early embryonic development.

  9. APECS: A Network for Polar Early Career Scientist Professional Development (United States)

    Enderlin, E. M.


    The Association of Polar Early Career Researchers (APECS) is an international and interdisciplinary organization for undergraduate and graduate students, postdoctoral researchers, early faculty members, educators and others with interests in the polar regions, alpine regions and the wider Cryosphere. APECS is a scientific, non-profit organization with free individual membership that aims to stimulate research collaborations and develop effective future leaders in polar research, education, and outreach. APECS grew out of the 4th International Polar Year (2007-08), which emphasized the need to stimulate and nurture the next generation of scientists in order to improve the understanding and communication of the polar regions and its global connections. The APECS organizational structure includes a Council and an elected Executive Committee that are supported by a Directorate. These positions are open to all individual members through a democratic process. The APECS Directorate is funded by the Norwegian Research Council, the University of Tromsø and the Norwegian Polar Institute and is hosted by the University of Tromsø. Early career scientists benefit from a range of activities hosted/organized by APECS. Every year, numerous activities are run with partner organizations and in conjunction with major polar conferences and meetings. In-person and online panels and workshops focus on a range of topics, from developing field skills to applying for a job after graduate school. Career development webinars are hosted each fall and topical research webinars are hosted throughout the year and archived online ( The APECS website also contains abundant information on polar news, upcoming conferences and meetings, and job postings for early career scientists. To better respond to members' needs, APECS has national/regional committees that are linked to the international overarching organization. Many of these committees organize regional meetings or

  10. The rostral migratory stream plays a key role in intranasal delivery of drugs into the CNS.

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    Robert A Scranton


    Full Text Available The blood brain barrier (BBB is impermeable to most drugs, impeding the establishment of novel neuroprotective therapies and strategies for many neurological diseases. Intranasal administration offers an alternative path for efficient drug delivery into the CNS. So far, the anatomical structures discussed to be involved in the transport of intranasally administered drugs into the CNS include the trigeminal nerve, olfactory nerve and the rostral migratory stream (RMS, but the relative contributions are debated.In the present study we demonstrate that surgical transection, and the resulting structural disruption of the RMS, in mice effectively obstructs the uptake of intranasally administered radioligands into the CNS. Furthermore, using a fluorescent cell tracer, we demonstrate that intranasal administration in mice allows agents to be distributed throughout the entire brain, including olfactory bulb, hippocampus, cortex and cerebellum.This study provides evidence of the vital role the RMS has in the CNS delivery of intranasally administered agents. The identification of the RMS as the major access path for intranasally administered drugs into the CNS may contribute to the development of treatments that are tailored for efficient transport within this structure. Research into the RMS needs to continue to elucidate its limitations, capabilities, mechanisms of transport and potential hazards before we are able to advance this technique into human research.

  11. Microglia and CNS Interleukin-1: Beyond Immunological Concepts

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    Xiaoyu Liu


    Full Text Available Activation of microglia and expression of the inflammatory cytokine interleukin-1 (IL-1 in the CNS have become almost synonymous with neuroinflammation. In numerous studies, increased CNS IL-1 expression and altered microglial morphology have been used as hallmarks of CNS inflammation. A central concept of how CNS IL-1 and microglia influence functions of the nervous system was derived from the notion initially generated in the peripheral immune system: IL-1 stimulates monocyte/macrophage (the peripheral counterparts of microglia to amplify inflammation. It is increasingly clear, however, CNS IL-1 acts on other targets in the CNS and microglia participates in many neural functions that are not related to immunological activities. Further, CNS exhibits immunological privilege (although not as absolute as previously thought, rendering amplification of inflammation within CNS under stringent control. This review will analyze current literature to evaluate the contribution of immunological and non-immunological aspects of microglia/IL-1 interaction in the CNS to gain insights for how these aspects might affect health and disease in the nervous tissue.

  12. Influence of seizures on early development in tuberous sclerosis complex. (United States)

    Capal, Jamie K; Bernardino-Cuesta, Beatriz; Horn, Paul S; Murray, Donna; Byars, Anna Weber; Bing, Nicole M; Kent, Bridget; Pearson, Deborah A; Sahin, Mustafa; Krueger, Darcy A


    Epilepsy is commonly seen in Tuberous Sclerosis Complex (TSC). The relationship between seizures and developmental outcomes has been reported, but few studies have examined this relationship in a prospective, longitudinal manner. The objective of the study was to evaluate the relationship between seizures and early development in TSC. Analysis of 130 patients ages 0-36months with TSC participating in the TSC Autism Center of Excellence Network, a large multicenter, prospective observational study evaluating biomarkers predictive of autism spectrum disorder (ASD), was performed. Infants were evaluated longitudinally with standardized evaluations, including cognitive, adaptive, and autism-specific measures. Seizure history was collected continuously throughout, including seizure type and frequency. Data were analyzed at 6, 12, 18, and 24months of age. Patients without a history of seizures performed better on all developmental assessments at all time points compared to patients with a history of seizures and exhibited normal development at 24months. Patients with a history of seizures not only performed worse, but developmental progress lagged behind the group without seizures. All patients with a history of infantile spasms performed worse on all developmental assessments at 12, 18, and 24months. Higher seizure frequency correlated with poorer outcomes on developmental testing at all time points, but particularly at 12months and beyond. Patients with higher seizure frequency during infancy continued to perform worse developmentally through 24months. A logistic model looking at the individual impact of infantile spasms, seizure frequency, and age of seizure onset as predictors of developmental delay revealed that age of seizure onset was the most important factor in determining developmental outcome. Results of this study further define the relationship between seizures and developmental outcomes in young children with TSC. Early seizure onset in infants with TSC

  13. Early Development of the Gut Microbiota and Immune Health

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    M. Pilar Francino


    Full Text Available In recent years, the increase in human microbiome research brought about by the rapidly evolving “omic” technologies has established that the balance among the microbial groups present in the human gut, and their multipronged interactions with the host, are crucial for health. On the other hand, epidemiological and experimental support has also grown for the ‘early programming hypothesis’, according to which factors that act in utero and early in life program the risks for adverse health outcomes later on. The microbiota of the gut develops during infancy, in close interaction with immune development, and with extensive variability across individuals. It follows that the specific process of gut colonization and the microbe-host interactions established in an individual during this period have the potential to represent main determinants of life-long propensity to immune disease. Although much remains to be learnt on the progression of events by which the gut microbiota becomes established and initiates its intimate relationships with the host, and on the long-term repercussions of this process, recent works have advanced significatively in this direction.

  14. Early Childhood Development and Iranian Parents' Knowledge: A Qualitative Study. (United States)

    Habibi, Elham; Sajedi, Firouzeh; Afzali, Hosein Malek; Hatamizadeh, Nikta; Shahshahanipour, Soheila; Glascoe, Frances Page


    Early childhood is the most important step throughout the lifespan and it is a critical period continuing to the end of 8-year-old. Mothers' knowledge is one of the important aspects of child development. The goals of this study were to determine the situation of knowledge in Iranian parents about the concept and the importance of early childhood development (ECD) and determining the sources of parental knowledge about ECD from the perspective of parents and grandparents. This qualitative study was conducted based on the directional content analysis in 2016. The purposive sampling method is utilized to select 24 participants among parents and grandparents in Tehran. The inclusion criteria consisted of speaking in Persian and having a child or grandchild growth of children. According to the results, the knowledge of Iranian parent is not enough about ECD; therefore, actions must be taken to increase their knowledge in these domains. Parents look for reliable and valid sources to enhance their knowledge and they rely the most on pediatricians in this regard. Therefore, more studies on assessing parents' knowledge in community and the practical methods for knowledge promotion in this field is recommended.

  15. Development of children’s early understanding of numeric structure

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    Vasilyeva, Marina


    Full Text Available Understanding of the base-10 structure of multi-digit numbers is one of the critical aspects in early mathematics learning. It has been documented that children from different countries vary in their use of base-10 representations. Questions concerning potential sources of this variability have been debated for decades. One commonly posited explanation is that some languages provide explicit cues about the structure of multi-digit numbers, facilitating the development of base-10 representations. In the present study, we tested this view against an alternative view, positing that variability in children’s learning of numeric structure may reflect differences in their experiences with numbers. The study examined kindergartners and first-graders from four countries: Taiwan, South Korea, the USA, and Russia. Results showed that the use of base-10 representations by American first-graders increased dramatically over the last decades, following changes in curricular guidelines. First-graders across the four countries showed some differences in performance (however, not consistent with the language account, whereas kindergartners performed comparably despite the differences in their languages. The results suggest that the nature of early math instruction may be critical for children’s developing understanding of numeric structure.

  16. Rem sleep, early experience, and the development of reproductive strategies. (United States)

    McNamara, Patrick; Dowdall, Jayme; Auerbach, Sanford


    We hypothesize that rapid eye movement or REM sleep evolved, in part, to mediate sexual/reproductive behaviors and strategies. Because development of sexual and mating strategies depends crucially on early attachment experiences, we further hypothesize that REM functions to mediate attachment processes early in life. Evidence for these hypotheses comes from (1) the correlation of REM variables with both attachment and sexual/reproductive variables; (2) attachment-related and sex-related hormonal release during REM; (3) selective activation during REM of brain sites implicated in attachment and sexual processes; (4) effects of maternal deprivation on REM; (5) effects of REM deprivation on sexual behaviors; and (6) the REM-associated sexual excitation. To explain why we find associations among REM sleep, attachment, and adult reproductive strategies, we rely on recent extensions of parent-offspring conflict theory. Using data from recent findings on genomic imprinting, Haig (2000) and others suggest that paternally expressed genes are selected to promote growth of the developing fetus/child at the expense of the mother, while maternally expressed genes counter these effects. Because developmental REM facilitates attachment-related outcomes in the child, developmental REM may be regulated by paternally expressed genes. In that case, REM may have evolved to support the "aims" of paternal genes at the expense of maternal genes.

  17. Does bilingual experience affect early visual perceptual development?

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    Christina eSchonberg


    Full Text Available Visual attention and perception develop rapidly during the first few months after birth, and these behaviors are critical components in the development of language and cognitive abilities. Here we ask how early bilingual experiences might lead to differences in visual attention and perception. Experiments 1-3 investigated the looking behavior of monolingual and bilingual infants when presented with social (Experiment 1, mixed (Experiment 2, or nonsocial (Experiment 3 stimuli. In each of these experiments, infants’ dwell times (DT and number of fixations to areas of interest (AOIs were analyzed, giving a sense of where the infants looked. To examine how the infants looked at the stimuli in a more global sense, Experiment 4 combined and analyzed the saccade data collected in Experiments 1-3. There were no significant differences between monolingual and bilingual infants’ DTs, AOI fixations, or saccade characteristics (specifically, frequency and amplitude in any of the experiments. These results suggest that monolingual and bilingual infants process their visual environments similarly, supporting the idea that the substantial cognitive differences between monolinguals and bilinguals in early childhood are more related to active vocabulary production than perception of the environment.

  18. Language, bilingualism, and executive functioning in early development. (United States)

    Morton, J Bruce


    Okanda, et al. (2010) reported new evidence concerning associations between language ability, bilingualism, and executive functioning early in development. The paper adds to a growing body of literature suggesting that bilingualism is associated with advantages in executive functioning generally, and the Dimensional Change Card Sort task in particular. However, as with all findings that hinge on between-group comparisons, there is a need to exercise caution before drawing firm conclusions about the effects of bilingualism on the development of executive control. Several lines of recent evidence are outlined that challenge key assumptions underlying the standard account of the bilingual advantage. Okanda, et al.'s findings are discussed in light of this evidence.

  19. Challenges facing the early childhood development sector in South Africa

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    Eric Atmore


    Full Text Available In this review article, the context of young children in South Africa in 2012 is described and the main challenges affecting children and the early childhood development sector (ECD in South Africa are investigated. A situation analysis of ECD in South Africa was undertaken using South African government ECD policy and programme implementation reports. There has been progress since 1994, both quantitatively and qualitatively. The number of children in Grade R has trebled since 2001, government education and social development budgets have increased substantially and 58% of children at ECD centres nationally are now subsidised. More children are in provision and in better quality provision than before. However, much still remains to be done before we can say with confidence that the needs of our youngest children are being met. This study identifies infrastructure, nutrition, ECD programmes, teacher training, institutional capacity and funding as the major gaps in ECD provision.

  20. Early Vocabulary Development of Australian Indigenous Children: Identifying Strengths

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    Brad M. Farrant


    Full Text Available The current study sought to increase our understanding of the factors involved in the early vocabulary development of Australian Indigenous children. Data from the Longitudinal Study of Indigenous Children were available for 573 Indigenous children (291 boys who spoke English (M=37.0 months, SD=5.4 months, at wave 3. Data were also available for 86 children (51 boys who spoke an Indigenous language (M=37.1 months, SD=6.0 months, at wave 3. As hypothesised, higher levels of parent-child book reading and having more children’s books in the home were associated with better English vocabulary development. Oral storytelling in Indigenous language was a significant predictor of the size of children’s Indigenous vocabulary.

  1. Distinctive response of CNS glial cells in oro-facial pain associated with injury, infection and inflammation

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    Ribeiro-da-Silva Alfredo


    Full Text Available Abstract Oro-facial pain following injury and infection is frequently observed in dental clinics. While neuropathic pain evoked by injury associated with nerve lesion has an involvement of glia/immune cells, inflammatory hyperalgesia has an exaggerated sensitization mediated by local and circulating immune mediators. To better understand the contribution of central nervous system (CNS glial cells in these different pathological conditions, in this study we sought to characterize functional phenotypes of glial cells in response to trigeminal nerve injury (loose ligation of the mental branch, infection (subcutaneous injection of lipopolysaccharide-LPS and to sterile inflammation (subcutaneous injection of complete Freund's adjuvant-CFA on the lower lip. Each of the three insults triggered a specific pattern of mechanical allodynia. In parallel with changes in sensory response, CNS glial cells reacted distinctively to the challenges. Following ligation of the mental nerve, both microglia and astrocytes in the trigeminal nuclear complex were highly activated, more prominent in the principal sensory nucleus (Pr5 and subnucleus caudalis (Sp5C area. Microglial response was initiated early (days 3-14, followed by delayed astrocytes activation (days 7-28. Although the temporal profile of microglial and astrocyte reaction corresponded respectively to the initiation and chronic stage of neuropathic pain, these activated glial cells exhibited a low profile of cytokine expression. Local injection of LPS in the lower lip skin also triggered a microglial reaction in the brain, which started in the circumventricular organs (CVOs at 5 hours post-injection and diffused progressively into the brain parenchyma at 48 hours. This LPS-induced microglial reaction was accompanied by a robust induction of IκB-α mRNA and pro-inflammatory cytokines within the CVOs. However, LPS induced microglial activation did not specifically occur along the pain signaling pathway. In

  2. Clinical Potential of Neurosteroids for CNS Disorders (United States)

    Reddy, Doodipala Samba; Estes, William A.


    Summary Neurosteroids are key endogenous molecules in the brain that affect many neural functions. Here, we describe recent advances in NIH-sponsored and other clinical studies of neurosteroids for CNS disorders. The neuronal GABA-A receptor chloride channel is one of the prime molecular targets of neurosteroids. Allopregnanolone-like neurosteroids are potent allosteric agonists as well as direct activators of both synaptic and extrasynaptic GABA-A receptors. Hence, neurosteroids can maximally enhance synaptic phasic and extrasynaptic tonic inhibition. The resulting chloride current conductance generates a form of shunting inhibition that controls network excitability, seizures, and behavior. Such mechanisms of neurosteroids are providing innovative therapies for epilepsy, status epilepticus, brain injury, Fragile X syndrome, and chemical neurotoxicity. The neurosteroid field has entered a new era, as many compounds have reached advanced clinical trials. Synthetic analogs have several advantages over natural neurosteroids for clinical use because of their superior bioavailability and safety trends. PMID:27156439

  3. The role of the psychosocial oncology CNS in a rural cancer outreach program. (United States)

    Watson, A C


    The high cancer mortality rates in rural areas of Virginia are discussed, and cancer risk factors particular to the rural population are delineated. Rural health beliefs and their relationship to delay in seeking cancer care in rural areas are examined. A rural cancer outreach program and the role of the oncology clinical nurse specialist (CNS) in the program are described in terms of Psychosocial Oncology CNS subroles, i.e., clinician, consultant-liaison, networker/linker, coach, educator, change agent, researcher, and supervisor/supervisee. Effectiveness of the role in the program is analyzed. An innovative urban-rural nurse oncology program is delineated, and recommendations for research in rural nursing cancer care and actions for fostering CNS role development are suggested.

  4. Multilevel Analysis of Air Pollution and Early Childhood Neurobehavioral Development (United States)

    Lin, Ching-Chun; Yang, Shih-Kuan; Lin, Kuan-Chia; Ho, Wen-Chao; Hsieh, Wu-Shiun; Shu, Bih-Ching; Chen, Pau-Chung


    To investigate the association between the ambient air pollution levels during the prenatal and postnatal stages and early childhood neurobehavioral development, our study recruited 533 mother-infant pairs from 11 towns in Taiwan. All study subjects were asked to complete childhood neurobehavioral development scales and questionnaires at 6 and 18 months. Air pollution, including particulate matter ≤10 μm (PM10), carbon monoxide (CO), sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3), and hydrocarbons, was measured at air quality monitoring stations in the towns where the subjects lived. Multilevel analyses were applied to assess the association between air pollution and childhood neurobehavioral development during pregnancy and when the children were 0 to 6 months, 7 to 12 months, and 13 to 18 months old. At 18 months, poor subclinical neurodevelopment in early childhood is associated with the average SO2 exposure of prenatal, during all trimesters of pregnancy and at postnatal ages up to 12 months (first trimester β = −0.083, se = 0.030; second and third trimester β = −0.114, se = 0.045; from birth to 12 months of age β = −0.091, se = 0.034). Furthermore, adverse gross motor below average scores at six months of age were associated with increased average non-methane hydrocarbon, (NMHC) levels during the second and third trimesters (β = −8.742, se = 3.512). Low-level SO2 exposure prenatally and up to twelve months postnatal could cause adverse neurobehavioral effects at 18 months of age. Maternal NMHC exposure during the 2nd and 3rd trimesters of pregnancy would be also associated with poor gross motor development in their children at 6 months of age. PMID:24992486

  5. Early life precursors, epigenetics, and the development of food allergy. (United States)

    Hong, Xiumei; Wang, Xiaobin


    Food allergy (FA), a major clinical and public health concern worldwide, is caused by a complex interplay of environmental exposures, genetic variants, gene-environment interactions, and epigenetic alterations. This review summarizes recent advances surrounding these key factors, with a particular focus on the potential role of epigenetics in the development of FA. Epidemiologic studies have reported a number of nongenetic factors that may influence the risk of FA, such as timing of food introduction and feeding pattern, diet/nutrition, exposure to environmental tobacco smoking, prematurity and low birth weight, microbial exposure, and race/ethnicity. Current studies on the genetics of FA are mainly conducted using candidate gene approaches, which have linked more than 10 genes to the genetic susceptibility of FA. Studies on gene-environment interactions of FA are very limited. Epigenetic alteration has been proposed as one of the mechanisms to mediate the influence of early life environmental exposures and gene-environment interactions on the development of diseases later in life. The role of epigenetics in the regulation of the immune system and the epigenetic effects of some FA-associated environmental exposures are discussed in this review. There is a particular lack of large-scale prospective birth cohort studies that simultaneously assess the interrelationships of early life exposures, genetic susceptibility, epigenomic alterations, and the development of FA. The identification of these key factors and their independent and joint contributions to FA will allow us to gain important insight into the biological mechanisms by which environmental exposures and genetic susceptibility affect the risk of FA and will provide essential information to develop more effective new paradigms in the diagnosis, prevention, and management of FA.

  6. Identifying targets of the Sox domain protein Dichaete in the Drosophila CNS via targeted expression of dominant negative proteins. (United States)

    Shen, Shih Pei; Aleksic, Jelena; Russell, Steven


    Group B Sox domain transcription factors play important roles in metazoan central nervous system development. They are, however, difficult to study as mutations often have pleiotropic effects and other Sox family members can mask phenotypes due to functional compensation. In Drosophila melanogaster, the Sox gene Dichaete is dynamically expressed in the embryonic CNS, where it is known to have functional roles in neuroblasts and the ventral midline. In this study, we use inducible dominant negative proteins in combination with ChIP, immunohistochemistry and genome-wide expression profiling to further dissect the role of Dichaete in these two tissues. We generated two dominant negative Dichaete constructs, one lacking a DNA binding domain and the other fused to the Engrailed transcriptional repressor domain. We expressed these tissue-specifically in the midline and in neuroblasts using the UAS/GAL4 system, validating their use at the phenotypic level and with known target genes. Using ChIP and immunohistochemistry, we identified two new likely direct Dichaete target genes, commisureless in the midline and asense in the neuroectoderm. We performed genome-wide expression profiling in stage 8-9 embryos, identifying almost a thousand potential tissue-specific Dichaete targets, with half of these genes showing evidence of Dichaete binding in vivo. These include a number of genes with known roles in CNS development, including several components of the Notch, Wnt and EGFR signalling pathways. As well as identifying commisureless as a target, our data indicate that Dichaete helps establish its expression during early midline development but has less effect on its established later expression, highlighting Dichaete action on tissue specific enhancers. An analysis of the broader range of candidate Dichaete targets indicates that Dichaete plays diverse roles in CNS development, with the 500 or so Dichaete-bound putative targets including a number of transcription factors

  7. Clinical features and early treatment response of central nervous system involvement in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Levinsen, Mette; Taskinen, Mervi; Abrahamsson, Jonas


    BACKGROUND: Central nervous system (CNS) involvement in childhood acute lymphoblastic leukemia (ALL) remains a therapeutic challenge. PROCEDURE: To explore leukemia characteristics of patients with CNS involvement at ALL diagnosis, we analyzed clinical features and early treatment response of 744...... had higher leukocyte count compared with patients with CNS1 (P symptoms....... Symptoms or clinical findings were present among 27 of 54 patients with CNS3 versus only 7 of 39 patients with CNS2 and 15 of 75 patients with TLP+ (P 

  8. Intraoperative squash smear cytology in CNS lesions: A study of 150 pediatric cases

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    Arpita Jindal


    Full Text Available Background: Tumors of the central nervous system in the pediatric age group occur relatively frequently during the early years of life. Brain tumors are the most common solid malignancies of childhood and only second to acute childhood leukemia. Squash cytology is an indispensable diagnostic aid to central nervous system (CNS lesions. The definitive diagnosis of brain lesions is confirmed by histological examination. Aim: To study the cytology of CNS lesions in pediatric population and correlate it with histopathology. Materials and Methods: One hundred and fifty cases of CNS lesions in pediatric patients were studied over a period of 2 years. Intraoperative squash smears were prepared, stained with hematoxylin and eosin, and examined. Remaining sample was subjected to histopathological examination. Results: Medulloblastoma (24.0% was the most frequently encountered tumor followed by pilocyctic astrocytoma (21.33% and ependymoma (13.33%. Diagnostic accuracy of squash smear technique was 94.67% when compared with histological diagnosis. Conclusion: Smear cytology is a fairly accurate tool for intraoperative CNS consultations.

  9. Alterations of myelin morphology and oligodendrocyte development in early stage of Alzheimer's disease mouse model. (United States)

    Wu, Yu; Ma, Yuanlin; Liu, Zhuo; Geng, Qi; Chen, Zexin; Zhang, Yan


    Alzheimer's disease (AD) is the most common cause to dementia and predicted to influence about 35 million people by the end of 2050. In this study, we discover alterations of myelin morphology in hippocampus tissues of 2-month-old APP/PS1 mouse. Myelin sheath is thicker and internodal distance is shorter in APP/PS1 mouse. Oligodendrocytes, differentiated from oligodendrocytes progenitor cells (OPCs), are responsible for formation and maintenance of myelin sheath in central nervous system (CNS). Our current results demonstrate that the oligodendrocytes development is disordered in 2-month-old APP/PS1 mouse. Neuregulin-1 type III, which is critical for both oligodendrocytes development and CNS myelination, is found up-regulated in hippocampus tissues of APP/PS1 mouse by western blots. Furthermore, we find active-caspase-6 can cleave neuregulin-1 type III at the cytoplasmic region. Given together, this study indicates the alterations of myelin morphology and oligodendrocytes development in 2-month-old APP/PS1 mouse, and the alterations might be highly associated with neuregulin-1 type III and active-caspase-6. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Dual effects of fluoxetine on mouse early embryonic development

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    Kim, Chang-Woon [Department of Physiology and Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-751 (Korea, Republic of); Department of Obstetrics and Gynecology, Samsung Changwon Hospital, Sungkyunkwan University, Changwon 630-723 (Korea, Republic of); Choe, Changyong [National Institute of Animal Science, RDA, Cheonan 330-801 (Korea, Republic of); Kim, Eun-Jin [Department of Physiology and Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-751 (Korea, Republic of); Lee, Jae-Ik [Department of Obstetrics and Gynecology, Gyeongsang National University Hospital, Jinju 660-702 (Korea, Republic of); Yoon, Sook-Young [Fertility Center of CHA Gangnam Medical Center, CHA University, Seoul 135-081 (Korea, Republic of); Cho, Young-Woo; Han, Sunkyu; Tak, Hyun-Min; Han, Jaehee [Department of Physiology and Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-751 (Korea, Republic of); Kang, Dawon, E-mail: [Department of Physiology and Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-751 (Korea, Republic of)


    Fluoxetine, a selective serotonin reuptake inhibitor, regulates a variety of physiological processes, such as cell proliferation and apoptosis, in mammalian cells. Little is known about the role of fluoxetine in early embryonic development. This study was undertaken to investigate the effect of fluoxetine during mouse early embryonic development. Late two-cell stage embryos (2-cells) were cultured in the presence of various concentrations of fluoxetine (1 to 50 μM) for different durations. When late 2-cells were incubated with 5 μM fluoxetine for 6 h, the percentage that developed into blastocysts increased compared to the control value. However, late 2-cells exposed to fluoxetine (5 μM) over 24 h showed a reduction in blastocyst formation. The addition of fluoxetine (5 μM) together with KN93 or KN62 (calcium/calmodulin-dependent protein kinase II (CaMKII) inhibitors) failed to increase blastocyst formation. Fluoxetine treatment inhibited TREK-1 and TREK-2, members of the two-pore domain K{sup +} channel family expressed in mouse embryos, activities, indicating that fluoxetine-induced membrane depolarization in late 2-cells might have resulted from TREK inhibition. In addition, long-term exposure to fluoxetine altered the TREK mRNA expression levels. Furthermore, injection of siRNA targeting TREKs significantly decreased blastocyst formation by ∼ 30% compared to injection of scrambled siRNA. Long-term exposure of fluoxetine had no effect on blastocyst formation of TREK deficient embryos. These results indicate that low-dose and short-term exposures of late 2-cells to fluoxetine probably increase blastocyst formation through activation of CaMKII-dependent signal transduction pathways, whereas long-term exposure decreases mouse early embryonic development through inhibition of TREK channel gating. Highlights: ► Short-term exposure of 2-cells to fluoxetine enhances mouse blastocyst formation. ► The enhancive effect of fluoxetine is resulted from Ca

  11. PTEN hamartoma tumour syndrome: early tumour development in children. (United States)

    Smpokou, Patroula; Fox, Victor L; Tan, Wen-Hann


    The aim of this study was to report the earliest age of diagnosis of common clinical findings in children with PTEN hamartoma tumour syndrome (PHTS). Medical records of children with PHTS were reviewed; data included growth measurements, presence or absence of specific clinical manifestations and tumours, and documented ages of diagnosis. Children with PHTS evaluated at Boston Children's Hospital from 1996 to 2011. The cohort included 34 children diagnosed with PHTS via genetic testing, under the age of 21 years. Of these, 23 were male and 11 female. The mean age at their last documented clinical evaluation was 13.6 years. The mean follow-up time was 7.5 years. Macrocephaly and developmental/intellectual disability were consistent findings. Pigmented penile macules were noted in all males examined for this finding. Thyroid nodules, found in half the children screened with ultrasound, were diagnosed as early as at 5 years of age. Thyroid carcinoma, identified in 12% of the children in this cohort, was diagnosed as early as at 7 years of age. Other tumours included renal cell carcinoma diagnosed at 11 years of age and granulosa cell tumour of the ovary and colonic ganglioneuroma, each diagnosed at 16 years of age. Specific clinical findings and tumours are characteristic in children with PHTS. Tumour development occurs in young children with this condition, which necessitates early surveillance, especially of the thyroid. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to

  12. Macrosomia has its roots in early placental development. (United States)

    Schwartz, N; Quant, H S; Sammel, M D; Parry, S


    We sought to determine if early placental size, as measured by 3-dimensional ultrasonography, is associated with an increased risk of delivering a macrosomic or large-for-gestational age (LGA) infant. We prospectively collected 3-dimensional ultrasound volume sets of singleton pregnancies at 11-14 weeks and 18-24 weeks. Birth weights were collected from the medical records. After delivery, the ultrasound volume set were used to measure the placental volume (PV) and placental quotient (PQ = PV/gestational age), as well as the mean placental and chorionic diameters (MPD and MCD, respectively). Placental measures were analyzed as predictors of macrosomia (birth weight ≥4000 g) and LGA (birth weight ≥90th percentile). The 578 pregnancies with first trimester volumes included 44 (7.6%) macrosomic and 43 (7.4%) LGA infants. 373 subjects also had second trimester volumes available. A higher PV and PQ were both significantly associated with macrosomia and LGA in both the first and second trimesters. Second trimester MPD was significantly associated with both outcomes as well, while second trimester MCD was only associated with LGA. The above associations remained significant after adjusting for maternal demographic variables such as race, ethnicity, age and diabetes. Adjusted models yielded moderate prediction of macrosomia and LGA (AUC: 0.71-0.77). Sonographic measurement of the early placenta can identify pregnancies at greater risk of macrosomia and LGA. Macrosomia and LGA are already determined in part by early placental growth and development. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Early motor development and cognitive abilities among Mexican preschoolers. (United States)

    Osorio-Valencia, Erika; Torres-Sánchez, Luisa; López-Carrillo, Lizbeth; Rothenberg, Stephen J; Schnaas, Lourdes


    Psychomotricity plays a very important role in children's development, especially for learning involving reading-writing and mathematical calculations. Evaluate motor development in children 3 years old and its relationship with their cognitive abilities at the age of 5 years. Based on a cohort study, we analyzed the information about motor performance evaluated at 3 years old by Peabody Motor Scale and cognitive abilities at 5 years old. The association was estimated using linear regression models adjusted by mother's intelligence quotient, sex, Bayley mental development index at 18 months, and quality of the environment at home (HOME scale). 148 children whose motor performance was determined at age 3 and was evaluated later at age 5 to determine their cognitive abilities. Cognitive abilities (verbal, quantitative, and memory) measured by McCarthy Scales. Significant positive associations were observed between stationary balance at age 3 with verbal abilities (β = 0.67, p = .04) and memory (β = 0.81, p = .02) at 5 years. Grasping and visual-motor integration were significant and positively associated with quantitative abilities (β = 0.74, p = .005; β = 0.61, p = .01) and memory (β = 2.11, p = .001; β = 1.74, p = .004). The results suggest that early motor performance contributes to the establishment of cognitive abilities at 5 years. Evaluation and early motor stimulation before the child is faced with formal learning likely helps to create neuronal networks that facilitate the acquisition of academic knowledge.

  14. A novel CNS gene required for neuronal migration and involved in X-linked subcortical laminar heterotopia and lissencephaly syndrome. (United States)

    des Portes, V; Pinard, J M; Billuart, P; Vinet, M C; Koulakoff, A; Carrié, A; Gelot, A; Dupuis, E; Motte, J; Berwald-Netter, Y; Catala, M; Kahn, A; Beldjord, C; Chelly, J


    X-SCLH/LIS syndrome is a neuronal migration disorder with disruption of the six-layered neocortex. It consists of subcortical laminar heterotopia (SCLH, band heterotopia, or double cortex) in females and lissencephaly (LIS) in males, leading to epilepsy and cognitive impairment. We report the characterization of a novel CNS gene encoding a 40 kDa predicted protein that we named Doublecortin and the identification of mutations in four unrelated X-SCLH/LIS cases. The predicted protein shares significant homology with the N-terminal segment of a protein containing a protein kinase domain at its C-terminal part. This novel gene is highly expressed during brain development, mainly in fetal neurons including precursors. The complete disorganization observed in lissencephaly and heterotopia thus seems to reflect a failure of early events associated with neuron dispersion.

  15. Investing in the foundation of sustainable development: pathways to scale up for early childhood development. (United States)

    Richter, Linda M; Daelmans, Bernadette; Lombardi, Joan; Heymann, Jody; Boo, Florencia Lopez; Behrman, Jere R; Lu, Chunling; Lucas, Jane E; Perez-Escamilla, Rafael; Dua, Tarun; Bhutta, Zulfiqar A; Stenberg, Karin; Gertler, Paul; Darmstadt, Gary L


    Building on long-term benefits of early intervention (Paper 2 of this Series) and increasing commitment to early childhood development (Paper 1 of this Series), scaled up support for the youngest children is essential to improving health, human capital, and wellbeing across the life course. In this third paper, new analyses show that the burden of poor development is higher than estimated, taking into account additional risk factors. National programmes are needed. Greater political prioritisation is core to scale-up, as are policies that afford families time and financial resources to provide nurturing care for young children. Effective and feasible programmes to support early child development are now available. All sectors, particularly education, and social and child protection, must play a role to meet the holistic needs of young children. However, health provides a critical starting point for scaling up, given its reach to pregnant women, families, and young children. Starting at conception, interventions to promote nurturing care can feasibly build on existing health and nutrition services at limited additional cost. Failure to scale up has severe personal and social consequences. Children at elevated risk for compromised development due to stunting and poverty are likely to forgo about a quarter of average adult income per year, and the cost of inaction to gross domestic product can be double what some countries currently spend on health. Services and interventions to support early childhood development are essential to realising the vision of the Sustainable Development Goals. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Investigational drugs in early development for treating dengue infection. (United States)

    Beesetti, Hemalatha; Khanna, Navin; Swaminathan, Sathyamangalam


    Dengue has emerged as the most significant arboviral disease of the current century. A drug for dengue is an urgent unmet need. As conventional drug discovery efforts have not produced any promising clinical candidates, there is a shift toward re-positioning pre-existing drugs for dengue to fast-track dengue drug development. This article provides an update on the current status of recently completed and ongoing dengue drug trials. All dengue drug trials described in this article were identified from a list of >230 trials that were returned upon searching the World Health Organization's International Clinical Trials Registry Platform web portal using the search term 'dengue' on December 31(st), 2015. None of the handful of drugs tested so far has yielded encouraging results. Early trial experience has served to emphasize the challenge of drug testing in the short therapeutic time window available, the need for tools to predict 'high-risk' patients early on and the limitations of the existing pre-clinical model systems. Significant investment of efforts and resources is a must before the availability of a safe, effective and inexpensive dengue drug becomes a reality. Currently, supportive fluid therapy remains the only option available for dengue treatment.

  17. Early development of the thymus in Xenopus laevis (United States)

    Lee, Young-Hoon; Williams, Allison; Hong, Chang-Soo; You, Youngjae; Senoo, Makoto; Saint-Jeannet, Jean-Pierre


    Background Although Xenopus laevis has been a model of choice for comparative and developmental studies of the immune system, little is known about organogenesis of the thymus, a primary lymphoid organ in vertebrates. Here we examined the expression of three transcription factors that have been functionally associated with pharyngeal gland development, gcm2, hoxa3 and foxn1, and evaluated the neural crest contribution to thymus development. Results In most species Hoxa3 is expressed in the third pharyngeal pouch endoderm where it directs thymus formation. In Xenopus, the thymus primordium is derived from the second pharyngeal pouch endoderm, which is hoxa3-negative, suggesting that a different mechanism regulates thymus formation in frogs. Unlike other species foxn1 is not detected in the epithelium of the pharyngeal pouch in Xenopus, rather, its expression is initiated as thymic epithelial cell starts to differentiate and express MHC class II molecules. Using transplantation experiments we show that while neural crest cells populate the thymus primordia, they are not required for the specification and initial development of this organ or for T cell differentiation in frogs. Conclusions These studies provide novel information on early thymus development in Xenopus, and highlight a number of features that distinguish Xenopus from other organisms. PMID:23172757

  18. Mini-review: hyaluronidases in early embryonic development. (United States)

    Stern, C D


    The foregoing discussion indicates that hyaluronidases probably play an important part in the control of development. In morphogenesis, they may be involved in epithelial-mesenchymal inductive interactions, in non-malignant invasion when one tissue displaces another in normal development, in controlling cell movements, in modulating changes of shape of cells and sheets of cells, in controlling the permeability of tissues and regulating the ionic environment within the embryo. There is also evidence indicating that hyaluronidases are involved in the initiation of cytodifferentiation pathways, perhaps via direct or indirect effects upon the cell division cycle and histone-DNA interactions. The evidence presented indicates that hyaluronidases are important repeatedly at different stages of embryonic development and differentiation, where periods of high activity follow others of reduced activity in localized regions of the embryo. Some new results were also presented, showing the presence of different hyaluronidase activities at early stages of chick embryo development. The highest levels of hyaluronidase activity were found in the primitive streak and mesoderm.

  19. Lack of carbon air filtration impacts early embryo development. (United States)

    Munch, Erika M; Sparks, Amy E; Duran, Hakan E; Van Voorhis, Bradley J


    To assess human fertilization and preimplantation embryo development in the presence and in the absence of carbon filtration This is a retrospective cohort analysis of fresh, controlled ovarian hyperstimulation cycles as well as previously cryopreserved pronuclear stage embryo transfer cycles in a single IVF center. Embryo development and cycle-based outcomes were compared among three groups: 1) when carbon filtration was present, 2) when carbon filtration was absent, and 3) when carbon filtration had been restored. A total of 524 fresh cycles and 156 cryopreserved embryo cycles were analyzed. Fertilization, cleavage, and blastocyst conversion rates for fresh cycles all declined during the period of absent carbon filtration and recovered after the restoration of carbon filtration. Cryopreserved embryos that were thawed and cultured during the period of absent filtration did not have changes in cleavage or blastocyst conversion rates compared to periods where carbon filtration was present. Clinical pregnancy and live birth rates were unchanged among the three time periods. The absence of carbon filtration in an IVF laboratory air handler is associated with poor fertilization and early embryo development for fresh cycles. Because development of previously frozen pronuclear stage embryos was unaffected, the lack of carbon filtration may preferentially affect embryos in the peri-fertilization period. Carbon filtration is an integral part to a successful human in-vitro fertilization laboratory.

  20. Mechanical origins of rightward torsion in early chick brain development (United States)

    Chen, Zi; Guo, Qiaohang; Dai, Eric; Taber, Larry


    During early development, the neural tube of the chick embryo undergoes a combination of progressive ventral bending and rightward torsion. This torsional deformation is one of the major organ-level left-right asymmetry events in development. Previous studies suggested that bending is mainly due to differential growth, however, the mechanism for torsion remains poorly understood. Since the heart almost always loops rightwards that the brain twists, researchers have speculated that heart looping affects the direction of brain torsion. However, direct evidence is lacking, nor is the mechanical origin of such torsion understood. In our study, experimental perturbations show that the bending and torsional deformations in the brain are coupled and that the vitelline membrane applies an external load necessary for torsion to occur. Moreover, the asymmetry of the looping heart gives rise to the chirality of the twisted brain. A computational model and a 3D printed physical model are employed to help interpret these findings. Our work clarifies the mechanical origins of brain torsion and the associated left-right asymmetry, and further reveals that the asymmetric development in one organ can induce the asymmetry of another developing organ through mechanics, reminiscent of D'Arcy Thompson's view of biological form as ``diagram of forces''. Z.C. is supported by the Society in Science - Branco Weiss fellowship, administered by ETH Zurich. L.A.T acknowledges the support from NIH Grants R01 GM075200 and R01 NS070918.

  1. Recent psychological explanations of infant development and scales of early mental development

    Directory of Open Access Journals (Sweden)

    Maja Zupančič


    Full Text Available This paper reviews early infant measures based on standardised scales of development – both traditional ones and those based on Piaget's sensory-motor theory – and assesses their validity in predicting later mental development. The extremely low predictive power of test scores based on these measures in infancy has provided additional support for discontinuity theories of mental development from infancy to childhood. Conversely, the constructs implicit in earlier measures have been thoroughly criticised, and the search for valid measures of infant development that would reflect a construct similar to mental abilities in childhood has begun. At the outset, research was mostly influenced by the information processing theory. Two broad measures of information processing have been shown to be the most relevant indicators of an infant's mental development, namely habituation and dishabituation. Recent mental scales, such as the Bayley Scales of Infant Development-II, thus include items that measure the efficiency of an infant's information processing. Examples of such items are presented and interpreted, as are items reflecting the development of object permanence, the only early sensory-motor measure that shows better predictive effectiveness when compared to traditional developmental test scores. Several newly-developed indicators of infants' mental development, which utilize other measures than those derived from the information-processing approach, are surveyed (understanding causal relations, joint attention behaviours, representation of number, and their possible application within the context of potential items for early mental scales is discussed. Finally, the Bayley Scales of Infant Development-II, currently one of the best measures of early development, and presently undergoing a standardisation procedure in Slovenia, is evaluated, with analyses of some items from the Mental scale presented within the text.

  2. Life cycle assessment of nanoadsorbents at early stage technological development

    DEFF Research Database (Denmark)

    Kazemi, Ali; Bahramifar, Nader; Heydari, Akbar


    the process of the functionalization of nanoadsorbents leads to the increase of the adsorption capacity of nanoadsorbents, it is also paired with a significant enhancement of negative environmental impacts. The results of t-test comparing the cradle-to-use life cycle impacts of studied impact categories for 1......Increasing pressure to the environment due to human activities manifests the necessity of applying new approaches to determine the environmental impact of a new product before scale-up. Nanoadsorbents as an emerging product and a special application of nanomaterial play an important role...... in the control and removal of environmental pollutants. This application is still an emerging technology at the early stages of development. Hence, the heart of this study enables an environmental assessment of nanoadsorbents as an emerging product. In addition, the environmental impacts of synthesized...

  3. Roles of Pel and Psl in very early biofilm development (United States)

    Cooley, B. J.; Thatcher, Travis; L'Her, Guillaume; Reed, Erin; Stuart, Jamie; Kissinger, April; Gordon, Vernita


    Biofilms are dynamic, multicellular communities of unicellular organisms. Biofilms cause many chronic infections; an important case is the opportunistic human pathogen Pseudomonas aeruginosa. Bacteria in biofilms produce an extracellular matrix that binds bacteria to each other and to a surface. The two primary extracellular matrix components produced by P. aeruginosa are the polysaccharides Pel and Psl. Here we examine the roles of Pel and Psl in the very early stages of biofilm development, just after initial surface attachment. We use high-throughput automated tracking and analysis to compare wild-type bacteria with mutants incapable of producing Pel, Psl, or both. We examine motion on a surface as well as inter-bacterial interactions. These results quantify the unique roles played by Pel and Psl and show an unexpected relationship between Pel expression and adhesion to a surface.

  4. Women, "Star Trek," and the early development of fannish vidding

    Directory of Open Access Journals (Sweden)

    Francesca Coppa


    Full Text Available This paper argues that the practices and aesthetics of vidding were structured by the relationship of Star Trek's female fans to that particular televisual text. Star Trek fandom was the crucible within which vidding developed because Star Trek's narrative impelled female fans to take on two positions often framed as contradictory in mainstream culture: the desiring body, and the controlling voice of technology. To make a vid, to edit footage to subtext-revealing music, is to unite these positions: to put technology at the service of desire. Although the conflict between desire and control was particularly thematized in Star Trek, most famously through the divided character of Spock, the practices of vidding are now applied to other visual texts. This essay examines the early history of vidding and demonstrates, through the close reading of particular vids made for Star Trek and Quantum Leap, how vidding heals the wounds created by the displacement and fragmentation of women on television.

  5. From universal to language-specific in early grammatical development. (United States)

    Bowerman, M


    Attempts to explain children's grammatical development often assume a close initial match between units of meaning and units of form; for example, agents are said to map to sentence-subjects and actions to verbs. The meanings themselves, according to this view, are not influenced by language, but reflect children's universal non-linguistic way of understanding the world. This paper argues that, contrary to this position, meaning as it is expressed in children's early sentences is, from the beginning, organized on the basis of experience with the grammar and lexicon of a particular language. As a case in point, children learning English and Korean are shown to express meanings having to do with direct motion according to language-specific principles of semantic and grammatical structuring from the earliest stages of word combination.

  6. Nuclear lamins during gametogenesis, fertilization and early development (United States)

    Maul, G. G.; Schatten, G.


    The distribution of lamins (described by Gerace, 1978, as major proteins of nuclear envelope) during gametogenesis, fertilization, and early development was investigated in germ cells of a mouse (Mus musculus), an echinoderm (Lytechinus variegatus), and the surf clam (Spisula solidissima) was investigated in order to determine whether the differences detected could be correlated with differences in the function of cells in these stages of the germ cells. In order to monitor the behavior of lamins, the gametes and embryos were labeled with antibodies to lamins A, C, and B extracted from autoimmune sera of patients with scleroderma and Lupus erythematosus. Results indicated that lamin B could be identified in nuclear envelopes on only those nuclei where chromatin is attached and where RNA synthesis takes place.

  7. Late Cretaceous-Early Palaeogene tectonic development of SE Asia (United States)

    Morley, C. K.


    The Late Cretaceous-Early Palaeogene history of the continental core of SE Asia (Sundaland) marks the time prior to collision of India with Asia when SE Asia, from the Tethys in the west to the Palaeo-Pacific in the east, lay in the upper plate of subduction zones. In Myanmar and Sumatra, subduction was interrupted in the Aptian-Albian by a phase of arc accretion (Woyla and Mawgyi arcs) and in Java, eastern Borneo and Western Sulawesi by collision of continental fragments rifted from northern Australia. Subsequent resumption of subduction in the Myanmar-Thailand sector explains: 1) early creation of oceanic crust in the Andaman Sea in a supra-subduction zone setting ~ 95 Ma, 2) the belt of granite plutons of Late Cretaceous-Early Palaeogene age (starting ~ 88 Ma) in western Thailand and central Myanmar, and 3) amphibolite grade metamorphism between 70 and 80 Ma seen in gneissic outcrops in western and central Thailand, and 4) accretionary prism development in the Western Belt of Myanmar, until glancing collision with the NE corner of Greater India promoted ophiolite obduction, deformation and exhumation of marine sediments in the early Palaeogene. The Ranong strike-slip fault and other less well documented faults, were episodically active during the Late Cretaceous-Palaeogene time. N to NW directed subduction of the Palaeo-Pacific ocean below Southern China, Vietnam and Borneo created a major magmatic arc, associated with rift basins, metamorphic core complexes and strike-slip deformation which continued into the Late Cretaceous. The origin and timing of termination of subduction has recently been explained by collision of a large Luconia continental fragment either during the Late Cretaceous or Palaeogene. Evidence for such a collision is absent from the South China Sea well and seismic reflection record and here collision is discounted. Instead relocation of the subducting margin further west, possibly in response of back-arc extension (which created the Proto

  8. GSK-3 inhibitors: preclinical and clinical focus on CNS

    Directory of Open Access Journals (Sweden)

    Hagit eEldar-Finkelman


    Full Text Available Inhibiting glycogen synthase kinase-3 (GSK-3 activity via pharmacological intervention has become an important target for treating neurodegenerative and psychiatric disorders. The reported GSK-3 inhibitors are of diverse chemotypes and mechanisms of action that include compounds isolated from natural sources, cations, synthetic small-molecule ATP-competitive inhibitors, non-ATP-competitive inhibitors, and substrate-competitive inhibitors. Here we describe the variety of GSK-3 inhibitors with a specific emphasis on their biological activities in neurons and neurological disorders. We further highlight our current progress in the development of non-ATP-competitive inhibitors of GSK-3.The available data raises the hope that one or more of these drug design approaches will prove successful at stabilizing or even reversing the aberrant neuropathology and cognitive deficits of certain CNS disorders.

  9. Serum Amyloid A Facilitates Early Lesion Development in Ldlr-/- Mice. (United States)

    Krishack, Paulette A; Bhanvadia, Clarissa V; Lukens, John; Sontag, Timothy J; De Beer, Maria C; Getz, Godfrey S; Reardon, Catherine A


    Atherosclerosis is a chronic inflammatory disorder, and several studies have demonstrated a positive association between plasma serum amyloid A (SAA) levels and cardiovascular disease risk. The aim of the study was to examine whether SAA has a role in atherogenesis, the underlying basis of most cardiovascular disease. Mice globally deficient in acute-phase isoforms Saa1 and Saa2 (Saa(-/-)) were crossed to Ldlr(-/-) mice (Saa(-/-)Ldlr(-/-)). Saa(-/-)Ldlr(-/-) mice demonstrated a 31% reduction in lesional area in the ascending aorta but not in the aortic root or innominate artery after consuming a high-fat, high-cholesterol Western-type diet for 6 weeks. The lesions were predominantly macrophage foam cells. The phenotype was lost in more mature lesions in mice fed a Western-type diet for 12 weeks, suggesting that SAA is involved in early lesion development. The decreased atherosclerosis in the Saa(-/-)Ldlr(-/-) mice occurred despite increased levels of blood monocytes and was independent of plasma lipid levels. SAA is produced predominantly by hepatocytes and macrophages. To determine which source of SAA may have a dominant role in lesion development, bone marrow transplantation was performed. Ldlr(-/-) mice that received bone marrow from Saa(-/-)Ldlr(-/-) mice had slightly reduced ascending aorta atherosclerosis compared with Saa(-/-)Ldlr(-/-) mice receiving bone marrow from Ldlr(-/-) mice, indicating that the expression of SAA by macrophages may have an important influence on atherogenesis. The results indicate that SAA produced by macrophages promotes early lesion formation in the ascending aorta. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  10. Diversity. Early Developments. Volume 8, Number 1, Spring 2004 (United States)

    Manuel, John


    What is it about cultural diversity that challenges early childhood programs? One factor is that children enter early childhood and early intervention programs from families with a wide range of values and cultural experiences. Sometimes those values and experiences differ from those of the teachers and caregivers in those programs. Another factor…

  11. Napping facilitates word learning in early lexical development. (United States)

    Horváth, Klára; Myers, Kyle; Foster, Russell; Plunkett, Kim


    Little is known about the role that night-time sleep and daytime naps play in early cognitive development. Our aim was to investigate how napping affects word learning in 16-month-olds. Thirty-four typically developing infants were assigned randomly to nap and wake groups. After teaching two novel object-word pairs to infants, we tested their initial performance with an intermodal preferential looking task in which infants are expected to increase their target looking time compared to a distracter after hearing its auditory label. A second test session followed after approximately a 2-h delay. The delay contained sleep for the nap group or no sleep for the wake group. Looking behaviour was measured with an automatic eye-tracker. Vocabulary size was assessed using the Oxford Communicative Development Inventory. A significant interaction between group and session was found in preferential looking towards the target picture. The performance of the nap group increased after the nap, whereas that of the wake group did not change. The gain in performance correlated positively with the expressive vocabulary size in the nap group. These results indicate that daytime napping helps consolidate word learning in infancy. © 2015 European Sleep Research Society.

  12. Structural and Maturational Covariance in Early Childhood Brain Development. (United States)

    Geng, Xiujuan; Li, Gang; Lu, Zhaohua; Gao, Wei; Wang, Li; Shen, Dinggang; Zhu, Hongtu; Gilmore, John H


    Brain structural covariance networks (SCNs) composed of regions with correlated variation are altered in neuropsychiatric disease and change with age. Little is known about the development of SCNs in early childhood, a period of rapid cortical growth. We investigated the development of structural and maturational covariance networks, including default, dorsal attention, primary visual and sensorimotor networks in a longitudinal population of 118 children after birth to 2 years old and compared them with intrinsic functional connectivity networks. We found that structural covariance of all networks exhibit strong correlations mostly limited to their seed regions. By Age 2, default and dorsal attention structural networks are much less distributed compared with their functional maps. The maturational covariance maps, however, revealed significant couplings in rates of change between distributed regions, which partially recapitulate their functional networks. The structural and maturational covariance of the primary visual and sensorimotor networks shows similar patterns to the corresponding functional networks. Results indicate that functional networks are in place prior to structural networks, that correlated structural patterns in adult may arise in part from coordinated cortical maturation, and that regional co-activation in functional networks may guide and refine the maturation of SCNs over childhood development. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail:

  13. The Early Stages of Heart Development: Insights from Chicken Embryos

    Directory of Open Access Journals (Sweden)

    Johannes G. Wittig


    Full Text Available The heart is the first functioning organ in the developing embryo and a detailed understanding of the molecular and cellular mechanisms involved in its formation provides insights into congenital malformations affecting its function and therefore the survival of the organism. Because many developmental mechanisms are highly conserved, it is possible to extrapolate from observations made in invertebrate and vertebrate model organisms to humans. This review will highlight the contributions made through studying heart development in avian embryos, particularly the chicken. The major advantage of chick embryos is their accessibility for surgical manipulation and functional interference approaches, both gain- and loss-of-function. In addition to experiments performed in ovo, the dissection of tissues for ex vivo culture, genomic, or biochemical approaches is straightforward. Furthermore, embryos can be cultured for time-lapse imaging, which enables tracking of fluorescently labeled cells and detailed analysis of tissue morphogenesis. Owing to these features, investigations in chick embryos have led to important discoveries, often complementing genetic studies in mice and zebrafish. As well as including some historical aspects, we cover here some of the crucial advances made in understanding early heart development using the chicken model.

  14. The development of numerical representations in early childhood

    Directory of Open Access Journals (Sweden)

    Matija Svetina


    Full Text Available Recent studies of numerosity in the field of developmental psychology indicate that numerical representation in children might be regarded in terms of Fechner's law of logarithmic relations between stimuli and response. The data also suggest that the shift from logarithmic to linear pattern of mental representation relates to different factors such as age, number scale, and culture. However, very little is known whether cognitive factors such as procedural and conceptual development have any impact on numerical representations, particularly in the preschoolers. The aim of our study was to provide an explanation of relations between numerical concepts and numerical representations in preschool children. In the study, 39 3-6 year-olds were presented with both, task of conceptual understanding of numbers and the number line task. The results indicate that the development of conceptual understanding of numbers may act as a threshold condition to the development of linear numerical representations in early childhood. Implications of these findings, such as representations of height, distance or value are further discussed.

  15. Ethnic Group Differences in Early Head Start Parents Parenting Beliefs and Practices and Links to Children's Early Cognitive Development (United States)

    Keels, Micere


    Data from the Early Head Start Research and Evaluation study were used to examine the extent to which several factors mediate between- and within-ethnic-group differences in parenting beliefs and behaviors, and children's early cognitive development (analysis sample of 1198 families). The findings indicate that Hispanic-, European-, and…

  16. Improving Latino Children's Early Language and Literacy Development: Key Features of Early Childhood Education within Family Literacy Programmes (United States)

    Jung, Youngok; Zuniga, Stephen; Howes, Carollee; Jeon, Hyun-Joo; Parrish, Deborah; Quick, Heather; Manship, Karen; Hauser, Alison


    Noting the lack of research on how early childhood education (ECE) programmes within family literacy programmes influence Latino children's early language and literacy development, this study examined key features of ECE programmes, specifically teacher-child interactions and child engagement in language and literacy activities and how these…

  17. Exploring Parental Involvement in Early Years Education in China: Development and Validation of the Chinese Early Parental Involvement Scale (CEPIS) (United States)

    Lau, Eva Yi Hung; Li, Hui; Rao, Nirmala


    This study developed and validated an instrument, the Chinese Early Parental Involvement Scale (CEPIS), that can be widely used in both local and international contexts to assess Chinese parental involvement in early childhood education. The study was carried out in two stages: (1) focus group interviews were conducted with 41 teachers and 35…

  18. pDC therapy induces recovery from EAE by recruiting endogenous pDC to sites of CNS inflammation

    DEFF Research Database (Denmark)

    Duraes, Fernanda V; Lippens, Carla; Steinbach, Karin


    ) initiation, myelin-antigen presentation by pDCs is associated with suppressive Treg development and results in attenuated EAE. Here, we show that pDCs transferred during acute disease phase confer recovery from EAE. Clinical improvement is associated with migration of injected pDCs into inflamed CNS...... and is dependent on the subsequent and selective chemerin-mediated recruitment of endogenous pDCs to the CNS. The protective effect requires pDC pre-loading with myelin antigen, and is associated with the modulation of CNS-infiltrating pDC phenotype and inhibition of CNS encephalitogenic T cells. This study may...... pave the way for novel pDC-based cell therapies in autoimmune diseases, aiming at specifically modulating pathogenic cells that induce and sustain autoimmune inflammation....

  19. Preschoolers Know, but How Do They Know? Developing a Framework for Early Epistemology Development (United States)

    Winsor, Denise L.; Blake, Sally


    Two areas that are lacking for the purpose of training high-quality preschool teachers; and constructing developmentally appropriate learning standards and curriculum for preschool children are awareness of early epistemic development (beliefs about knowledge and knowing) and understanding preschoolers' cognitive processes during epistemic…

  20. Molecular Basis of the interactions of the Nogo-66 Receptor and its homologue NgR2 with Myelin-Associated Glycoprotein: Development of NgROMNI-Fc a Novel Antagonist of CNS Myelin Inhibition (United States)

    Robak, Laurie A.; Venkatesh, Karthik; Lee, Hakjoo; Raiker, Stephen J.; Duan, Yuntao; Lee-Osbourne, Jane; Hofer, Thomas; Mage, Rose G.; Rader, Christoph; Giger, Roman J.


    Myelin-associated glycoprotein (MAG) is a sialic acid binding Ig-family lectin that functions in neuronal growth inhibition and stabilization of axon-glia interactions. The ectodomain of MAG is comprised of five Ig-like domains and employs neuronal cell-type specific mechanisms to signal growth inhibition. We show that the first three Ig-like domains of MAG bind with high-affinity and in a sialic acid dependent manner to the Nogo-66 receptor-1 (NgR1) and its homologue NgR2. Domains Ig3-Ig5 of MAG are sufficient to inhibit neurite outgrowth but fail to associate with NgR1 or NgR2. Nogo receptors are sialoglycoproteins comprised of 8.5 canonical leucine-rich repeats (LRR) flanked by LRR N-terminal (NT) and C-terminal (CT)-cap domains. The LRR cluster is connected through a stalk region to a membrane lipid anchor. The CT-cap domain and stalk region of NgR2, but not NgR1, are sufficient for MAG binding, and when expressed in neurons, exhibit constitutive growth inhibitory activity. The LRR cluster of NgR1 supports binding of Nogo-66, OMgp and MAG. Deletion of disulfide loop Cys309-Cys336 of NgR1 selectively increases its affinity for Nogo-66 and OMgp. A chimeric Nogo receptor variant (NgROMNI) in which Cys309-Cys336 is deleted and followed by a 13 amino acid MAG binding motif of the NgR2 stalk, shows superior binding of OMgp, Nogo-66, and MAG compared to wild-type NgR1 or NgR2. Soluble NgROMNI (NgROMNI-Fc) binds strongly to membrane bound inhibitors and promotes neurite outgrowth on both MAG and CNS myelin substrates. Thus, NgROMNI-Fc may offer therapeutic opportunities following nervous system injury or disease where myelin inhibits neuronal regeneration. PMID:19420245

  1. Developing an Early Warning System for Machu Picchu Pueblo, Peru. (United States)

    Bulmer, Mark; Farquhar, Tony


    The town of Machu Picchu, Peru, is linked to Ollantaytambo and Cusco by rail and serves as the main station for the 400,000+ tourists visiting Machu Picchu. Due to the tourist industry the town grown threefold in population in the past two decades. Today, due to the limited availability of low-lying ground, construction is occurring higher up on the unstable valley slopes. The town is located at 2000 m asl while the surrounding peaks rise to over 4000 m asl. Slopes range from 70° in the surrounding granite mountains. The town has grown on the downstream right bank of the Vilcanota River, at the confluence of the Alcamayo and the Aguas Calientes Rivers. Broadly, a dry winter season runs from May to August with a rainy summer season running from October to March. The rainy months provide around 80% of the annual rainfall average, which ranges from 1,600 to 2,300 mm. Seasonal temperature variations are considered modest. An assessment of the geohazards in and around the town has been undertaken. Those of particular concern to the town are 1) large rocks falling onto the town and/or the rail line, 2) flash flooding by any one of its three rivers, and 3) mudflows and landslides. To improve the existing municipal warning system a prototype early warning system incorporating suitable technologies that could monitor weather, river flow and slope satability was installed along the Aguas Calientes River in 2009. This has a distributed modular construction allowing most components to be installed, maintained, swapped, salvaged, repaired and/or replaced by local technicians. A diverse set of candidate power, communication and sensor technologies was deployed and evaluated. Most of the candidate technologies had never been deployed in similar terrain, altitude or weather. The successful deployment of the prototype proved that it is technically feasible to develop early warning capacity in the town.

  2. Impact of early postnatal androgen exposure on voice development.

    Directory of Open Access Journals (Sweden)

    Leila Grisa

    Full Text Available BACKGROUND: The impact of early postnatal androgen exposure on female laryngeal tissue may depend on certain characteristics of this exposure. We assessed the impact of the dose, duration, and timing of early androgen exposure on the vocal development of female subjects who had been treated for adrenocortical tumor (ACT in childhood. METHODS: The long-term effects of androgen exposure on the fundamental vocal frequency (F0, vocal pitch, and final height and the presence of virilizing signs were examined in 9 adult (age, 18.4 to 33.5 years and 10 adolescent (13.6 to 17.8 years female ACT patients. We also compared the current values with values obtained 0.9 years to 7.4 years after these subjects had undergone ACT surgery, a period during which they had shown normal androgen levels. RESULTS: Of the 19 subjects, 17 (89% had been diagnosed with ACT before 4 years of age, 1 (5% at 8.16 years, and 1 (5% at 10.75 years. Androgen exposure (2 to 30 months was sufficiently strong to cause pubic hair growth in all subjects and clitoromegaly in 74% (14/19 of the subjects, but did not reduce their height from the target value. Although androgen exposure induced a remarkable reduction in F0 (132 Hz and moderate pitch virilization in 1 subject and partial F0 virilization, resulting in F0 of 165 and 169 Hz, in 2 subjects, the majority had normal F0 ranging from 189 to 245 Hz. CONCLUSIONS: Female laryngeal tissue is less sensitive to androgen exposure between birth and adrenarche than during other periods. Differential larynx sensitivity to androgen exposure in childhood and F0 irreversibility in adulthood are age-, concentration-, duration-, and timing-dependent events that may also be affected by exposure to inhibitory or stimulatory hormones. Further studies are required to better characterize each of these factors.

  3. Origins and early development of human body knowledge. (United States)

    Slaughter, Virginia; Heron, Michelle


    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. Sensorimotor 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 visuo-spatial 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 picture sat 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

  4. Infant feeding effects on early neurocognitive development in Asian children. (United States)

    Cai, Shirong; Pang, Wei Wei; Low, Yen Ling; Sim, Lit Wee; Sam, Suet Chian; Bruntraeger, Michaela Bianka; Wong, Eric Qinlong; Fok, Doris; Broekman, Birit F P; Singh, Leher; Richmond, Jenny; Agarwal, Pratibha; Qiu, Anqi; Saw, Seang Mei; Yap, Fabian; Godfrey, Keith M; Gluckman, Peter D; Chong, Yap-Seng; Meaney, Michael J; Kramer, Michael S; Rifkin-Graboi, Anne


    Breastfeeding has been shown to enhance global measures of intelligence in children. However, few studies have examined associations between breastfeeding and specific cognitive task performance in the first 2 y of life, particularly in an Asian population. We assessed associations between early infant feeding and detailed measures of cognitive development in the first 2 y of life in healthy Asian children born at term. In a prospective cohort study, neurocognitive testing was performed in 408 healthy children (aged 6, 18, and 24 mo) from uncomplicated pregnancies (i.e., birth weight >2500 and <4000 g, gestational age ≥37 wk, and 5-min Apgar score ≥9). Tests included memory (deferred imitation, relational binding, habituation) and attention tasks (visual expectation, auditory oddball) as well as the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). Children were stratified into 3 groups (low, intermediate, and high) on the basis of breastfeeding duration and exclusivity. After potential confounding variables were controlled for, significant associations and dose-response relations were observed for 4 of the 15 tests. Higher breastfeeding exposure was associated with better memory at 6 mo, demonstrated by greater preferential looking toward correctly matched items during early portions of a relational memory task (i.e., relational binding task: P-trend = 0.015 and 0.050 for the first two 1000-ms time bins, respectively). No effects of breastfeeding were observed at 18 mo. At 24 mo, breastfed children were more likely to display sequential memory during a deferred imitation memory task (P-trend = 0.048), and toddlers with more exposure to breastfeeding scored higher in receptive language [+0.93 (0.23, 1.63) and +1.08 (0.10, 2.07) for intermediate- and high-breastfeeding groups, respectively, compared with the low-breastfeeding group], as well as expressive language [+0.58 (-0.06, 1.23) and +1.22 (0.32, 2.12) for intermediate- and high

  5. Loss of primary cilia occurs early in breast cancer development (United States)


    Background Primary cilia are microtubule-based organelles that protrude from the cell surface. Primary cilia play a critical role in development and disease through regulation of signaling pathways including the Hedgehog pathway. Recent mouse models have also linked ciliary dysfunction to cancer. However, little is known about the role of primary cilia in breast cancer development. Primary cilia expression was characterized in cancer cells as well as their surrounding stromal cells from 86 breast cancer patients by counting cilia and measuring cilia length. In addition, we examined cilia expression in normal epithelial and stromal cells from reduction mammoplasties as well as histologically normal adjacent tissue for comparison. Results We observed a statistically significant decrease in the percentage of ciliated cells on both premalignant lesions as well as in invasive cancers. This loss of cilia does not correlate with increased proliferative index (Ki67-positive cells). However, we did detect rare ciliated cancer cells present in patients with invasive breast cancer and found that these express a marker of basaloid cancers that is associated with poor prognosis (Cytokeratin 5). Interestingly, the percentage of ciliated stromal cells associated with both premalignant and invasive cancers decreased when compared to stromal cells associated with normal tissue. To understand how cilia may be lost during cancer development we analyzed the expression of genes required for ciliogenesis and/or ciliary function and compared their expression in normal versus breast cancer samples. We found that expression of ciliary genes were frequently downregulated in human breast cancers. Conclusions These data suggest that primary cilia are lost early in breast cancer development on both the cancer cells and their surrounding stromal cells. PMID:24987519

  6. Controls on development and diversity of Early Archean stromatolites. (United States)

    Allwood, Abigail C; Grotzinger, John P; Knoll, Andrew H; Burch, Ian W; Anderson, Mark S; Coleman, Max L; Kanik, Isik


    The approximately 3,450-million-year-old Strelley Pool Formation in Western Australia contains a reef-like assembly of laminated sedimentary accretion structures (stromatolites) that have macroscale characteristics suggestive of biological influence. However, direct microscale evidence of biology--namely, organic microbial remains or biosedimentary fabrics--has to date eluded discovery in the extensively-recrystallized rocks. Recently-identified outcrops with relatively good textural preservation record microscale evidence of primary sedimentary processes, including some that indicate probable microbial mat formation. Furthermore, we find relict fabrics and organic layers that covary with stromatolite morphology, linking morphologic diversity to changes in sedimentation, seafloor mineral precipitation, and inferred microbial mat development. Thus, the most direct and compelling signatures of life in the Strelley Pool Formation are those observed at the microscopic scale. By examining spatiotemporal changes in microscale characteristics it is possible not only to recognize the presence of probable microbial mats during stromatolite development, but also to infer aspects of the biological inputs to stromatolite morphogenesis. The persistence of an inferred biological signal through changing environmental circumstances and stromatolite types indicates that benthic microbial populations adapted to shifting environmental conditions in early oceans.

  7. Investigational antiarrhythmic agents: promising drugs in early clinical development. (United States)

    Heijman, Jordi; Ghezelbash, Shokoufeh; Dobrev, Dobromir


    Although there have been important technological advances for the treatment of cardiac arrhythmias (e.g., catheter ablation technology), antiarrhythmic drugs (AADs) remain the cornerstone therapy for the majority of patients with arrhythmias. Most of the currently available AADs were coincidental findings and did not result from a systematic development process based on known arrhythmogenic mechanisms and specific targets. During the last 20 years, our understanding of cardiac electrophysiology and fundamental arrhythmia mechanisms has increased significantly, resulting in the identification of new potential targets for mechanism-based antiarrhythmic therapy. Areas covered: Here, we review the state-of-the-art in arrhythmogenic mechanisms and AAD therapy. Thereafter, we focus on a number of antiarrhythmic targets that have received significant attention recently: atrial-specific K+-channels, the late Na+-current, the cardiac ryanodine-receptor channel type-2, and the small-conductance Ca2+-activated K+-channel. We highlight for each of these targets available antiarrhythmic agents and the evidence for their antiarrhythmic effect in animal models and early clinical development. Expert opinion: Targeting AADs to specific subgroups of well-phenotyped patients is likely necessary to detect improved outcomes that may be obscured in the population at large. In addition, specific combinations of selective AADs may have synergistic effects and may enable a mechanism-based tailored antiarrhythmic therapy.

  8. Early phonetic and lexical development: a productivity approach. (United States)

    McCune, L; Vihman, M M


    Researchers frequently examine the development of the single-word lexicon in the absence of phonetic data. Yet a large body of literature demonstrates relationships between the phonetics of babble and early speech, and it is clear that production skill is essential for establishing a lexicon. This study uses longitudinal productivity criteria to establish children's phonetic skill. Twenty children were followed from age 9 to 16 months, and their level of consistency of vocal patterns was examined in relation to their lexical production, providing a relatively large-sample demonstration of phonetic/lexical relationships at the transition to language. Number of specific consonants produced consistently across the months of observation predicted referential lexical use at 16 months, whereas the transition to reference itself signaled the onset of a sharp increase in numbers of different words produced in a session. The earliest referential speakers exhibited prior consistency in the production of [p/b], which also predominated in their words. Prior use of at least two supraglottal consonants characterized the referential group. Children varied in the specific consonants they produced consistently, and these same consonants, varying according to individual child repertoire, characterized nearly all consonant-based words produced by each child in both of the final 2 months of observation. These findings are interpreted in relation to the children's contemporaneous development of representational ability and pragmatic skill.

  9. Molecular dissection of heterosis manifestation during early maize root development. (United States)

    Paschold, Anja; Marcon, Caroline; Hoecker, Nadine; Hochholdinger, Frank


    Heterosis is of paramount agronomic importance and has been successfully exploited in maize hybrid breeding for decades. Nevertheless, the molecular basis of heterosis remains elusive. Heterosis is not only observed in adult traits like yield or plant height, but is already detected during embryo and seedling development. Hence, the maize (Zea mays L.) primary root which is the first organ that emerges after germination is a suitable model to study heterosis manifestation. Various seedling root traits including primary root length and lateral root density display heterosis. Microarray studies suggest organ specific patterns of nonadditive gene expression in maize hybrids. Moreover, such experiments support the notion that global expression trends in maize primary roots are conserved between different hybrids. Furthermore, nonadditive expression patterns of specific genes such as a SUPEROXIDE DISMUTASE 2 might contribute to the early manifestation of heterosis. Proteome profiling experiments of maize hybrid primary roots revealed nonadditive accumulation patterns that were distinct from the corresponding RNA profiles underscoring the importance of posttranscriptional processes such as protein modifications that might be related to heterosis. Finally, analysis of selected metabolites imply that a subtle regulation of particular biochemical pathways such as the phenylpropanoid pathway in hybrids might contribute to the manifestation of heterosis in maize primary roots. In the future, recently developed molecular tools will facilitate the analysis of the molecular principles underlying heterosis in maize roots.

  10. 3-D imaging of the CNS. (United States)

    Runge, V M; Gelblum, D Y; Wood, M L


    3-D gradient echo techniques, and in particular FLASH, represent a significant advance in MR imaging strategy allowing thin section, high resolution imaging through a large region of interest. Anatomical areas of application include the brain, spine, and extremities, although the majority of work to date has been performed in the brain. Superior T1 contrast and thus sensitivity to the presence of GdDTPA is achieved with 3-D FLASH when compared to 2-D spin echo technique. There is marked arterial and venous enhancement following Gd DTPA administration on 3-D FLASH, a less common finding with 2-D spin echo. Enhancement of the falx and tentorium is also more prominent. From a single data acquisition, requiring less than 11 min of scan time, high resolution reformatted sagittal, coronal, and axial images can obtained in addition to sections in any arbitrary plane. Tissue segmentation techniques can be applied and lesions displayed in three dimensions. These results may lead to the replacement of 2-D spin echo with 3-D FLASH for high resolution T1-weighted MR imaging of the CNS, particularly in the study of mass lesions and structural anomalies. The application of similar T2-weighted gradient echo techniques may follow, however the signal-to-noise ratio which can be achieved remains a potential limitation.

  11. Preliminary Results of Management for Primary CNS Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Seung Do; Chang, Hye Sook; Choi, Eun Kyong [Ulsan University College of Medicine, Seoul (Korea, Republic of)


    From October 1989 to March 1992, ten patients diagnosed as primary central nervous system(CNS) lymphoma were treated with radiation therapy at Asan Medical Center. To obtain pathologic diagnosis, five patients had stereotactic biopsy and the others underwent craniotomy and tumor removal. According to the classification by International Working Formulation, seven of 10 patients showed diffuse large cell types and the remaining 3 had diffuse mixed cell types. Computed tomographic scans of the brain disclosed solitary (6 cases) or multiple (4 cases) intracranial lesions. All patients received 4000cGy/20 fx to the whole brain followed by an additional 2000cGy/10 fx boost to the primary lesion. Six patients with initial cerebrospinal fluid (CSF) involvement were treated with whole brain irradiation and intrathecal Methotrexate(IT-MTX) chemotherapy. One of them received an additional spinal irradiation after 3 cycles of IT-MTX chemotherapy because of MTX induced arachnoiditis. One patient received 3 cycles of systemic chemotherapy prior to radiation therapy and one received 5 cycles of salvage chemotherapy for recurrence. With a median follow up time of 8 months, all patients were followed from 7 to 26 months. Radiologically seven patients showed complete remission and the remaining three showed partial remission at one month after radiotherapy. The 1 and 2 year survival rate was 86% and 69% respectively. Until now, two patients expired at 7 and 14 months. These patients developed extensive CSF seeding followed by local failure. Considering initial good response to radiation therapy and low incidence of extraneural dissemination in primary CNS lymphoma, we propose to increase total tumor dose to the primary lesion by hyperfractionated radiotherapy or stereotactic radiosurgery. For the patients with CSF involvement at diagnosis, we propose craniospinal irradiation with IT MTX chemotherapy.

  12. CNS safety pharmacology: A focus on cognitive functions. (United States)

    Hernier, Anne Marie; Froger-Colléaux, Christelle; Castagné, Vincent


    The guidelines from different agencies do not include studies on cognitive functions as part of safety pharmacology. This is unfortunate as it seems important to verify that drugs entering into the central nervous system (CNS) are devoid of detrimental effects on cognition. Our aim is to show examples on how an evaluation of unwanted effects of drugs on cognitive functions may be included in preclinical studies. Rather than a review of the scientific context, the present text is an appeal for a wider consideration of cognition as a safety pharmacology endpoint. The following procedures provide an index of the ability of substances to induce cognitive deficits in rodents. In the passive avoidance (PA) test, rats receiving an electric shock show on a later occasion an avoidance of the shock-associated environment. In the social recognition (SR) test, rats recognize familiar congeners. In the Morris water maze (MWM) test, rats placed into a tank containing water learn to find an invisible escape platform using extra-maze visual cues. In the delayed alternation (DA) test, rats placed in a Skinner box learn to alternate their pressing behavior between two levers in order to obtain food rewards. In the operant reversal (OR) test, rats adapt their behavior following a change of the reinforcement rule. Standard reference agents were used to confirm that the different assays were able to detect pharmacologically induced cognitive impairments. Diazepam decreased associative memory performances in the PA test. MK-801-induced memory deficits in SR. Haloperidol increased escape latencies in the MWM test. Scopolamine decreased the number of correct responses in the DA test, and nicotine decreased the number of correct responses in the OR test. The relationship between the doses administered and the effects observed was also evaluated. Cognitive assays may provide utility in determining potential undesirable effects or discharging perceived risks with novel CNS drugs under

  13. Early stages in the development of bipolar disorder. (United States)

    Duffy, Anne; Alda, Martin; Hajek, Tomas; Sherry, Simon B; Grof, Paul


    Numerous studies have observed that offspring of bipolar parents manifest a broad spectrum of psychiatric disorders. We tested the hypothesis that in high risk offspring, bipolar disorder evolves in a predictable clinical sequence from non-specific (non-mood) to specific (mood) psychopathology. Offspring from well-characterized families with one bipolar parent (high risk) or two well parents (controls) were assessed annually or at anytime symptoms developed using KSADS-PL interviews for up to 15 years. DSM-IV diagnoses were made on blind consensus review using all available clinical material. We compared the age-adjusted risks of lifetime psychopathology between high risk and control subjects and assessed the conditional probability of developing a mood disorder given a history of non-mood disorders. In subjects meeting full DSM-IV criteria for bipolar disorder, we assessed the sequence of psychopathology against a clinical staging model. High risk offspring manifest higher rates of anxiety and sleep disorders, as well as major mood and substance use disorders compared to controls. Antecedent anxiety increased the age-adjusted risk of mood disorder from 40 to 85% (hazard ratio of 2.6). High risk subjects who developed a mood disorder had an increased risk of a substance use disorder (hazard ratio of 2.4), typically meeting diagnostic criteria during or after the first major mood episode. The evolution of psychopathology leading to bipolar disorder generally followed the proposed sequence, although not all subjects manifest all stages. Larger numbers of high risk offspring prospectively assessed over the risk period would allow confirmation of these preliminary findings. Clinical staging may be a useful approach to refine the early diagnosis and facilitate research into the evolution of bipolar disorder in those at familial risk. 2009 Elsevier B.V. All rights reserved.

  14. The NGF Metabolic Pathway in the CNS and its Dysregulation in Down Syndrome and Alzheimer's Disease. (United States)

    Iulita, M Florencia; Cuello, A Claudio


    It is well established that individuals with Down syndrome develop Alzheimer's disease neuropathology by middle age. Both in Alzheimer's disease and Down syndrome, this is accompanied by the atrophy of NGF-dependent cholinergic neurons of the basal forebrain. An NGF trophic compromise in Alzheimer's disease had been early suspected. This hypothesis was discarded with the finding of unaltered NGF mRNA synthesis and of increased NGF precursor levels (proNGF) in postmortem Alzheimer's disease brains. The possibility of an NGF trophic disconnection has been recently revisited at the light of a newly discovered extracellular NGF metabolic pathway; where proNGF is released in an activity-dependent manner and converted by plasmin to mature NGF in the extracellular space. Mature NGF is ultimately degraded by the metalloprotease MMP-9. This pathway has been shown to be compromised in Alzheimer's disease and Down syndrome brains, thus reviving the trophic factor hypothesis to explain the atrophy of basal forebrain cholinergic neurons in these disorders. This chapter will discuss the physiological role of NGF and its biological significance to cholinergic neurons of the CNS, and present the evidence for a dysregulation of the NGF metabolism in Alzheimer's disease and Down syndrome.


    Directory of Open Access Journals (Sweden)

    O. V. Nikogosova


    Full Text Available Abstract. The aim of the study was to verify etiological agents of CNS perinatal damages in children of early age and to study peculiarities of immune and cytokine statuses during pathogenetically grounded therapy.618 children aged from 1 month till 3 years were examined. Changes of neurologic status were interrogated and complete standard paraclinical examination was carried out. Basic clinical groups were formed.Immunoassay program, which included verification of a causative agent and determination of indices of cellular and humoral immunities, was used to identify a causative agent and to determin infectious activity. Direct methods of investigation which reveal a causative agent and indirect methods which register specific immune response were used. Patients were divided into groups on the basis of etiological agent.The program of pharmacotherapy was based on findings, immune status and in particular immune mediators. This program included specific anti-infectious therapy and adequate immunorehabilitation. Data analysis was made for groups of patients who got symptomatic therapy in neurologic disease and who got immunocorrective and anti-infectious therapy in addition to standard treatment. Comparison of clinical characteristics showed considerable improvement of patients in the latter group, what correlated with laboratorial data. Normalization of principal indices of immune and cytokine statuses which ensure development of anti-infectious immunity resulted in persistent infectious remission, noticeable improvement of clinical state of the invalidity rate.


    Directory of Open Access Journals (Sweden)

    Francisco Capani


    of estradiol treatment we were able to revert some of these alterations using PI3K/Akt/GSK3. Overall these results demonstrate that synaptic dysfunction following PA might be produced by early changes in the actin organization and long-term misfolding and aggregation of proteins in the PSDs. Therefore, we hypothesize that the synaptic and neuronal cytoskeleton changes induced by PA in the rat CNS could lead to the cellular dysfunction and death in adult animals. Estradiol appears as a new therapeutic tool to slacken the damage induces by perinatal asphyxia on the CNS.

  17. Development of SED Camera for Quasars in Early Universe (SQUEAN) (United States)

    Kim, Sanghyuk; Jeon, Yiseul; Lee, Hye-In; Park, Woojin; Ji, Tae-Geun; Hyun, Minhee; Choi, Changsu; Im, Myungshin; Pak, Soojong


    We describe the characteristics and performance of a camera system, Spectral energy distribution Camera for Quasars in Early Universe (SQUEAN). It was developed to measure SEDs of high-redshift quasar candidates (z ≳ 5) and other targets, e.g., young stellar objects, supernovae, and gamma-ray bursts, and to trace the time variability of SEDs of objects such as active galactic nuclei (AGNs). SQUEAN consists of an on-axis focal plane camera module, an autoguiding system, and mechanical supporting structures. The science camera module is composed of a focal reducer, a customizable filter wheel, and a CCD camera on the focal plane. The filter wheel uses filter cartridges that can house filters with different shapes and sizes, enabling the filter wheel to hold 20 filters of 50 mm × 50 mm size, 10 filters of 86 mm × 86 mm size, or many other combinations. The initial filter mask was applied to calibrate the filter wheel with high accuracy, and we verified that the filter position is repeatable at much less than one pixel accuracy. We installed and tested 50 nm medium bandwidth filters of 600-1050 nm and other filters at the commissioning observation in 2015 February. We found that SQUEAN can reach limiting magnitudes of 23.3-25.3 AB mag at 5σ in a one-hour total integration time.

  18. Early Environment and Neurobehavioral Development Predict Adult Temperament Clusters (United States)

    Congdon, Eliza; Service, Susan; Wessman, Jaana; Seppänen, Jouni K.; Schönauer, Stefan; Miettunen, Jouko; Turunen, Hannu; Koiranen, Markku; Joukamaa, Matti; Järvelin, Marjo-Riitta; Veijola, Juha; Mannila, Heikki; Paunio, Tiina; Freimer, Nelson B.


    Background Investigation of the environmental influences on human behavioral phenotypes is important for our understanding of the causation of psychiatric disorders. However, there are complexities associated with the assessment of environmental influences on behavior. Methods/Principal Findings We conducted a series of analyses using a prospective, longitudinal study of a nationally representative birth cohort from Finland (the Northern Finland 1966 Birth Cohort). Participants included a total of 3,761 male and female cohort members who were living in Finland at the age of 16 years and who had complete temperament scores. Our initial analyses (Wessman et al., in press) provide evidence in support of four stable and robust temperament clusters. Using these temperament clusters, as well as independent temperament dimensions for comparison, we conducted a data-driven analysis to assess the influence of a broad set of life course measures, assessed pre-natally, in infancy, and during adolescence, on adult temperament. Results Measures of early environment, neurobehavioral development, and adolescent behavior significantly predict adult temperament, classified by both cluster membership and temperament dimensions. Specifically, our results suggest that a relatively consistent set of life course measures are associated with adult temperament profiles, including maternal education, characteristics of the family’s location and residence, adolescent academic performance, and adolescent smoking. Conclusions Our finding that a consistent set of life course measures predict temperament clusters indicate that these clusters represent distinct developmental temperament trajectories and that information about a subset of life course measures has implications for adult health outcomes. PMID:22815688

  19. Early experiences in developing and managing the neuroscience gateway. (United States)

    Sivagnanam, Subhashini; Majumdar, Amit; Yoshimoto, Kenneth; Astakhov, Vadim; Bandrowski, Anita; Martone, MaryAnn; Carnevale, Nicholas T


    The last few decades have seen the emergence of computational neuroscience as a mature field where researchers are interested in modeling complex and large neuronal systems and require access to high performance computing machines and associated cyber infrastructure to manage computational workflow and data. The neuronal simulation tools, used in this research field, are also implemented for parallel computers and suitable for high performance computing machines. But using these tools on complex high performance computing machines remains a challenge because of issues with acquiring computer time on these machines located at national supercomputer centers, dealing with complex user interface of these machines, dealing with data management and retrieval. The Neuroscience Gateway is being developed to alleviate and/or hide these barriers to entry for computational neuroscientists. It hides or eliminates, from the point of view of the users, all the administrative and technical barriers and makes parallel neuronal simulation tools easily available and accessible on complex high performance computing machines. It handles the running of jobs and data management and retrieval. This paper shares the early experiences in bringing up this gateway and describes the software architecture it is based on, how it is implemented, and how users can use this for computational neuroscience research using high performance computing at the back end. We also look at parallel scaling of some publicly available neuronal models and analyze the recent usage data of the neuroscience gateway.

  20. Regulation of protein synthesis during sea urchin early development

    Energy Technology Data Exchange (ETDEWEB)

    Kelso, L.C.


    Fertilization of the sea urchin egg results in a 20-40 fold increase in the rate of protein synthesis. The masked message hypothesis proposes that mRNAs are masked or unavailable for translation in the egg. We devised an in vivo assay to test this hypothesis. Our results show that masked mRNAs limit protein synthesis in the unfertilized egg. In addition, we show that protein synthesis is also regulated at the level of translational machinery. Following fertilization is a period of rapid cell divisions. This period, known as the rapid cleavage stage, is characterized by the transient synthesis of a novel set of proteins. The synthesis of these proteins is programmed by maternal mRNAs stored in the unfertilized egg. To study the behavior of these mRNAs, we prepared a cDNA library from polysomal poly (A+) RNA from 2-hour embryos. ({sup 32}P) labeled probes, prepared from the cDNA library, were used to monitor the levels of individual mRNAs in polysomes at fertilization and during early development.

  1. 3rd ENRI International Workshop on ATM/CNS

    CERN Document Server


    The Electronic Navigation Research Institute (ENRI) held its third International Workshop on ATM / CNS in 2013 with the theme of "Drafting the future sky". There is worldwide activity taking place in the research and development of modern air traffic management (ATM) and its enabling technologies in Communication, Navigation and Surveillance (CNS). Pioneering work is necessary to contribute to the global harmonization of air traffic management and control. At this workshop, leading experts in  research, industry and academia from around the world met to share their ideas and approaches on ATM/CNS related topics.

  2. LINGO-1 and its role in CNS repair. (United States)

    Mi, Sha; Sandrock, Alfred; Miller, Robert H


    LINGO-1 is selectively expressed in the CNS on both oligodendrocyte precursor cells (OPCs) and neurons. Its expression is developmentally regulated in the normal CNS, as well as up-regulated in human or rat models of neuropathologies. LINGO-1 functions as a negative regulator of oligodendrocyte differentiation and myelination, neuronal survival and axonal regeneration. Across diverse animal CNS disease models, targeted LINGO-1 inhibition was found to promote neuron and oligodendrocyte survival, axon regeneration, oligodendrocyte differentiation, remyelination and improved functional recovery. The targeted inhibition of LINGO-1 therefore presents a novel therapeutic approach for the treatment of neurological diseases.

  3. Early Holocene lake ecosystem development in the southern Baltic lowlands (United States)

    Słowiński, Michał; Ott, Florian; Kramkowski, Mateusz; Noryśkiewicz, Agnieszka M.; Zawiska, Izabela; Dräger, Nadine; Theuerkauf, Martin; Hass, Christoph; Obremska, Milena; Błaszkiewicz, Mirosław; Kordowski, Jarosław; Tjallingii, Rik; Rzodkiewicz, Monika; Schwab, Markus; Brauer, Achim


    The first millennia of the Holocene are characterized by gradual and rapid environmental changes following the warming at the beginning of the Holocene superimposed by short-term climatic instability. Landscape evolution during this period occurred at different time scales due to specific response times of landscape compartments like vegetation succession, soil formation and permafrost thawing. As a consequence, a spatiotemporally heterogeneous pattern of changes occurred particularly in regions close to the margins of the continental ice sheets like the Baltic region. Regional atmospheric circulation patterns were affected by cold catabatic winds from the remains of the Fennoscandian ice sheet. The ongoing deglaciation further influenced the regional climate through meltwater release and related changes in the North Atlantic thermohaline circulation. Both effects declined with the progressive ice sheet melt down. Additionally, the land-sea distribution in the North Sea changed drastically during the final melting phase of the glacial ice sheets. The Baltic Sea development is even more complex due to the strong glacio-isostatic adjustments effects that resulted in open and closed water stages affecting the entire Baltic realm. Consequently, the early Holocene interval of sediment records from the southern Baltic lowlands are not considered as straightforward palaeoclimate archives but need to be interpreted in a broader context. We present five partly varved lake records from northern Poland all including an intriguing highly organic-rich interval interrupting biochemical calcite precipitation at about the same time between 10.5 and 10.2 cal kyr BP. These sediment records have been correlated by independent age models based on varve counting, AMS 14C dating, biostratigraphy and tephrochronology. We present multi-proxy records of early Holocene sediments and our preliminary interpretation suggests hydrological processes as the main reason for the intriguing shifts

  4. Acute disseminated encephalomyelitis: Updates on an inflammatory CNS syndrome. (United States)

    Pohl, Daniela; Alper, Gulay; Van Haren, Keith; Kornberg, Andrew J; Lucchinetti, Claudia F; Tenembaum, Silvia; Belman, Anita L


    Acute disseminated encephalomyelitis (ADEM) is an immune-mediated demyelinating CNS disorder with predilection to early childhood. ADEM is generally considered a monophasic disease. However, recurrent ADEM has been described and defined as multiphasic disseminated encephalomyelitis. ADEM often occurs postinfectiously, although a causal relationship has never been established. ADEM and multiple sclerosis are currently viewed as distinct entities, generally distinguishable even at disease onset. However, pathologic studies have demonstrated transitional cases of yet unclear significance. ADEM is clinically defined by acute polyfocal neurologic deficits including encephalopathy. MRI typically demonstrates reversible, ill-defined white matter lesions of the brain and often also the spinal cord, along with frequent involvement of thalami and basal ganglia. CSF analysis may reveal a mild pleocytosis and elevated protein, but is generally negative for intrathecal oligoclonal immunoglobulin G synthesis. In the absence of a specific diagnostic test, ADEM is considered a diagnosis of exclusion, and ADEM mimics, especially those requiring a different treatment approach, have to be carefully ruled out. The role of biomarkers, including autoantibodies like anti-myelin oligodendrocyte glycoprotein, in the pathogenesis and diagnosis of ADEM is currently under debate. Based on the presumed autoimmune etiology of ADEM, the current treatment approach consists of early immunotherapy. Outcome of ADEM in pediatric patients is generally favorable, but cognitive deficits have been reported even in the absence of other neurologic sequelae. This review summarizes the current knowledge on epidemiology, pathology, clinical presentation, neuroimaging features, CSF findings, differential diagnosis, therapy, and outcome, with a focus on recent advances and controversies. © 2016 American Academy of Neurology.

  5. SPARC and GluA1-Containing AMPA Receptors Promote Neuronal Health Following CNS Injury

    Directory of Open Access Journals (Sweden)

    Emma V. Jones


    Full Text Available The proper formation and maintenance of functional synapses in the central nervous system (CNS requires communication between neurons and astrocytes and the ability of astrocytes to release neuromodulatory molecules. Previously, we described a novel role for the astrocyte-secreted matricellular protein SPARC (Secreted Protein, Acidic and Rich in Cysteine in regulating α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs and plasticity at developing synapses. SPARC is highly expressed by astrocytes and microglia during CNS development but its level is reduced in adulthood. Interestingly, SPARC has been shown to be upregulated in CNS injury and disease. However, the role of SPARC upregulation in these contexts is not fully understood. In this study, we investigated the effect of chronic SPARC administration on glutamate receptors on mature hippocampal neuron cultures and following CNS injury. We found that SPARC treatment increased the number of GluA1-containing AMPARs at synapses and enhanced synaptic function. Furthermore, we determined that the increase in synaptic strength induced by SPARC could be inhibited by Philanthotoxin-433, a blocker of homomeric GluA1-containing AMPARs. We then investigated the effect of SPARC treatment on neuronal health in an injury context where SPARC expression is upregulated. We found that SPARC levels are increased in astrocytes and microglia following middle cerebral artery occlusion (MCAO in vivo and oxygen-glucose deprivation (OGD in vitro. Remarkably, chronic pre-treatment with SPARC prevented OGD-induced loss of synaptic GluA1. Furthermore, SPARC treatment reduced neuronal death through Philanthotoxin-433 sensitive GluA1 receptors. Taken together, this study suggests a novel role for SPARC and GluA1 in promoting neuronal health and recovery following CNS damage.

  6. Early development of Moniliophthora perniciosa basidiomata and developmentally regulated genes

    Directory of Open Access Journals (Sweden)

    Pereira Gonçalo AG


    mycelium with primordia and a second in basidiomata, confirming their distinctiveness. The number of transcripts of the gene for plerototolysin B increased in reddish-pink mycelium and indicated an activation of the initial basidiomata production even at this culturing stage. Expression of the glucose transporter gene increased in mycelium after the stress, coinciding with a decrease of adenylate cyclase gene transcription. This indicated that nutrient uptake can be an important signal to trigger fruiting in this fungus. Conclusion The identification of genes with increased expression in this phase of the life cycle of M. perniciosa opens up new possibilities of controlling fungus spread as well as of genetic studies of biological processes that lead to basidiomycete fruiting. This is the first comparative morphologic study of the early development both in vivo and in vitro of M. perniciosa basidiomata and the first description of genes expressed at this stage of the fungal life cycle.

  7. Association of Polar Early Career Scientists: a model for experiential learning in professional development for students and early career researchers (United States)

    Bradley, A. C.; Hindshaw, R. S.; Fugmann, G.; Mariash, H.


    The Association of Polar Early Career Scientists was established by early career researchers during the 2007-2008 International Polar Year as an organization for early career researchers in the polar and cryospheric sciences. APECS works to promote early career researchers through soft-skills training in both research and outreach activities, through advocating for including early career researchers in all levels of the scientific process and scientific management, and through supporting a world-wide network of researchers in varied fields. APECS is lead by early career researchers; this self-driven model has proved to be an effective means for developing the leadership, management, and communication skills that are essential in the sciences, and has shown to be sustainable even in a community where frequent turn-over is inherent to the members. Since its inception, APECS has reached over 5,500 members in more than 80 countries, and we have placed more than 50 early career researchers on working groups and steering committees with organizations around the world in the last two years alone. The close partnerships that APECS has with national and international organizations exposes members to both academic and alternative career paths, including those at the science-policy interface. This paper describes APECS's approach to experiential learning in professional development and the best practices identified over our nearly ten years as an organization.

  8. Diagnostic and therapeutic challenges in superficial CNS siderosis

    DEFF Research Database (Denmark)

    Kondziella, Daniel; Lindelof, M.; Haziri, Donika


    INTRODUCTION: Superficial CNS siderosis was previously almost unknown but is now diagnosed with increasing frequency owing to magnetic resonance imaging. Patients may present with sensory deafness, gait ataxia, various sensorimotor signs and, eventually, cognitive decline. They typically have a h...

  9. Pharmacokinetic, Pharmacogenetic, and Other Factors Influencing CNS Penetration of Antiretrovirals

    Directory of Open Access Journals (Sweden)

    Jacinta Nwamaka Nwogu


    Full Text Available Neurological complications associated with the human immunodeficiency virus (HIV are a matter of great concern. While antiretroviral (ARV drugs are the cornerstone of HIV treatment and typically produce neurological benefit, some ARV drugs have limited CNS penetration while others have been associated with neurotoxicity. CNS penetration is a function of several factors including sieving role of blood-brain and blood-CSF barriers and activity of innate drug transporters. Other factors are related to pharmacokinetics and pharmacogenetics of the specific ARV agent or mediated by drug interactions, local inflammation, and blood flow. In this review, we provide an overview of the various factors influencing CNS penetration of ARV drugs with an emphasis on those commonly used in sub-Saharan Africa. We also summarize some key associations between ARV drug penetration, CNS efficacy, and neurotoxicity.

  10. Neuro-intensive care of patients with acute CNS infections. (United States)

    Beckham, J David; Tyler, Kenneth L


    Infections in the central nervous system (CNS) are caused by a wide range of microorganisms resulting in distinct clinical syndromes including meningitis, encephalitis, and pyogenic infections, such as empyema and brain abscess. Bacterial and viral infections in the CNS can be rapidly fatal and can result in severe disability in survivors. Appropriate identification and acute management of these infections often occurs in a critical care setting and is vital to improving outcomes in this group of patients. This review of diagnosis and management of acute bacterial and viral infections in the CNS provides a general approach to patients with a suspected CNS infection and also provides a more detailed review of the diagnosis and management of patients with suspected bacterial meningitis, viral encephalitis, brain abscess, and subdural empyema.

  11. Fetal MRI in Prenatal Diagnosis of CNS Abnormalities

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap


    Full Text Available The value of fetal MRI (fMRI compared to ultrasound in the prenatal detection of CNS abnormalities and impact on counseling were determined in 25 pregnant women examined at University of Dusseldorf, Germany.

  12. The effects of military deployment on early child development. (United States)

    Nguyen, Dana R; Ee, Juliana; Berry-Cabán, Cristobal S; Hoedebecke, Kyle


    The purpose of this observational, point prevalence study is to determine if parental deployment affects the cognitive, social and emotional development of preschool age children in the military family. Demographic information was collected and an age-appropriate Ages and Stages Questionnaire (ASQ-3) and Ages and Stages Social-Emotional Inventory (ASQ:SE) were administered. The primary outcome measure was the failure rates on the developmental instruments. We identified 151 parents of eligible children; 95 children had a parent that deployed during their lifetime. We found a significant difference in ASQ-3 failure rates for children in the deployed group compared to those in the nondeployed group. Children of deployed parents were at least twice as often to fail the ASQ-3 or ASQ:SE developmental screen compared to children whose parents did not deploy. 30.5% of children in the deployed group failed the ASQ-3 screen while 12.5% of children who did not have a deployed parent failed (P=.009). On the ASQ:SE developmental screen, 16.8% of children who had a parent deploy failed versus 5.4% of children who did not have a parent deploy (P=.031). This study suggests that parental deployment is related to adverse risk for developmental delays in children in military families. The psychological burden on military children could be life-long or require significant resources to address. These adverse outcomes could be possibly mitigated by early detection of developmental delay and firm attention to aggressive screening techniques in military communities.

  13. Early successful orchidopexy does not prevent from developing azoospermia

    Directory of Open Access Journals (Sweden)

    Faruk Hadziselimovic


    Full Text Available INTRODUCTION: The incidence of Ad spermatogonia (stem cells for fertility was assessed in 20 cryptorchid patients, all of whom had a successful orchidopexy in childhood but developed azoospermia following puberty. MATERIALS AND METHODS: From a cohort of 231 patients who had a semen analysis following successful orchidopexy 20 patients (9% had azoospermia. The patients were classified into 2 groups according to the time of surgery: A = < 21 months of age (n = 5, mean = 10.7 ± 8.6 months and B = during childhood (n = 15, mean = 10.1 ± 3 years. Nine of the 20 patients (45% had bilateral cryptorchidism: A = 1 and B = 8. Testicular biopsies were performed during orchidopexy and analyzed with semi-thin technique. The number of Ad spermatogonia and entire number of germ cells was determined. The patients' semen analyses were evaluated at least twice; FSH and testosterone plasma values were estimated. RESULTS: In group A, all patients had germ cells at the time of surgery (mean = 1.04 ± 1.4 germ cells per tubular cross section; only 6 patients in group B (40% had no germ cells (mean = 0.17 ± 0.4; A vs. B, p = 0.0133. Importantly, Ad spermatogonia were absent in the entire study population. The plasma FSH of 16 patients (80% was abnormal [median = 16.35 IU/L (Interquartile range of sample - IQR 9.075-27.85 95% CI, 3-53] while the plasma testosterone of all the patients was normal. CONCLUSIONS: The most severe cause of infertility in cryptorchid patients cannot be mitigated by an early successful surgery alone.

  14. CNS Involvement in AML Patient Treated with 5-Azacytidine

    Directory of Open Access Journals (Sweden)

    Diamantina Vasilatou


    Full Text Available Central nervous system (CNS involvement in acute myeloid leukemia (AML is a rare complication of the disease and is associated with poor prognosis. Sometimes the clinical presentation can be unspecific and the diagnosis can be very challenging. Here we report a case of CNS infiltration in a patient suffering from AML who presented with normal complete blood count and altered mental status.

  15. Nanotechnology for CNS Delivery of Bio-Therapeutic Agents


    Shah, Lipa; Yadav, Sunita; Amiji, Mansoor


    The current therapeutic strategies are not efficient in treating disorders related to the central nervous system (CNS) and have only shown partial alleviation of symptoms, as opposed to, disease modifying effects. With change in population demographics, the incidence of CNS disorders, especially neurodegenerative diseases, is expected to rise dramatically. Current treatment regimens are associated with severe side-effects, especially given that most of these are chronic therapies and involve ...

  16. Cerebrospinal fluid Alzheimer's biomarker profiles in CNS infections


    Krut, JJ; Zetterberg, H.; Blennow, K.; Cinque, P.; Hagberg, L; Price, Rw; Studahl, M; Gisslén, M.


    The cerebrospinal fluid (CSF) biomarker profile in Alzheimer's disease (AD) is characterized by decreased beta amyloid (Aβ 1-42 ), increased total and hyperphosphorylated tau (t-tau and p-tau, respectively), which is a useful diagnostic tool and gives insight in the pathogenesis of AD. It is of importance to study how these biomarkers react in other CNS diseases; therefore, we decided to analyse amyloid and tau biomarkers in different CNS infections. We also included analysis of soluble amylo...

  17. Recombinant human tripeptidyl peptidase-1 infusion to the monkey CNS: Safety, pharmacokinetics, and distribution

    Energy Technology Data Exchange (ETDEWEB)

    Vuillemenot, Brian R., E-mail: [BioMarin Pharmaceutical Inc., Novato, CA (United States); Kennedy, Derek [BioMarin Pharmaceutical Inc., Novato, CA (United States); Reed, Randall P.; Boyd, Robert B. [Northern Biomedical Research, Inc., Muskegon, MI (United States); Butt, Mark T. [Tox Path Specialists, LLC, Hagerstown, MD (United States); Musson, Donald G.; Keve, Steve; Cahayag, Rhea; Tsuruda, Laurie S.; O' Neill, Charles A. [BioMarin Pharmaceutical Inc., Novato, CA (United States)


    CLN2 disease is caused by deficiency in tripeptidyl peptidase-1 (TPP1), leading to neurodegeneration and death. The safety, pharmacokinetics (PK), and CNS distribution of recombinant human TPP1 (rhTPP1) were characterized following a single intracerebroventricular (ICV) or intrathecal-lumbar (IT-L) infusion to cynomolgus monkeys. Animals received 0, 5, 14, or 20 mg rhTPP1, ICV, or 14 mg IT-L, in artificial cerebrospinal fluid (aCSF) vehicle. Plasma and CSF were collected for PK analysis. Necropsies occurred at 3, 7, and 14 days post-infusion. CNS tissues were sampled for rhTPP1 distribution. TPP1 infusion was well tolerated and without effect on clinical observations or ECG. A mild increase in CSF white blood cells (WBCs) was detected transiently after ICV infusion. Isolated histological changes related to catheter placement and infusion were observed in ICV treated animals, including vehicle controls. The CSF and plasma exposure profiles were equivalent between animals that received an ICV or IT-L infusion. TPP1 levels peaked at the end of infusion, at which point the enzyme was present in plasma at 0.3% to 0.5% of CSF levels. TPP1 was detected in brain tissues with half-lives of 3–14 days. CNS distribution between ICV and IT-L administration was similar, although ICV resulted in distribution to deep brain structures including the thalamus, midbrain, and striatum. Direct CNS infusion of rhTPP1 was well tolerated with no drug related safety findings. The favorable nonclinical profile of ICV rhTPP1 supports the treatment of CLN2 by direct administration to the CNS. - Highlights: • TPP1 enzyme replacement therapy to the CNS is in development for CLN2 disease. • Toxicology, pharmacokinetics, and CNS distribution were assessed in monkeys. • TPP1 infusion directly to the brain did not result in any safety concerns. • A positive pharmacokinetic and distribution profile resulted from TPP1 infusion. • This study demonstrates the feasibility of ICV administered

  18. How Immune-inflammatory Processes Link CNS and Psychiatric Disorders: Classification and Treatment Implications. (United States)

    Anderson, George; Maes, Michael


    In this article the emerging biological overlaps of CNS disorders and psychiatric conditions are reviewed. Recent work has highlighted how immune-inflammatory processes and their interactions with oxidative and nitrosative stress, couple to drive changes in neuroregulatory tryptophan catabolites, with consequences for serotonin availability, including as a precursor for the melatonergic pathways. Subsequent alterations in the regulation of local melatonin synthesis are likely to have direct impacts on the reactivity of immune cells, both centrally and systemically. These inflammatory processes also lead to the activation of wider immune processes. Such wider processes can include the production of immunoglobulin (Ig)A and IgM antibody responses, including to tryptophan catabolites, emphasizing the importance of immune responses, and their interactions with inflammatory processes, in the etiology and course of an array of medical conditions, including CNS disorders and psychiatric conditions. Such work poses questions as to the validity and utility of current, non-biologically based classification systems for psychiatric and CNS disorders. In this article, the biological underpinnings of CNS disorders and psychiatric conditions are reviewed in the context of how recent data, in reconceptualizing key processes in these classically-conceived brain-associated disorders, provides scope for novel, and hopefully more clinically useful, treatments. These processes are looked at in detail in Alzheimer's disease and major depressive disorder. One important treatment target is the gut. Alterations in the gut, including gut permeability and the composition of the microbiome, have now become an important target for treatment across an array of medical conditions, emphasizing the importance of targeting regulators of the immune system in developing novel treatments that are based on a more comprehensive and 'wholistic' understanding of currently poorly managed medical conditions

  19. Older Siblings Affect Gut Microbiota Development in Early Childhood

    DEFF Research Database (Denmark)

    Laursen, Martin Frederik; Zachariassen, Gitte; Bahl, Martin Iain

    at three years of age. Bacterial compositions and diversity indices were determined in fecal samples collected from 114 infants in the SKOT cohort at age 9 and 18 months by 16S rRNA gene sequencing. These were compared to the presence of older siblings, furred pets and early life infections.......006) at 18 months. Further, having older siblings was associated with increased relative abundance of several bacterial taxa at both 9 and 18 months of age. Compared to the effect of having siblings, presence of household furred pets and early life infections had less pronounced effects on the gut microbiota....... Gut microbiota characteristics were not significantly associated with cumulative occurrence of eczema and asthmatic bronchitis during the first three years of life. Conclusions: Presence of older siblings is associated with increased gut microbial diversity and richness during early childhood, which...

  20. Dynamics of learner affective development in early FLL

    Directory of Open Access Journals (Sweden)

    Jelena Mihaljević Djigunović


    Full Text Available Affective learner factors were first considered as a cause of success in language learning. This was followed by a change in approach and recently authors (e.g., Edelenbos, Johnstone, & Kubanek, 2006 have considered them an important outcome, especially in early foreign language learning (FLL. Current research into affective learner factors in early FLL tries to catch the developmental aspects too, and studies are emerging that take a contextual view as well. This paper describes a study on affective characteristics of young FL learners that combines the developmental and contextual perspectives. Using the case study methodology the author analyses the affective profiles of three young learners of English as a foreign language who were followed for 4 years. The analyses are done taking into account their immediate language learning environment, home support, out-of-school exposure to English and language achievement. The findings suggest that affective learner factors contribute to the dynamic complexity of early FLL.

  1. Development of a Tier 3 Curriculum to Teach Early Literacy Skills (United States)

    Kaminski, Ruth A.; Powell-Smith, Kelly A.; Hommel, Annie; McMahon, Rose; Aguayo, Katherine Bravo


    Children with the lowest oral language and early literacy skills at entry to kindergarten are the most vulnerable to poor literacy outcomes. This article describes the programmatic development of a Tier 3 early literacy intervention for preschool children who are most in need of intensive support to achieve early literacy outcomes. The…

  2. Developing Home-Based Early Learning Systems in East Yakima and White Center. Better Beginnings (United States)

    Hallgren, Kristin; Paulsell, Diane; Del Grosso, Patricia


    In 2006, the Gates Foundation launched the Early Learning Initiative to improve the school readiness of Washington State's children through three main strategies: (1) development of high-quality, community-wide early learning initiatives in two communities; (2) enhancement of statewide systems that support early learning; and (3) support for…

  3. Linking Play to Early Learning and Development Guidelines: Possibility or Polemic? (United States)

    Kagan, Sharon Lynn; Scott-Little, Catherine; Frelow, Victoria Stebbins


    Early learning and development guidelines have often been regarded as a deterrent to an emphasis on play within early learning settings for infants and toddlers. In examining the context for, and the evolution of, early learning guidelines, the article delineates the need to scrutinize and help reverse this mindset. To that end, the authors…

  4. Media representations of early human development: protecting, feeding and loving the developing brain. (United States)

    O'Connor, Cliodhna; Joffe, Helene


    The public profile of neurodevelopmental research has expanded in recent years. This paper applies social representations theory to explore how early brain development was represented in the UK print media in the first decade of the 21st century. A thematic analysis was performed on 505 newspaper articles published between 2000 and 2010 that discussed early brain development. Media coverage centred around concern with 'protecting' the prenatal brain (identifying threats to foetal neurodevelopment), 'feeding' the infant brain (indicating the patterns of nutrition that enhance brain development) and 'loving' the young child's brain (elucidating the developmental significance of emotionally nurturing family environments). The media focused almost exclusively on the role of parental action in promoting optimal neurodevelopment, rarely acknowledging wider structural, cultural or political means of supporting child development. The significance of parental care was intensified by deterministic interpretations of critical periods, which implied that inappropriate parental input would produce profound and enduring neurobiological impairments. Neurodevelopmental research was also used to promulgate normative judgements concerning the acceptability of certain gender roles and family contexts. The paper argues that media representations of neurodevelopment stress parental responsibility for shaping a child's future while relegating the contributions of genetic or wider societal factors, and examines the consequences of these representations for society and family life. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Future Directions for Research on the Development and Prevention of Early Conduct Problems


    Shaw, Daniel S.


    This paper describes our state of knowledge regarding the development and prevention of conduct problems in early childhood, then identifies directions that would benefit future basic and applied research. Our understanding about the course and risk factors associated with early-developing conduct problems has been significantly enhanced during the past three decades; however, many challenges remain in understanding the development of early conduct problems for girls, the contribution of pove...

  6. Early Childhood Development Operations in Latin and Caribbean Region (LCR) : Jamaica, Mexico, and Brazil in Focus


    Holland, Peter; Evans, David


    The rationale and evidence of the effectiveness of investing early in children is compelling: early childhood is the most rapid period of development in a human life, with incredible brain development occurring (85 percent of the brain is wired by age 5). Investments in Early Childhood Development (ECD) are among the most effective and cost-effective investments a country can make in its p...

  7. Early Childhood Development and Education in Sierra Leone: Constraints and Possibilities


    Athinodorou, Eleni


    The importance of early childhood education as the process for building strong foundation for children’s further learning has been supported by scientific research. Currently, countries in Africa are incorporating early childhood development and education into their country development and policy plans. This study explored the post-war early childhood development through a critical ethnographic case study in order to identify and critically analyse the facilitators and barriers...

  8. The Development of Prosocial Behaviour in Early Childhood: Contributions of Early Parenting and Self-Regulation (United States)

    Williams, Kate E.; Berthelsen, Donna


    This research considers the role of parenting practices and early self-regulation, on children's prosocial behaviour when they begin school. Data for 4007 children were drawn from "Growing Up in Australia: The Longitudinal Study of Australian Children" (LSAC). The analyses explored relations between self-reported parenting practices for…

  9. Development of nap neurophysiology: preliminary insights into sleep regulation in early childhood

    National Research Council Canada - National Science Library

    Kurth, Salome; Lassonde, Jonathan M; Pierpoint, Lauren A; Rusterholz, Thomas; Jenni, Oskar G; McClain, Ian J; Achermann, Peter; LeBourgeois, Monique K


    .... Longitudinal studies of napping physiology are fundamental to understanding sleep regulation during early childhood, a sensitive period in brain and behaviour development and a time when children...

  10. Effects of child development accounts on early social-emotional development: an experimental test. (United States)

    Huang, Jin; Sherraden, Michael; Kim, Youngmi; Clancy, Margaret


    This study, based on Oklahoma's statewide Child Development Accounts (CDAs) program, presents findings from the first experimental test of the hypothesis that creating lifelong savings accounts for children at birth promotes their long-term well-being. To examine the effects of CDAs, an innovative social policy to encourage lifelong saving and asset building for long-term development, on parent-reported social-emotional development in early childhood. A statewide randomized experiment of CDAs was conducted in 2008, drawing a probability sample of 7328 children from all infants born in two 3-month periods in Oklahoma (April 1 through June 30 and August 1 through October 31, 2007). After agreeing to participate in the experiment, caregivers of 2704 infants completed a baseline survey and were randomly assigned to treatment (n = 1358) and control groups (n = 1346). Approximately 84% of participants completed a follow-up survey in the spring of 2011. The intervention offered CDAs, built on the existing Oklahoma 529 college-savings plan, to treatment participants. It also provided additional financial incentives and information. The primary outcome-child social-emotional development-is measured by scores from a 17-item version of the Ages and Stages Questionnaire: Social-Emotional. Caregivers completed it in the 3-year follow-up survey. Lower scores indicate better functioning. The CDAs have positive effects on social-emotional development for children at approximately age 4 years. The nonweighted treatment-control difference is -1.56 (90% CI, -2.87 to -0.22; P = .06), but the weighted difference is nonsignificant. The effects appear to be greater for disadvantaged subsamples, such as low-income households (weighted mean difference, -2.21; 90% CI, -4.01 to -0.42; P = .04). As a complement to other early education and health interventions, CDAs may improve social-emotional development in early childhood. Their effects may be explained as a mediating

  11. Investing in Kids: Early Childhood Programs and Local Economic Development (United States)

    Bartik, Timothy J.


    Early childhood programs, if designed correctly, pay big economic dividends down the road because they increase the skills of their participants. And since many of those participants will remain in the same state or local area as adults, the local economy benefits: more persons with better skills attract business, which provides more and better…

  12. Developing Pedagogical Strategies to Promote Structural Thinking in Early Mathematics (United States)

    Mulligan, Joanne T.; Mitchelmore, Michael C.


    The Pattern and Structure Mathematical Awareness Program (PASMAP) is an early mathematics program designed to promote structural thinking. PASMAP pedagogy removes the structure commonly provided for students in order to challenge them to construct their own, focusing student attention on spatial and numerical patterns and leading them to formulate…

  13. Boarding Neurath's Boat : The Early Development of Quine's Naturalism

    NARCIS (Netherlands)

    Verhaegh, Sander


    W.V. Quine is arguably the intellectual father of contemporary naturalism, the idea that there is no distinctively philosophical perspective on reality. Yet even though Quine has always been a science-minded philosopher, he did not adopt a fully naturalistic perspective until the early 1950s. In

  14. Boarding Neurath's Boat : The Early Development of Quine's Naturalism

    NARCIS (Netherlands)

    Verhaegh, Sander

    W.V. Quine is arguably the intellectual father of contemporary naturalism, the idea that there is no distinctively philosophical perspective on reality. Yet even though Quine has always been a science-minded philosopher, he did not adopt a fully naturalistic perspective until the early 1950s. In

  15. Do Fine Motor Skills Contribute to Early Reading Development? (United States)

    Suggate, Sebastian; Pufke, Eva; Stoeger, Heidrun


    Background: Little is known about how fine motor skills (FMS) relate to early literacy skills, especially over and above cognitive variables. Moreover, a lack of distinction between FMS, grapho-motor and writing skills may have hampered previous work. Method: In Germany, kindergartners (n = 144, aged 6;1) were recruited before beginning formal…

  16. Discontinuities in Early Development of the Understanding of Physical Causality (United States)

    Aschersleben, Gisa; Henning, Anne; Daum, Moritz M.


    Research on early physical reasoning has shown surprising discontinuities in developmental trajectories. Infants possess some skills that seem to disappear and then re-emerge in childhood. It has been suggested that prediction skills required in search tasks might cause these discontinuities (Keen, 2003). We tested 3.5- to 5-year-olds'…

  17. Developing students' writing skills: an early intervention approach. (United States)

    Hanson Diehl, Susan


    In what seems to be a universal situation, nurse educators are reading student papers and lamenting the fact that their students cannot write. The author explains a successful model of early intervention aimed at improving academic writing for new graduate students. The model and teaching strategies are helpful to nurse educators who struggle with the quality of their students' written work.

  18. Positive Home Environment and Behaviour Development in Early Adolescents (United States)

    Jayalekshmi, N. B.; Dharma Raja, B. William


    Early adolescence is a period of transition when the individual changes physically and psychologically from a child to an adult. This transition involves physical, cognitive and socio- emotional changes. The developmental changes that occur during this period cause varying degree of disturbance. The changes they undergo sometimes results in…

  19. The Structure and Development of Dispositional Compassion in Early Adolescence (United States)

    Bengtsson, Hans; Söderström, Micael; Terjestam, Yvonne


    Compassion may be directed at a broad range of targets. The present study investigated interrelations among other-directed compassion, self-compassion, and environmental compassion in early adolescence (age = 12-14; n = 256) and examined how the different manifestations of compassion related to age and sex during this age period. Dispositional…

  20. Early development and larval behaviour of a minnow, Barbus anopius

    African Journals Online (AJOL)

    Cape Department of Nature and Environmental Conservation, Vanderkloof. The chubbyhead barb, Barbus anoplus, underwent a popula- tion explosion in the early ... of the eastern Cape (Gaigher, Ntloko & Visser 1975), Barbus holubi from the Vaal River (Groenewald 1961) and B. natalen- sis of Natal (Wright & Coke 1975) ...

  1. Agency in Early Childhood Learning and Development in Cameroon (United States)

    Nsamenang, A. Bame


    This article focuses on agency, as a natural disposition in children to be active and participative. Africa's parenting attitudes and education in African family traditions encourage and foster children's responsible agency in family life, cultural and economic activities, and their own developmental learning from an early, especially within the…

  2. Sustaining Care: Cultivating Mindful Practice in Early Years Professional Development (United States)

    Taggart, Geoff


    The practitioner's own self is a resource in early childhood education and care (ECEC). It is proposed that an experiential training focusing on the "professional self" helps to raise awareness of how psychological dispositions may impair or enhance quality of provision. A key concept in such training is emotional labour, explored with…

  3. Early gonad development in zebrafish ( Danio rerio ) | Okuthe ...

    African Journals Online (AJOL)

    This study investigated events of early gonadogenesis in zebrafish with the aim of unraveling the events surrounding the mitotic/meiotic transition in juvenile ovaries. Primordial germ cells were identified at eight days post fertilization (dpf). Mitotic divisions were apparent at 15 dpf, and meiosis initiated in some gonads after ...

  4. Early Childhood Professionalism in Serbia: Current Issues and Developments (United States)

    Bankovic, Ivana


    This article explores early childhood professionalism in the Republic of Serbia. The concept of professionalism in this context is examined in light of current international debates about professionalism. More specifically, how the use of specific nomenclature, the existence of multi-professional teams of practitioners and state-regulated but…

  5. Early Development of Graphical Literacy through Knowledge Building (United States)

    Gan, Yongcheng; Scardamalia, Marlene; Hong, Huang-Yao; Zhang, Jianwei


    This study examined growth in graphical literacy for students contributing to an online, multimedia, communal environment as they advanced their understanding of biology, history and optics. Their science and history studies started early in Grade 3 and continued to the end of Grade 4; students did not receive instruction in graphics production,…

  6. An Early Childhood Educator's Guide to Prosocial Development. (United States)

    Floody, Dale R.

    This paper reviews research findings that are related to fostering prosocial behavior in the early childhood and elementary classroom. A collection of "experimental best bets" for increasing prosocial behavior in young children is outlined. This collection covers the role of reinforcement and modeling or imitation, the importance of group norms,…

  7. Spatial and temporal profiles of growth factor expression during CNS demyelination reveal the dynamics of repair priming.

    Directory of Open Access Journals (Sweden)

    Viktoria Gudi

    Full Text Available Demyelination is the cause of disability in various neurological disorders. It is therefore crucial to understand the molecular regulation of oligodendrocytes, the myelin forming cells in the CNS. Growth factors are known to be essential for the development and maintenance of oligodendrocytes and are involved in the regulation of glial responses in various pathological conditions. We employed the well established murine cuprizone model of toxic demyelination to analyze the expression of 13 growth factors in the CNS during de- and remyelination. The temporal mRNA expression profile during demyelination and the subsequent remyelination were analyzed separately in the corpus callosum and cerebral cortex using laser microdissection and real-time PCR techniques. During demyelination a similar pattern of growth factor mRNA expression was observed in both areas with a strong up-regulation of NRG1 and GDNF and a slight increase of CNTF in the first week of cuprizone treatment. HGF, FGF-2, LIF, IGF-I, and TGF-ß1 were up-regulated mainly during peak demyelination. In contrast, during remyelination there were regional differences in growth factor mRNA expression levels. GDNF, CNTF, HGF, FGF-2, and BDNF were elevated in the corpus callosum but not in the cortex, suggesting tissue differences in the molecular regulation of remyelination in the white and grey matter. To clarify the cellular source we isolated microglia from the cuprizone lesions. GDNF, IGF-1, and FGF mRNA were detected in the microglial fraction with a temporal pattern corresponding to that from whole tissue PCR. In addition, immunohistochemical analysis revealed IGF-1 protein expression also in the reactive astrocytes. CNTF was located in astrocytes. This study identified seven different temporal expression patterns for growth factors in white and grey matter and demonstrated the importance of early tissue priming and exact orchestration of different steps during callosal and cortical de

  8. The extended trajectory of hippocampal development: Implications for early memory development and disorder. (United States)

    Gómez, Rebecca L; Edgin, Jamie O


    Hippocampus has an extended developmental trajectory, with refinements occurring in the trisynaptic circuit until adolescence. While structural change should suggest a protracted course in behavior, some studies find evidence of precocious hippocampal development in the first postnatal year and continuity in memory processes beyond. However, a number of memory functions, including binding and relational inference, can be cortically supported. Evidence from the animal literature suggests that tasks often associated with hippocampus (visual paired comparison, binding of a visuomotor response) can be mediated by structures external to hippocampus. Thus, a complete examination of memory development will have to rule out cortex as a source of early memory competency. We propose that early memory must show properties associated with full function of the trisynaptic circuit to reflect "adult-like" memory function, mainly (1) rapid encoding of contextual details of overlapping patterns, and (2) retention of these details over sleep-dependent delays. A wealth of evidence suggests that these functions are not apparent until 18-24 months, with behavioral discontinuities reflecting shifts in the neural structures subserving memory beginning approximately at this point in development. We discuss the implications of these observations for theories of memory and for identifying and measuring memory function in populations with typical and atypical hippocampal function. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.


    Directory of Open Access Journals (Sweden)

    Vasilka RAZMOVSKA


    Full Text Available Introduction;· Causes for disorders in the speech development;· Disorders in the speech development, mental retardation and treatment;· Disorders in the speech development, hearing remainders and treatment;· Autism and disorders in the speech development;· Bilingual and disordered speech development;· Speech of neglected children



    Vasilka RAZMOVSKA; Vasilka DOLEVSKA


    Introduction;· Causes for disorders in the speech development;· Disorders in the speech development, mental retardation and treatment;· Disorders in the speech development, hearing remainders and treatment;· Autism and disorders in the speech development;· Bilingual and disordered speech development;· Speech of neglected children

  11. Study of Early Child Care and Youth Development (SECCYD) (United States)

    ... Snapshot of Pregnancy & Infant Development Advances Snapshot of Child Development Advances Snapshot of Adult & Family Health Advances NICHD ... Meetings and Events BACK TO TOP Content Owner Child Development and Behavior Branch Last Reviewed Date 12/30/ ...

  12. The development and arithmetic foundations of early functional thinking


    Xolocotzin, Ulises; Rojano, Teresa


    International audience; Functional reasoning is a key strand of early algebrai-zation. This paper presents a cross-sectional study that analysed functional thinking in a sample of 94 elementary school students. Aspects such as following and identifying covariation rules showed dramatic differences between Grade 2, Grade 4, and Grade 6, whereas increases in the abilities to command verbal and symbolic representations were much smaller. After controlling for the influence of nonverbal reasoning...

  13. VP-shunt dysfunction caused by malaria CNS infection. (United States)

    Fehrenbach, Michael Karl; Bernhard, Matthias; Siekmeyer, Manuela; Lippmann, Norman; Kiess, Wieland; Nestler, Ulf; Meixensberger, Jürgen; Preuss, Matthias


    Malaria is a widespread mosquito-borne infectious disease with over 300 million cases and roughly 900 thousand deaths in 2013. Cerebral involvement of malaria causes 50 % of all infection-associated deaths, especially in children below the age of 5 years. Hydrocephalus is a medical condition with abnormal accumulation of cerebrospinal fluid in physiological cavities and ventricles. Standard treatment is the implantation of a cerebrospinal fluid shunt device. A common problem associated with shunt treatment especially in pediatric patients is infection and consecutive shunt dysfunction caused by bacteriae or high protein levels clogging the valve. In these cases, Staphylococcus aureus and Staphylococcus epidermidis are predominantly found in CSF cultures. We present a case of a 2-year old boy from Saudi Arabia with a ventriculoperitoneal (VP)-shunt-dependent congenital hydrocephalus who suffered from cerebral malaria and developed consecutive shunt failure. To the best of our knowledge, shunt failure caused by malaria CNS infection with Plasmodium falciparum has not yet been reported in the literature and should be considered as a rare cause of VP-shunt failure in patients with atypical VP-shunt infections living in or traveling from endemic areas.

  14. Using nanotechnology to design potential therapies for CNS regeneration. (United States)

    Ellis-Behnke, R G; Teather, L A; Schneider, G E; So, K-F


    The nanodelivery of therapeutics into the brain will require a step-change in thinking; overcoming the blood brain barrier is one of the major challenges to any neural therapy. The promise of nanotechnology is that the selective delivery of therapeutics can be delivered through to the brain without causing secondary damage. There are several formidable barriers that must be overcome in order to achieve axonal regeneration after injury in the CNS. The development of new biological materials, in particular biologically compatible scaffolds that can serve as permissive substrates for cell growth, differentiation and biological function is a key area for advancing medical technology. This review focuses on four areas: First, the barriers of delivering therapies to the central nervous system and how nanotechnology can potentially solve them; second, current research in neuro nanomedicine featuring brain repair, brain imaging, nanomachines, protein misfolding diseases, nanosurgery, implanted devices and nanotechnologies for crossing the blood brain barrier; third, health and safety issues and fourth, the future of neuro nanomedicine as it relates to the pharmaceutical industry.

  15. Role of Gut Microbiota in Early Infant Development

    Directory of Open Access Journals (Sweden)

    R Wall


    Full Text Available Early colonization of the infant gastrointestinal tract is crucial for the overall health of the infant, and establishment and maintenance of non-pathogenic intestinal microbiota may reduce several neonatal inflammatory conditions. Much effort has therefore been devoted to manipulation of the composition of the microbiota through 1 the role of early infant nutrition, particularly breast milk, and supplementation of infant formula with prebiotics that positively influence the enteric microbiota by selectively promoting growth of beneficial bacteria and 2 oral administration of probiotic bacteria which when administered in adequate amounts confer a health benefit on the host. While the complex microbiota of the adult is difficult to change in the long-term, there is greater impact of the diet on infant microbiota as this is not as stable as in adults. Decreasing excessive use of antibiotics and increasing the use of pre- and probiotics have shown to be beneficial in the prevention of several important infant diseases such as necrotizing enterocolitis and atopic eczema as well as improvement of short and long-term health. This review addresses how the composition of the gut microbiota becomes established in early life, its relevance to infant health, and dietary means by which it can be manipulated.

  16. Professional Development for Early Childhood Educators: Efforts to Improve Math and Science Learning Opportunities in Early Childhood Classrooms (United States)

    Piasta, Shayne B.; Logan, Jessica A. R.; Pelatti, Christina Yeager; Capps, Janet L.; Petrill, Stephen A.


    Because recent initiatives highlight the need to better support preschool-aged children's math and science learning, the present study investigated the impact of professional development in these domains for early childhood educators. Sixty-five educators were randomly assigned to experience 10.5 days (64 hr) of training on math and science or on…

  17. Neonatal infraorbital nerve crush-induced CNS synaptic plasticity and functional recovery


    Lo, Fu-Sun; Zhao, Shuxin; Erzurumlu, Reha S.


    Infraorbital nerve (ION) transection in neonatal rats leads to disruption of whisker-specific neural patterns (barrelettes), conversion of functional synapses into silent synapses, and reactive gliosis in the brain stem trigeminal principal nucleus (PrV). Here we tested the hypothesis that neonatal peripheral nerve crush injuries permit better functional recovery of associated central nervous system (CNS) synaptic circuitry compared with nerve transection. We developed an in vitro whisker pad...

  18. Nanomedicine in Central Nervous System (CNS Disorders: A Present and Future Prospective

    Directory of Open Access Journals (Sweden)

    Shringika Soni


    Conclusion: Although impressive advancement has made via innovative potential drug development, but their efficacy is still moderate due to limited brain permeability. To overcome this constraint,powerful tool in CNS therapeutic intervention provided by nanotechnology-based drug delivery methods. Due to its small and biofunctionalization characteristics, nanomedicine can easily penetrate and facilitate the drug through the barrier. But still, understanding of their toxicity level, optimization and standardization are a long way to go.

  19. DIALOG: Fostering Early Career Development Across the Aquatic Sciences

    Energy Technology Data Exchange (ETDEWEB)

    Caroline Susan Weiler, PhD


    A total of 447 dissertation abstracts were received for the DIALOG V Program, with 146 individuals applying for the DIALOG V Symposium; 47 were invited and 45 have accepted. This represents a significant increase compared to the DIALOG IV Program in which 221 abstracts were registered and 124 applied for the symposium. The importance of the dissertation registration service is indicated by the increasing number of individuals who take time to register their dissertation even when they are not interested in applying to the symposium. The number of visits to the webpage has also increased significantly over the years. This also reflects graduate interest in being part of the on-line Dissertation Registry and receiving the weekly electronic DIALOG Newsletter. See for details. The DIALOG symposium reaches approximately 40 new PI's at a pivotal point in their research careers. Based on their comments, the symposium changes the way participants think, communicate, and approach their research. The science community and the general population will benefit from the perspectives these new PI's bring back to their home institutions and share with their students and colleagues. This group should act as a catalyst to move the entire field in exciting new, interdisciplinary directions. To reach more graduates, plans are underway to establish the symposium on an annual basis. By facilitating the development of close collegial ties, symposium participants come away with a network of colleagues from around the globe with interests in aquatic science research and education. Past participants are collaborating on research proposals, and all have noted that participation has enabled them to develop a more interdisciplinary view of their field, influencing the way they interpret, communicate, and approacli their research. The dissertation registry provides a unique introduction to the work of this most recent generation of aquatic scientists. Each

  20. Sox2 Is Essential for Oligodendroglial Proliferation and Differentiation during Postnatal Brain Myelination and CNS Remyelination. (United States)

    Zhang, Sheng; Zhu, Xiaoqing; Gui, Xuehong; Croteau, Christopher; Song, Lanying; Xu, Jie; Wang, Aijun; Bannerman, Peter; Guo, Fuzheng


    In the CNS, myelination and remyelination depend on the successful progression and maturation of oligodendroglial lineage cells, including proliferation and differentiation of oligodendroglial progenitor cells (OPCs). Previous studies have reported that Sox2 transiently regulates oligodendrocyte (OL) differentiation in the embryonic and perinatal spinal cord and appears dispensable for myelination in the postnatal spinal cord. However, the role of Sox2 in OL development in the brain has yet to be defined. We now report that Sox2 is an essential positive regulator of developmental myelination in the postnatal murine brain of both sexes. Stage-specific paradigms of genetic disruption demonstrated that Sox2 regulated brain myelination by coordinating upstream OPC population supply and downstream OL differentiation. Transcriptomic analyses further supported a crucial role of Sox2 in brain developmental myelination. Consistently, oligodendroglial Sox2-deficient mice developed severe tremors and ataxia, typical phenotypes indicative of hypomyelination, and displayed severe impairment of motor function and prominent deficits of brain OL differentiation and myelination persisting into the later CNS developmental stages. We also found that Sox2 was required for efficient OPC proliferation and expansion and OL regeneration during remyelination in the adult brain and spinal cord. Together, our genetic evidence reveals an essential role of Sox2 in brain myelination and CNS remyelination, and suggests that manipulation of Sox2 and/or Sox2-mediated downstream pathways may be therapeutic in promoting CNS myelin repair. SIGNIFICANCE STATEMENT Promoting myelin formation and repair has translational significance in treating myelin-related neurological disorders, such as periventricular leukomalacia and multiple sclerosis in which brain developmental myelin formation and myelin repair are severely affected, respectively. In this report, analyses of a series of genetic conditional

  1. The Place of the Arts in Early Childhood Learning and Development


    French, Geraldine


    This paper has been commissioned by Arts Council Ireland to inform the development of a national strategy for early childhood arts in Ireland. The paper is based on contemporary thinking and knowledge of child psychology, early learning and development and childhood studies, in particular the theoretical principles and pedagogical approaches to early childhood art-based learning. It begins with an exploration of the concept of pedagogy. International research on the importance of effective pe...

  2. HIV-1 Induced CNS Dysfunction: Current Overview and Research Priorities. (United States)

    Joseph, Jeymohan; Colosi, Deborah A; Rao, Vasudev R


    Over the past three decades, the clinical presentation of HIV infection of the Central Nervous System (CNS) has evolved. Prior to wide spread use of effective antiretroviral therapy (ART), more than a third of infected individuals exhibited a range of neurocognitive and motor deficits that frequently progressed to severe dementia and paralysis. However, the use of ART has significantly decreased the prevalence of severe forms of HIV-1 associated neurocognitive disorders (HAND). Studies of neurocognitive dysfunction have reported variable prevalence, ranging from 21% to 77.6%, defined primarily by mild to moderate neurocognitive impairment. HIV-associated chronic inflammation and associated neurotoxicity of long term ART, as well as the aging of the HIV-infected population, likely influence the pathogenesis of HAND. Despite significant research efforts directed towards a better understanding of the mechanisms underlying HIV neuropathogenesis, definitive causal pathophysiology of HAND and thus effective prevention or treatment remain elusive. Furthermore, HIV therapeutic research now includes efforts to effect a cure, by eliminating or silencing HIV within infected cells, which must include efforts to target the latently infected cells within the CNS. Prevention and treatment of the neurological complications of HIV, and eradication of persistent virus from the CNS compartment are major priorities for the HIV-CNS research. Here we give an overview of the progress of research on HIV-CNS disease, define new challenges and research areas, and highlight domestic and global priorities.

  3. Care for Child Development: an intervention in support of responsive caregiving and early child development. (United States)

    Lucas, J E; Richter, L M; Daelmans, B


    An estimated 43% of children younger than 5 years of age are at elevated risk of failing to achieve their human potential. In response, the World Health Organization and UNICEF developed Care for Child Development (CCD), based on the science of child development, to improve sensitive and responsive caregiving and promote the psychosocial development of young children. In 2015, the World Health Organization and UNICEF identified sites where CCD has been implemented and sustained. The sites were surveyed, and responses were followed up by phone interviews. Project reports provided information on additional sites, and a review of published studies was undertaken to document the effectiveness of CCD for improving child and family outcomes, as well as its feasibility for implementation in resource-constrained communities. The inventory found that CCD had been integrated into existing services in diverse sectors in 19 countries and 23 sites, including child survival, health, nutrition, infant day care, early education, family and child protection and services for children with disabilities. Published and unpublished evaluations have found that CCD interventions can improve child development, growth and health, as well as responsive caregiving. It has also been reported to reduce maternal depression, a known risk factor for poor pregnancy outcomes and poor child health, growth and development. Although CCD has expanded beyond initial implementation sites, only three countries reported having national policy support for integrating CCD into health or other services. Strong interest exists in many countries to move beyond child survival to protect and support optimal child development. The United Nations Sustainable Development Goals depend on children realizing their potential to build healthy and emotionally, cognitively and socially competent future generations. More studies are needed to guide the integration of the CCD approach under different conditions. Nevertheless

  4. Perceptions and Attitudes of Early Childhood Teachers in Korea about Education for Sustainable Development (United States)

    Park, Eunhye; Kim, Heejin; Yu, Sunyoung


    This study investigates the perceptions and attitudes of Korean early childhood teachers about education for sustainable development (ESD). A total of 301 Korean early childhood teachers participated in a survey which was purposefully developed for this research. The survey focused on three areas of interest: understanding of concepts about…

  5. Early Infections of Toxoplasma gondii and the Later Development of Schizophrenia

    DEFF Research Database (Denmark)

    Mortensen, Preben Bo; Nørgaard-Pedersen, Bent; Waltoft, Berit Lindum


    Early exposure to several infectious agents has been associated with the later development of schizophrenia. Two recent studies assessed in utero or early postnatal exposure to Toxoplasma gondii. In one study of 63 individuals, who developed schizophrenia spectrum disorders, maternal sera obtained...

  6. Early assessment of medical devices in development for company decision making : An exploration of best practices

    NARCIS (Netherlands)

    Markiewicz, Katarzyna; Van Til, Janine; IJzerman, Maarten


    To improve successful development and clinical use of medical technologies, it is suggested that manufacturers should start collecting evidence on devices effectiveness and eficiency early in their development. The aim of this study was to explore whether and how Dutch manufacturers perform an early

  7. First-Time Mothers' Knowledge and Beliefs Regarding Early Communication Development (United States)

    Williams, Vicki; Pearce, Wendy M.; Devine, Sue


    Limited literature exists in the Australian context about first-time mothers' knowledge of early communication milestones, their strategies to facilitate speech and language development and understanding of the relationship between early communication skills and future development. A cross-sectional online survey was administered to 53 first-time…

  8. Future Directions for Research on the Development and Prevention of Early Conduct Problems (United States)

    Shaw, Daniel S.


    This article describes our state of knowledge regarding the development and prevention of conduct problems in early childhood, then identifies directions that would benefit future basic and applied research. Our understanding about the course and risk factors associated with early-developing conduct problems has been significantly enhanced during…

  9. State of Early Child Development Research, Practice, and Policy for Most Vulnerable Children: A Global Perspective (United States)

    Young, Mary Eming


    Interventions to enhance development of children ages 0-6 have profound benefits for children, families, and societies. The benefits are well documented, recognized internationally, and supportive of policies and programs targeting early child development (ECD). Intervening in the early years is a critical first step toward alleviating poverty,…

  10. Home and Preschool Learning Environments and Their Relations to the Development of Early Numeracy Skills (United States)

    Anders, Yvonne; Rossbach, Hans-Gunther; Weinert, Sabine; Ebert, Susanne; Kuger, Susanne; Lehrl, Simone; von Maurice, Jutta


    This study examined the influence of the quality of home and preschool learning environments on the development of early numeracy skills in Germany, drawing on a sample of 532 children in 97 preschools. Latent growth curve models were used to investigate early numeracy skills and their development from the first (average age: 3 years) to the third…

  11. Use of Racial Identity Development Theory to Explore Cultural Competence among Early Childhood Educators (United States)

    Han, Heejeong Sophia; West-Olatunji, Cirecie; Thomas, M. Shelley


    In order to explore early childhood educators' cultural competence through a lens of racial identity development theory, a case study was conducted with four White Kindergarten teachers. Participants were surveyed and interviewed to understand their racial identity development as well as perspectives of teaching culturally diverse early childhood…

  12. Early Writing Development: Kindergarten Teachers' Beliefs about Emergent Writing in Qatari Preschool Settings (United States)

    Al-Maadadi, Fatima; Ihmeideh, Fathi


    Writing often begins during the very early years of childhood; however, some children first learn writing when they begin attending school. Teachers' beliefs about early writing development can influence when and how children learn to write. The purpose of this study was to determine kindergarten teachers' beliefs about the development of…

  13. Early human brain development : the impact of periconceptional maternal and fetal factors

    NARCIS (Netherlands)

    I.V. Koning (Irene)


    textabstractEarly human brain development is an extremely complex process which is highly susceptible to genetic and environmental conditions. These factors may cause subtle changes in early brain development and subsequent neurodevelopmental impairment. The main objective of this thesis is to

  14. Building the blocks of executive functioning: differentiating early developing processes contributing to executive functioning skills

    NARCIS (Netherlands)

    Mandell, D.J.; Ward, S.E.


    The neural processes that underlie executive function begin to develop in infancy. However, it is unclear how the behavior manifested by these processes are related or if they can be differentiated early in development. This study seeks to examine early emerging executive functioning skills in

  15. Early or pre-coeliac mucosa: development of gluten enteropathy. (United States)

    Egan-Mitchell, B; Fottrell, P F; McNicholl, B


    Duodenal mucosa showed normal morphology, interepithelial lymphocytes, alkaline phosphatase, and sucrase in a girl with growth retardation and iron deficiency, but normal absorption of lactose and xylose after two years of abnormal stools. Mucosal lactase was low. Fourteen months later mucosal damage consistent with coeliac disease was evident, and gluten intolerance was subsequently confirmed by gluten challenge. It is probable that, in some children, the mucosal lesion occurs very gradually, so that at an early stage with normal morphology, suppression of lactase activity and possibly interference with iron absorption may be the only abnormalities. Images Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:7461478

  16. How Do Meningeal Lymphatic Vessels Drain the CNS? (United States)

    Raper, Daniel; Louveau, Antoine; Kipnis, Jonathan


    The many interactions between the nervous and the immune systems, which are active in both physiological and pathological states, have recently become more clearly delineated with the discovery of a meningeal lymphatic system capable of carrying fluid, immune cells, and macromolecules from the central nervous system (CNS) to the draining deep cervical lymph nodes. However, the exact localization of the meningeal lymphatic vasculature and the path of drainage from the cerebrospinal fluid (CSF) to the lymphatics remain poorly understood. Here, we discuss the potential differences between peripheral and CNS lymphatic vessels and examine the purported mechanisms of CNS lymphatic drainage, along with how these may fit into established patterns of CSF flow. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Organotypic Cultures as a Model to Study Adult Neurogenesis in CNS Disorders

    Directory of Open Access Journals (Sweden)

    Fabio Cavaliere


    Full Text Available Neural regeneration resides in certain specific regions of adult CNS. Adult neurogenesis occurs throughout life, especially from the subgranular zone of hippocampus and the subventricular zone, and can be modulated in physiological and pathological conditions. Numerous techniques and animal models have been developed to demonstrate and observe neural regeneration but, in order to study the molecular and cellular mechanisms and to characterize multiple types of cell populations involved in the activation of neurogenesis and gliogenesis, investigators have to turn to in vitro models. Organotypic cultures best recapitulate the 3D organization of the CNS and can be explored taking advantage of many techniques. Here, we review the use of organotypic cultures as a reliable and well defined method to study the mechanisms of neurogenesis under normal and pathological conditions. As an example, we will focus on the possibilities these cultures offer to study the pathophysiology of diseases like Alzheimer disease, Parkinson’s disease, and cerebral ischemia.

  18. Local tissue interactions across the dorsal midline of the forebrain establish CNS laterality. (United States)

    Concha, Miguel L; Russell, Claire; Regan, Jennifer C; Tawk, Marcel; Sidi, Samuel; Gilmour, Darren T; Kapsimali, Marika; Sumoy, Lauro; Goldstone, Kim; Amaya, Enrique; Kimelman, David; Nicolson, Teresa; Gründer, Stefan; Gomperts, Miranda; Clarke, Jonathan D W; Wilson, Stephen W


    The mechanisms that establish behavioral, cognitive, and neuroanatomical asymmetries are poorly understood. In this study, we analyze the events that regulate development of asymmetric nuclei in the dorsal forebrain. The unilateral parapineal organ has a bilateral origin, and some parapineal precursors migrate across the midline to form this left-sided nucleus. The parapineal subsequently innervates the left habenula, which derives from ventral epithalamic cells adjacent to the parapineal precursors. Ablation of cells in the left ventral epithalamus can reverse laterality in wild-type embryos and impose the direction of CNS asymmetry in embryos in which laterality is usually randomized. Unilateral modulation of Nodal activity by Lefty1 can also impose the direction of CNS laterality in embryos with bilateral expression of Nodal pathway genes. From these data, we propose that laterality is determined by a competitive interaction between the left and right epithalamus and that Nodal signaling biases the outcome of this competition.

  19. The imaging appearances of intracranial CNS infections in adult HIV and AIDS patients

    Energy Technology Data Exchange (ETDEWEB)

    Offiah, C.E. [Department of Neuroradiology, Hope Hospital, Stott Lane, Salford, Manchester (United Kingdom)]. E-mail:; Turnbull, I.W. [Department of Neuroradiology, Hope Hospital, Stott Lane, Salford, Manchester (United Kingdom)


    The spectrum of pathology affecting the central nervous system (CNS) in patients suffering from acquired immunodeficiency syndrome (AIDS) is broad and comprises predominantly opportunistic infections and neoplasms. It is estimated that approximately one-third of all patients with AIDS develop neurological complications. The organisms responsible for AIDS are human retroviruses: primarily the human immunodeficiency virus type 1 (HIV). In this review we shall focus on the neurological complications of HIV and AIDS which are applicable to the more frequently occurring intracranial infective organisms. Attention will be paid specifically to those CNS manifestations occurring in the adult HIV and AIDS population as infection in the paediatric HIV and AIDS group, although bearing some similarities, demonstrates some important differences.

  20. Sleep as a window into early neural development: Shifts in sleep-dependent learning effects across early childhood. (United States)

    Gómez, Rebecca L; Edgin, Jamie O


    Sleep is an important physiological state for the consolidation and generalization of new learning in children and adults. We review the literature on sleep-dependent memory consolidation and generalization in infants and preschool children and place the findings in the context of the development of the neural systems underlying memory (hippocampus and its connections to cortex). Based on the extended trajectory of hippocampal development, transitions in the nature of sleep-dependent learning are expected. The studies reviewed here show shifts in the nature of sleep-dependent learning across early childhood, with sleep facilitating generalization in infants but enhancing precise memory after 18-24 months of age. Future studies on sleep-dependent learning in infants and young children must take these transitions in early brain development into account.

  1. Global CNS transduction of adult mice by intravenously delivered rAAVrh.8 and rAAVrh.10 and nonhuman primates by rAAVrh.10. (United States)

    Yang, Bin; Li, Shaoyong; Wang, Hongyan; Guo, Yansu; Gessler, Dominic J; Cao, Chunyan; Su, Qin; Kramer, Joshua; Zhong, Li; Ahmed, Seemin Seher; Zhang, Hongwei; He, Ran; Desrosiers, Ronald C; Brown, Robert; Xu, Zuoshang; Gao, Guangping


    Some recombinant adeno-associated viruses (rAAVs) can cross the neonatal blood-brain barrier (BBB) and efficiently transduce cells of the central nervous system (CNS). However, in the adult CNS, transduction levels by systemically delivered rAAVs are significantly reduced, limiting their potential for CNS gene therapy. Here, we characterized 12 different rAAVEGFPs in the adult mouse CNS following intravenous delivery. We show that the capability of crossing the adult BBB and achieving widespread CNS transduction is a common character of AAV serotypes tested. Of note, rAAVrh.8 is the leading vector for robust global transduction of glial and neuronal cell types in regions of clinical importance such as cortex, caudate-putamen, hippocampus, corpus callosum, and substantia nigra. It also displays reduced peripheral tissue tropism compared to other leading vectors. Additionally, we evaluated rAAVrh.10 with and without microRNA (miRNA)-regulated expressional detargeting from peripheral tissues for systemic gene delivery to the CNS in marmosets. Our results indicate that rAAVrh.8, along with rh.10 and 9, hold the best promise for developing novel therapeutic strategies to treat neurological diseases in the adult patient population. Additionally, systemically delivered rAAVrh.10 can transduce the CNS efficiently, and its transgene expression can be limited in the periphery by endogenous miRNAs in adult marmosets.

  2. Molecular mimicry as an inducing trigger for CNS autoimmune demyelinating disease. (United States)

    Chastain, Emily M L; Miller, Stephen D


    Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that affects about 0.1% of the worldwide population. This deleterious disease is marked by infiltration of myelin-specific T cells that attack the protective myelin sheath that surrounds CNS nerve axons. Upon demyelination, saltatory nerve conduction is disrupted, and patients experience neurologic deficiencies. The exact cause for MS remains unknown, although most evidence supports the hypothesis that both genetic and environmental factors contribute to disease development. Epidemiologic evidence supports a role for environmental pathogens, such as viruses, as potentially key contributors to MS induction. Pathogens can induce autoimmunity via several well-studied mechanisms with the most postulated being molecular mimicry. Molecular mimicry occurs when T cells specific for peptide epitopes derived from pathogens cross-react with self-epitopes, leading to autoimmune tissue destruction. In this review, we discuss an in vivo virus-induced mouse model of MS developed in our laboratory, which has contributed greatly to our understanding of the mechanisms underlying molecular mimicry-induced CNS autoimmunity. © 2011 John Wiley & Sons A/S.

  3. Inactivation of NF1 in CNS causes increased glial progenitor proliferation and optic glioma formation (United States)

    Zhu, Yuan; Harada, Takayuki; Liu, Li; Lush, Mark E.; Guignard, Frantz; Harada, Chikako; Burns, Dennis K.; Bajenaru, M. Livia; Gutmann, David H.; Parada, Luis F.


    Summary The gene responsible for neurofibromatosis type 1 (NF1) encodes a tumor suppressor that functions as a negative regulator of the Ras proto-oncogene. Individuals with germline mutations in NF1 are predisposed to the development of benign and malignant tumors of the peripheral and central nervous system (CNS). Children with this disease suffer a high incidence of optic gliomas, a benign but potentially debilitating tumor of the optic nerve; and an increased incidence of malignant astrocytoma, reactive astrogliosis and intellectual deficits. In the present study, we have sought insight into the molecular and cellular basis of NF1-associated CNS pathologies. We show that mice genetically engineered to lack NF1 in CNS exhibit a variety of defects in glial cells. Primary among these is a developmental defect resulting in global reactive astrogliosis in the adult brain and increased proliferation of glial progenitor cells leading to enlarged optic nerves. As a consequence, all of the mutant optic nerves develop hyperplastic lesions, some of which progress to optic pathway gliomas. These data point to hyperproliferative glial progenitors as the source of the optic tumors and provide a genetic model for NF1-associated astrogliosis and optic glioma. PMID:16314489

  4. Identification of new therapeutic targets for prevention of CNS inflammation

    DEFF Research Database (Denmark)

    Owens, Trevor


    Multiple sclerosis (MS) is a disease of complex pathologies, which involves infiltration by CD4(+) and CD8(+) T cells of and response within the central nervous system. Expression in the CNS of cytokines, reactive nitrogen species and costimulator molecules have all been described in MS. Notably......, the cytokines IFN-gamma and TNF are strongly expressed. Microglial cells in the CNS express costimulator molecules and it is assumed that they play a role in directing or inducing the T cell response. Transgenic experiments have tested the effects of overexpression of these molecules in mice and have shown...

  5. Deiodinase knockdown during early zebrafish development affects growth, development, energy metabolism, motility and phototransduction. (United States)

    Bagci, Enise; Heijlen, Marjolein; Vergauwen, Lucia; Hagenaars, An; Houbrechts, Anne M; Esguerra, Camila V; Blust, Ronny; Darras, Veerle M; Knapen, Dries


    Thyroid hormone (TH) balance is essential for vertebrate development. Deiodinase type 1 (D1) and type 2 (D2) increase and deiodinase type 3 (D3) decreases local intracellular levels of T3, the most important active TH. The role of deiodinase-mediated TH effects in early vertebrate development is only partially understood. Therefore, we investigated the role of deiodinases during early development of zebrafish until 96 hours post fertilization at the level of the transcriptome (microarray), biochemistry, morphology and physiology using morpholino (MO) knockdown. Knockdown of D1+D2 (D1D2MO) and knockdown of D3 (D3MO) both resulted in transcriptional regulation of energy metabolism and (muscle) development in abdomen and tail, together with reduced growth, impaired swim bladder inflation, reduced protein content and reduced motility. The reduced growth and impaired swim bladder inflation in D1D2MO could be due to lower levels of T3 which is known to drive growth and development. The pronounced upregulation of a large number of transcripts coding for key proteins in ATP-producing pathways in D1D2MO could reflect a compensatory response to a decreased metabolic rate, also typically linked to hypothyroidism. Compared to D1D2MO, the effects were more pronounced or more frequent in D3MO, in which hyperthyroidism is expected. More specifically, increased heart rate, delayed hatching and increased carbohydrate content were observed only in D3MO. An increase of the metabolic rate, a decrease of the metabolic efficiency and a stimulation of gluconeogenesis using amino acids as substrates may have been involved in the observed reduced protein content, growth and motility in D3MO larvae. Furthermore, expression of transcripts involved in purine metabolism coupled to vision was decreased in both knockdown conditions, suggesting that both may impair vision. This study provides new insights, not only into the role of deiodinases, but also into the importance of a correct TH balance

  6. NFIA haploinsufficiency is associated with a CNS malformation syndrome and urinary tract defects.

    Directory of Open Access Journals (Sweden)

    Weining Lu


    Full Text Available Complex central nervous system (CNS malformations frequently coexist with other developmental abnormalities, but whether the associated defects share a common genetic basis is often unclear. We describe five individuals who share phenotypically related CNS malformations and in some cases urinary tract defects, and also haploinsufficiency for the NFIA transcription factor gene due to chromosomal translocation or deletion. Two individuals have balanced translocations that disrupt NFIA. A third individual and two half-siblings in an unrelated family have interstitial microdeletions that include NFIA. All five individuals exhibit similar CNS malformations consisting of a thin, hypoplastic, or absent corpus callosum, and hydrocephalus or ventriculomegaly. The majority of these individuals also exhibit Chiari type I malformation, tethered spinal cord, and urinary tract defects that include vesicoureteral reflux. Other genes are also broken or deleted in all five individuals, and may contribute to the phenotype. However, the only common genetic defect is NFIA haploinsufficiency. In addition, previous analyses of Nfia(-/- knockout mice indicate that Nfia deficiency also results in hydrocephalus and agenesis of the corpus callosum. Further investigation of the mouse Nfia(+/- and Nfia(-/- phenotypes now reveals that, at reduced penetrance, Nfia is also required in a dosage-sensitive manner for ureteral and renal development. Nfia is expressed in the developing ureter and metanephric mesenchyme, and Nfia(+/- and Nfia(-/- mice exhibit abnormalities of the ureteropelvic and ureterovesical junctions, as well as bifid and megaureter. Collectively, the mouse Nfia mutant phenotype and the common features among these five human cases indicate that NFIA haploinsufficiency contributes to a novel human CNS malformation syndrome that can also include ureteral and renal defects.

  7. Early Gesture Provides a Helping Hand to Spoken Vocabulary Development for Children with Autism, Down Syndrome, and Typical Development (United States)

    Özçaliskan, Seyda; Adamson, Lauren B.; Dimitrova, Nevena; Baumann, Stephanie


    Typically developing (TD) children refer to objects uniquely in gesture (e.g., point at a cat) before they produce verbal labels for these objects ("cat"). The onset of such gestures predicts the onset of similar spoken words, showing a strong positive relation between early gestures and early words. We asked whether gesture plays the…

  8. Early development of gait asymmetries in trotting standardbred colts. (United States)

    Drevemo, S; Fredricson, I; Hjertén, G; McMiken, D


    Ten trotting Standardbred colts were recorded by high-speed cinematography at the ages of eight, 12 and 18 months. The horses were trotting on a treadmill operating at 4.0 m/secs. Five horses were subjected to a programme of intensified training from eight months of age, whereas the others were not trained and acted as controls. The films were analysed on a semi-automatic film-reading equipment and a number of variables used to demonstrate the gait symmetry were calculated and scaled by computer. Certain differences between left and right diagonal and contralateral pair of limbs, respectively, were noted, suggesting that laterality in horses may be inherited. The most pronounced systematic differences were found in 18-month old horses in the trained group. The results show the importance of careful gait examination and comprehensive coordination training at an early age.

  9. Early development of executive functions: a differential study

    Directory of Open Access Journals (Sweden)

    Sylvia Sastre-Riba


    Full Text Available The ontogeny of executive functions is essential in explaining differential and normative developmental trends. Executive functions must be studied from an early age given their consequential effects on mental flexibility, monitoring information, planning, and cognitive control. We propose a differential study in alternative developmental courses through observing typical babies, Down syndrome babies, and babies with risk-factors at birth (due to low weight or to congenital hypothyroidism. Applymg Systematic Observational Methodology, spontaneous babies' activity was registered. The results indicated that: a Typical babies showed better shifting and action flexibility in order to obtain a goal, thus better results; b Among the higher risk-babies, the lower efficacy in executive functioning was observed in underweight babies. Those with hypothyroidism were more in line with the typical babies; c Underweight babies showed a good level of combining actions but they obtained inferior results; d Down syndrome babies displayed more executive functioning difficulty, lower flexibility, high perseveration and less error detection.

  10. Early Development of Graphical Literacy through Knowledge Building

    Directory of Open Access Journals (Sweden)

    Yongcheng Gan


    Full Text Available This study examined growth in graphical literacy for students contributing to an online, multimedia, communal environment as they advanced their understanding of biology, history and optics. Their science and history studies started early in Grade 3 and continued to the end of Grade 4; students did not receive instruction in graphics production, nor were they required to produce graphics. Results show that students spontaneously produced graphics that advanced along seven dimensions, including effective representation of complex ideas, use of source information and captions, and aesthetic quality. On average, the scores for the seven dimensions were higher for Grade 4 students with two years of experience with Knowledge Building pedagogy and technology (Knowledge Forum® than for Grade 6 students with one year of experience. The overall pattern of results suggests reciprocal enhancement of graphical, textual, digital, and scientific literacy, with students exceeding expectations by available norms, and performance enhanced through extended Knowledge Building experience.

  11. Utility of FDG-PETCT and magnetic resonance spectroscopy in differentiating between cerebral lymphoma and non-malignant CNS lesions in HIV-infected patients

    Energy Technology Data Exchange (ETDEWEB)

    Westwood, Thomas D., E-mail: [Department of Radiology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester (United Kingdom); Hogan, Celia, E-mail: [Monsall Unit, Department of Infectious Diseases and Tropical Medicine, North Manchester General Hospital, Pennine Acute Hospitals NHS Trust (United Kingdom); Julyan, Peter J., E-mail: [Christie Medical Physics and Engineering, The Christie NHS Foundation Trust, Wilmslow Road, Manchester (United Kingdom); Coutts, Glyn, E-mail: [Christie Medical Physics and Engineering, The Christie NHS Foundation Trust, Wilmslow Road, Manchester (United Kingdom); Bonington, Suzie, E-mail: [Department of Radiology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester (United Kingdom); Carrington, Bernadette, E-mail: [Department of Radiology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester (United Kingdom); Taylor, Ben, E-mail: [Department of Radiology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester (United Kingdom); Khoo, Saye, E-mail: [Department of Infectious Diseases and Tropical Medicine, Royal Liverpool Hospital, Liverpool (United Kingdom); Bonington, Alec, E-mail: [Monsall Unit, Department of Infectious Diseases and Tropical Medicine, North Manchester General Hospital, Pennine Acute Hospitals NHS Trust (United Kingdom)


    Background and purpose: In HIV infected patients, MRI cannot reliably differentiate between central nervous system (CNS) lymphoma and non-malignant CNS lesions, particularly cerebral toxoplasmosis (CTOX). This study prospectively investigates the utility of FDG PET-CT and magnetic resonance spectroscopy (MRS) in discriminating CNS lymphoma from non-malignant CNS lesions in HIV infected patients, and assesses the ability of FDG PET-CT to guide the use of early brain biopsy. Methods: 10 HIV patients with neurological symptoms and contrast enhancing lesions on MRI were commenced on anti-toxoplasmosis therapy before undergoing FDG PET-CT and MRS. Brain biopsies were sought in those with FDG PET-CT suggestive of CNS lymphoma, and in those with a negative FDG PET-CT scan who failed to respond to therapy. Final diagnosis was based on histology or treatment response. Results: Two patients were confirmed to have CNS lymphoma and FDG PET-CT was consistent with this diagnosis in both. Six patients had cerebral toxoplasmosis in all of whom FDG PET-CT was consistent with non-malignant disease. One patient had progressive multifocal leukoencephalopathy (PML), FDG PET-CT was equivocal. One patient had a haemorrhagic brain metastasis and FDG PET-CT wrongly suggested non-malignant disease. MRS was performed successfully in eight subjects: three results were suggestive of CNS lymphoma (one true positive, two false positive), four suggested CTOX (two false negative, two true negative), one scan was equivocal. Conclusion: FDG PET-CT correctly identified all cases of CNS lymphoma and CTOX, supporting its use in this situation. MRS was unhelpful in our cohort.

  12. Growth and Morphogenesis during Early Heart Development in Amniotes


    Kenzo Ivanovitch; Isaac Esteban; Miguel Torres


    In this review, we will focus on the growth and morphogenesis of the developing heart, an aspect of cardiovascular development to which Antoon Moorman and colleagues have extensively contributed. Over the last decades, genetic studies and characterization of regionally regulated gene programs have provided abundant novel insights into heart development essential to understand the basis of congenital heart disease. Heart morphogenesis, however, is inherently a complex and dynamic three-dimensi...

  13. Distributional effects of OPORTUNIDADES on early child development


    Figueroa, J.L.


    Adequate health, nutrition, and education during childhood are essential for human development. Deficits in these realms undermine the capacity to acquire the necessary skills to perform in life. Social policies addressing the causes of disadvantages in child development take up an important place in the social agenda. The Mexican Oportunidades program is such a policy. Investments in children’s health, nutrition, and education by the program are expected to facilitate children’s development....

  14. Comparative antibiogram of coagulase-negative Staphylococci (CNS associated with subclinical and clinical mastitis in dairy cows

    Directory of Open Access Journals (Sweden)

    B. K. Bansal


    Full Text Available Aim: The present study was planned to determine the in vitro antibiotic susceptibility of coagulase-negative Staphylococci (CNS strains isolated from clinical and subclinical cases of mastitis in dairy cows. Antibiotic sensitivity profile will be helpful to recommend early therapy at the field level prior to availability of CST results. Materials and Methods: The milk samples from cases of clinical mastitis received in Mastitis Laboratory, Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana and those of subclinical mastitis collected during routine screening of state dairy farms, were subjected to microbial culture. Identification of CNS organisms was done by standard biochemical tests. Antibiotic sensitivity testing, based on 30 antibiotics belonging to 12 groups, was done on 58 randomly selected CNS isolates (clinical isolates: 41, subclinical isolates: 17. Results: Isolates were highly susceptible to chloramphenicol (98.3%, gentamicin (93.1%, streptomycin (91.4%, linezolid (91.4%, ceftixozime (87.9%, cloxacillin (86.2%, clotrimazole (86.2%, bacitracin (86.2%, enrofloxacin (84.5% and ceftrioxone + tazobactum (70.7%, while resistance was observed against amoxicillin (77.6%, penicillin (75.9%, ampicillin (74.1% and cefoperazone (51.7%. Overall, isolates from clinical cases of mastitis had a higher resistance than subclinical isolates. Conclusion: CNS isolates were susceptible to chloramphenicol, gentamicin and streptomycin, while higher resistance was recorded against routinely used penicillin group.

  15. Comparative antibiogram of coagulase-negative Staphylococci (CNS) associated with subclinical and clinical mastitis in dairy cows (United States)

    Bansal, B. K.; Gupta, D. K.; Shafi, T. A.; Sharma, S.


    Aim: The present study was planned to determine the in vitro antibiotic susceptibility of coagulase-negative Staphylococci (CNS) strains isolated from clinical and subclinical cases of mastitis in dairy cows. Antibiotic sensitivity profile will be helpful to recommend early therapy at the field level prior to availability of CST results. Materials and Methods: The milk samples from cases of clinical mastitis received in Mastitis Laboratory, Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana and those of subclinical mastitis collected during routine screening of state dairy farms, were subjected to microbial culture. Identification of CNS organisms was done by standard biochemical tests. Antibiotic sensitivity testing, based on 30 antibiotics belonging to 12 groups, was done on 58 randomly selected CNS isolates (clinical isolates: 41, subclinical isolates: 17). Results: Isolates were highly susceptible to chloramphenicol (98.3%), gentamicin (93.1%), streptomycin (91.4%), linezolid (91.4%), ceftixozime (87.9%), cloxacillin (86.2%), clotrimazole (86.2%), bacitracin (86.2%), enrofloxacin (84.5%) and ceftrioxone + tazobactum (70.7%), while resistance was observed against amoxicillin (77.6%), penicillin (75.9%), ampicillin (74.1%) and cefoperazone (51.7%). Overall, isolates from clinical cases of mastitis had a higher resistance than subclinical isolates. Conclusion: CNS isolates were susceptible to chloramphenicol, gentamicin and streptomycin, while higher resistance was recorded against routinely used penicillin group. PMID:27047108

  16. Comparative antibiogram of coagulase-negative Staphylococci (CNS) associated with subclinical and clinical mastitis in dairy cows. (United States)

    Bansal, B K; Gupta, D K; Shafi, T A; Sharma, S


    The present study was planned to determine the in vitro antibiotic susceptibility of coagulase-negative Staphylococci (CNS) strains isolated from clinical and subclinical cases of mastitis in dairy cows. Antibiotic sensitivity profile will be helpful to recommend early therapy at the field level prior to availability of CST results. The milk samples from cases of clinical mastitis received in Mastitis Laboratory, Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana and those of subclinical mastitis collected during routine screening of state dairy farms, were subjected to microbial culture. Identification of CNS organisms was done by standard biochemical tests. Antibiotic sensitivity testing, based on 30 antibiotics belonging to 12 groups, was done on 58 randomly selected CNS isolates (clinical isolates: 41, subclinical isolates: 17). Isolates were highly susceptible to chloramphenicol (98.3%), gentamicin (93.1%), streptomycin (91.4%), linezolid (91.4%), ceftixozime (87.9%), cloxacillin (86.2%), clotrimazole (86.2%), bacitracin (86.2%), enrofloxacin (84.5%) and ceftrioxone + tazobactum (70.7%), while resistance was observed against amoxicillin (77.6%), penicillin (75.9%), ampicillin (74.1%) and cefoperazone (51.7%). Overall, isolates from clinical cases of mastitis had a higher resistance than subclinical isolates. CNS isolates were susceptible to chloramphenicol, gentamicin and streptomycin, while higher resistance was recorded against routinely used penicillin group.

  17. Annual Research Review: Epigenetic Mechanisms and Environmental Shaping of the Brain during Sensitive Periods of Development (United States)

    Roth, Tania L.; Sweatt, J. David


    Experiences during early development profoundly affect development of the central nervous system (CNS) to impart either risk for or resilience to later psychopathology. Work in the developmental neuroscience field is providing compelling data that epigenetic marking of the genome may underlie aspects of this process. Experiments in rodents…

  18. Early Lexical Development in Spanish-Speaking Infants and Toddlers. (United States)

    Jackson-Maldonado, Donna; And Others


    The development of a new parent report instrument, Inventario del Desarollo de Habilidades Communicativas, is reported and 5 studies carried out with the instrument for 328 children aged 8 months to 2 years/7 months are presented. Among the findings are similar trajectories of development for Spanish- and English-speaking children and for children…

  19. Early Grammatical Development in Spanish Children with Down Syndrome (United States)

    Galeote, Miguel; Soto, Pilar; Sebastian, Eugenia; Checa, Elena; Sanchez-Palacios, Concepcion


    The objective of this work was to analyze morphosyntactic development in a wide sample of children with Down syndrome (DS) ("n" = 92) and children with typical development (TD) ("n" = 92) with a mental age (MA) of 20 to 29 months. Children were individually matched for gender and MA (Analysis 1) and for vocabulary size…

  20. The Role of Parents in Early Childhood Development. (United States)

    Grotberg, Edith H.

    This address to the National Congress of Parents and Teachers (PTA) discusses programs and services, current knowledge of child development, and national policies relating to child and family development in relation to democratic principles such as cultural pluralism, individual rights, and parent involvement. Conditions which make it difficult…

  1. Comparative antibiogram of coagulase-negative Staphylococci (CNS) associated with subclinical and clinical mastitis in dairy cows


    Bansal, B. K.; Gupta, D. K.; T. A. Shafi; Sharma, S


    Aim: The present study was planned to determine the in vitro antibiotic susceptibility of coagulase-negative Staphylococci (CNS) strains isolated from clinical and subclinical cases of mastitis in dairy cows. Antibiotic sensitivity profile will be helpful to recommend early therapy at the field level prior to availability of CST results. Materials and Methods: The milk samples from cases of clinical mastitis received in Mastitis Laboratory, Guru Angad Dev Veterinary and Animal Sciences Univer...

  2. The effects of military deployment on early child development

    National Research Council Canada - National Science Library

    Nguyen, Dana R; Ee, Juliana; Berry-Cabán, Cristobal S; Hoedebecke, Kyle


    The purpose of this observational, point prevalence study is to determine if parental deployment affects the cognitive, social and emotional development of preschool age children in the military family...

  3. The neonatal brain : early connectome development and childhood cognition


    Keunen, K.


    The human brain is a vastly complex system that develops rapidly during human gestation. Its developmental pace is unprecedented in any other period of human development. By the time of normal birth the brain's layout verges on the adult human brain. All major structures have come into place, including the white matter pathways. The brain’s white matter forms an intricate network of connections between gray matter regions. This macroscale brain network is referred to as the ‘connectome’. Rece...

  4. The lysosomal sialic acid transporter sialin is required for normal CNS myelination. (United States)

    Prolo, Laura M; Vogel, Hannes; Reimer, Richard J


    Salla disease and infantile sialic acid storage disease are autosomal recessive lysosomal storage disorders caused by mutations in the gene encoding sialin, a membrane protein that transports free sialic acid out of the lysosome after it is cleaved from sialoglycoconjugates undergoing degradation. Accumulation of sialic acid in lysosomes defines these disorders, and the clinical phenotype is characterized by neurodevelopmental defects, including severe CNS hypomyelination. In this study, we used a sialin-deficient mouse to address how loss of sialin leads to the defect in myelination. Behavioral analysis of the sialin(-/-) mouse demonstrates poor coordination, seizures, and premature death. Analysis by histology, electron microscopy, and Western blotting reveals a decrease in myelination of the CNS but normal neuronal cytoarchitecture and normal myelination of the PNS. To investigate potential mechanisms underlying CNS hypomyelination, we studied myelination and oligodendrocyte development in optic nerves. We found reduced numbers of myelinated axons in optic nerves from sialin(-/-) mice, but the myelin that was present appeared grossly normal. Migration and density of oligodendrocyte precursor cells were normal; however, a marked decrease in the number of postmitotic oligodendrocytes and an associated increase in the number of apoptotic cells during the later stages of myelinogenesis were observed. These findings suggest that a defect in maturation of cells in the oligodendrocyte lineage leads to increased apoptosis and underlies the myelination defect associated with sialin loss.

  5. Exosomes Mediate Mobilization of Autocrine Wnt10b to Promote Axonal Regeneration in the Injured CNS

    Directory of Open Access Journals (Sweden)

    Nardos G. Tassew


    Full Text Available Developing strategies that promote axonal regeneration within the injured CNS is a major therapeutic challenge, as axonal outgrowth is potently inhibited by myelin and the glial scar. Although regeneration can be achieved using the genetic deletion of PTEN, a negative regulator of the mTOR pathway, this requires inactivation prior to nerve injury, thus precluding therapeutic application. Here, we show that, remarkably, fibroblast-derived exosomes (FD exosomes enable neurite growth on CNS inhibitory proteins. Moreover, we demonstrate that, upon treatment with FD exosomes, Wnt10b is recruited toward lipid rafts and activates mTOR via GSK3β and TSC2. Application of FD exosomes shortly after optic nerve injury promoted robust axonal regeneration, which was strongly reduced in Wnt10b-deleted animals. This work uncovers an intercellular signaling pathway whereby FD exosomes mobilize an autocrine Wnt10b-mTOR pathway, thereby awakening the intrinsic capacity of neurons for regeneration, an important step toward healing the injured CNS.

  6. Regulation of Adult CNS Axonal Regeneration by the Post-transcriptional Regulator Cpeb1

    Directory of Open Access Journals (Sweden)

    Wilson Pak-Kin Lou


    Full Text Available Adult mammalian central nervous system (CNS neurons are unable to regenerate following axonal injury, leading to permanent functional impairments. Yet, the reasons underlying this regeneration failure are not fully understood. Here, we studied the transcriptome and translatome shortly after spinal cord injury. Profiling of the total and ribosome-bound RNA in injured and naïve spinal cords identified a substantial post-transcriptional regulation of gene expression. In particular, transcripts associated with nervous system development were down-regulated in the total RNA fraction while remaining stably loaded onto ribosomes. Interestingly, motif association analysis of post-transcriptionally regulated transcripts identified the cytoplasmic polyadenylation element (CPE as enriched in a subset of these transcripts that was more resistant to injury-induced reduction at the transcriptome level. Modulation of these transcripts by overexpression of the CPE binding protein, Cpeb1, in mouse and Drosophila CNS neurons promoted axonal regeneration following injury. Our study uncovered a global evolutionarily conserved post-transcriptional mechanism enhancing regeneration of injured CNS axons.

  7. Distributional effects of Oportunidades on early child development. (United States)

    Figueroa, José Luis


    The Mexican Oportunidades program is designed to increase human capital through investments in education, health, and nutrition for children in extreme poverty. Although the program is not expressly designed to promote a child's cognitive and non-cognitive development, the set of actions carried out by the program could eventually facilitate improvements in these domains. Previous studies on the Oportunidades program have found little impact on children's cognition but have found positive effects on their non-cognitive development. However, the majority of these studies use the average outcome to measure the impact of the program and thus overlook other "non-average" effects. This paper uses stochastic dominance methods to investigate results beyond the mean by comparing cumulative distributions for both children who are and children who are not aided by the program. Four indicators of cognitive development and one indicator of non-cognitive development are analyzed using a sample of 2595 children aged two to six years. The sample was collected in rural communities in Mexico in 2003 as part of the program evaluation. Similar to previous studies, the program is found to positively influence children's non-cognitive abilities: children enrolled in the program manifest fewer behavioral problems compared with children who are not enrolled. In addition, different program effects are found for girls and boys and for indigenous and non-indigenous children. The ranges where the effect is measured cover a large part of the outcome's distribution, and these ranges include a large proportion of the children in the sample. With regard to cognitive development, only one indicator (short-term memory) shows positive effects. Nevertheless, the results for this indicator demonstrate that children with low values of cognitive development benefit from the program, whereas children with high values do not. Overall, the program has positive effects on child development, especially for

  8. A map of taste neuron projections in the Drosophila CNS

    Indian Academy of Sciences (India)

    We provide a map of the projections of taste neurons in the CNS of Drosophila. Using a collection of 67 GAL4 drivers representing the entire repertoire of Gr taste receptors, we systematically map the projections of neurons expressing these drivers in the thoracico-abdominal ganglion and the suboesophageal ganglion ...

  9. Molecularly-Driven Doublet Therapy for Recurrent CNS Malignant Neoplasms (United States)


    Anaplastic Astrocytoma; Anaplastic Ependymoma; Anaplastic Ganglioglioma; Anaplastic Meningioma; Anaplastic Oligodendroglioma; Pleomorphic Xanthoastrocytoma, Anaplastic; Atypical Teratoid/Rhabdoid Tumor; Brain Cancer; Brain Tumor; Central Nervous System Neoplasms; Choroid Plexus Carcinoma; CNS Embryonal Tumor With Rhabdoid Features; Ganglioneuroblastoma of Central Nervous System; CNS Tumor; Embryonal Tumor of CNS; Ependymoma; Glioblastoma; Glioma; Glioma, Malignant; Medulloblastoma; Medulloblastoma; Unspecified Site; Medulloepithelioma; Neuroepithelial Tumor; Neoplasms; Neoplasms, Neuroepithelial; Papillary Tumor of the Pineal Region (High-grade Only); Pediatric Brain Tumor; Pineal Parenchymal Tumor of Intermediate Differentiation (High-grade Only); Pineoblastoma; Primitive Neuroectodermal Tumor; Recurrent Medulloblastoma; Refractory Brain Tumor; Neuroblastoma. CNS; Glioblastoma, IDH-mutant; Glioblastoma, IDH-wildtype; Medulloblastoma, Group 3; Medulloblastoma, Group 4; Glioma, High Grade; Neuroepithelial Tumor, High Grade; Medulloblastoma, SHH-activated and TP53 Mutant; Medulloblastoma, SHH-activated and TP53 Wildtype; Medulloblastoma, Chromosome 9q Loss; Medulloblastoma, Non-WNT Non-SHH, NOS; Medulloblastoma, Non-WNT/Non-SHH; Medulloblastoma, PTCH1 Mutation; Medulloblastoma, WNT-activated; Ependymoma, Recurrent; Glioma, Recurrent High Grade; Glioma, Recurrent Malignant; Embryonal Tumor, NOS; Glioma, Diffuse Midline, H3K27M-mutant; Embryonal Tumor With Multilayered Rosettes (ETMR); Ependymoma, NOS, WHO Grade III; Ependymoma, NOS, WHO Grade II; Medulloblastoma, G3/G4; Ependymoma, RELA Fusion Positive

  10. Neurolymphomatosis: An International Primary CNS Lymphoma Collaborative Group report

    NARCIS (Netherlands)

    S. Grisariu (Sigal); B. Avni (Batia); T.T. Batchelor (Tracy); M.J. van den Bent (Martin); F. Bokstein (Felix); D. Schiff (David); O. Kuittinen (Outi); M.C. Chamberlain (Marc C.); P. Roth (Patrick); A. Nemets (Anatoly); E. Shalom (Edna); D. Ben-Yehuda (Dina); T. Siegal (Tali)


    textabstractNeurolymphomatosis (NL) is a rare clinical entity. The International Primary CNS Lymphoma Collaborative Group retrospectively analyzed 50 patients assembled from 12 centers in 5 countries over a 16-year period. NL was related to non-Hodgkin lymphoma in 90% and to acute leukemia in 10%.

  11. Sleep disorders in children after treatment for a CNS tumour

    NARCIS (Netherlands)

    Verberne, Lisa M.; Maurice-Stam, Heleen; Grootenhuis, Martha A.; van Santen, Hanneke M.; Schouten-van Meeteren, Antoinette Y. N.


    The long-term survival of children with a central nervous system (CNS) tumour is improving. However, they experience late effects, including altered habits and patterns of sleep. We evaluated the presence and type of sleep disorders and daytime sleepiness in these children, and its associations with

  12. A map of taste neuron projections in the Drosophila CNS

    Indian Academy of Sciences (India)


    Jul 8, 2014 ... Taste allows the fly to evaluate potential food sources. The presence of nutritious sugars, which taste sweet, and toxins, which taste bitter, is detected by gustatory organs. Their input is integrated in the CNS and provides a basis for feeding decisions. Drosophila is a valuable system in which to investigate ...

  13. Use Case Evaluation (UCE): A Method for Early Usability Evaluation in Software Development

    DEFF Research Database (Denmark)

    Stage, Jan; Høegh, Rune Thaarup; Hornbæk, K.


    t is often argued that usability problems should be identified as early as possible during software development, but many usability evaluation methods do not fit well in early development activities. We propose a method for usability evaluation of use cases, a widely used representation of design...... ideas produced early in software development processes. The method proceeds by systematic inspection of use cases with reference to a set of guidelines for usable design. To validate the method, four evaluators inspected a set of use cases for a health care application....

  14. Enhancing the Early Childhood Development System in Yakutia (Russia): Meeting the Challenges (United States)

    Kotnik, Jure; Shmis, Tigran


    The Yakutia Republic is currently working to update its early childhood development (ECD) system. Its goal is to ensure a high quality environment for early learning and child care and to enable higher enrolment levels. Currently, a high priority for the Government of Yakutia is to increase access to pre-school education, given the significant…

  15. Early Intervention Practices for Children with Hearing Loss: Impact of Professional Development (United States)

    Martin-Prudent, Angi; Lartz, Maribeth; Borders, Christina; Meehan, Tracy


    Early identification and appropriate intervention services for children who are deaf or hard of hearing significantly increase the likelihood of better language, speech, and social-emotional development. However, current research suggests that there is a critical shortage of professionals trained to provide early intervention services to deaf and…

  16. African Early Childhood Development Curriculum and Pedagogy for Turkana Nomadic Pastoralist Communities of Kenya (United States)

    Ng'asike, John T.


    Western conceptions of child development and the models of early education they engender predominantly shape services for young children in the first eight years of life all over Africa. This chapter brings a reconceptualist perspective to the critique of Kenya's continuing failure to ground early childhood programs and services in local cultural…

  17. Disregard for Rules: The Early Development and Predictors of a Specific Dimension of Disruptive Behavior Disorders (United States)

    Petitclerc, Amelie; Boivin, Michel; Dionne, Ginette; Zoccolillo, Mark; Tremblay, Richard E.


    Background: Disregard for rules, an important dimension of oppositional defiant and conduct disorders, is frequent during early childhood, but the development of its chronic form has not been studied during this key socialization period. This study aimed to describe the developmental trajectories of disregard for rules during early childhood and…

  18. The Organisation for Economic Co-Operation and Development's International Early Learning Study: What Happened Next (United States)

    Moss, Peter; Urban, Mathias


    In this article, the authors provide an update on what has happened over recent months with the Organisation for Economic Co-operation and Development's proposal for an International Early Learning Study, and review responses to the proposed International Early Learning Study, including the concerns that have been raised about this new venture in…

  19. Development of Early Handwriting: Visual-Motor Control during Letter Copying (United States)

    Maldarelli, Jennifer E.; Kahrs, Björn A.; Hunt, Sarah C.; Lockman, Jeffrey J.


    Despite the importance of handwriting for school readiness and early academic progress, prior research on the development of handwriting has focused primarily on the product rather than the process by which young children write letters. In contrast, in the present work, early handwriting is viewed as involving a suite of perceptual, motor, and…

  20. Early Identification for Special Education: Implications for Research and Development in the Pacific Rim (United States)

    Cook, Bryan; Gerber, Michael; Hong, Li-Yu; Mannan, Hasheem; Zhang, Weng-jing


    Early identification and intervention for children with disabilities can significantly improve longer term outcomes, but in developing nations like many in the Pacific Rim, such programs and practices can be expensive and must compete against other needs. We argue that early identification and intervention by schools leads not only to life…

  1. Predicting the integrated development of word reading and spelling in the early primary grades

    NARCIS (Netherlands)

    Schaars, M.M.H.; Segers, P.C.J.; Verhoeven, L.T.W.


    Word reading and spelling processes are assumed to be highly related to each other and to early literacy measures. However, the debate on how reading and spelling interact in early development is far from resolved yet. The present study examined the singular and integrated word reading and spelling

  2. Building the Leadership Capacity of Early Childhood Directors: An Evaluation of a Leadership Development Model (United States)

    Talan, Teri N.; Bloom, Paula J.; Kelton, Robyn E.


    While there is consensus among policymakers and practitioners about the importance of strong leadership in early childhood education, there is scant research on effective models of leadership development for administrators of early childhood programs, particularly those working in the child care sector. This is cause for concern because the…

  3. Erotic Love and the Development of Proto-Capitalist Ideology in Early Modern Comedy (United States)

    Damsen, Silver


    My dissertation, "Erotic Love and the Development of Proto-Capitalist Ideology in Early Modern Comedy" demonstrates how increased crown authority, and an expanded market combine with the mixed agency of the romantic comedy daughter to further encourage early modern economic growth. The triumph of rebelling daughter over blocking father has…


    Directory of Open Access Journals (Sweden)



    Full Text Available The aim of this paper is to present a systematic literature review of the researches conducted in the area of risk factors and difficulties in the early development of children born after assisted conception, to systematize current knowledge in this field and allocate the factors of importance for the early intervention.In order to evaluate the published data on risk factors and early development of children born after assisted conception, an extensive literature search was conducted to identify the published papers related to the obstetric and neonatal outcome of pregnancies after assisted repro­duction technology, the incidence of multiple pregnancy and the risk of preterm delivery, the neonatal status, the mean gestational age, the average birth weight, the neuro-developmental outcomes and early cognitive and motor development. The research identified the following factors as the most important for the early intervention: increased rates of multiple gestations, prematurity, delivery by cesarean section, lower average gestational development and average birth weight, small fetal development for gestational age and low Apgar score, related to the an increased risk of developing neurological problems, such as the cerebral palsy.Accepting this research results, it can be concluded that all of these information should be available for couples seeking an Assisted Reproductive Technology (ART treatment.The success of the early intervention is directly related to the early detection and assessment that precedes this treatment, creating individual programs and evaluation of the effects of the treatment.

  5. Oviduct: roles in fertilization and early embryo development. (United States)

    Li, Shuai; Winuthayanon, Wipawee


    Animal oviducts and human Fallopian tubes are a part of the female reproductive tract that hosts fertilization and pre-implantation development of the embryo. With an increasing understanding of roles of the oviduct at the cellular and molecular levels, current research signifies the importance of the oviduct on naturally conceived fertilization and pre-implantation embryo development. This review highlights the physiological conditions within the oviduct during fertilization, environmental regulation, oviductal fluid composition and its role in protecting embryos and supplying nutrients. Finally, the review compares different aspects of naturally occurring fertilization and assisted reproductive technology (ART)-achieved fertilization and embryo development, giving insight into potential areas for improvement in this technology. © 2017 Society for Endocrinology.

  6. Retinoic Acid Signaling during Early Spinal Cord Development

    Directory of Open Access Journals (Sweden)

    Ruth Diez del Corral


    Full Text Available Retinoic acid signaling is required at several steps during the development of the spinal cord, from the specification of generic properties to the final acquisition of neuronal subtype identities, including its role in trunk neural crest development. These functions are associated with the production of retinoic acid in specific tissues and are highly dependent on context. Here, we review the defects associated with retinoic acid signaling manipulations, mostly in chick and mouse models, trying to separate the different processes where retinoic acid signaling is involved and to highlight common features, such as its ability to promote transitions along the neuronal differentiation cascade.

  7. Developing analytic thinking skills in early undergraduate education. (United States)

    Bowers, B; McCarthy, D


    This article describes how a required prenursing health issues course was substantially restructured to increase the opportunities for students to develop analytic skills and for faculty to gain greater insight into how the students processed course content. Using writing-to-learn (WTL) strategies based on theories of adult cognitive development (Kinneavy, McCleary, & Nakadate, 1985; Kohlberg, 1978; Perry 1978), course readings, writing assignments, and exam questions were revised continuously over five semesters. This article describes the purpose and process of redesigning the course and some reflections on the outcome.

  8. Radioprotection of mouse CNS endothelial cells in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Lyubimova, N.; Coultas, P.; Martin, R. [Peter MacCallum Cancer institute, Melbourne, Victoria (Australia)


    After treatments with monoamine oxidase inhibitors and L-DOPA, the blood brain barrier causes a build-up of dopamine in brain capillary endothelial cells. Conversion of the dopamine to a fluorophore provides a marker which can be used to measure endothelial cell density by fluorescence microscopy. Earlier studies used this technique to monitor post-irradiation changes in endothelial cell density in rodent brain and showed loss within 24 hours of a sub-population of about 15 % of the endothelial cells. As a first step, rather than use the later endpoints of radionecrosis it was decided to examine directly whether Hoechst 33342 could protect against this rapid initial endothelial cell loss. Ten minutes after intravenous injection of Joechst 33342, in mouse brain the ligand was confined to endothelial cells and, for irradiation at this time, there was protection against endothelial cell loss over the first 24 hours after after exposure. Ablation of the sensitive subpopulation in unprotected mice took place over a dose range of 1 to 3 Gy {gamma}-rays but doses between 12 to 20 Gy were required in the presence of the ligand. This protection equated to a high dose modification factor of approximately 7 and may reflect suppression of apoptosis in this sensitive endothelial subpopulation. The extent to which there is enhanced survival in the endothelial population as a whole, and how the observed protection affects late CNS necrosis development, has yet to be determined. However these results suggest a potential use of DNA-binding radioprotectors with limited penetration in investigations of the relative significance of endothelial and parenchymal damage in normal tissue responses to ionising radiation. (authors)

  9. Activity-Driven CNS Changes in Learning and Development (United States)


    this reflex is the monosynaptic connection between mechanoreceptor sensory neurons that innervate the siphon skin and the motor neurons that supply the...substrate for memory consolidation. The nature and extent of the structural alterations at mechanoreceptor sensory neurons are consistent with changes in...Two types of presynaptic configurations in insect central synapses: An ultrastructural analysis. Brain Res. 130: 25-45. 14. VRENSEN. G. & J. NUNES

  10. Sociocultural Contexts for the Early Development of Semiotic Production (United States)

    Braswell, Gregory S.


    Children constantly encounter signs during cultural practices, although many theories do not fully acknowledge sociocultural aspects of semiotic development. The author examines research on cultural practices and contexts in which children learn to produce signs involving representational drawing and pretend play. This work is contrasted with more…

  11. Early Vocabulary Development in Children with Bilateral Cochlear Implants (United States)

    Välimaa, Taina; Kunnari, Sari; Laukkanen-Nevala, Päivi; Lonka, Eila


    Background: Children with unilateral cochlear implants (CIs) may have delayed vocabulary development for an extended period after implantation. Bilateral cochlear implantation is reported to be associated with improved sound localization and enhanced speech perception in noise. This study proposed that bilateral implantation might also promote…

  12. The Role of Early Visual Attention in Social Development (United States)

    Wagner, Jennifer B.; Luyster, Rhiannon J.; Yim, Jung Yeon; Tager-Flusberg, Helen; Nelson, Charles A.


    Faces convey important information about the social environment, and even very young infants are preferentially attentive to face-like over non-face stimuli. Eye-tracking studies have allowed researchers to examine which features of faces infants find most salient across development, and the present study examined scanning of familiar (i.e.,…

  13. Early Spatial Thinking and the Development of Number Sense (United States)

    Bobis, Janette


    Number sense has been recognised as central to young children's development of mathematics for a number of decades. A student with a "good" sense of number normally has a thorough understanding of relationships among numbers and operations--being able flexibly to partition and combine numbers in convenient ways to allow appropriate estimations and…

  14. Early embryo development in Fucus distichus is auxin sensitive (United States)

    Basu, Swati; Sun, Haiguo; Brian, Leigh; Quatrano, Ralph L.; Muday, Gloria K.


    Auxin and polar auxin transport have been implicated in controlling embryo development in land plants. The goal of these studies was to determine if auxin and auxin transport are also important during the earliest stages of development in embryos of the brown alga Fucus distichus. Indole-3-acetic acid (IAA) was identified in F. distichus embryos and mature tissues by gas chromatography-mass spectroscopy. F. distichus embryos accumulate [(3)H]IAA and an inhibitor of IAA efflux, naphthylphthalamic acid (NPA), elevates IAA accumulation, suggesting the presence of an auxin efflux protein complex similar to that found in land plants. F. distichus embryos normally develop with a single unbranched rhizoid, but growth on IAA leads to formation of multiple rhizoids and growth on NPA leads to formation of embryos with branched rhizoids, at concentrations that are active in auxin accumulation assays. The effects of IAA and NPA are complete before 6 h after fertilization (AF), which is before rhizoid germination and cell division. The maximal effects of IAA and NPA are between 3.5 and 5 h AF and 4 and 5.5 h AF, respectively. Although, the location of the planes of cell division was significantly altered in NPA- and IAA-treated embryos, these abnormal divisions occurred after abnormal rhizoid initiation and branching was observed. The results of this study suggest that auxin acts in the formation of apical basal patterns in F. distichus embryo development.

  15. Classroom Pets and Young Children: Supporting Early Development (United States)

    Meadan, Hedda; Jegatheesan, Brinda


    Many young children have a natural attraction to and curiosity about animals. They like to observe, touch, talk to, and ask questions about them. Teachers and parents both can use this broad interest to facilitate children's development and learning in a variety of domains. Research shows that children across ages find emotional comfort in their…

  16. Accelerating Early Language Development with Multi-Sensory Training (United States)

    Bjorn, Piia M.; Kakkuri, Irma; Karvonen, Pirkko; Leppanen, Paavo H. T.


    This paper reports the outcome of a multi-sensory intervention on infant language skills. A programme titled "Rhyming Game and Exercise Club", which included kinaesthetic-tactile mother-child rhyming games performed in natural joint attention situations, was intended to accelerate Finnish six- to eight-month-old infants' language development. The…

  17. DNA methylation plays a crucial role during early Nasonia development

    NARCIS (Netherlands)

    Zwier, M. V.; Verhulst, E. C.; Zwahlen, R. D.; Beukeboom, L. W.; van de Zande, L.

    Although the role of DNA methylation in insect development is still poorly understood, the number and role of DNA methyltransferases in insects vary strongly between species. DNA methylation appears to be widely present among the social hymenoptera and functional studies in Apis have suggested a

  18. Early life environment and the developing cardiovascular system

    NARCIS (Netherlands)

    Idris, N.S.


    Background The dynamics of cardiovascular system development in childhood are still largely unknown. Despite its known sensitivity to small perturbations, it has not been fully elucidated how the cardiovascular system evolves and responds to different stimuli and how these impact the future

  19. Correlates of Early Language Development in Chinese Children (United States)

    Zhang, Yiwen; Jin, Xingming; Shen, Xiamong; Zhang, Jinming; Hoff, Erika


    Caregivers of 608 (331 boys and 277 girls) children in Shanghai, China reported on their children's language development and on the language teaching practices used in the home. The children were between 24 and 47 months old. The relation of age-corrected language level to paternal education, child gender, and teaching practice use was examined.…

  20. Family-School Connectedness and Children's Early Social Development (United States)

    Serpell, Zewelanji N.; Mashburn, Andrew J.


    This study examined the extent to which teacher ratings of the frequency of parent-teacher contacts and quality of parent-teacher relationships in prekindergarten were associated with teachers' perceptions of the quality of their relationship with children and children's social development. Participants were a diverse sample of 2966 four-year-olds…