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Sample records for alpha-synuclein exhibit hyperactivity

  1. alpha-Synuclein budding yeast model: toxicity enhanced by impaired proteasome and oxidative stress.

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    Sharma, Nijee; Brandis, Katrina A; Herrera, Sara K; Johnson, Brandon E; Vaidya, Tulaza; Shrestha, Ruja; Debburman, Shubhik K

    2006-01-01

    Parkinson's disease (PD) is a common neurodegenerative disorder that results from the selective loss of midbrain dopaminergic neurons. Misfolding and aggregation of the protein alpha-synuclein, oxidative damage, and proteasomal impairment are all hypotheses for the molecular cause of this selective neurotoxicity. Here, we describe a Saccharomyces cerevisiae model to evaluate the misfolding, aggregation, and toxicity-inducing ability of wild-type alpha-synuclein and three mutants (A30P, A53T, and A30P/A53T), and we compare regulation of these properties by dysfunctional proteasomes and by oxidative stress. We found prominent localization of wild-type and A53T alpha-synuclein near the plasma membrane, supporting known in vitro lipid-binding ability. In contrast, A30P was mostly cytoplasmic, whereas A30P/A53T displayed both types of fluorescence. Surprisingly, alpha-synuclein was not toxic to several yeast strains tested. When yeast mutants for the proteasomal barrel (doa3-1) were evaluated, delayed alpha-synuclein synthesis and membrane association were observed; yeast mutant for the proteasomal cap (sen3-1) exhibited increased accumulation and aggregation of alpha-synuclein. Both sen3-1and doa3-1 mutants exhibited synthetic lethality with alpha-synuclein. When yeasts were challenged with an oxidant (hydrogen peroxide), alpha-synuclein was extremely lethal to cells that lacked manganese superoxide dismutase Mn-SOD (sod2Delta) but not to cells that lacked copper, zinc superoxide dismutase Cu,Zn-SOD (sod1Delta). Despite the toxicity, sod2Delta cells never displayed intracellular aggregates of alpha-synuclein. We suggest that the toxic alpha-synuclein species in yeast are smaller than the visible aggregates, and toxicity might involve alpha-synuclein membrane association. Thus, yeasts have emerged effective organisms for characterizing factors and mechanisms that regulate alpha-synuclein toxicity.

  2. Alpha-synuclein association with phosphatidylglycerol probed by lipid spin labels.

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    Ramakrishnan, Muthu; Jensen, Poul H; Marsh, Derek

    2003-11-11

    Alpha-synuclein is a small presynaptic protein, which is linked to the development of Parkinson's disease. Alpha-synuclein partitions between cytosolic and vesicle-bound states, where membrane binding is accompanied by the formation of an amphipathic helix in the N-terminal section of the otherwise unstructured protein. The impact on alpha-synuclein of binding to vesicle-like liposomes has been studied extensively, but far less is known about the impact of alpha-synuclein on the membrane. The interactions of alpha-synuclein with phosphatidylglycerol membranes are studied here by using spin-labeled lipid species and electron spin resonance (ESR) spectroscopy to allow a detailed analysis of the effect on the membrane lipids. Membrane association of alpha-synuclein perturbs the ESR spectra of spin-labeled lipids in bilayers of phosphatidylglycerol but not of phosphatidylcholine. The interaction is inhibited at high ionic strength. The segmental motion is hindered at all positions of spin labeling in the phosphatidylglycerol sn-2 chain, while still preserving the chain flexibility gradient characteristic of fluid phospholipid membranes. Direct motional restriction of the lipid chains, resulting from penetration of the protein into the hydrophobic interior of the membrane, is not observed. Saturation occurs at a protein/lipid ratio corresponding to approximately 36 lipids/protein added. Alpha-synuclein exhibits a selectivity of interaction with different phospholipid spin labels when bound to phosphatidylglycerol membranes in the following order: stearic acid > cardiolipin > phosphatidylcholine > phosphatidylglycerol approximately phosphatidylethanolamine > phosphatidic acid approximately phosphatidylserine > N-acyl phosphatidylethanolamine > diglyceride. Accordingly, membrane-bound alpha-synuclein associates at the interfacial region of the bilayer where it may favor a local concentration of certain phospholipids.

  3. alpha-synuclein and LRRK2: partners in crime.

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    Tong, Youren; Shen, Jie

    2009-12-24

    In this issue of Neuron, Lin et al. report that LRRK2 modulates age-related neurodegeneration caused by overexpression of alpha-synuclein in the forebrain of transgenic mice. Overexpression of LRRK2 accelerates the progression of alpha-synuclein-mediated neuropathological changes, whereas deletion of LRRK2 alleviates these alterations. The results reveal an interesting interaction between alpha-synuclein and LRRK2, two gene products linked to dominantly inherited Parkinson's disease.

  4. Unique copper-induced oligomers mediate alpha-synuclein toxicity.

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    Wright, Josephine A; Wang, Xiaoyan; Brown, David R

    2009-08-01

    Parkinson's disease and a number of other neurodegenerative diseases have been linked to either genetic mutations in the alpha-synuclein gene or show evidence of aggregates of the alpha-synuclein protein, sometimes in the form of Lewy bodies. There currently is no clear evidence of a distinct neurotoxic species of alpha-synuclein to explain the death of neurons in these diseases. We undertook to assess the toxicity of alpha-synuclein via exogenous application in cell culture. Initially, we showed that only aggregated alpha-synuclein is neurotoxic and requires the presence copper but not iron. Other members of the synuclein family showed no toxicity in any form and inherited point mutations did not alter the effective toxic concentration of alpha-synuclein. Through protein fractionation techniques, we were able to isolate an oligomeric species responsible for the toxicity of alpha-synuclein. This oligomeric species has a unique stellate appearance under EM and again, requires association with copper to induce cell death. The results allow us to suggest that the toxic species of alpha-synuclein in vivo could possibly be these stellate oligomers and not fibrils. Our data provide a link between the recently noted association of copper and alpha-synuclein and a potential role for the combination in causing neurodegeneration.

  5. Alpha-synuclein in cutaneous small nerve fibers

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    Siepmann, Timo; Illigens, Ben Min-Woo; Barlinn, Kristian

    2016-01-01

    Despite progression in the development of pharmacological therapy, treatment of alpha synucleinopathies, such as Parkinson’s disease (PD) and some atypical parkinsonism syndromes, is still challenging. To date, our knowledge of the mechanisms whereby the pathological form of alpha-synuclein causes structural and functional damage to the nervous system is limited and, consequently, there is a lack of specific diagnostic tools to evaluate pathology in these patients and differentiate PD from other neurodegenerative proteinopathies. Recent studies indicated that alpha-synuclein deposition in cutaneous small nerve fibers assessed by skin biopsies might be a valid disease marker of PD and facilitate early differentiation of PD from atypical parkinsonism syndromes. This observation is relevant since early diagnosis may enable timely treatment and improve quality of life. However, challenges include the necessity of standardizing immunohistochemical analysis techniques and the identification of potential distinct patterns of intraneural alpha-synuclein deposition among synucleinopathies. In this perspective, we explore the scientific and clinical opportunities arising from alpha-synuclein assessment using skin biopsies. These include elucidation of the peripheral nervous system pathology of PD and other synucleinopathies, identification of novel targets to study response to neuroprotective treatment, and improvement of clinical management. Furthermore, we discuss future challenges in exploring the diagnostic value of skin biopsy assessment for alpha-synuclein deposition and implementing the technique in clinical practice. PMID:27822045

  6. alpha-Synuclein fission yeast model: concentration-dependent aggregation without plasma membrane localization or toxicity.

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    Brandis, Katrina A; Holmes, Isaac F; England, Samantha J; Sharma, Nijee; Kukreja, Lokesh; DebBurman, Shubhik K

    2006-01-01

    Despite fission yeast's history of modeling salient cellular processes, it has not yet been used to model human neurodegeneration-linked protein misfolding. Because alpha-synuclein misfolding and aggregation are linked to Parkinson's disease (PD), here, we report a fission yeast (Schizosaccharomyces pombe) model that evaluates alpha-synuclein misfolding, aggregation, and toxicity and compare these properties with those recently characterized in budding yeast (Saccharomyces cerevisiae). Wild-type alpha-synuclein and three mutants (A30P, A53T, and A30P/A53T) were expressed with thiamine-repressible promoters (using vectors of increasing promoter strength: pNMT81, pNMT41, and pNMT1) to test directly in living cells the nucleation polymerization hypothesis for alpha-synuclein misfolding and aggregation. In support of the hypothesis, wild-type and A53T alpha-synuclein formed prominent intracellular cytoplasmic inclusions within fission yeast cells in a concentration- and time-dependent manner, whereas A30P and A30P/A53T remained diffuse throughout the cytoplasm. A53T alpha-synuclein formed aggregates faster than wild-type alpha-synuclein and at a lower alpha-synuclein concentration. Unexpectedly, unlike in budding yeast, wild-type and A53T alpha-synuclein did not target to the plasma membrane in fission yeast, not even at low alpha-synuclein concentrations or as a precursor step to forming aggregates. Despite alpha-synuclein's extensive aggregation, it was surprisingly nontoxic to fission yeast. Future genetic dissection might yield molecular insight into this protection against toxicity. We speculate that alpha-synuclein toxicity might be linked to its membrane binding capacity. To conclude, S. pombe and S. cerevisiae model similar yet distinct aspects of alpha-synuclein biology, and both organisms shed insight into alpha-synuclein's role in PD pathogenesis.

  7. Alpha-synuclein in cutaneous small nerve fibers

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    Siepmann T

    2016-10-01

    Full Text Available Timo Siepmann,1 Ben Min-Woo Illigens,2 Kristian Barlinn1 1Department of Neurology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; 2Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA Abstract: Despite progression in the development of pharmacological therapy, treatment of alpha synucleinopathies, such as Parkinson’s disease (PD and some atypical parkinsonism syndromes, is still challenging. To date, our knowledge of the mechanisms whereby the pathological form of alpha-synuclein causes structural and functional damage to the nervous system is limited and, consequently, there is a lack of specific diagnostic tools to evaluate pathology in these patients and differentiate PD from other neurodegenerative proteinopathies. Recent studies indicated that alpha-synuclein deposition in cutaneous small nerve fibers assessed by skin biopsies might be a valid disease marker of PD and facilitate early differentiation of PD from atypical parkinsonism syndromes. This observation is relevant since early diagnosis may enable timely treatment and improve quality of life. However, challenges include the necessity of standardizing immunohistochemical analysis techniques and the identification of potential distinct patterns of intraneural alpha-synuclein deposition among synucleinopathies. In this perspective, we explore the scientific and clinical opportunities arising from alpha-synuclein assessment using skin biopsies. These include elucidation of the peripheral nervous system pathology of PD and other synucleinopathies, identification of novel targets to study response to neuroprotective treatment, and improvement of clinical management. Furthermore, we discuss future challenges in exploring the diagnostic value of skin biopsy assessment for alpha-synuclein deposition and implementing the technique in clinical practice. Keywords: Parkinson’s disease, diagnosis, skin

  8. Alpha-synuclein suppression by targeted small interfering RNA in the primate substantia nigra.

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    Alison L McCormack

    Full Text Available The protein alpha-synuclein is involved in the pathogenesis of Parkinson's disease and other neurodegenerative disorders. Its toxic potential appears to be enhanced by increased protein expression, providing a compelling rationale for therapeutic strategies aimed at reducing neuronal alpha-synuclein burden. Here, feasibility and safety of alpha-synuclein suppression were evaluated by treating monkeys with small interfering RNA (siRNA directed against alpha-synuclein. The siRNA molecule was chemically modified to prevent degradation by exo- and endonucleases and directly infused into the left substantia nigra. Results compared levels of alpha-synuclein mRNA and protein in the infused (left vs. untreated (right hemisphere and revealed a significant 40-50% suppression of alpha-synuclein expression. These findings could not be attributable to non-specific effects of siRNA infusion since treatment of a separate set of animals with luciferase-targeting siRNA produced no changes in alpha-synuclein. Infusion with alpha-synuclein siRNA, while lowering alpha-synuclein expression, had no overt adverse consequences. In particular, it did not cause tissue inflammation and did not change (i the number and phenotype of nigral dopaminergic neurons, and (ii the concentrations of striatal dopamine and its metabolites. The data represent the first evidence of successful anti-alpha-synuclein intervention in the primate substantia nigra and support further development of RNA interference-based therapeutics.

  9. Alpha-synuclein gene deletion decreases brain palmitate uptake and alters the palmitate metabolism in the absence of alpha-synuclein palmitate binding

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    Golovko, Mikhail Y; Færgeman, Nils J.; Cole, Nelson B;

    2005-01-01

    . To better define a role for alpha-synuclein in brain fatty acid uptake and metabolism, we infused awake, wild-type, or alpha-synuclein gene-ablated mice with [1-(14)C]palmitic acid (16:0) and assessed fatty acid uptake and turnover kinetics in brain phospholipids. Alpha-synuclein deficiency decreased brain......Alpha-synuclein is an abundant protein in the central nervous system that is associated with a number of neurodegenerative disorders, including Parkinson's disease. Its physiological function is poorly understood, although recently it was proposed to function as a fatty acid binding protein...... 16:0 uptake 35% and reduced its targeting to the organic fraction. The incorporation coefficient for 16:0 entering the brain acyl-CoA pool was significantly decreased 36% in alpha-synuclein gene-ablated mice. Because incorporation coefficients alone are not predictive of fatty acid turnover...

  10. Molecular understanding of copper and iron interaction with alpha-synuclein by fluorescence analysis.

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    Bharathi; Rao, K S J

    2008-07-01

    Alpha-synuclein aggregation is a hallmark pathological feature in Parkinson's disease (PD). The conversion of alpha-synuclein from a soluble monomer to an insoluble fibril may underlie the neurodegeneration associated with PD. Redox-active metal ions such as iron (Fe) and copper (Cu) are known to enhance alpha-synuclein fibrillogenesis. In the present investigation, we analyzed the binding efficiency of Cu and Fe to alpha-synuclein by fluorescence studies. It is interesting to note that Cu and Fe showed differential binding pattern toward alpha-synuclein (wild type and A30P, A53T, and E46K mutant forms) as revealed by intrinsic tyrosine fluorescence, thioflavin-T fluorescence, 1-anilino-8-naphthalenesulfonate-binding studies, and scatchard plot analysis. The experimental data might prove useful in understanding the hierarchy of metals binding to alpha-synuclein and its role in neurodegeneration.

  11. Alpha-synuclein levels in blood plasma decline with healthy aging.

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    Koehler, Niklas K U; Stransky, Elke; Meyer, Mirjam; Gaertner, Susanne; Shing, Mona; Schnaidt, Martina; Celej, Maria S; Jovin, Thomas M; Leyhe, Thomas; Laske, Christoph; Batra, Anil; Buchkremer, Gerhard; Fallgatter, Andreas J; Wernet, Dorothee; Richartz-Salzburger, Elke

    2015-01-01

    There is unequivocal evidence that alpha-synuclein plays a pivotal pathophysiological role in neurodegenerative diseases, and in particular in synucleinopathies. These disorders present with a variable extent of cognitive impairment and alpha-synuclein is being explored as a biomarker in CSF, blood serum and plasma. Considering key events of aging that include proteostasis, alpha-synuclein may not only be useful as a marker for differential diagnosis but also for aging per se. To explore this hypothesis, we developed a highly specific ELISA to measure alpha-synuclein. In healthy males plasma alpha-synuclein levels correlated strongly with age, revealing much lower concentrations in older (avg. 58.1 years) compared to younger (avg. 27.6 years) individuals. This difference between the age groups was enhanced after acidification of the plasmas (phealthy aging. Thus, alpha-synuclein may be a novel biomarker of aging, a factor that should be considered when analyzing its presence in biological specimens.

  12. Increased intestinal permeability correlates with sigmoid mucosa alpha-synuclein staining and endotoxin exposure markers in early Parkinson's disease.

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    Christopher B Forsyth

    Full Text Available UNLABELLED: Parkinson's disease (PD is the second most common neurodegenerative disorder of aging. The pathological hallmark of PD is neuronal inclusions termed Lewy bodies whose main component is alpha-synuclein protein. The finding of these Lewy bodies in the intestinal enteric nerves led to the hypothesis that the intestine might be an early site of PD disease in response to an environmental toxin or pathogen. One potential mechanism for environmental toxin(s and proinflammatory luminal products to gain access to mucosal neuronal tissue and promote oxidative stress is compromised intestinal barrier integrity. However, the role of intestinal permeability in PD has never been tested. We hypothesized that PD subjects might exhibit increased intestinal permeability to proinflammatory bacterial products in the intestine. To test our hypothesis we evaluated intestinal permeability in subjects newly diagnosed with PD and compared their values to healthy subjects. In addition, we obtained intestinal biopsies from both groups and used immunohistochemistry to assess bacterial translocation, nitrotyrosine (oxidative stress, and alpha-synuclein. We also evaluated serum markers of endotoxin exposure including LPS binding protein (LBP. Our data show that our PD subjects exhibit significantly greater intestinal permeability (gut leakiness than controls. In addition, this intestinal hyperpermeability significantly correlated with increased intestinal mucosa staining for E. coli bacteria, nitrotyrosine, and alpha-synuclein as well as serum LBP levels in PD subjects. These data represent not only the first demonstration of abnormal intestinal permeability in PD subjects but also the first correlation of increased intestinal permeability in PD with intestinal alpha-synuclein (the hallmark of PD, as well as staining for gram negative bacteria and tissue oxidative stress. Our study may thus shed new light on PD pathogenesis as well as provide a new method for

  13. alpha-Synuclein enhances secretion and toxicity of amyloid beta peptides in PC12 cells

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    Kazmierczak, Anna; Strosznajder, Joanna B.; Adamczyk, Agata

    2008-01-01

    alpha-Synuclein is the fundamental component of Lewy bodies which occur in the brain of 60% of sporadic and familial Alzheimer's disease patients. Moreover, a proteolytic fragment of alpha-synuclein, the so-called non-amyloid component of Alzheimer's disease amyloid, was found to be an integral part

  14. Mutant and wild-type alpha-synuclein interact with mitochondrial cytochrome C oxidase.

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    Elkon, Hanock; Don, Jermy; Melamed, Eldad; Ziv, Ilan; Shirvan, Anat; Offen, Daniel

    2002-06-01

    Alpha-synuclein, a presynaptic protein, was found to be the major component in the Lewy bodies (LB) in both inherited and sporadic Parkinson's disease (PD). Furthermore, rare mutations of alpha-synuclein cause autosomal-dominant PD. However, it is unknown how alpha-synuclein is involved in the pathogenesis of nigral degeneration in PD. In this study, we examine the protein-protein interactions of wild-type and mutant (A53T) a-synuclein with adult human brain cDNA expression library using the yeast two-hybrid technique. We found that both normal and mutant alpha-synuclein specifically interact with the mitochondrial complex IV enzyme, cytochrome C oxidase (COX). Wild-type and mutant alpha-synuclein genes were further fused with c-Myc tag and translated in rabbit reticulocyte lysate. Using anti-c-Myc antibody, we demonstrated that both wild-type and mutant alpha-synuclein, coimmunoprecipitated with COX. We also showed that potassium cyanide, a selective COX inhibitor, synergistically enhanced the sensitivity of SH-SY5Y neuroblastoma cells to dopamine-induced cell death. In conclusion, we found specific protein-protein interactions of alpha-synuclein, a major LB protein, to COX, a key enzyme of the mithochondrial respiratory system. This interaction suggests that alpha-synuclein aggregation may contribute to enhance the mitochondrial dysfunction, which might be a key factor in the pathogenesis of PD.

  15. Increased CSF alpha-synuclein levels in Alzheimer's disease : Correlation with tau levels

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    Slaets, Sylvie; Vanmechelen, Eugeen; Le Bastard, Nathalie; Decraemer, Hilde; Vandijck, Manu; Martin, Jean-Jacques; De Deyn, Peter Paul; Engelborghs, Sebastiaan

    2014-01-01

    Background: Given the difficult clinical differential diagnosis between Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), growing interest resulted in research on alpha-synuclein as a potential cerebrospinal fluid biomarker (CSF) for synucleinopathies. Methods: CSF alpha-synuclein-140 co

  16. Exosomes of BV-2 cells induced by alpha-synuclein: important mediator of neurodegeneration in PD.

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    Chang, Chongwang; Lang, Hongjuan; Geng, Ning; Wang, Jing; Li, Nan; Wang, Xuelian

    2013-08-26

    Parkinson's disease (PD) is a progressive neurodegenerative disease. Alpha-synuclein aggregation, which can activate microglia to enhance its dopaminergic neurotoxicity, plays a central role in the progression of PD. However the mechanism is still unclear. To investigate how alpha-synuclein affects the neuron, exosomes were derived from alpha-synuclein treated mouse microglia cell line BV-2 cells by differential centrifugation and ultracentrifugation. We found that alpha-synuclein can induce an increase of exosomal secretion by microglia. These activated exosomes expressed a high level of MHC class II molecules and membrane TNF-α. In addition, the activated exosomes cause increased apoptosis. Exosomes secreted from activated microglias might be important mediator of alpha-synuclein-induced neurodegeneration in PD.

  17. Evidence for copper-dioxygen reactivity during alpha-synuclein fibril formation.

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    Lucas, Heather R; Debeer, Serena; Hong, Myoung-Soon; Lee, Jennifer C

    2010-05-19

    Alpha-synuclein (alpha-syn), a presynaptic protein implicated in Parkinson's disease, binds copper(II) ion (1:1) with submicromolar affinity in vitro. Insights on the molecular details of soluble- and fibrillar-Cu-alpha-syn are gained through X-ray absorption spectroscopy. Our results indicate that the copper coordination environment (3-to-4 N/O ligands, average Cu-ligand distance approximately 1.96 A) exhibits little structural rearrangement upon amyloid formation in spite of the overall polypeptide conformational change from disordered-to-beta-sheet. Interestingly, we find that some population of Cu(II)-alpha-syn reduces to Cu(I)-alpha-syn in the absence of O(2). This autoreduction event appears diminished in the presence of O(2) suggestive of preceding Cu(I)/O(2) chemistry. Evidence for generation of reactive oxygen species is obtained by the observation of new emission features attributed to dityrosine cross-links in fibrillar samples.

  18. Structure, function and toxicity of alpha-synuclein: the Bermuda triangle in synucleinopathies.

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    Villar-Piqué, Anna; Lopes da Fonseca, Tomás; Outeiro, Tiago Fleming

    2016-10-01

    Parkinson's disease belongs to a group of currently incurable neurodegenerative disorders characterized by the misfolding and accumulation of alpha-synuclein aggregates that are commonly known as synucleinopathies. Clinically, synucleinopathies are heterogeneous, reflecting the somewhat selective neuronal vulnerability characteristic of each disease. The precise molecular underpinnings of synucleinopathies remain unclear, but the process of aggregation of alpha-synuclein appears as a central event. However, there is still no consensus with respect to the toxic forms of alpha-synuclein, hampering our ability to use the protein as a target for therapeutic intervention. To decipher the molecular bases of synucleinopathies, it is essential to understand the complex triangle formed between the structure, function and toxicity of alpha-synuclein. Recently, important steps have been undertaken to elucidate the role of the protein in both physiological and pathological conditions. Here, we provide an overview of recent findings in the field of alpha-synuclein research, and put forward a new perspective over paradigms that persist in the field. Establishing whether alpha-synuclein has a causative role in all synucleinopathies will enable the identification of targets for the development of novel therapeutic strategies for this devastating group of disorders. Alpha-synuclein is the speculated cornerstone of several neurodegenerative disorders known as Synucleinopathies. Nevertheless, the mechanisms underlying the pathogenic effects of this protein remain unknown. Here, we review the recent findings in the three corners of alpha-synuclein biology - structure, function and toxicity - and discuss the enigmatic roads that have accompanied alpha-synuclein from the beginning. This article is part of a special issue on Parkinson disease.

  19. Differences in extinction of conditioned fear in C57BL/6 substrains are unrelated to expression of alpha-synuclein.

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    Siegmund, Anja; Langnaese, Kristina; Wotjak, Carsten T

    2005-02-28

    C57BL/6 mice are commonly used as background strains for genetically modified mice, and little attention is usually paid to the notification of the specific substrain. However, it is known that C57BL/6NCrl (B6N) and C57BL/6JOlaHsd (B6JOla) mice differ in the course of extinction of conditioned fear (Stiedl O, Radulovic J, Lohmann R, Birkenfeld K, Palve M, Kammermeier J, et al. Strain and substrain differences in context- and tone-dependent fear conditioning of inbred mice. Behav Brain Res 1999;104:1-12), as well as in the expression of alpha-synuclein (Specht CG, Schoepfer R. Deletion of the alpha-synuclein locus in a subpopulation of C57BL/6J inbred mice. BMC Neurosci 2001;2:11). We tested for a causal relationship between the two findings by employing B6N (expressing alpha-synuclein), B6JOla (not expressing alpha-syn) and the third strain C57BL/6JCrl (B6Jax, expressing alpha-syn). We show that alpha-syn does not account for differences in extinction in a fear conditioning task, as its expression did not covary with the decrease of freezing on repeated non-reinforced tone and context exposure in the three strains: B6Jax exhibited fastest extinction followed by B6JOla. In contrast, B6N showed persistent fear over the course of extinction training. The differences in extinction between B6JOla and B6N were unrelated to sensorimotor processing (pain threshold and basal tone reaction) and innate fear (light-dark test). However, B6Jax displayed less innate fear than B6JOla and B6N. Our results of marked differences in innate and conditioned fear in three B6 substrains illustrate the necessity of a strict adherence to an exact mouse strain nomenclature.

  20. Drift diffusion model of reward and punishment learning in rare alpha-synuclein gene carriers.

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    Moustafa, Ahmed A; Kéri, Szabolcs; Polner, Bertalan; White, Corey

    2017-03-20

    To understand the cognitive effects of alpha-synuclein polymorphism, we employed a drift diffusion model (DDM) to analyze reward- and punishment-guided probabilistic learning task data of participants with the rare alpha-synuclein gene duplication and age- and education-matched controls. Overall, the DDM analysis showed that, relative to controls, asymptomatic alpha-synuclein gene duplication carriers had significantly increased learning from negative feedback, while they tended to show impaired learning from positive feedback. No significant differences were found in response caution, response bias, or motor/encoding time. We here discuss the implications of these computational findings to the understanding of the neural mechanism of alpha-synuclein gene duplication.

  1. Testosterone regulates alpha-synuclein mRNA in the avian song system.

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    Hartman, V N; Miller, M A; Clayton, D F; Liu, W C; Kroodsma, D E; Brenowitz, E A

    2001-04-17

    Alpha-synuclein is a small, highly conserved protein in vertebrates that has been linked to several neurodegenerative diseases. The avian song control system is one of the model systems in which the protein was independently discovered. Alpha-synuclein is dynamically regulated in the song system during song learning, a process in which sex steroids play a central role. We compared alpha-synuclein mRNA expression in the brains of 12 adult male chipping sparrows (Spizella passerina) treated with either testosterone or blank s.c. implants. We saw pronounced upregulation of alpha-synuclein mRNA in, as well as an increase in the volume of, the song control nucleus area X in response to exogenous testosterone. To our knowledge this is the first report of steroid regulation of synuclein gene expression in any model system.

  2. DJ-1 and alpha-synuclein in human cerebrospinal fluid as biomarkers of Parkinson's disease.

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    Hong, Zhen; Shi, Min; Chung, Kathryn A; Quinn, Joseph F; Peskind, Elaine R; Galasko, Douglas; Jankovic, Joseph; Zabetian, Cyrus P; Leverenz, James B; Baird, Geoffrey; Montine, Thomas J; Hancock, Aneeka M; Hwang, Hyejin; Pan, Catherine; Bradner, Joshua; Kang, Un J; Jensen, Poul H; Zhang, Jing

    2010-03-01

    Biomarkers are urgently needed for the diagnosis and monitoring of disease progression in Parkinson's disease. Both DJ-1 and alpha-synuclein, two proteins critically involved in Parkinson's disease pathogenesis, have been tested as disease biomarkers in several recent studies with inconsistent results. These have been largely due to variation in the protein species detected by different antibodies, limited numbers of patients in some studies, or inadequate control of several important variables. In this study, the nature of DJ-1 and alpha-synuclein in human cerebrospinal fluid was studied by a combination of western blotting, gel filtration and mass spectrometry. Sensitive and quantitative Luminex assays detecting most, if not all, species of DJ-1 and alpha-synuclein in human cerebrospinal fluid were established. Cerebrospinal fluid concentrations of DJ-1 and alpha-synuclein from 117 patients with Parkinson's disease, 132 healthy individuals and 50 patients with Alzheimer's disease were analysed using newly developed, highly sensitive Luminex technology while controlling for several major confounders. A total of 299 individuals and 389 samples were analysed. The results showed that cerebrospinal fluid DJ-1 and alpha-synuclein levels were dependent on age and influenced by the extent of blood contamination in cerebrospinal fluid. Both DJ-1 and alpha-synuclein levels were decreased in Parkinson's patients versus controls or Alzheimer's patients when blood contamination was controlled for. In the population aged > or = 65 years, when cut-off values of 40 and 0.5 ng/ml were chosen for DJ-1 and alpha-synuclein, respectively, the sensitivity and specificity for patients with Parkinson's disease versus controls were 90 and 70% for DJ-1, and 92 and 58% for alpha-synuclein. A combination of the two markers did not enhance the test performance. There was no association between DJ-1 or alpha-synuclein and the severity of Parkinson's disease. Taken together, this represents

  3. C. elegans model identifies genetic modifiers of alpha-synuclein inclusion formation during aging.

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    Tjakko J van Ham

    2008-03-01

    Full Text Available Inclusions in the brain containing alpha-synuclein are the pathological hallmark of Parkinson's disease, but how these inclusions are formed and how this links to disease is poorly understood. We have developed a C. elegans model that makes it possible to monitor, in living animals, the formation of alpha-synuclein inclusions. In worms of old age, inclusions contain aggregated alpha- synuclein, resembling a critical pathological feature. We used genome-wide RNA interference to identify processes involved in inclusion formation, and identified 80 genes that, when knocked down, resulted in a premature increase in the number of inclusions. Quality control and vesicle-trafficking genes expressed in the ER/Golgi complex and vesicular compartments were overrepresented, indicating a specific role for these processes in alpha-synuclein inclusion formation. Suppressors include aging-associated genes, such as sir-2.1/SIRT1 and lagr-1/LASS2. Altogether, our data suggest a link between alpha-synuclein inclusion formation and cellular aging, likely through an endomembrane-related mechanism. The processes and genes identified here present a framework for further study of the disease mechanism and provide candidate susceptibility genes and drug targets for Parkinson's disease and other alpha-synuclein related disorders.

  4. Peculiarities of copper binding to alpha-synuclein.

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    Ahmad, Atta; Burns, Colin S; Fink, Anthony L; Uversky, Vladimir N

    2012-01-01

    Heavy metals have been implicated as the causative agents for the pathogenesis of the most prevalent neurodegenerative disease. Various mechanisms have been proposed to explain the toxic effects of metals ranging from metal-induced oxidation of protein to metal-induced changes in the protein conformation. Aggregation of a-synuclein is implicated in Parkinson's disease (PD), and various metals, including copper, constitute a prominent group of alpha-synuclein aggregation enhancers. In this study, we have systematically characterized the a-synuclein-Cu21 binding sites and analyzed the possible role of metal binding in a-synuclein fibrillation using a set of biophysical techniques, such as electron paramagnetic resonance (EPR), electron spin-echo envelope modulation (ESEEM), circular dichroism (CD), and size exclusion chromatography (SEC). Our analyses indicated that a-synuclein possesses at least two binding sites for Cu21. We have been able to locate one of the binding sites in the N-terminal region. Furthermore, based on the EPR studies of model peptides and Beta-synuclein, we concluded that the suspected His residue did not appear to participate in strong Cu21 binding.

  5. Impaired baroreflex function in mice overexpressing alpha-synuclein

    Directory of Open Access Journals (Sweden)

    Sheila eFleming

    2013-07-01

    Full Text Available Cardiovascular autonomic dysfunction, such as orthostatic hypotension consequent to baroreflex failure and cardiac sympathetic denervation, is frequently observed in the synucleinopathy Parkinson’s disease (PD. In the present study, the baroreceptor reflex was assessed in mice overexpressing human wildtype alpha-synuclein (Thy1-aSyn, a genetic mouse model of synucleinopathy. The beat-to-beat change in heart rate, computed from R-R interval, in relation to blood pressure was measured in anesthetized and conscious mice equipped with arterial blood pressure telemetry transducers during transient bouts of hypertension and hypotension. Compared to wildtype, tachycardia following nitroprusside-induced hypotension was significantly reduced in Thy1-aSyn mice. Thy1-aSyn mice also showed an abnormal cardiovascular response (i.e., diminished tachycardia to muscarinic blockade with atropine. We conclude that Thy1-aSyn mice have impaired basal and dynamic range of sympathetic and parasympathetic-mediated changes in heart rate and will be a useful model for long-term study of cardiovascular autonomic dysfunction associated with PD.

  6. Alpha-synuclein in motor neuron disease: an immunohistologic study.

    Science.gov (United States)

    Doherty, M J; Bird, T D; Leverenz, J B

    2004-02-01

    Alpha-synuclein (ASN) has been implicated in neurodegenerative disorders characterized by Lewy body inclusions such as Parkinson's disease and dementia with Lewy bodies. Lewy body-like inclusions have also been observed in spinal neurons of patients with amyotrophic lateral sclerosis (ALS) and reports suggest possible ASN abnormalities in ALS patients. We assessed ASN immunoreactivity in spinal and brain tissues of subjects who had died of progressive motor neuron disorders (MND). Clinical records of subjects with MND and a comparison group were reviewed to determine the diagnosis according to El-Escariol Criteria of ALS. Cervical, thoracic and lumbar cord sections were stained with an antibody to ASN. A blinded, semiquantitative review of sections from both groups included examination for evidence of spheroids, neuronal staining, cytoplasmic inclusions, anterior horn granules, white and gray matter glial staining, corticospinal tract axonal fiber and myelin changes. MND cases, including ALS and progressive muscular atrophy, displayed significantly increased ASN staining of spheroids ( Pgray and white matter ( P< or =0.05). Significant abnormal staining of corticospinal axon tract fibers and myelin was also observed ( P< or =0.05 and 0.01). Detection of possible ASN-positive neuronal inclusions did not differ between groups. Significant ASN abnormalities were observed in MND. These findings suggest a possible role for ASN in MND; however, the precise nature of this association is unclear.

  7. Copper binding regulates intracellular alpha-synuclein localisation, aggregation and toxicity.

    Science.gov (United States)

    Wang, Xiaoyan; Moualla, Dima; Wright, Josephine A; Brown, David R

    2010-05-01

    Alpha-synuclein is a natively unfolded protein that aggregates and forms inclusions that are associated with a range of diseases that include Parkinson's Disease and Dementia with Lewy Bodies. The mechanism behind the formation of these inclusions and their possible role in disease remains unclear. Alpha-synuclein has also been shown to bind metals including copper and iron. We used a cell culture model of alpha-synuclein aggregation to examine the relationship between metals and formation of aggregates of the protein. While the levels of iron appear to have no role in aggregate formation or localisation of the protein in cells, copper appears to be important for both aggregation and cellular localisation of alpha-synuclein. Reduction in cellular copper resulted in a great decrease in aggregate formation both in terms of large aggregates visible in cells and oligomers observed in western blot analysis of cell extracts. Reduction in copper also resulted in a change in localisation of the protein which became more intensely localised to the plasma membrane in medium with low copper. These changes were reversed when copper was restored to the cells. Mutants of the copper binding domains altered the response to copper. Deletion of either the N- or C-termini resulted in a loss of aggregation while deletion of the C-termini also resulted in a loss of membrane association. Increased expression of alpha-synuclein also increased cell sensitivity to the toxicity of copper. These results suggest that the potential pathological role of alpha-synuclein aggregates is dependent upon the copper binding capacity of the protein.

  8. Alpha-synuclein in peripheral tissues and body fluids as a biomarker for Parkinson's disease - a systematic review.

    Science.gov (United States)

    Malek, N; Swallow, D; Grosset, K A; Anichtchik, O; Spillantini, M; Grosset, D G

    2014-08-01

    Parkinson's disease (PD) is neuropathologically characterized as an alpha-synucleinopathy. Alpha-synuclein-containing inclusions are stained as Lewy bodies and Lewy neurites in the brain, which are the pathological hallmark of PD. However, alpha-synuclein-containing inclusions in PD are not restricted to the central nervous system, but are also found in peripheral tissues. Alpha-synuclein levels can also be measured in body fluids. The aim of this study was to conduct a systematic review of available evidence to determine the utility of alpha-synuclein as a peripheral biomarker of PD. We searched PubMed (1948 to 26 May 2013), Embase (1974 to 26 May 2013), the Cochrane Library (up to 26 May 2013), LILACS (up to 26 May 2013) and CINAHL (up to 26 May 2013) for the studies of alpha-synuclein in peripheral tissues or body fluids in PD. A total of 49 studies fulfilled the search criteria. Peripheral tissues such as colonic mucosa showed a sensitivity of 42-90% and a specificity of 100%; submandibular salivary glands showed sensitivity and specificity of 100%; skin biopsy showed 19% sensitivity and 80% specificity in detecting alpha-synuclein pathology. CSF alpha-synuclein had 71-94% sensitivity and 25-53% specificity for distinguishing PD from controls. Plasma alpha-synuclein had 48-53% sensitivity and 69-85% specificity. Neither plasma nor CSF alpha-synuclein is presently a reliable marker of PD. This differs from alpha-synuclein in solid tissue samples of the enteric and autonomic nervous system, which offer some potential as a surrogate marker of brain synucleinopathy.

  9. The Identification of Alpha-Synuclein as the First Parkinson Disease Gene

    Science.gov (United States)

    Nussbaum, Robert L.

    2017-01-01

    In this Commentary, I describe the events that led from an NINDS-sponsored Workshop on Parkinson Disease Research in 1995, where I was asked to speak about the genetics of Parkinson disease, to the identification a mere two years later of a mutation in alpha-synuclein as the cause of autosomal dominant Parkinson disease in the Contursi kindred. I review the steps we took to first map and then find the mutation in the alpha-synuclein locus and describe the obstacles and the role of serendipity in facilitating the work. Although alpha-synuclein mutations are a rare cause of hereditary PD, the importance of this finding goes far beyond the rare families with hereditary disease because it pinpointed alpha-synuclein as a key contributor to the far more common sporadic form of Parkinson disease. This work confirms William Harvey’s observation from 350 years ago that studying rarer forms of a disease is an excellent way to understand the more common forms of that disease. The identification of synuclein’s role in hereditary Parkinson disease has opened new avenues of research into the pathogenesis and potential treatments of the common form of Parkinson disease that affects many millions of Americans and tens of millions of human beings worldwide. PMID:28282812

  10. Increased frequency of alpha-synuclein in the substantia nigra in human immunodeficiency virus infection.

    Science.gov (United States)

    Khanlou, Negar; Moore, David J; Chana, Gursharan; Cherner, Mariana; Lazzaretto, Deborah; Dawes, Sharron; Grant, Igor; Masliah, Eliezer; Everall, Ian P

    2009-04-01

    The frequency of neurodegenerative markers among long surviving human immunodeficiency virus (HIV)-infected individuals is unknown, therefore, the present study investigated the frequency of alpha-synuclein, beta-amyloid, and HIV-associated brain pathology in the brains of older HIV-infected individuals. We examined the substantia nigra of 73 clinically well-characterized HIV-infected individuals aged 50 to 76 years from the National NeuroAIDS Tissue Consortium. We also examined the frontal and temporal cortical regions of a subset of 36 individuals. Neuritic alpha-synuclein expression was found in 16% (12/73) of the substantia nigra of the HIV+cases and none of the older control cases (0/18). beta-Amyloid deposits were prevalent and found in nearly all of the HIV+cases (35/36). Despite these increases of degenerative pathology, HIV-associated brain pathology was present in only 10% of cases. Among older HIV+adults, HIV-associated brain pathology does not appear elevated; however, the frequency of both alpha-synuclein and beta-amyloid is higher than that found in older healthy persons. The increased prevalence of alpha-synuclein and beta-amyloid in the brains of older HIV-infected individuals may predict an increased risk of developing neurodegenerative disease.

  11. Tri- and Pentamethine Cyanine Dyes for Fluorescent Detection of alpha-Synuclein Oligomeric Aggregates

    NARCIS (Netherlands)

    Kovalska, V.B.; Losytskyy, M.Y.; Tolmachev, O.I.; Slominskii, Y.L.; Segers-Nolten, G.M.; Subramaniam, V.; Yarmoluk, S.M.

    2012-01-01

    The pathogenesis of Parkinson's disease that is the second most common neurodegenerative disease is associated with formation of different aggregates of alpha-synuclein (ASN), namely oligomers and amyloid fibrils. Current research is aimed on the design of fluorescent dyes for the detection of oligo

  12. The Identification of Alpha-Synuclein as the First Parkinson Disease Gene.

    Science.gov (United States)

    Nussbaum, Robert L

    2017-01-01

    In this Commentary, I describe the events that led from an NINDS-sponsored Workshop on Parkinson Disease Research in 1995, where I was asked to speak about the genetics of Parkinson disease, to the identification a mere two years later of a mutation in alpha-synuclein as the cause of autosomal dominant Parkinson disease in the Contursi kindred. I review the steps we took to first map and then find the mutation in the alpha-synuclein locus and describe the obstacles and the role of serendipity in facilitating the work. Although alpha-synuclein mutations are a rare cause of hereditary PD, the importance of this finding goes far beyond the rare families with hereditary disease because it pinpointed alpha-synuclein as a key contributor to the far more common sporadic form of Parkinson disease. This work confirms William Harvey's observation from 350 years ago that studying rarer forms of a disease is an excellent way to understand the more common forms of that disease. The identification of synuclein's role in hereditary Parkinson disease has opened new avenues of research into the pathogenesis and potential treatments of the common form of Parkinson disease that affects many millions of Americans and tens of millions of human beings worldwide.

  13. CSF alpha-synuclein does not discriminate dementia with lewy bodies from Alzheimer's disease.

    NARCIS (Netherlands)

    Reesink, F.E.; Lemstra, A.W.; Dijk, K.D. van; Berendse, H.W.; Berg, W.D. van de; Klein, M.; Blankenstein, M.A.; Scheltens, P.; Verbeek, M.M.; Flier, W.M. van der

    2010-01-01

    In this study, we assessed whether cerebrospinal fluid (CSF) levels of the biomarker alpha-synuclein have a diagnostic value in differential diagnosis of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). We also analyzed associations between CSF biomarkers and cognitive performance in DL

  14. C-elegans model identifies genetic modifiers of alpha-synuclein inclusion formation during aging

    NARCIS (Netherlands)

    van Ham, Tjakko J.; Thijssen, Karen L.; Breitling, Rainer; Hofstra, Robert M. W.; Plasterk, Ronald H. A.; Nollen, Ellen A. A.

    2008-01-01

    Inclusions in the brain containing alpha-synuclein are the pathological hallmark of Parkinson's disease, but how these inclusions are formed and how this links to disease is poorly understood. We have developed a C. elegans model that makes it possible to monitor, in living animals, the formation of

  15. Trehalose does not improve neuronal survival on exposure to alpha-synuclein pre-formed fibrils

    Directory of Open Access Journals (Sweden)

    Matthew Redmann

    2017-04-01

    Full Text Available Parkinson's disease is a debilitating neurodegenerative disorder that is pathologically characterized by intracellular inclusions comprised primarily of alpha-synuclein (αSyn that can also be transmitted from neuron to neuron. Several lines of evidence suggest that these inclusions cause neurodegeneration. Thus exploring strategies to improve neuronal survival in neurons with αSyn aggregates is critical. Previously, exposure to αSyn pre-formed fibrils (PFFs has been shown to induce aggregation of endogenous αSyn resulting in cell death that is exacerbated by either starvation or inhibition of mTOR by rapamycin, both of which are able to induce autophagy, an intracellular protein degradation pathway. Since mTOR inhibition may also inhibit protein synthesis and starvation itself can be detrimental to neuronal survival, we investigated the effects of autophagy induction on neurons with αSyn inclusions by a starvation and mTOR-independent autophagy induction mechanism. We exposed mouse primary cortical neurons to PFFs to induce inclusion formation in the presence and absence of the disaccharide trehalose, which has been proposed to induce autophagy and stimulate lysosomal biogenesis. As expected, we observed that on exposure to PFFs, there was increased abundance of pS129-αSyn aggregates and cell death. Trehalose alone increased LC3-II levels, consistent with increased autophagosome levels that remained elevated with PFF exposure. Interestingly, trehalose alone increased cell viability over a 14-d time course. Trehalose was also able to restore cell viability to control levels, but PFFs still exhibited toxic effects on the cells. These data provide essential information regarding effects of trehalose on αSyn accumulation and neuronal survival on exposure to PFF.

  16. Copper(II) binding to alpha-synuclein, the Parkinson's protein.

    Science.gov (United States)

    Lee, Jennifer C; Gray, Harry B; Winkler, Jay R

    2008-06-04

    Variations in tryptophan fluorescence intensities confirm that copper(II) interacts with alpha-synuclein, a protein implicated in Parkinson's disease. Trp4 fluorescence decay kinetics measured for the F4W protein show that Cu(II) binds tightly (Kd 100 nM) near the N-terminus at pH 7. Work on a F4W/H50S mutant indicates that a histidine imidazole is not a ligand in this high-affinity site.

  17. The temporal expression pattern of alpha-synuclein modulates olfactory neurogenesis in transgenic mice.

    Directory of Open Access Journals (Sweden)

    Sebastian R Schreglmann

    Full Text Available Adult neurogenesis mirrors the brain´s endogenous capacity to generate new neurons throughout life. In the subventricular zone/ olfactory bulb system adult neurogenesis is linked to physiological olfactory function and has been shown to be impaired in murine models of neuronal alpha-Synuclein overexpression. We analyzed the degree and temporo-spatial dynamics of adult olfactory bulb neurogenesis in transgenic mice expressing human wild-type alpha-Synuclein (WTS under the murine Thy1 (mThy1 promoter, a model known to have a particularly high tg expression associated with impaired olfaction.Survival of newly generated neurons (NeuN-positive in the olfactory bulb was unchanged in mThy1 transgenic animals. Due to decreased dopaminergic differentiation a reduction in new dopaminergic neurons within the olfactory bulb glomerular layer was present. This is in contrast to our previously published data on transgenic animals that express WTS under the control of the human platelet-derived growth factor β (PDGF promoter, that display a widespread decrease in survival of newly generated neurons in regions of adult neurogenesis, resulting in a much more pronounced neurogenesis deficit. Temporal and quantitative expression analysis using immunofluorescence co-localization analysis and Western blots revealed that in comparison to PDGF transgenic animals, in mThy1 transgenic animals WTS is expressed from later stages of neuronal maturation only but at significantly higher levels both in the olfactory bulb and cortex.The dissociation between higher absolute expression levels of alpha-Synuclein but less severe impact on adult olfactory neurogenesis in mThy1 transgenic mice highlights the importance of temporal expression characteristics of alpha-Synuclein on the maturation of newborn neurons.

  18. Bioinorganic chemistry of copper coordination to alpha-synuclein: relevance to Parkinson's disease.

    OpenAIRE

    Binolfi, A.; L. Quintanar; Bertoncini, C.; Griesinger, C.; FERNANDEZ, C., LEOZ, J.

    2012-01-01

    Alpha-synuclein (AS) aggregation is associated with neurodegeneration in Parkinson'sdisease (PD). At the same time, alterations in metal ion homeostasis may play a pivotal role in the progression of AS amyloid assembly and the onset of PD. Elucidation of the structural basis directing AS–metal interactions and their effect on AS aggregation constitutes a key step toward understanding the role of metal ions in AS amyloid formation and neurodegeneration. This work provides a comprehensive revie...

  19. Granular assembly of alpha-synuclein leading to the accelerated amyloid fibril formation with shear stress.

    Science.gov (United States)

    Bhak, Ghibom; Lee, Jung-Ho; Hahn, Ji-Sook; Paik, Seung R

    2009-01-01

    alpha-Synuclein participates in the Lewy body formation of Parkinson's disease. Elucidation of the underlying molecular mechanism of the amyloid fibril formation is crucial not only to develop a controlling strategy toward the disease, but also to apply the protein fibrils for future biotechnology. Discernable homogeneous granules of alpha-synuclein composed of approximately 11 monomers in average were isolated in the middle of a lag phase during the in vitro fibrillation process. They were demonstrated to experience almost instantaneous fibrillation during a single 12-min centrifugal membrane-filtration at 14,000 x g. The granular assembly leading to the drastically accelerated fibril formation was demonstrated to be a result of the physical influence of shear force imposed on the preformed granular structures by either centrifugal filtration or rheometer. Structural rearrangement of the preformed oligomomeric structures is attributable for the suprastructure formation in which the granules act as a growing unit for the fibril formation. To parallel the prevailing notion of nucleation-dependent amyloidosis, we propose a double-concerted fibrillation model as one of the mechanisms to explain the in vitro fibrillation of alpha-synuclein, in which two consecutive concerted associations of monomers and subsequent oligomeric granular species are responsible for the eventual amyloid fibril formation.

  20. Granular assembly of alpha-synuclein leading to the accelerated amyloid fibril formation with shear stress.

    Directory of Open Access Journals (Sweden)

    Ghibom Bhak

    Full Text Available alpha-Synuclein participates in the Lewy body formation of Parkinson's disease. Elucidation of the underlying molecular mechanism of the amyloid fibril formation is crucial not only to develop a controlling strategy toward the disease, but also to apply the protein fibrils for future biotechnology. Discernable homogeneous granules of alpha-synuclein composed of approximately 11 monomers in average were isolated in the middle of a lag phase during the in vitro fibrillation process. They were demonstrated to experience almost instantaneous fibrillation during a single 12-min centrifugal membrane-filtration at 14,000 x g. The granular assembly leading to the drastically accelerated fibril formation was demonstrated to be a result of the physical influence of shear force imposed on the preformed granular structures by either centrifugal filtration or rheometer. Structural rearrangement of the preformed oligomomeric structures is attributable for the suprastructure formation in which the granules act as a growing unit for the fibril formation. To parallel the prevailing notion of nucleation-dependent amyloidosis, we propose a double-concerted fibrillation model as one of the mechanisms to explain the in vitro fibrillation of alpha-synuclein, in which two consecutive concerted associations of monomers and subsequent oligomeric granular species are responsible for the eventual amyloid fibril formation.

  1. The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia.

    Science.gov (United States)

    Zarranz, Juan J; Alegre, Javier; Gómez-Esteban, Juan C; Lezcano, Elena; Ros, Raquel; Ampuero, Israel; Vidal, Lídice; Hoenicka, Janet; Rodriguez, Olga; Atarés, Begoña; Llorens, Verónica; Gomez Tortosa, Estrella; del Ser, Teodoro; Muñoz, David G; de Yebenes, Justo G

    2004-02-01

    Familial parkinsonism and dementia with cortical and subcortical Lewy bodies is uncommon, and no genetic defect has been reported in the previously described sibships. We present a Spanish family with autosomal dominant parkinsonism, dementia, and visual hallucinations of variable severity. The postmortem examination showed atrophy of the substantia nigra, lack of Alzheimer pathology, and numerous Lewy bodies which were immunoreactive to alpha-synuclein and ubiquitin in cortical and subcortical areas. Sequencing of the alpha-synuclein gene showed a novel, nonconservative E46K mutation in heterozygosis. The E46K mutation was present in all affected family members and in three young asymptomatic subjects, but it was absent in healthy and pathological controls. The novel mutation, that substitutes a dicarboxylic amino acid, glutamic acid, with a basic amino acid such as lysine in a much conserved area of the protein, is likely to produce severe disturbance of protein function. Our data show that, in addition to the previously described hereditary alpha-synucleinopathies, dementia with Lewy bodies is related to mutation of alpha-synuclein.

  2. More than just two peas in a pod: common amyloidogenic properties of tau and alpha-synuclein in neurodegenerative diseases.

    Science.gov (United States)

    Lee, Virginia M-Y; Giasson, Benoit I; Trojanowski, John Q

    2004-03-01

    Intracytoplasmic filamentous aggregates, such as neurofibrillary tangles in Alzheimer's disease and Lewy bodies in Parkinson's disease, are composed of the proteins tau and alpha-synuclein, respectively. These pathological inclusions are linked directly to the etiology and mechanisms of disease in a wide spectrum of neurodegenerative disorders, termed 'tauopathies' and 'synucleinopathies'. Emerging evidence indicates that there is frequent overlap of the pathological and clinical features of patients with tauopathies and synucleinopathies, thereby re-enforcing the notion that these disorders might be linked mechanistically. Indeed, several lines of investigation suggest that tau and alpha-synuclein might constitute a unique class of unstructured proteins that assemble predominantly into homopolymeric (rather than heteropolymeric) fibrils, which deposit mainly in separate amyloid inclusions, but occasionally deposit together. Thus, the ability of tau and alpha-synuclein to affect each other directly or indirectly might contribute to the overlap in the clinical and pathological features of tauopathies and synucleinopathies.

  3. Identification of the minimal copper(II)-binding alpha-synuclein sequence.

    Science.gov (United States)

    Jackson, Mark S; Lee, Jennifer C

    2009-10-05

    Parkinson's disease has been long linked to environmental factors, such as transition metals and recently to alpha-synuclein, a presynaptic protein. Using tryptophan-containing peptides, we identified the minimal Cu(II)-binding sequence to be within the first four residues, MDV(F/W), anchored by the alpha-amino terminus. In addition, mutant peptide 1-10 (Lys --> Arg) verified that neither Lys6 nor Lys10 are necessary for Cu(II) binding. Interestingly, Trp4 excited-state decay kinetics measured for peptides and proteins reveal two quenching modes, possibly arising from two distinct Cu(II)-polypeptide structures.

  4. Novel Epigenetic Regulation of Alpha-Synuclein Expression in Down Syndrome.

    Science.gov (United States)

    Ramakrishna, Narayan; Meeker, Harry C; Brown, W Ted

    2016-01-01

    Alpha-synuclein (SNCA), a presynaptic protein, is significantly reduced in individuals with Down syndrome (DS) and Ts65Dn mice, a mouse model of DS. Methylation analyses of promoter proximal CpG sites indicate similar reduction in Ts65Dn mice compared to control mice. Epigallocatechin-3-gallate (EGCG), a polyphenolic catechin present in green tea extract, increases methylation of SNCA promoter proximal CpG sites and expression in Ts65Dn mice. These results suggest a positive link between CpG methylation and SNCA expression in Down syndrome.

  5. Specific fluorescent detection of fibrillar alpha-synuclein using mono- and trimethine cyanine dyes.

    Science.gov (United States)

    Volkova, K D; Kovalska, V B; Balanda, A O; Losytskyy, M Yu; Golub, A G; Vermeij, R J; Subramaniam, V; Tolmachev, O I; Yarmoluk, S M

    2008-02-01

    With the aim of searching of novel amyloid-specific fluorescent probes the ability of series of mono- and trimethine cyanines based on benzothiazole, pyridine and quinoline heterocycle end groups to recognize fibrillar formations of alpha-synuclein (ASN) was studied. For the first time it was revealed that monomethine cyanines can specifically increase their fluorescence in aggregated ASN presence. Dialkylamino-substituted monomethine cyanine T-284 and meso-ethyl-substituted trimethine cyanine SH-516 demonstrated the higher emission intensity and selectivity to aggregated ASN than classic amyloid stain Thioflavin T, and could be proposed as novel efficient fluorescent probes for fibrillar ASN detection. Studies of structure-function dependences have shown that incorporation of amino- or diethylamino- substituents into the 6-position of the benzothiazole heterocycle yields in a appearance of a selective fluorescent response to fibrillar alpha-synuclein presence. Performed calculations of molecular dimensions of studied cyanine dyes gave us the possibility to presume, that dyes bind with their long axes parallel to the fibril axis via insertion into the neat rows (so called 'channels') running along fibril.

  6. Single-molecule FRET studies on alpha-synuclein oligomerization of Parkinson’s disease genetically related mutants

    Science.gov (United States)

    Tosatto, Laura; Horrocks, Mathew H.; Dear, Alexander J.; Knowles, Tuomas P. J.; Dalla Serra, Mauro; Cremades, Nunilo; Dobson, Christopher M.; Klenerman, David

    2015-11-01

    Oligomers of alpha-synuclein are toxic to cells and have been proposed to play a key role in the etiopathogenesis of Parkinson’s disease. As certain missense mutations in the gene encoding for alpha-synuclein induce early-onset forms of the disease, it has been suggested that these variants might have an inherent tendency to produce high concentrations of oligomers during aggregation, although a direct experimental evidence for this is still missing. We used single-molecule Förster Resonance Energy Transfer to visualize directly the protein self-assembly process by wild-type alpha-synuclein and A53T, A30P and E46K mutants and to compare the structural properties of the ensemble of oligomers generated. We found that the kinetics of oligomer formation correlates with the natural tendency of each variant to acquire beta-sheet structure. Moreover, A53T and A30P showed significant differences in the averaged FRET efficiency of one of the two types of oligomers formed compared to the wild-type oligomers, indicating possible structural variety among the ensemble of species generated. Importantly, we found similar concentrations of oligomers during the lag-phase of the aggregation of wild-type and mutated alpha-synuclein, suggesting that the properties of the ensemble of oligomers generated during self-assembly might be more relevant than their absolute concentration for triggering neurodegeneration.

  7. Mapping the subcellular distribution of alpha-synuclein in neurons using genetically encoded probes for correlated light and electron microscopy: Implications for Parkinson’s disease pathogenesis

    Science.gov (United States)

    Boassa, D.; Berlanga, M.L.; Yang, M.-L.; Terada, M.; Hu, J.; Bushong, E.A.; Hwang, M.; Masliah, E.; George, J.M.; Ellisman, M.H.

    2013-01-01

    Modifications to the gene encoding human alpha-synuclein have been linked to development of Parkinson’s disease. The highly conserved structure of alpha-synuclein suggests a functional interaction with membranes, and several lines of evidence point to a role in vesicle-related processes within nerve terminals. Using recombinant fusions of human alpha-synuclein including new genetic tags developed for correlated LM and EM (the tetracysteine-biarsenical labeling system or the new fluorescent protein for EM, MiniSOG), we determined the distribution of alpha-synuclein when over-expressed in primary neurons at supramolecular and cellular scales, in three dimensions (3D). We observed specific association of alpha-synuclein with a large and otherwise poorly characterized membranous organelle system of the presynaptic terminal, as well as with smaller vesicular structures within these boutons. Furthermore, alpha-synuclein was localized to multiple elements of the protein degradation pathway, including multivesicular bodies in the axons and lysosomes within neuronal cell bodies. Examination of synapses in brains of transgenic mice over-expressing human alpha-synuclein revealed alterations of the presynaptic endomembrane systems similar to our findings in cell culture. 3D electron tomographic analysis of enlarged presynaptic terminals in several brain areas revealed that these terminals were filled with membrane-bounded organelles, including tubulo-vesicular structures similar to what observed in vitro. We propose that alpha-synuclein over-expression is associated with hypertrophy of membrane systems of the presynaptic terminal previously shown to have a role in vesicle recycling. Our data support the conclusion that alpha- synuclein is involved in processes associated with the sorting, channeling, packaging and transport of synaptic material destined for degradation. PMID:23392688

  8. Conformational equilibria in monomeric alpha-synuclein at the single molecule level

    CERN Document Server

    Sandal, Massimo; Tessari, Isabella; Mammi, Stefano; Bergantino, Elisabetta; Musiani, Francesco; Brucale, Marco; Bubacco, Luigi; Samori', Bruno

    2007-01-01

    Natively unstructured proteins defy the classical "one sequence-one structure" paradigm of protein science. Monomers of these proteins in pathological conditions can aggregate in the cell, a process that underlies socially relevant neurodegenerative diseases such as Alzheimer and Parkinson. A full comprehension of the formation and structure of the so-called misfolded intermediates from which the aggregated states ensue is still lacking. We characterized the folding and the conformational diversity of alpha-synuclein (aSyn), a natively unstructured protein involved in Parkinson disease, by mechanically stretching single molecules of this protein and recording their mechanical properties. These experiments permitted us to directly observe directly and quantify three main classes of conformations that, under in vitro physiological conditions, exist simultaneously in the aSyn sample, including disordered and "beta-like" structures. We found that this class of "beta-like" structures is directly related to aSyn ag...

  9. Alpha-synuclein gene ablation increases docosahexaenoic acid incorporation and turnover in brain phospholipids

    DEFF Research Database (Denmark)

    Golovko, Mikhail Y; Rosenberger, Thad A; Feddersen, Søren;

    2007-01-01

    Previously, we demonstrated that ablation of alpha-synuclein (Snca) reduces arachidonate (20:4n-6) turnover in brain phospholipids through modulation of an endoplasmic reticulum-localized acyl-CoA synthetase (Acsl). The effect of Snca ablation on docosahexaenoic acid (22:6n-3) metabolism is unknown....... In the present study, we examined the effect of Snca gene ablation on brain 22:6n-3 metabolism. We determined 22:6n-3 uptake and incorporation into brain phospholipids by infusing awake, wild-type and Snca-/- mice with [1-14C]22:6n-3 using steady-state kinetic modeling. In addition, because Snca modulates 20:4n...

  10. CpG demethylation enhances alpha-synuclein expression and affects the pathogenesis of Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Lumine Matsumoto

    Full Text Available BACKGROUND: Alpha-synuclein (SNCA gene expression is an important factor in the pathogenesis of Parkinson's disease (PD. Gene multiplication can cause inherited PD, and promoter polymorphisms that increase SNCA expression are associated with sporadic PD. CpG methylation in the promoter region may also influence SNCA expression. METHODOLOGY/PRINCIPAL FINDINGS: By using cultured cells, we identified a region of the SNCA CpG island in which the methylation status altered along with increased SNCA expression. Postmortem brain analysis revealed regional non-specific methylation differences in this CpG region in the anterior cingulate and putamen among controls and PD; however, in the substantia nigra of PD, methylation was significantly decreased. CONCLUSIONS/SIGNIFICANCE: This CpG region may function as an intronic regulatory element for SNCA gene. Our findings suggest that a novel epigenetic regulatory mechanism controlling SNCA expression influences PD pathogenesis.

  11. Domain a' of protein disulfide isomerase plays key role in inhibiting alpha-synuclein fibril formation.

    Science.gov (United States)

    Cheng, Han; Wang, Lei; Wang, Chih-chen

    2010-07-01

    alpha-Synuclein (alpha Syn) is the main component of Lewy bodies formed in midbrain dopaminergic neurons which is a pathological characteristic of Parkinson's disease. It has been recently showed to induce endoplasmic reticulum (ER) stress and impair ER functions. However, the mechanism of how ER responds to alpha Syn toxicity is poorly understood. In the present study, we found that protein disulfide isomerase (PDI), a stress protein abundant in ER, effectively inhibits alpha Syn fibril formation in vitro. In PDI molecule with a structure of abb'xa'c, domain a' was found to be essential and sufficient for PDI to inhibit alpha Syn fibril formation. PDI was further found to be more avid for binding with intermediate species formed during alpha Syn fibril formation, and the binding was more intensive in the later lag phase. Our results provide new insight into the role of PDI in protecting ER from the deleterious effects of misfolded protein accumulation in many neurodegenerative diseases.

  12. Abnormal colonic motility in mice overexpressing human wild-type alpha-synuclein.

    Science.gov (United States)

    Wang, Lixin; Fleming, Sheila M; Chesselet, Marie-Françoise; Taché, Yvette

    2008-05-28

    The presynaptic protein alpha-synuclein (alphaSyn) has been implicated in both familial and sporadic forms of Parkinson's disease. We examined whether human alphaSyn-overexpressing mice under Thy1 promoter (Thy1-alphaSyn) display alterations of colonic function. Basal fecal output was decreased in Thy1-alphaSyn mice fed ad libitum. Fasted/refed Thy1-alphaSyn mice had a slower distal colonic transit than the wild-type mice, as monitored by 2.2-fold increase in time to expel an intracolonic bead and 2.9-fold higher colonic fecal content. By contrast, Thy1-alphaSyn mice had an increased fecal response to novelty stress and corticotropin releasing factor injected intraperipherally. These results indicate that Thy1-alphaSyn mice display altered basal and stress-stimulated propulsive colonic motility and will be a useful model to study gut dysfunction associated with Parkinson's disease.

  13. Elevated alpha-synuclein impairs innate immune cell function and provides a potential peripheral biomarker for Parkinson's disease.

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    Shyra J Gardai

    Full Text Available Alpha-synuclein protein is strongly implicated in the pathogenesis Parkinson's disease. Increased expression of α-synuclein due to genetic multiplication or point mutations leads to early onset disease. While α-synuclein is known to modulate membrane vesicle dynamics, it is not clear if this activity is involved in the pathogenic process or if measurable physiological effects of α-synuclein over-expression or mutation exist in vivo. Macrophages and microglia isolated from BAC α-synuclein transgenic mice, which overexpress α-synuclein under regulation of its own promoter, express α-synuclein and exhibit impaired cytokine release and phagocytosis. These processes were affected in vivo as well, both in peritoneal macrophages and microglia in the CNS. Extending these findings to humans, we found similar results with monocytes and fibroblasts isolated from idiopathic or familial Parkinson's disease patients compared to age-matched controls. In summary, this paper provides 1 a new animal model to measure α-synuclein dysfunction; 2 a cellular system to measure synchronized mobilization of α-synuclein and its functional interactions; 3 observations regarding a potential role for innate immune cell function in the development and progression of Parkinson's disease and other human synucleinopathies; 4 putative peripheral biomarkers to study and track these processes in human subjects. While altered neuronal function is a primary issue in PD, the widespread consequence of abnormal α-synuclein expression in other cell types, including immune cells, could play an important role in the neurodegenerative progression of PD and other synucleinopathies. Moreover, increased α-synuclein and altered phagocytosis may provide a useful biomarker for human PD.

  14. Rab1A over-expression prevents Golgi apparatus fragmentation and partially corrects motor deficits in an alpha-synuclein based rat model of Parkinson's disease.

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    Coune, P G; Bensadoun, J C; Aebischer, P; Schneider, B L

    2011-01-01

    Although the overabundance of human alpha-synuclein in nigral dopaminergic neurons is considered to play a pathogenic role in Parkinson's disease (PD), it remains unclear how alpha-synuclein leads to neuronal degeneration and motor symptoms. Here, we explored the effect of human alpha-synuclein in the rat substantia nigra following AAV-mediated gene delivery inducing a moderate loss of dopaminergic neurons together with motor impairments. A significant fraction of the surviving nigral neurons were found to express human αSyn and displayed a pathological fragmentation of the Golgi apparatus. This observation prompted further investigation on the role of the secretory pathway, in particular at the ER/Golgi level, in alpha-synuclein toxicity. To address this question, we co-expressed human alpha-synuclein with Rab1A, a regulator of ER-to-Golgi vesicular trafficking, and found a significant reduction of Golgi fragmentation. Rab1A did not protect the dopaminergic neurons from the alpha-synuclein-induced degeneration that occurred within several months following vector injection. However, we observed in animals co-expressing Rab1A an improvement of motor behavior that correlates with the rescue of normal Golgi morphology in alpha-synuclein-expressing dopaminergic neurons. The non-prenylable mutant Rab1A-DeltaCC did not produce any of the effects observed with the wild-type form of Rab1A, linking the protective role of Rab1A with its activity in ER-to-Golgi vesicular trafficking. In conclusion, Rab1A can rescue the Golgi fragmentation caused by the overabundance of alpha-synuclein in nigral dopaminergic neurons, improving the ability of the surviving neurons to control motor function in hemiparkinsonian animals.

  15. A Swedish family with de novo alpha-synuclein A53T mutation: evidence for early cortical dysfunction

    DEFF Research Database (Denmark)

    Puschmann, Andreas; Ross, Owen A; Vilariño-Güell, Carles;

    2009-01-01

    A de novo alpha-synuclein A53T (p.Ala53 Th; c.209G > A) mutation has been identified in a Swedish family with autosomal dominant Parkinson's disease (PD). Two affected individuals had early-onset (before 31 and 40 years), severe levodopa-responsive PD with prominent dysphasia, dysarthria, and cog......A de novo alpha-synuclein A53T (p.Ala53 Th; c.209G > A) mutation has been identified in a Swedish family with autosomal dominant Parkinson's disease (PD). Two affected individuals had early-onset (before 31 and 40 years), severe levodopa-responsive PD with prominent dysphasia, dysarthria......, and cognitive decline. Longitudinal clinical follow-up, EEG, SPECT and CSF biomarker examinations suggested an underlying encephalopathy with cortical involvement. The mutated allele (c.209A) was present within a haplotype different from that shared among mutation carriers in the Italian (Contursi...

  16. Concentration dependence of alpha-synuclein fibril length assessed by quantitative atomic force microscopy and statistical-mechanical theory.

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    van Raaij, Martijn E; van Gestel, Jeroen; Segers-Nolten, Ine M J; de Leeuw, Simon W; Subramaniam, Vinod

    2008-11-15

    The initial concentration of monomeric amyloidogenic proteins is a crucial factor in the in vitro formation of amyloid fibrils. We use quantitative atomic force microscopy to study the effect of the initial concentration of human alpha-synuclein on the mean length of mature alpha-synuclein fibrils, which are associated with Parkinson's disease. We determine that the critical initial concentration, below which low-molecular-weight species dominate and above which fibrils are the dominant species, lies at approximately 15 muM, in good agreement with earlier measurements using biochemical methods. In the concentration regime where fibrils dominate, we find that their mean length increases with initial concentration. These results correspond well to the qualitative predictions of a recent statistical-mechanical model of amyloid fibril formation. In addition, good quantitative agreement of the statistical-mechanical model with the measured mean fibril length as a function of initial protein concentration, as well as with the fibril length distributions for several protein concentrations, is found for reasonable values of the relevant model parameters. The comparison between theory and experiment yields, for the first time to our knowledge, an estimate of the magnitude of the free energies associated with the intermolecular interactions that govern alpha-synuclein fibril formation.

  17. Oxidative stress-induced posttranslational modifications of alpha-synuclein: specific modification of alpha-synuclein by 4-hydroxy-2-nonenal increases dopaminergic toxicity.

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    Xiang, Wei; Schlachetzki, Johannes C M; Helling, Stefan; Bussmann, Julia C; Berlinghof, Marvin; Schäffer, Tilman E; Marcus, Katrin; Winkler, Jürgen; Klucken, Jochen; Becker, Cord-Michael

    2013-05-01

    Aggregation and neurotoxicity of misfolded alpha-synuclein (αSyn) are crucial mechanisms for progressive dopaminergic neurodegeneration associated with Parkinson's disease (PD). Posttranslational modifications (PTMs) of αSyn caused by oxidative stress, including modification by 4-hydroxy-2-nonenal (HNE-αSyn), nitration (n-αSyn), and oxidation (o-αSyn), have been implicated to promote oligomerization of αSyn. However, it is yet unclear if these PTMs lead to different types of oligomeric intermediates. Moreover, little is known about which PTM-derived αSyn species exerts toxicity to dopaminergic cells. In this study, we directly compared aggregation characteristics of HNE-αSyn, n-αSyn, and o-αSyn. Generally, all of them promoted αSyn oligomerization. Particularly, HNE-αSyn and n-αSyn were more prone to forming oligomers than unmodified αSyn. Moreover, these PTMs prevented the formation of amyloid-like fibrils, although HNE-αSyn and o-αSyn were able to generate protofibrillar structures. The cellular effects associated with distinct PTMs were studied by exposing modified αSyn to dopaminergic Lund human mesencephalic (LUHMES) neurons. The cellular toxicity of HNE-αSyn was significantly higher than other PTM species. Furthermore, we tested the toxicity of HNE-αSyn in dopaminergic LUHMES cells and other cell types with low tyrosine hydroxylase (TH) expression, and additionally analyzed the loss of TH-immunoreactive cells in HNE-αSyn-treated LUHMES cells. We observed a selective toxicity of HNE-αSyn to neurons with higher TH expression. Further mechanistic studies showed that HNE-modification apparently increased the interaction of extracellular αSyn with neurons. Moreover, exposure of differentiated LUHMES cells to HNE-αSyn triggered the production of intracellular reactive oxygen species, preceding neuronal cell death. Antioxidant treatment effectively protected cells from the damage triggered by HNE-αSyn. Our findings suggest a specific

  18. Features of alpha-synuclein that could explain the progression and irreversibility of Parkinson's disease

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    Scarlet eGallegos

    2015-03-01

    Full Text Available Alpha-synuclein is a presynaptic protein expressed throughout the central nervous system, and it is the main component of Lewy bodies, one of the histopathological features of Parkinson’s disease (PD which is a progressive and irreversible neurodegenerative disorder. The conformational flexibility of α-synuclein allows it to adopt different conformations, i.e. bound to membranes or form aggregates, the oligomers are believed to be the more toxic species. In this review, we will focus on two major features of α-synuclein, transmission and toxicity that could help to understand the pathological characteristics of PD. One important feature of α-synuclein is its ability to be transmitted from neuron to neuron using mechanisms such as endocytosis, plasma membrane penetration or through exosomes, thus propagating the Lewy body pathology to different brain regions thereby contributing to the progressiveness of PD. The second feature of α-synuclein is that it confers cytotoxicity to recipient cells, principally when it is in an oligomeric state. This form causes mitochondrial dysfunction, endoplasmic reticulum stress, oxidative stress, proteasome impairment, disruption of plasma membrane and pore formation, and lead to apoptosis pathway activation and consequent cell death. The complexity of α-synuclein oligomerization and formation of toxic species could be a major factor for the irreversibility of PD and could also explain the lack of successful therapies to halt the disease.

  19. Exogenous Alpha-Synuclein Alters Pre- and Post-Synaptic Activity by Fragmenting Lipid Rafts

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    Marco Emanuele

    2016-05-01

    Full Text Available Alpha-synuclein (αSyn interferes with multiple steps of synaptic activity at pre-and post-synaptic terminals, however the mechanism/s by which αSyn alters neurotransmitter release and synaptic potentiation is unclear. By atomic force microscopy we show that human αSyn, when incubated with reconstituted membrane bilayer, induces lipid rafts' fragmentation. As a consequence, ion channels and receptors are displaced from lipid rafts with consequent changes in their activity. The enhanced calcium entry leads to acute mobilization of synaptic vesicles, and exhaustion of neurotransmission at later stages. At the post-synaptic terminal, an acute increase in glutamatergic transmission, with increased density of PSD-95 puncta, is followed by disruption of the interaction between N-methyl-d-aspartate receptor (NMDAR and PSD-95 with ensuing decrease of long term potentiation. While cholesterol loading prevents the acute effect of αSyn at the presynapse; inhibition of casein kinase 2, which appears activated by reduction of cholesterol, restores the correct localization and clustering of NMDARs.

  20. Arachidonic acid mediates the formation of abundant alpha-helical multimers of alpha-synuclein

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    Iljina, Marija; Tosatto, Laura; Choi, Minee L.; Sang, Jason C.; Ye, Yu; Hughes, Craig D.; Bryant, Clare E.; Gandhi, Sonia; Klenerman, David

    2016-09-01

    The protein alpha-synuclein (αS) self-assembles into toxic beta-sheet aggregates in Parkinson’s disease, while it is proposed that αS forms soluble alpha-helical multimers in healthy neurons. Here, we have made αS multimers in vitro using arachidonic acid (ARA), one of the most abundant fatty acids in the brain, and characterized them by a combination of bulk experiments and single-molecule Fӧrster resonance energy transfer (sm-FRET) measurements. The data suggest that ARA-induced oligomers are alpha-helical, resistant to fibril formation, more prone to disaggregation, enzymatic digestion and degradation by the 26S proteasome, and lead to lower neuronal damage and reduced activation of microglia compared to the oligomers formed in the absence of ARA. These multimers can be formed at physiologically-relevant concentrations, and pathological mutants of αS form less multimers than wild-type αS. Our work provides strong biophysical evidence for the formation of alpha-helical multimers of αS in the presence of a biologically relevant fatty acid, which may have a protective role with respect to the generation of beta-sheet toxic structures during αS fibrillation.

  1. High-Throughput Screening Methodology to Identify Alpha-Synuclein Aggregation Inhibitors.

    Science.gov (United States)

    Pujols, Jordi; Peña-Díaz, Samuel; Conde-Giménez, María; Pinheiro, Francisca; Navarro, Susanna; Sancho, Javier; Ventura, Salvador

    2017-03-02

    An increasing number of neurodegenerative diseases are being found to be associated with the abnormal accumulation of aggregated proteins in the brain. In Parkinson's disease, this process involves the aggregation of alpha-synuclein (α-syn) into intraneuronal inclusions. Thus, compounds that inhibit α-syn aggregation represent a promising therapeutic strategy as disease-modifying agents for neurodegeneration. The formation of α-syn amyloid aggregates can be reproduced in vitro by incubation of the recombinant protein. However, the in vitro aggregation of α-syn is exceedingly slow and highly irreproducible, therefore precluding fast high throughput anti-aggregation drug screening. Here, we present a simple and easy-to-implement in-plate method for screening large chemical libraries in the search for α-syn aggregation modulators. It allows us to monitor aggregation kinetics with high reproducibility, while being faster and requiring lower protein amounts than conventional aggregation assays. We illustrate how the approach enables the identification of strong aggregation inhibitors in a library of more than 14,000 compounds.

  2. Network Analysis Implicates Alpha-Synuclein (Snca) in the Regulation of Ovariectomy-Induced Bone Loss

    Science.gov (United States)

    Calabrese, Gina; Mesner, Larry D.; Foley, Patricia L.; Rosen, Clifford J.; Farber, Charles R.

    2016-01-01

    The postmenopausal period in women is associated with decreased circulating estrogen levels, which accelerate bone loss and increase the risk of fracture. Here, we gained novel insight into the molecular mechanisms mediating bone loss in ovariectomized (OVX) mice, a model of human menopause, using co-expression network analysis. Specifically, we generated a co-expression network consisting of 53 gene modules using expression profiles from intact and OVX mice from a panel of inbred strains. The expression of four modules was altered by OVX, including module 23 whose expression was decreased by OVX across all strains. Module 23 was enriched for genes involved in the response to oxidative stress, a process known to be involved in OVX-induced bone loss. Additionally, module 23 homologs were co-expressed in human bone marrow. Alpha synuclein (Snca) was one of the most highly connected “hub” genes in module 23. We characterized mice deficient in Snca and observed a 40% reduction in OVX-induced bone loss. Furthermore, protection was associated with the altered expression of specific network modules, including module 23. In summary, the results of this study suggest that Snca regulates bone network homeostasis and ovariectomy-induced bone loss. PMID:27378017

  3. Exogenous Alpha-Synuclein Alters Pre- and Post-Synaptic Activity by Fragmenting Lipid Rafts.

    Science.gov (United States)

    Emanuele, Marco; Esposito, Alessandro; Camerini, Serena; Antonucci, Flavia; Ferrara, Silvia; Seghezza, Silvia; Catelani, Tiziano; Crescenzi, Marco; Marotta, Roberto; Canale, Claudio; Matteoli, Michela; Menna, Elisabetta; Chieregatti, Evelina

    2016-05-01

    Alpha-synuclein (αSyn) interferes with multiple steps of synaptic activity at pre-and post-synaptic terminals, however the mechanism/s by which αSyn alters neurotransmitter release and synaptic potentiation is unclear. By atomic force microscopy we show that human αSyn, when incubated with reconstituted membrane bilayer, induces lipid rafts' fragmentation. As a consequence, ion channels and receptors are displaced from lipid rafts with consequent changes in their activity. The enhanced calcium entry leads to acute mobilization of synaptic vesicles, and exhaustion of neurotransmission at later stages. At the post-synaptic terminal, an acute increase in glutamatergic transmission, with increased density of PSD-95 puncta, is followed by disruption of the interaction between N-methyl-d-aspartate receptor (NMDAR) and PSD-95 with ensuing decrease of long term potentiation. While cholesterol loading prevents the acute effect of αSyn at the presynapse; inhibition of casein kinase 2, which appears activated by reduction of cholesterol, restores the correct localization and clustering of NMDARs.

  4. Alpha-synuclein-induced aggregation of cytoplasmic vesicles in Saccharomyces cerevisiae.

    Science.gov (United States)

    Soper, James H; Roy, Subhojit; Stieber, Anna; Lee, Eliza; Wilson, Robert B; Trojanowski, John Q; Burd, Christopher G; Lee, Virginia M-Y

    2008-03-01

    Aggregated alpha-synuclein (alpha-syn) fibrils form Lewy bodies (LBs), the signature lesions of Parkinson's disease (PD) and related synucleinopathies, but the pathogenesis and neurodegenerative effects of LBs remain enigmatic. Recent studies have shown that when overexpressed in Saccharomyces cerevisiae, alpha-syn localizes to plasma membranes and forms cytoplasmic accumulations similar to human alpha-syn inclusions. However, the exact nature, composition, temporal evolution, and underlying mechanisms of yeast alpha-syn accumulations and their relevance to human synucleinopathies are unknown. Here we provide ultrastructural evidence that alpha-syn accumulations are not comprised of LB-like fibrils, but are associated with clusters of vesicles. Live-cell imaging showed alpha-syn initially localized to the plasma membrane and subsequently formed accumulations in association with vesicles. Imaging of truncated and mutant forms of alpha-syn revealed the molecular determinants and vesicular trafficking pathways underlying this pathological process. Because vesicular clustering is also found in LB-containing neurons of PD brains, alpha-syn-mediated vesicular accumulation in yeast represents a model system to study specific aspects of neurodegeneration in PD and related synucleinopathies.

  5. Alpha synuclein is transported into and out of the brain by the blood-brain barrier.

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    Sui, Yu-Ting; Bullock, Kristin M; Erickson, Michelle A; Zhang, Jing; Banks, W A

    2014-12-01

    Alpha-synuclein (α-Syn), a small protein with multiple physiological and pathological functions, is one of the dominant proteins found in Lewy Bodies, a pathological hallmark of Lewy body disorders, including Parkinson's disease (PD). More recently, α-Syn has been found in body fluids, including blood and cerebrospinal fluid, and is likely produced by both peripheral tissues and the central nervous system. Exchange of α-Syn between the brain and peripheral tissues could have important pathophysiologic and therapeutic implications. However, little is known about the ability of α-Syn to cross the blood-brain barrier (BBB). Here, we found that radioactively labeled α-Syn crossed the BBB in both the brain-to-blood and the blood-to-brain directions at rates consistent with saturable mechanisms. Low-density lipoprotein receptor-related protein-1 (LRP-1), but not p-glycoprotein, may be involved in α-Syn efflux and lipopolysaccharide (LPS)-induced inflammation could increase α-Syn uptake by the brain by disrupting the BBB.

  6. Mitochondrial Dysfunction: The Road to Alpha-Synuclein Oligomerization in PD

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    A. R. Esteves

    2011-01-01

    Full Text Available While the etiology of Parkinson's disease remains largely elusive, there is accumulating evidence suggesting that mitochondrial dysfunction occurs prior to the onset of symptoms in Parkinson's disease. Mitochondria are remarkably primed to play a vital role in neuronal cell survival since they are key regulators of energy metabolism (as ATP producers, of intracellular calcium homeostasis, of NAD+/NADH ratio, and of endogenous reactive oxygen species production and programmed cell death. In this paper, we focus on mitochondrial dysfunction-mediated alpha-synuclein aggregation. We highlight some of the findings that provide proof of evidence for a mitochondrial metabolism control in Parkinson's disease, namely, mitochondrial regulation of microtubule-dependent cellular traffic and autophagic lysosomal pathway. The knowledge that microtubule alterations may lead to autophagic deficiency and may compromise the cellular degradation mechanisms that culminate in the progressive accumulation of aberrant protein aggregates shields new insights to the way we address Parkinson's disease. In line with this knowledge, an innovative window for new therapeutic strategies aimed to restore microtubule network may be unlocked.

  7. Expression of alpha-synuclein in different brain parts of adult and aged rats.

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    Adamczyk, A; Solecka, J; Strosznajder, J B

    2005-03-01

    The synucleins are a family of presynaptic proteins that are abundant in neurons and include alpha-, beta, and gamma-synuclein. Alpha-synuclein (ASN) is involved in several neurodegenerative age-related disorders but its relevance in physiological aging is unknown. In the present study we investigated the expression of ASN mRNA and protein in the different brain parts of the adult (4-month-old) and aged (24-month-old) rats by using RT-PCR technique and Western blot, respectively. Our results indicated that mRNA expression and immunoreactivity of ASN is similar in brain cortex, hippocampus and striatum but markedly lower in cerebellum comparing to the other brain parts. Aging lowers ASN mRNA expression in striatum and cerebellum by about 40%. The immunoreactivity of ASN in synaptic plasma membranes (SPM) from aged brain cortex, hippocampus and cerebellum is significantly lower comparing to adult by 39%, 24% and 65%, respectively. Beta-synuclein (BSN) was not changed in aged brain comparing to adult. Age-related alteration of ASN may affect the nerve terminals structure and function.

  8. Nigrostriatal dynein changes in A53T alpha-synuclein transgenic mice [v1; ref status: indexed, http://f1000r.es/2wb

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    Yan Liu

    2014-03-01

    Full Text Available The accumulation of misfolded a-synuclein is mechanistically linked to neurodegeneration in Parkinson’s disease (PD and other alpha-synucleinopathies. However, how alpha-synuclein causes neurodegeneration is unresolved. Several studies have supported the involvement of dynein, the major motor for retrograde axonal transport in alpha-synuclein-dependent neurodegeneration, especially in the nigrostriatal system. Therefore, we examined the nigrostriatal dyneins in transgenic mice that overexpress human A53T alpha-synuclein and recapitulate key features of a PD-like neuronal synucleinopathy. Age-matched nontransgenic littermates were used as controls. The results demonstrated that the protein level of dynein was decreased in the striatum, whereas it was elevated in the substantia nigra. Double immunostaining results revealed that the reduction in dynein level was associated with aggregation of A53T a-synuclein in the striatum. Furthermore, we performed a quantitative analysis of motor behaviors in A53T alpha-synuclein transgenic mice and controls using a modified open field test. We demonstrated that the protein level of dynein in the striatum was significantly correlated with the motor behaviors. Together, our data indicate that dynein changes in the nigrostriatal system of A53T alpha-synuclein transgenic mice may contribute to their severe movement disorder.

  9. Modelling Ser129 phosphorylation inhibits membrane binding of pore-forming alpha-synuclein oligomers.

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    Georg Sebastian Nübling

    Full Text Available BACKGROUND: In several neurodegenerative diseases, hyperphosphorylation at position Ser129 is found in fibrillar deposits of alpha-synuclein (asyn, implying a pathophysiological role of asyn phosphorylation in neurodegeneration. However, recent animal models applying asyn phosphorylation mimics demonstrated a protective effect of phosphorylation. Since metal-ion induced asyn oligomers were identified as a potential neurotoxic aggregate species with membrane pore-forming abilities, the current study was undertaken to determine effects of asyn phosphorylation on oligomer membrane binding. METHODS: We investigated the influence of S129 phosphorylation on interactions of metal-ion induced asyn oligomers with small unilamellar lipid vesicles (SUV composed of POPC and DPPC applying the phosphorylation mimic asyn129E. Confocal single-particle fluorescence techniques were used to monitor membrane binding at the single-particle level. RESULTS: Binding of asyn129E monomers to gel-state membranes (DPPC-SUV is slightly reduced compared to wild-type asyn, while no interactions with membranes in the liquid-crystalline state (POPC-SUV are seen for both asyn and asyn129E. Conversely, metal-ion induced oligomer formation is markedly increased in asyn129E. Surprisingly, membrane binding to POPC-SUV is nearly absent in Fe(3+ induced asyn129E oligomers and markedly reduced in Al(3+ induced oligomers. CONCLUSION: The protective effect of pseudophosphorylation seen in animal models may be due to impeded oligomer membrane binding. Phosphorylation at Ser129 may thus have a protective effect against neurotoxic asyn oligomers by preventing oligomer membrane binding and disruption of the cellular electrophysiological equilibrium. Importantly, these findings put a new complexion on experimental pharmaceutical interventions against POLO-2 kinase.

  10. Conformational equilibria in monomeric alpha-synuclein at the single-molecule level.

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    Massimo Sandal

    2008-01-01

    Full Text Available Human alpha-Synuclein (alphaSyn is a natively unfolded protein whose aggregation into amyloid fibrils is involved in the pathology of Parkinson disease. A full comprehension of the structure and dynamics of early intermediates leading to the aggregated states is an unsolved problem of essential importance to researchers attempting to decipher the molecular mechanisms of alphaSyn aggregation and formation of fibrils. Traditional bulk techniques used so far to solve this problem point to a direct correlation between alphaSyn's unique conformational properties and its propensity to aggregate, but these techniques can only provide ensemble-averaged information for monomers and oligomers alike. They therefore cannot characterize the full complexity of the conformational equilibria that trigger the aggregation process. We applied atomic force microscopy-based single-molecule mechanical unfolding methodology to study the conformational equilibrium of human wild-type and mutant alphaSyn. The conformational heterogeneity of monomeric alphaSyn was characterized at the single-molecule level. Three main classes of conformations, including disordered and "beta-like" structures, were directly observed and quantified without any interference from oligomeric soluble forms. The relative abundance of the "beta-like" structures significantly increased in different conditions promoting the aggregation of alphaSyn: the presence of Cu2+, the pathogenic A30P mutation, and high ionic strength. This methodology can explore the full conformational space of a protein at the single-molecule level, detecting even poorly populated conformers and measuring their distribution in a variety of biologically important conditions. To the best of our knowledge, we present for the first time evidence of a conformational equilibrium that controls the population of a specific class of monomeric alphaSyn conformers, positively correlated with conditions known to promote the formation of

  11. Is alpha-synuclein loss-of-function a contributor to parkinsonian pathology? Evidence from non-human primates

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    Timothy J Collier

    2016-01-01

    Full Text Available Accumulation of alpha-synuclein (α-syn in Lewy bodies and neurites of midbrain dopamine neurons is diagnostic for Parkinson’s disease (PD, leading to the proposal that PD is a toxic gain-of-function synucleinopathy. Here we discuss the alternative viewpoint that α-syn displacement from synapses by misfolding and aggregation results in a toxic loss-of-function. In support of this hypothesis we provide evidence from our pilot study demonstrating that knockdown of endogenous α-syn in dopamine neurons of nonhuman primates reproduces the pattern of nigrostriatal degeneration characteristic of PD.

  12. Targeted overexpression of human alpha-synuclein in oligodendroglia induces lesions linked to MSA-like progressive autonomic failure.

    Science.gov (United States)

    Stemberger, Sylvia; Poewe, Werner; Wenning, Gregor K; Stefanova, Nadia

    2010-08-01

    Multiple system atrophy (MSA) is a rare neurodegenerative disease of undetermined cause manifesting with progressive autonomic failure (AF), cerebellar ataxia and parkinsonism due to neuronal loss in multiple brain areas associated with (oligodendro)glial cytoplasmic alpha-synuclein (alpha SYN) inclusions (GCIs). Using proteolipid protein (PLP)-alpha-synuclein (alpha SYN) transgenic mice we have previously reported parkinsonian motor deficits triggered by MSA-like alpha SYN inclusions. We now extend these observations by demonstrating degeneration of brain areas that are closely linked to progressive AF and other non-motor symptoms in MSA, in (PLP)-alpha SYN transgenic mice as compared to age-matched non-transgenic controls. We show delayed loss of cholinergic neurons in nucleus ambiguus at 12 months of age as well as early neuronal loss in laterodorsal tegmental nucleus, pedunculopontine tegmental nucleus and Onuf's nucleus at 2 months of age associated with alpha SYN oligodendroglial overexpression. We also report that neuronal loss triggered by MSA-like alpha SYN inclusions is absent up to 12 months of age in the thoracic intermediolateral cell column suggesting a differential dynamic modulation of alpha SYN toxicity within the murine autonomic nervous system. Although the spatial and temporal evolution of central autonomic pathology in MSA is unknown our findings corroborate the utility of the (PLP)-alpha SYN transgenic mouse model as a testbed for the study of oligodendroglial alpha SYN mediated neurodegeneration replicating both motor and non-motor aspects of MSA.

  13. The role of alpha-synuclein in melanin synthesis in melanoma and dopaminergic neuronal cells.

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    Tianhong Pan

    Full Text Available The relatively high co-occurrence of Parkinson's disease (PD and melanoma has been established by a large number of epidemiological studies. However, a clear biological explanation for this finding is still lacking. Ultra-violet radiation (UVR-induced skin melanin synthesis is a defense mechanism against UVR-induced damage relevant to the initiation of melanoma, whereas, increased neuromelanin (NM, the melanin synthesized in dopaminergic neurons, may enhance the susceptibility to oxidative stress-induced neuronal injury relevant to PD. SNCA is a PD-causing gene coding for alpha-Synuclein (α-Syn that expresses not only in brain, but also in skin as well as in tumors, such as melanoma. The findings that α-Syn can interact with tyrosinase (TYR and inhibit tyrosine hydroxylase (TH, both of which are enzymes involved in the biosynthesis of melanin and dopamine (DA, led us to propose that α-Syn may participate in the regulation of melanin synthesis. In this study, by applying ultraviolet B (UVB light, a physiologically relevant stimulus of melanogenesis, we detected melanin synthesis in A375 and SK-MEL-28 melanoma cells and in SH-SY5Y and PC12 dopaminergic neuronal cells and determined effects of α-Syn on melanin synthesis. Our results showed that UVB light exposure increased melanin synthesis in all 4 cell lines. However, we found that α-Syn expression reduced UVB light-induced increase of melanin synthesis and that melanin content was lower when melanoma cells were expressed with α-Syn, indicating that α-Syn may have inhibitory effects on melanin synthesis in melanoma cells. Different from melanoma cells, the melanin content was higher in α-Syn-over-expressed dopaminergic neuronal SH-SY5Y and PC12 cells, cellular models of PD, than that in non-α-Syn-expressed control cells. We concluded that α-Syn could be one of the points responsible for the positive association between PD and melanoma via its differential roles in melanin synthesis in

  14. Reciprocal signals between microglia and neurons regulate alpha-synuclein secretion by exophagy through a neuronal cJU-N-Nterminal kinase-signaling axis

    DEFF Research Database (Denmark)

    Christensen, Dan Ploug; Ejlerskov, Patrick; Rasmussen, Izabela

    2016-01-01

    Background: Secretion of proteopathic alpha-synuclein (alpha-SNC) species from neurons is a suspected driving force in the propagation of Parkinson's disease (PD). We have previously implicated exophagy, the exocytosis of autophagosomes, as a dominant mechanism of alpha-SNC secretion in different...

  15. Evidence for Intramolecular Antiparallel Beta-Sheet Structure in Alpha-Synuclein Fibrils from a Combination of Two-Dimensional Infrared Spectroscopy and Atomic Force Microscopy

    NARCIS (Netherlands)

    Roeters, Steven J.; Iyer, Aditya; Pletikapic, Galja; Kogan, Vladimir; Subramaniam, Vinod; Woutersen, Sander

    2017-01-01

    The aggregation of the intrinsically disordered protein alpha-synuclein (αS) into amyloid fibrils is thought to play a central role in the pathology of Parkinson’s disease. Using a combination of techniques (AFM, UV-CD, XRD, and amide-I 1D- and 2D-IR spectroscopy) we show that the structure of αS fi

  16. 5-HT2A Receptor Binding in the Frontal Cortex of Parkinson's Disease Patients and Alpha-Synuclein Overexpressing Mice

    DEFF Research Database (Denmark)

    Rasmussen, Nadja Bredo; Olesen, Mikkel Vestergaard; Brudek, Tomasz;

    2016-01-01

    function are also steadily being associated with this disease. Not much is known about the pathophysiology behind this. The aim of this study was thereby twofold: (1) to investigate receptor binding levels in Parkinson’s brains and (2) to investigate whether PD associated pathology, alpha-synuclein (AS...... by increased receptor binding in PD brains. In a separate study, we looked for changes in receptors in the prefrontal cortex in 52-week-old transgenic mice overexpressing human AS. We performed region-specific receptor binding measurements followed by gene expression analysis. The transgenic mice showed lower...... binding in the frontal association cortex that was not accompanied by changes in gene expression levels. This study is one of the first to look at differences in serotonin receptor levels in PD and in relation to AS overexpression....

  17. Characterization of cognitive deficits in rats overexpressing human alpha-synuclein in the ventral tegmental area and medial septum using recombinant adeno-associated viral vectors.

    Directory of Open Access Journals (Sweden)

    Hélène Hall

    Full Text Available Intraneuronal inclusions containing alpha-synuclein (a-syn constitute one of the pathological hallmarks of Parkinson's disease (PD and are accompanied by severe neurodegeneration of A9 dopaminergic neurons located in the substantia nigra. Although to a lesser extent, A10 dopaminergic neurons are also affected. Neurodegeneration of other neuronal populations, such as the cholinergic, serotonergic and noradrenergic cell groups, has also been documented in PD patients. Studies in human post-mortem PD brains and in rodent models suggest that deficits in cholinergic and dopaminergic systems may be associated with the cognitive impairment seen in this disease. Here, we investigated the consequences of targeted overexpression of a-syn in the mesocorticolimbic dopaminergic and septohippocampal cholinergic pathways. Rats were injected with recombinant adeno-associated viral vectors encoding for either human wild-type a-syn or green fluorescent protein (GFP in the ventral tegmental area and the medial septum/vertical limb of the diagonal band of Broca, two regions rich in dopaminergic and cholinergic neurons, respectively. Histopathological analysis showed widespread insoluble a-syn positive inclusions in all major projections areas of the targeted nuclei, including the hippocampus, neocortex, nucleus accumbens and anteromedial striatum. In addition, the rats overexpressing human a-syn displayed an abnormal locomotor response to apomorphine injection and exhibited spatial learning and memory deficits in the Morris water maze task, in the absence of obvious spontaneous locomotor impairment. As losses in dopaminergic and cholinergic immunoreactivity in both the GFP and a-syn expressing animals were mild-to-moderate and did not differ from each other, the behavioral impairments seen in the a-syn overexpressing animals appear to be determined by the long term persisting neuropathology in the surviving neurons rather than by neurodegeneration.

  18. Bioinorganic chemistry of Parkinson's disease: structural determinants for the copper-mediated amyloid formation of alpha-synuclein.

    Science.gov (United States)

    Binolfi, Andrés; Rodriguez, Esaú E; Valensin, Daniela; D'Amelio, Nicola; Ippoliti, Emiliano; Obal, Gonzalo; Duran, Rosario; Magistrato, Alessandra; Pritsch, Otto; Zweckstetter, Markus; Valensin, Gianni; Carloni, Paolo; Quintanar, Liliana; Griesinger, Christian; Fernández, Claudio O

    2010-11-15

    The aggregation of alpha-synuclein (AS) is a critical step in the etiology of Parkinson's disease (PD). A central, unresolved question in the pathophysiology of PD relates to the role of AS-metal interactions in amyloid fibril formation and neurodegeneration. Our previous works established a hierarchy in alpha-synuclein-metal ion interactions, where Cu(II) binds specifically to the protein and triggers its aggregation under conditions that might be relevant for the development of PD. Two independent, non-interacting copper-binding sites were identified at the N-terminal region of AS, with significant difference in their affinities for the metal ion. In this work we have solved unknown details related to the structural binding specificity and aggregation enhancement mediated by Cu(II). The high-resolution structural characterization of the highest affinity N-terminus AS-Cu(II) complex is reported here. Through the measurement of AS aggregation kinetics we proved conclusively that the copper-enhanced AS amyloid formation is a direct consequence of the formation of the AS-Cu(II) complex at the highest affinity binding site. The kinetic behavior was not influenced by the His residue at position 50, arguing against an active role for this residue in the structural and biological events involved in the mechanism of copper-mediated AS aggregation. These new findings are central to elucidate the mechanism through which the metal ion participates in the fibrillization of AS and represent relevant progress in the understanding of the bioinorganic chemistry of PD.

  19. In vivo visualization of alpha-synuclein deposition by carbon-11-labelled 2-[2-(2-dimethylaminothiazol-5-yl)ethenyl]-6-[2-(fluoro)ethoxy]benzoxazole positron emission tomography in multiple system atrophy.

    Science.gov (United States)

    Kikuchi, Akio; Takeda, Atsushi; Okamura, Nobuyuki; Tashiro, Manabu; Hasegawa, Takafumi; Furumoto, Shozo; Kobayashi, Michiko; Sugeno, Naoto; Baba, Toru; Miki, Yasuo; Mori, Fumiaki; Wakabayashi, Koichi; Funaki, Yoshihito; Iwata, Ren; Takahashi, Shoki; Fukuda, Hiroshi; Arai, Hiroyuki; Kudo, Yukitsuka; Yanai, Kazuhiko; Itoyama, Yasuto

    2010-06-01

    The histopathological hallmark of multiple system atrophy is the appearance of intracellular inclusion bodies, named glial cytoplasmic inclusions, which are mainly composed of alpha-synuclein fibrils. In vivo visualization of alpha-synuclein deposition should be used for the diagnosis and assessment of therapy and severity of pathological progression in multiple system atrophy. Because 2-[2-(2-dimethylaminothiazol-5-yl)ethenyl]-6-[2-(fluoro)ethoxy] benzoxazole could stain alpha-synuclein-containing glial cytoplasmic inclusions in post-mortem brains, we compared the carbon-11-labelled 2-[2-(2-dimethylaminothiazol-5-yl)ethenyl]-6-[2-(fluoro)ethoxy] benzoxazole positron emission tomography findings of eight multiple system atrophy cases to those of age-matched normal controls. The positron emission tomography data demonstrated high distribution volumes in the subcortical white matter (uncorrected P benzoxazole positron emission tomography is a promising surrogate marker for monitoring intracellular alpha-synuclein deposition in living brains.

  20. Physiological and Pathological Role of Alpha-Synuclein in Parkinson’s Disease through Iron Mediated Oxidative Stress; The Role of a Putative Iron-Responsive Element

    OpenAIRE

    David Olivares; Xudong Huang; Lars Branden; Greig, Nigel H.; Jack T. Rogers

    2009-01-01

    Parkinson’s disease (PD) is the second most common progressive neurodegenerative disorder after Alzheimer’s disease (AD) and represents a large health burden to society. Genetic and oxidative risk factors have been proposed as possible causes, but their relative contribution remains unclear. Dysfunction of alpha-synuclein (\\(\\alpha\\)-syn) has been associated with PD due to its increased presence, together with iron, in Lewy bodies. Brain oxidative damage caused by iron may be partly mediated ...

  1. Loss of β-glucocerebrosidase activity does not affect alpha-synuclein levels or lysosomal function in neuronal cells.

    Science.gov (United States)

    Dermentzaki, Georgia; Dimitriou, Evangelia; Xilouri, Maria; Michelakakis, Helen; Stefanis, Leonidas

    2013-01-01

    To date, a plethora of studies have provided evidence favoring an association between Gaucher disease (GD) and Parkinson's disease (PD). GD, the most common lysosomal storage disorder, results from the diminished activity of the lysosomal enzyme β-glucocerebrosidase (GCase), caused by mutations in the β-glucocerebrosidase gene (GBA). Alpha-synuclein (ASYN), a presynaptic protein, has been strongly implicated in PD pathogenesis. ASYN may in part be degraded by the lysosomes and may itself aberrantly impact lysosomal function. Therefore, a putative link between deficient GCase and ASYN, involving lysosomal dysfunction, has been proposed to be responsible for the risk for PD conferred by GBA mutations. In this current work, we aimed to investigate the effects of pharmacological inhibition of GCase on ASYN accumulation/aggregation, as well as on lysosomal function, in differentiated SH-SY5Y cells and in primary neuronal cultures. Following profound inhibition of the enzyme activity, we did not find significant alterations in ASYN levels, or any changes in the clearance or formation of its oligomeric species. We further observed no significant impairment of the lysosomal degradation machinery. These findings suggest that additional interaction pathways together with aberrant GCase and ASYN must govern this complex relation between GD and PD.

  2. Structural characterization of copper(II) binding to alpha-synuclein: Insights into the bioinorganic chemistry of Parkinson's disease.

    Science.gov (United States)

    Rasia, Rodolfo M; Bertoncini, Carlos W; Marsh, Derek; Hoyer, Wolfgang; Cherny, Dmitry; Zweckstetter, Markus; Griesinger, Christian; Jovin, Thomas M; Fernández, Claudio O

    2005-03-22

    The aggregation of alpha-synuclein (AS) is characteristic of Parkinson's disease and other neurodegenerative synucleinopathies. We demonstrate here that Cu(II) ions are effective in accelerating AS aggregation at physiologically relevant concentrations without altering the resultant fibrillar structures. By using numerous spectroscopic techniques (absorption, CD, EPR, and NMR), we have located the primary binding for Cu(II) to a specific site in the N terminus, involving His-50 as the anchoring residue and other nitrogen/oxygen donor atoms in a square planar or distorted tetragonal geometry. The carboxylate-rich C terminus, originally thought to drive copper binding, is able to coordinate a second Cu(II) equivalent, albeit with a 300-fold reduced affinity. The NMR analysis of AS-Cu(II) complexes reveals the existence of conformational restrictions in the native state of the protein. The metallobiology of Cu(II) in Parkinson's disease is discussed by a comparative analysis with other Cu(II)-binding proteins involved in neurodegenerative disorders.

  3. Alpha-synuclein A53T mutation is not frequent on a sample of Brazilian Parkinson’s disease patients

    Directory of Open Access Journals (Sweden)

    Gabriela S. Longo

    2015-06-01

    Full Text Available Introduction The pathogenesis of Parkinson’s disease (PD involves both genetic susceptibility and environmental factors, with focus on the mutation in the alpha-synuclein gene (SNCA.Objective To analyse the polymorphism SNCA-A53T in patients with familial PD (FPD and sporadic PD (SPD.Method A total of 294 individuals were studied, regardless of sex and with mixed ethnicity. The study group with 154 patients with PD, and the control group included 140 individuals without PD. The genotyping of SNCA-A53T was performed by PCR/RFLP. Significance level was p < 0.05.Results Among all patients, 37 (24% had FPD and 117 (75.9% had SPD. The absence of SNCA-A53T mutation was observed in all individuals.Conclusion SPD is notably observed in patients. However, the SNCA-A53T mutation was absent in all individuals, which does not differ controls from patients. This fact should be confirmed in a Brazilian study case with a more numerous and older population.

  4. Alpha-synuclein pathology and axonal degeneration of the peripheral motor nerves innervating pharyngeal muscles in Parkinson disease.

    Science.gov (United States)

    Mu, Liancai; Sobotka, Stanislaw; Chen, Jingming; Su, Hungxi; Sanders, Ira; Adler, Charles H; Shill, Holly A; Caviness, John N; Samanta, Johan E; Beach, Thomas G

    2013-02-01

    Parkinson disease (PD) is a neurodegenerative disease primarily characterized by cardinal motor manifestations and CNS pathology. Current drug therapies can often stabilize these cardinal motor symptoms, and attention has shifted to the other motor and nonmotor symptoms of PD that are resistant to drug therapy. Dysphagia in PD is perhaps the most important drug-resistant symptom because it leads to aspiration and pneumonia, the leading cause of death. Here, we present direct evidence for degeneration of the pharyngeal motor nerves in PD. We examined the cervical vagal nerve (cranial nerve X), pharyngeal branch of nerve X, and pharyngeal plexus innervating the pharyngeal muscles in 14 postmortem specimens, that is, from 10 patients with PD and 4 age-matched control subjects. Synucleinopathy in the pharyngeal nerves was detected using an immunohistochemical method for phosphorylated α-synuclein. Alpha-synuclein aggregates were revealed in nerve X and the pharyngeal branch of nerve X, and immunoreactive intramuscular nerve twigs and axon terminals within the neuromuscular junctions were identified in all of the PD patients but in none of the controls. These findings indicate that the motor nervous system of the pharynx is involved in the pathologic process of PD. Notably, PD patients who have had dysphagia had a higher density of α-synuclein aggregates in the pharyngeal nerves than those without dysphagia. These findings indicate that motor involvement of the pharynx in PD is one of the factors leading to oropharyngeal dysphagia commonly seen in PD patients.

  5. Structured Regions of Alpha-synuclein Fibrils Include the Early Onset Parkinson's Disease Mutation Sites

    Energy Technology Data Exchange (ETDEWEB)

    Comellas Canal, Gemma; Lemkau, Luisel R.; Nieuwkoop, Andrew J.; Kloepper, Kathryn D.; Ladror, Daniel T.; Ebisu, Reika; Woods, Wendy S.; Lipton, Andrew S.; George, Julia M.; Rienstra, Chad M.

    2011-08-26

    Alpha-Synuclein (AS) fibrils constitute the major proteinaceous component of Lewy bodies (LBs), the pathological hallmark of Parkinson’s disease (PD) and other neurodegenerative diseases. Three single point mutations in the AS gene, as well as multiplication of the wild-type (WT) AS allele, have been previously identified in families with early-onset PD. Although AS fibrils have been the subject of intense study, critical details about their structure including the precise location of the B-strands and the extent of the core, the three-dimensional structure and the effects of the mutations—remain unknown. Here, we have used magic-angle spinning solid-state NMR spectroscopy to present a detailed characterization of the full-length WT AS fibrils. With improved sample preparations, isotopic labeling patterns and NMR experiments, we have confidently assigned more than 90% of the 13C and 15N backbone and sidechain chemical shifts of the detected residues from residue 39 to 97, and quantified the conformational dynamics throughout this region. Our results demonstrate that the core of AS fibrils extends with a repeated motif and that residues 30, 46 and 53-the early-onset PD mutant sites-are located in structured regions of AS fibrils.

  6. Leucine-rich repeat kinase 2 and alpha-synuclein: intersecting pathways in the pathogenesis of Parkinson's disease?

    Directory of Open Access Journals (Sweden)

    Civiero Laura

    2011-01-01

    Full Text Available Abstract Although Parkinson's disease (PD is generally a sporadic neurological disorder, the discovery of monogenic, hereditable forms of the disease has been crucial in delineating the molecular pathways that lead to this pathology. Genes responsible for familial PD can be ascribed to two categories based both on their mode of inheritance and their suggested biological function. Mutations in parkin, PINK1 and DJ-1 cause of recessive Parkinsonism, with a variable pathology often lacking the characteristic Lewy bodies (LBs in the surviving neurons. Intriguingly, recent findings highlight a converging role of all these genes in mitochondria function, suggesting a common molecular pathway for recessive Parkinsonism. Mutations in a second group of genes, encoding alpha-synuclein (α-syn and LRRK2, are transmitted in a dominant fashion and generally lead to LB pathology, with α-syn being the major component of these proteinaceous aggregates. In experimental systems, overexpression of mutant proteins is toxic, as predicted for dominant mutations, but the normal function of both proteins is still elusive. The fact that α-syn is heavily phosphorylated in LBs and that LRRK2 is a protein kinase, suggests that a link, not necessarily direct, exists between the two. What are the experimental data supporting a common molecular pathway for dominant PD genes? Do α-syn and LRRK2 target common molecules? Does LRRK2 act upstream of α-syn? In this review we will try to address these of questions based on the recent findings available in the literature.

  7. A rapid, semi-quantitative assay to screen for modulators of alpha-synuclein oligomerization ex vivo

    Directory of Open Access Journals (Sweden)

    Marion eDelenclos

    2016-01-01

    Full Text Available Alpha synuclein (αsyn aggregates are associated with the pathogenesis of Parkinson’s disease and others related disorders. Although modulation of αsyn aggregation is an attractive therapeutic target, new powerful methodologies are desperately needed to facilitate in vivo screening of novel therapeutics. Here we describe an in vivo rodent model with the unique ability to rapidly track αsyn-αsyn interactions and thus oligomerization using a bioluminescent protein complementation strategy that monitors spatial and temporal αsyn oligomerization ex vivo. We find that αsyn forms oligomers in vivo as early as 1 week after stereotactic AAV injection into rat substantia nigra. Strikingly, although abundant αsyn expression is also detected in striatum at one week, no αsyn oligomers are detected at this time point. By 4 weeks, oligomerization of αsyn is detected in both striatum and substantia nigra homogenates. Moreover, in a proof-of-principle experiment, the effect of a previously described Hsp90 inhibitor known to prevent αsyn oligomer formation, demonstrates the utility of this rapid and sensitive animal model to monitor αsyn oligomerization status in the rat brain.

  8. Charge state dependent fragmentation of gaseous [alpha]-synuclein cations via ion trap and beam-type collisional activation

    Science.gov (United States)

    Chanthamontri, Chamnongsak; Liu, Jian; McLuckey, Scott A.

    2009-06-01

    Ions derived from nano-electrospray ionization (nano-ESI) of [alpha]-synuclein, a 14.5 kDa, 140 amino acid residue protein that is a major component of the Lewy bodies associated with Parkinson's disease, have been subjected to ion trap and beam-type collisional activation. The former samples products from fragmentation at rates generally lower than 100 s-1 whereas the latter samples products from fragmentation at rates generally greater than 103 s-1. A wide range of protein charge states spanning from as high as [M+17H]17+ to as low as [M+4H]4+ have been formed either directly from nano-ESI or via ion/ion proton transfer reactions involving the initially formed protein cations and have been subjected to both forms of collision-induced dissociation (CID). The extent of sequence information (i.e., number of distinct amide bond cleavages) available from either CID method was found to be highly sensitive to protein precursor ion charge state. Furthermore, the relative contributions of the various competing dissociation channels were also dependent upon precursor ion charge state. The qualitative trends in the changes in extent of amide bond cleavages and identities of bonds cleaved with precursor ion charge state were similar for two forms of CID. However, for every charge state examined, roughly twice the primary sequence information resulted from beam-type CID relative to ion trap CID. For example, evidence for cleavage of 86% of the protein amide bonds was observed for the [M+9H]9+ precursor ion using beam-type CID whereas 41% of the bonds were cleaved for the same precursor ion using ion trap CID. The higher energies required to drive fragmentation reactions at rates necessary to observe products in the beam experiment access more of the structurally informative fragmentation channels, which has important implications for whole protein tandem mass spectrometry.

  9. Differential effects of UCHL1 modulation on alpha-synuclein in PD-like models of alpha-synucleinopathy.

    Directory of Open Access Journals (Sweden)

    Anna E Cartier

    Full Text Available Parkinson's disease (PD is a progressive neurodegenerative disorder caused by genetic and environmental factors. Abnormal accumulation and aggregation of alpha-synuclein (a-syn within neurons, and mutations in the a-syn and UCH-L1 genes have been shown to play a role in the pathogenesis of PD. In light of recent reports suggesting an interaction between a-synuclein and UCH-L1, we investigated the effects of UCH-L1 inhibition on a-syn distribution and expression levels in primary neurons and hippocampal tissues derived from non transgenic (non tg and a-syn over expressing tg mice. We show that suppression of UCH-L1 activity increased a-syn levels in control, non tg neurons, and resulted in a concomitant accumulation of presynaptic a-syn in these neurons. In contrast, blocking UCH-L1 activity in a-syn over expressing neurons decreased a-syn levels, and enhanced its synaptic clearance. In vitro studies verified the LDN-induced inhibition of UCH-L1 had minimal effect on LC3 (a marker of autophagy in control cells, in cells over expressing a-syn UCH-L1 inhibition resulted in increased LC3 activity. These findings suggest a possible differential role of UCH-L1 function under normal and pathological conditions. Furthermore, in the context of a-syn-induced pathology, modulation of UCH-L1 activity could serve as a therapeutic tool to enhance the autophagy pathway and induce clearance of the observed accumulated/aggregated a-syn species in the PD brain.

  10. The loss of glucose-regulated protein 78 (GRP78) during normal aging or from siRNA knockdown augments human alpha-synuclein (α-syn) toxicity to rat nigral neurons.

    Science.gov (United States)

    Salganik, Maxim; Sergeyev, Valeriy G; Shinde, Vishal; Meyers, Craig A; Gorbatyuk, Marina S; Lin, Jonathan H; Zolotukhin, Sergey; Gorbatyuk, Oleg S

    2015-06-01

    Age-related structural changes and gradual loss of key enzymes significantly affect the ability of the endoplasmic reticulum (ER) to facilitate proper protein folding and maintain homeostasis. In this work, we present several lines of evidence supporting the hypothesis that the age-related decline in expression of the ER chaperone glucose-regulated protein 78 (GRP78) could be related to the development of Parkinson's disease. We first determined that old (24 months) rats exhibit significantly lower levels of GRP78 protein in the nigrostriatal system as compared with young (2 months) animals. Then using recombinant adeno-associate virus-mediated gene transfer, we found that GRP78 downregulation by specific small interfering RNAs (siRNAs) aggravates alpha-synuclein (α-syn) neurotoxicity in nigral dopamine (DA) neurons. Moreover, the degree of chaperone decline corresponds with the severity of neurodegeneration. Additionally, comparative analysis of nigral tissues obtained from old and young rats revealed that aging affects the capacity of nigral DA cells to upregulate endogenous GRP78 protein in response to human α-syn neurotoxicity. Finally, we demonstrated that a sustained increase of GRP78 protein over the course of 9 months protected aging nigral DA neurons in the α-syn-induced rat model of Parkinson's-like neurodegeneration. Our data indicate that the ER chaperone GRP78 may have therapeutic potential for preventing and/or slowing age-related neurodegeneration.

  11. Propagation of alpha-synuclein pathology: hypotheses, discoveries, and yet unresolved questions from experimental and human brain studies.

    Science.gov (United States)

    Uchihara, Toshiki; Giasson, Benoit I

    2016-01-01

    Progressive aggregation of alpha-synuclein (αS) through formation of amorphous pale bodies to mature Lewy bodies or in neuronal processes as Lewy neurites may be the consequence of conformational protein changes and accumulations, which structurally represents "molecular template". Focal initiation and subsequent spread along anatomically connected structures embody "structural template". To investigate the hypothesis that both processes might be closely associated and involved in the progression of αS pathology, which can be observed in human brains, αS amyloidogenic precursors termed "seeds" were experimentally injected into the brain or peripheral nervous system of animals. Although these studies showed that αS amyloidogenic seeds can induce αS pathology, which can spread in the nervous system, the findings are still not unequivocal in demonstrating predominant transsynaptic or intraneuronal spreads either in anterograde or retrograde directions. Interpretation of some of these studies is further complicated by other concurrent aberrant processes including neuroimmune activation, injury responses and/or general perturbation of proteostasis. In human brain, αS deposition and neuronal degeneration are accentuated in distal axon/synapse. Hyperbranching of axons is an anatomical commonality of Lewy-prone systems, providing a structural basis for abundance in distal axons and synaptic terminals. This neuroanatomical feature also can contribute to such distal accentuation of vulnerability in neuronal demise and the formation of αS inclusion pathology. Although retrograde progression of αS aggregation in hyperbranching axons may be a consistent feature of Lewy pathology, the regional distribution and gradient of Lewy pathology are not necessarily compatible with a predictable pattern such as upward progression from lower brainstem to cerebral cortex. Furthermore, "focal Lewy body disease" with the specific isolated involvement of autonomic, olfactory or cardiac

  12. Dopamine Cytotoxicity Involves Both Oxidative and Nonoxidative Pathways in SH-SY5Y Cells: Potential Role of Alpha-Synuclein Overexpression and Proteasomal Inhibition in the Etiopathogenesis of Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Kalpita Banerjee

    2014-01-01

    Full Text Available Background. The cytotoxic effects of dopamine (DA on several catecholaminergic cell lines involve DA oxidation products like reactive oxygen species (ROS and toxic quinones and have implications in the pathogenesis of sporadic Parkinson's disease (PD. However, many molecular details are yet to be elucidated, and the possible nonoxidative mechanism of dopamine cytotoxicity has not been studied in great detail. Results. Cultured SH-SY5Y cells treated with DA (up to 400 μM or lactacystin (5 μM or DA (400 μM plus N-acetylcysteine (NAC, 2.5 mM for 24 h are processed accordingly to observe the cell viability, mitochondrial dysfunctions, oxidative stress parameters, proteasomal activity, expression of alpha-synuclein gene, and intracellular accumulation of the protein. DA causes mitochondrial dysfunction and extensive loss of cell viability partially inhibited by NAC, potent inhibition of proteasomal activity marginally prevented by NAC, and overexpression with accumulation of intracellular alpha-synuclein partially preventable by NAC. Under similar conditions of incubation, NAC completely prevents enhanced production of ROS and increased formation of quinoprotein adducts in DA-treated SH-SY5Y cells. Separately, proteasomal inhibitor lactacystin causes accumulation of alpha-synuclein as well as mitochondrial dysfunction and cell death. Conclusions. DA cytotoxicity includes both oxidative and nonoxidative modes and may involve overexpression and accumulation of alpha-synuclein as well as proteasomal inhibition.

  13. 表达alpha-synuclein A53T神经干细胞系的建立%Establishment of murine neural stem cells with expression of alpha-synuclein A53T

    Institute of Scientific and Technical Information of China (English)

    沈雁飞; 柳明杰

    2013-01-01

    目的 建立表达alpha-synuleinA53T突变体的神经干细胞.方法 采用Xho Ⅰ/Hpa Ⅰ双酶切paSynA53T-DsRed,将含SynA53T-DsRed片段连接到pBudCE4.1-1X-aSynA53T-DsRed的Xho Ⅰ/Pme Ⅰ位点构建pBudCE4.1-2X-aSynA53T-DsRed质粒.利用Lipofectamine2000介导转染2μg的pBudCE4.1-2X-aSynA53T-DsRed到鼠源性神经干细胞(mNSCs)后24h和72 h观察转染结果.结果 成功构建重组质粒pBudCE4.1-2X-aSynA53T-DsRed,转染24h后其表达率达到(57±3.52)%,72 h的表达率达到了(27.14±3.21)%.结论 通过质粒重组及转染技术,成功获得了表达aSynA53T的神经干细胞,为揭示α-synA53T导致帕金森氏症的病理过程提供了平台.%Objective To produce murine neural stem cells (mNSCs)with expression of alpha-synuclein A53T.Methods The Xho Ⅰ/Hpa Ⅰ fragment of SynA53T-DsRed was released from paSynA53T-DsRed and cloned into Xho Ⅰ/Pme Ⅰ sites of pBudCE4.1-1X-aSynA53T-DsRed plasmid.Then 2 μg of recombinant plasmid was transfected into murine neural stem cells to establish the mNSCs with overexpression of aSynA53T.Results The pBudCE4.1-2X-aSynA53T-DsRed plasmid containing double aSynA53T expressing inserts downstream of CMV and EF-1αpromoters was successfully constructed.Expression levels of the recombinant plasmid reached to (57 ±3.52)% and (27.14 ±3.21)% after 24 h and 72 h transfection,respectively.Conclusions A recombinant plasmid pBudCF4.1-2X-aSynA53T-DsRed and mNSCs with expression of aSynA53T should be useful for the investigation of the pathogenesis of Parkinson's disease (PD) and development of drug for treatment of PD.

  14. Exhibition

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    China[Guangzheu] International Trade Fair for Home Textiles Date:March 18th- March 21st,2011 Venue:China Import and Export Fair Complex(Guangzhou,China) Organizers:China National Textile&Apparel Council China Foreign Trade Center(Group) China Home Textile Association China Foreign Trade Guangzhou Exhibition Corp.

  15. Exhibition

    CERN Multimedia

    Staff Association

    2016-01-01

    Encounters Hanne Blitz From February 1st to 12th 2016 CERN Meyrin, Main Building What is our reaction to a first encounter with a tourist attraction? Contemporary Dutch painter Hanne Blitz captures visitors' responses to art and architecture, sweeping vistas and symbolic memorials. Encounters, a series of oil paintings curated specially for this CERN exhibition, depicts tourists visiting cultural highlights around the world. A thought-provoking journey not to be missed, and a tip of the hat to CERN's large Hadron Collider.

  16. A triple-emission fluorescent probe reveals distinctive amyloid fibrillar polymorphism of wild-type alpha-synuclein and its familial Parkinson's disease mutants.

    Science.gov (United States)

    Celej, M Soledad; Caarls, Wouter; Demchenko, Alexander P; Jovin, Thomas M

    2009-08-11

    Intracytoplasmic neuronal deposits containing amyloid fibrils of the 140-amino acid presynaptic protein alpha-synuclein (AS) are the hallmark of Parkinson's (PD) disease and related neurodegenerative disorders. Three point mutations (A53T, A30P, and E46K) are linked to early onset PD. Compared to the wild-type (WT) protein, the mutants aggregate faster in vitro, but their fibrillar products are quite similar. Using the extrinsic multiple-emission probe 4'-(diethylamino)-3-hydroxyflavone (FE), we demonstrate unique and distinct spectroscopic signatures for the amyloid fibrils formed by the WT and mutant AS, presumably indicative of subtle differences in supramolecular structure. The two well-separated emission bands of the FE probe originate from a proton transfer reaction in the excited state. The ratiometric response constitutes a sensitive, tunable reporter of microenvironmental properties such as polarity and hydrogen bonding. The very distinctive fluorescence spectra of the FE probe bound to the four AS variants reflect different tautomeric equilibria in the excited state and the existence of at least two different binding sites in the fibrils for the dye. Deconvolution of the two-dimensional excitation-emission spectra leads to estimations of different local dielectric constants and extents of hydration characteristic of the proteins. The sensitivity of such a simple external probe to conformational alterations induced by point mutations is unprecedented and provides new insight into key phenomena related to amyloid fibrils: plasticity, polymorphism, propagation of structural features, and structure-function relationships underlying toxicity.

  17. Alpha-Synuclein Expression in the Oligodendrocyte Lineage: an In Vitro and In Vivo Study Using Rodent and Human Models

    Directory of Open Access Journals (Sweden)

    Mehdi Djelloul

    2015-08-01

    Full Text Available In this study, we sought evidence for alpha-synuclein (ASYN expression in oligodendrocytes, as a possible endogenous source of ASYN to explain its presence in glial inclusions found in multiple system atrophy (MSA and Parkinson’s disease (PD. We identified ASYN in oligodendrocyte lineage progenitors isolated from the rodent brain, in oligodendrocytes generated from embryonic stem cells, and in induced pluripotent stem cells produced from fibroblasts of a healthy individual and patients diagnosed with MSA or PD, in cultures in vitro. Notably, we observed a significant decrease in ΑSYN during oligodendrocyte maturation. Additionally, we show the presence of transcripts in PDGFRΑ/CD140a+ cells and SOX10+ oligodendrocyte lineage nuclei isolated by FACS from rodent and human healthy and diseased brains, respectively. Our work identifies ASYN in oligodendrocyte lineage cells, and it offers additional in vitro cellular models that should provide significant insights of the functional implication of ASYN during oligodendrocyte development and disease.

  18. Autophagy down regulates pro-inflammatory mediators in BV2 microglial cells and rescues both LPS and alpha-synuclein induced neuronal cell death

    Science.gov (United States)

    Bussi, Claudio; Ramos, Javier Maria Peralta; Arroyo, Daniela S.; Gaviglio, Emilia A.; Gallea, Jose Ignacio; Wang, Ji Ming; Celej, Maria Soledad; Iribarren, Pablo

    2017-01-01

    Autophagy is a fundamental cellular homeostatic mechanism, whereby cells autodigest parts of their cytoplasm for removal or turnover. Neurodegenerative disorders are associated with autophagy dysregulation, and drugs modulating autophagy have been successful in several animal models. Microglial cells are phagocytes in the central nervous system (CNS) that become activated in pathological conditions and determine the fate of other neural cells. Here, we studied the effects of autophagy on the production of pro-inflammatory molecules in microglial cells and their effects on neuronal cells. We observed that both trehalose and rapamycin activate autophagy in BV2 microglial cells and down-regulate the production of pro-inflammatory cytokines and nitric oxide (NO), in response to LPS and alpha-synuclein. Autophagy also modulated the phosphorylation of p38 and ERK1/2 MAPKs in BV2 cells, which was required for NO production. These actions of autophagy modified the impact of microglial activation on neuronal cells, leading to suppression of neurotoxicity. Our results demonstrate a novel role for autophagy in the regulation of microglial cell activation and pro-inflammatory molecule secretion, which may be important for the control of inflammatory responses in the CNS and neurotoxicity. PMID:28256519

  19. Similar patterns of mitochondrial vulnerability and rescue induced by genetic modification of alpha-synuclein, parkin, and DJ-1 in Caenorhabditis elegans.

    Science.gov (United States)

    Ved, Rina; Saha, Shamol; Westlund, Beth; Perier, Celine; Burnam, Lucinda; Sluder, Anne; Hoener, Marius; Rodrigues, Cecilia M P; Alfonso, Aixa; Steer, Clifford; Liu, Leo; Przedborski, Serge; Wolozin, Benjamin

    2005-12-30

    How genetic and environmental factors interact in Parkinson disease is poorly understood. We have now compared the patterns of vulnerability and rescue of Caenorhabditis elegans with genetic modifications of three different genetic factors implicated in Parkinson disease (PD). We observed that expressing alpha-synuclein, deleting parkin (K08E3.7), or knocking down DJ-1 (B0432.2) or parkin produces similar patterns of pharmacological vulnerability and rescue. C. elegans lines with these genetic changes were more vulnerable than nontransgenic nematodes to mitochondrial complex I inhibitors, including rotenone, fenperoximate, pyridaben, or stigmatellin. In contrast, the genetic manipulations did not increase sensitivity to paraquat, sodium azide, divalent metal ions (Fe(II) or Cu(II)), or etoposide compared with the nontransgenic nematodes. Each of the PD-related lines was also partially rescued by the antioxidant probucol, the mitochondrial complex II activator, D-beta-hydroxybutyrate, or the anti-apoptotic bile acid tauroursodeoxycholic acid. Complete protection in all lines was achieved by combining d-beta-hydroxybutyrate with tauroursodeoxycholic acid but not with probucol. These results show that diverse PD-related genetic modifications disrupt the mitochondrial function in C. elegans, and they raise the possibility that mitochondrial disruption is a pathway shared in common by many types of familial PD.

  20. Cerebrospinal Fluid Amyloid β1-42, Tau, and Alpha-Synuclein Predict the Heterogeneous Progression of Cognitive Dysfunction in Parkinson's Disease.

    Science.gov (United States)

    Kang, Ju-Hee

    2016-05-01

    Parkinson's disease (PD) is a neurodegenerative disease with heterogeneous pathological and clinical features. Cognitive dysfunction, a frequent non-motor complication, is a risk factor for poor prognosis and shows inter-individual variation in its progression. Of the clinical studies performed to identify biomarkers of PD progression, the Parkinson's Progression Markers Initiative (PPMI) study is the largest study that enrolled drug-naïve and very early stage PD patients. The baseline characteristics of the PPMI cohort were recently published. The diagnostic utility of cerebrospinal fluid (CSF) biomarkers, including alpha-synuclein (α-syn), total tau, phosphorylated tau at Thr181, and amyloid β1-42, was not satisfactory. However, the baseline data on CSF biomarkers in the PPMI study suggested that the measurement of the CSF biomarkers enables the prediction of future cognitive decline in PD patients, which was consistent with previous studies. To prove the hypothesis that the interaction between Alzheimer's pathology and α-syn pathology is important to the progression of cognitive dysfunction in PD, longitudinal observational studies must be followed. In this review, the neuropathological nature of heterogeneous cognitive decline in PD is briefly discussed, followed by a summarized interpretation of baseline CSF biomarkers derived from the data in the PPMI study. The combination of clinical, biochemical, genetic and imaging biomarkers of PD constitutes a feasible strategy to predict the heterogeneous progression of PD.

  1. Analysis of striatal transcriptome in mice overexpressing human wild-type alpha-synuclein supports synaptic dysfunction and suggests mechanisms of neuroprotection for striatal neurons

    Directory of Open Access Journals (Sweden)

    Cabeza-Arvelaiz Yofre

    2011-12-01

    Full Text Available Abstract Background Alpha synuclein (SNCA has been linked to neurodegenerative diseases (synucleinopathies that include Parkinson's disease (PD. Although the primary neurodegeneration in PD involves nigrostriatal dopaminergic neurons, more extensive yet regionally selective neurodegeneration is observed in other synucleinopathies. Furthermore, SNCA is ubiquitously expressed in neurons and numerous neuronal systems are dysfunctional in PD. Therefore it is of interest to understand how overexpression of SNCA affects neuronal function in regions not directly targeted for neurodegeneration in PD. Results The present study investigated the consequences of SNCA overexpression on cellular processes and functions in the striatum of mice overexpressing wild-type, human SNCA under the Thy1 promoter (Thy1-aSyn mice by transcriptome analysis. The analysis revealed alterations in multiple biological processes in the striatum of Thy1-aSyn mice, including synaptic plasticity, signaling, transcription, apoptosis, and neurogenesis. Conclusion The results support a key role for SNCA in synaptic function and revealed an apoptotic signature in Thy1-aSyn mice, which together with specific alterations of neuroprotective genes suggest the activation of adaptive compensatory mechanisms that may protect striatal neurons in conditions of neuronal overexpression of SNCA.

  2. TRAF6 promotes atypical ubiquitination of mutant DJ-1 and alpha-synuclein and is localized to Lewy bodies in sporadic Parkinson's disease brains.

    Science.gov (United States)

    Zucchelli, Silvia; Codrich, Marta; Marcuzzi, Federica; Pinto, Milena; Vilotti, Sandra; Biagioli, Marta; Ferrer, Isidro; Gustincich, Stefano

    2010-10-01

    Parkinson's disease (PD) is a neurodegenerative disorder characterized by loss of dopaminergic neurons in the Substantia Nigra and the formation of ubiquitin- and alpha-synuclein (aSYN)-positive cytoplasmic inclusions called Lewy bodies (LBs). Although most PD cases are sporadic, families with genetic mutations have been found. Mutations in PARK7/DJ-1 have been associated with autosomal recessive early-onset PD, while missense mutations or duplications of aSYN (PARK1, PARK4) have been linked to dominant forms of the disease. In this study, we identify the E3 ubiquitin ligase tumor necrosis factor-receptor associated factor 6 (TRAF6) as a common player in genetic and sporadic cases. TRAF6 binds misfolded mutant DJ-1 and aSYN. Both proteins are substrates of TRAF6 ligase activity in vivo. Interestingly, rather than conventional K63 assembly, TRAF6 promotes atypical ubiquitin linkage formation to both PD targets that share K6-, K27- and K29- mediated ubiquitination. Importantly, TRAF6 stimulates the accumulation of insoluble and polyubiquitinated mutant DJ-1 into cytoplasmic aggregates. In human post-mortem brains of PD patients, TRAF6 protein colocalizes with aSYN in LBs. These results reveal a novel role for TRAF6 and for atypical ubiquitination in PD pathogenesis.

  3. Exhibition

    CERN Document Server

    Staff Association

    2017-01-01

    Sintropie Flavio Pellegrini From 13 to 24 March 2017 CERN Meyrin, Main Building Energia imprigionata - Flavio Pellegrini. The exhibition is composed by eleven wood artworks with the expression of movement as theme. The artworks are the result of harmonics math applied to sculpture. The powerful black colour is dominated by the light source, generating reflexes and modulations. The result is a continuous variation of perspective visions. The works generate, at a first approach, an emotion of mystery and incomprehension, only a deeper contemplation lets one discover entangling and mutative details, evidencing the elegance of the lines and letting the meaning emerge. For more information : staff.association@cern.ch | Tél: 022 766 37 38

  4. The heterozygous A53T mutation in the alpha-synuclein gene in a Chinese Han patient with Parkinson disease: case report and literature review.

    Science.gov (United States)

    Xiong, Wei-Xi; Sun, Yi-Min; Guan, Rong-Yuan; Luo, Su-Shan; Chen, Chen; An, Yu; Wang, Jian; Wu, Jian-Jun

    2016-10-01

    The missense mutation A53T of alpha-synuclein gene (SNCA) was reported to be a rare but definite cause of sporadic and familial Parkinson disease (PD). It seemed to be restricted geographically in Greece and Italy. We aimed to identify the SNCA mutations in a Chinese PD cohort. Ninety-one early onset PD patients or familial PD probands were collected consecutively for the screening of PD-related genes. The genetic analysis was carried out by target sequencing of the exons and the corresponding flanking regions of the PD-related genes using Illumina HiSeq 2000 sequencer and further confirmed by Sanger sequencing or restriction fragment length polymorphism. Dosage mutations of exons in these genes were carried out by multiple ligation-dependent probe amplification. Among the 91 patients, we found only one heterozygous mutation of SNCA A53T, in a 23-year-old male patient with negative family history. The [(11)C]-2β-carbomethoxy-3β-(4-fluorophenyl) tropan (CFT) PET and PD-related spatial covariance pattern (PDRP) via [(18)F]-fluorodeoxyglucos (FDG) PET confirmed a typical pattern of PD. After examining his parents, we found his mother was an asymptomatic carrier, with declined hand dexterity detected by quantitative motor tests. Reduced dopamine transporter uptake of his mother was identified by CFT PET, and abnormal PDRP pattern was found by FDG PET. Our investigation expanded the clinical and genetic spectrum of Chinese PD patients, and we suggested SNCA mutations to be screened in familial and early onset Chinese PD patients.

  5. Cuminaldehyde as the Major Component of Cuminum cyminum, a Natural Aldehyde with Inhibitory Effect on Alpha-Synuclein Fibrillation and Cytotoxicity.

    Science.gov (United States)

    Morshedi, Dina; Aliakbari, Farhang; Tayaranian-Marvian, Amir; Fassihi, Afshin; Pan-Montojo, Francisco; Pérez-Sánchez, Horacio

    2015-10-01

    Fibrillation of alpha-synuclein (α-SN) is a critical process in the pathophysiology of several neurodegenerative diseases, especially Parkinson's disease. Application of bioactive inhibitory compounds from herbal extracts is a potential therapeutic approach for this cytotoxic process. Here, we investigated the inhibitory effects of the Iranian Cuminum cyminum essential oil on the fibrillation of α-SN. Analysis of different fractions from the total extract identified cuminaldehyde as the active compound involved in the antifibrillation activity. In comparison with baicalein, a well-known inhibitor of α-SN fibrillation, cuminaldehyde showed the same activity in some aspects and a different activity on other parameters influencing α-SN fibrillation. The presence of spermidine, an α-SN fibrillation inducer, dominantly enforced the inhibitory effects of cuminaldehyde even more intensively than baicalein. Furthermore, the results from experiments using preformed fibrils and monobromobimane-labeled monomeric protein also suggest that cuminaldehyde prevents α-SN fibrillation even in the presence of seeds, having no disaggregating impact on the preformed fibrils. Structural studies showed that cuminaldehyde stalls protein assembly into β-structural fibrils, which might be achieved by the interaction with amine groups through its aldehyde group as a Schiff base reaction. This assumption was supported by FITC labeling efficiency assay. In addition, cytotoxicity assays on PC12 cells showed that cuminaldehyde is a nontoxic compound, treatment with cuminaldehyde throughout α-SN fibrillation showed no toxic effects on the cells. Taken together, these results show for the first time that the small abundant natural compound, cuminaldehyde, can modulate α-SN fibrillation. Hence, suggesting that such natural active aldehyde could have potential therapeutic applications.

  6. At low concentrations, 3,4-dihydroxyphenylacetic acid (DOPAC) binds non-covalently to alpha-synuclein and prevents its fibrillation.

    Science.gov (United States)

    Zhou, Wenbo; Gallagher, Amy; Hong, Dong-Pyo; Long, Chunmei; Fink, Anthony L; Uversky, Vladimir N

    2009-05-01

    Several studies have shown that catecholamines can inhibit the fibrillation of alpha-synuclein (alpha-Syn), a small presynaptic protein whose aggregation is believed to be a critical step in the etiology of Parkinson's disease and several other neurodegenerative disorders. However, the mechanism of this inhibition is uncertain. We show here that substoichiometric concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC), a normal product of the metabolism of dopamine, can inhibit the fibrillation of alpha-Syn, due to non-covalent binding of DOPAC to alpha-Syn monomer. Intriguingly, the presence of alpha-Syn accelerates the spontaneous oxidation of DOPAC, and the oxidized form of DOPAC (the quinone) is responsible for the fibrillation inhibition. In addition, the presence of DOPAC leads to the oxidation of the methionine residues of alpha-Syn, probably due to the H(2)O(2) production as a by-product of DOPAC oxidation. The lack of fibrillation results from the formation of stable oligomers, which are very similar to those observed transiently at early stages of the alpha-Syn fibrillation. A possible explanation for this phenomenon is that DOPAC stabilizes the normally transient oligomers and prevents them from subsequent fibril formation. The analysis of the alpha-Syn Y39W variant suggests that DOPAC binds non-covalently to the same N-terminal region of alpha-Syn as lipid vesicles, probably in the vicinity of residue 39. In contrast to the compounds with 1,2-dihydroxyphenyl groups (DOPAC and catechol), their 1,4-dihydroxyphenyl isomers (hydroquinone and homogentisic acid) are able to modify alpha-Syn covalently, probably due to the less steric hindrance in the Michael addition.

  7. Evidence for Intramolecular Antiparallel Beta-Sheet Structure in Alpha-Synuclein Fibrils from a Combination of Two-Dimensional Infrared Spectroscopy and Atomic Force Microscopy

    Science.gov (United States)

    Roeters, Steven J.; Iyer, Aditya; Pletikapić, Galja; Kogan, Vladimir; Subramaniam, Vinod; Woutersen, Sander

    2017-01-01

    The aggregation of the intrinsically disordered protein alpha-synuclein (αS) into amyloid fibrils is thought to play a central role in the pathology of Parkinson’s disease. Using a combination of techniques (AFM, UV-CD, XRD, and amide-I 1D- and 2D-IR spectroscopy) we show that the structure of αS fibrils varies as a function of ionic strength: fibrils aggregated in low ionic-strength buffers ([NaCl] ≤ 25 mM) have a significantly different structure than fibrils grown in higher ionic-strength buffers. The observations for fibrils aggregated in low-salt buffers are consistent with an extended conformation of αS molecules, forming hydrogen-bonded intermolecular β-sheets that are loosely packed in a parallel fashion. For fibrils aggregated in high-salt buffers (including those prepared in buffers with a physiological salt concentration) the measurements are consistent with αS molecules in a more tightly-packed, antiparallel intramolecular conformation, and suggest a structure characterized by two twisting stacks of approximately five hydrogen-bonded intermolecular β-sheets each. We find evidence that the high-frequency peak in the amide-I spectrum of αS fibrils involves a normal mode that differs fundamentally from the canonical high-frequency antiparallel β-sheet mode. The high sensitivity of the fibril structure to the ionic strength might form the basis of differences in αS-related pathologies.

  8. Microglia acquire distinct activation profiles depending on the degree of alpha-synuclein neuropathology in a rAAV based model of Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Vanesa Sanchez-Guajardo

    Full Text Available Post-mortem analysis of brains from Parkinson's disease (PD patients strongly supports microglia activation and adaptive immunity as factors contributing to disease progression. Such responses may be triggered by alpha-synuclein (alpha-syn, which is known to be the main constituent of the aggregated proteins found in Lewy bodies in the brains of PD patients. To investigate this we used a recombinant viral vector to express human alpha-syn in rat midbrain at levels that induced neuronal pathology either in the absence or the presence of dopaminergic cell death, thereby mimicking early or late stages of the disease. Microglia activation was assessed by stereological quantification of Mac1+ cells, as well as the expression patterns of CD68 and MCH II. In our study, when alpha-syn induced neuronal pathology but not cell death, a fast transient increase in microglia cell numbers resulted in the long-term induction of MHC II+ microglia, denoting antigen-presenting ability. On the other hand, when alpha-syn induced both neuronal pathology and cell death, there was a delayed increase in microglia cell numbers, which correlated with long-lasting CD68 expression and a morphology reminiscent of peripheral macrophages. In addition T-lymphocyte infiltration, as judged by the presence of CD4+ and CD8+ cells, showed distinct kinetics depending on the degree of neurodegeneration, and was significantly higher when cell death occurred. We have thus for the first time shown that the microglial response differs depending on whether alpha-syn expression results on cell death or not, suggesting that microglia may play different roles during disease progression. Furthermore, our data suggest that the microglial response is modulated by early events related to alpha-syn expression in substantia nigra and persists at the long term.

  9. Diacylglycerol kinase β knockout mice exhibit attention-deficit behavior and an abnormal response on methylphenidate-induced hyperactivity.

    Directory of Open Access Journals (Sweden)

    Mitsue Ishisaka

    Full Text Available BACKGROUND: Diacylglycerol kinase (DGK is an enzyme that phosphorylates diacylglycerol to produce phosphatidic acid. DGKβ is one of the subtypes of the DGK family and regulates many intracellular signaling pathways in the central nervous system. Previously, we demonstrated that DGKβ knockout (KO mice showed various dysfunctions of higher brain function, such as cognitive impairment (with lower spine density, hyperactivity, reduced anxiety, and careless behavior. In the present study, we conducted further tests on DGKβ KO mice in order to investigate the function of DGKβ in the central nervous system, especially in the pathophysiology of attention deficit hyperactivity disorder (ADHD. METHODOLOGY/PRINCIPAL FINDINGS: DGKβ KO mice showed attention-deficit behavior in the object-based attention test and it was ameliorated by methylphenidate (MPH, 30 mg/kg, i.p.. In the open field test, DGKβ KO mice displayed a decreased response to the locomotor stimulating effects of MPH (30 mg/kg, i.p., but showed a similar response to an N-methyl-d-aspartate (NMDA receptor antagonist, MK-801 (0.3 mg/kg, i.p., when compared to WT mice. Examination of the phosphorylation of extracellular signal-regulated kinase (ERK, which is involved in regulation of locomotor activity, indicated that ERK1/2 activation induced by MPH treatment was defective in the striatum of DGKβ KO mice. CONCLUSIONS/SIGNIFICANCE: These findings suggest that DGKβ KO mice showed attention-deficit and hyperactive phenotype, similar to ADHD. Furthermore, the hyporesponsiveness of DGKβ KO mice to MPH was due to dysregulation of ERK phosphorylation, and that DGKβ has a pivotal involvement in ERK regulation in the striatum.

  10. Female mucopolysaccharidosis IIIA mice exhibit hyperactivity and a reduced sense of danger in the open field test.

    Directory of Open Access Journals (Sweden)

    Alex Langford-Smith

    Full Text Available Reliable behavioural tests in animal models of neurodegenerative diseases allow us to study the natural history of disease and evaluate the efficacy of novel therapies. Mucopolysaccharidosis IIIA (MPS IIIA or Sanfilippo A, is a severe, neurodegenerative lysosomal storage disorder caused by a deficiency in the heparan sulphate catabolising enzyme, sulfamidase. Undegraded heparan sulphate accumulates, resulting in lysosomal enlargement and cellular dysfunction. Patients suffer a progressive loss of motor and cognitive function with severe behavioural manifestations and premature death. There is currently no treatment. A spontaneously occurring mouse model of the disease has been described, that has approximately 3% of normal enzyme activity levels. Behavioural phenotyping of the MPS IIIA mouse has been previously reported, but the results are conflicting and variable, even after full backcrossing to the C57BL/6 background. Therefore we have independently backcrossed the MPS IIIA model onto the C57BL/6J background and evaluated the behaviour of male and female MPS IIIA mice at 4, 6 and 8 months of age using the open field test, elevated plus maze, inverted screen and horizontal bar crossing at the same circadian time point. Using a 60 minute open field, we have demonstrated that female MPS IIIA mice are hyperactive, have a longer path length, display rapid exploratory behaviour and spend less time immobile than WT mice. Female MPS IIIA mice also display a reduced sense of danger and spend more time in the centre of the open field. There were no significant differences found between male WT and MPS IIIA mice and no differences in neuromuscular strength were seen with either sex. The altered natural history of behaviour that we observe in the MPS IIIA mouse will allow more accurate evaluation of novel therapeutics for MPS IIIA and potentially other neurodegenerative disorders.

  11. Alpha synuclein in Parkinson's disease

    DEFF Research Database (Denmark)

    Kragh, Christine Lund; Romero-Ramos, Marina; Halliday, Glenda M

    2014-01-01

    The perception of Parkinson’s disease (PD) as a disease centered on dopaminergic striatonigral neurodegeneration has changed fundamentally since 1997 when the first mutation in the SNCA gene (PARK1) encoding a-synuclein was discovered (Polymeropoulos et al. 1997). This discovery formed the basis...... the last decade (Gai et al. 1998; Spillantini and Goedert 2000; Huang et al. 2004; Ubhi et al. 2011). This review will briefly highlight the historical breakthroughs but focus on a-synuclein modifications, human neuropathology, biomarker potential, current animal models and the new concepts emerging after...

  12. Site-specific perturbations of alpha-synuclein fibril structure by the Parkinson's disease associated mutations A53T and E46K.

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    Luisel R Lemkau

    Full Text Available Parkinson's disease (PD is pathologically characterized by the presence of Lewy bodies (LBs in dopaminergic neurons of the substantia nigra. These intracellular inclusions are largely composed of misfolded α-synuclein (AS, a neuronal protein that is abundant in the vertebrate brain. Point mutations in AS are associated with rare, early-onset forms of PD, although aggregation of the wild-type (WT protein is observed in the more common sporadic forms of the disease. Here, we employed multidimensional solid-state NMR experiments to assess A53T and E46K mutant fibrils, in comparison to our recent description of WT AS fibrils. We made de novo chemical shift assignments for the mutants, and used these chemical shifts to empirically determine secondary structures. We observe significant perturbations in secondary structure throughout the fibril core for the E46K fibril, while the A53T fibril exhibits more localized perturbations near the mutation site. Overall, these results demonstrate that the secondary structure of A53T has some small differences from the WT and the secondary structure of E46K has significant differences, which may alter the overall structural arrangement of the fibrils.

  13. Alpha-synuclein is a cellular ferrireductase.

    Directory of Open Access Journals (Sweden)

    Paul Davies

    Full Text Available α-synuclein (αS is a cellular protein mostly known for the association of its aggregated forms with a variety of diseases that include Parkinson's disease and Dementia with Lewy Bodies. While the role of αS in disease is well documented there is currently no agreement on the physiological function of the normal isoform of the protein. Here we provide strong evidence that αS is a cellular ferrireductase, responsible for reducing iron (III to bio available iron (II. The recombinant form of the protein has a V(Max of 2.72 nmols/min/mg and K(m 23 µM. This activity is also evident in lysates from neuronal cell lines overexpressing αS. This activity is dependent on copper bound to αS as a cofactor and NADH as an electron donor. Overexpression of α-synuclein by cells significantly increases the percentage of iron (II in cells. The common disease mutations associated with increased susceptibility to PD show no [corrected] differences in activity or iron (II levels. This discovery may well provide new therapeutic targets for PD and Lewy body dementias.

  14. Assays for alpha-synuclein aggregation

    DEFF Research Database (Denmark)

    Giehm, Lise; Lorenzen, Nikolai; Otzen, Daniel

    2011-01-01

    leading to their formation is important for designing new drugs as well as in development of new nano-biomaterials such as nano-tubes, wires, scaffolds etc. 6. Understanding the process of amyloid formation requires an ability to reproduce this aggregation under controlled circumstances, in other words...

  15. Alpha-synuclein and Parkinson disease

    Institute of Scientific and Technical Information of China (English)

    Hui Liu; Xiaozhong Wang

    2007-01-01

    OBJECTIVE: To review the recent progresses on the studies of α-synuclein in the pathogenesis of Parkinson disease (PD) and look into the perspective of α-synuclein as a new therapy target.DATA SOURCES: To search the literatures on the progresses of PD studies, especially on the structure, gene expression of α-synuclein and the pathogenesis of PD in Medline from January 1998 to February 2007.Search terms were "Parkinson's disease, α -synuclein" in English.STUDY SELECTION: Initial check the data and choose the original and review articles directly linked to the role of α -synuclein in PD pathogenesis and screening out indirectly discussing articles. Collect the full text and trace the quoting articles and the quoted articles. Only the latest reviews were chosen in Chinese articles.DATA EXTRACTION: There were 424 articles on α-synuclein and its role in the pathogenesis of PD and 43 articles directly related with α -synuclein were chosen among which 12 were reviews.DATA SYNTHESIS: α-synuclein is a kind of soluble protein expressed in pre-synapse in central nervous system encoded by gene in homologous chromosome 4q21. It has physiological function in modulating the stability of membrane and neural plasticity. There is a close relationship between gene mutation in α -synuclein and the pathogenesis of PD. Environmental and genetic factors can induce the misfolding of α-synuclein, and secondary structural change can result in oligomer formation which induces a series of cascade reaction to damage dopaminergic system subsequently. Cell and animal transgenic and non-transgenic models are established recently and the important role of α -synuclein in the pathogenesis both of familial and sporadic PD is confirmed. Studies reveal that inhibiting the aggregation of α -synuclein can prevent its neurotoxicity;gene parkin can intercept the cell death pathway triggered by the aggregation of α -synuclein in cytoplasm.CONCLUSION: Gene mutation of α -synuclein and the impairment in its structure and function are important in the pathogenesis of PD. Intervention of the gene mutations and abnormal protein aggregation of α -synuclein may be a new strategy for preventing and treating PD.

  16. Hyperactivity and sugar

    Science.gov (United States)

    ... medlineplus.gov/ency/article/002426.htm Hyperactivity and sugar To use the sharing features on this page, ... more likely to be hyperactive if they eat sugar, artificial sweeteners, or certain food colorings. Other experts ...

  17. Expression of human A53T alpha-synuclein in the rat substantia nigra using a novel AAV1/2 vector produces a rapidly evolving pathology with protein aggregation, dystrophic neurite architecture and nigrostriatal degeneration with potential to model the pathology of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Sun Xuan

    2010-10-01

    Full Text Available Abstract Background The pathological hallmarks of Parkinson's disease (PD include the presence of alpha-synuclein (α-syn rich Lewy bodies and neurites and the loss of dopaminergic (DA neurons of the substantia nigra (SN. Animal models of PD based on viral vector-mediated over-expression of α-syn have been developed and show evidence of DA toxicity to varying degrees depending on the type of virus used, its concentration, and the serotype of vector employed. To date these models have been variable, difficult to reproduce, and slow in their evolution to achieve a desired phenotype, hindering their use as a model for testing novel therapeutics. To address these issues we have taken a novel vector in this context, that can be prepared in high titer and which possesses an ability to produce neuronally-directed expression, with expression dynamics optimised to provide a rapid rise in gene product expression. Thus, in the current study, we have used a high titer chimeric AAV1/2 vector, to express human A53T α-syn, an empty vector control (EV, or green fluorescent protein (GFP, the latter to control for the possibility that high levels of protein in themselves might contribute to damage. Results We show that following a single 2 μl injection into the rat SN there is near complete coverage of the structure and expression of A53T α-syn or GFP appears throughout the striatum. Within 3 weeks of SN delivery of their respective vectors, aggregations of insoluble α-syn were observed in SN DA neurons. The numbers of DA neurons in the SN were significantly reduced by expression of A53T α-syn (52%, and to a lesser extent by GFP (24%, compared to EV controls (both P P Conclusions In the current implementation of the model, we recapitulate the primary pathological hallmarks of PD, although a proportion of the SN damage may relate to general protein overload and may not be specific for A53T α-syn. Future studies will thus be required to optimise the dose of

  18. Mechanisms of Alpha-synuclein Aggregation and Toxicity

    Science.gov (United States)

    2004-09-01

    receptor (Pael-R) [14,36]. The interaction of parkin with Brain samples CHIP suggests that it operates in the endoplasmic re- Case PMI Age Sex Diagnosis...that Car2 is significantly oxidized in A30P α- synuclein mice and since oxidative preteen generally have decreased acitivity [35], this result

  19. Alpha-synuclein gene structure,evolution,and protein aggregation

    Institute of Scientific and Technical Information of China (English)

    Lili Xiong; Peng Zhao; Zhiyun Guo; Jianhua Zhang; Diqiang Li; Canquan Mao

    2010-01-01

    α-synuclein,a member of the synuclein family,is predominately expressed in brain tissues,where it is the major component of Lewy bodies,the major hallmark of Parkinson's disease.We analyzed the phylogenetics,gene structure,and effects of different forms of α-synuclein on in vitro protein aggregation.The synuclein phylogenetic tree showed that sequences could be classified into α,β,and γ protein groups.The orthologous gene α-,β-and γ-synuclein showed similar evolutionary distance to the paralogous gene α-,β-and γ-synuclein.Bioinformatics analysis suggests that the amino-acid sequence of human α-synuclein can be divided into three regions: N-terminal amphipathic region(1-60),central hydrophobic non-amyloid beta component segment(61-95),and the C-terminal acidic part(96-140).The mutant site of A30P is at the second exon of α-synuclein,whereas E46K is located at the third exon of α-synuclein.α-synuclein alternative splicing results in four isomers,and five exons,all of which participate in protein coding,comprising 140 amino acids to produce the major α-synuclein in vivo.The threeα-synuclein isoforms are products of alternative splicing,α-synuclein 126,112 and 98.We also review the genetic and cellular factors that affect the aggregation of α-synuclein and compounds that inhibit aggregation.A better understanding of α-synuclein sequences,structure,and function may allow better targeted therapy and diagnosis of α-synuclein in Parkinson's disease and other neurodegenerative diseases.

  20. Neuropathology in mice expressing mouse alpha-synuclein.

    Directory of Open Access Journals (Sweden)

    Claus Rieker

    Full Text Available α-Synuclein (αSN in human is tightly linked both neuropathologically and genetically to Parkinson's disease (PD and related disorders. Disease-causing properties in vivo of the wildtype mouse ortholog (mαSN, which carries a threonine at position 53 like the A53T human mutant version that is genetically linked to PD, were never reported. To this end we generated mouse lines that express mαSN in central neurons at levels reaching up to six-fold compared to endogenous mαSN. Unlike transgenic mice expressing human wildtype or mutant forms of αSN, these mαSN transgenic mice showed pronounced ubiquitin immunopathology in spinal cord and brainstem. Isoelectric separation of mαSN species revealed multiple isoforms including two Ser129-phosphorylated species in the most severely affected brain regions. Neuronal Ser129-phosphorylated αSN occurred in granular and small fibrillar aggregates and pathological staining patterns in neurites occasionally revealed a striking ladder of small alternating segments staining either for Ser129-phosphorylated αSN or ubiquitin but not both. Axonal degeneration in long white matter tracts of the spinal cord, with breakdown of myelin sheaths and degeneration of neuromuscular junctions with loss of integrity of the presynaptic neurofilament network in mαSN transgenic mice, was similar to what we have reported for mice expressing human αSN wildtype or mutant forms. In hippocampal neurons, the mαSN protein accumulated and was phosphorylated but these neurons showed no ubiquitin immunopathology. In contrast to the early-onset motor abnormalities and muscle weakness observed in mice expressing human αSN, mαSN transgenic mice displayed only end-stage phenotypic alterations that manifested alongside with neuropathology. Altogether these findings show that increased levels of wildtype mαSN does not induce early-onset behavior changes, but drives end-stage pathophysiological changes in murine neurons that are strikingly similar to those evoked by expression of human wildtype or mutant forms.

  1. Mutant alpha-synuclein and autophagy in PC12 cells

    Institute of Scientific and Technical Information of China (English)

    Kangyong Liu; Chunfeng Liu; Chuancheng Ren; Yaping Yang; Liwei Shen; Xuezhong Li; Fen Wang; Zhenghong Qin

    2011-01-01

    Several studies have demonstrated that overexpression of mutant α-synuclein in PC12 cells is related to occurrence of autophagy.The present study established mutant a-synuclein (A30P)-transfected PC12 cells and treated them with the autophagy inducer rapamycin and autophagy inhibitor wortmannin, respectively.Results demonstrated that mutant o-synuclein resulted in cell death via autophagy and involved α-synuclein accumulation, membrane lipid oxidation, and loss of plasma membrane integrity.Mutant α-synuclein (A30P) also mediated toxicity of1-methyl-4-phenylpyridinium ion.Moreover, rapamycin inhibited a-synuclein aggregation, while wortmannin promoted o-synuclein aggregation and cell death.To further determine the role of autophagy due to mutant a-synuclein, the present study measured expression of microtubule-associated protein light chain 3.Results revealed that wortmannin and 1-methyl-4-phenylpyridinium ion inhibited expression of microtubule-associated protein light chain 3,while rapamycin promoted its expression.These findings suggested that abnormal aggregation of a-synuclein induced autophagic programmed cell death in PC12 cells.

  2. Interactions between Calcium and Alpha-Synuclein in Neurodegeneration

    Directory of Open Access Journals (Sweden)

    Alex Rcom-H'cheo-Gauthier

    2014-08-01

    Full Text Available In Parkinson’s disease and some atypical Parkinson’s syndromes, aggregation of the α-synuclein protein (α-syn has been linked to neurodegeneration. Many triggers for pathological α-syn aggregation have been identified, including port-translational modifications, oxidative stress and raised metal ions, such as Ca2+. Recently, it has been found using cell culture models that transient increases of intracellular Ca2+ induce cytoplasmic α-syn aggregates. Ca2+-dependent α-syn aggregation could be blocked by the Ca2+ buffering agent, BAPTA-AM, or by the Ca2+ channel blocker, Trimethadione. Furthermore, a greater proportion of cells positive for aggregates occurred when both raised Ca2+ and oxidative stress were combined, indicating that Ca2+ and oxidative stress cooperatively promote α-syn aggregation. Current on-going work using a unilateral mouse lesion model of Parkinson’s disease shows a greater proportion of calbindin-positive neurons survive the lesion, with intracellular α-syn aggregates almost exclusively occurring in calbindin-negative neurons. These and other recent findings are reviewed in the context of neurodegenerative pathologies and suggest an association between raised Ca2+, α-syn aggregation and neurotoxicity.

  3. Mechanisms of alpha-Synuclein Aggregation and Toxicity

    Science.gov (United States)

    2006-09-01

    K. R., Krajcarski, D. T., and Rayner, D. M. (1978) FEBS Lett. 94, 249–252 31. Thomson, A. M., Rogers , J. T., and Leedman, P. J. (1999) Int. J...McNaught, K.S., and Jenner, P. (2001). Proteasomal function is im- Chartier -Harlin, M. (2000). Linkage exclusion in French families with paired in

  4. Exhibit Engineering

    DEFF Research Database (Denmark)

    Mortensen, Marianne Foss

    ) a synthesis of the findings from the first two studies with findings from the literature to generate two types of results: a coherent series of suggestions for a design iteration of the studied exhibit as well as a more general normative model for exhibit engineering. Finally, another perspective...

  5. Alpha-Synuclein Oligomers: an Amyloid Pore? Insights into Mechanisms of alpha-Synuclein Oligomer-Lipid Interactions

    NARCIS (Netherlands)

    Stockl, Martin T.; Zijlstra, Niels; Subramaniam, Vinod

    2013-01-01

    In many human diseases, oligomeric species of amyloid proteins may play a pivotal role in cytotoxicity. Many lines of evidence indicate that permeabilization of cellular membranes by amyloid oligomers may be the key factor in disrupting cellular homeostasis. However, the exact mechanisms by which th

  6. alpha-Synuclein Oligomers: an Amyloid Pore? : Insights into Mechanisms of alpha-Synuclein Oligomer-Lipid Interactions

    NARCIS (Netherlands)

    Stockl, M.T.; Zijlstra, N.; Subramaniam, V.

    2013-01-01

    In many human diseases, oligomeric species of amyloid proteins may play a pivotal role in cytotoxicity. Many lines of evidence indicate that permeabilization of cellular membranes by amyloid oligomers may be the key factor in disrupting cellular homeostasis. However, the exact mechanisms by which th

  7. Human Exhibitions

    DEFF Research Database (Denmark)

    Andreassen, Rikke

    From 1870s to 1910s, more than 50 exhibitions of so-called exotic people took place in Denmark. Here large numbers of people of Asian and African origin were exhibited for the entertainment and ‘education’ of a mass audience. Several of these exhibitions took place in Copenhagen Zoo. Here different...... light on the staging of exhibitions, the daily life of the exhibitees, the wider connections between shows across Europe and the thinking of the time on matters of race, science, gender and sexuality. A window onto contemporary racial understandings, the book presents interviews with the descendants...... of displayed people, connecting the attitudes and science of the past with both our (continued) modern fascination with ‘the exotic’, and contemporary language and popular culture. As such, it will be of interest to scholars of sociology, anthropology and history working in the areas of gender and sexuality...

  8. Attention deficit hyperactivity disorder (ADHD)

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/001551.htm Attention deficit hyperactivity disorder To use the sharing features on this page, please enable JavaScript. Attention deficit hyperactivity disorder (ADHD) is a problem caused by the presence ...

  9. Exhibit Engineering

    DEFF Research Database (Denmark)

    Mortensen, Marianne Foss

    of tools and processes to guide the design of educational science exhibits. The guiding paradigm for this development is design-based research, which is characterised by an iterative cycle of design, enactment, and analysis. In the design phase, an educational intervention is planned and carried out based...... on a hypothesised learning process and the means of supporting it. In the enactment phase, the educational intervention is implemented (i.e. the planned lesson is taught, or the museum exhibit is opened to the public). Finally, the analysis phase establishes causality between emergent characteristics...... of the learning outcomes and the design characteristics of the intervention. The analysis process can yield two types of outcomes: Suggestions for the refinement of the specific design in question, and “humble” theory, which is theory that can guide the design of a category of educational interventions...

  10. Faking attention deficit hyperactivity disorder.

    Science.gov (United States)

    Sansone, Randy A; Sansone, Lori A

    2011-08-01

    Attention-deficit hyperactivity disorder is a common malady in the general population, with up to 8.1 percent of adults meeting criteria for this syndrome. In the college setting, the diagnosis of attention deficit hyperactivity disorder may offer specific academic advantages. Once the diagnosis is assigned, the prescription of stimulant medication may provide additional secondary gains through misuse and/or diversion. For example, these drugs may be used by college consumers to increase alertness, energy, academic performance, and athletic performance. Stimulants may also decrease psychological distress, alleviate restlessness and weight concerns, and be used for recreational purposes. According to the findings of five studies, the symptoms of attention deficit hyperactivity disorder can be believably faked, particularly when assessed with attention deficit hyperactivity disorder symptom checklists. Thus, the faking of attention deficit hyperactivity disorder is a realistic concern in both psychiatric and primary care settings.

  11. Behaviors of Children Referred by Classroom Teachers as Hyperactive.

    Science.gov (United States)

    Shecket, Susan M.; Shecket, William C.

    In this study, a classroom observation technique was employed to examine the behaviors of a group of teacher-referred hyperactive children in order to determine the frequency of specific behaviors exhibited. The purpose behind the study was the further investigation of behavioral observation and intervention techniques used by other researchers as…

  12. Perivascular nerve fiber α-synuclein regulates contractility of mouse aorta: a link to autonomic dysfunction in Parkinson's disease.

    Science.gov (United States)

    Marrachelli, Vannina G; Miranda, Francisco J; Alabadí, José A; Milán, Miguel; Cano-Jaimez, Marifé; Kirstein, Martina; Alborch, Enrique; Fariñas, Isabel; Pérez-Sánchez, Francisco

    2010-07-01

    Parkinson's disease and other neurodegenerative disorders associated to changes in alpha-synuclein often result in autonomic dysfunction, most of the time accompanied by abundant expression of this synaptic protein in peripheral autonomic neurons. Given that expression of alpha-synuclein in vascular elements has been previously reported, the present study was undertaken to determine whether alpha-synuclein directly participates in the regulation of vascular responsiveness. We detected by immunohistochemistry perivascular nerve fibers containing alpha-synuclein in the aorta of mice while aortic endothelial cells and muscular fibers themselves did not exhibit detectable levels of this protein. To assess the effect of alpha-synuclein on vascular reactivity, aortic ring preparations obtained from alpha-synuclein-deficient knockout mice and from transgenic mice overexpressing human wild-type alpha-synuclein under the control of the tyrosine hydroxylase-promoter were mounted and equilibrated in organ baths for isometric tension recording. Lack of alpha-synuclein did not modify the relaxant responses to the endothelium-dependent (acetylcholine) and -independent (sodium nitroprusside) vasodilators, but resulted in a greater than normal norepinephrine-induced vasoconstriction along with a lowered response to dopamine, suggesting potential presynaptic changes in dopamine and norepinephrine releases in knockout mice. Overexpression of alpha-synuclein in TH-positive fibers resulted in complex abnormal responses, characterized by lowered acetylcholine-induced relaxation and lowered norepinephrin-induced contraction. Taken together, our data show for the first time that alpha-synuclein is present in sympathetic fibers supplying the murine aorta and provide evidence that changes in alpha-synuclein levels in perivascular fibers play a physiological role in the regulation of vascular function.

  13. Treatment of the Hyperactive Child

    Science.gov (United States)

    Wunderlich, Ray C.

    1973-01-01

    Described individually are the following forms of medical treatment for the hyperactive child: stimulants, tranquilizers, megavitamins, corticosteroids, antihistamines, anticonvulsants, food elimination, air filtration, allergic desensitization, perceptual motor training, and behavioral counseling. (DB)

  14. Faking Attention Deficit Hyperactivity Disorder

    OpenAIRE

    2011-01-01

    Attention-deficit hyperactivity disorder is a common malady in the general population, with up to 8.1 percent of adults meeting criteria for this syndrome. In the college setting, the diagnosis of attention deficit hyperactivity disorder may offer specific academic advantages. Once the diagnosis is assigned, the prescription of stimulant medication may provide additional secondary gains through misuse and/or diversion. For example, these drugs may be used by college consumers to increase aler...

  15. [Attention deficit hyperactivity disorder].

    Science.gov (United States)

    Cunill, Ruth; Castells, Xavier

    2015-04-20

    Attention deficit hyperactivity disorder (ADHD) is one of the most common childhood psychiatric disorders and can persist into the adulthood. ADHD has important social, academic and occupational consequences. ADHD diagnosis is based on the fulfillment of several clinical criteria, which can vary depending on the diagnostic system used. The clinical presentation can show great between-patient variability and it has been related to a dysfunction in the fronto-striatal and meso-limbic circuits. Recent investigations support a model in which multiple genetic and environmental factors interact to create a neurobiological susceptibility to develop the disorder. However, no clear causal association has yet been identified. Although multimodal treatment including both pharmacological and psychosocial interventions is usually recommended, no convincing evidence exists to support this recommendation. Pharmacological treatment has fundamentally shown to improve ADHD symptoms in the short term, while efficacy data for psychosocial interventions are scarce and inconsistent. Yet, drug treatment is increasingly popular and the last 2 decades have witnessed a sharp increase in the prescription of anti-ADHD medications coinciding with the marketing of new drugs to treat ADHD.

  16. Faststats: Attention Deficit Hyperactivity Disorder (ADHD)

    Science.gov (United States)

    ... this? Submit What's this? Submit Button NCHS Home Attention Deficit Hyperactivity Disorder (ADHD)* Recommend on Facebook Tweet Share Compartir Data ... attention deficit disorder (ADD)" is used rather than "attention deficit hyperactivity disorder (ADHD)" in some data sources. More data Association ...

  17. Expectancies and Attributions for Hyperactive and Medicated Hyperactive Students.

    Science.gov (United States)

    Amirkhan, James

    1982-01-01

    Eighty students and 15 teachers provided expectancies and attributions for the academic performance of hypothetical medicated and nonmedicated hyperactive children. Both teachers and peers had higher expectancies for the medicated than for the nonmedicated child. Data suggested that these differential expectancies may arise from different…

  18. Parallel Exhibits: Combining Physical and Virtual Exhibits

    NARCIS (Netherlands)

    L. Lischke; T. Dingler; S. Schneegaß; A. Schmidt; M. van der Vaart; P. Wozniak

    2014-01-01

    People have a special fascination for original physical objects, their texture, and visible history. However, the digitization of exhibits and the use of these data is a current challenge for museums. We believe that museums need to capitalize on the affordances of physical exhibits to help users na

  19. Inhibition of prolyl oligopeptidase increases the survival of alpha-synuclein overexpressing cells after rotenone exposure by reducing alpha-synuclein oligomers.

    Science.gov (United States)

    Dokleja, Lana; Hannula, Mirva J; Myöhänen, Timo T

    2014-11-07

    α-Synuclein (aSyn) aggregation, mitochondrial dysfunction and oxidative damage has been shown to be related to the death of dopaminergic neurons in Parkinson's disease (PD). Prolyl oligopeptidase (PREP) is proposed to increase aSyn aggregation, and PREP inhibition has been shown to inhibit the aggregation process in vitro and in vivo. In this study, we investigated the effects of a specific PREP inhibitor, KYP-2047, on rotenone induced aSyn aggregation and increased the production of reactive oxygen species (ROS) in cells overexpressing A53T mutation of aSyn. Rotenone, a mitochondrial toxin that induces oxidative damage and aSyn aggregation, associated with PD pathology, was selected as a model for this study. The results showed that rotenone induced the formation of high-molecular-weight aSyn oligomers, and this was countered by simultaneous incubation with KYP-2047. Inhibition of PREP also decreased the production of ROS in [A53T]aSyn overexpressing cells, leading to improved cell viability.

  20. Britain exhibition at CERN

    CERN Multimedia

    Bertin; CERN PhotoLab

    1969-01-01

    The United Kingdom inaugurated the Industrial Exhibitions in 1968, and it wasn't till 1971 that other countries staged exhibitions at CERN. This photo was taken in 1969, at the second British exhibition, where 16 companies were present.

  1. Hyperactivity, Learning Disabilities, and Alcohol.

    Science.gov (United States)

    Gold, Sandra; Sherry, Lee

    1984-01-01

    A review of research on the effects of alcohol consumption by pregnant women supports the U.S. Food and Drug Administration's warning about the possible negative effects (learning disabilities, hyperactivity, short attention span, and emotional liability) of children. (Author/CL)

  2. Hyperactivity: Exceptional Child Bibliography Series.

    Science.gov (United States)

    Council for Exceptional Children, Reston, VA. Information Center on Exceptional Children.

    Containing 27 references on hyperactivity selected from "Exceptional Child Education Abstracts", the bibliography cites research reports, conference papers, journal articles, texts, and program guides. Each entry provides bibliographical data, availability information, indexing and retrieval descriptors, and abstracts of the documents. The…

  3. Attention Deficit Hyperactivity Disorder (ADHD)

    Centers for Disease Control (CDC) Podcasts

    2014-04-10

    This podcast discusses Attention Deficit Hyperactivity Disorder, or ADHD, the most common behavioral disorder in children. Learn about symptoms, risk factors, and treatment.  Created: 4/10/2014 by National Center on Birth Defects and Developmental Disabilities (NCBDDD).   Date Released: 5/7/2014.

  4. Testosterone and Androgen Receptor Sensitivity in Relation to Hyperactivity Symptoms in Boys with Autism Spectrum Disorders

    Science.gov (United States)

    2016-01-01

    Introduction Autism spectrum disorders (ASD) and hyperactivity symptoms exhibit an incidence that is male-biased. Thus androgen activity can be considered a plausible biological risk factor for these disorders. However, there is insufficient information about the association between increased androgen activity and hyperactivity symptoms in children with ASD. Methods In the present study, the relationship between parameters of androgenicity (plasmatic testosterone levels and androgen receptor sensitivity) and hyperactivity in 60 boys (age 3–15) with ASD is investigated. Given well documented differences in parent and trained examiners ratings of symptom severity, we employed a standardized parent`s questionnaire (Nisonger Child Behavior Rating Form) as well as a direct examiner`s rating (Autism diagnostic observation schedule) for assessment of hyperactivity symptoms. Results Although it was found there was no significant association between actual plasmatic testosterone levels and hyperactivity symptoms, the number of CAG triplets was significantly negatively correlated with hyperactivity symptoms (R2 = 0.118, p = 0.007) in the sample, indicating increased androgen receptor sensitivity in association with hyperactivity symptoms. Direct trained examiner´s assessment appeared to be a relevant method for evaluating of behavioral problems in the investigation of biological underpinnings of these problems in our study. Conclusions A potential ASD subtype characterized by increased rates of hyperactivity symptoms might have distinct etiopathogenesis and require a specific behavioral and pharmacological approach. We propose an increase of androgen receptor sensitivity as a biomarker for a specific ASD subtype accompanied with hyperactivity symptoms. Findings are discussed in terms of their implications for practice and future research. PMID:26910733

  5. Statistical Evidence Suggests that Inattention Drives Hyperactivity/Impulsivity in Attention Deficit-Hyperactivity Disorder

    NARCIS (Netherlands)

    Sokolova, E; Groot, P.; Claassen, T.; Hulzen, K.J.E. van; Glennon, J.C.; Franke, B.; Heskes, T.; Buitelaar, J.K.

    2016-01-01

    BACKGROUND: Numerous factor analytic studies consistently support a distinction between two symptom domains of attention-deficit/hyperactivity disorder (ADHD), inattention and hyperactivity/impulsivity. Both dimensions show high internal consistency and moderate to strong correlations with each othe

  6. Diagnostic value of minor salivary glands biopsy for the detection of Lewy pathology.

    Science.gov (United States)

    Folgoas, Emmanuelle; Lebouvier, Thibaud; Leclair-Visonneau, Laurène; Cersosimo, Maria-Graciela; Barthelaix, Annick; Derkinderen, Pascal; Letournel, Franck

    2013-09-13

    The recent demonstration of the presence of Lewy pathology in the submandibular glands of Parkinson's disease (PD) patients prompted us to evaluate the diagnostic performance of minor salivary gland biopsy for PD. Minor salivary glands were examined for Lewy pathology using phosphorylated alpha-synuclein antibody in 16 patients with clinically diagnosed PD and 11 control subjects with other neurological disorders. Abnormal accumulation of alpha-synuclein was found in 3 out of 16 PD patients. Two control subjects exhibited weak phosphorylated alpha-synuclein immunoreactivity. Our results do not support the use of minor salivary glands biopsy for the detection of Lewy pathology in living subjects.

  7. Digital collections and exhibits

    CERN Document Server

    Denzer, Juan

    2015-01-01

    Today's libraries are taking advantage of cutting-edge technologies such as flat panel displays using touch, sound, and hands-free motions to design amazing exhibits using everything from simple computer hardware to advanced technologies such as the Microsoft Kinect. Libraries of all types are striving to add new interactive experiences for their patrons through exciting digital exhibits, both online and off. Digital Collections and Exhibits takes away the mystery of designing stunning digital exhibits to spotlight library trea

  8. Ethics on Exhibit

    Science.gov (United States)

    Vick, Randy M.

    2011-01-01

    This article discusses ethical questions raised by an exhibition of work by an artist with a history of mental illness and the exhibition's relevance to art therapy and “outsider art” discourse on the subject. Considerations for how such an exhibit could be handled had the circumstances included an art therapist and art therapy client are…

  9. Etruscan Culture Exhibition

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    EARLY this year an exhibition on the ancient civilization of Etruria was held at the Beijing-based China Millennium Monument.The theme of the exhibition was Etruscan Culture and on show were the most representative cultural and historical relics of this ancient civilization unearthed in the past 20 years. The 349 exhibits from various

  10. Exhibiting Mozart: Rethinking Biography

    OpenAIRE

    Spring, Ulrike

    2010-01-01

    Abstract: The article analyses the new permanent exhibition in the composer Wolfgang A. Mozart’s apartment in Vienna, opened in 2006, from the curator’s perspective. The exhibition presents an approach to biographical display in which the exhibited person becomes part of a multifaceted web of contexts, and the article argues for the active deployment of the polysemic character of objects as a means of grasping the complexity of a person’s biography. Presenting a concept for the...

  11. Hyperactivity in a Sample of Omani Schoolboys

    Science.gov (United States)

    Al-Sharbati, Marwan; Al-Adawi, Samir; Ganguly, Shyam; Al-Lawatiya, Salwa; Al-Mshefri, Faysal

    2008-01-01

    Objective: There is a dearth of cross-cultural research on hyperactivity. This article aims to quantify the prevalence of hyperactivity in schoolboys residing in an Arab/Islamic country, Oman. Method: 1,502 Omani schoolboys from eight randomly selected schools representing the urban population of Oman were screened for various indices of…

  12. Rorschach Indices of Children Classified as Hyperactive.

    Science.gov (United States)

    Gordon, Michael; Oshman, Harvey

    1981-01-01

    The Rorschach protocols of 20 boys (ages 6-11 years) rated by their teachers as hyperactive and those of 20 nonhyperactive boys were compared along 16 indices. Findings are discussed in terms of the assessment of hyperactivity within a conceptual framework which regards impulsivity as a major underlying dimension. (Author/SJL)

  13. Medication Treatment for Attention Deficit Hyperactivity Disorder

    Science.gov (United States)

    Ryan, Joseph B.; Katsiyannis, Antonis; Hughes, Elizabeth M.

    2011-01-01

    Attention deficit hyperactivity disorder (ADHD) has become the most commonly diagnosed psychiatric disorder among school-age children. For more than half a century, physicians have prescribed medications to help manage behaviors such as hyperactivity, impulsivity, and inattention. Today, there is a growing consensus that ADHD is a biologically…

  14. Attention deficit hyperactivity disorder (ADHD

    Directory of Open Access Journals (Sweden)

    Fabio de Almeida Bolognani

    2011-07-01

    Full Text Available The objective of this study, stated as Previous Notation, is to demonstrate that Attention Deficit Hyperactivity Disorder Pathology presents a differentiated condition in carriers where a significant percentage, close to 60%, present a higher level of zinc elimination by kidneys. In this study, a direct relation of Zinc Mettalicum pathogenetic symptoms, this disturbance and the elimination of this element which participates in neurotransmission process were identified, and the relation with elements from regular diet, which can act as zinc chelating agents would be involved in the evolution of this disturbance, justifying the issue of individual susceptibility, essential in homeopathic investigation

  15. Shortened Conditioned Eyeblink Response Latency in Male but not Female Wistar-Kyoto Hyperactive Rats

    Science.gov (United States)

    Thanellou, Alexandra; Schachinger, Kira M.; Green, John T.

    2014-01-01

    Reductions in the volume of the cerebellum and impairments in cerebellar-dependent eyeblink conditioning have been observed in attention-deficit/hyperactivity disorder (ADHD). Recently, it was reported that subjects with ADHD as well as male spontaneously hypertensive rats (SHR), a strain that is frequently employed as an animal model in the study of ADHD, exhibit a parallel pattern of timing deficits in eyeblink conditioning. One criticism that has been posed regarding the validity of the SHR strain as an animal model for the study of ADHD is that SHRs are not only hyperactive but also hypertensive. It is conceivable that many of the behavioral characteristics seen in SHRs that seem to parallel the behavioral symptoms of ADHD are not solely due to hyperactivity but instead are the net outcome of the interaction between hyperactivity and hypertension. We used Wistar-Kyoto Hyperactive (WKHA) and Wistar-Kyoto Hypertensive (WKHT) rats (males and females), strains generated from recombinant inbreeding of SHRs and their progenitor strain, Wistar-Kyoto (WKY) rats, to compare eyeblink conditioning in strains that are exclusively hyperactive or hypertensive. We used a long-delay eyeblink conditioning task in which a tone conditioned stimulus was paired with a periorbital stimulation unconditioned stimulus (750-ms delay paradigm). Our results showed that WKHA and WKHT rats exhibited similar rates of conditioned response (CR) acquisition. However, WKHA males displayed shortened CR latencies (early onset and peak latency) in comparison to WKHT males. In contrast, female WKHAs and WKHTs did not differ. In subsequent extinction training, WKHA rats extinguished at similar rates in comparison to WKHT rats. The current results support the hypothesis of a relationship between cerebellar abnormalities and ADHD in an animal model of ADHD-like symptoms that does not also exhibit hypertension, and suggest that cerebellar-related timing deficits are specific to males. PMID:19485572

  16. Cathepsin D expression level affects alpha-synuclein processing, aggregation, and toxicity in vivo

    Directory of Open Access Journals (Sweden)

    Cullen Valerie

    2009-02-01

    Full Text Available Abstract Background Elevated SNCA gene expression and intracellular accumulation of the encoded α-synuclein (aSyn protein are associated with the development of Parkinson disease (PD. To date, few enzymes have been examined for their ability to degrade aSyn. Here, we explore the effects of CTSD gene expression, which encodes the lysosomal protease cathepsin D (CathD, on aSyn processing. Results Over-expression of human CTSD cDNA in dopaminergic MES23.5 cell cultures induced the marked proteolysis of exogenously expressed aSyn proteins in a dose-dependent manner. Unexpectedly, brain extractions, Western blotting and ELISA quantification revealed evidence for reduced levels of soluble endogenous aSyn in ctsd knock-out mice. However, these CathD-deficient mice also contained elevated levels of insoluble, oligomeric aSyn species, as detected by formic acid extraction. In accordance, immunohistochemical studies of ctsd-mutant brain from mice, sheep and humans revealed selective synucleinopathy-like changes that varied slightly among the three species. These changes included intracellular aSyn accumulation and formation of ubiquitin-positive inclusions. Furthermore, using an established Drosophila model of human synucleinopathy, we observed markedly enhanced retinal toxicity in ctsd-null flies. Conclusion We conclude from these complementary investigations that: one, CathD can effectively degrade excess aSyn in dopaminergic cells; two, ctsd gene mutations result in a lysosomal storage disorder that includes microscopic and biochemical evidence of aSyn misprocessing; and three, CathD deficiency facilitates aSyn toxicity. We therefore postulate that CathD promotes 'synucleinase' activity, and that enhancing its function may lower aSyn concentrations in vivo.

  17. Alpha-synuclein promotes clathrin-mediated endocytosis of NMDA receptors in dopaminergic cells

    Institute of Scientific and Technical Information of China (English)

    Shun Yu; Furong Cheng; Xin Li; Yaohua Li; Tao Wang; Guangwei Liu; Andrius Baskys

    2012-01-01

    Loss of dopaminergic i a compensatory increase in nput to the striatum associated with Parkinson' s disease brings about glutamate release onto the dopaminergic cell bodies in the substantia nigra pars compacta (SNpc)[1] Glutamate over-activation of NMDA receptors on these cells can cause excitotoxicity and contribute to their further loss. NMDA receptor-mediated neuronal death is reduced by group I mGluR-mediated up-regulation of endocytosis protein RAB5B[2.3] Among proteins shown to interact with RAB5 proteins is a-synuclein

  18. Protective effect of alpha-synuclein knockdown on methamphetamine-induced neurotoxicity in dopaminergic neurons

    Institute of Scientific and Technical Information of China (English)

    Yunchun Tai; Ling Chen; Enping Huang; Chao Liu; Xingyi Yang; Pingming Qiu; Huijun Wang

    2014-01-01

    The over-expression of α-synuclein is a major factor in the death of dopaminergic neurons in a methamphetamine-induced model of Parkinson’s disease. In the present study, α-synuclein knockdown rats were created by injecting α-synuclein-shRNA lentivirus stereotaxically into the right striatum of experimental rats. At 2 weeks post-injection, the rats were injected intraper-itoneally with methamphetamine to establish the model of Parkinson’s disease. Expression ofα-synuclein mRNA and protein in the right striatum of the injected rats was significantly down-regulated. Food intake and body weight were greater in α-synuclein knockdown rats, and water intake and stereotyped behavior score were lower than in model rats. Striatal dopamine and tyrosine hydroxylase levels were significantly elevated in α-synuclein knockdown rats. Moreover, superoxide dismutase activity was greater in α-synuclein knockdown rat striatum, but the levels of reactive oxygen species, malondialdehyde, nitric oxide synthase and nitrogen monoxide were lower compared with model rats. We also found that α-synuclein knockdown inhibited metham-phetamine-induced neuronal apoptosis. These results suggest that α-synuclein has the capacity to reverse methamphetamine-induced apoptosis of dopaminergic neurons in the rat striatum by inhibiting oxidative stress and improving dopaminergic system function.

  19. Membrane-Bound Alpha Synuclein Clusters Induce Impaired Lipid Diffusion and Increased Lipid Packing.

    NARCIS (Netherlands)

    Iyer, Aditya; Schilderink, Nathalie; Claessens, Mireille M A E; Subramaniam, Vinod

    2016-01-01

    The aggregation of membrane-bound α-synuclein (αS) into oligomers and/or amyloid fibrils has been suggested to cause membrane damage in in vitro model phospholipid membrane systems and in vivo. In this study, we investigate how αS interactions that precede the formation of well-defined aggregates in

  20. Alpha-synuclein cell-to-cell transfer and seeding in grafted dopaminergic neurons in vivo.

    Directory of Open Access Journals (Sweden)

    Elodie Angot

    Full Text Available Several people with Parkinson's disease have been treated with intrastriatal grafts of fetal dopaminergic neurons. Following autopsy, 10-22 years after surgery, some of the grafted neurons contained Lewy bodies similar to those observed in the host brain. Numerous studies have attempted to explain these findings in cell and animal models. In cell culture, α-synuclein has been found to transfer from one cell to another, via mechanisms that include exosomal transport and endocytosis, and in certain cases seed aggregation in the recipient cell. In animal models, transfer of α-synuclein from host brain cells to grafted neurons has been shown, but the reported frequency of the event has been relatively low and little is known about the underlying mechanisms as well as the fate of the transferred α-synuclein. We now demonstrate frequent transfer of α-synuclein from a rat brain engineered to overexpress human α-synuclein to grafted dopaminergic neurons. Further, we show that this model can be used to explore mechanisms underlying cell-to-cell transfer of α-synuclein. Thus, we present evidence both for the involvement of endocytosis in α-synuclein uptake in vivo, and for seeding of aggregation of endogenous α-synuclein in the recipient neuron by the transferred α-synuclein. Finally, we show that, at least in a subset of the studied cells, the transmitted α-synuclein is sensitive to proteinase K. Our new model system could be used to test compounds that inhibit cell-to-cell transfer of α-synuclein and therefore might retard progression of Parkinson neuropathology.

  1. Interplay between desolvation and secondary structure in mediating cosolvent and temperature induced alpha-synuclein aggregation

    Science.gov (United States)

    Anderson, V. L.; Webb, W. W.; Eliezer, D.

    2012-10-01

    Both increased temperature and moderate concentrations of fluorinated alcohols enhance aggregation of the Parkinson's disease-associated protein α-synuclein (αS). Here, we investigate the secondary structural rearrangements induced by heating and trifluoroethanol [TFE]. At low TFE concentrations, CD spectra feature a negative peak characteristic of disordered polypeptides near 200 nm and a slight shoulder around 220 nm suggesting some polyproline-II content. Upon heating, these peaks weaken, while a weak negative signal develops at 222 nm. At high TFE concentrations, the spectra show distinct minima at 208 and 222 nm, indicative of considerable α-helical structure, which diminish upon heating. We observe a crossover between the low-TFE and high-TFE behavior near 15% TFE, where we previously showed that a partially helical intermediate is populated. We postulate that the protein is well solvated by water at low TFE concentrations and by TFE at high TFE concentrations, but may become desolvated at the crossover point. We discuss the potential roles and interplay of desolvation and helical secondary structure in driving αS aggregation.

  2. Alpha-synuclein oligomers - neurotoxic molecules in Parkinson’s disease and other Lewy body disorders

    Directory of Open Access Journals (Sweden)

    Martin Ingelsson

    2016-09-01

    Full Text Available Adverse intra- and extracellular effects of toxic α-synuclein are believed to be central to the pathogenesis in Parkinson’s disease and other disorders with Lewy body pathology in the nervous system. One of the physiological roles of α-synuclein relates to the regulation of neurotransmitter release at the presynapse, although it is still unclear whether this mechanism depends on the action of monomers or smaller oligomers. As for the pathogenicity, accumulating evidence suggest that prefibrillar species, rather than the deposits per se, are responsible for the toxicity in affected cells. In particular, larger oligomers or protofibrils of α-synuclein have been shown to impair protein degradation as well as the function of several organelles, such as the mitochondria and the endoplasmic reticulum. Accumulating evidence further suggest that oligomers/protofibrils may have a toxic effect on the synapse, which may lead to disrupted electrophysiological properties. In addition, recent data indicate that oligomeric α-synuclein species can spread between cells, either as free-floating proteins or via extracellular vesicles, and thereby act as seeds to propagate disease between interconnected brain regions. Taken together, several lines of evidence suggest that α-synuclein have neurotoxic properties and therefore should be an appropriate molecular target for therapeutic intervention in Parkinson’s disease and other disorders with Lewy pathology. In this context, immunotherapy with monoclonal antibodies against α-synuclein oligomers/protofibrils should be a particularly attractive treatment option.

  3. Tri- and pentamethine cyanine dyes for fluorescent detection of alpha-synuclein oligomeric aggregates

    NARCIS (Netherlands)

    Kovalska, V.B.; Yu Losytskyy, M.; Tolmachev, O.I.; Slominskii, Yu.L.; Segers-Nolten, G.M.J.; Subramaniam, V.; Yarmoluk, S.M.

    2012-01-01

    The pathogenesis of Parkinson’s disease that is the second most common neurodegenerative disease is associated with formation of different aggregates of α-synuclein (ASN), namely oligomers and amyloid fibrils. Current research is aimed on the design of fluorescent dyes for the detection of oligomeri

  4. Neuroinflammation in Multiple System Atrophy: Response to and Cause of alpha-Synuclein Aggregation

    Directory of Open Access Journals (Sweden)

    Bruno eDi Marco Vieira

    2015-11-01

    Full Text Available Multiple system atrophy (MSA is a progressive neurodegenerative disease presenting with combinations of autonomic dysfunction, parkinsonism, cerebellar ataxia and/or pyramidal signs. Oligodendroglial cytoplasmic inclusions rich in α-synuclein (α-syn constitute the disease hallmark, accompanied by neuronal loss and activation of glial cells which indicate neuroinflammation. Recent studies demonstrate that α-syn may be released from degenerating neurons to mediate formation of abnormal inclusion bodies and to induce neuroinflammation which, interestingly, might also favour the formation of intracellular α-syn aggregates as a consequence of cytokine release and the shift to a pro-inflammatory environment. Here we critically review the relationships between α-syn and astrocytic and microglial activation in MSA to explore the potential of therapeutics which target neuroinflammation.

  5. Alpha-Synuclein Stimulation of Astrocytes: Potential Role for Neuroinflammation and Neuroprotection

    Directory of Open Access Journals (Sweden)

    He-Jin Lee

    2010-01-01

    Full Text Available Selective loss of neurons, abnormal protein deposition and neuroinflammation are the common pathological features of neurodegenerative diseases, and these features are closely related to one another. In Parkinson's disease, abnormal aggregation and deposition of α-synuclein is known as a critical event in pathogenesis of the disease, as well as in other related neurodegenerative disorders, such as dementia with Lewy bodies and multiple system atrophy. Increasing evidence suggests that α-synuclein aggregates can activate glial cells to induce neuroinflammation. However, how an inflammatory microenvironment is established and maintained by this protein remains unknown. Findings from our recent study suggest that neuronal α-synuclein can be directly transferred to astrocytes through sequential exocytosis and endocytosis and induce inflammatory responses from astrocytes. Here we discuss potential roles of astrocytes in a cascade of events leading to α-synuclein-induced neuroinflammation.

  6. Direct and/or Indirect Roles for SUMO in Modulating Alpha-Synuclein Toxicity

    Directory of Open Access Journals (Sweden)

    Shamini Vijayakumaran

    2015-07-01

    Full Text Available α-Synuclein inclusion bodies are a pathological hallmark of several neurodegenerative diseases, including Parkinson’s disease, and contain aggregated α-synuclein and a variety of recruited factors, including protein chaperones, proteasome components, ubiquitin and the small ubiquitin-like modifier, SUMO-1. Cell culture and animal model studies suggest that misfolded, aggregated α-synuclein is actively translocated via the cytoskeletal system to a region of the cell where other factors that help to lessen the toxic effects can also be recruited. SUMO-1 covalently conjugates to various intracellular target proteins in a way analogous to ubiquitination to alter cellular distribution, function and metabolism and also plays an important role in a growing list of cellular pathways, including exosome secretion and apoptosis. Furthermore, SUMO-1 modified proteins have recently been linked to cell stress responses, such as oxidative stress response and heat shock response, with increased SUMOylation being neuroprotective in some cases. Several recent studies have linked SUMOylation to the ubiquitin-proteasome system, while other evidence implicates the lysosomal pathway. Other reports depict a direct mechanism whereby sumoylation reduced the aggregation tendency of α-synuclein, and reduced the toxicity. However, the precise role of SUMO-1 in neurodegeneration remains unclear. In this review, we explore the potential direct or indirect role(s of SUMO-1 in the cellular response to misfolded α-synuclein in neurodegenerative disorders.

  7. Effects of Trehalose on Thermodynamic Properties of Alpha-synuclein Revealed through Synchrotron Radiation Circular Dichroism

    Directory of Open Access Journals (Sweden)

    Paolo Ruzza

    2015-05-01

    Full Text Available Many neurodegenerative diseases, including Huntington’s, Alzheimer’s and Parkinson’s diseases, are characterized by protein misfolding and aggregation. The capability of trehalose to interfere with protein misfolding and aggregation has been recently evaluated by several research groups. In the present work, we studied, by means of synchrotron radiation circular dichroism (SRCD spectroscopy, the dose-effect of trehalose on α-synuclein conformation and/or stability to probe the capability of this osmolyte to interfere with α-synuclein’s aggregation. Our study indicated that a low trehalose concentration stabilized α-synuclein folding much better than at high concentration by blocking in vitro α-synuclein’s polymerisation. These results suggested that trehalose could be associated with other drugs leading to a new approach for treating Parkinson’s and other brain-related diseases.

  8. Blood Plasma of Patients with Parkinson's Disease Increases Alpha-Synuclein Aggregation and Neurotoxicity

    Science.gov (United States)

    Wang, Peng; Li, Xin; Li, Xuran; Yang, Weiwei

    2016-01-01

    A pathological hallmark of Parkinson's disease (PD) is formation of Lewy bodies in neurons of the brain. This has been attributed to the spread of α-synuclein (α-syn) aggregates, which involves release of α-syn from a neuron and its reuptake by a neighboring neuron. We found that treatment with plasma from PD patients induced more α-syn phosphorylation and oligomerization than plasma from normal subjects (NS). Compared with NS plasma, PD plasma added to primary neuron cultures caused more cell death in the presence of extracellular α-syn. This was supported by the observations that phosphorylated α-syn oligomers entered neurons, rapidly increased accumulated thioflavin S-positive inclusions, and induced a series of metabolic changes that included activation of polo-like kinase 2, inhibition of glucocerebrosidase and protein phosphatase 2A, and reduction of ceramide levels, all of which have been shown to promote α-syn phosphorylation and aggregation. We also analyzed neurotoxicity of α-syn oligomers relative to plasma from different patients. Neurotoxicity was not related to age or gender of the patients. However, neurotoxicity was positively correlated with H&Y staging score. The modification in the plasma may promote spreading of α-syn aggregates via an alternative pathway and accelerate progression of PD. PMID:27965913

  9. Wildtype and A30P mutant alpha-synuclein form different fibril structures.

    Directory of Open Access Journals (Sweden)

    Søren Bang Nielsen

    Full Text Available Parkinson's Disease (PD is a neurodegenerative movement disorder affecting millions of people worldwide. One of the key players in the development of the disease is the protein α-synuclein (aSN, which aggregates in the brain of PD patients. The aSN mutant A30P has been reported to cause early-onset familial PD and shows different aggregation behavior compared to wt aSN. Here we use a multidisciplinary approach to compare the aggregation process of wt and A30P aSN. In agreement with previous studies, we observe an initial lag phase followed by a continuous structural development of fibrils until reaching an apparent monomer-aggregate equilibrium state and a plateau in Thioflavin T (ThT fluorescence intensity. However, at later timepoints A30P shows greater propensity than αSN wt to form dense bundled fibril networks. Combining small angle x-ray scattering, x-ray fibre diffraction and linear dichroism, we demonstrate that while the microscopic structure of the individual fibril essentially remains constant throughout the experiment, the formation of dense A30P fibril networks occur through a continuous assembly pathway while the formation of less dense wt fibril networks with fewer contact points follows a continuous path during the elongation phase and a second rearrangement phase after reaching the ThT fluorescence plateau. Our work thus highlights that structural rearrangements proceed beyond the plateau in ThT-based monitoring of the fibrillation process, and the density and morphology of the resulting fibril networks is highly dependent on the aSN form studied.

  10. Protective effect of alpha-synuclein knockdown on methamphetamine-induced neurotoxicity in dopaminergic neurons

    OpenAIRE

    Tai, Yunchun; Chen, Ling; Huang, Enping; Liu, Chao; Yang, Xingyi; Qiu, Pingming; Wang, Huijun

    2014-01-01

    The over-expression of α-synuclein is a major factor in the death of dopaminergic neurons in a methamphetamine-induced model of Parkinson's disease. In the present study, α-synuclein knockdown rats were created by injecting α-synuclein-shRNA lentivirus stereotaxically into the right striatum of experimental rats. At 2 weeks post-injection, the rats were injected intraperitoneally with methamphetamine to establish the model of Parkinson's disease. Expression of α-synuclein mRNA and protein in ...

  11. Long-term polarization of microglia upon alpha-synuclein overexpression in nonhuman primates

    DEFF Research Database (Denmark)

    Barkholt, Pernille; Sanchez-Guajardo, Vanesa Maria; Kirik, Denis

    2012-01-01

    We have previously shown that persistent ﰇ-sy- nuclein overexpression in ventral midbrain of marmoset leads to a distinctive neurodegenerative process and motor defects. The neurodegeneration was confined to caudate putamen dopaminergic fibers in animals overexpressing wild-type (wt) ﰇ-synuclein.......We have previously shown that persistent ﰇ-sy- nuclein overexpression in ventral midbrain of marmoset leads to a distinctive neurodegenerative process and motor defects. The neurodegeneration was confined to caudate putamen dopaminergic fibers in animals overexpressing wild-type (wt) ﰇ...

  12. Polychlorinated biphenyls alter expression of alpha-synuclein, synaptophysin and parkin in the rat brain

    DEFF Research Database (Denmark)

    Malkiewicz, Katarzyna; Mohammed, Roma; Folkesson, Ronnie;

    2006-01-01

    Polychlorinated Biphenyls (PCBs)-induced changes in synaptic transmission are one of the effects of their neurotoxicity but the mechanism remains unknown. We assessed the in vivo effects of the PCBs mixture, Aroclor 1254 on the expression of neuronal proteins that are involved in the synaptic...

  13. Mutant alpha-synuclein causes age-dependent neuropathology in monkey brain.

    Science.gov (United States)

    Yang, Weili; Wang, Guohao; Wang, Chuan-En; Guo, Xiangyu; Yin, Peng; Gao, Jinquan; Tu, Zhuchi; Wang, Zhengbo; Wu, Jing; Hu, Xintian; Li, Shihua; Li, Xiao-Jiang

    2015-05-27

    Parkinson's disease (PD) is an age-dependent neurodegenerative disease that often occurs in those over age 60. Although rodents and small animals have been used widely to model PD and investigate its pathology, their short life span makes it difficult to assess the aging-related pathology that is likely to occur in PD patient brains. Here, we used brain tissues from rhesus monkeys at 2-3, 7-8, and >15 years of age to examine the expression of Parkin, PINK1, and α-synuclein, which are known to cause PD via loss- or gain-of-function mechanisms. We found that α-synuclein is increased in the older monkey brains, whereas Parkin and PINK1 are decreased or remain unchanged. Because of the gain of toxicity of α-synuclein, we performed stereotaxic injection of lentiviral vectors expressing mutant α-synuclein (A53T) into the substantia nigra of monkeys and found that aging also increases the accumulation of A53T in neurites and its associated neuropathology. A53T also causes more extensive reactive astrocytes and axonal degeneration in monkey brain than in mouse brain. Using monkey brain tissues, we found that A53T interacts with neurofascin, an adhesion molecule involved in axon subcellular targeting and neurite outgrowth. Aged monkey brain tissues show an increased interaction of neurofascin with A53T. Overexpression of A53T causes neuritic toxicity in cultured neuronal cells, which can be attenuated by transfected neurofascin. These findings from nonhuman primate brains reveal age-dependent pathological and molecular changes that could contribute to the age-dependent neuropathology in PD.

  14. Role of alpha-synuclein in neuronal apoptosis induced by rotenone

    Institute of Scientific and Technical Information of China (English)

    Yanying Liu; Hui Yang

    2006-01-01

    BACKGROUND: Aggregation of α-synuclein is the major component of Lewy bodies, which are the pathological hallmarks of Parkinson disease (PD). Although the mechanism of this protein aggregates is unclear,previous study showed that environmental toxins such as rotenone could induce the expression and aggregation of α-synuclein.OBJECTIVE: To observe the role of α-synuclein in PD.DESIGN: A randomized controlled trial.SETTING: Beijing Institute for Neuroscience, Capital University of Medical Sciences.MATERIALS: This study was performed from July 2005 to January 2006 at the Beijing Institute for Neuroscience, Capital University of Medical Sciences. Human dopaminergic neuroblastoma SH-SY5Y cells were provided by Beijing Institute for Neuroscience, Capital University of Medical Sciences.METHODS: Human dopaminergic neuroblastoma SH-SY5Y cells were treated to make α-synuclein over express. Rotenone was added into the medium of cultured both native SH-SY5Y cells and α-synuclein-overexpression SH-SY5Y cells. Lactate dehydrogenase (LDH) assay was used to detect with the cell viability. Flow cytometry and electrophoresis were adopted to measure the cell apoptosis.MAIN OUTCOME MEASURES: Cell viability, DNA fragmentation, and the number of cell apoptosis.RESULTS: After being treated with rotenone, LDH activity of α-synuclein overexpressed SH-SY5Y cells was (76.625±6.34) μ kat/L, which was significantly lower than that of control group (P < 0.05). As compared with normal SH-SY5Y cell, α-synuclein over-expressed SH-SY5Y cells had less DNA fragments and apoptotic cells. Α-synuclein might play a role in cell apoptosis induced by rotenone, which was also confirmed by using of antioxidant reagent.CONCLUSION: α-synuclein may partially protect against cell apoptosis induced by rotenone in SH-SY5Y cells.

  15. Role of alpha-synuclein in autophagy modulation of primary human T lymphocytes.

    Science.gov (United States)

    Colasanti, T; Vomero, M; Alessandri, C; Barbati, C; Maselli, A; Camperio, C; Conti, F; Tinari, A; Carlo-Stella, C; Tuosto, L; Benincasa, D; Valesini, G; Malorni, W; Pierdominici, M; Ortona, E

    2014-05-29

    It has been demonstrated that α-synuclein can aggregate and contribute to the pathogenesis of some neurodegenerative diseases and it is capable of hindering autophagy in neuronal cells. Here, we investigated the implication of α-synuclein in the autophagy process in primary human T lymphocytes. We provide evidence that: (i) knocking down of the α-synuclein gene resulted in increased autophagy, (ii) autophagy induction by energy deprivation was associated with a significant decrease of α-synuclein levels, (iii) autophagy inhibition by 3-methyladenine or by ATG5 knocking down led to a significant increase of α-synuclein levels, and (iv) autophagy impairment, constitutive in T lymphocytes from patients with systemic lupus erythematosus, was associated with abnormal accumulation of α-synuclein aggregates. These results suggest that α-synuclein could be considered as an autophagy-related marker of peripheral blood lymphocytes, potentially suitable for use in the clinical practice.

  16. Alpha-synuclein mRNA expression in oligodendrocytes in MSA.

    Science.gov (United States)

    Asi, Yasmine T; Simpson, Julie E; Heath, Paul R; Wharton, Stephen B; Lees, Andrew J; Revesz, Tamas; Houlden, Henry; Holton, Janice L

    2014-06-01

    Multiple system atrophy (MSA) is a progressive neurodegenerative disease presenting clinically with parkinsonian, cerebellar, and autonomic features. α-Synuclein (αsyn), encoded by the gene SNCA, is the main constituent of glial cytoplasmic inclusion (GCI) found in oligodendrocytes in MSA, but the methods of its accumulation have not been established. The aim of this study is to investigate alterations in regional and cellular SNCA mRNA expression in MSA as a possible substrate for GCI formation. Quantitative reverse transcription polymerase chain reaction (qPCR) was performed on postmortem brain samples from 15 MSA, 5 IPD, and 5 control cases to investigate regional expression in the frontal and occipital regions, dorsal putamen, pontine base, and cerebellum. For cellular expression analysis, neurons and oligodendrocytes were isolated by laser-capture microdissection from five MSA and five control cases. SNCA mRNA expression was not significantly different between the MSA, IPD and control cases in all regions (multilevel model, P = 0.14). After adjusting for group effect, the highest expression was found in the occipital cortex while the lowest was in the putamen (multilevel model, P MSA oligodendrocytes expressed more SNCA than control oligodendrocytes and expression in MSA neurons was slightly lower than that in controls, however, these results did not reach statistical significance. We have demonstrated regional variations in SNCA expression, which is higher in cortical than subcortical regions. This study is the first to demonstrate SNCA mRNA expression by oligodendrocytes in human postmortem tissue using qPCR and, although not statistically significant, could suggest that this may be increased in MSA compared to controls.

  17. Test Control Center exhibit

    Science.gov (United States)

    2000-01-01

    Have you ever wondered how the engineers at John C. Stennis Space Center in Hancock County, Miss., test fire a Space Shuttle Main Engine? The Test Control Center exhibit at StenniSphere can answer your questions by simulating the test firing of a Space Shuttle Main Engine. A recreation of one of NASA's test control centers, the exhibit explains and portrays the 'shake, rattle and roar' that happens during a real test firing.

  18. Gamma aminobutyric acid transporter subtype 1 gene knockout mice: a new model for attention deficit/hyperactivity disorder

    Institute of Scientific and Technical Information of China (English)

    Ping Yang; Guoqiang Cai; Youqing Cai; Jian Fei; Guoxiang Liu

    2013-01-01

    Attention deficit/hyperactivity disorder (ADHD) is characterized by hyperactivity,impaired sustained attention,impulsivity,and is usually accompanied by varying degrees of learning difficulties and lack of motor coordination.However,the pathophysiology and etiology of ADHD remain inconclusive so far.Our previous studies have demonstrated that the gamma aminobutyric acid transporter subtype 1 (GAT1) gene knockout (ko) mouse (gat1-/-)is hyperactive and exhibited impaired memory performance in the Morris water maze.In the current study,we found that the gat1-/-mice showed low levels of attentional focusing and increased impulsivity.In addition,the gat1-/-mice displayed ataxia characterized by defects in motor coordination and balance skills.The hyperactivity in the ko mice was reduced by both methylphenidate and amphetamine.Collectively,these results suggest that GAT1 ko mouse is a new animal model for ADHD studying and GAT1 may be a new target to treat ADHD.

  19. Council Chamber exhibition

    CERN Multimedia

    CERN Bulletin

    2010-01-01

    To complete the revamp of CERN’s Council Chamber, a new exhibition is being installed just in time for the June Council meetings.   Panels will showcase highlights of CERN’s history, using some of the content prepared for the exhibitions marking 50 years of the PS, which were displayed in the main building last November. The previous photo exhibition in the Council Chamber stopped at the 1970s. To avoid the new panels becoming quickly out of date, photos are grouped together around specific infrastructures, rather than following a classic time-line. “We have put the focus on the accelerators – the world-class facilities that CERN has been offering researchers over the years, from the well-known large colliders to the lesser-known smaller facilities,” says Emma Sanders, who worked on the content. The new exhibition will be featured in a future issue of the Bulletin with photos and an interview with Fabienne Marcastel, designer of the exhibit...

  20. EXHIBITION: Accelerated Particles

    CERN Multimedia

    2004-01-01

    An exhibition of plastic arts and two evenings of performances by sound and visual artists as part of CERN's 50th anniversary celebrations. Fifty candles for CERN, an international laboratory renowned for fundamental research, is a cause for celebration. Since March this year, Geneva and neighbouring parts of France have been the venues for a wealth of small and large-scale events, which will continue until November. Given CERN's location in the commune of Meyrin, the ForuMeyrin is hosting exhibitions of plastic arts and performances entitled: Accelerated Particles. Several works will be exhibited and performed in two 'salons'. Salon des matières: An exhibition of plastic arts From Tues 12 October to Wed 3 November 2004 Tuesdays to Fridays: 16:00 to 19:00 Saturdays: 14:00 to 18:00 Exhibition open late on performance nights, entrance free Salon des particules: Musical and visual performances Tues 12 and Mon 25 October from 20:00 to 23:00 Preview evening for both events: Tues 12 October from 18:...

  1. Behavioural characterisation of rats exposed neonatally to bisphenol-A: responses to a novel environment and to methylphenidate challenge in a putative model of attention-deficit hyperactivity disorder.

    NARCIS (Netherlands)

    Kiguchi, M.; Fujita, S.; Oki, H.; Shimizu, N.; Cools, A.R.; Koshikawa, N.

    2008-01-01

    Neonatal exposure of rats to bisphenol-A, an endocrine disruptor, has recently been proposed as a possible animal model of attention-deficit hyperactivity disorder (ADHD), because such rats exhibit motor hyperactivity. To strengthen the face validity of this animal model, the present study replicate

  2. EXHIBITION: Accelerated Particles

    CERN Multimedia

    2004-01-01

    http://www.cern.ch/cern50/ An exhibition of plastic arts and two evenings of performances by sound and visual artists as part of CERN's fiftieth anniversary celebrations. The fiftieth anniversary of a world famous organization like CERN, an international laboratory specializing in fundamental research, is a cause for celebration. Since March this year, Geneva and neighbouring parts of France have been the venues for a wealth of small and large-scale events, which will continue until November. Given CERN's location in the commune of Meyrin, the ForuMeyrin is hosting two "salons" consisting of an exhibition of plastic arts and evenings of music and visual arts performances with the collective title of "Accelerated Particles". Several works will be exhibited and performed. Salon des matières: An exhibition of plastic arts Until Wednesday 3 November 2004. Tuesdays to Fridays: 4.00 p.m. to 7.00 p.m. Saturdays: 2.00 p.m. to 6.00 p.m. Doors open late on the evening of the performances. Salon des ...

  3. Exhibition in Sight

    Science.gov (United States)

    Wasserman, Burton

    1978-01-01

    Ludwig Mies van der Rohe is known primarily as an architect. However, he also designed chairs and tables. Discusses an exhibit held in New York City a few months ago which showed how well the famous architect achieved his goals in the area of furniture design. (Author/RK)

  4. ADHD Diet: Do Food Additives Cause Hyperactivity?

    Science.gov (United States)

    ... There's no solid evidence that food additives cause attention-deficit/hyperactivity disorder (ADHD). However, the topic of food additives and their possible effects is controversial. Some studies indicate that certain food ...

  5. Did goethe describe attention deficit hyperactivity disorder?

    Science.gov (United States)

    Bonazza, Sara; Scaglione, Cesa; Poppi, Massimo; Rizzo, Giovanni

    2011-01-01

    As early as 1846, the typical symptoms of attention deficit hyperactivity disorder (ADHD) were described by Heinrich Hoffmann (1809-1894). However, in Goethe's masterpiece Faust (1832), the character of Euphorion strongly suggests ADHD diagnosis.

  6. Attention-Deficit Hyperactivity Disorder (ADHD)

    Science.gov (United States)

    ... of ADHD behaviors and problems can cause low self-esteem and problems with relationships. Individual counseling and support ... was contributed by: familydoctor.org editorial staff Tags: Adolescent, adult, Attention Deficit Hyperactivity, child, Neurologic, Overview Family ...

  7. CERN permanent exhibitions

    CERN Multimedia

    2016-01-01

    Explore by yourself the issues CERN's physicists are trying to solve: given that the entire universe is made of particles, where do they come from? Why do they behave in the way they do? Discover the massive apparatus used by physicists at CERN, like the LHC, and see how each part works. And if you have more time on site, follow the LHC circuit at ground level to understand in situ this giant machine. Enter our exhibitions. Welcome!

  8. Droplet Lamp Design exhibition

    OpenAIRE

    Unver, Ertu; Dean, Lionel Theodore

    2011-01-01

    This paper describes experiments in the use of digital fluid simulation techniques within a\\ud product design context. It discusses the adoption and adaptation of virtual modelling tools in\\ud 3D creative practice. This work is exhibited at EuroMold, the world-wide fair in Germany for\\ud mold making, tooling, design and application development with around 60.000 visitors and lasts\\ud 4 days. The fair brings together professionals from design, prototyping and manufacturing.

  9. Upcycling CERN Exhibitions

    CERN Multimedia

    Katarina Anthony

    2015-01-01

    Summer is coming - and with it, a new Microcosm exhibition showcasing CERN (see here). But while the new exhibit is preparing to enchant visitors, many have been asking about the site's former content. Will it simply be out with the old and in with the new? Not as such!   The plasma ball from Microcosm is now on display at the LHCb site. As Microcosm's new content is moving in, its old content is moving up. From LHCb to IdeaSquare, former Microcosm displays and objects are being installed across the CERN site. "Microcosm featured many elements that were well suited to life outside of the exhibition," says Emma Sanders, Microcosm project leader in the EDU group. "We didn't want this popular content to go to waste, and so set out to find them new homes across CERN." The LHCb experiment has received a number of Microcosm favourites, including the Rutherford experiment, the cosmic ray display and the Thomson experiment. "We&...

  10. Online Exhibits & Concept Maps

    Science.gov (United States)

    Douma, M.

    2009-12-01

    Presenting the complexity of geosciences to the public via the Internet poses a number of challenges. For example, utilizing various - and sometimes redundant - Web 2.0 tools can quickly devour limited time. Do you tweet? Do you write press releases? Do you create an exhibit or concept map? The presentation will provide participants with a context for utilizing Web 2.0 tools by briefly highlighting methods of online scientific communication across several dimensions. It will address issues of: * breadth and depth (e.g. from narrow topics to well-rounded views), * presentation methods (e.g. from text to multimedia, from momentary to enduring), * sources and audiences (e.g. for experts or for the public, content developed by producers to that developed by users), * content display (e.g. from linear to non-linear, from instructive to entertaining), * barriers to entry (e.g. from an incumbent advantage to neophyte accessible, from amateur to professional), * cost and reach (e.g. from cheap to expensive), and * impact (e.g. the amount learned, from anonymity to brand awareness). Against this backdrop, the presentation will provide an overview of two methods of online information dissemination, exhibits and concept maps, using the WebExhibits online museum (www.webexhibits.org) and SpicyNodes information visualization tool (www.spicynodes.org) as examples, with tips on how geoscientists can use either to communicate their science. Richly interactive online exhibits can serve to engage a large audience, appeal to visitors with multiple learning styles, prompt exploration and discovery, and present a topic’s breadth and depth. WebExhibits, which was among the first online museums, delivers interactive information, virtual experiments, and hands-on activities to the public. While large, multidisciplinary exhibits on topics like “Color Vision and Art” or “Calendars Through the Ages” require teams of scholars, user interface experts, professional writers and editors

  11. Space Shuttle Cockpit exhibit

    Science.gov (United States)

    2000-01-01

    Want to sit in the cockpit of the Space Shuttle and watch astronauts work in outer space? At StenniSphere, you can do that and much more. StenniSphere, the visitor center at John C. Stennis Space Center in Hancock County, Miss., presents 14,000-square-feet of interactive exhibits that depict America's race for space as well as a glimpse of the future. StenniSphere is open free of charge from 9 a.m. to 5 p.m. daily.

  12. Mutation of Elfn1 in mice causes seizures and hyperactivity.

    Directory of Open Access Journals (Sweden)

    Jackie Dolan

    Full Text Available A growing number of proteins with extracellular leucine-rich repeats (eLRRs have been implicated in directing neuronal connectivity. We previously identified a novel family of eLRR proteins in mammals: the Elfns are transmembrane proteins with 6 LRRs, a fibronectin type-3 domain and a long cytoplasmic tail. The recent discovery that Elfn1 protein, expressed postsynaptically, can direct the elaboration of specific electrochemical properties of synapses between particular cell types in the hippocampus strongly reinforces this hypothesis. Here, we present analyses of an Elfn1 mutant mouse line and demonstrate a functional requirement for this gene in vivo. We first carried out detailed expression analysis of Elfn1 using a β-galactosidase reporter gene in the knockout line. Elfn1 is expressed in distinct subsets of interneurons of the hippocampus and cortex, and also in discrete subsets of cells in the habenula, septum, globus pallidus, dorsal subiculum, amygdala and several other regions. Elfn1 is expressed in diverse cell types, including local GABAergic interneurons as well as long-range projecting GABAergic and glutamatergic neurons. Elfn1 protein localises to axons of excitatory neurons in the habenula, and long-range GABAergic neurons of the globus pallidus, suggesting the possibility of additional roles for Elfn1 in axons or presynaptically. While gross anatomical analyses did not reveal any obvious neuroanatomical abnormalities, behavioural analyses clearly illustrate functional effects of Elfn1 mutation. Elfn1 mutant mice exhibit seizures, subtle motor abnormalities, reduced thigmotaxis and hyperactivity. The hyperactivity is paradoxically reversible by treatment with the stimulant amphetamine, consistent with phenotypes observed in animals with habenular lesions. These analyses reveal a requirement for Elfn1 in brain function and are suggestive of possible relevance to the etiology and pathophysiology of epilepsy and attention

  13. Anniversary Exhibition. Nechvolodov.

    Directory of Open Access Journals (Sweden)

    - -

    2006-03-01

    Full Text Available On the 10th of August, 2005 in Tartu (the second biggest educational and cultural city in Estonia Stanislav Nechvolodov's exhibition was opened to show the 5-year cycle of his work, traditional for the author and his admirers. At the opening ceremony Nechvolodov said that the exhibition was the last one and appointed on his 70th anniversary.The architectural and building society in Irkutsk remembers Stanislav Nechvolodov as an architect working on dwelling and civil buildings in 1960-70s. Below are some extracts from the Estonian press.«Postimees» newspaper, December 1993. The interview «Expressionistic naturalist, conservative Nechvolodov» by journalist Eric Linnumyagi. He asks about all the details and describes the troubles experienced by Nechvolodov during the perestroika period in Estonia, for example: the Tartu University refused to install the sculpture of Socrat, the art school refused to engage him as an instructor, the sculpture of Socrat moved to Vrotzlav, Poland, and Nechvolodov moved to Poland to read lectures there.«Tartu» newspaper, November 2000. Mats Oun, artist, says in the article «Nechvolodov: a man of Renaissance»: «Nechvolodov works in Estonia, his works are placed in many local and foreign museums. Regardless some insignificant faults, he deserves a high estimation, and his manysided open exhibition can be an example for other artists. He is a man of Renaissance».

  14. Attention Deficit Hyperactivity Disorder and Tuberous Sclerosis Complex

    Science.gov (United States)

    ... Privacy Policy Sitemap Learn Engage Donate About TSC Attention Deficit Hyperactivity Disorder and TSC What is ADHD? Attention Deficit Hyperactivity Disorder (ADHD) is a common neurobehavioral disorder. It is ...

  15. Dansk standardisering af attention deficit/hyperactivity disorder-ratingskalaen

    DEFF Research Database (Denmark)

    Poulsen, Lotte; Jørgensen, Siv Lykke; Dalsgaard, Søren

    2009-01-01

    INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is characterized by inattention, hyperactivity and impulsivity. The diagnostic classification is based on developmental anamnesis, objective examination, neuropsychological tests, observation of the child, and evaluation of the symptoms...

  16. Attention in Hyperactive Children and the Effect of Methylphenidate (Ritalin)

    Science.gov (United States)

    Sykes, Donald H.; And Others

    1971-01-01

    Hyperactive children treated with methylphenidate (ritalin) showed a significant improvement in all aspects of performance in an experimenter-paced task when compared to a control group of hyperactive children given a placebo. (Author/WY)

  17. Sympathetic hyperactivity in patients with chronic kidney disease

    NARCIS (Netherlands)

    Neumann, N.

    2007-01-01

    Sympathetic hyperactivity in patients with chronic kidney disease Chronic kidney disease (CKD) is often characterized by the presence of sympathetic hyperactivity. This contributes to the pathogenesis of renal hypertension. It is also associated with cardiovascular (CV) morbidity and mortality indep

  18. Developmental pesticide exposure reproduces features of attention deficit hyperactivity disorder.

    Science.gov (United States)

    Richardson, Jason R; Taylor, Michele M; Shalat, Stuart L; Guillot, Thomas S; Caudle, W Michael; Hossain, Muhammad M; Mathews, Tiffany A; Jones, Sara R; Cory-Slechta, Deborah A; Miller, Gary W

    2015-05-01

    Attention-deficit hyperactivity disorder (ADHD) is estimated to affect 8-12% of school-age children worldwide. ADHD is a complex disorder with significant genetic contributions. However, no single gene has been linked to a significant percentage of cases, suggesting that environmental factors may contribute to ADHD. Here, we used behavioral, molecular, and neurochemical techniques to characterize the effects of developmental exposure to the pyrethroid pesticide deltamethrin. We also used epidemiologic methods to determine whether there is an association between pyrethroid exposure and diagnosis of ADHD. Mice exposed to the pyrethroid pesticide deltamethrin during development exhibit several features reminiscent of ADHD, including elevated dopamine transporter (DAT) levels, hyperactivity, working memory and attention deficits, and impulsive-like behavior. Increased DAT and D1 dopamine receptor levels appear to be responsible for the behavioral deficits. Epidemiologic data reveal that children aged 6-15 with detectable levels of pyrethroid metabolites in their urine were more than twice as likely to be diagnosed with ADHD. Our epidemiologic finding, combined with the recapitulation of ADHD behavior in pesticide-treated mice, provides a mechanistic basis to suggest that developmental pyrethroid exposure is a risk factor for ADHD.

  19. [Parenting styles and their relationship with hyperactivity].

    Science.gov (United States)

    Raya Trenas, Antonio Félix; Herreruzo Cabrera, Javier; Pino Osuna, María José

    2008-11-01

    The present study aims to determine the relationship among factors that make up the parenting styles according to the PCRI (Parent-Child Relationship Inventory) and hyperactivity reported by parents through the BASC (Behaviour Assessment System for Children). We selected a sample of 32 children between 3 and 14 years old (23 male and 9 female) with risk scores in hyperactivity and another similar group with low scores in hyperactivity. After administering both instruments to the parents, we carried out a binomial logistic regression analysis which resulted in a prediction model for 84.4% of the sample, made up of the PCRI factors: fathers' involvement, communication and role orientation, mothers' parental support, and both parents' limit-setting and autonomy. Moreover, our analysis of the variance produced significant differences in the support perceived by the fathers and mothers of both groups. Lastly, the utility of results to propose intervention strategies within the family based on an authoritative style is discussed.

  20. Visuomotor perception in children with attention deficit hyperactivity disorder--combined type.

    Science.gov (United States)

    Raggio, D J

    1999-04-01

    Children with Attention Deficit Hyperactivity Disorder--Combined Type (ADHD-CT) defined by behavioral characteristics of inattention, impulsivity, and hyperactivity including weaknesses in fine motor coordination and poor motor inhibition frequently exhibit poor handwriting and penmanship. Performance of children on visuomotor tasks is further complicated, as most studies have not excluded children with specific learning disabilities who are known to do poorly on these tests. This study was designed to examine the performance of children diagnosed with this disorder, without learning disabilities on visuomotor tasks. 26 preadolescent patients were administered a battery of tests that included the Bender-Gestalt, Conners' Parent Rating Scale, Continuous Performance Task, and Wide Range Achievement Test-Third Edition Scores on the Bender-Gestalt test averaged significantly lower than Koppitz normative data. This study lends support to the hypothesis that ADHD-CT children without learning disabilities exhibit deficits on tasks requiring visuomotor perception.

  1. ADHD-hyperactive/impulsive subtype in adults

    Directory of Open Access Journals (Sweden)

    Stephen V. Faraone

    2010-01-01

    Full Text Available This is the first study to evaluate ADHD-hyperactive/impulsive subtype in a large clinical sample of adults with ADHD. The Quality of Life, Effectiveness, Safety and Tolerability (QuEST study included 725 adults who received clinician diagnoses of any ADHD subtype. Cross-sectional baseline data from 691 patients diagnosed with the hyperactive/impulsive (HI, inattentive (IA and combined subtypes were used to compare the groups on the clinician administered ADHD-RS, clinical features and health-related quality of life. A consistent pattern of differences was found between the ADHD-I and combined subtypes, with the combined subtype being more likely to be diagnosed in childhood, more severe symptom severity and lower HRQL. Twenty-three patients out of the total sample of 691 patients (3% received a clinician diagnosis of ADHD - hyperactive/impulsive subtype. Review of the ratings on the ADHD-RS-IV demonstrated, however, that this group had ratings of inattention comparable to the inattentive group. There were no significant differences found between the ADHD-HI and the other subtypes in symptom severity, functioning or quality of life. The hyperactive/impulsive subtype group identified by clinicians in this study was not significantly different from the rest of the sample. By contrast, significant differences were found between the inattentive and combined types. This suggests that in adults, hyperactivity declines and inattention remains significant, making the hyperactive/impulsive subtype as defined by childhood criteria a very rare condition and raising questions as to the validity of the HI subtype in adults.

  2. Peer-mediated reinforcement plus prompting as treatment for off-task behavior in children with attention deficit hyperactivity disorder.

    OpenAIRE

    Flood, William A; Wilder, David A; Flood, Amy L; Masuda, Akihiko

    2002-01-01

    Functional analyses revealed that peer attention was one variable maintaining the off-task behavior exhibited by 3 students with a diagnosis of attention deficit hyperactivity disorder (ADHD). Peer-mediated reinforcement plus prompting was then used to reduce off-task behavior in a simulated classroom environment. Implications for future applications of this procedure with children diagnosed with ADHD are discussed.

  3. Treatment Programs for Students With Attention Deficit Hyperactivity Disorder: A Meta-Analysis Study

    OpenAIRE

    Mihandoost, Zeinab

    2015-01-01

    Context: The aim of this study was to determine the experimental evidence of treatment/intervention programs for deficits in social skills, attention, and behavioral disorder in children and adolescents with attention deficit hyperactivity disorder (ADHD). Evidence Acquisition: Meta-analysis procedures were employed to investigate whether children and adolescents with ADHD exhibit deficits in attention and social skills. A total of 17 empirical research studies published between 2000 and 2013...

  4. 2007Fairs & Exhibitions in China

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ The 6th China (Guangzhou) International Seasoning Exhibition Date: May 11-13 Founded in: 2003.05 Venues: Guangzhou Int'l Convention &Exhibition Center (Pazhou) Exhibits: Seasonings, food additives, relevant material,equipment, service and publications

  5. 2005 Fairs & Exhibitions in China

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    @@ Harbin China International Winter Goods Exhibition DATE: Jan. 5-9 FREQUENCY: Annual FOUNDED TIME: Dec. 2001 VENUE: Harbin China International Conference & Exhibition Center EXHIBITS: winter sports goods and outdoor devices

  6. Adolescent methylphenidate treatment differentially alters adult impulsivity and hyperactivity in the Spontaneously Hypertensive Rat model of ADHD.

    Science.gov (United States)

    Somkuwar, S S; Kantak, K M; Bardo, M T; Dwoskin, L P

    2016-02-01

    Impulsivity and hyperactivity are two facets of attention deficit/hyperactivity disorder (ADHD). Impulsivity is expressed as reduced response inhibition capacity, an executive control mechanism that prevents premature execution of an intermittently reinforced behavior. During methylphenidate treatment, impulsivity and hyperactivity are decreased in adolescents with ADHD, but there is little information concerning levels of impulsivity and hyperactivity in adulthood after adolescent methylphenidate treatment is discontinued. The current study evaluated impulsivity, hyperactivity as well as cocaine sensitization during adulthood after adolescent methylphenidate treatment was discontinued in the Spontaneously Hypertensive Rat (SHR) model of ADHD. Treatments consisted of oral methylphenidate (1.5mg/kg) or water vehicle provided Monday-Friday from postnatal days 28-55. During adulthood, impulsivity was measured in SHR and control strains (Wistar Kyoto and Wistar rats) using differential reinforcement of low rate (DRL) schedules. Locomotor activity and cocaine sensitization were measured using the open-field assay. Adult SHR exhibited decreased efficiency of reinforcement under the DRL30 schedule and greater levels of locomotor activity and cocaine sensitization compared to control strains. Compared to vehicle, methylphenidate treatment during adolescence reduced hyperactivity in adult SHR, maintained the lower efficiency of reinforcement, and increased burst responding under DRL30. Cocaine sensitization was not altered following adolescent methylphenidate in adult SHR. In conclusion, adolescent treatment with methylphenidate followed by discontinuation in adulthood had a positive benefit by reducing hyperactivity in adult SHR rats; however, increased burst responding under DRL compared to SHR given vehicle, i.e., elevated impulsivity, constituted an adverse consequence associated with increased risk for cocaine abuse liability.

  7. Imipramine and Methylphenidate in Hyperactive Children.

    Science.gov (United States)

    Werry, John S.; And Others

    1980-01-01

    A double blind, placebo controlled, crossover study using methylphenidate as a standard and two doses of imipramine was carried out in 30 hyperactive children (mean age 8.5 years). Particular emphasis was placed upon imipramine's action on cognitive function, physiological function, and self-esteem, and upon dosage effects. (MP)

  8. Detection of feigned attention deficit hyperactivity disorder

    NARCIS (Netherlands)

    Tucha, Lara; Fuermaier, Anselm B.M.; Koerts, Janneke; Groen, Yvonne; Thome, Johannes

    2015-01-01

    In recent years, there is an increasing awareness that individuals may purposely feign or exaggerate symptoms of attention deficit hyperactivity disorder (ADHD) to gain external incentives, including access to stimulant drugs or special academic accommodations. There are vast consequences of undetec

  9. Stigma in attention deficit hyperactivity disorder

    NARCIS (Netherlands)

    Müller, Kathi; Fuermaier, Anselm B M; Koerts, Janneke; Tucha, Lara

    2012-01-01

    Attention deficit hyperactivity disorder (ADHD) is a frequently diagnosed disorder in child- and adulthood with a high impact affecting multiple facets of social life. Therefore, patients suffering from ADHD are at high risk to be confronted with stigma, prejudices, and discrimination. A review of t

  10. Bupropion hydrochloride produces conditioned hyperactivity in rats.

    Science.gov (United States)

    Wilkinson, Jamie L; Bevins, Rick A

    2007-04-23

    Bupropion is marketed as an antidepressant, Wellbutrin and smoking cessation aid, Zyban. Although the therapeutic neurological mechanisms of bupropion have not been fully elucidated, bupropion shares some behavioral similarities with classic psychomotor stimulants. The present study sought to further investigate these psychomotor stimulant effects of bupropion by assessing whether repeated administration of bupropion in a distinct environment produced conditioned hyperactivity. Paired rats received 10 daily i.p. injections of bupropion (2.5-30 mg/kg) before placement in locomotor chambers for 30 min. Bupropion (10-30 mg/kg) produced acute locomotor hyperactivity compared to Unpaired controls. After repeated administration, there was no progressive increase or decrease in bupropion-induced activity. In a subsequent drug-free session conditioned hyperactivity was observed at 5-30 mg/kg doses. In a follow-up experiment, we examined whether responsiveness to novelty predicted the subsequent unconditioned and conditioned locomotor effect of bupropion. Reactivity to inescapable novelty, novel environment approach, and novel-object interaction were measured before locomotor conditioning with 30 mg/kg bupropion. We replicated the previous experiment, but scores on the novelty screens did not predict locomotor response to bupropion. This study extends the literature by demonstrating that environmental cues repeatedly paired with the stimulant effects of bupropion come to evoke elevated activity in the absence of drug (i.e., conditioned hyperactivity). This finding is consistent with the literature suggesting that bupropion shares many behavioral similarities with other psychomotor stimulants which also produce conditioned hyperactivity. However, a predictive relation between reactivity to forced novelty and the subsequent locomotor effect of bupropion may not be one of these similarities.

  11. Psychological mechanisms in hyperactivity: II. The role of genetic factors.

    Science.gov (United States)

    Kuntsi, J; Stevenson, J

    2001-02-01

    The main aim of this study was to combine two research approaches to hyperactivity: the behaviour genetic approach and the testing of psychological theories of hyperactivity. For a sample of 268 twin pairs aged 7-11 years we obtained ratings on the Conners' scales from both teachers (CTRS-28) and parents (CPRS-48). Forty-six hyperactive twin pairs (pairs in which at least one twin was pervasively hyperactive) and 47 control twin pairs were assessed on a psychological test battery. Confirming findings from previous twin studies, a substantial proportion of the variance in hyperactivity considered as a dimension was due to genetic effects. There was significant evidence of genetic effects also on extreme hyperactivity, although the present group heritability estimates were somewhat lower than those reported in most previous studies. We investigated the possibility that the psychological mechanisms we reported to be associated with hyperactivity (Kuntsi, Oosterlaan, & Stevenson, 2001) share common genetic factors with hyperactive behaviour. The data produced significant evidence of such shared genetic effects only on hyperactivity and the variability of reaction times. Given that the high variability in speed of responding would indicate a state-regulation problem, this is the psychological mechanism that could possibly be the "link" between genetic effects and hyperactive behaviour.

  12. Comorbidity of Learning Disorders and Attention Deficit Hyperactivity Disorder in a Sample of Omani Schoolchildren

    Directory of Open Access Journals (Sweden)

    Watfa S. Al-Mamari

    2015-11-01

    Full Text Available Objectives: The estimated worldwide prevalence of learning disorders (LDs is approximately 2‒10% among school-aged children. LDs have variable clinical features and are often associated with other disorders. This study aimed to examine the comorbidity of LDs and attention deficit hyperactivity disorder (ADHD among a sample of schoolchildren in Oman. Methods: This study was conducted between January 2014 and January 2015 at the Sultan Qaboos University, Muscat, Oman. The Learning Disabilities Diagnostic Inventory (LDDI and the 28- item version of the Conners’ Teacher Rating Scale was completed by classroom teachers to determine the existence of LD and ADHD symptoms in 321 children in grades 1‒4 who had been referred to a learning support unit for LDs from elementary schools in Muscat. Results: The mean age of the students was 8.5 years. Among the cohort, 30% were reported to have symptoms of ADHD, including conduct problems (24%, hyperactivity (24% and inattentivepassive behaviours (41%. Male students reportedly exhibited greater conduct problems and hyperactivity than females. However, there were no gender differences noted between LDDI scores. Conclusion: This study suggests that Omani schoolchildren with LDs are likely to exhibit signs of ADHD. The early identification of this disorder is essential considering the chronic nature of ADHD. For interventional purposes, multidisciplinary teams are recommended, including general and special educators, clinical psychologists, school counsellors, developmental or experienced general paediatricians and child psychiatrists.

  13. Exhibition

    CERN Multimedia

    Staff Association

    2017-01-01

    Le Point Isabelle Gailland Du 20 février au 3 mars 2017 CERN Meyrin, Bâtiment principal La Diagonale - Isabelle Gailland. Au départ, un toujours même point minuscule posé au centre de ce que la toile est un espace. Une réplique d'autres points, condensés, alignés, isolés, disséminés construiront dans leur extension, la ligne. Ces lignes, croisées, courbées, déviées, prolongées, seront la structure contenant et séparant la matière des couleurs. La rotation de chaque toile en cours d'exécution va offrir un accès illimité à la non-forme et à la forme. Le point final sera l'ouverture sur différents points de vue de ce que le point et la ligne sont devenus une représentation pour l'œil et l'im...

  14. Exhibition

    CERN Multimedia

    Staff Association

    2014-01-01

    Energie sombre, matière noire J.-J. Dalmais - J. Maréchal Du 11 au 27 novembre 2014, CERN Meyrin, Bâtiment principal A l’image des particules atomiques qui ont tissé des liens pour créer la matière, deux artistes haut bugistes croisent leurs regards et conjuguent leurs expressions singulières pour faire naître une vision commune de l’univers, produit des forces primordiales. Les sculptures de Jean-Jacques Dalmais et les peintures de Jacki Maréchal se rencontrent pour la première fois et se racontent par un enrichissement mutuel la belle histoire de la Vie. Dialogue magique des œuvres en mouvement qui questionnent en écho l’énergie sombre et la matière noire. Cette harmonieuse confluence de jeux de miroir et de résonnance illumine de poésie et de sobriété l’espace expos&...

  15. Exhibition

    CERN Multimedia

    Staff Association

    2016-01-01

    COLORATION Sandra Duchêne From September 5 to 16, 2016 CERN Meyrin, Main Building La recherche de l’Universel. Après tout ! C’est de l’Amour ! What else to say ? …La couleur, l’ENERGIE de la vie…

  16. Exhibition

    CERN Multimedia

    Staff Association

    2016-01-01

    La mosaïque ou quand détruire permet de construire Lauren Decamps Du 28 novembre au 9 décembre 2016 CERN Meyrin, Bâtiment principal Paysage d'Amsterdam - Lauren Decamps On ne doit jamais rien détruire qu'on ne soit sûr de pouvoir remplacer aussi avantageusement " écrivait Plutarque dans ses Œuvres morales du 1er siècle après JC. L'artiste mosaïste Lauren Decamps adhère à cette idée et tente à sa manière de donner une nouvelle vie à ses matériaux en les taillant puis les réassemblant, créant ainsi des œuvres abstraites et figuratives.

  17. Exhibition

    CERN Multimedia

    Staff Association

    2016-01-01

    The Elementary Particles of Painting Alfonso Fratteggiani Bianchi and Ermanno Imbergamo From September 26 to October 7, 2016 CERN Meyrin, Main Building With intentions similar to those of CERN physicists, the artist Alfonso Fratteggiani Bianchi investigates the color pigment, studying its interaction with light and with the support on which it is deposited. He creates monochrome paintings by spreading the color pigment in the pure state on stones, without using glue or any other type of adhesive. With intentions similar to artists, the physicist Ermanno Imbergamo investigates the use of luminescent wavelength shifters, materials commonly used in Particle Physics, for art. He creates other monochrome artworks, which disclose further aspects of interaction among light, color pigments and support. For more information: staff.association@cern.ch | Tel: 022 767 28 19

  18. Exhibition

    CERN Multimedia

    Staff Association

    2014-01-01

      Parallels vision Astronomical subjects which evoke extrasensory kinetic visions Alberto Di Fabio From 8 to 10 October, CERN Meyrin, Main Building In the framework of Italy@cern, the Staff Association presents Alberto Di Fabio. Di Fabio’s work is inspired by the fundamental laws of the physical world, as well as organic elements and their interrelation. His paintings and works on paper merge the worlds of art and science, depicting natural forms and biological structures in vivid colour and imaginative detail. For all additional information: staff.association@cern.ch | Tel: 022 767 28 19

  19. Exhibition

    CERN Multimedia

    Staff Association

    2011-01-01

    Jan Hladky, physicien de l'Institut de Physique de l'Académie des Sciences de la République tchèque, et membre de la collaboration Alice, expose ses œuvres au Bâtiment principal du 20 avril au 6 mai. Son exposition est dédiée aux victimes du séisme de Sendai. Des copies de ses œuvres seront mises en vente et les sommes récoltées seront versées au profit des victimes.

  20. Exhibition

    CERN Document Server

    Staff Association

    2017-01-01

    Gaïa Manuella Cany Du 10 au 28 avril 2017 CERN Meyrin, Bâtiment principal Oiseau - Manuella Cany. Tableaux abstraits inspirés de vues satellites ou photos prises du ciel. Certains sont à la frontière du figuratif alors que d'autres permettent de laisser libre cours à son imagination. Aux détails infinis, ces tableaux sont faits pour être vus de loin et de près grâce à une attention toute particulière apportée aux effets de matières et aux couleurs le long de volutes tantôt nuancées tantôt contrastées.   Pour plus d’informations : staff.association@cern.ch | Tél: 022 766 37 38

  1. Exhibition

    CERN Multimedia

    Staff Association

    2017-01-01

    Œuvres recentes Fabienne Wyler Du 6 au 17 février 2017 CERN Meyrin, Bâtiment principal L'escalier du diable B - aquarelle, encre de Chine XLV - Fabienne Wyler. En relation avec certains procédés d’écriture contemporaine (par ex. Webern ou certaines musiques conçues par ordinateur), les compositions picturales de Fabienne Wyler s’élaborent à partir de « modules » (groupes de quadrangles) qu’elle reproduit en leur faisant subir toutes sortes de transformations et de déplacements : étirements, renversements, rotations, effet miroir, transpositions, déphasages, superpositions, etc., et ceci à toutes les échelles. Au fil des œuvres sont apparues des séries intitulées, Bifurcations, Intermittences, Attracteurs étranges, Polyrythmies. Ces titres ont un lien &e...

  2. Combat Veterans with Comorbid PTSD and Mild TBI Exhibit a Greater Inhibitory Processing ERP from the Dorsal Anterior Cingulate Cortex

    Science.gov (United States)

    2014-08-08

    bipolar disorder , attention deficit hyperactivity disorder , or psychotic disorders ; or (4) acute medical problems. Included subjects returned for Session...event-related potential study of attention deficits in posttraumatic stress disorder during auditory and visual Go/NoGo continuous performance tasks...varying effects of depressive symptoms on N200 amplitudes likely arise from depression being a heterogeneous disorder , with some patients exhibiting

  3. Inattentiveness in attention-deficit/hyperactivity disorder

    Institute of Scientific and Technical Information of China (English)

    Ariane Sroubek; Mary Kelly; Xiaobo Li

    2013-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder with a long-term impact on functioning,productivity and quality of life of patients.This impact is largely due to the symptoms of inattentiveness.However,despite its impairing role in the lives of ADHD patients,inattentiveness has been studied relatively less frequently than have symptoms of impulsivity/hyperactivity and problems with executive function.This review therefore seeks to integrate the neuropsychological theories and current findings in the research fields of neuropsychology,neurophysiology,and neuroimaging,in an attempt to gain a more complete understanding of the role that inattentiveness plays in ADHD,as well as to suggest directions for future studies.The need for a more comprehensive understanding of inattentiveness and ADHD,which integrates findings from each of the three disciplines mentioned above,is emphasized.

  4. Stigma in attention deficit hyperactivity disorder

    OpenAIRE

    Anna K Mueller; Fuermaier, Anselm B. M.; Koerts, Janneke; Tucha, Lara

    2012-01-01

    Attention deficit hyperactivity disorder (ADHD) is a frequently diagnosed disorder in child- and adulthood with a high impact affecting multiple facets of social life. Therefore, patients suffering from ADHD are at high risk to be confronted with stigma, prejudices, and discrimination. A review of the empirical research in the field of ADHD with regard to stigma was performed. The findings of investigations in this field were clustered in different categories, including stigma in children wit...

  5. Medical Comorbidities in Attention Deficit Hyperactivity Disorder

    Directory of Open Access Journals (Sweden)

    Irem Yalug

    2009-09-01

    Full Text Available Attention Deficit Hyperactivity Disorder is one of the most common developmental disorders of childhood with a reported world-wide prevalence of 8 to 12 %. In studies conducted in our country the prevalence rates in community were reported to vary between 8.6 to 8.1 % while clinical prevalence rates were reported to vary between 8.6 to 29.44 %. Fifty to eighty percent of cases were reported to continue into adolescence while thirty to fifty percent may continue into adulthood. Attention deficit hyperactivity disorder is known to accompany subtle physical anomalies, allergic and neurologic disorders, obesity and eating disorders, traumatic injuries, risky sexual behavior, sleep disorders, substance and alcohol use, axis I and II disorders, occupational, legal and academic problems and increased treatment expenditures. Though the effects of this disorder continue throughout life, create burdens to the society along with its treatment as well as disabling the affected patients through their lives, and receive increasing attention in recent years, reviews focusing on problems associated with it are lacking. Therefore, this study aimed to summarize the results of previous studies conducted about medical comorbidities in attention deficit hyperactivity disorder.

  6. The World of Virtual Exhibitions

    Directory of Open Access Journals (Sweden)

    Irena Eiselt

    2013-09-01

    Full Text Available EXTENDED ABSTRACTSpecial collections of the National and University Library (NUK hide a lot of items of precious value. The Slovenian cultural heritage is stored on paper or on other media as a part of the library’s Manuscripts, Incunabula and Rare Books Collection, Old Prints Collection, Maps and Pictorial Collection, Music Collection, Ephemera Collection, Serials Collection, and Slovenian Diaspora Publications Collection. Only a small part of the treasures is temporary revealed to the public on special exhibitions. The idea of virtual exhibitions of library treasures was born in 2005. The library aimed to exhibit precious items of special collections of high historical or artistic value. In 2008 the first two virtual exhibitions were created in-house offering access to the rich collections of old postcards of Ljubljana at the beginning of 20th century kept in the Maps and Pictorial Collection of NUK. They were soon followed by other virtual exhibitions. At the beginning they were organised in the same way as physical exhibitions, afterwards different programs were used for creation of special effects (for ex. 3D wall. About two years ago it was decided that the creation of virtual exhibitions will be simplified. Files of digitised and borndigital library materials in jpg format are imported to MS PowerPoint 2010. Each jpg file is now formatted by adding a frame, a description … to the slides which are saved as jpg files. The last step is the import of jpg files into Cooliris application used for NUK web exhibitions. In the paper the virtual exhibition design and creation, the technical point of view and criteria for the selection of exhibition content are explained following the example of the virtual exhibitions the Old Postcards of Ljubljana, Photo Ateliers in Slovenia, a collection of photographs Four Seasons by Fran Krašovec and photos of Post-Earthquake Ljubljana in 1895.

  7. Functional connectivity of child and adolescent attention deficit hyperactivity disorder patients: correlation with IQ

    Directory of Open Access Journals (Sweden)

    Bo-yong Park

    2016-11-01

    Full Text Available Attention deficit hyperactivity disorder (ADHD is a pervasive neuropsychological disorder that affects both children and adolescents. Child and adolescent ADHD patients exhibit different behavioral symptoms such as hyperactivity and impulsivity, but not much connectivity research exists to help explain these differences. We analyzed openly accessible resting-state functional magnetic resonance imaging (rs-fMRI data on 112 patients (28 child ADHD, 28 adolescent ADHD, 28 child normal control, and 28 adolescent normal control. We used group independent component analysis (ICA and weighted degree values to identify interaction effects of age (child and adolescent and symptom (ADHD and NC in brain networks. The frontoparietal network showed significant interaction effects (p = 0.0068. The frontoparietal network is known to be related to hyperactive and impulsive behaviors. Intelligence quotient (IQ is an important factor in ADHD, and we predicted IQ scores using the results of our connectivity analysis. IQ was predicted using degree centrality values of networks with significant interaction effects of age and symptom. Actual and predicted IQ scores demonstrated significant correlation values, with an error of about 10%. Our study might provide imaging biomarkers for future ADHD and intelligence studies.

  8. Intravenous Prenatal Nicotine Exposure Alters METH-Induced Hyperactivity, Conditioned Hyperactivity, and BDNF in Adult Rat Offspring.

    Science.gov (United States)

    Lacy, Ryan T; Brown, Russell W; Morgan, Amanda J; Mactutus, Charles F; Harrod, Steven B

    2016-01-01

    compared to PS controls. PN rats treated with METH showed significant enhancement of locomotor behavior compared to PS rats following acute and repeated injections; however, PN did not produce differential initiation or expression of behavioral sensitization. METH produced conditioned hyperactivity, and PN rats exhibited a greater conditioned response of hyperactivity relative to controls. PN and METH exposure produced changes in BDNF protein levels in all three regions, and complex interactions were observed between these two factors. Logistic regression revealed that BDNF protein levels, throughout the mesocorticolimbic system, significantly predicted the difference in the conditioned hyperactive response of the animals: both correlations were significant, but the predicted relationship between BDNF and context-elicited activity was stronger in the PN (r = 0.67) compared to the PS rats (r = 0.42). These findings indicate that low-dose PN exposure produces long-term changes in activity and enhanced sensitivity to the locomotor effects of METH. The enhanced METH-induced contextual conditioning shown by the PN animals suggests that offspring of in utero tobacco smoke exposure have greater susceptibility to learn about drug-related conditional stimuli, such as the context. The PN-induced alterations in mesocorticolimbic BDNF protein lend further support for the hypothesis that maternal smoking during pregnancy produces alterations in neuronal plasticity that contribute to drug abuse vulnerability. The current findings demonstrate that these changes are persistent into adulthood.

  9. No hyperactive-impulsive subtype in teacher-rated attention-deficit/hyperactivity problems

    NARCIS (Netherlands)

    de Nijs, Pieter F. A.; Ferdinand, Robert F.; Verhulst, Frank C.

    2007-01-01

    The aim of this study was to investigate which homogeneous groups, according to teacher reports of attention-deficit/hyperactivity (ADH) Problems on the Teacher's Report Form (TRF), can be identified in a referred sample (n = 4,422; age = 6-18 years; mean age = 9.9 years; 66% boys, 34% girls). Laten

  10. The Relationship between Attention Deficit Hyperactivity Disorder and Child Temperament

    Science.gov (United States)

    Foley, Marie; McClowry, Sandra Graham; Castellanos, Francisco X.

    2008-01-01

    This study examined empirical and theoretical differences and similarities between attention deficit hyperactivity disorder (ADHD) and child temperament in 32 ADHD children aged 6-11 years, and a comparison group of 23 children with similar sociodemographic characteristics. Children were assessed for ADHD symptoms (hyperactivity, impulsivity, and…

  11. Fathering and Mothering of Preschool Boys with Hyperactivity

    Science.gov (United States)

    Keown, Louise

    2011-01-01

    This study examined links between paternal and maternal parenting factors and preschool hyperactivity in a community sample. Forty-one hyperactive and 38 comparison boys (aged 47-62 months) and their fathers and mothers were assessed on a range of interview, parent questionnaire, and observational measures of parenting and child behavior. Results…

  12. Attention Deficit/Hyperactivity Disorder (ADHD): The Basics

    Science.gov (United States)

    ... Signs Treating ADHD Reprints For More Information Share Attention-Deficit/Hyperactivity Disorder (ADHD): The Basics Download PDF Download ePub Order ... daily life, it could be a sign of attention-deficit/hyperactivity disorder (ADHD). ADHD is a disorder that makes it ...

  13. Attention-Deficit / Hyperactivity Disorder (ADHD): Data and Statistics

    Science.gov (United States)

    ... Form Controls ADHD Cancel Submit Search The CDC Attention-Deficit / Hyperactivity Disorder (ADHD) Note: Javascript is disabled or is not ... therapy is the recommended first line treatment for Attention-Deficit/Hyperactivity Disorder (ADHD) in young children, and should be tried ...

  14. The impact of maternal neglect on genetic hyperactivity.

    Science.gov (United States)

    Majdak, Petra; Grogan, Elizabeth L; Gogola, Joseph V; Sorokina, Anastassia; Tse, Stephen; Rhodes, Justin S

    2016-10-15

    Early environmental conditions are increasingly appreciated as critical in shaping behavior and cognition. Evidence suggests that stressful rearing environments can have an enduring impact on behaviors in adulthood, but few studies have explored the possibility that rearing environment could exacerbate genetic hyperactivity disorders. Uncovering a strong environmental influence on the transmission of hyperactivity could provide novel avenues for translational research. Recently we developed a selectively bred High-Active line of mice to model ADHD, providing a unique resource to address the question of environmental transmission. The High-Active line demonstrates transgenerational hyperactivity, but the influence of the postnatal environment (i.e. maternal care provided by dams) on hyperactivity had not been systemically quantified. This study employed a cross-fostering method to simultaneously address 1) whether High-Active and Control pups are provided with similar levels of care in the early environment, and 2) whether any differences in rearing environment influence hyperactive behavior. High-Active dams demonstrated impairment in all measures of maternal competence relative to Controls, which reduced survival rates and significantly reduced the body mass of offspring in early life and at weaning. While the deteriorated postnatal environment provided by High-Active dams was ultimately sufficient to depress Control activity, the hyperactivity of High-Active offspring remained unaffected by fostering condition. These data not only confirm the power of genetics to influence hyperactivity across generations, but also provide evidence that early rearing environments may not have a significant impact on the extreme end of hyperactive phenotypes.

  15. Case Studies of Effects of Artificial Food Colors on Hyperactivity.

    Science.gov (United States)

    Spring, Carl; And Others

    1981-01-01

    A double blind, double crossover study with six hyperactive boys (8 to 13 years old) tested B. Feingold's hypothesis that synthetic food colors cause hyperactivity in some children. All Ss were on the Feingold diet, eliminating artificial colors and flavors. The authors conclude that evidence for Feingold's hypothesis is weak. (Author)

  16. Sympathetic hyperactivity - A hidden enemy in chronic kidney disease patients

    NARCIS (Netherlands)

    Blankestijn, Peter J.

    2007-01-01

    Chronic kidney disease is often characterized by the presence of sympathetic hyperactivity. The aim of this brief review is to summarize available knowledge on the pathogenesis of sympathetic hyperactivity and to discuss its clinical relevance, the consequences of this knowledge for the choice of tr

  17. Neurocognitive psychotherapy for adult attention deficit hyperactive disorder

    Directory of Open Access Journals (Sweden)

    Susmita Halder

    2009-01-01

    Full Text Available Previously thought as a childhood disorder, attention-deficit hyperactivity disorder (ADHD is reported to be spreading at an increasing rate and affecting 4% to 5% of the adult population. It is characterized by persistent problems of inattention, hyperactivity and impulsivity. We present the case of an adult ADHD patient intervened with neurocognitive psychotherapy.

  18. Neurocognitive psychotherapy for adult attention deficit hyperactive disorder

    OpenAIRE

    Susmita Halder; Akash Kumar Mahato

    2009-01-01

    Previously thought as a childhood disorder, attention-deficit hyperactivity disorder (ADHD) is reported to be spreading at an increasing rate and affecting 4% to 5% of the adult population. It is characterized by persistent problems of inattention, hyperactivity and impulsivity. We present the case of an adult ADHD patient intervened with neurocognitive psychotherapy.

  19. Neurobiology of hyperactivity and reward : Agreeable restlessness in Anorexia Nervosa

    NARCIS (Netherlands)

    Scheurink, Anton J. W.; Boersma, Gretha J.; Nergardh, Ricard; Sodersten, Per; Nergårdh, Ricard; Södersten, Per

    2010-01-01

    Restricted food intake is associated with increased physical activity, very likely an evolutionary advantage, initially both functional and rewarding. The hyperactivity of patients with Anorexia Nervosa, however, is a main problem for recovery. This seemingly paradoxical reward of hyperactivity in A

  20. Behavioral impairments in rats with chronic epilepsy suggest comorbidity between epilepsy and attention deficit/hyperactivity disorder.

    Science.gov (United States)

    Pineda, Eduardo; Jentsch, J David; Shin, Don; Griesbach, Grace; Sankar, Raman; Mazarati, Andrey

    2014-02-01

    Attention deficit/hyperactivity disorder (ADHD) is encountered among patients with epilepsy at a significantly higher rate than in the general population. Mechanisms of epilepsy-ADHD comorbidity remain largely unknown. We investigated whether a model of chronic epilepsy in rats produces signs of ADHD, and thus, whether it can be used for studying mechanisms of this comorbidity. Epilepsy was induced in male Wistar rats via pilocarpine status epilepticus. Half of the animals exhibited chronic ADHD-like abnormalities, particularly increased impulsivity and diminished attention in the lateralized reaction-time task. These impairments correlated with the suppressed noradrenergic transmission in locus coeruleus outputs. The other half of animals exhibited depressive behavior in the forced swimming test congruently with the diminished serotonergic transmission in raphe nucleus outputs. Attention deficit/hyperactivity disorder and depressive behavior appeared mutually exclusive. Therefore, the pilocarpine model of epilepsy affords a system for reproducing and studying mechanisms of comorbidity between epilepsy and both ADHD and/or depression.

  1. Atypical outcome in attention deficit hyperactivity disorder.

    Science.gov (United States)

    Schmidt, K; Freidson, S

    1990-07-01

    This report describes the course of psychiatric illness in two boys. Both presented with attention deficit hyperactivity disorder (ADHD) in midchildhood; after puberty, one boy developed a schizophrenic illness while the other boy developed a major affective illness. Although the major ADHD outcome studies have found no link between the childhood occurrence of ADHD and psychosis in adulthood, occasionally such a link may exist. The theoretical and practical implications of this finding are discussed. It should be noted, however, that such outcome is highly atypical and very rare.

  2. Attention-deficit/hyperactivity disorder (ADHD)

    DEFF Research Database (Denmark)

    Dalsgaard, S.

    2013-01-01

    The proposed revision of the diagnostic criteria in DSM-5 for attention-deficit/hyperactivity disorder (ADHD) will not fundamentally change the concept of ADHD. This is mainly due to the fact that, DSM-5 will retain the exact DSM-IV wording of all 18 symptoms, but will add new examples that make...... the criteria more appropriate for children, adolescents and adults. The age of onset will also be changed from 7 to 12 years, the subtyping of the disorder will change, and pervasive developmental disorders will no longer be an exclusion criterion. Although the main concept is unchanged, the suggested changes...

  3. The Effects of Classroom Interventions on Off-Task and Disruptive Classroom Behavior in Children with Symptoms of Attention-Deficit/Hyperactivity Disorder : A Meta-Analytic Review

    NARCIS (Netherlands)

    Gaastra, Geraldina F; Groen, Yvonne; Tucha, Lara; Tucha, Oliver

    2016-01-01

    Children with attention-deficit/hyperactivity disorder (ADHD) often exhibit problem behavior in class, which teachers often struggle to manage due to a lack of knowledge and skills to use classroom management strategies. The aim of this meta-analytic review was to determine the effectiveness of seve

  4. Photowalk Exhibition opens at Microcosm

    CERN Multimedia

    Katarina Anthony

    2011-01-01

    The winning photographs from the 2010 Global Particle Physics Photowalk competition will go on display at Microcosm from 11 February to 2 April. The exhibition is part of a global photography event taking place over three continents, with Photowalk exhibitions opening simultaneously at Fermilab in the US, KEK in Japan and here at CERN.   DESY wire chamber - First place people's choice; second place global jury competition. Photographer: Hans-Peter Hildebrandt  If you were one of the 1,300 photography lovers who voted in last year’s Photowalk competition, this exhibition is your chance to see the winning entries in print. The exhibition will take place in the downstairs gallery of Microcosm, overlooking the garden. 15 photographs will be on display, with each of the laboratories that participated in Photowalk represented by their 3 winning entries. Among them will be the “people’s choice” sunburst photo of a particle detector at DESY (Photo 1), and...

  5. Auto Technology Exhibition in Tianjing

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    @@ The 4th International Automotive Technology Exhibition Tianjing2009,jointly hosted by the Society of Automotive Engineers of China(SAE-China),China Automotive Technology and Research Center(CATRC)and Tianjin Economic-Technological Development Area(TETD),is to be held in Tianjin Binhai International Convention and Exhibition Center from August 27 to August 30 this year.In line with China's national 11th Five-year Plan,The Automobile Industry Revitalization and Adjustments Planning and The Equipment Manufacturing Revitalization and Adjustments Planning,this Exhibition,centered on the theme of automobile and equipment manufacturing,arranges the exhibition halls respectively for private autos,commercial autos and equipment manufacturing etc.

  6. Neural markers of social and monetary rewards in children with Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder

    OpenAIRE

    Maria Luz Gonzalez-Gadea; Mariano Sigman; Alexia Rattazzi; Claudio Lavin; Alvaro Rivera-Rei; Julian Marino; Facundo Manes; Agustin Ibanez

    2016-01-01

    Recent theories of decision making propose a shared value-related brain mechanism for encoding monetary and social rewards. We tested this model in children with Attention-Deficit/Hyperactivity Disorder (ADHD), children with Autism Spectrum Disorder (ASD) and control children. We monitored participants’ brain dynamics using high density-electroencephalography while they played a monetary and social reward tasks. Control children exhibited a feedback Error-Related Negativity (fERN) modulation ...

  7. Globe exhibit wins international acclaim

    CERN Multimedia

    Katarina Anthony

    2011-01-01

    The Globe’s “Universe of Particles” exhibition has recently received four prestigious awards for its avant-garde design. This external praise is great encouragement for the CERN exhibitions currently on the drawing board.   The Universe of Particles exhibition has won 4 awards for its avant-garde design. Back in 2008, the design company Atelier Brückner was presented with a challenge: to design the layout of a new permanent exhibition for CERN, one that would epitomize both the Organization and its research. The brief was concise but complex: the exhibit had to be symbolic of the Organization, use modern technology, engage and immerse visitors, and, preferably, use touch-screen technology. With the help of IArt, an interactive technology firm, and based on the content provided by CERN’s Education Group, Atelier Brückner developed the “Universe of Particles” exhibit as it is today. Its principal concept centred on the s...

  8. ATTENTION DEFICIT HYPERACTIVITY DISORDER. A CLINICAL LECTURE

    Directory of Open Access Journals (Sweden)

    A. S. Kotov

    2015-01-01

    Full Text Available Attention deficit hyperactivity disorder (ADHD is a serious problem to pediatric neurologists. The prevalence of ADHD in developed countries ranges from 1 to 20 %. ADHD is characterized by a triad of symptoms: inattention, hyperactivity, and impulsivity (the International Statistical Classification of Diseases, 10th revision, codes it as F90 and it is the most common conduct disorder in children. The etiology of ADHD remains disсutable to the present day; there are a few basic concepts of the origin of this disorder. Its manifestations may be a reason for family conflicts, poor peer relationships, social and school maladjustment, learning problems, lower academic performance, accidents and injuries, smoking, psychoactive substance abuse (toxicomania, narcomania, delinquencies, deviant social behavior, thus having a negative impact on all spheres of a patient’s life. The manifestations of ADHD may continue in adulthood, resulting in work and family life problems, low self-evaluation, alcohol and psychoactive substance abuse, and other unfavorable consequences. The authors describe the etiology, pathogenesis, diagnostic principles (diagnostic scales and tests, differential diagnosis (by setting out a large group of different diseases, the manifestations of which can mimic ADHD, treatment, and prognosis of the disorder. Within its therapeutic correction framework, the authors present the definition and general principles of Montessori therapy, including recommendations for parents and relatives to deal with children with ADHD. 

  9. [Prevention in attention deficit hyperactivity disorder].

    Science.gov (United States)

    Quintero, J; Martin, M; Alcindor, P; Perez-Templado, J

    2016-01-01

    Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that begins at an early age and can be present until adulthood. Subjects with ADHD not only have symptoms such as inattention, impulsivity or hyperactivity but also have their social and emotional areas affected. In addition, they have an associated increased risk for presenting comorbilities with other psychiatric disorders, overshadowing the development. Considering ADHD as a evolutionary risk factor, prevention should be considered as a primary goal. Most preventive actions on ADHD have been focused on tertiary prevention. The present review aims to study the factors involved in the development of ADHD in order to form a prevention model beyond tertiary prevention. This research focuses on models of primary prevention (early detection of disease) and secondary prevention (to prevent or delay the disease), trying to incorporate them into daily practice. This study reviews risk factors that affect ADHD. Through actions aimed to pursue an early detection, development of the disorder could be improved, and by identifying population at risk, efforts could be concentrated on developing a true primary prevention (perinatal period and early childhood) that eventually could contribute to reduce the incidence of ADHD.

  10. [Attention deficit hyperactivity disorder outcome in adults].

    Science.gov (United States)

    Bange, F

    2011-07-01

    Attention deficit hyperactivity disorder (ADHD) is among the most common psychiatric disorders of childhood. Although some symptoms of ADHD may diminish this does not mean that functioning is unimpaired in adults. Follow-up studies of children with ADHD show that it persists into adulthood in the majority of cases. Due to genetic factors high rates of ADHD exist among the parents of children with ADHD. More females are identified and become diagnosed in adulthood. There is a greater persistence of inattentive than of hyperactive/impulsive childhood symptoms of ADHD in adulthood. Some experts conceptualise ADHD as primarily a deficit of executive functions impairing planification, time perception and emotional regulation. ADHD often presents as a lifelong condition in adults associated with a range of clinical and psychosocial impairments. Young adults with comorbid antisocial or substance use disorder in adolescence are at significantly increased risk for criminal behaviors. Some predictors of the outcome have been identified such as childhood symptom profile and severity, comorbidity and childhood family adversities.

  11. SMG1 identified as a regulator of Parkinson's disease-associated alpha-synuclein through siRNA screening.

    Directory of Open Access Journals (Sweden)

    Adrienne Henderson-Smith

    Full Text Available Synucleinopathies are a broad class of neurodegenerative disorders characterized by the presence of intracellular protein aggregates containing α-synuclein protein. The aggregated α-synuclein protein is hyperphosphorylated on serine 129 (S129 compared to the unaggregated form of the protein. While the precise functional consequences of S129 hyperphosphorylation are still being clarified, numerous in vitro and in vivo studies suggest that S129 phosphorylation is an early event in α-synuclein dysfunction and aggregation. Identifying the kinases and phosphatases that regulate this critical phosphorylation event may ultimately prove beneficial by allowing pharmacological mitigation of synuclein dysfunction and toxicity in Parkinson's disease and other synucleinopathies. We report here the development of a high-content, fluorescence-based assay to quantitate levels of total and S129 phosphorylated α-synuclein protein. We have applied this assay to conduct high-throughput loss-of-function screens with siRNA libraries targeting 711 known and predicted human kinases and 206 phosphatases. Specifically, knockdown of the phosphatidylinositol 3-kinase related kinase SMG1 resulted in significant increases in the expression of pS129 phosphorylated α-synuclein (p-syn. Moreover, SMG1 protein levels were significantly reduced in brain regions with high p-syn levels in both dementia with Lewy bodies (DLB and Parkinson's disease with dementia (PDD. These findings suggest that SMG1 may play an important role in increased α-synuclein pathology during the course of PDD, DLB, and possibly other synucleinopathies.

  12. Application of MALDI-TOF mass spectrometry for study on fibrillar and oligomeric aggregates of alpha-synuclein

    Directory of Open Access Journals (Sweden)

    Severinovskaya O. V.

    2014-05-01

    Full Text Available Aim. To study the -synuclein (ASN aggregates of different structural origin, namely amyloid fibrils and spherical oligomers, in comparison with a native protein. Methods. MALDI TOF mass spectrometry and atomic for- ce microscopy (AFM. Results. The mass spectra of native and fibrillar ASN have similar character, i. e. they are characterized by the well pronounced peak of protein molecular ion, the low molecular weight associates, and rather low contain of fragmentation products. The spectrum of oligomeric aggregate is characterized by the high contain of fragmentation products, low intensity of protein molecular ion and the absence of peaks of associates. Conclusions. The difference between the spectra of fibrillar and oligomeric ASN could be explained, first, by the different content of the «residual» monomeric ASN and the protein degradation products in the studied samples, and, second, by the different structure-depended mechanisms of the protein degradation induced by the laser ionization. We suggested that the MALDI-TOF mass spectroscopy is a method useful for the investigation of ASN aggregation and characterization of its high order self-associates; besides, there is an interest in estimating the potency of the MALDI-TOF for the analysis of aggregation of various amyloidogenic proteins.

  13. Photobiomodulation Suppresses Alpha-Synuclein-Induced Toxicity in an AAV-Based Rat Genetic Model of Parkinson's Disease.

    Directory of Open Access Journals (Sweden)

    Abid Oueslati

    Full Text Available Converging lines of evidence indicate that near-infrared light treatment, also known as photobiomodulation (PBM, may exert beneficial effects and protect against cellular toxicity and degeneration in several animal models of human pathologies, including neurodegenerative disorders. In the present study, we report that chronic PMB treatment mitigates dopaminergic loss induced by unilateral overexpression of human α-synuclein (α-syn in the substantia nigra of an AAV-based rat genetic model of Parkinson's disease (PD. In this model, daily exposure of both sides of the rat's head to 808-nm near-infrared light for 28 consecutive days alleviated α-syn-induced motor impairment, as assessed using the cylinder test. This treatment also significantly reduced dopaminergic neuronal loss in the injected substantia nigra and preserved dopaminergic fibers in the ipsilateral striatum. These beneficial effects were sustained for at least 6 weeks after discontinuing the treatment. Together, our data point to PBM as a possible therapeutic strategy for the treatment of PD and other related synucleinopathies.

  14. Photobiomodulation Suppresses Alpha-Synuclein-Induced Toxicity in an AAV-Based Rat Genetic Model of Parkinson’s Disease

    Science.gov (United States)

    Oueslati, Abid; Lovisa, Blaise; Perrin, John; Wagnières, Georges; van den Bergh, Hubert; Tardy, Yanik; Lashuel, Hilal A.

    2015-01-01

    Converging lines of evidence indicate that near-infrared light treatment, also known as photobiomodulation (PBM), may exert beneficial effects and protect against cellular toxicity and degeneration in several animal models of human pathologies, including neurodegenerative disorders. In the present study, we report that chronic PMB treatment mitigates dopaminergic loss induced by unilateral overexpression of human α-synuclein (α-syn) in the substantia nigra of an AAV-based rat genetic model of Parkinson’s disease (PD). In this model, daily exposure of both sides of the rat’s head to 808-nm near-infrared light for 28 consecutive days alleviated α-syn-induced motor impairment, as assessed using the cylinder test. This treatment also significantly reduced dopaminergic neuronal loss in the injected substantia nigra and preserved dopaminergic fibers in the ipsilateral striatum. These beneficial effects were sustained for at least 6 weeks after discontinuing the treatment. Together, our data point to PBM as a possible therapeutic strategy for the treatment of PD and other related synucleinopathies. PMID:26484876

  15. Role of N-terminal methionine residues in the redox activity of copper bound to alpha-synuclein.

    Science.gov (United States)

    Rodríguez, Esaú E; Arcos-López, Trinidad; Trujano-Ortiz, Lidia G; Fernández, Claudio O; González, Felipe J; Vela, Alberto; Quintanar, Liliana

    2016-09-01

    Amyloid aggregation of α-synuclein (AS) is one of the hallmarks of Parkinson's disease. The interaction of copper ions with the N-terminal region of AS promotes its amyloid aggregation and metal-catalyzed oxidation has been proposed as a plausible mechanism. The AS(1-6) fragment represents the minimal sequence that models copper coordination to this intrinsically disordered protein. In this study, we evaluated the role of methionine residues Met1 and Met5 in Cu(II) coordination to the AS(1-6) fragment, and in the redox activity of the Cu-AS(1-6) complex. Spectroscopic and electronic structure calculations show that Met1 may play a role as an axial ligand in the Cu(II)-AS(1-6) complex, while Met5 does not participate in metal coordination. Cyclic voltammetry and reactivity studies demonstrate that Met residues play an important role in the reduction and reoxidation processes of this complex. However, Met1 plays a more important role than Met5, as substitution of Met1 by Ile decreases the reduction potential of the Cu-AS(1-6) complex by ~80 mV, causing a significant decrease in its rate of reduction. Reoxidation of the complex by oxygen results in oxidation of the Met residues to sulfoxide, being Met1 more susceptible to copper-catalyzed oxidation than Met5. The sulfoxide species can suffer elimination of methanesulfenic acid, rendering a peptide with no thioether moiety, which would impair the ability of AS to bind Cu(I) ions. Overall, our study underscores the important roles that Met1 plays in copper coordination and the reactivity of the Cu-AS complex.

  16. Inhibition by Multifunctional Magnetic Nanoparticles Loaded with Alpha-Synuclein RNAi Plasmid in a Parkinson's Disease Model

    Science.gov (United States)

    Niu, Shuiqin; Zhang, Ling-Kun; Zhang, Li; Zhuang, Siyi; Zhan, Xiuyu; Chen, Wu-Ya; Du, Shiwei; Yin, Liang; You, Rong; Li, Chu-Hua; Guan, Yan-Qing

    2017-01-01

    Lewy bodies are considered as the main pathological characteristics of Parkinson's disease (PD). The major component of Lewy bodies is α-synuclein (α-syn). The use of gene therapy that targeting and effectively interfere with the expression of α-syn in neurons has received tremendous attention. In this study, we used magnetic Fe3O4 nanoparticles coated with oleic acid molecules as a nano-carrier. N-isopropylacrylamide derivative (NIPAm-AA) was photo-immobilized onto the oleic acid molecules, and shRNA (short hairpin RNA) was absorbed. The same method was used to absorb nerve growth factor (NGF) to NIPAm-AA to specifically promote neuronal uptake via NGF receptor-mediated endocytosis. Additionally, shRNA plasmid could be released into neurons because of the temperature and pH sensitivity of NIPAm-AA interference with α-syn synthesis. We investigated apoptosis in neurons with abrogated α-syn expression in vitro and in vivo. The results demonstrated that multifunctional superparamagnetic nanoparticles carrying shRNA for α-syn could provide effective repair in a PD model. PMID:28042339

  17. [Frequency of single nucleotide polymorphisms and alpha-synuclein haplotypes associated with sporadic Parkinson's disease in the Mexican population].

    Science.gov (United States)

    Davila-Ortiz de Montellano, D J; Rodriguez-Violante, M; Fresan, A; Monroy-Jaramillo, N; Yescas-Gomez, P

    2016-10-16

    Introduccion. La enfermedad de Parkinson (EP) es una entidad neurodegenerativa comun de inicio en la etapa adulta. Su incidencia en Mexico se estima en 40-50 casos por 100.000 habitantes/año y constituye la cuarta causa de atencion medica en el Instituto Nacional de Neurologia y Neurocirugia. La proteina alfa-sinucleina, SNCA, es clave en la patologia de la EP y sus polimorfismos se han asociado a un riesgo aumentado de desarrollarla. Objetivo. Evaluar el riesgo que representan los polimorfismos rs2619364, rs2619363, rs2736990, rs7684318, rs17016074, rs356219, rs356220 y rs356203 de SNCA en una muestra de sujetos mexicanos para la EP. Sujetos y metodos. Se evaluaron 171 pacientes con diagnostico de EP y 171 controles pareados por sexo y edad mediante reaccion en cadena de la polimerasa en tiempo real, y se realizo un analisis estadistico para determinar la asociacion de los polimorfismos con la enfermedad. Resultados. Las variantes rs356220, rs356203, rs7684318 y rs2736990 de SNCA estan asociadas a la enfermedad y forman dos haplotipos de riesgo elevado para desarrollar EP esporadica en la poblacion mexicana. Conclusiones. Las variaciones en SNCA son un factor de riesgo para desarrollar EP y pueden ser biomarcadores geneticos especificos para pacientes mestizos mexicanos como herramienta de apoyo diagnostico en la EP esporadica.

  18. Structural variation of alpha-synuclein with temperature by a coarse-grained approach with knowledge-based interactions

    Directory of Open Access Journals (Sweden)

    Peter Mirau

    2015-09-01

    Full Text Available Despite enormous efforts, our understanding the structure and dynamics of α-synuclein (ASN, a disordered protein (that plays a key role in neurodegenerative disease is far from complete. In order to better understand sequence-structure-property relationships in α-SYNUCLEIN we have developed a coarse-grained model using knowledge-based residue-residue interactions and used it to study the structure of free ASN as a function of temperature (T with a large-scale Monte Carlo simulation. Snapshots of the simulation and contour contact maps show changes in structure formation due to self-assembly as a function of temperature. Variations in the residue mobility profiles reveal clear distinction among three segments along the protein sequence. The N-terminal (1-60 and C-terminal (96-140 regions contain the least mobile residues, which are separated by the higher mobility non-amyloid component (NAC (61-95. Our analysis of the intra-protein contact profile shows a higher frequency of residue aggregation (clumping in the N-terminal region relative to that in the C-terminal region, with little or no aggregation in the NAC region. The radius of gyration (Rg of ASN decays monotonically with decreasing the temperature, consistent with the finding of Allison et al. (JACS, 2009. Our analysis of the structure function provides an insight into the mass (N distribution of ASN, and the dimensionality (D of the structure as a function of temperature. We find that the globular structure with D ≈ 3 at low T, a random coil, D ≈ 2 at high T and in between (2 ≤ D ≤ 3 at the intermediate temperatures. The magnitudes of D are in agreement with experimental estimates (J. Biological Chem 2002.

  19. The anti-parkinsonian drug selegiline (R(-)-deprenyl) inhibits the nucleation phase of {alpha}-synuclein aggregation

    Energy Technology Data Exchange (ETDEWEB)

    Follmer, Cristian; Braga, Carolina A.; Khattar, Elias; Palhano, Fernando; Freitas, Monica S.; Silva, Jerson L.; Foguel, Debora [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Inst. de Bioquimica Medica; Lara, Flavio Alves [Fundacao Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, RJ (Brazil). Lab. de Microbiologia Celular; Lashuel, Hilal [Ecole Polytechnique Federale de Lausanne (EPFL), Lausanne (Switzerland)

    2008-07-01

    Full text: Parkinson's disease (P D) is a chronic disorder characterized by the formation of intra neuronal inclusions called Le wy bodies mainly composed of a-synuclein (a-syn), a natively- unfolded protein with unknown function. Its implication in P D is due to the fact that two mutations (A30P and A53T) are linked to early-onset forms of P D. Selegiline (R(-)-deprenyl) is a noncompetitive monoamino oxidase-B inhibitor which has ne uroprotective effects. It has been administered to P D patients either as monotherapy or in combination with L-dopa. However, its mechanism is unknown. We evaluated the effect of Sel in the in vitro aggregation of A30P either in the presence or absence of amyloid seeds (small fibrils acting as a nucleus). We observed that Sel (1:0.5 or 1:1.5 protein:Sel ratio ) delays fibril formation by enhancing the nucleation phase. Sel effects on fibril formation are abolished when previously added seeds are present, suggesting that Sel interferes with nucleus formation, and is dependent of the A30P:Sel ratio. This inhibitory effect of Sel on the nucleation phase was also evaluated by using another amyloidogenic, natively- unfolded protein, Sup35, but in this case, the effect of Sel was not abolished when Sel was added after the end of the lag phase. We also observed that Sel in combination with dopamine (DA) favors fibril formation. Currently, we are mapping A30P-Sel interaction by NMR. We observed that in the presence of Sel (1:2 p tn:Sel ratio), very little changes occur in the HSQC spectra of the isotopically labeled protein. These results suggest that in the presence of DA, Sel favors the conversion of the toxic prot ofibrils into the non-toxic fibrils, alleviating the dopaminergic neurons from toxic effects. In the non-dopaminergic neurons, Sel would slow down the fibrillation process, probably by forming large spherical aggregates.

  20. Validation of a quantitative cerebrospinal fluid alpha-synuclein assay in a European-wide interlaboratory study

    DEFF Research Database (Denmark)

    Kruse, N.; Persson, S.; Alcolea, D.

    2015-01-01

    assay (ELISA) for the quantification of aSyn in CSF, we carried out a round robin trial with 18 participating laboratories trained in CSF ELISA analyses within the BIOMARKAPD project in the EU Joint Program -Neurodegenerative Disease Research. CSF samples (homogeneous aliquots from pools) and ELISA kits...

  1. A small-angle X-ray scattering study of alpha-synuclein from human red blood cells.

    Science.gov (United States)

    Araki, Katsuya; Yagi, Naoto; Nakatani, Rie; Sekiguchi, Hiroshi; So, Masatomo; Yagi, Hisashi; Ohta, Noboru; Nagai, Yoshitaka; Goto, Yuji; Mochizuki, Hideki

    2016-07-29

    α-synuclein (α-syn) is the main component of Lewy bodies, which are neuropathological hallmarks of patients with Parkinson's disease. As it has been controversial whether human α-syn from erythrocytes exists as a tetramer under physiological conditions, we tried solving this issue by the small-angle X-ray solution scattering method. Under two different conditions (high ionic strength with a Tris buffer and low ionic strength with an ammonium acetate buffer), no evidence was found for the presence of tetramer. When comparing erythrocyte and recombinant α-syn molecules, we found no significant difference of the molecular weight and the secondary structure although the buffer conditions strongly affect the radius of gyration of the protein. The results indicate that, even though a stable tetramer may not be formed, conformation of α-syn depends much on its environment, which may be the reason for its tendency to aggregate in cells.

  2. 5-HT2A Receptor Binding in the Frontal Cortex of Parkinson's Disease Patients and Alpha-Synuclein Overexpressing Mice

    DEFF Research Database (Denmark)

    Rasmussen, Nadja Bredo; Olesen, Mikkel Vestergaard; Brudek, Tomasz;

    2016-01-01

    The receptor is highly involved in aspects of cognition and executive function and seen to be affected in neurodegenerative diseases like Alzheimer’s disease and related to the disease pathology. Even though Parkinson’s disease (PD) is primarily a motor disorder, reports of impaired executive fun...

  3. Structural variation of alpha-synuclein with temperature by a coarse-grained approach with knowledge-based interactions

    Science.gov (United States)

    Mirau, Peter; Farmer, B. L.; Pandey, R. B.

    2015-09-01

    Despite enormous efforts, our understanding the structure and dynamics of α-synuclein (ASN), a disordered protein (that plays a key role in neurodegenerative disease) is far from complete. In order to better understand sequence-structure-property relationships in α-SYNUCLEIN we have developed a coarse-grained model using knowledge-based residue-residue interactions and used it to study the structure of free ASN as a function of temperature (T) with a large-scale Monte Carlo simulation. Snapshots of the simulation and contour contact maps show changes in structure formation due to self-assembly as a function of temperature. Variations in the residue mobility profiles reveal clear distinction among three segments along the protein sequence. The N-terminal (1-60) and C-terminal (96-140) regions contain the least mobile residues, which are separated by the higher mobility non-amyloid component (NAC) (61-95). Our analysis of the intra-protein contact profile shows a higher frequency of residue aggregation (clumping) in the N-terminal region relative to that in the C-terminal region, with little or no aggregation in the NAC region. The radius of gyration (Rg) of ASN decays monotonically with decreasing the temperature, consistent with the finding of Allison et al. (JACS, 2009). Our analysis of the structure function provides an insight into the mass (N) distribution of ASN, and the dimensionality (D) of the structure as a function of temperature. We find that the globular structure with D ≈ 3 at low T, a random coil, D ≈ 2 at high T and in between (2 ≤ D ≤ 3) at the intermediate temperatures. The magnitudes of D are in agreement with experimental estimates (J. Biological Chem 2002).

  4. Region-specific tauopathy and synucleinopathy in brain of the alpha-synuclein overexpressing mouse model of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Masliah Eliezer

    2011-08-01

    Full Text Available Abstract Background α-synuclein [α-Syn]-mediated activation of GSK-3β leading to increases in hyperphosphorylated Tau has been shown by us to occur in striata of Parkinson's diseased [PD] patients and in animal models of PD. In Alzheimer's disease, tauopathy exists in several brain regions; however, the pattern of distribution of tauopathy in other brain regions of PD or in animal models of PD is not known. The current studies were undertaken to analyze the distribution of tauopathy in different brain regions in a widely used mouse model of PD, the α-Syn overexpressing mouse. Results High levels of α-Syn levels were seen in the brain stem, with a much smaller increase in the frontal cortex; neither cerebellum nor hippocampus showed any overexpression of α-Syn. Elevated levels of p-Tau, hyperphosphorylated at Ser202, Ser262 and Ser396/404, were seen in brain stem, with lower levels seen in hippocampus. In both frontal cortex and cerebellum, increases were seen only in p-Ser396/404 Tau, but not in p-Ser202 and p-Ser262. p-GSK-3β levels were not elevated in any of the brain regions, although total GSK-3β was elevated in brain stem. p-p38MAPK levels were unchanged in all brain regions examined, while p-ERK levels were elevated in brain stem, hippocampus and cerebellum, but not the frontal cortex. p-JNK levels were increased in brain stem and cerebellum but not in the frontal cortex or hippocampus. Elevated levels of free tubulin, indicating microtubule destabilization, were seen only in the brain stem. Conclusion Our combined data suggest that in this animal model of PD, tauopathy, along with microtubule destabilization, exists primarily in the brain stem and striatum, which are also the two major brain regions known to express high levels of α-Syn and undergo the highest levels of degeneration in human PD. Thus, tauopathy in PD may have a very restricted pattern of distribution.

  5. The mechanism of sirtuin 2–mediated exacerbation of alpha-synuclein toxicity in models of Parkinson disease

    Science.gov (United States)

    Francelle, Laetitia; Pinho, Raquel; Szegö, Éva M.; Martinho, Renato; Munari, Francesca; Lázaro, Diana F.; Moniot, Sébastien; Guerreiro, Patrícia; Fonseca, Luis; Marijanovic, Zrinka; Antas, Pedro; Gerhardt, Ellen; Enguita, Francisco Javier; Fauvet, Bruno; Penque, Deborah; Pais, Teresa Faria; Tong, Qiang; Becker, Stefan; Kügler, Sebastian; Lashuel, Hilal Ahmed; Steegborn, Clemens; Zweckstetter, Markus; Outeiro, Tiago Fleming

    2017-01-01

    Sirtuin genes have been associated with aging and are known to affect multiple cellular pathways. Sirtuin 2 was previously shown to modulate proteotoxicity associated with age-associated neurodegenerative disorders such as Alzheimer and Parkinson disease (PD). However, the precise molecular mechanisms involved remain unclear. Here, we provide mechanistic insight into the interplay between sirtuin 2 and α-synuclein, the major component of the pathognomonic protein inclusions in PD and other synucleinopathies. We found that α-synuclein is acetylated on lysines 6 and 10 and that these residues are deacetylated by sirtuin 2. Genetic manipulation of sirtuin 2 levels in vitro and in vivo modulates the levels of α-synuclein acetylation, its aggregation, and autophagy. Strikingly, mutants blocking acetylation exacerbate α-synuclein toxicity in vivo, in the substantia nigra of rats. Our study identifies α-synuclein acetylation as a key regulatory mechanism governing α-synuclein aggregation and toxicity, demonstrating the potential therapeutic value of sirtuin 2 inhibition in synucleinopathies. PMID:28257421

  6. Characterizing the dynamics of alpha-synuclein oligomers using hydrogen/deuterium exchange monitored by mass spectrometry

    DEFF Research Database (Denmark)

    Mysling, Simon; Betzer, Cristine; Jensen, Poul H;

    2013-01-01

    hydrogen/deuterium exchange monitored by mass spectrometry (HDX-MS), we have analyzed the structural dynamics of soluble αSN oligomers. The analyzed oligomers were metastable, slowly dissociating to monomers over a period of 21 days, after excess monomer had been removed. The C-terminal region of α......-shielded structure. The protected regions were interspersed by two somewhat more dynamic regions (residues 18-38 and 55-70). In the oligomeric state, the isotopic exchange pattern of the region of residues 35-95 of αSN corresponded well with previous nuclear magnetic resonance and electron paramagnetic resonance...

  7. 5-HT2A Receptor Binding in the Frontal Cortex of Parkinson's Disease Patients and Alpha-Synuclein Overexpressing Mice

    DEFF Research Database (Denmark)

    Rasmussen, Nadja Bredo; Olesen, Mikkel Vestergaard; Brudek, Tomasz;

    2016-01-01

    The 5-HT2A receptor is highly involved in aspects of cognition and executive function and seen to be affected in neurodegenerative diseases like Alzheimer's disease and related to the disease pathology. Even though Parkinson's disease (PD) is primarily a motor disorder, reports of impaired...... executive function are also steadily being associated with this disease. Not much is known about the pathophysiology behind this. The aim of this study was thereby twofold: (1) to investigate 5-HT2A receptor binding levels in Parkinson's brains and (2) to investigate whether PD associated pathology, alpha...

  8. Exhibition - Mathematics, A Beautiful Elsewhere

    CERN Multimedia

    2011-01-01

    From 21 October 2011 to 18 March 2012, the Fondation Cartier pour l’art contemporain will present the exhibition Mathematics: A Beautiful Elsewhere, an exhibition developed in association with the Institut des Hautes Études Scientifiques (IHÉS) and under the patronage of UNESCO. For this unprecedented event, the foundation invited mathematicians to work with artists with whom it has previously worked to create an exhibition that allows visitors to see, hear, do, interpret and think about mathematics. By bringing mathematics into its premises, the Fondation Cartier is itself undergoing the “sudden change of scenery” described by mathematician Alexandre Grothendieck. More information is available here. Fondation Cartier pour l’art contemporain 261, boulevard Raspail 75014 Paris http://fondation.cartier.com Private Visit For professors, researchers and all the staff of Mathematics departments...

  9. Hyperactivity, perseveration and increased responding during attentional rule acquisition in the Fragile X mouse model.

    Science.gov (United States)

    Kramvis, Ioannis; Mansvelder, Huibert D; Loos, Maarten; Meredith, Rhiannon

    2013-01-01

    Attentional deficits and executive function impairments are common to many neurodevelopmental disorders of intellectual disability and autism, including Fragile X syndrome (FXS). In the knockout mouse model for FXS, significant changes in synaptic plasticity and connectivity are found in the prefrontal cortex (PFC)-a prominent region for attentional processing and executive control. Given these alterations in PFC synaptic function, we tested whether adult Fragile X knockout mice exhibited corresponding impairments in inhibitory control, perseveration, and sustained attention. Furthermore, we investigated individual performance during attentional rule acquisition. Using the 5-choice serial reaction time task, our results show no impairments in inhibitory control and sustained attention. Fragile X knockout mice exhibited enhanced levels of correct and incorrect responding, as well as perseveration of responding during initial phases of rule acquisition, that normalized with training. For both knockout and wild type mice, pharmacological attenuation of metabotropic glutamate receptor 5 signaling did not affect response accuracy but reduced impulsive responses and increased omission errors. Upon rule reversal, Fragile X knockout mice made more correct and incorrect responses, similar to the initial phases of rule acquisition. Analogous to heightened activity upon novel rule acquisition, Fragile X knockout mice were transiently hyperactive in both a novel open field (OF) arena and novel home cage. Hyperactivity ceased with familiarization to the environment. Our findings demonstrate normal inhibitory control and sustained attention but heightened perseveration, responding, and hyperactivity during novel rule acquisition and during exposure to novel environments in Fragile X knockout mice. We therefore provide evidence for subtle but significant differences in the processing of novel stimuli in the mouse model for the FXS.

  10. Effect of atomoxetine on hyperactivity in an animal model of attention-deficit/hyperactivity disorder (ADHD.

    Directory of Open Access Journals (Sweden)

    Su Jin Moon

    Full Text Available Hyperactivity related behaviors as well as inattention and impulsivity are regarded as the nuclear symptoms of attention-deficit/hyperactivity disorder (ADHD.To investigate the therapeutic effects of atomoxetine on the motor activity in relation to the expression of the dopamine (DA D2 receptor based on the hypothesis that DA system hypofunction causes ADHD symptoms, which would correlate with extensive D2 receptor overproduction and a lack of DA synthesis in specific brain regions: prefrontal cortex (PFC, striatum, and hypothalamus.Young male spontaneously hypertensive rats (SHR, animal models of ADHD, were randomly divided into four groups according to the daily dosage of atomoxetine and treated for 21 consecutive days. The animals were assessed using an open-field test, and the DA D2 receptor expression was examined.The motor activity improved continuously in the group treated with atomoxetine at a dose of 1 mg/Kg/day than in the groups treated with atomoxetine at a dose of 0.25 mg/Kg/day or 0.5 mg/Kg/day. With respect to DA D2 receptor immunohistochemistry, we observed significantly increased DA D2 receptor expression in the PFC, striatum, and hypothalamus of the SHRs as compared to the WKY rats. Treatment with atomoxetine significantly decreased DA D2 expression in the PFC, striatum, and hypothalamus of the SHRs, in a dose-dependent manner.Hyperactivity in young SHRs can be improved by treatment with atomoxetine via the DA D2 pathway.

  11. Attention-deficit/hyperactivity disorder: management.

    Science.gov (United States)

    Szymanski, M L; Zolotor, A

    2001-10-15

    Attention-deficit/hyperactivity disorder (ADHD) is the most common psychiatric disorder of childhood and often persists into adulthood. ADHD is a neurophysiologic disorder defined in behavioral terms and associated with significant morbidity in the realms of social and academic success, and self-esteem. ADHD is often associated with comorbid psychiatric disorders and learning disabilities, which further impede the successful development of these persons. It is essential that family physicians be knowledgeable about the presentation and diagnosis of ADHD. Stimulant medications continue to be the mainstay of treatment, although many other medications (such as antidepressants and alpha blockers) are helpful adjuvants to therapy. Current recommendations for treatment include an individualized, multimodal approach involving parents, teachers, counselors and the school system. Treatment follow-up includes monitoring response to medications in various settings, as well as side effects. With time and interest, the family physician can develop the skills needed to treat this disorder.

  12. What causes attention deficit hyperactivity disorder?

    Science.gov (United States)

    Thapar, Anita; Cooper, Miriam; Jefferies, Rachel; Stergiakouli, Evangelia

    2012-03-01

    Attention deficit hyperactivity disorder (ADHD) affects around 1-3% of children. There is a high level of comorbidity with developmental and learning problems as well as with a variety of psychiatric disorders. ADHD is highly heritable, although there is no single causal risk factor and non-inherited factors also contribute to its aetiology. The genetic and environmental risk factors that have been implicated appear to be associated with a range of neurodevelopmental and neuropsychiatric outcomes, not just ADHD. The evidence to date suggests that both rare and multiple common genetic variants likely contribute to ADHD and modify its phenotype. ADHD or a similar phenotype also appears to be more common in extreme low birth weight and premature children and those exposed to exceptional early adversity. In this review, the authors consider recent developments in the understanding of risk factors that influence ADHD.

  13. Green Revolution for Exhibition Industry

    Institute of Scientific and Technical Information of China (English)

    Yan Manman

    2010-01-01

    @@ Shanghai World Expo is widely regarded as another grand international pageant, so many people thought that the opening ceremony must be as much magnificent and brilliant as the opening ceremony for Beijing Olympics.However, it was revealed by Wan Jifei, Executive Director of the ExecutiveCommittee of the Shanghai World Expo that the opening ceremony of the Expo was not that luxurious and extravagant as that for the Beijing Olympics, but would have its own characteristics under the elaborate design and thorough arrangement conducted by the host. The veto against that luxurious opening ceremony was actually a practice echoing for the concept of Green World Expo, which would be applied for every corner from the beginning to the end of the Expo, including the construction of exhibition hall, building of exhibition stand and advertisement etc.

  14. A New Exhibition in Microcosm

    CERN Multimedia

    2000-01-01

    Sebastien Pelletier explains states of matter to an enthusiastic group of youngsters during the opening of a new exhibition in Microcosm last week. The Fun with Physics workshop will be offered to all 13-14 year olds in school groups visiting CERN this year. The new Microcosm contents have been developed in collaboration with the local teaching community, and cover particles and the forces that act between them.

  15. World Expo and Exhibition Industry

    Institute of Scientific and Technical Information of China (English)

    Guo Liqin

    2010-01-01

    @@ February 8 witnessed the construction of 2010 World Expo's China Pavilion completed after two years' work. The pavilion, in the shape of an oriental crown,showcases the spirit of traditional Chinese culture. It is significant since all other nation's pavilion constructed only for temporary exhibition, but China's Pavilion will be lasting architecture as the symbol of world civilization. Another similar famous case is Eiffel Tower which was built as the entrance of the world expo held in. 1889.

  16. [Neurobiology of attention deficit/hyperactivity disorder].

    Science.gov (United States)

    Purper-Ouakil, Diane; Lepagnol-Bestel, Aude-Marie; Grosbellet, Edith; Gorwood, Philip; Simonneau, Michel

    2010-05-01

    Attention deficit/hyperactivity disorder (ADHD) is a frequent and disabling condition in school children, with cognitive and behavioral symptoms persisting into adulthood in a majority of patients. Etiology of ADHD is considered multifactorial and heterogenous, with an important contribution of genetic factors. Apart from genetic risk factors, emphasis has been put on the early environment, and prenatal exposure to nicotine, alcohol, prematurity and low birth weight have been associated with subsequent ADHD symptoms. This article reviews recent findings in neurobiology, genetics and neuroimaging of ADHD. Despite their clinical heterogeneity and frequent comorbidities, key symptoms of ADHD, such as impulsivity, hyperactivity and inattention are regularly improved by dopaminergic agonists, leading to consider dopaminergic dysfunction a possibly contributing factor in ADHD. Norepinephrine agonists also have clinical efficacy on ADHD symptoms and several other neurotransmission systems are likely involved in the etiology of ADHD. Dysfunction of neurotransmitter systems have been related to impairments of sustained attention, inhibitory control and working memory. Cognitive tasks focusing on reaction time and verbal working memory fit certain criteria for ADHD endophenotypes, offering a pathway to bridge the gap between observed traits and genetic vulnerability. Despite ADHD being a highly heritable disorder, most candidate genes with replicated findings across association studies only account for a small proportion of genetic variance. Neuroimaging studies using treatment effect or cognitive tasks show differential activation patterns in ADHD patients, with trends towards normalization under treatment. Further insight into neurobiological mechanisms involved in ADHD will arise from collaborative networks and combination of imaging, genetic and neurobiological techniques with consideration of the developmental aspects of ADHD.

  17. "Big Science" exhibition at Balexert

    CERN Multimedia

    2008-01-01

    CERN is going out to meet those members of the general public who were unable to attend the recent Open Day. The Laboratory will be taking its "Big Science" exhibition from the Globe of Science and Innovation to the Balexert shopping centre from 19 to 31 May 2008. The exhibition, which shows the LHC and its experiments through the eyes of a photographer, features around thirty spectacular photographs measuring 4.5 metres high and 2.5 metres wide. Welcomed and guided around the exhibition by CERN volunteers, shoppers at Balexert will also have the opportunity to discover LHC components on display and watch films. "Fun with Physics" workshops will be held at certain times of the day. Main hall of the Balexert shopping centre, ground floor, from 9.00 a.m. to 7.00 p.m. Monday to Friday and from 10 a.m. to 6 p.m. on the two Saturdays. Call for volunteers All members of the CERN personnel are invited to enrol as volunteers to help welcom...

  18. Mobile Technologies in Museum Exhibitions

    Directory of Open Access Journals (Sweden)

    Sandra Medić

    2014-10-01

    Full Text Available In order to be up–to–date and give visitors a memorable and unique experience, museums are including usage of digital technologies in their exhibitions. Even though museums in Serbia are very important part of tourism offer, they still have traditional settings that are poorly interpreted. The majority of them have a scientific and historical review which is unattractive for various target groups of visitors and for museums it’s important to continually try out new ways in interpretation of their settings. Because technology continues to rapidly change the way we communicate, cultural institutions should adapt to new ways of communication with their visitors. This paper examines mobile technologies that can be used in museums to give visitors a different experience and transfer the knowledge innovatively. In that way it will be presented the modern concept of presentation of museum exhibitions, focusing on usage of mobile devices through mobile applications and QR codes. The paper provides the broad understanding of usage mobile technologies in museum exhibitions with its advantages and limitations. The research results can help the museums management to improve interpretation and communication with visitors and enrich the visitor experience.

  19. Stigmatization in teachers towards adults with attention deficit hyperactivity disorder

    NARCIS (Netherlands)

    Fuermaier, Anselm B.M.; Tucha, Lara; Müller, Kathi; Koerts, Janneke; Hauser, Joachim; Lange, Klaus W; Tucha, Oliver

    2014-01-01

    OBJECTIVES: Attention deficit hyperactivity disorder (ADHD) is understood as a developmental disorder which shares common characteristics between childhood, adolescence and adulthood. However, ADHD is widely associated with misconceptions and misbeliefs which can lead to stigmatization. Teachers hav

  20. Attention-Deficit / Hyperactivity Disorder (ADHD): Symptoms and Diagnosis

    Science.gov (United States)

    ... Form Controls ADHD Cancel Submit Search The CDC Attention-Deficit / Hyperactivity Disorder (ADHD) Note: Javascript is disabled ... for developmental level: Often fails to give close attention to details or makes careless mistakes in schoolwork, ...

  1. The Hyperactive Child. Should We Be Paying More Attention?

    Science.gov (United States)

    Varga, James

    1979-01-01

    Current literature on hyperactivity stresses the central role of short attention, distractibility, and impulsivity in contributing to the child's behavioral and learning difficulties. Journal availability: American Medical Association, 535 North Dearborn Street, Chicago, Illinois 60610. (Author)

  2. The hyperactive child at adolescence: cognitive, emotional, and social functioning.

    Science.gov (United States)

    Hoy, E; Weiss, G; Minde, K; Cohen, N

    1978-09-01

    In view of the paucity of detailed follow-up studies on hyperactive children, the performance of 15 adolescents diagnosed hyperactive 5 years previously was compared to that of a control group of equivalent age, sex, intelligence, and social class. Eleven cognitive tests measuring sustained attention, visual-motor and motor skills, abstraction, and reading ability, as well as three self-assessment tests examining self-esteem, activity level, social functioning, academic status, and career aspirations were administered. The hyperactives performed significantly worse than the controls on the sustained attention, visual-motor, and motor tasks, and on two of the four reading tests. They also gave themselves significantly lower ratings on some of the self-esteem and sociability items. It would appear that the hyperactives at adolescence still have attentional and stimulus-processing difficulties, which affect not only their academic performance but also their social functioning.

  3. Neurofibromatosis type 1 and attention deficit hyperactivity disorder: a case study and literature review

    Directory of Open Access Journals (Sweden)

    Miguel CS

    2015-03-01

    Full Text Available Carmen Sílvia Miguel, Tiffany M Chaim-Avancini, Maria Aparecida Silva, Mario Rodrigues LouzãAdult Attention Deficit Hyperactivity Disorder Program (PRODATH, Institute of Psychiatry, University of São Paulo, São Paulo, BrazilBackground: The cognitive profile of children with neurofibromatosis type 1 (NF1 and attention deficit hyperactivity disorder (ADHD has been well characterized, but few studies have evaluated the cognitive abilities of adults with NF1 and ADHD.Objectives: We investigated 1 the cognitive profile of an adult patient with NF1 and inattention problems, 2 changes in his cognition after 14 months of follow-up, and 3 whether the patient exhibited comorbid NF1 and ADHD or secondary ADHD-like symptoms.Methods: We administered neuropsychological tests of executive function, attention, verbal and visual memory, visuospatial function, and language during two evaluations separated by 14 months.Results: We found no changes in sustained attention, language, or verbal memory. Visual memory, verbal learning, selective attention inhibitory control, and problem solving declined over time, whereas visual search, psychomotor speed, visuospatial function, and mental flexibility improved.Conclusion: Our patient exhibited a cognitive profile characteristic of both NF1 and ADHD, leading to the hypothesis that the patient had comorbid ADHD instead of secondary ADHD-like symptoms. More studies are necessary to characterize the cognition of patients with NF1 and ADHD.Keywords: ADHD, executive function, NF1, low-grade pontine glioma, cognition

  4. CERN Permanent exhibitions short version

    CERN Multimedia

    2016-01-01

    Visits Explore by yourself the issues CERN's physicists are trying to solve: given that the entire universe is made of particles, where do they come from? Why do they behave in the way they do? Discover the massive apparatus used by physicists at CERN, like the LHC, and see how each part works. CERN invites the public to discover the mysteries of the Universe and the work of the world's biggest physics laboratory through free of charge guided tours and permanent exhibitions. As a group, with friends, individually, on foot, on your bike, come and discover CERN or explore it virtually. Welcome!

  5. Borneo 2007. Three European Exhibitions

    Directory of Open Access Journals (Sweden)

    Bernard Sellato

    2013-01-01

    Full Text Available The year 2007 appears to have been an exceptionally good one for Borneo in Europe. Two exhibitions were held in France, and one in Switzerland, which prominently featured the big island, its forests, its peoples, its cultures, and its arts. Here a brief review of these three events. Bornéo... Dayak et Punan. Peuples de la forêt tropicale humide, Musée d’Art et d’Archéologie, Laon, France, 25 November 2006 – 11 March 2007 The beautiful city of Laon, only a short distance by train or by car fro...

  6. Meditation-based training: a possible intervention for attention deficit hyperactivity disorder.

    Science.gov (United States)

    Baijal, Shruti; Gupta, Rashmi

    2008-04-01

    Recent studies suggest that training-based measures are effective in improving cognitive skills. Meditation-based training has produced lasting changes in brain and cognitive functions. This technique of mental training exhibits neuroplasticity in the attentional networks, exhibiting superior performance, especially in the domain of attention and executive control processing, which is impaired in attention deficit hyperactivity disorder (ADHD). Although intervention techniques for ADHD are well researched, many individuals continue to experience significant functional impairment despite the symptom improvement. This emphasizes a need for a comprehensive approach that requires an effective behavioral intervention. The present paper provides a converging review of meditation-based effects on the brain, dysfunctions of ADHD, and suggestions for enhancement of cognitive abilities in patients with ADHD using meditational training combined with existing measures of intervention. The idea proposed herein should be considered a step for initiation of empirical studies on meditation-based training intervention and outcome effects.

  7. Hyperactivity in boys with attention deficit/hyperactivity disorder (ADHD): the association between deficient behavioral inhibition, attentional processes, and objectively measured activity.

    Science.gov (United States)

    Alderson, R Matt; Rapport, Mark D; Kasper, Lisa J; Sarver, Dustin E; Kofler, Michael J

    2012-01-01

    Contemporary models of ADHD hypothesize that hyperactivity reflects a byproduct of inhibition deficits. The current study investigated the relationship between children's motor activity and behavioral inhibition by experimentally manipulating demands placed on the limited-resource inhibition system. Twenty-two boys (ADHD = 11, TD = 11) between the ages of 8 and 12 years completed a conventional stop-signal task, two choice-task variants (no-tone, ignore-tone), and control tasks while their motor activity was measured objectively by actigraphs placed on their nondominant wrist and ankles. All children exhibited significantly higher activity rates under all three experimental tasks relative to control conditions, and children with ADHD moved significantly more than typically developing children across conditions. No differences in activity level were observed between the inhibition and noninhibition experimental tasks for either group, indicating that activity level was primarily associated with basic attentional rather than behavioral inhibition processes.

  8. Enrico Fermi exhibition at CERN

    CERN Document Server

    2002-01-01

    A touring exhibition celebrating the centenary of Enrico Fermi's birth in 1901 will be on display at CERN (Main Building, Mezzanine) from 12-27 September. You are cordially invited to the opening celebration on Thursday 12 September at 16:00 (Main Building, Council Chamber), which will include speechs from: Luciano Maiani Welcome and Introduction Arnaldo Stefanini Celebrating Fermi's Centenary in Documents and Pictures Antonino Zichichi The New 'Centro Enrico Fermi' at Via Panisperna Ugo Amaldi Fermi at Via Panisperna and the birth of Nuclear Medicine Jack Steinberger Fermi in Chicago Valentin Telegdi A Close-up of Fermi and the screening of a documentary video about Fermi: Scienziati a Pisa: Enrico Fermi (Scientists at Pisa: Enrico Fermi) created by Francesco Andreotti for La Limonaia from early film, photographs and sound recordings (In Italian, with English subtitles - c. 30 mins). This will be followed by an aperitif on the Mezz...

  9. Attention-deficit/hyperactivity disorder dimensionality: the reliable 'g' and the elusive 's' dimensions.

    Science.gov (United States)

    Wagner, Flávia; Martel, Michelle M; Cogo-Moreira, Hugo; Maia, Carlos Renato Moreira; Pan, Pedro Mario; Rohde, Luis Augusto; Salum, Giovanni Abrahão

    2016-01-01

    The best structural model for attention-deficit/hyperactivity disorder (ADHD) symptoms remains a matter of debate. The objective of this study is to test the fit and factor reliability of competing models of the dimensional structure of ADHD symptoms in a sample of randomly selected and high-risk children and pre-adolescents from Brazil. Our sample comprised 2512 children aged 6-12 years from 57 schools in Brazil. The ADHD symptoms were assessed using parent report on the development and well-being assessment (DAWBA). Fit indexes from confirmatory factor analysis were used to test unidimensional, correlated, and bifactor models of ADHD, the latter including "g" ADHD and "s" symptom domain factors. Reliability of all models was measured with omega coefficients. A bifactor model with one general factor and three specific factors (inattention, hyperactivity, impulsivity) exhibited the best fit to the data, according to fit indices, as well as the most consistent factor loadings. However, based on omega reliability statistics, the specific inattention, hyperactivity, and impulsivity dimensions provided very little reliable information after accounting for the reliable general ADHD factor. Our study presents some psychometric evidence that ADHD specific ("s") factors might be unreliable after taking common ("g" factor) variance into account. These results are in accordance with the lack of longitudinal stability among subtypes, the absence of dimension-specific molecular genetic findings and non-specific effects of treatment strategies. Therefore, researchers and clinicians might most effectively rely on the "g" ADHD to characterize ADHD dimensional phenotype, based on currently available symptom items.

  10. Depression and the hyperactive right-hemisphere.

    Science.gov (United States)

    Hecht, David

    2010-10-01

    Depression is associated with an inter-hemispheric imbalance; a hyperactive right-hemisphere (RH) and a relatively hypoactive left-hemisphere (LH). Nevertheless, the underlying mechanisms which can explain why depression is associated with a RH dominance remain elusive. This article points out the potential links between functional cerebral asymmetries and specific symptoms and features of depression. There is evidence that the RH is selectively involved in processing negative emotions, pessimistic thoughts and unconstructive thinking styles--all which comprise the cognitive phenomenology of depression and in turn contribute to the elevated anxiety, stress and pain associated with the illness. Additionally, the RH mediates vigilance and arousal which may explain the sleep disturbances often reported in depression. The RH had also been linked with self-reflection, accounting for the tendency of depressed individuals to withdraw from their external environments and focus attention inward. Physiologically, RH activation is associated with hyprecortisolemia, which contributes to the deterioration of the immune system functioning and puts depressed patients at a greater risk of developing other illnesses, accounting for depression's high comorbidity with other diseases. Conversely, the LH is specifically involved in processing pleasurable experiences, and its relative attenuation is in line with the symptoms of anhedonia that characterize depression. The LH is also relatively more involved in decision-making processes, accounting for the indecisiveness that is often accompanied with depression.

  11. Paroxysmal sympathetic hyperactivity in neurological critical care

    Directory of Open Access Journals (Sweden)

    Rajesh Verma

    2015-01-01

    Full Text Available Introduction: Paroxysmal sympathetic hyperactivity (PSH is a clinical disorder mainly caused by traumatic brain injury, stroke, encephalitis and other types of brain injury. The clinical features are episodes of hypertension, tachycardia, tachypnea, fever and dystonic postures. In this study, we described clinical profile and outcome of six patients of PSH admitted in neurocritical care unit. Materials and Methods: This was a prospective observational study conducted at neurology critical care unit of a tertiary care center. All patients admitted at neurology critical unit during 6-month period from August 2013 to January 2014 were screened for the occurrence of PSH. The clinical details and outcome was documented. Results: PSH was observed in 6 patients. Male to female ratio was 5:1. Mean age ± SD was 36.67 ± 15.19 years. The leading causes were traumatic brain injury (two patients, stroke (two patients and Japanese encephalitis (JE (one patient and tuberculous meningitis (one patient. Conclusion: PSH is an unusual complication in neurocritical care. It prolonged the hospitalization and hampers recovery. The other life-threatening conditions that mimic PSH should be excluded. The association with JE and tuberculous meningitis was not previously described in literature.

  12. Developmental psychopathology: Attention Deficit Hyperactivity Disorder (ADHD

    Directory of Open Access Journals (Sweden)

    Petermann Franz

    2009-09-01

    Full Text Available Abstract Background Attention Deficit/Hyperactivity Disorder (ADHD, formerly regarded as a typical childhood disorder, is now known as a developmental disorder persisting over the lifespan. Starting in preschool-age, symptoms vary depending on the age group affected. Method According to the variability of ADHD-symptoms and the heterogeneity of comorbid psychiatric disorders, a broad review of recent studies was performed. These findings were summarized in a developmental psychopathological model, documenting relevant facts on a timeline. Results Based on a genetic disposition and a neuropsychological deregulation, there is evidence for factors which persist across the lifespan, change age-dependently, or show validity in a specific developmental phase. Qualitative changes can be found for children in preschool-age and adults. Conclusion These differences have implications for clinical practice as they can be used for prevention, diagnostic proceedings, and therapeutic intervention as well as for planning future studies. The present article is a translated and modified version of the German article "Entwicklungspsychopathologie der ADHS", published in Zeitschrift für Psychiatrie, Psychologie und Psychotherapie, 56, 2008, S. 265-274.

  13. [A survey on attention deficit hyperactivity disorder].

    Science.gov (United States)

    Quiviger, S; Caci, H

    2014-10-01

    Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder described in international classifications and thought to affect about 5% of school-aged children and 3% of adults in the general population. In France, most clinicians are not formally trained in assessing and treating ADHD, leading to underdiagnosis of the disorder. ADHD impacts all the aspects of these children's daily life (school performance, family and social life) and later their adult life. We invited all the private-practice pediatricians in the east of the Provence-Alpes-Côte d'Azur region (southeast France) to participate in a survey: 57 out of 81 accepted. The results show that their knowledge on ADHD could be improved, and that their a priori conception of the etiology of the disorder (neurodevelopmental syndrome versus societal syndrome) guides their clinical approach. We recommend pediatricians be trained to improve screening, diagnosis, and ADHD treatment monitoring in children. This recommendation might also apply to general practitioners for children and parents/adults.

  14. Cystamine preparations exhibit anticoagulant activity.

    Science.gov (United States)

    Aleman, Maria M; Holle, Lori A; Stember, Katherine G; Devette, Christa I; Monroe, Dougald M; Wolberg, Alisa S

    2015-01-01

    Transglutaminases are a superfamily of isoenzymes found in cells and plasma. These enzymes catalyze the formation of ε-N-(γ-glutamyl)-lysyl crosslinks between proteins. Cystamine blocks transglutaminase activity and is used in vitro in human samples and in vivo in mice and rats in studies of coagulation, immune dysfunction, and inflammatory disease. These studies have suggested cystamine blocks fibrin crosslinking and has anti-inflammatory effects, implicating transglutaminase activity in the pathogenesis of several diseases. We measured the effects of cystamine on fibrin crosslinking, tissue factor-triggered plasma clot formation and thrombin generation, and coagulation factor enzymatic activity. At concentrations that blocked fibrin crosslinking, cystamine also inhibited plasma clot formation and reduced thrombin generation. Cystamine inhibited the amidolytic activity of coagulation factor XI and thrombin towards chromogenic substrates. These findings demonstrate that cystamine exhibits anticoagulant activity during coagulation. Given the close relationship between coagulation and inflammation, these findings suggest prior studies that used cystamine to implicate transglutaminase activity in disease pathogenesis warrant re-examination.

  15. Cystamine preparations exhibit anticoagulant activity.

    Directory of Open Access Journals (Sweden)

    Maria M Aleman

    Full Text Available Transglutaminases are a superfamily of isoenzymes found in cells and plasma. These enzymes catalyze the formation of ε-N-(γ-glutamyl-lysyl crosslinks between proteins. Cystamine blocks transglutaminase activity and is used in vitro in human samples and in vivo in mice and rats in studies of coagulation, immune dysfunction, and inflammatory disease. These studies have suggested cystamine blocks fibrin crosslinking and has anti-inflammatory effects, implicating transglutaminase activity in the pathogenesis of several diseases. We measured the effects of cystamine on fibrin crosslinking, tissue factor-triggered plasma clot formation and thrombin generation, and coagulation factor enzymatic activity. At concentrations that blocked fibrin crosslinking, cystamine also inhibited plasma clot formation and reduced thrombin generation. Cystamine inhibited the amidolytic activity of coagulation factor XI and thrombin towards chromogenic substrates. These findings demonstrate that cystamine exhibits anticoagulant activity during coagulation. Given the close relationship between coagulation and inflammation, these findings suggest prior studies that used cystamine to implicate transglutaminase activity in disease pathogenesis warrant re-examination.

  16. EU Climate Change Exhibition Held

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    <正>On April 25, the CPAFFC, the China-EU Association (CEUA) and the Delegation of the European Commission to China jointly held the opening ceremony for the EU Exhibition on Climate Change in the CPAFFC. He Luli, former vice chairperson of the NPC Standing Committee and honorary president of the CEUA, Jose Manuel Barroso, president of the European Commission, and Li Jianping, vice president of the CPAFFC, attended the opening ceremony and made speeches. Honorary President He Luli highly praised the achievements made by China and the EU in their longtime cooperation of mutual benefits in various fields including environmental protection. She said, for many years China and EU have both committed to the development of all-round strategic partnership and establishment of a multi-level mechanism of political dialogue. She expressed, with increasing enthusiasm the CEUA would continue to actively carry out nongovernmental exchanges between China and the EU, and promote cooperation between the two sides in the fields of economy, society, environmental protection, science and technology, culture, etc.

  17. Cadherin-13 gene is associated with hyperactive/impulsive symptoms in attention/deficit hyperactivity disorder.

    Science.gov (United States)

    Salatino-Oliveira, Angélica; Genro, Julia Pasqualini; Polanczyk, Guilherme; Zeni, Cristian; Schmitz, Marcelo; Kieling, Christian; Anselmi, Luciana; Menezes, Ana Maria Baptista; Barros, Fernando Cde; Polina, Evelise Regina; Mota, Nina R; Grevet, Eugênio Horácio; Bau, Claiton Henrique Dotto; Rohde, Luis Augusto; Hutz, Mara Helena

    2015-04-01

    Several efforts have been made to find new genetic risk variants which explain the high heritability of ADHD. At the genome level, genes involved in neurodevelopmental pathways were pointed as candidates. CDH13 and CTNNA2 genes are within GWAS top hits in ADHD and there are emerging notions about their contribution to ADHD pathophysiology. The main goal of this study is to test the association between SNPs in CDH13 and CTNNA2 genes and ADHD across the life cycle in subjects with ADHD. This study included 1,136 unrelated ADHD cases and 946 individuals without ADHD. No significant association between CDH13 and CTNNA2 was observed between cases and controls across different samples (P ≥ 0.096 for all comparisons). No allele was significantly more transmitted than expected from parents to ADHD probands. The CDH13 rs11150556 CC genotype was associated with more hyperactive/impulsive symptoms in youths with ADHD (children/adolescents clinical sample: F = 7.666, P = 0.006, FDR P-value = 0.032; Pelotas Birth Cohort sample: F = 6.711, P = 0.011, FDR P-value = 0.032). Although there are many open questions regarding the role of neurodevelopmental genes in ADHD symptoms, the present study suggests that CDH13 is associated with hyperactive/impulsive symptoms in youths with ADHD.

  18. Altered regional homogeneity patterns in adults with attention-deficit hyperactivity disorder

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xunheng [School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096 (China); Key Laboratory of Child Development and Learning Science (Ministry of Education), Southeast University, Nanjing 210096 (China); Jiao, Yun, E-mail: yunjiao@seu.edu.cn [Jiangsu Key Laboratory of Molecular Imaging and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009 (China); Tang, Tianyu; Wang, Hui; Lu, Zuhong [School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096 (China); Key Laboratory of Child Development and Learning Science (Ministry of Education), Southeast University, Nanjing 210096 (China)

    2013-09-15

    Purpose: Investigating the discriminative brain map for patients with attention-deficit/hyperactivity disorder (ADHD) based on feature selection and classifier; and identifying patients with ADHD based on the discriminative model. Materials and methods: A dataset of resting state fMRI contains 23 patients with ADHD and 23 healthy subjects were analyzed. Regional homogeneity (ReHo) was extracted from resting state fMRI signals and used as model inputs. Raw ReHo features were ranked and selected in a loop according to their p values. Selected features were trained and tested by support vector machines (SVM) in a cross validation procedure. Cross validation was repeated in feature selection loop to produce optimized model. Results: Optimized discriminative map indicated that the ADHD brains exhibit more increased activities than normal controls in bilateral occipital lobes and left front lobe. The altered brain regions included portions of basal ganglia, insula, precuneus, anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), thalamus, and cerebellum. Correlation coefficients indicated significant positive correlation of inattentive scores with bilateral cuneus and precuneus, and significant negative correlation of hyperactive/impulsive scores with bilateral insula and claustrum. Additionally, the optimized model produced total accuracy of 80% and sensitivity of 87%. Conclusion: ADHD brain regions were more activated than normal controls during resting state. Linear support vector classifier can provide useful discriminative information of altered ReHo patterns for ADHD; and feature selection can improve the performances of classification.

  19. A multidimensional approach of impulsivity in adult attention deficit hyperactivity disorder.

    Science.gov (United States)

    Lopez, Régis; Dauvilliers, Yves; Jaussent, Isabelle; Billieux, Joël; Bayard, Sophie

    2015-06-30

    We aimed to compare adult patients with attention deficit hyperactivity disorder (ADHD) and matched controls on four dimensions of impulsivity (urgency, lack of premeditation, lack of perseverance, and sensation seeking) and to examine the association between impulsivity and ADHD symptoms. The study was conducted on 219 participants: 72 adult ADHD patients and 147 aged and gender matched controls. All participants completed questionnaires measuring the various facets of impulsivity (UPPS Impulsive Behavior Scale), ADHD and depressive symptoms severity. Patients were also assessed for ADHD subtypes, mood disorders, and addictive behaviors. ADHD patients exhibited higher urgency, lower premeditation and lower perseverance in comparison to controls. Lack of perseverance showed the strongest association with ADHD (area under curve=0.95). Patients with combined inattentive and hyperactive/impulsive subtypes reported more frequently substance abuse problems and had higher scores on urgency and sensation seeking dimensions of impulsivity than those with predominantly inattentive subtype. We report for the first time a multidimensional evaluation of impulsivity in adult ADHD patients. The UPPS Impulsive Behavior Scale may constitute a useful screening tool for ADHD in adults and may help to further understanding the psychological mechanisms underlying the differences between the ADHD subgroups.

  20. [Methylphenidate use in dogs with attention deficit hyperactivity disorder (ADHD). A case report of a Weimaraner bitch].

    Science.gov (United States)

    Piturru, P

    2014-04-16

    A 10-month-old Weimaraner bitch was presented at the practice exhibiting agitation, hyperactivity, inability to learn and attention deficit. The diagnostic findings were excessive, long-lasting acoustic and locomotory activity with unexpected inappropriate reactions. Hematological and biochemical blood analyses did not demonstrate abnormal findings. The first attempts at behavioral therapy and fluoxetine application were unsatisfactory. Therefore, a test was conducted with medication for central nervous system stimulation to confirm a diagnosis of hyperkinesis. Following the diagnosis of attention deficit hyperactivity disorder, the therapy was continued with behavioral modifications, with special consideration of rehabituation and resocialization as well as the use of methylphenidate. During the course of the therapy the bitch developed hyperactivity again when on heat. After changing the dosage of methylphenidate and additionally using dog appeasing pheromone, the behavior of the bitch became normal after 8 days. Two months later endoscopic ovarioectomy was performed. Twelve months after the initial use of methylphenidate the medication could be discontinued completely and the dog's behavior was normal. The methylphenidate dosage used during this therapy was much higher than recommended in the literature.

  1. Right hemisphere dysfunction in subjects with attention-deficit disorder with and without hyperactivity.

    Science.gov (United States)

    García-Sánchez, C; Estévez-González, A; Suárez-Romero, E; Junqué, C

    1997-02-01

    The attention-deficit disorder, with and without hyperactivity, is associated with defective attention, response inhibition and, in attention-deficit disorder with hyperactivity, with motor restlessness. In adults, inattention, defective response inhibition, and impersistence are more commonly seen in right hemisphere lesions. In the present study, we investigate possible right hemisphere dysfunctions in attention-deficit disorder with hyperactivity and attention-deficit disorder without hyperactivity. The right hemisphere performance of 60 teenagers, 16 having attention-deficit disorder with hyperactivity, 9 having attention-deficit disorder without hyperactivity, and 35 controls, selected clinically (DSM-III) and experimentally (through Continuous Performance Test and Paced Auditory Addition Task), with normal IQ was assessed using a wide-ranging battery of visuospatial, visuoperceptive, and visuoconstructive functions (Benton's Line Orientation, Benton's Visual Retention, Raven's Progressive Matrices, Wechsler Adult Intelligence Scale [WAIS] Block-Design, Rey's Complex Figure). Teenagers with attention-deficit disorder with and without hyperactivity performed significantly worse than controls. Greater differences were found between subjects with attention-deficit disorder without hyperactivity and control than between subjects with attention-deficit disorder with hyperactivity and control subjects. Our results seem to be consistent with right-hemisphere dysfunction, especially in subjects with attention-deficit disorder without hyperactivity. Additionally, WAIS Block-Design and Benton's Line Orientation are the visuospatial tests with the highest discriminant power to differentiate between controls, subjects with attention-deficit disorder without hyperactivity, and subjects with attention-deficit disorder with hyperactivity.

  2. Helping Children and Youth with Attention-Deficit/Hyperactivity Disorder: Systems of Care

    Science.gov (United States)

    ... Health and Human Services. Children and Adults With Attention-Deficit/ Hyperactivity Disorder www.chadd.org Tel: 301.306.7070 Federation ... information, contact: 4 Helping Children and Youth With Attention-Deficit/Hyperactivity Disorder: Systems of Care Attention -Deficit /Hyperactivity Disorder Helping ...

  3. A Longitudinal Twin Study on the Association between Inattentive and Hyperactive-Impulsive ADHD Symptoms

    Science.gov (United States)

    Greven, Corina U.; Asherson, Philip; Rijsdijk, Fruhling V.; Plomin, Robert

    2011-01-01

    DSM-IV distinguishes two symptom domains of attention deficit hyperactivity disorder (ADHD): inattentiveness and hyperactivity-impulsivity. The present study examines the aetiologies and developmental relations underlying the associations between inattentiveness and hyperactivity-impulsivity over time, based on a representative population sample…

  4. Teacher Response to the Methylphenidate (Ritalin) versus Placebo Status of Hyperactive Boys in the Classroom.

    Science.gov (United States)

    Whalen, Carol K.; And Others

    1981-01-01

    Teacher behaviors toward hyperactive boys on methylphenidate (ritalin), toward hyperactive boys on placebo, and toward normal comparison peers were compared. Teachers were more intense and controlling toward hyperactive boys on placebo, but no differences emerged between comparison and medicated groups. Need for broader monitoring of treatment…

  5. Hyperactivity and motoric activity in ADHD: Characterization, assessment, and intervention

    Directory of Open Access Journals (Sweden)

    Caterina eGawrilow

    2014-11-01

    Full Text Available The aim of the present literature review is threefold. (1 We will review theories, models, and studies on symptomatic hyperactivity and motoric activity in ADHD. (2 Another focus will be on assessment methods that have been proven to be effective in the detection of hyperactivity and motoric activity in children, adolescents, and adults with and without ADHD and emerging areas of research in the field of ADHD. We will compare subjective methods (i.e., rating scales and objective methods (i.e., accelerometers. (3 Finally, physical activity intervention studies aiming at a modification of activity and overactive behavior will be summarized that seem to be promising candidates for alleviating hyperactivity symptoms in children, adolescents, and adults with ADHD.

  6. Quality of life of children with attention deficit hyperactivity disorder.

    Science.gov (United States)

    Klassen, Anne F

    2005-02-01

    To review the results of studies of quality of life in children with attention deficit hyperactivity disorder, three databases were searched and quality of life findings were reviewed. Comparisons were made with population norms for four studies that used the 50-item parent-reported Child Health Questionnaire (CHQ-PF50). Effect sizes were computed to estimate the clinical importance of differences in quality of life. In total, ten publications were identified representing 1382 children with attention deficit hyperactivity disorder. Five different quality of life measures were used and compared with norms for the CHQ-PF50. Children with attention deficit hyperactivity disorder had more problems in all psychosocial domains and family activities. Effect sizes for aspects of physical health domains were small in size. Pooled effect sizes for the CHQ-PF50 psychosocial domains and family activities were as follows: mental health = -0.55; self-esteem = -0.75; parental impact - time = -0.85; role emotional/behavioral = -1.22; behavior = -1.44; parental impact - emotions = -1.45 and family activities = -1.67. Children with attention deficit hyperactivity disorder have a poorer quality of life than children in the general population. Quality of life is an important outcome that is starting to receive attention in studies of children with attention deficit hyperactivity disorder. The use of tools such as the CHQ-PF50 shows how additional and useful information can be obtained that is relevant to a child with attention deficit hyperactivity disorder and their family.

  7. Diacylglycerol kinase β knockout mice exhibit lithium-sensitive behavioral abnormalities.

    Directory of Open Access Journals (Sweden)

    Kenichi Kakefuda

    Full Text Available BACKGROUND: Diacylglycerol kinase (DGK is an enzyme that phosphorylates diacylglycerol (DG to produce phosphatidic acid (PA. DGKβ is widely distributed in the central nervous system, such as the olfactory bulb, cerebral cortex, striatum, and hippocampus. Recent studies reported that the splice variant at the COOH-terminal of DGKβ was related to bipolar disorder, but its detailed mechanism is still unknown. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we performed behavioral tests using DGKβ knockout (KO mice to investigate the effects of DGKβ deficits on psychomotor behavior. DGKβ KO mice exhibited some behavioral abnormalities, such as hyperactivity, reduced anxiety, and reduced depression. Additionally, hyperactivity and reduced anxiety were attenuated by the administration of the mood stabilizer, lithium, but not haloperidol, diazepam, or imipramine. Moreover, DGKβ KO mice showed impairment in Akt-glycogen synthesis kinase (GSK 3β signaling and cortical spine formation. CONCLUSIONS/SIGNIFICANCE: These findings suggest that DGKβ KO mice exhibit lithium-sensitive behavioral abnormalities that are, at least in part, due to the impairment of Akt-GSK3β signaling and cortical spine formation.

  8. Living with a child with attention deficit hyperactivity disorder

    DEFF Research Database (Denmark)

    Laugesen, Britt; Lauritsen, Marlene Briciet; Jørgensen, Rikke

    2016-01-01

    AIM: This systematic review is aimed to identify and synthesize the best available evidence on parenting experiences of living with a child with attention-deficit hyperactivity disorder, including their experiences of healthcare and other services. METHODS: A meta-synthesis was conducted following...... multiple challenges, it is not all bad. CONCLUSION: The findings illustrate the complexity of parental experiences that are influenced by guilt, hope, blame, stigmatization, exhaustion, reconciliation, and professional collaboration. The findings address the impact that attention-deficit hyperactivity...... disorder has on everyday family life, and how parents seem to adapt to their life situation in the process of accepting their child's disorder....

  9. Atypical within- and between-hemisphere motor network functional connections in children with developmental coordination disorder and attention-deficit/hyperactivity disorder

    OpenAIRE

    2016-01-01

    Developmental coordination disorder (DCD) and attention-deficit hyperactivity disorder (ADHD) are highly comorbid neurodevelopmental disorders; however, the neural mechanisms of this comorbidity are poorly understood. Previous research has demonstrated that children with DCD and ADHD have altered brain region communication, particularly within the motor network. The structure and function of the motor network in a typically developing brain exhibits hemispheric dominance. It is plausible that...

  10. The Speed of Visual Attention and Motor-Response Decisions in Adult Attention-Deficit/Hyperactivity Disorder

    DEFF Research Database (Denmark)

    Cross-Villasana, Fernando; Finke, Kathrin; Hennig-Fast, Kristina

    2015-01-01

    Abstract Background: Adults with Attention Deficit/Hyperactivity Disorder (ADHD) exhibit slowed reaction times (RTs) in various attention tasks. The exact origins of this slowing, however, have not been yet established. Potential candidates are early sensory processes mediating the deployment......-related potentials (ERP) during the performance of a visual-search task to differentiate potential sources of slowing at separable levels of processing: the posterior contralateral negativity (PCN) was used to index focalattentional selection times, while the lateralized readiness potentials synchronized to stimulus...

  11. Liu Hong: no trivial on exhibitions

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    To Work for Tomorrow Liu Hong, General Manager of TUTTI Exhibition Service (Xiamen) Co., Ltd, has set up TUTTI Exhibition Service (Xiamen) Co., Ltd in 2001, when exhibition industry firstly appear in Xiamen. Furthermore, the company has developed rapidly in recent years. As Liu Hong regards, exhibition industry, as well as advertisement industry, is an industry filled with challenges and followed

  12. Hyperactivity in Attention-Deficit/Hyperactivity Disorder (ADHD): Impairing Deficit or Compensatory Behavior?

    Science.gov (United States)

    Sarver, Dustin E; Rapport, Mark D; Kofler, Michael J; Raiker, Joseph S; Friedman, Lauren M

    2015-10-01

    Excess gross motor activity (hyperactivity) is considered a core diagnostic feature of childhood ADHD that impedes learning. This view has been challenged, however, by recent models that conceptualize excess motor activity as a compensatory mechanism that facilitates neurocognitive functioning in children with ADHD. The current study investigated competing model predictions regarding activity level's relation with working memory (WM) performance and attention in boys aged 8-12 years (M = 9.64, SD = 1.26) with ADHD (n = 29) and typically developing children (TD; n = 23). Children's phonological WM and attentive behavior were objectively assessed during four counterbalanced WM tasks administered across four separate sessions. These data were then sequenced hierarchically based on behavioral observations of each child's gross motor activity during each task. Analysis of the relations among intra-individual changes in observed activity level, attention, and performance revealed that higher rates of activity level predicted significantly better, but not normalized WM performance for children with ADHD. Conversely, higher rates of activity level predicted somewhat lower WM performance for TD children. Variations in movement did not predict changes in attention for either group. At the individual level, children with ADHD and TD children were more likely to be classified as reliably Improved and Deteriorated, respectively, when comparing their WM performance at their highest versus lowest observed activity level. These findings appear most consistent with models ascribing a functional role to hyperactivity in ADHD, with implications for selecting behavioral treatment targets to avoid overcorrecting gross motor activity during academic tasks that rely on phonological WM.

  13. Response acquisition with delayed reinforcement in a rodent model of attention-deficit/hyperactivity disorder (ADHD).

    Science.gov (United States)

    Hand, Dennis J; Fox, Andrew T; Reilly, Mark P

    2006-12-15

    The spontaneously hypertensive rat (SHR) has been shown to exhibit behavioral characteristics analogous to those exhibited by humans diagnosed with attention-deficit/hyperactivity disorder (ADHD). The present study was conducted to further evaluate the validity of the SHR model of ADHD by characterizing learning of a novel response under conditions of delayed reinforcement. Seven experimentally naïve SHRs and a control group of seven normotensive Wistar-Kyoto (WKY) rats were exposed to a contingency where one lever press initiated pellet delivery after a 15-s, resetting delay. Rats in both groups acquired lever pressing, and the pattern of acquisition was well described with a three-parameter, sigmoidal equation. Response acquisition was retarded in the SHRs; they took longer to acquire the behavior, exhibited lower response rates and earned fewer reinforcers over the course of the experiment. When reinforcer delivery was made immediate in a subsequent condition, the SHRs exhibited higher response rates than the WKY, suggesting that the lower rates of responding seen in the SHRs were due to the reinforcer delay. The results replicate previous research on response acquisition with delayed reinforcement and provide further validation of the SHR strain as a model of ADHD. Like humans diagnosed with ADHD, the SHRs appear to be hypersensitive to delayed consequences, which in the present context, interfered with learning a novel behavior.

  14. Collicular dysfunction in attention deficit hyperactivity disorder.

    Science.gov (United States)

    Overton, Paul G

    2008-01-01

    Attention deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder characterised by (inter alia) an increase in distractibility. The current front-line pharmacotherapies for the treatment of ADHD, namely the psychostimulants methylphenidate and amphetamines, have clear abuse potential, hence there is a strong need to develop new drug treatments for this disorder. Central to this process is the identification of the pathophysiological changes which underlie ADHD. Given the heterogeneity of the disorder, multiple loci are probably involved, providing multiple potential therapeutic targets. Here, we hypothesise (Hypothesis 1) that one such locus is the superior colliculus (SC), a sensory structure intimately linked with distractibility and the production of eye and head movements. It is proposed that in ADHD, the colliculus is hyper-responsive, leading to the core symptom of increased distractibility. Hypothesis 1 is supported by: 1. ADHD patients show increased distractibility in tasks which are sensitive to collicular function; 2. ADHD patients have a general problem inhibiting saccades, the generation of which involves the SC; 3. Saccadic deficits in ADHD include defects in the production of saccadic types (anti-saccades and express saccades) which are particularly associated with the colliculus; 4. Covert shifts in attention (which also have been argued to involve the SC) are also impaired in ADHD; 5. Reading disorders are frequently co-morbid with ADHD; dyslexia (which is associated with eye movement problems) is linked to a specific visual perceptual deficit in the M pathway, a major recipient of which is the colliculus. Whether or not the SC is indeed hyper-responsive in ADHD as Hypothesis 1 suggests, the SC may well represent an important therapeutic target for drugs. In fact current psychostimulant therapies, which reduce distractibility, may already work at that level (Hypothesis 2), a contention which is supported by: 1. The

  15. Disentangling deficits in adults with attention-deficit/hyperactivity disorder.

    NARCIS (Netherlands)

    Bekker, E.M.; Overtoom, C.C.; Kooij, J.J.; Buitelaar, J.K.; Verbaten, M.N.; Kenemans, J.L.

    2005-01-01

    CONTEXT: A lack of inhibitory control has been suggested to be the core deficit in attention-deficit/hyperactivity disorder (ADHD), especially in adults. This means that a primary deficit in inhibition mediates a cascade of secondary deficits in other executive functions, such as attention. Impaired

  16. School Experiences of Adolescents with Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Wiener, Judith; Daniels, Lesley

    2016-01-01

    This article reports on a qualitative study of the school experiences of adolescents with attention-deficit/hyperactivity disorder (ADHD) in the context of quantitative research on teacher attitudes and practices, adolescent self-appraisals, and social and family relationships. Twelve adolescents with ADHD participated in in-depth, semistructured…

  17. Infant Crying and Risk of Hyperactivity and Learning Disorders

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2002-06-01

    Full Text Available Infants with persistent crying (PC in the first 6 months (mean age 3.8 months were reassessed at 8 to 10 years of age and compared with 64 classroom controls for hyperactivity, conduct problems and academic difficulties in a prospective study at the University of Hertfordshire, UK.

  18. Attention-deficit/hyperactivity disorder and social dysfunctioning

    NARCIS (Netherlands)

    Nijmeijer, Judith S.; Minderaa, Ruud B.; Buitelaar, Jan K.; Mulligan, Aisling; Hartman, Catharina A.; Hoekstra, Pieter J.

    2008-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is associated with functional impairments in different areas of daily life. One such area is social functioning. The purpose of this paper is to critically review research on social dysfunctioning in children with ADHD. Children with ADHD often have co

  19. Parents Psychopathology of Children with Attention Deficit Hyperactivity Disorder

    Science.gov (United States)

    Margari, Francesco; Craig, Francesco; Petruzzelli, Maria Giuseppina; Lamanna, Annalinda; Matera, Emilia; Margari, Lucia

    2013-01-01

    Attention Deficit Hyperactivity Disorder (ADHD) is a disorder with extremely complex etiology, not yet well defined but certainly multi-factorial. This study investigated the possible etiopathogenetic role of ADHD symptoms and psychopathology disorders in parents of children with ADHD. We present a case-control study of parents of 50 children…

  20. Test Anxiety and College Students with Attention Deficit Hyperactivity Disorder

    Science.gov (United States)

    Nelson, Jason M.; Lindstrom, Will; Foels, Patricia A.

    2014-01-01

    Test anxiety was examined in college students with and without attention deficit hyperactivity disorder (ADHD). Results indicated that, relative to college students without ADHD, college students with ADHD reported higher total test anxiety as well as specific aspects of test anxiety, including worry (i.e., cognitive aspects of test anxiety) and…

  1. DSM-5 Further Inflates Attention Deficit Hyperactivity Disorder

    NARCIS (Netherlands)

    Batstra, Laura; Frances, Allen

    2012-01-01

    Since the publication of DSM-IV in 1994, attention deficit hyperactivity disorder (ADHD) prevalence and medication use unexpectedly increased significantly. In this article, we explore the DSM-5 proposals for ADHD that are likely to further increase its prevalence. We also address the possible harmf

  2. Hippocampus and amygdala morphology in attention-deficit/hyperactivity disorder

    DEFF Research Database (Denmark)

    Plessen, Kerstin J; Bansal, Ravi; Zhu, Hongtu

    2006-01-01

    CONTEXT: Limbic structures are implicated in the genesis of attention-deficit/hyperactivity disorder (ADHD) by the presence of mood and cognitive disturbances in affected individuals and by elevated rates of mood disorders in family members of probands with ADHD. OBJECTIVE: To study the morphology...

  3. School-Based Treatment of Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Schultz, Brandon K.; Storer, Jennifer; Watabe, Yuko; Sadler, Joanna; Evans, Steven W.

    2011-01-01

    The authors review the research literature regarding school-based treatment of attention-deficit/hyperactivity disorder (ADHD). Students with ADHD often do not receive access to special services, even though the impairments associated with the disorder often compromise learning and cause concerns for classroom teachers, school administrators, and…

  4. Professor Perceptions of College Students with Attention Deficit Hyperactivity Disorder

    Science.gov (United States)

    Vance, Teresa Ann; Weyandt, Lisa

    2008-01-01

    Objective: From April to June 2005, the authors investigated professor perceptions of college students with attention deficit hyperactivity disorder (ADHD). Participants: 253 participants completed the ADHD Beliefs Survey-Revised, a 40-question survey measuring professor perceptions of ADHD. Methods: Analysis of variance measured false and…

  5. Playfulness in Children with Attention Deficit Hyperactivity Disorder.

    Science.gov (United States)

    Leipold, Elizabeth E.; Bundy, Anita C.

    2000-01-01

    Scores on the Test of Playfulness for 25 children with Attention Deficit Hyperactivity Disorder (ADHD) were significantly lower than those of 25 children without, especially on internal control, intrinsic motivation, and framing. Three items (mischief, teasing/joking, clowning) yielded unexpectedly higher scores for ADHD children. (SK)

  6. Attention Deficit Hyperactivity Disorder Symptoms Mediate Early-Onset Smoking

    NARCIS (Netherlands)

    Huizink, A.C.; Lier, P.A.C. van; Crijnen, A.A.M.

    2009-01-01

    Background/Aims: Symptoms of attention deficit hyperactivity disorder (ADHD) have often been associated with early-onset smoking. We hypothesize that reductions in ADHD symptoms due to an intervention have a mediating effect on early-onset smoking. Methods: In a universal, school-based, randomized c

  7. Attention deficit hyperactivity disorder symptoms mediate early-onset smoking

    NARCIS (Netherlands)

    Huizink, A.C.; Van Lier, P.A.C.; Crijnen, A.A.M.

    2009-01-01

    Background/Aims: Symptoms of attention deficit hyperactivity disorder (ADHD) have often been associated with early-onset smoking. We hypothesize that reductions in ADHD symptoms due to an intervention have a mediating effect on early-onset smoking. Methods: In a universal, school-based, randomized c

  8. Attention deficit hyperactivity disorder symptoms mediate early-onset smoking

    NARCIS (Netherlands)

    A.C. Huizink (Anja); P.A.C. van Lier (Pol); A.A.M. Crijnen (Alfons)

    2008-01-01

    textabstractBackground/Aims: Symptoms of attention deficit hyperactivity disorder (ADHD) have often been associated with early-onset smoking. We hypothesize that reductions in ADHD symptoms due to an intervention have a mediating effect on early-onset smoking. Methods: In a universal, school-based,

  9. Assessing Stimulant Treatment of Hyperactivity by Bristol Social Adjustment Guides.

    Science.gov (United States)

    Broad, James

    Eighteen medically diagnosed hyperactive boys, matched individually for age, sex, teacher defined ability, and school class, took part in a double blind, placebo controlled trial of the effects of Ritalin on social behavior as measured by global rating scales. Behavior ratings by parents and teachers improved significantly when Ss were given…

  10. The Role of Drugs, Diet, and Food Additives in Hyperactivity.

    Science.gov (United States)

    Harshbarger, Mary E.

    A variety of causes have been suggested for hyperactivity: anoxia and other adverse birth conditions, genetic factors, delayed maturation, maternal smoking and drinking during pregnancy, interaction of temperament and environment, lead poisoning, radiation stress, allergy and food additives, and deprivation of required stimulation. Treatments…

  11. Attention Deficits, Attention-Deficit Hyperactivity Disorder, and Intellectual Disabilities

    Science.gov (United States)

    Deutsch, Curtis K.; Dube, William V.; McIlvane, William J.

    2008-01-01

    Attention-Deficit Hyperactivity Disorder (ADHD) and its earlier nosologic classifications have been extensively investigated since the 1960s, with PubMed listings alone exceeding 13,000 entries. Strides have been made in the diagnosis and treatment of ADHD in individuals with intellectual function in the normal range, as described in companion…

  12. Language Impairment in the Attention-Deficit/Hyperactivity Disorder Context

    Science.gov (United States)

    Redmond, Sean M.

    2016-01-01

    Purpose: Attention-deficit/hyperactivity disorder (ADHD) is a ubiquitous designation that affects the identification, assessment, treatment, and study of pediatric language impairments (LIs). Method: Current literature is reviewed in 4 areas: (a) the capacity of psycholinguistic, neuropsychological, and socioemotional behavioral indices to…

  13. Brain differences between persistent and remitted attention deficit hyperactivity disorder.

    Science.gov (United States)

    Mattfeld, Aaron T; Gabrieli, John D E; Biederman, Joseph; Spencer, Thomas; Brown, Ariel; Kotte, Amelia; Kagan, Elana; Whitfield-Gabrieli, Susan

    2014-09-01

    Previous resting state studies examining the brain basis of attention deficit hyperactivity disorder have not distinguished between patients who persist versus those who remit from the diagnosis as adults. To characterize the neurobiological differences and similarities of persistence and remittance, we performed resting state functional magnetic resonance imaging in individuals who had been longitudinally and uniformly characterized as having or not having attention deficit hyperactivity disorder in childhood and again in adulthood (16 years after baseline assessment). Intrinsic functional brain organization was measured in patients who had a persistent diagnosis in childhood and adulthood (n = 13), in patients who met diagnosis in childhood but not in adulthood (n = 22), and in control participants who never had attention deficit hyperactivity disorder (n = 17). A positive functional correlation between posterior cingulate and medial prefrontal cortices, major components of the default-mode network, was reduced only in patients whose diagnosis persisted into adulthood. A negative functional correlation between medial and dorsolateral prefrontal cortices was reduced in both persistent and remitted patients. The neurobiological dissociation between the persistence and remittance of attention deficit hyperactivity disorder may provide a framework for the relation between the clinical diagnosis, which indicates the need for treatment, and additional deficits that are common, such as executive dysfunctions.

  14. Very Low Birth Weight and Attention Deficit/Hyperactivity Disorder

    NARCIS (Netherlands)

    van der Meere, Jaap; Börger, Norbert A.; Potgieter, Stephanus Theron; Pirila, Silja; De Cock, Paul

    2009-01-01

    It is well recognized that reaction time performance of term-born children with a normal birth weight (NBW > 2500 g) who fulfill the DSM-IV criteria for attention deficit/hyperactivity disorder (ADHD) in the primary school age is sensitive for the presentation rate of stimuli. They have been found t

  15. Impulse Control or Selective Attention: Remedial Programs for Hyperactivity.

    Science.gov (United States)

    Brown, Ronald T.; Conrad, Kendon J.

    1982-01-01

    Compared various cognitive treatment approaches for ameliorating the difficulties of hyperactive children on tasks requiring sustained vigilance and accuracy. Differential training techniques comparing training in attention to inhibitory control indicated that a combination of attentional and inhibitory control strategies was most efficacious in…

  16. Executive Function in Attention Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Sinha, Preeti; Sagar, Rajesh; Mehta, Manju

    2008-01-01

    Aim: To assess executive functions in medication naive children with attention deficit/hyperactivity (ADHD). Method: Group matched (age and gender) children with ADHD (N=30) and healthy children (N=30) in the age range of 6-14 years were compared on measures of executive functions (response inhibition, working memory, cognitive flexibility,…

  17. Nurse evaluation of hyperactivity in anorexia nervosa : A comparative study

    NARCIS (Netherlands)

    van Elburg, Annemarie A.; Hoek, Hans W.; Kas, Martien J.H.; van Engeland, Herman

    2007-01-01

    Up to 80% of patients with anorexia nervosa (AN) manifest elevated levels of physical activity or hyperactivity. A variety of methods have been used to evaluate activity levels, mostly questionnaires but also expensive and invasive methods such as actometry or other measurements of energy expenditur

  18. Adolescents with Attention Deficit Hyperactivity Disorder Benefit from Massage Therapy.

    Science.gov (United States)

    Field, Tiffany M.; Quintino, Olga; Hernandez-Reif, Maria; Koslovsky, Gabrielle

    1998-01-01

    Twenty-eight adolescents with attention-deficit hyperactivity disorder were provided either massage therapy or relaxation therapy for 10 consecutive school days. The massage therapy group, but not the relaxation therapy group, self-rated as happier, and observers rated them as fidgeting less following the sessions. Teachers reported more time on…

  19. Hyperactive galaxy NGC 7673 [heic0205

    Science.gov (United States)

    2002-03-01

    Hyperactive galaxy NGC 7673 hi-res Size hi-res: 116 kb Credits: European Space Agency & Nicole Homeier (European Southern Observatory and University of Wisconsin-Madison) Hyperactive galaxy NGC 7673 The disturbed spiral galaxy NGC 7673 is ablaze with the light from millions of new stars. Each of its infant giant blue star clusters shines 100 times as brightly in the ultraviolet as similar immense star clusters in our own Galaxy. Scientists studying this object have two pressing questions: "What has triggered this enormous burst of star formation and how will this galaxy evolve in the future?" Telltale patches of blue light are signs of the formation of millions of new stars in the tangled spiral galaxy NGC 7673. Each of the bluish areas in this image consists of immense star clusters containing thousands of young stars. These clusters lie on the spiral arms of NGC 7673 and so emphasise its somewhat ragged look. This image, taken from Earth orbit by the ESA/NASA Hubble Space Telescope in 1996 and 1997, also shows two other galaxies seen in the background of the image, to the left and right of NGC 7673. These galaxies are further away and so appear redder, due to their higher redshift, an effect caused by the expansion of the Universe. The youngest blue stars in NGC 7673 are blazing with intense ultraviolet radiation. Each star cluster radiates 100 times more ultraviolet light than the famous Tarantula Nebula (30 Doradus), the largest star-forming region known in the local group of galaxies. Telltale patches of blue light are signs of the formation of millions of new stars in the tangled spiral galaxy NGC 7673. Each of the bluish areas in this image consists of immense star clusters containing thousands of young stars. These clusters lie on the spiral arms of NGC 7673 and so emphasise its somewhat ragged look. This image, taken from Earth orbit by the ESA/NASA Hubble Space Telescope in 1996 and 1997, also shows two other galaxies seen in the background of the image

  20. In vivo occupancy of dopamine D3 receptors by antagonists produces neurochemical and behavioral effects of potential relevance to attention-deficit-hyperactivity disorder.

    Science.gov (United States)

    Barth, V; Need, A B; Tzavara, E T; Giros, B; Overshiner, C; Gleason, S D; Wade, M; Johansson, A M; Perry, K; Nomikos, G G; Witkin, J M

    2013-02-01

    Dopamine D(3) receptors have eluded definitive linkage to neurologic and psychiatric disorders since their cloning over 20 years ago. We report a new method that does not employ a radiolabel for simultaneously defining in vivo receptor occupancy of D(3) and D(2) receptors in rat brain after systemic dosing using the tracer epidepride (N-[[(2S)-1-ethylpyrrolidin-2-yl]methyl]-5-iodo-2,3-dimethoxybenzamide). Decreases in epidepride binding in lobule 9 of cerebellum (rich in D(3) receptors) were compared with nonspecific binding in the lateral cerebellum. The in vivo occupancy of the dopamine D(3) receptors was dose dependently increased by SB-277011A (trans-N-[4-[2-(6-cyano-1,2,3,4-tetrahydroisoquinolin-2-yl)ethyl]cyclohexyl]-4-quinolinecarboxamide) and U99194 (2,3-dihydro-5,6-dimethoxy- N,N-dipropyl-1H-inden-2-amine). Both antagonists increased extracellular levels of acetylcholine (ACh) in the medial prefrontal cortex of rats and modified brain-tissue levels of ACh and choline. Consistent with these findings, the D(3) receptor antagonists enhanced the acquisition of learning of rats either alone or in the presence of the norepinephrine uptake blocker reboxetine as with the attention-deficit-hyperactivity disorder (ADHD) drug methylphenidate. Like reboxetine, the D(3) receptor antagonists also prevented deficits induced by scopolamine in object recognition memory of rats. Mice in which the dopamine transporter (DAT) has been deleted exhibit hyperactivity that is normalized by compounds that are effective in the treatment of ADHD. Both D(3) receptor antagonists decreased the hyperactivity of DAT(-/-) mice without affecting the activity of wild type controls. The present findings indicate that dopamine D(3) receptor antagonists engender cognition-enhancing and hyperactivity-dampening effects. Thus, D(3) receptor blockade could be considered as a novel treatment approach for cognitive deficits and hyperactivity syndromes, including those observed in ADHD.

  1. White matter microstructure and developmental improvement of hyperactive/impulsive symptoms in Attention-Deficit/Hyperactivity Disorder

    NARCIS (Netherlands)

    Francx, W.C.L.; Zwiers, M.P.; Mennes, M.J.J.; Oosterlaan, J.; Heslenfeld, D.J.; Hoekstra, P.J.; Hartman, C.A.; Franke, B.; Faraone, S.V; O'Dwyer, L.G.; Buitelaar, J.

    2015-01-01

    Background A developmental improvement of symptoms in Attention-Deficit/Hyperactivity Disorder (ADHD) is frequently reported, but the underlying neurobiological substrate has not been identified. The aim of this study was to determine whether white matter microstructure is related to developmental i

  2. White matter microstructure and developmental improvement of hyperactive/impulsive symptoms in attention-deficit/hyperactivity disorder

    NARCIS (Netherlands)

    Francx, Winke; Zwiers, Marcel P.; Mennes, Maarten; Oosterlaan, Jaap; Heslenfeld, Dirk; Hoekstra, Pieter J.; Hartman, Catharina A.; Franke, Barbara; Faraone, Stephen V.; O'Dwyer, Laurence; Buitelaar, Jan K.

    2015-01-01

    Background: A developmental improvement of symptoms in attention-deficit/hyperactivity disorder (ADHD) is frequently reported, but the underlying neurobiological substrate has not been identified. The aim of this study was to determine whether white matter microstructure is related to developmental

  3. VNU Exhibitions Asia: Two factors are crucial

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Reporter: How to appraises the Chinese exhibition industry market? Jime Essink :The Chinese exhibition market will experience a fast growth in the coming years. This will mainly be the result of an increase of international visitors who

  4. Report on Exhibition Industry in Shanghai

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    @@ 1. General Characteristics of Shanghai Exhibitions As the leader of economic development in the Yangtze River Delta,Shanghai has basically formed a certain scale and strength in the aspects of urban transportation, exhibition venues, supporting facilities, service levels, etc.

  5. Development Report on Exhibition Industry in Guangzhou

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    @@ Ⅰ. Generat Features of Guangzhou Exhibitions (Ⅰ) Quantity of Exhibitions and Industry Features. Overall, after suf-fering from global financial crisis in 2008 as well as the interference of Beijing Olympic Games and other major events, the exhibition industry in Guangzhou has still not encountered an easy condition in 2009.

  6. Beijing Lack of "Carrier"Exhibition Center

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    An Interview towards Mr. Chu Xiangyin, Vice Chairman of Beijing Subcouncil, CCPIT Reporter: Would you please tell us development of exhibition industry in Beijing? Chu Xiangyin: Beijing Statistical Bureau and us have been designing and analyzing statistical system for exhibition industry from 2003. As the largest exhibition center in Beijing,

  7. Affordances and distributed cognition in museum exhibitions

    DEFF Research Database (Denmark)

    Achiam, Marianne; May, Michael; Marandino, Martha

    2014-01-01

    consistent framework. Here, we invoke the notions of affordance and distributed cognition to explain in a coherent way how visitors interact with exhibits and exhibit spaces and make meaning from those interactions, and we exemplify our points using observations of twelve visitors to exhibits at a natural...... history museum. We show how differences in exhibit characteristics give rise to differences in the interpretive strategies used by visitors in their meaning-making process, and conclude by discussing how the notions of affordance and distributed cognition can be used in an exhibit design perspective....

  8. Characterizing operant hyperactivity in the Spontaneously Hypertensive Rat

    Directory of Open Access Journals (Sweden)

    Hill Jade C

    2012-01-01

    Full Text Available Abstract Background Operant hyperactivity, the emission of reinforced responses at an inordinately high rate, has been reported in children with ADHD and in the Spontaneously Hypertensive Rat (SHR, the most widely studied animal model of ADHD. The SHR emits behavior at hyperactive levels, relative to a normoactive strain, only when such behavior is seldom reinforced. Because of its dependence on rate of reinforcement, operant hyperactivity appears to be driven primarily by incentive motivation, not motoric capacity. This claim was evaluated in the present study using a novel strategy, based on the organization of behavior in bouts of reinforced responses separated by pauses. Method Male SHR, Wistar-Kyoto (WKY and Wistar rats (WIS were exposed each to a multiple variable-interval schedule of sucrose reinforcement (12, 24, 48, 96, and 192 s between post-natal days (PND 48 and 93. Responding in each schedule was examined in two epochs, PND 58-62 and 89-93. Parameters of response-reinforcement functions (Herrnstein's hyperbola and bout-organized behavior were estimated in each epoch. Results SHR emitted higher response rates than WKY and WIS, but only when rate of reinforcement was low (fewer than 2 reinforcers per minute, and particularly in the second epoch. Estimates of Herrnstein's hyperbola parameters suggested the primacy of motivational over motoric factors driving the response-rate differential. Across epochs and schedules, a more detailed analysis of response bouts by SHR revealed that these were shorter than those by WKY, but more frequent than those by WKY and WIS. Differences in bout length subsided between epochs, but differences in bout-initiation rate were exacerbated. These results were interpreted in light of robust evidence linking changes in bout-organization parameters and experimental manipulations of motivation and response-reinforcement contingency. Conclusions Operant hyperactivity in SHR was confirmed. Although incentive

  9. Identification of a Glycogen Synthase Kinase-3[beta] Inhibitor that Attenuates Hyperactivity in CLOCK Mutant Mice

    Energy Technology Data Exchange (ETDEWEB)

    Kozikowski, Alan P.; Gunosewoyo, Hendra; Guo, Songpo; Gaisina, Irina N.; Walter, Richard L.; Ketcherside, Ariel; McClung, Colleen A.; Mesecar, Andrew D.; Caldarone, Barbara (Psychogenics); (Purdue); (UIC); (UTSMC)

    2012-05-02

    Bipolar disorder is characterized by a cycle of mania and depression, which affects approximately 5 million people in the United States. Current treatment regimes include the so-called 'mood-stabilizing drugs', such as lithium and valproate that are relatively dated drugs with various known side effects. Glycogen synthase kinase-3{beta} (GSK-3{beta}) plays a central role in regulating circadian rhythms, and lithium is known to be a direct inhibitor of GSK-3{beta}. We designed a series of second generation benzofuran-3-yl-(indol-3-yl)maleimides containing a piperidine ring that possess IC{sub 50} values in the range of 4 to 680 nM against human GSK-3{beta}. One of these compounds exhibits reasonable kinase selectivity and promising preliminary absorption, distribution, metabolism, and excretion (ADME) data. The administration of this compound at doses of 10 to 25 mg kg{sup -1} resulted in the attenuation of hyperactivity in amphetamine/chlordiazepoxide-induced manic-like mice together with enhancement of prepulse inhibition, similar to the effects found for valproate (400 mg kg{sup -1}) and the antipsychotic haloperidol (1 mg kg{sup -1}). We also tested this compound in mice carrying a mutation in the central transcriptional activator of molecular rhythms, the CLOCK gene, and found that the same compound attenuates locomotor hyperactivity in response to novelty. This study further demonstrates the use of inhibitors of GSK-3{beta} in the treatment of manic episodes of bipolar/mood disorders, thus further validating GSK-3{beta} as a relevant therapeutic target in the identification of new therapies for bipolar patients.

  10. Attention deficit hyperactivity disorder and intellectual giftedness: a study of symptom frequency and minor physical anomalies

    Directory of Open Access Journals (Sweden)

    Daniel Minahim

    2015-12-01

    Full Text Available Objective: To evaluate the presence of symptoms of attention deficit and hyperactivity disorder (ADHD in intellectually gifted adults and children. Methods: Two cross-sectional studies were performed in children and adults whose intelligence quotient (IQ had been previously evaluated using Raven’s Progressive Matrices (RPM test. Seventy-seven adults displaying IQ scores above the 98th percentile were assessed using the Adult Self-Report Scale (ASRS-18 for signs of ADHD and a modified Waldrop scale for minor physical anomalies (MPAs. Thirty-nine children (grades 1-5 exhibiting IQ scores above the 99th percentile, as well as an equally matched control group, were assessed for ADHD by teachers using the Swanson, Nolan and Pelham IV Rating Scale (SNAP-IV as used in the NIMH Collaborative Multisite Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder (MTA-SNAP-IV. Results: In gifted adults, the frequency of ADHD-positive cases was 37.8%, and the total MPA score was significantly associated with ADHD (p < 0.001. In children, the ADHD-positive case frequency was 15.38% in the gifted group and 7.69% in the control group (odds ratio [OR] = 2.18, p = 0.288. Conclusions: The high frequency of ADHD symptoms observed, both in gifted adults and in gifted (and non-gifted children, further supports the validity of this diagnosis in this population. Furthermore, the significant association between MPAs and ADHD suggests that a neurodevelopmental condition underlies these symptoms.

  11. Quaternary naltrexone reverses radiogenic and morphine-induced locomotor hyperactivity

    Energy Technology Data Exchange (ETDEWEB)

    Mickley, G.A.; Stevens, K.E.; Galbraith, J.A.; White, G.A.; Gibbs, G.L.

    1984-04-01

    The present study attempted to determine the relative role of the peripheral and central nervous system in the production of morphine-induced or radiation-induced locomotor hyperactivity of the mouse. Toward this end, we used a quaternary derivative of an opiate antagonist (naltrexone methobromide), which presumably does not cross the blood-brain barrier. Quaternary naltrexone was used to challenge the stereotypic locomotor response observed in these mice after either an i.p. injection of morphine or exposure to 1500 rads /sup 60/Co. The quaternary derivative of naltrexone reversed the locomotor hyperactivity normally observed in the C57BL/6J mouse after an injection of morphine. It also significantly attenuated radiation-induced locomotion. The data reported here support the hypothesis of endorphin involvement in radiation-induced and radiogenic behaviors. However, these conclusions are contingent upon further research which more fully evaluates naltrexone methobromide's capacity to cross the blood-brain barrier.

  12. Intervention for executive functions in attention deficit and hyperactivity disorder

    Directory of Open Access Journals (Sweden)

    Amanda Menezes

    2015-03-01

    Full Text Available This study aimed to investigate if an executive functions (EF intervention could promote these skills in individuals with attention deficit and hyperactivity disorder (ADHD. Eighteen children and adolescents, 7-13 years old, divided into experimental (EG, N = 8 and control (CG, N = 10 groups, were assessed in the Block Design and Vocabulary subtests of the WISC III and seven tests of EF. Parents answered two scales, measuring EF and inattention and hyperactivity signs. EG children participated in a program to promote EF in twice-weekly group sessions of one hour each. After 8 months of intervention, groups were assessed again. ANCOVA, controlling for age, intelligence quotient and pretest performance, revealed gains in attention/inhibition and auditory working memory measures for the EG. No effect was found for scales or measures of more complex EF. Results are not conclusive, but they illustrate some promising data about EF interventions in children and adolescents with ADHD.

  13. Propranolol for Paroxysmal Sympathetic Hyperactivity with Lateralizing Hyperhidrosis after Stroke

    Directory of Open Access Journals (Sweden)

    Jason W. Siefferman

    2015-01-01

    Full Text Available Brain injury can lead to impaired cortical inhibition of the hypothalamus, resulting in increased sympathetic nervous system activation. Symptoms of paroxysmal sympathetic hyperactivity may include hyperthermia, tachycardia, tachypnea, vasodilation, and hyperhidrosis. We report the case of a 41-year-old man who suffered from a left middle cerebral artery stroke and subsequently developed central fever, contralateral temperature change, and hyperhidrosis. His symptoms abated with low-dose propranolol and then returned upon discontinuation. Restarting propranolol again stopped his symptoms. This represents the first report of propranolol being used for unilateral dysautonomia after stroke. Propranolol is a lipophilic nonselective beta-blocker which easily crosses the blood-brain barrier and may be used to treat paroxysmal sympathetic hyperactivity.

  14. Reducing hyperactivity with a feedback actigraph: initial findings.

    Science.gov (United States)

    Tryon, Warren W; Tryon, Georgiana Shick; Kazlausky, Thomas; Gruen, William; Swanson, James M

    2006-10-01

    Schulman and colleagues demonstrated that classroom activity level can be reduced in hyperactive boys using activity-level feedback and positive reinforcement. This article reports preliminary results using a device that combines modern beeper and actigraphy technology for the purpose of measuring, monitoring, and modifying motor excess in children with confirmed diagnoses of Attention Deficit Hyperactivity Disorder (ADHD). Nine boys ranging in age from 8 to 9 years with the ADHD Combined Type wore prototype BuzzBee feedback actigraphs during school periods and were reinforced for activity-level reductions in the context of a simple pre/post research design. The findings indicated that 7 of the 9 boys reduced their activity level from 20 to 47% of baseline levels while the activity levels of the two remaining boys increased from 2 to 7% of baseline levels. These changes were statistically significant and constitute a large effect.

  15. Drug therapy of attention deficit hyperactivity disorder: Current trends

    Directory of Open Access Journals (Sweden)

    Avinash De Sousa

    2012-01-01

    Full Text Available Attention deficit hyperactivity disorder is a developmental disorder with an age onset prior to 7 years. Children with ADHD have significantly lower ability to focus and sustain attention and also score higher on impulsivity and hyperactivity. Stimulants, such as methylphenidate, have remained the mainstay of ADHD treatment for decades with evidence supporting their use. However, recent years have seen emergence of newer drugs and drug delivery systems, like osmotic release oral systems and transdermal patches, to mention a few. The use of nonstimulant drugs like atomoxetine and various other drugs, such as a-agonists, and a few antidepressants, being used in an off-label manner, have added to the pharmacotherapy of ADHD. This review discusses current trends in drug therapy of ADHD and highlights the promise pharmacogenomics may hold in the future.

  16. Intervention for executive functions in attention deficit and hyperactivity disorder.

    Science.gov (United States)

    Menezes, Amanda; Dias, Natália Martins; Trevisan, Bruna Tonietti; Carreiro, Luiz Renato R; Seabra, Alessandra Gotuzo

    2015-03-01

    This study aimed to investigate if an executive functions (EF) intervention could promote these skills in individuals with attention deficit and hyperactivity disorder (ADHD). Eighteen children and adolescents, 7-13 years old, divided into experimental (EG, N = 8) and control (CG, N = 10) groups, were assessed in the Block Design and Vocabulary subtests of the WISC III and seven tests of EF. Parents answered two scales, measuring EF and inattention and hyperactivity signs. EG children participated in a program to promote EF in twice-weekly group sessions of one hour each. After 8 months of intervention, groups were assessed again. ANCOVA, controlling for age, intelligence quotient and pretest performance, revealed gains in attention/inhibition and auditory working memory measures for the EG. No effect was found for scales or measures of more complex EF. Results are not conclusive, but they illustrate some promising data about EF interventions in children and adolescents with ADHD.

  17. Investigating Design Research Landscapes through Exhibition

    DEFF Research Database (Denmark)

    Jönsson, Li; Hansen, Flemming Tvede; Mäkelä, Maarit;

    2013-01-01

    What characterizes a design research exhibition compared to a traditional design and art exhibition? How do you show the very materialities of the design experiments as a means for communicating knowledge of research and of practice? How do you present, review and utilize such an exhibition......? With those questions in mind, the intention and challenge for the Nordes 2013 Design Research Exhibition was to expand on current notions of staging research enquires in design research conference contexts. Artefacts, installations, performances, and other materialities that relate to the theme...... of the conference - Experiments in Design Research – were displayed as tools to express and communicate different design research enquires. Through this paper we will describe the Nordes exhibition as a specific case that renders questions visible in relation to how to utilize a design research exhibition...

  18. No objectively measured sleep disturbances in children with attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Bergwerff, Catharina E; Luman, Marjolein; Oosterlaan, Jaap

    2016-10-01

    The main goal of this study was to gain more insight into sleep disturbances in children with attention-deficit/hyperactivity disorder, using objective measures of sleep quality and quantity. The evidence for sleep problems in children with attention-deficit/hyperactivity disorder thus far is inconsistent, which might be explained by confounding influences of comorbid internalizing and externalizing problems and low socio-economic status. We therefore investigated the mediating and moderating role of these factors in the association between attention-deficit/hyperactivity disorder and sleep problems. To control for the effects of stimulant medication use, all participants were tested free of medication. Sixty-three children with attention-deficit/hyperactivity disorder and 61 typically developing children, aged 6-13 years, participated. Sleep was monitored for one to three school nights using actigraphy. Parent and teacher questionnaires assessed symptoms of attention-deficit/hyperactivity disorder, internalizing behaviour, oppositional defiant disorder and conduct disorder. Results showed no differences between the attention-deficit/hyperactivity disorder and typically developing group in any sleep parameter. Within the attention-deficit/hyperactivity disorder group, severity of attention-deficit/hyperactivity disorder symptoms was not related to sleep quality or quantity. Moderation analyses in the attention-deficit/hyperactivity disorder group showed an interaction effect between attention-deficit/hyperactivity disorder symptoms and internalizing and externalizing behaviour on total sleep time, time in bed and average sleep bout duration. The results of our study suggest that having attention-deficit/hyperactivity disorder is not a risk factor for sleep problems. Internalizing and externalizing behaviour moderate the association between attention-deficit/hyperactivity disorder and sleep, indicating a complex interplay between psychiatric symptoms and sleep.

  19. Reading and listening comprehension and their relation to inattention and hyperactivity

    OpenAIRE

    Cain, Kate; Bignell, Simon

    2014-01-01

    Background: Children with diagnoses of attention-deficit/hyperactivity disorder (ADHD) frequently have reading problems. To date, it is not clear whether poor reading is associated with both inattention and hyperactivity and also whether poor reading comprehension is the result of poor word reading skills or more general language comprehension weaknesses. Aims: We report two studies to examine how reading and listening comprehension skills are related to inattention and hyperactivity/impulsiv...

  20. Diagnosing and treating attention-deficit/hyperactivity disorder in adults

    OpenAIRE

    Faraone, Stephen V.; Antshel, Kevin M.

    2008-01-01

    Adult attention deficit/hyperactivity disorder (ADHD) is a valid and impairing psychiatric disorder. In this article, we review the diagnosis of ADHD in adults, focusing on symptom presentation differences between pediatric and adult ADHD as well as the importance of assessing functional impairments. Differentiating ADHD from other clinical disorders is often the most difficult part of making an ADHD diagnosis in adults. Psychiatric comorbidities are also described and discussed as potential ...

  1. Attention-deficit/hyperactivity disorder in postsecondary students

    OpenAIRE

    2014-01-01

    Kevin Nugent,1 Wallace Smart2,3 1Kinark Child and Family Services, Trent University and Sir Sanford Fleming College, Peterborough, ON, Canada; 2Department of Psychiatry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada; 3University of Lethbridge Health Centre, Lethbridge, AB, Canada Abstract: A PubMed review was conducted for papers reporting on attention-deficit/ hyperactivity disorder (ADHD) in postsecondary students. The review was performed in order to determ...

  2. Hyperactive Somatostatin Interneurons Contribute to Excitotoxicity in Neurodegenerative Disorders

    Science.gov (United States)

    Liang, Bo; Schroeder, David; Zhang, Zhong-wei; Cox, Gregory A.; Li, Yun; Lin, Da-Ting

    2016-01-01

    Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are overlapping neurodegenerative disorders whose pathogenesis remains largely unknown. Here using TDP-43A315T mice, an ALS and FTD model with profound cortical pathology, we demonstrated that hyperactive somatostatin interneurons disinhibited layer 5 pyramidal neurons (L5-PN) and contributed to their excitotoxicity. Focal ablation of somatostatin interneurons efficiently restored normal excitability of L5-PN and alleviated neurodegeneration, suggesting a novel therapeutic target for ALS and FTD. PMID:26900927

  3. A hyperactive sleeping beauty transposase enhances transgenesis in zebrafish embryos

    Directory of Open Access Journals (Sweden)

    Lardelli Michael

    2010-11-01

    Full Text Available Abstract Background Transposons are useful molecular tools for transgenesis. The 'sleeping beauty' transposon is a synthetic member of the Tc1/mariner transposon family. Davidson et al. (2003 previously described a vector for zebrafish transgenesis consisting of the inverted repeats of 'sleeping beauty' flanking the gene to be transposed. Subsequently, there have been attempts to enhance the transpositional activity of 'sleeping beauty' by increasing the activity of its transposase. Recently, Mates et al. (2009 generated a hyperactive transposase giving a 100-fold increased transposition rate in mouse embryos. Findings The aim of this experiment was to determine whether this novel hyperactive transposase enhances transgenesis in zebrafish embryos. Using our previously characterised mitfa-amyloidβ-GFP transgene, we observed an eight-fold enhancement in transient transgenesis following detection of transgene expression in melanophores by whole mount in-situ hybridisation. However, high rates of defective embryogenesis were also observed. Conclusion The novel hyperactive 'sleeping beauty' transposase enhances the rate of transgenesis in zebrafish embryos.

  4. Giant piezoelectricity on Si for hyperactive MEMS.

    Science.gov (United States)

    Baek, S H; Park, J; Kim, D M; Aksyuk, V A; Das, R R; Bu, S D; Felker, D A; Lettieri, J; Vaithyanathan, V; Bharadwaja, S S N; Bassiri-Gharb, N; Chen, Y B; Sun, H P; Folkman, C M; Jang, H W; Kreft, D J; Streiffer, S K; Ramesh, R; Pan, X Q; Trolier-McKinstry, S; Schlom, D G; Rzchowski, M S; Blick, R H; Eom, C B

    2011-11-18

    Microelectromechanical systems (MEMS) incorporating active piezoelectric layers offer integrated actuation, sensing, and transduction. The broad implementation of such active MEMS has long been constrained by the inability to integrate materials with giant piezoelectric response, such as Pb(Mg(1/3)Nb(2/3))O(3)-PbTiO(3) (PMN-PT). We synthesized high-quality PMN-PT epitaxial thin films on vicinal (001) Si wafers with the use of an epitaxial (001) SrTiO(3) template layer with superior piezoelectric coefficients (e(31,f) = -27 ± 3 coulombs per square meter) and figures of merit for piezoelectric energy-harvesting systems. We have incorporated these heterostructures into microcantilevers that are actuated with extremely low drive voltage due to thin-film piezoelectric properties that rival bulk PMN-PT single crystals. These epitaxial heterostructures exhibit very large electromechanical coupling for ultrasound medical imaging, microfluidic control, mechanical sensing, and energy harvesting.

  5. Exhibition Economy Set to Boost City Development

    Institute of Scientific and Technical Information of China (English)

    Li Zhen

    2010-01-01

    @@ Awell-developed exhibition industry is usually regarded as an important cri terion in measuring a city's economic and social development level. In recent years, much attention has been paid to exhibition economy for its positive effect on dining, transportation, tourism, advertising, and shopping.

  6. Artefacts and the performance of an exhibition

    DEFF Research Database (Denmark)

    Svabo, Connie

    2008-01-01

    The article explores the role of mediating artefacts in children's encounters with a museum of natural history. Using actor network theory it explores how a specific artefact shapes the way users relate to exhibited objects and how the artefact guides users' movements in the exhibition. The media...

  7. Science Fiction Exhibits as STEM Gateways

    Science.gov (United States)

    Robie, Samantha

    Women continue to hold less than a quarter of all STEM jobs in the United States, prompting many museums to develop programs and exhibits with the express goal of interesting young girls in scientific fields. At the same time, a number of recent museum exhibits have harnessed the popularity of pop culture and science fiction in order to interest general audiences in STEM subject matter, as well as using the exhibits as springboards to expand or shift mission goals and focus. Because science fiction appears to be successful at raising interest in STEM fields, it may be an effective way to garner the interest of young girls in STEM in particular. This research seeks to describe the ways in which museums are currently using science fiction exhibits to interest young girls in STEM fields and careers. Research focused on four institutions across the country hosting three separate exhibits, and included staff interviews and content analysis of exhibit descriptions, promotional materials, a summative evaluation and supplementary exhibit productions. In some ways, science fiction exhibits do serve young girls, primarily through the inclusion of female role models, staff awareness, and prototype testing to ensure interactives are attractive to girls as well as to boys. However, STEM appears to be underutilized, which may be partly due to a concern within the field that the outcome of targeting a specific gender could be construed as "stereotyping".

  8. Encountering Nanotechnology in an Interactive Exhibition

    Science.gov (United States)

    Murriello, Sandra E.; Knobel, Marcelo

    2008-01-01

    This article offers findings from a learning sciences-informed evaluation of a nanoscience and nanotechnology exhibition called Nano-Aventura (NanoAdventure), based on four interactive-collaborative games and two narrated videos. This traveling exhibition was developed in Brazil by the Museu Exploratorio de Ciencias for children and teenagers…

  9. The Culture of Exhibitions and Conservation

    Directory of Open Access Journals (Sweden)

    Dimitrios Doumas

    2013-11-01

    Full Text Available The article reflects on temporary exhibitions from a theoretical as well as practical perspective. Regarded as a particularly effective mass-communication medium, exhibitions have a dual nature: they are scholarly undertakings, bringing off a curator’s vision and, simultaneously, they are projects with economic implications that need to be well managed and administered. The role of conservation in the making of temporary exhibitions, either in-house or touring, is here discussed in relation to how work is planned and prioritized as well as how time is managed and staff is allocated. Reference to weaknesses that lessen the crucial input of conservation in the decision-making process is also made. Much of the debate, which focuses on art exhibitions, concerns practicalities encountered in a private museum that extend from the very early stages of selecting objects for display to the mounting of an exhibition.

  10. High Quality Virtual Reality for Architectural Exhibitions

    DEFF Research Database (Denmark)

    Kreutzberg, Anette

    2016-01-01

    This paper will summarise the findings from creating and implementing a visually high quality Virtual Reality (VR) experiment as part of an international architecture exhibition. It was the aim to represent the architectural spatial qualities as well as the atmosphere created from combining natural...... and artificial lighting in a prominent not yet built project. The outcome is twofold: Findings concerning the integration of VR in an exhibition space and findings concerning the experience of the virtual space itself. In the exhibition, an important aspect was the unmanned exhibition space, requiring the VR...... and quantitative methods at two different occasions and setups after the exhibition, both showing a high degree of immersion and experience of reality....

  11. Holland at CERN – Industrial exhibition

    CERN Multimedia

    GS Department

    2010-01-01

    Sponsored by EVD, an agency of the Dutch Ministry of the Economy From 8 to 11 November 2010 Industrial Exhibition Administration Building Bldg. 61 9-00 - 17-30 Twenty seven companies will present their latest technology at the industrial exhibition "Holland at CERN". Dutch industry will exhibit products and technologies which are related to the field of particle physics. Individual interviews will take place directly at the stands in the Main Building. The firms will contact relevant users/technicians but any user wishing to make contact with a particular firm is welcome to use the contact details which are available from each departmental secretariat or at the following URL: http://gs-dep.web.cern.ch/gs-dep/groups/sem/ls/Industrial_Exhibitions.htm#Industrial_exhibitions You will find the list of exhibitors below. LIST OF EXHIBITORS: Schelde Exotech Vernooy BV Triumph Group INCAA Computers DeMaCo Holland bv TNO Science & Industry Janssen Precision Engi...

  12. Mice Lacking Brinp2 or Brinp3, or Both, Exhibit Behaviors Consistent with Neurodevelopmental Disorders

    Science.gov (United States)

    Berkowicz, Susan R.; Featherby, Travis J.; Whisstock, James C.; Bird, Phillip I.

    2016-01-01

    Background: Brinps 1–3, and Astrotactins (Astn) 1 and 2, are members of the Membrane Attack Complex/Perforin (MACPF) superfamily that are predominantly expressed in the mammalian brain during development. Genetic variation at the human BRINP2/ASTN1 and BRINP1/ASTN2 loci has been implicated in neurodevelopmental disorders. We, and others, have previously shown that Brinp1−/− mice exhibit behavior reminiscent of autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Method: We created Brinp2−/− mice and Brinp3−/− mice via the Cre-mediated LoxP system to investigate the effect of gene deletion on anatomy and behavior. Additionally, Brinp2−/−Brinp3−/− double knock-out mice were generated by interbreeding Brinp2−/− and Brinp3−/− mice. Genomic validation was carried out for each knock-out line, followed by histological, weight and behavioral examination. Brinp1−/−Brinp2−/−Brinp3−/− triple knock-out mice were also generated by crossing Brinp2/3 double knock-out mice with previously generated Brinp1−/− mice, and examined by weight and histological analysis. Results: Brinp2−/− and Brinp3−/− mice differ in their behavior: Brinp2−/− mice are hyperactive, whereas Brinp3−/− mice exhibit marked changes in anxiety-response on the elevated plus maze. Brinp3−/− mice also show evidence of altered sociability. Both Brinp2−/− and Brinp3−/− mice have normal short-term memory, olfactory responses, pre-pulse inhibition, and motor learning. The double knock-out mice show behaviors of Brinp2−/− and Brinp3−/− mice, without evidence of new or exacerbated phenotypes. Conclusion: Brinp3 is important in moderation of anxiety, with potential relevance to anxiety disorders. Brinp2 dysfunction resulting in hyperactivity may be relevant to the association of ADHD with chromosome locus 1q25.2. Brinp2−/− and Brinp3−/− genes do not compensate in the mammalian brain and likely have

  13. Selenoprotein T Deficiency Leads to Neurodevelopmental Abnormalities and Hyperactive Behavior in Mice.

    Science.gov (United States)

    Castex, Matthieu T; Arabo, Arnaud; Bénard, Magalie; Roy, Vincent; Le Joncour, Vadim; Prévost, Gaëtan; Bonnet, Jean-Jacques; Anouar, Youssef; Falluel-Morel, Anthony

    2016-11-01

    Selenoprotein T (SelT) is a newly discovered thioredoxin-like protein, which is abundantly but transiently expressed in the neural lineage during brain ontogenesis. Because its physiological function in the brain remains unknown, we developed a conditional knockout mouse line (Nes-Cre/SelT(fl/fl)) in which SelT gene is specifically disrupted in nerve cells. At postnatal day 7 (P7), these mice exhibited reduced volume of different brain structures, including hippocampus, cerebellum, and cerebral cortex. This phenotype, which is observed early during the first postnatal week, culminated at P7 and was associated with increased loss of immature neurons but not glial cells, through apoptotic cell death. This phenomenon was accompanied by elevated levels of intracellular reactive oxygen species, which may explain the increased neuron demise and reduced brain structure volumes. At the second postnatal week, an increase in neurogenesis was observed in the cerebellum of Nes-Cre/SelT(fl/fl) mice, suggesting the occurrence of developmental compensatory mechanisms in the brain. In fact, the brain volume alterations observed at P7 were attenuated in adult mice. Nevertheless, SelT mutant mice exhibited a hyperactive behavior, suggesting that despite an apparent morphological compensation, SelT deficiency leads to cerebral malfunction in adulthood. Altogether, these results demonstrate that SelT exerts a neuroprotective role which is essential during brain development, and that its loss impairs mice behavior.

  14. Dissociation of working memory impairments and attention-deficit/hyperactivity disorder in the brain

    Directory of Open Access Journals (Sweden)

    Aaron T. Mattfeld

    2016-01-01

    Full Text Available Prevailing neuropsychological models of attention-deficit/hyperactivity disorder (ADHD propose that ADHD arises from deficits in executive functions such as working memory, but accumulating clinical evidence suggests a dissociation between ADHD and executive dysfunctions. This study examined whether ADHD and working memory capacity are behaviorally and neurobiologically separable using functional magnetic resonance imaging (fMRI. Participants diagnosed with ADHD in childhood who subsequently remitted or persisted in their diagnosis as adults were characterized at follow-up in adulthood as either impaired or unimpaired in spatial working memory relative to controls who never had ADHD. ADHD participants with impaired spatial working memory performed worse than controls and ADHD participants with unimpaired working memory during an n-back working memory task while being scanned. Both controls and ADHD participants with unimpaired working memory exhibited significant linearly increasing activation in the inferior frontal junction, precuneus, lingual gyrus, and cerebellum as a function of working-memory load, and these activations did not differ significantly between these groups. ADHD participants with impaired working memory exhibited significant hypoactivation in the same regions, which was significantly different than both control participants and ADHD participants with unimpaired working memory. These findings support both a behavioral and neurobiological dissociation between ADHD and working memory capacity.

  15. Dissociation of working memory impairments and attention-deficit/hyperactivity disorder in the brain.

    Science.gov (United States)

    Mattfeld, Aaron T; Whitfield-Gabrieli, Susan; Biederman, Joseph; Spencer, Thomas; Brown, Ariel; Fried, Ronna; Gabrieli, John D E

    2016-01-01

    Prevailing neuropsychological models of attention-deficit/hyperactivity disorder (ADHD) propose that ADHD arises from deficits in executive functions such as working memory, but accumulating clinical evidence suggests a dissociation between ADHD and executive dysfunctions. This study examined whether ADHD and working memory capacity are behaviorally and neurobiologically separable using functional magnetic resonance imaging (fMRI). Participants diagnosed with ADHD in childhood who subsequently remitted or persisted in their diagnosis as adults were characterized at follow-up in adulthood as either impaired or unimpaired in spatial working memory relative to controls who never had ADHD. ADHD participants with impaired spatial working memory performed worse than controls and ADHD participants with unimpaired working memory during an n-back working memory task while being scanned. Both controls and ADHD participants with unimpaired working memory exhibited significant linearly increasing activation in the inferior frontal junction, precuneus, lingual gyrus, and cerebellum as a function of working-memory load, and these activations did not differ significantly between these groups. ADHD participants with impaired working memory exhibited significant hypoactivation in the same regions, which was significantly different than both control participants and ADHD participants with unimpaired working memory. These findings support both a behavioral and neurobiological dissociation between ADHD and working memory capacity.

  16. A mini-exhibition with maximum content

    CERN Multimedia

    Laëtitia Pedroso

    2011-01-01

    The University of Budapest has been hosting a CERN mini-exhibition since 8 May. While smaller than the main travelling exhibition it has a number of major advantages: its compact design alleviates transport difficulties and makes it easier to find suitable venues in the Member States. Its content can be updated almost instantaneously and it will become even more interactive and high-tech as time goes by.   The exhibition on display in Budapest. The purpose of CERN's new mini-exhibition is to be more interactive and easier to install. Due to its size, the main travelling exhibition cannot be moved around quickly, which is why it stays in the same country for 4 to 6 months. But this means a long waiting list for the other Member States. To solve this problem, the Education Group has designed a new exhibition, which is smaller and thus easier to install. Smaller maybe, but no less rich in content, as the new exhibition conveys exactly the same messages as its larger counterpart. However, in the slimm...

  17. A feasibility study on the effectiveness of a full-body videogame intervention for decreasing attention deficit hyperactivity disorder symptoms

    NARCIS (Netherlands)

    Weerdmeester, J.W.; Cima, M.; Granic, I.; Hashemian, Y.; Gotsis, M.

    2016-01-01

    OBJECTIVE: The current study assessed the feasibility and effectiveness of a full-body-driven intervention videogame targeted at decreasing attention deficit hyperactivity disorder (ADHD) symptoms, specifically inattention, hyperactivity, impulsivity, and motor deficiency. MATERIALS AND METHODS: The

  18. Footprints of China Auto Internatienal Exhibition Tour

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ November 2008,the Sixth China Auto International(Algeria & Egypt)Exhibition Tour is ready.Since the first session was held in 1995,the Chinese auto enterprises have been to Vietnam,Cambodia,Syria,and Russian.

  19. The Report of Virtual Exhibition Software Development

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The main structure and key techniques of our Vir tual ExhibitionSoftware are summarized. It demonstrates the practice of Softwa re Engineering during the development of our project and discusses the use of UML in it.

  20. 49 CFR 250.2 - Required exhibits.

    Science.gov (United States)

    2010-10-01

    ... and detail for Class II railroads. (14) As Exhibit 14, a statement showing actual cash balance at the beginning of each month and the actual cash receipts and disbursements during each month of the current...

  1. Exhibition 2004: Never-falling Stand

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Another year for reform and development Reform and development, key words and melodies for present life, may reflect future changes definitely. Rapid progress of convention & exhibition industry undoubtedly predicates future development of this industry in China.

  2. France at CERN – Industrial exhibition

    CERN Multimedia

    FP Department

    2012-01-01

    Industrial Exhibition Administration Building Bldg 61 – 1st Floor Tuesday 27 March: 9 a.m. – 5.30 p.m. Wednesday 28 March: 9 a.m. – 2 p.m.   About thirty French companies are presenting their latest technological advances during the industrial exhibition "France at CERN", featuring products and technologies specifically related to CERN activities. Individual B2B meetings can be organized with the sales and technical representatives of participating firms and will take place at either the companies’ exhibition stands or in conference rooms in the Main Building. Individuals wishing to make contact with one or more companies must use the contact details available from each secretariat of department or by using this link. B2B meetings will be coordinated by UBIFRANCE. You will also find the list of exhibiting and participating companies online here. This event is sponsored by the French subsidiary of RS Components, the most important distri...

  3. Communicating Complex Sciences by Means of Exhibitions

    Science.gov (United States)

    Schneider, S.

    2011-12-01

    Earth Sciences will have to take over the leading role in global sustainable policy and in discussions about climate change. Efforts to raise attention within the politically responsible communities as well as in the public are getting more and more support by executive and advisory boards all over the world. But how can you successfully communicate complex sciences? For example, to start communication about climate change, the first step is to encourage people to be concerned about climate change. After that, one has to start thinking about how to present data and how to include the presented data into an unprejudiced context. Therefore, the communication toolbox offers various methods to reach diverse audiences. The R&D programme GEOTECHNOLOGIEN conducts roving exhibitions as one of its most successful communication tools. With roving exhibitions GEOTECHNOLOGIEN is able to get in touch with different audiences at once. The main purpose and theme of these exhibitions is to convey the everyday means of climate change to the visitors. It is within the responsibility of science to communicate the effects of a phenomenon like climate change as well as the impact of research results to the everyday life of people. Currently, a GEOTECHNOLOGIEN roving exhibition on remote sensing with satellites deals with various issues of environmental research, including a chapter on climate change. By following the 3M-concept (Meaning - Memorable - Moving), exhibitions allow to connect the visitors daily environment and personal experiences with the presented issues and objects. Therefore, hands-on exhibits, exciting multimedia effects and high-tech artefacts have to be combined with interpretive text elements to highlight the daily significance of the scientific topics and the exhibition theme respectively. To create such an exhibition, strong conceptual planning has to be conducted. This includes the specification of stern financial as well as time wise milestones. In addition

  4. [All-Russian hygienic exhibitions and museums].

    Science.gov (United States)

    Kuzybaeva, M P

    2011-01-01

    The material about the popularization of hygiene and health education in Russia in the second half of the 19th century to early 20th century through exhibition and museum activities has been collected for the first time and analyzed in the paper. The role of scientists and scientific medical societies in this process is noted. The significance of museum and exhibition activities in this area for the development of medical science is defined.

  5. When Do Children Exhibit a "Yes" Bias?

    Science.gov (United States)

    Okanda, Mako; Itakura, Shoji

    2010-01-01

    This study investigated whether one hundred and thirty-five 3- to 6-year-old children exhibit a yes bias to various yes-no questions and whether their knowledge status affects the production of a yes bias. Three-year-olds exhibited a yes bias to all yes-no questions such as "preference-object" and "knowledge-object" questions pertaining to…

  6. An Astrobiology Microbes Exhibit and Education Module

    Science.gov (United States)

    Lindstrom, Marilyn M.; Allen, Jaclyn S.; Stocco, Karen; Tobola, Kay; Olendzenski, Lorraine

    2001-01-01

    Telling the story of NASA-sponsored scientific research to the public in exhibits is best done by partnerships of scientists and museum professionals. Likewise, preparing classroom activities and training teachers to use them should be done by teams of teachers and scientists. Here we describe how we used such partnerships to develop a new astrobiology augmentation to the Microbes! traveling exhibit and a companion education module. "Additional information is contained in the original extended abstract."

  7. Reaching the Public through Traveling Exhibitions

    Science.gov (United States)

    Dusenbery, P. B.; Harold, J. B.; Morrow, C. A.

    2004-11-01

    The Space Science Institute (SSI) of Boulder, Colorado has recently developed two museum exhibits called Alien Earths and MarsQuest. It has just started to develop another exhibit called Giant Planets. These exhibitions provide research scientists the opportunity to engage in a number of activities that are vital to the success of these major outreach programs. Alien Earths was developed in partnership with various research missions. The focus of the presentation will be on MarsQuest and Giant Planets. MarsQuest is a 5000 square-foot, \\$3M, traveling exhibition that is now touring the country. The exhibit's second 3-year tour will enable millions of Americans to share in the excitement of the scientific exploration of Mars and learn more about their own planet in the process. The associated planetarium show and education program will also be described, with particular emphasis on workshops to orient museum staff (e.g. museum educators and docents) and workshops for master educators near host museums and science centers. The workshops make innovative connections between the exhibition's interactive experiences and lesson plans aligned with the National Science Education Standards. These exhibit programs are good models for actively involving scientists and their discoveries to help improve informal science education in the museum community and for forging a stronger connection between formal and informal education. The presentation will also discuss how Giant Planets, a proposed 3500 square-foot traveling exhibition on the mysteries and discoveries of the outer planets, will be able to take advantage of the connections and resources that have been developed by the MarsQuest project.

  8. Exhibition by Gozitan artist Mark Sagona

    OpenAIRE

    Calleja, Joseph

    2004-01-01

    Mark Sagona's exhibition, entitled "Recent Insights" was held at the Banca Giuratale in Victoria, Gozo between the 24th January and the 8th February 2004. It brought together twenty-four paintings, all produced in 2003 and the majority of which were realised in oil on canvas. The exhibition was curated by Dr Joseph Paul Cassar, and inaugurated by the Minister for Gozo, the Hon. Giovanna Debono.

  9. Teacher Attitudes towards Students Who Exhibit ADHD-Type Behaviours

    Science.gov (United States)

    Mulholland, Sarah M.; Cumming, Therese M.; Jung, Jae Yup

    2015-01-01

    Attention-deficit/hyperactivity disorder, its diagnosis and its treatment have been controversial since the 1970s (Kean, 2012), with opinions differing with respect to the diagnostic process, whether it in fact exists, or if it is an excuse for poor parenting and teaching (Maras, Redmayne, Hall, Braithwaite, & Prior, 1997). There are currently…

  10. Electrophysiological Indices of Abnormal Error-Processing in Adolescents with Attention Deficit Hyperactivity Disorder (ADHD)

    Science.gov (United States)

    Groom, Madeleine J.; Cahill, John D.; Bates, Alan T.; Jackson, Georgina M.; Calton, Timothy G.; Liddle, Peter F.; Hollis, Chris

    2010-01-01

    Background: Impaired cognitive control has been frequently observed in children and young people with attention deficit hyperactivity disorder (ADHD) and might underlie the excessive hyperactivity and impulsivity in this population. We investigated behavioural and electrophysiological indices relevant to one domain of cognitive control; namely…

  11. A Meta-Analysis of Behavioral Parent Training for Children with Attention Deficit Hyperactivity Disorder

    Science.gov (United States)

    Lee, Pei-chin; Niew, Wern-ing; Yang, Hao-jan; Chen, Vincent Chin-hung; Lin, Keh-chung

    2012-01-01

    This meta-analysis examined the effect of behavioral parent training on child and parental outcomes for children with attention deficit hyperactivity disorder. Meta-analytic procedures were used to estimate the effect of behavioral parent training on children with attention deficit hyperactivity disorder. Variables moderating the intervention…

  12. Reading and Listening Comprehension and Their Relation to Inattention and Hyperactivity

    Science.gov (United States)

    Cain, Kate; Bignell, Simon

    2014-01-01

    Background: Children with diagnoses of attention-deficit/hyperactivity disorder (ADHD) frequently have reading problems. To date, it is not clear whether poor reading is associated with both inattention and hyperactivity and also whether poor reading comprehension is the result of poor word reading skills or more general language comprehension…

  13. Factor Structure of Attention Deficit Hyperactivity Disorder Symptoms for Children Age 3 to 5 Years

    Science.gov (United States)

    McGoey, Kara E.; Schreiber, James; Venesky, Lindsey; Westwood, Wendy; McGuirk, Lindsay; Schaffner, Kristen

    2015-01-01

    The diagnosis of attention deficit hyperactivity disorder (ADHD) distinguishes two dimensions of symptoms, inattention and hyperactivity-impulsivity for ages 3 to adulthood. Currently, no separate classification for preschool-age children exists, whereas preliminary research suggests that the two-factor structure of ADHD may not match the…

  14. Students Diagnosed with Attention Deficit Hyperactivity Disorder: Collaborative Strategies for School Counselors

    Science.gov (United States)

    Shillingford-Butler, M. Ann; Theodore, Lea

    2013-01-01

    The school setting can be a difficult place for children with attention deficit hyperactivity disorder (ADHD). The core symptoms of ADHD, which include inattention, hyperactivity, and impulsivity, make meeting the curriculum demands of the classroom challenging. That ADHD negatively impacts not only academic performance but also social and…

  15. Altered brain structural networks in attention deficit/hyperactivity disorder children revealed by cortical thickness.

    Science.gov (United States)

    Liu, Tian; Chen, Yanni; Li, Chenxi; Li, Youjun; Wang, Jue

    2017-01-18

    This study investigated the cortical thickness and topological features of human brain anatomical networks related to attention deficit/hyperactivity disorder. Data were collected from 40 attention deficit/hyperactivity disorder children and 40 normal control children. Interregional correlation matrices were established by calculating the correlations of cortical thickness between all pairs of cortical regions (68 regions) of the whole brain. Further thresholds were applied to create binary matrices to construct a series of undirected and unweighted graphs, and global, local, and nodal efficiencies were computed as a function of the network cost. These experimental results revealed abnormal cortical thickness and correlations in attention deficit/hyperactivity disorder, and showed that the brain structural networks of attention deficit/hyperactivity disorder subjects had inefficient small-world topological features. Furthermore, their topological properties were altered abnormally. In particular, decreased global efficiency combined with increased local efficiency in attention deficit/hyperactivity disorder children led to a disorder-related shift of the network topological structure toward regular networks. In addition, nodal efficiency, cortical thickness, and correlation analyses revealed that several brain regions were altered in attention deficit/hyperactivity disorder patients. These findings are in accordance with a hypothesis of dysfunctional integration and segregation of the brain in patients with attention deficit/hyperactivity disorder and provide further evidence of brain dysfunction in attention deficit/hyperactivity disorder patients by observing cortical thickness on magnetic resonance imaging.

  16. Attention Deficit Hyperactivity Disorder and Sensory Modulation Disorder: A Comparison of Behavior and Physiology

    Science.gov (United States)

    Miller, Lucy Jane; Nielsen, Darci M.; Schoen, Sarah A.

    2012-01-01

    Children with attention deficit hyperactivity disorder (ADHD) are impulsive, inattentive and hyperactive, while children with sensory modulation disorder (SMD), one subtype of Sensory Processing Disorder, have difficulty responding adaptively to daily sensory experiences. ADHD and SMD are often difficult to distinguish. To differentiate these…

  17. Voluntary access to a warm plate reduces hyperactivity in activity-based anorexia

    NARCIS (Netherlands)

    Hillebrand, Jacquelien J G; de Rijke, Corine E; Brakkee, Jan H; Kas, Martien J H; Adan, Roger A H

    2005-01-01

    Activity-based anorexia (ABA) is considered an animal model of anorexia nervosa. In ABA, scheduled feeding in combination with voluntary wheel running leads to hyperactivity, reduced food intake, severe body weight loss and hypothermia. In this study it was investigated whether hyperactivity in ABA

  18. Efficacy of Methylphenidate among Children with Autism and Symptoms of Attention-Deficit Hyperactivity Disorder.

    Science.gov (United States)

    Handen, Benjamin L.; Johnson, Cynthia R.; Lubetsky, Martin

    2000-01-01

    Thirteen children (ages 5-11) with autism and symptoms of attention-deficit hyperactivity disorder participated in a double-blind, placebo-controlled crossover study of methylphenidate. Eight subjects responded positively, decreasing their hyperactivity. Ratings of stereotypy and inappropriate speech also decreased, however, no changes were found…

  19. The Cheshire Cat Enigma: Emotion Recognition Abilities of Preschool Boys with and without Hyperactivity and Aggression

    Science.gov (United States)

    Arnold, Megan

    2010-01-01

    This research examined the emotion recognition abilities of preschoolers with and without hyperactivity and aggression. Previous research identified that school age children with Attention Deficit Hyperactivity Disorder (ADHD) have more difficulty understanding facial expressions associated with emotions, take longer than their age-matched peers…

  20. Effects of Age and Ritalin Dosage on the Mother-Child Interactions of Hyperactive Children.

    Science.gov (United States)

    Barkley, Russell A.; And Others

    1984-01-01

    Observed the mother-child interactions of three age groups of hyperactive children (N=54) during free play and task settings using two dose levels of Ritalin. Results indicated that the interactions of hyperactive boys with their mothers improve with age, and that Ritalin produces further improvements regardless of age examined. (LLL)

  1. Effects of the Psychoactive Drug: Methylphenidate (Ritalin) on Classroom Disorders: Hyperactivity, Emotional Disturbance and Learning Disorders.

    Science.gov (United States)

    Hirst, Irene

    Reviewed were several research studies using varying dosages of methylphenidate (Ritalin) in contrast with thioridazine and amphetamine under various behavioral conditions and situations with hyperactive, emotionally disturbed, and learning disabled children. Results from the studies with hyperactive children indicated that drug treatment was…

  2. Causal Attributions of Hyperactive Children: Implications for Teaching Strategies and Self-Control.

    Science.gov (United States)

    Reid, Molly K.; Borkowski, John G.

    1987-01-01

    The influence of attribution and self-control training on short- and long-term maintenance of strategic behavior, impulsivity, and beliefs about self-efficacy was assessed in 77 underachieving, hyperactive children. Results supported the use of attribution and self control training in treating strategic deficits in hyperactive and learning…

  3. An Experimental Evaluation of Hyperactivity and Food Additives. 1977-Phase I.

    Science.gov (United States)

    Harley, J. Preston

    Reported are findings of a study involving 46 families in which the effect of the Feingold (additive free) diet on hyperactivity in preschool and elementary age children was investigated. Eleven sections cover the following project components: introduction (definition of hyperactivity and the B. Feingold hypothesis), methodology, demographic…

  4. Maternal Positive Parenting Style Is Associated with Better Functioning in Hyperactive/Inattentive Preschool Children

    Science.gov (United States)

    Healey, Dione M.; Flory, Janine D.; Miller, Carlin J.; Halperin, Jeffrey M.

    2011-01-01

    Many preschoolers are highly inattentive, impulsive, and hyperactive; but only some are impaired in their functioning. Yet factors leading to functional impairment, above and beyond the severity of inattentive and hyperactive symptoms, have not been systematically examined. This study examined a model suggesting that after controlling for…

  5. Attention Deficit Hyperactivity Disorder: A Rasch Analysis of the SWAN Rating Scale

    Science.gov (United States)

    Young, Deidra J.; Levy, Florence; Martin, Neilson C.; Hay, David A.

    2009-01-01

    The prevalence of attention-deficit/hyperactivity disorder (ADHD) has been estimated at 3-7% in the population. Children with this disorder are often characterized by symptoms of inattention and/or impulsivity and hyperactivity, which can significantly impact on many aspects of their behaviour and performance. This study investigated the…

  6. Use of Digital Console Game for Children with Attention Deficit Hyperactivity Disorder

    Science.gov (United States)

    Chuang, Tsung-Yen; Lee, I-Ching; Chen, Wen-Chih

    2010-01-01

    ADHD or ADD (Attention Deficit/Hyperactivity Disorder) is one of the most frequently diagnosed mental and behavioral disorders of children. Children with ADHD are characterized by poor attention and distractibility and/or hyperactive and impulsive behaviors. Although there is no "cure" for ADHD, there are accepted treatments that…

  7. Relationship between sphenomandibular muscle hyperactivity and visual symptoms

    Directory of Open Access Journals (Sweden)

    Raulino Naves Borges

    2012-01-01

    Full Text Available This was an observational, descriptive study developed after an anatomical investigation of cadavers to identify the sphenomandibular muscle as an independent entity. The objective here was to perform a clinical and interpretative evaluation of the physiological relationships between the functions of the sphenomandibular muscle and various symptoms, thereby associating temporomandibular disorders with ocular pain. Ten anatomical sets (fi ve cadavers in the Department of Anatomy of the Medicine School of the Catholic University of Goiás were examined. This study was conducted between April, 2006 and December, 2008. Patients (181 subjects suffering from temporomandibular disorder were treated in the Federal University of Goiás Dental School. Two groups were compared: Group I consisted of 58 patients with temporomandibular disorder, referred ocular pain, and hyperactivity of the sphenomandibular muscles; Group II was comprised of 45 patients with temporomandibular disorder, ocular pain, but no hyperactivity of the sphenomandibular muscles. After a clinical exam, treatments were conducted with semi-yearly follow-up exams for 2 years. Responses to the treatment were evaluated by questionnaires thereby quantifying existing levels of ocular pain. Pain was eliminated in 46 of the 58 patients in Group I (79.31% and 8 of the 45 patients in Group II (17.77%. Our evaluation affi rms that the sphenomandibular muscle, independent of the temporal muscle, has an intimate relationship with the orbit. The clinical exam allowed an evaluation of the sphenomandibular muscles in temporomandibular disorder episodes. The hyperactivity of the sphenomandibular muscle is thus signifi cantly related to the presence of ocular-referred pain (p < 0.05.

  8. Drug holidays and attention deficit/hyperactivity disorder

    Institute of Scientific and Technical Information of China (English)

    Christopher P. SZABO

    2011-01-01

    The concept of ‘drug holidays’ (defined as "...the structured interruption of pharmacological treatment..."[1]) in the management of attention deficit hyperactivity disorder (ADHD) is well established,but poorly researched[1].The question is whether there is indeed a justifiable basis for the practice.In the opinion piece by Professors Du and Wang[2],they argue that on the balance of available evidence it is not justified.Herein lies the issue-the evidence.In reality significant numbers of parents both report side effects[3] and stop medication intermittently[1],and many sufferers stop treatment prematurely[4] (generally due to adverse effects).

  9. Attention-deficit/hyperactivity disorder and suicide: A systematic review

    Science.gov (United States)

    Balazs, Judit; Kereszteny, Agnes

    2017-01-01

    AIM To investigate suicidality and attention-deficit/hyperactivity disorder (ADHD), this paper aims to systematically review the literature as an extension of previous reviews. METHODS We searched five databases (Ovid MEDLINE, Psychinfo, PubMed, Scopus, Web of Science) with two categories of search terms: (1) suicide; suicidal; suicide behavior; suicide attempt; suicidal thought; and (2) ADHD. RESULTS The search resulted 26 articles. There is a positive association between ADHD and suicidality in both sexes and in all age groups. Comorbid disorders mediate between suicidality and ADHD. CONCLUSION Recognizing ADHD, comorbid conditions and suicidality is important in prevention.

  10. The nursing student with attention deficit hyperactivity disorder.

    Science.gov (United States)

    Bradshaw, Martha J; Salzer, Judith Schurr

    2003-01-01

    Attention deficit hyperactivity disorder (ADHD) in college-age students presents a complex challenge of coping with academic coursework, refining life skills, and addressing self-limitations. Behaviors that characterize ADHD are particularly problematic for nursing students, especially when the student has difficulty with behaviors that exemplify executive functioning. The authors discuss symptoms and treatments associated with the diagnosis of ADHD and evaluation and interventions for college students, based on guidelines from the Americans With Disabilities Act. Nursing faculty can facilitate academic success by recognizing the problem in nursing students and implementing strategies useful for self-management of ADHD.

  11. Sleep in Autism Spectrum Disorder and Attention Deficit Hyperactivity Disorder.

    Science.gov (United States)

    Singh, Kanwaljit; Zimmerman, Andrew W

    2015-06-01

    Sleep problems are common in autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Sleep problems in these disorders may not only worsen daytime behaviors and core symptoms of ASD and ADHD but also contribute to parental stress levels. Therefore, the presence of sleep problems in ASD and ADHD requires prompt attention and management. This article is presented in 2 sections, one each for ASD and ADHD. First, a detailed literature review about the burden and prevalence of different types of sleep disorders is presented, followed by the pathophysiology and etiology of the sleep problems and evaluation and management of sleep disorders in ASD and ADHD.

  12. MAKING SENSE OF ATTENTION DEFICIT/HYPERACTIVITY DISORDER

    OpenAIRE

    Lensch, Carol

    1998-01-01

    In recent years there has been a notable increase in the number of students being identified with Attention Deficit/Hyperactivity Disorder (AD/HD) in American schools. Although there is a tremendous amount of research being done in the area of AD/HD, parents, educators and individuals with AD/HD are ill-equipped to deal with the demands of the disorder. Only through extensive research and a better understanding of what AD/HD is can we expect to develop more effective mean...

  13. CERN exhibition a big hit in Bulgaria

    CERN Multimedia

    2005-01-01

    The first CERN exhibition in Bulgaria attracted many visitors. In the first ever CERN exhibition to be held in Bulgaria, over 1,400 visitors, many of them students and young physicists, visited the 10-day event in Sofia. The CERN mini-exhibition took place at the National Earth and Mankind Museum between 8 and 17 November. Permanently staffed by young physicists from Sofia University, there were exhibits on display about research activities at CERN, as well as four additional posters describing Bulgaria's participation. The inauguration took place on the morning of 8 November in the presence of the Vice-Minister for Science and Education, Mrs. Vanya Dobreva, and some 200 guests. A series of short speeches were followed by a visit to the exhibition. CERN's representative at the event, Ray Lewis, was then asked by Professor Matey Mateev, President of the Union of Physicists in Bulgaria, to say a few words on behalf of the Organization. Numerous journalists were also present at the inauguration. A painting enti...

  14. The Gravity- Powered Calculator, a Galilean Exhibit

    Science.gov (United States)

    Cerreta, Pietro

    2014-04-01

    The Gravity-Powered Calculator is an exhibit of the Exploratorium in San Francisco. It is presented by its American creators as an amazing device that extracts the square roots of numbers, using only the force of gravity. But if you analyze his concept construction one can not help but recall the research of Galileo on falling bodies, the inclined plane and the projectile motion; exactly what the American creators did not put into prominence with their exhibit. Considering the equipment only for what it does, in my opinion, is very reductive compared to the historical roots of the Galilean mathematical physics contained therein. Moreover, if accurate deductions are contained in the famous study of S. Drake on the Galilean drawings and, in particular on Folio 167 v, the parabolic paths of the ball leaping from its launch pad after descending a slope really actualize Galileo's experiments. The exhibit therefore may be best known as a `Galilean calculator'.

  15. Functional connectivity of neural motor networks is disrupted in children with developmental coordination disorder and attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    McLeod, Kevin R; Langevin, Lisa Marie; Goodyear, Bradley G; Dewey, Deborah

    2014-01-01

    Developmental coordination disorder (DCD) and attention deficit/hyperactivity disorder (ADHD) are prevalent childhood disorders that frequently co-occur. Evidence from neuroimaging research suggests that children with these disorders exhibit disruptions in motor circuitry, which could account for the high rate of co-occurrence. The primary objective of this study was to investigate the functional connections of the motor network in children with DCD and/or ADHD compared to typically developing controls, with the aim of identifying common neurophysiological substrates. Resting-state fMRI was performed on seven children with DCD, 21 with ADHD, 18 with DCD + ADHD and 23 controls. Resting-state connectivity of the primary motor cortex was compared between each group and controls, using age as a co-factor. Relative to controls, children with DCD and/or ADHD exhibited similar reductions in functional connectivity between the primary motor cortex and the bilateral inferior frontal gyri, right supramarginal gyrus, angular gyri, insular cortices, amygdala, putamen, and pallidum. In addition, children with DCD and/or ADHD exhibited different age-related patterns of connectivity, compared to controls. These findings suggest that children with DCD and/or ADHD exhibit disruptions in motor circuitry, which may contribute to problems with motor functioning and attention. Our results support the existence of common neurophysiological substrates underlying both motor and attention problems.

  16. Functional connectivity of neural motor networks is disrupted in children with developmental coordination disorder and attention-deficit/hyperactivity disorder

    Directory of Open Access Journals (Sweden)

    Kevin R. McLeod

    2014-01-01

    Full Text Available Developmental coordination disorder (DCD and attention deficit/hyperactivity disorder (ADHD are prevalent childhood disorders that frequently co-occur. Evidence from neuroimaging research suggests that children with these disorders exhibit disruptions in motor circuitry, which could account for the high rate of co-occurrence. The primary objective of this study was to investigate the functional connections of the motor network in children with DCD and/or ADHD compared to typically developing controls, with the aim of identifying common neurophysiological substrates. Resting-state fMRI was performed on seven children with DCD, 21 with ADHD, 18 with DCD + ADHD and 23 controls. Resting-state connectivity of the primary motor cortex was compared between each group and controls, using age as a co-factor. Relative to controls, children with DCD and/or ADHD exhibited similar reductions in functional connectivity between the primary motor cortex and the bilateral inferior frontal gyri, right supramarginal gyrus, angular gyri, insular cortices, amygdala, putamen, and pallidum. In addition, children with DCD and/or ADHD exhibited different age-related patterns of connectivity, compared to controls. These findings suggest that children with DCD and/or ADHD exhibit disruptions in motor circuitry, which may contribute to problems with motor functioning and attention. Our results support the existence of common neurophysiological substrates underlying both motor and attention problems.

  17. Voxel-based statistical analysis of regional cerebral glucose metabolism in children with attention-deficit hyperactivity disorder

    Institute of Scientific and Technical Information of China (English)

    Ji-Hoon Kim; Young-In Chung; Jung Sub Lee; In-Joo Kim; Yong-Ki Kim; Seong-Jang Kim

    2011-01-01

    The technique of region of interest-based positron emission tomography is limited by its poor reliability and relatively few examined brain regions. In the present study, we compared brain metabolism assessed using fluorine-18-fluorodeoxyglucose positron emission tomography between 14 attention-deficit hyperactivity disorder (ADHD) patients and 15 normal controls with scoliosis at resting state by statistical parametric mapping. Glucose metabolism was decreased in the left parahippocampal gyrus, left hippocampus, left anterior cingulate gyrus, right anterior and posterior lobes of the cerebellum, left superior temporal gyrus, left insula, left medial and middle frontal gyri, right medial frontal gyrus, and left basal ganglia (putamen, amygdala, and caudate nucleus) in children with ADHD. These data suggest that children with ADHD exhibit hypometabolism in various brain regions compared to controls, indicating that ADHD symptoms are unlikely the result of abnormalities in specific areas.

  18. An analysis of challenging behavior, comorbid psychopathology, and Attention-Deficit/Hyperactivity Disorder in Fragile X Syndrome.

    LENUS (Irish Health Repository)

    Newman, Isabel

    2015-03-01

    The present study sought to investigate the relationship between challenging behavior, comorbid psychopathology, and Attention-Deficit\\/Hyperactivity Disorder (AD\\/HD) in Fragile X Syndrome (FRAX). Additionally, this study sought to examine how such disorders are predicted by gender, presence of autism spectrum disorder (ASD), and presence of intellectual disability (ID). A total of 47 children and adolescents with FRAX were assessed. Results revealed high levels of challenging behavior and AD\\/HD symptoms within the sample, with some participants exhibiting symptoms of comorbid psychopathology. Further analysis revealed that challenging behavior and comorbid psychopathology were positively correlated, with stereotypy correlating most strongly with comorbid psychopathology. In addition, ASD was found to predict challenging behavior, and gender was found to predict AD\\/HD symptoms. The implications of these findings are discussed.

  19. Mice lacking the synaptic adhesion molecule Neph2/Kirrel3 display moderate hyperactivity and defective novel object preference

    Directory of Open Access Journals (Sweden)

    Su Yeon eChoi

    2015-07-01

    Full Text Available Synaptic adhesion molecules regulate diverse aspects of neuronal synapse development, including synapse specificity, formation, and maturation. Neph2, also known as Kirrel3, is an immunoglobulin superfamily adhesion molecule implicated in intellectual disability, neurocognitive delay associated with Jacobsen syndrome, and autism spectrum disorders. We here report mice lacking Neph2 (Neph2–/– mice display moderate hyperactivity in a familiar but not novel environment and novel object recognition deficit with normal performances in Morris water maze spatial learning and memory, contextual fear conditioning and extinction, and pattern separation tests. These mice show normal levels of anxiety-like behaviors, social interaction, and repetitive behaviors. At the synapse level, Neph2–/– dentate gyrus granule cells exhibit unaltered dendritic spine density and spontaneous excitatory synaptic transmission. These results suggest that Neph2 is important for normal locomotor activity and object recognition memory.

  20. Enhancing academic achievement for children with Attention-Deficit Hyperactivity Disorder: evidence from school-based intervention research.

    Science.gov (United States)

    Jitendra, Asha K; Dupaul, George J; Someki, Fumio; Tresco, Katy E

    2008-01-01

    Although children with Attention-Deficit Hyperactivity Disorder (ADHD) exhibit significant academic difficulties in school settings, considerably less attention is devoted to remediating their academic problems when compared to behavioral and social difficulties. The purpose of this article is to review empirically supported academic interventions for children with ADHD. Specific evidence-based academic interventions are described under the categories of reading and mathematics, with examples that illustrate teacher-mediated interventions focusing on basic skills (e.g., phonological awareness in reading, mathematics computation) and higher-level cognitive skills (e.g., collaborative strategic reading, CSR; schema-based instruction, SBI). Finally, implications for educational practice and directions for future research on school-based academic interventions for students with ADHD are discussed.

  1. Cognitive Inhibitory Control and Arithmetic Word Problem Solving in Children with Attention Deficit/ Hyperactivity Disorder: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Sigem Sabagh-Sabbagh

    2010-02-01

    Full Text Available A sample of 30 subjects, 10 with Attention Deficit and Hyperactivity Disorder(ADHD and 20 non-ADHD children, statistically controlled byage, gender, academic grades and normal full scale intelligence quotient,was selected. To measure cognitive inhibitory control, a math problem solving ability test containing four problems for each level with verbal and numerical irrelevant content was administered. ADHD children exhibited significantly inferior performance in choosing correct answers (p = 0.011 with a large effect size (d = 1.00 and a significantly superior number of irrelevant answers (p = 0.004 with a very large effect size. In conclusion ADHD children showed a cognitive inhibitory control disorder, measured by math problem solving ability.

  2. Understanding paroxysmal sympathetic hyperactivity after traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Kimberly S Meyer

    2014-01-01

    Full Text Available Background: Paroxysmal sympathetic hyperactivity (PSH is a condition occurring in a small percentage of patients with severe traumatic brain injury (TBI. It is characterized by a constellation of symptoms associated with excessive adrenergic output, including tachycardia, hypertension, tachypnea, and diaphoresis. Diagnosis is one of exclusion and, therefore, is often delayed. Treatment is aimed at minimizing triggers and pharmacologic management of symptoms. Methods: A literature review using medline and cinahl was conducted to identify articles related to PSH. Search terms included paroxysmal sympathetic hyperactivity, autonomic storming, diencephalic seizures, and sympathetic storming. Reference lists of pertinent articles were also reviewed and these additional papers were included. Results: The literature indicates that the understanding of PSH following TBI is in its infancy. The majority of information is based on small case series. The review revealed treatments that may be useful in treating PSH. Conclusions: Nurses play a critical role in the identification of at-risk patients, symptom complexes, and in the education of family. Early detection and treatment is likely to decrease overall morbidity and facilitate recovery. Further research is needed to establish screening tools and treatment algorithms for PSH.

  3. Attention deficit hyperactivity disorder: A review for family physicians

    Directory of Open Access Journals (Sweden)

    Karande Sunil

    2005-12-01

    Full Text Available Attention deficit hyperactivity disorder (ADHD is a chronic behavioral disorder characterized by persistent hyperactivity, impulsivity, and inattention that impairs educational achievement and/or social functioning. Its diagnosis is made by ascertaining whether the child′s specific behaviors meet the diagnostic and statistical manual of mental disorders-IV-revised criteria. Its etiology is still unclear but recent studies suggest that genetics plays a major role in conferring susceptibility. Comorbidity with psychiatric disorders such as anxiety disorder, depression, oppositional defiant disorder and conduct disorder; and with specific learning disability is not uncommon. Although medication works well in most cases of ADHD, optimal treatment requires integrated medical and behavioral treatment. Methylphenidate (MPH and atomoxetine are the two drugs being currently prescribed and their efficacy in decreasing the symptoms of ADHD is well documented. Pyschoeducational interventions in school can help increase the successful functioning of affected children and improve their academic performance. Almost half of affected children continue to show significant symptoms of the disorder into adolescence and young adulthood. The family physician can play an important role in detecting this condition early, coordinating its assessment and treatment, counseling the parents and classroom teacher, and monitoring the child′s academic and psychosocial progress on a long-term basis.

  4. Socio-emotional intervention in attention deficit hyperactive disorder

    Directory of Open Access Journals (Sweden)

    María Jesús Cardoso-Moreno

    2015-06-01

    Full Text Available Attention-deficit-hyperactivity disorder (ADHD is a common neuro-behavioural disorder with onset in childhood. These children have impaired emotional self-control, self-regulation of drive and motivation. Numerous studies have reported cognitive disabilities in memory, executive functions, spatial abilities and language skills. The main objective of this work is to determine whether a socio-emotional intervention programme could improve executive functions in children with Attention Deficit Hyperactivity Disorder. The sample of this study consisted of 25 children (8 female and 17 male aged between 8 and 12 years, diagnosed with ADHD and who were not taking any psychopharmacological treatment at the time of the study, and had not taken medication previously. Executive functioning was assessed through the Zoo Map test and Tower of Hanoi puzzle in pre-/post-test design. A socio-emotional intervention programme was implemented. The training consisted of 8 one-hour weekly sessions, on an individual basis. Results indicate that such a programme does lead to improved performance in the execution of tasks that evaluate executive functions. After the intervention, the children took less time to resolve the Zoo Map test. Results for the Hanoi Tower puzzle were also improved after intervention. The children needed a lower number of movements to complete the task.

  5. Addressing attention-deficit/hyperactivity disorder in the workplace.

    Science.gov (United States)

    Sarkis, Elias

    2014-09-01

    Although generally considered a childhood disorder, attention-deficit/hyperactivity disorder (ADHD) can persist into adulthood and impede achievement in the workplace. Core ADHD symptoms of inattention, hyperactivity, and impulsivity can be associated with poor organization, time management, and interpersonal relationships. Employment levels, earning power, and productivity are reduced among individuals with ADHD compared with those without ADHD. Furthermore, the costs of employing individuals with ADHD are higher because of work absences and lost productivity. The primary care provider plays an integral role in managing ADHD symptoms and providing the necessary resources that will help individuals with ADHD succeed in the workplace. Pharmacotherapy can reduce ADHD symptoms and improve functioning; however, it is also important to consider how positive traits associated with ADHD, such as creative thinking, can be used in the workplace. Workplace accommodations and behavioral therapies, such as coaching, can also enhance time management and organizational skills. This review describes how ADHD symptoms affect workplace behaviors, the effect of ADHD on employment and workplace performance, and the management of ADHD in working adults.

  6. How do exhibition visitors describe aesthetic qualities?

    DEFF Research Database (Denmark)

    Thomsen, Bente Dahl; Ravn, Anders Peter

    2007-01-01

    In this investigation, visitors to an art and design exhibition have used an interactive computer program to express the qualities they consider important for an art or design object (artefact). They have then used the program with their individually selected qualities to assess the artefacts. In...

  7. Retrospect of China International Auto Exhibition Tours

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ "Fengfan Cup" the Frist China International Auto Exhibition Tour In 1995, the first session gathered 28 national motorcycles and autos from four big groups---China North Industries Group Corporation, China Aviation Industry Corporation, China Aerospace Science and Industry Cooperation and PLA General Logistics Department.

  8. Exhibition Ethics - An Overview of Major Issues

    Directory of Open Access Journals (Sweden)

    Andromache Gazi

    2014-05-01

    Full Text Available Museum ethics are about value judgements. In making such judgements museum personnel is constantly valuing one option over another. This holds true for every aspect of museum work; from collecting policies and conservation to store priorities and exhibition. In recent decades there has been a growing concern in addressing ethical issues in museums as museum workers have developed cultural sensitivity and social responsiveness to a degree unseen before. Most codes of ethics urge museums to give appropriate consideration to represented groups or beliefs. In light of this, it has been recognised that exhibition of sensitive material, for example, must be done with great tact and respect for the feelings of religious, ethnic or other groups represented. Another issue concerns the display of unprovenanced material and repatriation. Yet, these are not the only ethical issues which exhibition developers are faced with. As museum workers we should constantly be reminded that exhibitions are active agents in the construction of knowledge. This paper discusses the hidden assumptions on which museum presentation and interpretation are often based. Decisions about what to include and what to exclude, what is valued and what is not, the means of presentation, language, and so on, all lead to presentational styles which may shape the public’s perception in unintended ways.

  9. 18 CFR 50.7 - Applications: exhibits.

    Science.gov (United States)

    2010-04-01

    ... data that represent system operating conditions. (i) Exhibit I—Project Cost and Financing. (1) A statement of estimated costs of any new construction or modification. (2) The estimated capital cost and...) Provide all files to model normal, single contingency, multiple contingency, and special...

  10. CCPIT Machinery Exhibition Succeeded in Kuala Lumpur

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

      From August 18 to 20, 2005, China Council for the Promotion of International Trade(CCPIT) held China Machinery and Electronics Trade Exhibition, CME 2005 in Kuala Lumpur, the capital of Malaysia on behalf of China, a good job has been done.……

  11. CCPIT Machinery Exhibition Succeeded in Kuala Lumpur

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    @@ From August 18 to 20, 2005, China Council for the Promotion of International Trade(CCPIT) held China Machinery and Electronics Trade Exhibition, CME 2005 in Kuala Lumpur, the capital of Malaysia on behalf of China, a good job has been done.

  12. CERN exhibition wins yet another design prize

    CERN Multimedia

    Joannah Caborn Wengler

    2012-01-01

    The “Universe of Particles” exhibition in CERN’s Globe wins the silver design prize from the German direct business communications association FAMAB.   Not only do tens of thousands of people visit the “Universe of Particles” exhibition each year, but juries for design prizes are crossing its threshold more and more frequently too. In 2011 alone it claimed 8 awards, including winning outright the 2011 Annual Multimedia award, the iF Communication Design for Corporate Architecture award and the Modern Decoration Media award (the Bulletin already reported on some of these in July 2011). The FAMAB award is the latest to join the prestigious list. The jury of FAMAB’s “ADAM 2011” award was particularly impressed by the hands-on nature of the exhibition, which encourages visitors to get interested in science. They also appreciated the way that the space in the Globe is not just a container for the exhibits, but itself ...

  13. Comic Strips to Accompany Science Museum Exhibits

    Science.gov (United States)

    Chung, Beom Sun; Park, Eun-mi; Kim, Sang-Hee; Cho, Sook-kyoung; Chung, Min Suk

    2016-01-01

    Science museums make the effort to create exhibits with amusing explanations. However, existing explanation signs with lengthy text are not appealing, and as such, visitors do not pay attention to them. In contrast, conspicuous comic strips composed of simple drawings and humors can attract science museum visitors. This study attempted to reveal…

  14. Autoimmune pancreatitis exhibiting multiple mass lesions.

    Science.gov (United States)

    Shiokawa, Masahiro; Kodama, Yuzo; Hiramatsu, Yukiko; Kurita, Akira; Sawai, Yugo; Uza, Norimitsu; Watanabe, Tomohiro; Chiba, Tsutomu

    2011-09-01

    Our case is a first report of autoimmune pancreatitis with multiple masses within the pancreas which was pathologically diagnosed by endoscopic ultrasound-guided fine needle aspiration and treated by steroid. The masses disappeared by steroid therapy. Our case is informative to know that autoimmune pancreatitis sometimes exhibits multiple masses within the pancreas and to diagnose it without unnecessary surgery.

  15. Autoimmune Pancreatitis Exhibiting Multiple Mass Lesions

    Directory of Open Access Journals (Sweden)

    Masahiro Shiokawa

    2011-09-01

    Full Text Available Our case is a first report of autoimmune pancreatitis with multiple masses within the pancreas which was pathologically diagnosed by endoscopic ultrasound-guided fine needle aspiration and treated by steroid. The masses disappeared by steroid therapy. Our case is informative to know that autoimmune pancreatitis sometimes exhibits multiple masses within the pancreas and to diagnose it without unnecessary surgery.

  16. Multi-dimensional correlates of Internet addiction symptoms in adolescents with attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Chou, Wen-Jiun; Liu, Tai-Ling; Yang, Pinchen; Yen, Cheng-Fang; Hu, Huei-Fan

    2015-01-30

    This study examined the associations of the severity of Internet addiction symptoms with reinforcement sensitivity, family factors, Internet activities, and attention-deficit/hyperactivity disorder (ADHD) symptoms among adolescents in Taiwan diagnosed with ADHD. A total of 287 adolescents diagnosed with ADHD and aged between 11 and 18 years participated in this study. Their levels of Internet addiction symptoms, ADHD symptoms, reinforcement sensitivity, family factors, and various Internet activities in which the participants engaged were assessed. The correlates of the severities of Internet addiction symptoms were determined using multiple regression analyses. The results indicated that low satisfaction with family relationships was the strongest factor predicting severe Internet addiction symptoms, followed by using instant messaging, watching movies, high Behavioral Approach System (BAS) fun seeking, and high Behavioral Inhibition System scores. Meanwhile, low paternal occupational SES, low BAS drive, and online gaming were also significantly associated with severe Internet addiction symptoms. Multiple factors are significantly associated with the severity of Internet addiction symptoms among adolescents with ADHD. Clinicians, educational professionals, and parents of adolescents with ADHD should monitor the Internet use of adolescents who exhibit the factors identified in this study.

  17. Hyperactive mTOR pathway promotes lymphoproliferation and abnormal differentiation in autoimmune lymphoproliferative syndrome.

    Science.gov (United States)

    Völkl, Simon; Rensing-Ehl, Anne; Allgäuer, Andrea; Schreiner, Elisabeth; Lorenz, Myriam Ricarda; Rohr, Jan; Klemann, Christian; Fuchs, Ilka; Schuster, Volker; von Bueren, André O; Naumann-Bartsch, Nora; Gambineri, Eleonora; Siepermann, Kathrin; Kobbe, Robin; Nathrath, Michaela; Arkwright, Peter D; Miano, Maurizio; Stachel, Klaus-Daniel; Metzler, Markus; Schwarz, Klaus; Kremer, Anita N; Speckmann, Carsten; Ehl, Stephan; Mackensen, Andreas

    2016-07-14

    Autoimmune lymphoproliferative syndrome (ALPS) is a human disorder characterized by defective Fas signaling, resulting in chronic benign lymphoproliferation and accumulation of TCRαβ(+) CD4(-) CD8(-) double-negative T (DNT) cells. Although their phenotype resembles that of terminally differentiated or exhausted T cells, lack of KLRG1, high eomesodermin, and marginal T-bet expression point instead to a long-lived memory state with potent proliferative capacity. Here we show that despite their terminally differentiated phenotype, human ALPS DNT cells exhibit substantial mitotic activity in vivo. Notably, hyperproliferation of ALPS DNT cells is associated with increased basal and activation-induced phosphorylation of serine-threonine kinases Akt and mechanistic target of rapamycin (mTOR). The mTOR inhibitor rapamycin abrogated survival and proliferation of ALPS DNT cells, but not of CD4(+) or CD8(+) T cells in vitro. In vivo, mTOR inhibition reduced proliferation and abnormal differentiation by DNT cells. Importantly, increased mitotic activity and hyperactive mTOR signaling was also observed in recently defined CD4(+) or CD8(+) precursor DNT cells, and mTOR inhibition specifically reduced these cells in vivo, indicating abnormal programming of Fas-deficient T cells before the DNT stage. Thus, our results identify the mTOR pathway as a major regulator of lymphoproliferation and aberrant differentiation in ALPS.

  18. Evaluating reading and metacognitive deficits in children and adolescents with attention deficit hyperactivity disorder.

    Science.gov (United States)

    Alvarado, Jesús Ma; Puente, Aníbal; Jiménez, Virginia; Arrebillaga, Lorena

    2011-05-01

    The reading achievement of children and adolescents with Attention Deficit Hyperactivity Disorder (ADHD) has scarcely been explored in research conducted in the Spanish language and when it has, the results have been contradictory. The focus of the present research is to analyze participants' reading competency and metacognitive strategies as they carry out reading comprehension tasks. The sample was comprised of 187 Argentine schoolchildren aged 9 to 13 years old. 94 constituted the control group and the clinical group consisted of 93 schoolchildren diagnosed with ADHD. The metacognitive assessment was made up of two metacognitive tests, the Reading Awareness Scale (ESCOLA; acronym in Spanish) and a Spanish adaptation of Metacognitive Awareness of Reading Strategies Inventory (MARSI), and one test of reading comprehension, the Evaluation of Reading Processes for Secondary Education Students (PROLEC-SE; acronym in Spanish). Students with ADHD had lower achievement on tests o reading comprehension compared to the control group. Nevertheless, our results suggest their difficulties did not stem from readin comprehension problems, but rather from alterations in their Executive Functions, because when subjects' reading comprehensio was equalized, students with ADHD still exhibited a lower level of Metacognition, particularly when it came to planning.

  19. Predictive coding in autism spectrum disorder and attention deficit hyperactivity disorder.

    Science.gov (United States)

    Gonzalez-Gadea, Maria Luz; Chennu, Srivas; Bekinschtein, Tristan A; Rattazzi, Alexia; Beraudi, Ana; Tripicchio, Paula; Moyano, Beatriz; Soffita, Yamila; Steinberg, Laura; Adolfi, Federico; Sigman, Mariano; Marino, Julian; Manes, Facundo; Ibanez, Agustin

    2015-11-01

    Predictive coding has been proposed as a framework to understand neural processes in neuropsychiatric disorders. We used this approach to describe mechanisms responsible for attentional abnormalities in autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). We monitored brain dynamics of 59 children (8-15 yr old) who had ASD or ADHD or who were control participants via high-density electroencephalography. We performed analysis at the scalp and source-space levels while participants listened to standard and deviant tone sequences. Through task instructions, we manipulated top-down expectation by presenting expected and unexpected deviant sequences. Children with ASD showed reduced superior frontal cortex (FC) responses to unexpected events but increased dorsolateral prefrontal cortex (PFC) activation to expected events. In contrast, children with ADHD exhibited reduced cortical responses in superior FC to expected events but strong PFC activation to unexpected events. Moreover, neural abnormalities were associated with specific control mechanisms, namely, inhibitory control in ASD and set-shifting in ADHD. Based on the predictive coding account, top-down expectation abnormalities could be attributed to a disproportionate reliance (precision) allocated to prior beliefs in ASD and to sensory input in ADHD.

  20. Overexpression of alpha-synuclein at non-toxic levels increases dopaminergic cell death induced by copper exposure via modulation of protein degradation pathways.

    Science.gov (United States)

    Anandhan, Annadurai; Rodriguez-Rocha, Humberto; Bohovych, Iryna; Griggs, Amy M; Zavala-Flores, Laura; Reyes-Reyes, Elsa M; Seravalli, Javier; Stanciu, Lia A; Lee, Jaekwon; Rochet, Jean-Christophe; Khalimonchuk, Oleh; Franco, Rodrigo

    2015-09-01

    Gene multiplications or point mutations in alpha (α)-synuclein are associated with familial and sporadic Parkinson's disease (PD). An increase in copper (Cu) levels has been reported in the cerebrospinal fluid and blood of PD patients, while occupational exposure to Cu has been suggested to augment the risk to develop PD. We aimed to elucidate the mechanisms by which α-synuclein and Cu regulate dopaminergic cell death. Short-term overexpression of wild type (WT) or mutant A53T α-synuclein had no toxic effect in human dopaminergic cells and primary midbrain cultures, but it exerted a synergistic effect on Cu-induced cell death. Cell death induced by Cu was potentiated by overexpression of the Cu transporter protein 1 (Ctr1) and depletion of intracellular glutathione (GSH) indicating that the toxic effects of Cu are linked to alterations in its intracellular homeostasis. Using the redox sensor roGFP, we demonstrated that Cu-induced oxidative stress was primarily localized in the cytosol and not in the mitochondria. However, α-synuclein overexpression had no effect on Cu-induced oxidative stress. WT or A53T α-synuclein overexpression exacerbated Cu toxicity in dopaminergic and yeast cells in the absence of α-synuclein aggregation. Cu increased autophagic flux and protein ubiquitination. Impairment of autophagy by overexpression of a dominant negative Atg5 form or inhibition of the ubiquitin/proteasome system (UPS) with MG132 enhanced Cu-induced cell death. However, only inhibition of the UPS stimulated the synergistic toxic effects of Cu and α-synuclein overexpression. Our results demonstrate that α-synuclein stimulates Cu toxicity in dopaminergic cells independent from its aggregation via modulation of protein degradation pathways.

  1. Dose-dependent striatal changes in dopaminergic terminals and alpha-synuclein reactivity in a porcine model of progressive Parkinson’s disease

    DEFF Research Database (Denmark)

    Nielsen, Mette Slot; Glud, Andreas Nørgaard; Møller, Arne

    2011-01-01

    of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and here present the neuropatholigical findings. Sixteen Göttingen minipigs were used in the study. Twelve were implanted subcutaneously with infusion pumps for continuous intramuscular chronic MPTP delivery for 11 weeks (4-18 mg MPTP/day, n=12...

  2. LARGE ANIMAL PARKINSONS DISEASE MODELS USING VIRAL VECTORS AND INOCULATION OF PREFORMED FIBRILS TO MEDIATE ALPHA-SYNUCLEIN OVEREXPRESSION AND MISFOLDING IN THE GOTTINGEN MINIPIG CNS

    DEFF Research Database (Denmark)

    Glud, Andreas Nørgaard; Landau, A.M.; Johnsen, Erik Lisbjerg

    2015-01-01

    and histology. Evaluation of gait, PET, autoradiography and histology are ongoing on AAV-models and awaiting on inoculation fibril-models. Discussion: We predict that these animal models will be useful and beneficial in the understanding of pathological mechanisms of human PD, novel therapeutic strategies...

  3. Alpha-synuclein oligomers and fibrils originate in two distinct conformer pools: a small angle X-ray scattering and ensemble optimisation modelling study.

    Science.gov (United States)

    Curtain, Cyril C; Kirby, Nigel M; Mertens, Haydyn D T; Barnham, Kevin J; Knott, Robert B; Masters, Colin L; Cappai, Roberto; Rekas, Agata; Kenche, Vijaya B; Ryan, Timothy

    2015-01-01

    The 140 residue intrinsically disordered protein α-synuclein (α-syn) self-associates to form fibrils that are the major constituent of the Lewy body intracellular protein inclusions, and neurotoxic oligomers. Both of these macromolecular structures are associated with a number of neurodegenerative diseases, including Parkinson's disease and dementia with Lewy bodies. Using ensemble optimisation modelling (EOM) and small angle X-ray scattering (SAXS) on a size-exclusion column equipped beamline, we studied how the distribution of structural conformers in α-syn may be influenced by the presence of the familial early-onset mutations A30P, E45K and A53T, by substituting the four methionine residues with alanines and by reaction with copper (Cu2+) or an anti-fibril organic platinum (Pt) complex. We found that the WT had two major conformer groups, representing ensembles of compact and extended structures. The population of the extended group was increased in the more rapidly fibril-forming E45K and A53T mutants, while the compact group was enlarged in the oligomer-forming A30P mutant. Addition of Cu2+ resulted in the formation of an ensemble of compact conformers, while the anti-fibril agent and alanine substitution substantially reduced the population of extended conformers. Since our observations with the mutants suggest that fibrils may be drawn from the extended conformer ensemble, we propose that the compact and extended ensembles represent the beginning of oligomer and fibril formation pathways respectively, both of which have been reported to lead to a toxic gain of function. Manipulating these pathways and monitoring the results by EOM and SAXS may be useful in the development of anti-Parkinson's disease therapies.

  4. Selective expression of alpha-synuclein-immunoreactivity in vesicular acetylcholine transporter-immunoreactive axons in the guinea pig rectum and human colon

    NARCIS (Netherlands)

    Sharrad, Dale F.; de Vries, Elsbeth; Brookes, Simon J. H.

    2013-01-01

    Parkinson's disease is a neurodegenerative disorder characterized by motor and nonmotor impairments, including constipation. The hallmark pathological features of Parkinson's disease are Lewy bodies and neurites, of which aggregated a-synuclein is a major constituent. Frequently, Lewy pathology is i

  5. Construction and expression of nucleic acid vaccine pVAXl-h-alpha S1-14o coding human alpha-synuclein

    Institute of Scientific and Technical Information of China (English)

    Jiacai Wang; Yingsong Ouyang; Shaojun Wang; Guoguang Peng; Qin Luo; Side Jiang; Faxiang Wang

    2008-01-01

    BACKGROUND: The deposition of α-synuclein (α-syn) aggregates is a neuropathological feature of Parkinson's disease. It remains impossible to involve α-syn aggregation in the treatment of Parkinson's disease. A nucleic acid vaccine will provide a new pathway to immunotherapy for Parkinson's disease.OBJECTIVE: To construct a recombinant eukaryotic expression vector pVAX1 coding human α-syn and to observe its expression level in COS-7 cells.DESIGN AND SETTING: The present bioengineering and molecular biology experiment was performed at Department of Neurology, First Affiliated Hospital of Chongqing Medical University & Chongqing Key Laboratory of Neurology.MATERIALS: The eukaryotic expression plasmid pVAX1, human embryonic brain tissue, healthy human blood cells, and COS-7 cells were purchased from Promega Company, USA.METHODS: The full-length CDS sequence of the human α-syn gene was amplified by RT-PCR, which contained restriction sites for the enzymes Kpn I, Xba I and Kozak consensus sequence. Then the PCR products and eukaryotic expression vector pVAX1 were digested with Kpn I and Xba I simultaneously, and were extracted and ligated by T4 ligase. The recombinant constructs pVAXI-hα-S1-14o were transformed into competent E. coli TOP 10 cells and the positive clones were screened and selected using PCR analysis,restriction digestion analysis, and DNA sequencing. The constructs were then tested for protein expression in COS-7 cells by RT-PCR and Western blotting.MAIN OUTCOME MEASURES: Identification of an eukaryotic expression vector containing the human α-syn gene, pVAX1-hα-S1-140, and detection of the expression in mammalian cell COS-7.RESULTS: The pVAXi vector was successfully cloned with human a -syn in the correct orientation and in-frame. The DNA vaccine constructs pVAX1-hα-S1-140 with the human α-syn gene were shown to be expressed in COS-7 cells. Human α-syn was successfully expressed in the mammalian cell line and was detected by RT-PCR and western blotting.CONCLUSION: Nucleic acid vaccine pVAX1-hα S1-140 was successfully constructed and expressed in COS-7 cells.

  6. A Comparative Study on the Visual Perceptions of Children with Attention Deficit Hyperactivity Disorder

    Science.gov (United States)

    Ahmetoglu, Emine; Aral, Neriman; Butun Ayhan, Aynur

    This study was conducted in order to (a) compare the visual perceptions of seven-year-old children diagnosed with attention deficit hyperactivity disorder with those of normally developing children of the same age and development level and (b) determine whether the visual perceptions of children with attention deficit hyperactivity disorder vary with respect to gender, having received preschool education and parents` educational level. A total of 60 children, 30 with attention deficit hyperactivity disorder and 30 with normal development, were assigned to the study. Data about children with attention deficit hyperactivity disorder and their families was collected by using a General Information Form and the visual perception of children was examined through the Frostig Developmental Test of Visual Perception. The Mann-Whitney U-test and Kruskal-Wallis variance analysis was used to determine whether there was a difference of between the visual perceptions of children with normal development and those diagnosed with attention deficit hyperactivity disorder and to discover whether the variables of gender, preschool education and parents` educational status affected the visual perceptions of children with attention deficit hyperactivity disorder. The results showed that there was a statistically meaningful difference between the visual perceptions of the two groups and that the visual perceptions of children with attention deficit hyperactivity disorder were affected meaningfully by gender, preschool education and parents` educational status.

  7. Concordance of actigraphy with polysomnography in children with and without attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Waldon, Jessica; Begum, Esmot; Gendron, Melissa; Rusak, Benjamin; Andreou, Pantelis; Rajda, Malgorzata; Corkum, Penny

    2016-10-01

    This study sought to: (1) compare actigraphy-derived estimated sleep variables to the same variables based on the gold-standard of sleep assessment, polysomnography; (2) examine whether the correlations between the measures differ between children with attention-deficit/hyperactivity disorder and typically developing children; and (3) determine whether these correlations are altered when children with attention-deficit/hyperactivity disorder are treated with medication. Participants (24 attention-deficit/hyperactivity disorder; 24 typically developing), aged 6-12 years, completed a 1-week baseline assessment of typical sleep and daytime functioning. Following the baseline week, participants in the attention-deficit/hyperactivity disorder group completed a 4-week blinded randomized control trial of methylphenidate hydrochloride, including a 2-week placebo and 2-week methylphenidate hydrochloride treatment period. At the end of each observation (typically developing: baseline; attention-deficit/hyperactivity disorder: baseline, placebo and methylphenidate hydrochloride treatment), all participants were invited to a sleep research laboratory, where overnight polysomnography and actigraphy were recorded concurrently. Findings from intra-class correlations and Bland-Altman plots were consistent. Actigraphy was found to provide good estimates (e.g. intra-class correlations >0.61) of polysomnography results for sleep duration for all groups and conditions, as well as for sleep-onset latency and sleep efficiency for the typically developing group and attention-deficit/hyperactivity disorder group while on medication, but not for the attention-deficit/hyperactivity disorder group during baseline or placebo. Based on the Bland-Altman plots, actigraphy tended to underestimate for sleep duration (8.6-18.5 min), sleep efficiency (5.6-9.3%) and sleep-onset latency, except for attention-deficit/hyperactivity disorder during placebo in which actigraphy overestimated (-2.1 to 6

  8. The nucleus accumbens 5-HTR₄-CART pathway ties anorexia to hyperactivity.

    Science.gov (United States)

    Jean, A; Laurent, L; Bockaert, J; Charnay, Y; Dusticier, N; Nieoullon, A; Barrot, M; Neve, R; Compan, V

    2012-12-11

    In mental diseases, the brain does not systematically adjust motor activity to feeding. Probably, the most outlined example is the association between hyperactivity and anorexia in Anorexia nervosa. The neural underpinnings of this 'paradox', however, are poorly elucidated. Although anorexia and hyperactivity prevail over self-preservation, both symptoms rarely exist independently, suggesting commonalities in neural pathways, most likely in the reward system. We previously discovered an addictive molecular facet of anorexia, involving production, in the nucleus accumbens (NAc), of the same transcripts stimulated in response to cocaine and amphetamine (CART) upon stimulation of the 5-HT(4) receptors (5-HTR(4)) or MDMA (ecstasy). Here, we tested whether this pathway predisposes not only to anorexia but also to hyperactivity. Following food restriction, mice are expected to overeat. However, selecting hyperactive and addiction-related animal models, we observed that mice lacking 5-HTR(1B) self-imposed food restriction after deprivation and still displayed anorexia and hyperactivity after ecstasy. Decryption of the mechanisms showed a gain-of-function of 5-HTR(4) in the absence of 5-HTR(1B), associated with CART surplus in the NAc and not in other brain areas. NAc-5-HTR(4) overexpression upregulated NAc-CART, provoked anorexia and hyperactivity. NAc-5-HTR(4) knockdown or blockade reduced ecstasy-induced hyperactivity. Finally, NAc-CART knockdown suppressed hyperactivity upon stimulation of the NAc-5-HTR(4). Additionally, inactivating NAc-5-HTR(4) suppressed ecstasy's preference, strengthening the rewarding facet of anorexia. In conclusion, the NAc-5-HTR(4)/CART pathway establishes a 'tight-junction' between anorexia and hyperactivity, suggesting the existence of a primary functional unit susceptible to limit overeating associated with resting following homeostasis rules.

  9. Childhood hyperactivity, physical aggression and criminality: a 19-year prospective population-based study.

    Directory of Open Access Journals (Sweden)

    Jean-Baptiste Pingault

    Full Text Available BACKGROUND: Research shows that children with Attention Deficit/Hyperactivity Disorder are at elevated risk of criminality. However, several issues still need to be addressed in order to verify whether hyperactivity in itself plays a role in the prediction of criminality. In particular, co-occurrence with other behaviors as well as the internal heterogeneity in ADHD symptoms (hyperactivity and inattention should be taken into account. The aim of this study was to assess the unique and interactive contributions of hyperactivity to the development of criminality, whilst considering inattention, physical aggression and family adversity. METHODOLOGY/PRINCIPAL FINDINGS: We monitored the development of a population-based sample of kindergarten children (N = 2,741. Hyperactivity, inattention, and physical aggression were assessed annually between the ages of 6 and 12 years by mothers and teachers. Information on the presence, the age at first charge and the type of criminal charge was obtained from official records when the participants were aged 25 years. We used survival analysis models to predict the development of criminality in adolescence and adulthood: high childhood hyperactivity was highly predictive when bivariate analyses were used; however, with multivariate analyses, high hyperactivity was only marginally significant (Hazard Ratio: 1.38; 95% CI: 0.94-2.02. Sensitivity analyses revealed that hyperactivity was not a consistent predictor. High physical aggression was strongly predictive (Hazard Ratio: 3.44; 95% CI: 2.43-4.87 and its role was consistent in sensitivity analyses and for different types of crime. Inattention was not predictive of later criminality. CONCLUSIONS/SIGNIFICANCE: Although the contribution of childhood hyperactivity to criminality may be detected in large samples using multi-informant longitudinal designs, our results show that it is not a strong predictor of later criminality. Crime prevention should instead target

  10. Generation of mice lacking DUF1220 protein domains: effects on fecundity and hyperactivity.

    Science.gov (United States)

    Keeney, J G; O'Bleness, M S; Anderson, N; Davis, J M; Arevalo, N; Busquet, N; Chick, W; Rozman, J; Hölter, S M; Garrett, L; Horsch, M; Beckers, J; Wurst, W; Klingenspor, M; Restrepo, D; de Angelis, M Hrabě; Sikela, J M

    2015-02-01

    Sequences encoding DUF1220 protein domains show the most extreme human lineage-specific copy number increase of any coding region in the genome and have been linked to human brain evolution. In addition, DUF1220 copy number (dosage) has been implicated in influencing brain size within the human species, both in normal populations and in individuals associated with brain size pathologies (1q21-associated microcephaly and macrocephaly). More recently, increasing dosage of a subtype of DUF1220 has been linked with increasing severity of the primary symptoms of autism. Despite these intriguing associations, a function for these domains has not been described. As a first step in addressing this question, we have developed the first transgenic model of DUF1220 function by removing the single DUF1220 domain (the ancestral form) encoded in the mouse genome. In a hypothesis generating exercise, these mice were evaluated by 197 different phenotype measurements. While resulting DUF1220-minus (KO) mice show no obvious anatomical peculiarities, they exhibit a significantly reduced fecundity (χ(2) = 19.1, df = 2, p = 7.0 × 10(-5)). Further extensive phenotypic analyses suggest hyperactivity (p < 0.05) of DUF1220 mice and changes in gene expression levels of brain associated with distinct neurological functions and disease. Other changes that met statistical significance include an increase in plasma glucose concentration (as measured by area under the curve, AUC 0-30 and AUC 30-120) in male mutants, fasting glucose levels, reduce sodium levels in male mutants, increased levels of the liver functional indicator ALAT/GPT in males, levels of alkaline phosphatase (also an indicator of liver function), mean R and SR amplitude by electrocardiography, elevated IgG3 levels, a reduced ratio of CD4:CD8 cells, and a reduced frequency of T cells; though it should be noted that many of these differences are quite small and require further examination. The linking of DUF1220 loss to a

  11. Active Cyber Defense Dynamics Exhibiting Rich Phenomena

    CERN Document Server

    Zheng, Ren; Xu, Shouhuai

    2016-01-01

    The Internet is a man-made complex system under constant attacks (e.g., Advanced Persistent Threats and malwares). It is therefore important to understand the phenomena that can be induced by the interaction between cyber attacks and cyber defenses. In this paper, we explore the rich phenomena that can be exhibited when the defender employs active defense to combat cyber attacks. To the best of our knowledge, this is the first study that shows that {\\em active cyber defense dynamics} (or more generally, {\\em cybersecurity dynamics}) can exhibit the bifurcation and chaos phenomena. This has profound implications for cyber security measurement and prediction: (i) it is infeasible (or even impossible) to accurately measure and predict cyber security under certain circumstances; (ii) the defender must manipulate the dynamics to avoid such {\\em unmanageable situations} in real-life defense operations.

  12. Exhibition: Women and Sciences by Fiami

    CERN Multimedia

    Globe Info

    2011-01-01

    The 19-panel exhibition is on display at CERN's Microcosm from Monday to Saturday from 10.00 a.m. to 5.00 p.m.   Marie Curie won the Nobel Prize for Chemistry one hundred years ago. She is the only woman ever to win two Nobel Prizes, which is a testament to her remarkable work. But throughout history, women have played a role in science either in their own right or alongside other scientists. In this special exhibition, the comic-strip artist Fiami takes a look back at the relationship between women and science through his portraits of Mileva Einstein, Marie-Anne Lavoisier and, of course, Marie Curie. Fiami has recently published an entire album devoted to Marie Curie. Texts in French All ages - Entrance free Femmes et Sciences is on display at Microcosm: From Wednesday 21 September 2011 to Tuesday 20 December 2011.

  13. Ikuo Hirayama Painting Exhibition Held in Beijing

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    <正>To celebrate the 30th anniversary of the signing of the Sino-Japanese Peace and Friendship Treaty, the Ikuo Hirayama Painting Exhibition jointly sponsored by the China-Japan Friendship Association (CJFA), the China International Culture Association (CICA) and the Japan-China Friendship Association (JCFA), was held in the National Art Museum of China from April 17 to 26. At the invitation of the CJFA, Tomiichi Murayama, former Japanese prime minister, and Ikuo Hirayama, president of the JCFA and famous painter, who led a delegation of over 200 people of various circles, paid a visit to China to attend the opening ceremony of the exhibition and take part in the relevant activities from April 16 to 20.

  14. The palaeontological exhibition: a venue for dialogue.

    Science.gov (United States)

    Murriello, Sandra

    2015-01-01

    Understanding the dialogue between museums and their visitors enables museums to subsist, undergo transformations and become consolidated as socially valued cultural venues. The Museo de La Plata (Argentina) was created in the late nineteenth century as a natural history museum, and this study shows that currently the museum is valued socially as a venue for family leisure and education, at which people make sense to the objects exhibited through characteristics conferred upon them by both the institution and the visitor. Nevertheless, such dialogue is somehow affected by the museographic proposal and the public interpretation of the institutional narrative, which could be analysed within the frame of contextual learning. As a consequence, the evolutionary idea that the museum aims to communicate is distorted by the public. This article highlights the importance of considering the visitors' interpretations when planning museum exhibitions, a perspective that has been rather absent in the Argentinian museums.

  15. LHC INAUGURATION, LHC Fest highlights: exhibition time!

    CERN Multimedia

    2008-01-01

    David Gross, one of the twenty-one Nobel Laureates who have participated in the project.Tuesday 21 October 2008 Accelerating Nobels Colliding Charm, Atomic Cuisine, The Good Anomaly, A Quark Somewhere on the White Paper, Wire Proliferation, A Tale of Two Liquids … these are just some of the titles given to artworks by Physics Nobel Laureates who agreed to make drawings of their prize-winning discoveries (more or less reluctantly) during a special photo session. Science photographer Volker Steger made portraits of Physics Nobel Laureates and before the photo sessions he asked them to make a drawing of their most important discovery. The result is "Accelerating Nobels", an exhibition that combines unusual portraits of and original drawings by twenty-one Nobel laureates in physics whose work is closely related to CERN and the LHC. This exhibition will be one of the highlights of the LHC celebrations on 21 October in the SM18 hall b...

  16. CERN's new microcosm exhibition is now open

    CERN Multimedia

    2016-01-01

    After a major revamp in 2015, CERN’s microcosm exhibition is once again open to visitors. The exhibition is free and open to all without reservation and visitors are encouraged to share their #microcosm @CERN experiences on social media. Read more: http://cern.ch/go/7HWC -Producer- CERN Video Productions -Director- Kate Kahle -Camera- indissoluble.com and Julien Ordan -Editor- Julien Ordan -Infography- Daniel Dominguez Noemi Caraban -Music- “Light Years” by Stellardrone http://freemusicarchive.org/music/Ste... You can follow us on: cern.ch youtube.com/cerntv google.com/+CERN facebook.com/cern twitter.com/cern/ linkedin.com/company/cern instagram.com/cern Copyright © 2016 CERN. Terms of use: http://copyright.web.cern.ch/

  17. Pingyao Traditional Cultural Exhibition Mounted in France

    Institute of Scientific and Technical Information of China (English)

    Ni; Yuan

    2014-01-01

    <正>On the initiative of Provins,a commune in the Nord Department of Northern France and a friendship city of Pingyao in Shanxi Province,an exhibition of Pingyao traditional cultural and art works was staged from June 14 to 17.On display in the ancient SaintQuiriace Collegiate Church were 40 artworks characteristic of the traditional folk art of North China including old photos of Pingyao,calligraphic works,paintings,paper-cut,embroidery and shadow puppets.

  18. Cinema Film Distribution and Exhibition in Ireland

    OpenAIRE

    O'Donnell, Damien

    1992-01-01

    This study of cinema film distribution and exhibition practices In Ireland examines key aspects of the Industry: firstly, the basic mechanics of the Industry and Its operations: secondly, the various alignments between exhibitors and distributors and consequences of those alignments: thirdly, the impact of the arrival of British multiplex companies: fourthly, the costs of film censorship; and finally, the idea of an 'art-house' circuit In Ireland.

  19. Synchronization in multicell systems exhibiting dynamic plasticity

    Indian Academy of Sciences (India)

    C Suguna; Somdatta Sinha

    2008-08-01

    Collective behaviour in multicell systems arises from exchange of chemicals/signals between cells and may be different from their intrinsic behaviour. These chemicals are products of regulated networks of biochemical pathways that underlie cellular functions, and can exhibit a variety of dynamics arising from the non-linearity of the reaction processes. We have addressed the emergent synchronization properties of a ring of cells, diffusively coupled by the end product of an intracellular model biochemical pathway exhibiting non-robust birhythmic behaviour. The aim is to examine the role of intercellular interaction in stabilizing the non-robust dynamics in the emergent collective behaviour in the ring of cells. We show that, irrespective of the inherent frequencies of individual cells, depending on the coupling strength, the collective behaviour does synchronize to only one type of oscillations above a threshold number of cells. Using two perturbation analyses, we also show that this emergent synchronized dynamical state is fairly robust under external perturbations. Thus, the inherent plasticity in the oscillatory phenotypes in these model cells may get suppressed to exhibit collective dynamics of a single type in a multicell system, but environmental influences can sometimes expose this underlying plasticity in its collective dynamics.

  20. Exhibition: Linus Pauling and the Twentieth Century

    CERN Multimedia

    2003-01-01

    On April 28 the exhibit Linus Pauling and the Twentieth Century organised by UNIDIR (United Nations Institute for Disarmament Research) and SGI (Soka Gakkai International) as well as with the contributions of CERN and the University of Geneva, opens at the United Nations Office of Geneva. Linus Pauling is the only person to date to have won two unshared Nobel Prizes: Chemistry in 1954 and Peace in 1962. The first was awarded for his landmark research on the nature of the chemical bond and its application in understanding the structure of complex substances. The second one acknowledged his courageous protest against atmospheric nuclear testing and his championship of international peace. The exhibit, for all ages' audiences, traces seven decades of Linus Pauling's life and influence on the 20th century. Before starting its European tour at the UNESCO headquarters in Paris, the exhibit opened in 1998 in San Francisco and then travelled within the United-States and to Japan with an attendance of more than one m...

  1. Exhibition: Linus Pauling and the Twentieth Century

    CERN Multimedia

    2003-01-01

    On April 28 the exhibit Linus Pauling and the Twentieth Century organised by UNIDIR (United Nations Institute for Disarmament Research) and SGI (Soka Gakkai International) as well as with the contributions of CERN and the University of Geneva, opened at the United Nations Office of Geneva. Linus Pauling is the only person to date to have won two unshared Nobel Prizes: Chemistry in 1954 and Peace in 1962. The first was awarded for his landmark research on the nature of the chemical bond and its application in understanding the structure of complex substances. The second one acknowledged his courageous protest against atmospheric nuclear testing and his championship of international peace. The exhibit, for audience of all ages, traces seven decades of Linus Pauling's life and influence on the 20th century. Before starting its European tour at the UNESCO headquarters in Paris, the exhibit opened in 1998 in San Francisco and then travelled within the United-States and to Japan with an attendance of more than one...

  2. Exhibition: Dialogue between Science and religion

    CERN Multimedia

    2001-01-01

    Can the theory of the Big Bang reached by physicists and the concept of creation beloved of religion ever be reconciled? The two approaches have at least one point in common: they do not provide a final answer to the mysteries of the birth of the Universe. And this means that dialogue is alays possible between the two. It is to show the potential of such an exchange that Geneva's Société Evangélique organization is opening an exhibition under the title 'Big Bang and Creation', at the Planète Charmilles shopping centre, to run from 19 to 30 March. View of the 'Big Bang and Creation' exhibition. The exhibition is divided into three sections, showing the views of the scientist and those of the believer without setting them up in opposition to one another. In the first section, under a representation of the vault of heaven, the visitor will discover the different ideas explaining the birth of the Universe: Genesis and the Big Bang, and the different dominant theories ...

  3. Mice lacking TrkB in parvalbumin-positive cells exhibit sexually dimorphic behavioral phenotypes.

    Science.gov (United States)

    Lucas, Elizabeth K; Jegarl, Anita; Clem, Roger L

    2014-11-01

    Activity-dependent brain-derived neurotrophic factor (BDNF) signaling through receptor tyrosine kinase B (TrkB) is required for cued fear memory consolidation and extinction. Although BDNF is primarily secreted from glutamatergic neurons, TrkB is expressed by other genetically defined cells whose contributions to the behavioral effects of BDNF remain poorly understood. Parvalbumin (PV)-positive interneurons, which are highly enriched in TrkB, are emerging as key regulators of fear memory expression. We therefore hypothesized that activity-dependent BDNF signaling in PV-interneurons may modulate emotional learning. To test this hypothesis, we utilized the LoxP/Cre system for conditional deletion of TrkB in PV-positive cells to examine the impact of cell-autonomous BDNF signaling on Pavlovian fear conditioning and extinction. However, behavioral abnormalities indicative of vestibular dysfunction precluded the use of homozygous conditional knockouts in tests of higher cognitive functioning. While vestibular dysfunction was apparent in both sexes, female conditional knockouts exhibited an exacerbated phenotype, including extreme motor hyperactivity and circling behavior, compared to their male littermates. Heterozygous conditional knockouts were spared of vestibular dysfunction. While fear memory consolidation was unaffected in heterozygotes of both sexes, males exhibited impaired extinction consolidation compared to their littermate controls. Our findings complement evidence from human and rodent studies suggesting that BDNF signaling promotes consolidation of extinction and point to PV-positive neurons as a discrete population that mediates these effects in a sex-specific manner.

  4. Methylphenidate use in children with attention deficit hyperactivity disorder

    Science.gov (United States)

    Machado, Felipe Salles Neves; Caetano, Sheila Cavalcante; Hounie, Ana Gabriela; Scivoletto, Sandra; Muszkat, Mauro; Gattás, Ivete Gianfaldoni; Casella, Erasmo Barbante; de Andrade, Ênio Roberto; Polanczyk, Guilherme Vanoni; do Rosário, Maria Conceição

    2015-01-01

    A Brazilian Health Technology Assessment Bulletin (BRATS) article regarding scientific evidence of the efficacy and safety of methylphenidate for treating attention deficit hyperactivity disorder (ADHD) has caused much controversy about its methods. Considering the relevance of BRATS for public health in Brazil, we critically reviewed this article by remaking the BRATS search and discussing its methods and results. Two questions were answered: did BRATS include all references available in the literature? Do the conclusions reflect the reviewed articles? The results indicate that BRATS did not include all the references from the literature on this subject and also that the proposed conclusions are different from the results of the articles chosen by the BRATS authors themselves. The articles selected by the BRATS authors showed that using methylphenidate is safe and effective. However, the BRATS final conclusion does not reflect the aforementioned and should not be used to support decisions on the use of methylphenidate. PMID:26061456

  5. Updates on attention-deficit/hyperactivity disorder and learning disorders.

    Science.gov (United States)

    Semrud-Clikeman, Margaret; Bledsoe, Jesse

    2011-10-01

    The relationship of attention-deficit/hyperactivity disorder (ADHD) to learning disorders was reviewed and included reading disability, mathematics learning disability, and nonverbal learning disability. Genetic, neuroimaging, and neuropsychological functioning were examined for each disorder, along with a discussion of any existing literature when ADHD co-occurred with the disorder. All the disorders were found to frequently co-occur with ADHD. A review of the underlying neuroanatomic and neurofunctional data found specific structures that frequently co-occur in these disorders with others that are specific to the individual diagnosis. Aberrations in structure and/or function were found for the caudate, corpus callosum, and cerebellum, making these structures sensitive for the disorder but not specific. Suggestions for future research, particularly in relation to intervention, are provided.

  6. Attention-deficit/hyperactivity disorder and telemental health.

    Science.gov (United States)

    Palmer, Nancy B; Myers, Kathleen M; Vander Stoep, Ann; McCarty, Carolyn A; Geyer, John R; Desalvo, Amy

    2010-10-01

    Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent psychiatric disorders diagnosed in children and adolescents (youth). ADHD is equally distributed geographically, but services are not. Access to expert evaluation and treatment remains limited for youth with ADHD living in rural areas, as well as for ethnic and racial minority youth. Telepsychiatry is a service delivery model with the potential to reach these youth and to develop collaborative models of care among local primary care physicians, remote telepsychiatrists, and local families. Care delivered through telepsychiatry can readily adhere to the practice parameters of the American Academy of Child and Adolescent Psychiatry. Work to date indicates that ADHD is the most common disorder treated through telepsychiatry. This article reviews the status of child and adolescent telepsychiatry, with particular focus on its potential to improve the care and outcomes of underserved populations of youth diagnosed with ADHD.

  7. Attention-deficit/hyperactivity disorder genomics: update for clinicians.

    Science.gov (United States)

    Elia, Josephine; Sackett, Jillan; Turner, Terri; Schardt, Martin; Tang, Shih-Ching; Kurtz, Nicole; Dunfey, Maura; McFarlane, Nadia A; Susi, Aita; Danish, David; Li, Alice; Nissley-Tsiopinis, Jenelle; Borgmann-Winter, Karin

    2012-10-01

    Attention deficit, hyperactivity disorder (ADHD) is familial and highly heritable. Several candidate genes involved in neurotransmission have been identified, however these confer minimal risk, suggesting that for the most part, ADHD is not caused by single common genetic variants. Advances in genotyping enabling investigation at the level of the genome have led to the discovery of rare structural variants suggesting that ADHD is a genomic disorder, with potentially thousands of variants, and common neuronal pathways disrupted by numerous rare variants resulting in similar ADHD phenotypes. Heritability studies in humans also indicate the importance of epigenetic factors, and animal studies are deciphering some of the processes that confer risk during gestation and throughout the post-natal period. These and future discoveries will lead to improved diagnosis, individualized treatment, cures, and prevention. These advances also highlight ethical and legal issues requiring management and interpretation of genetic data and ensuring privacy and protection from misuse.

  8. Attention-deficit/hyperactivity disorder and adverse health outcomes

    Science.gov (United States)

    Nigg, Joel

    2015-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is defined by extreme levels of inattention–disorganization and/or hyperactivity–impulsivity. In DSM-IV, the diagnostic criteria required impairment in social, academic, or occupational functioning. With DSM-5 publication imminent in 2013, further evaluation of impairment in ADHD is timely. This article reviews the current state of knowledge on health-related impairments of ADHD, including smoking, drug abuse, accidental injury, sleep, obesity, hypertension, diabetes, and suicidal behavior. It concludes by suggesting the need for new avenues of research on mechanisms of association and the potential for ADHD to be an early warning sign for secondary prevention of some poor health outcomes. PMID:23298633

  9. Methylphenidate use in children with attention deficit hyperactivity disorder

    Directory of Open Access Journals (Sweden)

    Felipe Salles Neves Machado

    2015-01-01

    Full Text Available A Brazilian Health Technology Assessment Bulletin (BRATS article regarding scientific evidence of the efficacy and safety of methylphenidate for treating attention deficit hyperactivity disorder (ADHD has caused much controversy about its methods. Considering the relevance of BRATS for public health in Brazil, we critically reviewed this article by remaking the BRATS search and discussing its methods and results. Two questions were answered: did BRATS include all references available in the literature? Do the conclusions reflect the reviewed articles? The results indicate that BRATS did not include all the references from the literature on this subject and also that the proposed conclusions are different from the results of the articles chosen by the BRATS authors themselves. The articles selected by the BRATS authors showed that using methylphenidate is safe and effective. However, the BRATS final conclusion does not reflect the aforementioned and should not be used to support decisions on the use of methylphenidate.

  10. Handwriting performance in children with attention deficit hyperactivity disorder (ADHD).

    Science.gov (United States)

    Racine, Marie Brossard; Majnemer, Annette; Shevell, Michael; Snider, Laurie

    2008-04-01

    Attention deficit hyperactivity disorder (ADHD) is the most common neurobehavioral condition of childhood. Consequences are multifaceted and include activity limitations in daily-living skills, academic challenges, diminished socialization skills, and motor difficulties. Poor handwriting performance is an example of an affected life skill that has been anecdotally observed by educators and clinicians for this population and can negatively impact academic performance and self-esteem. To guide health and educational service delivery needs, the authors reviewed the evidence in the literature on handwriting difficulties in children with ADHD. Existing evidence would suggest that children with ADHD have impaired handwriting performance, characterized by illegible written material and/or inappropriate speed of execution compared to children without ADHD. Studies with larger sample sizes using standardized measures of handwriting performance are needed to evaluate the prevalence of the problem and to better understand the nature of handwriting difficulties and their impact in this population.

  11. Cognitive control in adults with attention-deficit/hyperactivity disorder

    DEFF Research Database (Denmark)

    Dramsdahl, Margaretha; Westerhausen, René; Haavik, Jan

    2011-01-01

    The objective of the present study was to investigate the ability of adults with Attention-Deficit/Hyperactivity Disorder (ADHD) to direct their attention and exert cognitive control in a forced instruction dichotic listening (DL) task. The performance of 29 adults with ADHD was compared with 58......-forced condition), or to focus and report either the right- or left-ear syllable (forced-right and forced-left condition). This procedure is presumed to tap distinct cognitive processes: perception (non-forced condition), orienting of attention (forced-right condition), and cognitive control (forced-left condition......). Adults with ADHD did not show significant impairment in the conditions tapping perception and attention orientation, but were significantly impaired in their ability to report the left-ear syllable during the forced-left instruction condition, whereas the control group showed the expected left...

  12. Attention-deficit/hyperactivity disorder in postsecondary students.

    Science.gov (United States)

    Nugent, Kevin; Smart, Wallace

    2014-01-01

    A PubMed review was conducted for papers reporting on attention-deficit/hyperactivity disorder (ADHD) in postsecondary students. The review was performed in order to determine the prevalence and symptomatology of ADHD in postsecondary students, to examine its effects on academic achievement, and discuss appropriate management. The prevalence of ADHD symptoms among postsecondary students ranges from 2% to 12%. Students with ADHD have lower grade point averages and are more likely to withdraw from courses, to indulge in risky behaviors, and to have other psychiatric comorbidities than their non-ADHD peers. Ensuring that students with ADHD receive appropriate support requires documented evidence of impairment to academic and day-to-day functioning. In adults with ADHD, stimulants improve concentration and attention, although improved academic productivity remains to be demonstrated. ADHD negatively impacts academic performance in students and increases the likelihood of drug and alcohol problems. Affected students may therefore benefit from disability support services, academic accommodations, and pharmacological treatment.

  13. Attention deficit hyperactivity disorder in imprisoned individuals--a review.

    Science.gov (United States)

    Ghanizadeh, Ahmad; Mohammadi, Mohammad Reza; Akhondzadeh, Shahin; Sanaei-Zadeh, Hossein

    2011-06-01

    Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent psychiatric disorders with lifelong impact of the affected individuals. It is usually co-morbid with other psychiatric disorders. This paper aims to review current knowledge about ADHD in imprisoned individuals. The rate of ADHD in prisoners ranges from 10% to 70% and it has been suggested that ADHD, even without co-morbidity with conduct disorder, is a risk factor for imprisonment. Based on these findings, it may be wise to include the assessment of ADHD symptoms in all adult and adolescent prisoners. This is while available psychiatric resources for the adequate management of ADHD in prisoners are limited. Most of current knowledge on the topic comes from western countries. There is an urgent need for studies that will explore the effect of other cultures on the interactions between ADHD and imprisonment, especially in developing countries worldwide. At this point, ADHD seems to be an ignored research area in developing countries.

  14. Attention deficit hyperactivity disorder (ADHD): a practical scale for pediatricians.

    Science.gov (United States)

    Oktem, F; Semerci, Z B

    1998-01-01

    Attention deficit hyperactivity disorder (ADHD) is a common disturbance causing school failure and social problems. Early diagnosis and intervention allow ADHD children to adjust and succeed at school and in daily life. To identify these patients, we designed a practical questionnaire for parents. When tested on children with ADHD (n = 100), children with psychiatric problems (n = 35), and on age- and sex-mached control children (n = 100), this scale was found to be highly useful in distinguishing these three groups from each other, especially after the identification and elimination of items with lower specificity. The use of the Hacettepe ADHD scale is recommended for pediatricians, general practitioners and teachers to allow earlier diagnosis of this condition.

  15. Attention-deficit/hyperactivity disorder: associations with overeating and obesity.

    Science.gov (United States)

    Davis, Caroline

    2010-10-01

    In the past decade, we have become increasingly aware of strong associations between overweight/obesity and symptoms of attention-deficit/hyperactivity disorder (ADHD) in children, adolescents, and adults. This review addresses the prevalence of the comorbidity and discusses some of the mechanisms that could account for their relationship. It is suggested that the inattentive and impulsive behaviors that characterize ADHD could contribute to overeating in our current food environment, with its emphasis on fast food consumption and its many food temptations. It is also proposed-based on the compelling evidence that foods high in fat, sugar, and salt are as addictive as some drugs of abuse-that excessive food consumption could be a form of self-medication. This view conforms with the well-established evidence that drug use and abuse are substantially higher among those with ADHD than among the general population.

  16. [Psychotherapy in children with attention deficit hyperactivity disorder].

    Science.gov (United States)

    George, Gisèle

    2002-11-15

    Alone or used with psychostimulants, psychotherapy is the keystone of the treatment in children attention deficit disorder hyperactivity (ADHD). This article explains in which matter psychotherapy is essential. To be well done, it's necessary before starting the treatment to analyze precisely the disorder and how it interferes with the child's environment. It describes how this functional analysis must be done in order to be more precise in the choice of the treatment objectives. This article explains why in children ADHD treatment, the individual therapy must be associated with a family training and describes briefly the more studied and recognized psychotherapy techniques in those children ADHD and how other partners (teacher, speech or motor therapist) are also useful.

  17. Mars in their eyes - a cartoon exhibition

    Science.gov (United States)

    Pillinger, Pi.

    Recently a collection of 120 cartoons which tell the story of Mars exploration and scientific discovery, past, present and future, was held in London. We discuss the aims of the exhibition, to what extent we believe the original aims were met and report on additional outreach opportunities resulting from the project. The overriding aim was to capitalise on the popular appeal of accessible art - most people admit to enjoying cartoons. This was strengthened by hanging the originals of cartoons which had, mostly, been published in newspapers and magazines in a wide selection of countries. The provenances served to indicate the attraction of Mars to a wide public. We were fortunate to work with the Cartoon Art Trust of the UK who was in the process of relocating to new premises and opening as The Cartoon Museum, in the tourist area of Bloomsbury, central London, very close to the British Museum. "Mars in their Eyes" ran for 10 weeks during April to July 2006; immediately following which a selection of the cartoons was displayed at the week-long Royal Society Summer Exhibition. We explore the differences between the two exhibitions and comment on the various audience responses. We use this comparison to discuss whether a project which is primarily art can be extended to explain science. Does the coupling merely result in dumbing-down of both cultures or is there a true synergy? The experience has led us to coin the phrase "extreme outreach". Projects which are as ambitious as "Mars in their Eyes", without the security of a safe, captive audience, for example at a Science Centre, must be judged by different criteria. Indeed if the project does not meet comparable targets like large visitor numbers, then the honest evaluation of such details can only inform future activities and must not be reflected in the future funding of only "safe" outreach activities.

  18. Art Therapy Exhibitions: Exploitation or Advocacy?

    Science.gov (United States)

    Davis, Terri

    2017-01-01

    Promoting awareness of human trafficking by sharing trauma survivors' art and summaries of their life stories suggests ethical complexities that have been typically neglected by bioethicists. Although these survivors voluntarily share the objects they created during art therapy sessions, they are still at risk of harm, including further exploitation, due to their vulnerability, high rates of victim sensitivity, and the mental health consequences of their traumatic experiences. While some argue that the benefits of sublimation and art therapy for human trafficking survivors make sharing their art worth the risk, anti-trafficking organizations and supporters of such art exhibitions have responsibilities to be trauma informed.

  19. Library exhibits and programs boost science education

    Science.gov (United States)

    Dusenbery, Paul B.; Curtis, Lisa

    2012-05-01

    Science museums let visitors explore and discover, but for many families there are barriers—such as cost or distance—that prevent them from visiting museums and experiencing hands-on science, technology, engineering, and mathematics (STEM) learning. Now educators are reaching underserved audiences by developing STEM exhibits and programs for public libraries. With more than 16,000 outlets in the United States, public libraries serve almost every community in the country. Nationwide, they receive about 1.5 billion visits per year, and they offer their services for free.

  20. Abnormal amygdala functional connectivity associated with emotional lability in children with attention-deficit/hyperactivity disorder

    NARCIS (Netherlands)

    Hulvershorn, L.A.; Mennes, M.; Castellanos, F.X.; Martino, A. Di; Milham, M.P.; Hummer, T.A.; Roy, A.K.

    2014-01-01

    OBJECTIVE: A substantial proportion of children with attention-deficit/hyperactivity disorder (ADHD) also display emotion regulation deficits manifesting as chronic irritability, severe temper outbursts, and aggression. The amygdala is implicated in emotion regulation, but its connectivity and relat

  1. Attentional Lapses of Adults with Attention Deficit Hyperactivity Disorder in Tasks of Sustained Attention

    NARCIS (Netherlands)

    Gmehlin, Dennis; Fuermaier, Anselm B.M.; Walther, Stephan; Tucha, Lara; Koerts, Janneke; Lange, Klaus W.; Tucha, Oliver; Weisbrod, Matthias; Aschenbrenner, Steffen

    2016-01-01

    Adults with attention deficit hyperactivity disorder (ADHD) show attentional dysfunction such as distractibility and mind-wandering, especially in lengthy tasks. However, fundamentals of dysfunction are ambiguous and relationships of neuropsychological test parameters with self-report measures of AD

  2. Dopamine Transporter Genotype Conveys Familial Risk of Attention-Deficit/Hyperactivity Disorder through Striatal Activation

    Science.gov (United States)

    Durston, Sarah; Fossella, John A.; Mulder, Martijn J.; Casey B. J.; Ziermans, Tim B.; Vessaz, M. Nathalie; Van Engeland, Herman

    2008-01-01

    The study examines the effect of the dopamine transporter (DAT1) genotype in attention-deficit/hyperactivity disorder (ADHD). The results confirm that DAT1 translates the genetic risk of ADHD through striatal activation.

  3. Methylphenidate for attention deficit hyperactivity disorder (ADHD) in children and adolescents

    DEFF Research Database (Denmark)

    Storebø, Ole Jakob; Pedersen, Nadia; Ramstad, Erica

    2016-01-01

    This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the harmful effects of methylphenidate treatment for children and adolescents with attention deficit hyperactivity disorder (ADHD) in non-randomised studies....

  4. Oculomotor Anomalies in Attention-Deficit/Hyperactivity Disorder: Evidence for Deficits in Response Preparation and Inhibition

    Science.gov (United States)

    Mahone, E. Mark; Mostofsky, Stewart H.; Lasker, Adrian G.; Zee, David; Denckla, Martha B.

    2009-01-01

    Girls, but not boys, with attention deficit hyperactivity disorder (ADHD) have significantly longer visually guided saccades latencies. It is found that sex differences in children with ADHD extend beyond symptom presentation to the development of oculomotor control.

  5. Methylphenidate for Attention-Deficit/Hyperactivity Disorder in Children and Adolescents

    DEFF Research Database (Denmark)

    Storebø, Ole J; Simonsen, Erik; Gluud, Christian

    2016-01-01

    CLINICAL QUESTION: Is treatment with methylphenidate associated with benefits or harms for children and adolescents with attention-deficit/hyperactivity disorder (ADHD)? BOTTOM LINE: Methylphenidate is associated with improvement in ADHD symptoms, general behavior, and quality of life; however, due...

  6. Narrative Intervention: A School-Based Counseling Strategy for Students with Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Kamali, Khosrow; Yoosefi Looyeh, Majid

    2013-01-01

    This article describes a group narrative intervention for improving the behavior of 8- to 11-year-old children with attention-deficit/hyperactivity disorder at home and school. (Contains 2 tables and 1 note.)

  7. Parenting experiences of living with a child with attention deficit hyperactivity disorder

    DEFF Research Database (Denmark)

    Laugesen, Britt; Grønkjær, Mette

    2015-01-01

    BACKGROUND: Attention deficit hyperactivity disorder is the most prevalent mental disorder among children and adolescents worldwide. Parenting a child with attention deficit hyperactivity disorder is challenging and parents find it difficult to raise the child and struggle to get professional...... support. Research has shown how living with a child with Attention Deficit Hyperactivity Disorder influences the families' daily life. This includes how the parents manage to maintain a bearable family life, supportive or not supportive factors as well as parents' experiences of collaboration...... with professionals in diverse settings. OBJECTIVE: The objective of this systematic review was to identify and synthesize the best available evidence on parenting experiences of living with a child with attention deficit hyperactivity disorder, including their experiences of health care and other services. INCLUSION...

  8. Hyperactivity and lack of social discrimination in the adolescent Fmr1 knockout mouse

    DEFF Research Database (Denmark)

    Sørensen, Emilie M; Bertelsen, Freja; Weikop, Pia;

    2015-01-01

    The aims of this study were to investigate behaviour relevant to human autism spectrum disorder (ASD) and the fragile X syndrome in adolescent Fmr1 knockout (KO) mice and to evaluate the tissue levels of striatal monoamines. Fmr1 KO mice were evaluated in the open field, marble burying and three......-chamber test for the presence of hyperactivity, anxiety, repetitive behaviour, sociability and observation of social novelty compared with wild-type (WT) mice. The Fmr1 KO mice expressed anxiety and hyperactivity in the open field compared with WT mice. This increased level of hyperactivity was confirmed...... in the three-chamber test. Fmr1 KO mice spent more time with stranger mice compared with the WT. However, after a correction for hyperactivity, their apparent increase in sociability became identical to that of the WT. Furthermore, the Fmr1 KO mice could not differentiate between a familiar or a novel mouse...

  9. Baroreflex sensitivity during rest and executive functioning in attention-deficit/hyperactivity disorder. The TRAILS study

    NARCIS (Netherlands)

    Dietrich, A.; Althaus, M.; Hartman, C.A.; Buitelaar, J.K.; Minderaa, R.B.; van den Hoofdakker, B.J.; Hoekstra, P.J.

    2012-01-01

    Children with attention-deficit/hyperactivity disorder (ADHD) often show executive function (EF) problems and neurophysiological hypoarousal. Baroreceptor activation, as part of the baroreflex short-term blood pressure regulatory mechanism, has been linked to cortical inhibition and attenuated cogni

  10. Gendering attention deficit hyperactivity disorder: a discursive analysis of UK newspaper stories.

    Science.gov (United States)

    Horton-Salway, Mary

    2013-08-01

    Discursive psychology is used to study the gendering of attention deficit hyperactivity disorder in UK national newspapers in the period of 2009-2011. The analysis examines how gendering is embedded in causal attributions and identity constructions. Attention deficit hyperactivity disorder is portrayed as a predominantly male phenomenon with representations of attention deficit hyperactivity disorder being gendered through extreme stories about victims, villains or heroes that depict boys and men as marginalised, exceptional or dangerous. There is also a focus on mothers as the spokespersons and caretakers for parenting and family health while fathers are rendered more invisible. This contributes to our understanding of how attention deficit hyperactivity disorder is constructed in the media using a range of gendered representations that draw on cultural stereotypes familiar in Western societies.

  11. Baroreflex sensitivity during rest and executive functioning in attention-deficit/hyperactivity disorder. The TRAILS study.

    NARCIS (Netherlands)

    Dietrich, A.; Althaus, M.; Hartman, C.A.; Buitelaar, J.K.; Mindera, R.B.; Hoofdakker, B.J. van den; Hoekstra, P.J.

    2012-01-01

    Children with attention-deficit/hyperactivity disorder (ADHD) often show executive function (EF) problems and neurophysiological hypoarousal. Baroreceptor activation, as part of the baroreflex short-term blood pressure regulatory mechanism, has been linked to cortical inhibition and attenuated cogni

  12. Cognitive heterogeneity in adult attention deficit/hyperactivity disorder: A systematic analysis of neuropsychological measurements

    NARCIS (Netherlands)

    Mostert, J.C.; Onnink, A.M.H.; Klein, M.; Dammers, J.; Harneit, A.; Schulten, T.; Hulzen, K.J.E. van; Kan, C.C.; Slaats-Willemse, D.I.E.; Buitelaar, J.; Franke, B.; Hoogman, M.

    2015-01-01

    Attention Deficit/Hyperactivity Disorder (ADHD) in childhood is associated with impaired functioning in multiple cognitive domains: executive functioning (EF), reward and timing. Similar impairments have been described for adults with persistent ADHD, but an extensive investigation of neuropsycholog

  13. Children's drawings exhibited in the Globe

    CERN Multimedia

    Elizabeth Roe

    2010-01-01

    "Draw Me A Physicist" has been a success. Members of the public visiting the exhibition in the Globe of Science and Innovation have praised the scientific and creative balance the children of neighbouring France and the Canton of Geneva have obtained through their visit to CERN.   The Draw Me a Physicist exhibition in the Globe For a six-month period 9 to 11-year olds from the Pays de Gex, Meyrin, Satigny and Vernier have been able to enjoy a balance between science and art, through drawing and defining their interpretations of a physicist. In May, eight pairs of drawings from each participating class were selected by the schools to be displayed on the second floor of the Globe. Since the images have been put up, the viewers have enjoyed the contrast between the "before" pictures of vibrant Albert Einsteins to the "after" pictures of casual people sitting in an office. The large room in the Globe has been transformed from a hollow shell int...

  14. New Media Display Technology and Exhibition Experience

    Directory of Open Access Journals (Sweden)

    Chen-Wo Kuo

    2016-01-01

    Full Text Available As the inheritor of Chinese civilization, the National Palace Museum (hereafter referred to as the NPM, houses a world-class collection of cultural art and artifacts. Since the NPM began promoting the National Digital Archives Project in 2002, its efforts have expanded to develop a digital museum and various e-learning programs. Extending the use of digital archives to its educational and cultural industrial endeavors, the NPM has maximized the value of its exhibitions, publications, and educational programs.  In 2013, the NPM integrated creative thinking and interdisciplinary technologies, such as floating projection, augmented reality, and other sensory interactive media, to recreate the historical circumstance of 19th century East Asian maritime cultures in “Rebuilding the Tong-an Ships—New Media Art Exhibition," which opened at Huashan 1914 Creative Park and later won the Gold Award at the 2014 Digital Education Innovation Competition. Through a thorough exploration of the factors contributing to the success of "Rebuilding the Tong-an Ships," this study has isolated the two main factors of the exhibition’s popularity, namely, the compactness of the metadata and the atmosphere created by the interactive display technology.

  15. Radiation-related information at science exhibitions

    Energy Technology Data Exchange (ETDEWEB)

    Bannai, Tadaaki [Inst. for Environmental Sciences, Rokkasho, Aomori (Japan)

    1999-09-01

    The aim of the present report was to promote an efficient utilization of science museums providing with educational information concerning radiations. Investigations were made on radiation-related materials exhibited at 38 museums including PR event sites between April 1996 and July 1998 mainly located on Kanto and Tohoku area in Japan. The investigation concerned as to whether the displays on radiation-related material (cosmic rays, X-rays, etc) existed or not, and as to the background of the display as well. As the result, 14 locations had no relevant displays, 10 of them not having things about atomic energy at all. The locations belonging to electricity company mostly had displays related to radiations and atomic energy power generation. A spark chamber was exhibited at 9 locations and a cloud chamber at 3 locations, but only one location among them displayed both. Displays on the actual use of X-radiation were found at 4 locations. Needs to prepare further improved displays exist at the sites visited. (S. Ohno)

  16. CERN Inspires Art in Major New Exhibition

    CERN Multimedia

    2001-01-01

    Signatures of the Invisible, an exhibition inspired by CERN, opened at the Atlantis Gallery in London on Thursday, 1 March before going on a world tour. The fruit of a close collaboration between CERN and the London Institute, the exhibition brings together works from many leading European contemporary artists. White wooden boxes on a grey floor... the lids opened, unveiling brilliant white light from a bunch of optical fibres carefully stuck together in the shape of a square. Another holds a treasure of lead glass surrounded by enigmatic black mirrors. What's it all about? Signatures of the Invisible, that's what, a joint project organised by the London Institute, one of the world's largest college of art, and our Laboratory. Damien Foresy from the EST workshop putting finishing touches to the spinning tops of French artist Jérôme Basserode. Monica Sand's boxes are just one of the many works based around materials used in particle detection at CERN that was admired at the opening o...

  17. Neurofibromatosis type 1 and attention deficit hyperactivity disorder: a case study and literature review

    OpenAIRE

    Miguel CS; Chaim-Avancini TM; Silva MA; Louzã MR

    2015-01-01

    Carmen Sílvia Miguel, Tiffany M Chaim-Avancini, Maria Aparecida Silva, Mario Rodrigues LouzãAdult Attention Deficit Hyperactivity Disorder Program (PRODATH), Institute of Psychiatry, University of São Paulo, São Paulo, BrazilBackground: The cognitive profile of children with neurofibromatosis type 1 (NF1) and attention deficit hyperactivity disorder (ADHD) has been well characterized, but few studies have evaluated the cognitive abilities o...

  18. Social skills training for Attention Deficit Hyperactivity Disorder (ADHD) in children aged 5 to 18 years

    DEFF Research Database (Denmark)

    Storebø, Ole Jakob; Skoog, Maria; Damm, Dorte

    2011-01-01

    Attention Deficit Hyperactivity Disorder (ADHD) in children is associated with hyperactivity and impulsitivity, attention problems, and difficulties with social interactions. Pharmacological treatment may alleviate symptoms of ADHD but seldom solves difficulties with social interactions. Social...... skills training may benefit ADHD children in their social interactions. We examined the effects of social skills training on children's social competences, general behaviour, ADHD symptoms, and performance in school....

  19. Cognitive computer training in children with attention deficit hyperactivity disorder (ADHD) versus no intervention

    DEFF Research Database (Denmark)

    Bikic, Aida; Leckman, James F; Lindschou, Jane

    2015-01-01

    BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder characterized by symptoms of inattention and impulsivity and/or hyperactivity and a range of cognitive dysfunctions. Pharmacological treatment may be beneficial; however, many affected individuals...... of cognition, mostly on the working memory or attention but with poor generalization of training on other cognitive functions and functional outcome. Children with ADHD have a variety of cognitive dysfunctions, and it is important that cognitive training target multiple cognitive functions. METHODS...

  20. Telomere length is highly inherited and associated with hyperactivity-impulsivity in children with attention deficit/hyperactivity disorder

    Directory of Open Access Journals (Sweden)

    Danielle Souza Costa

    2015-07-01

    Full Text Available Telomere length (TL is highly heritable, and a shorter telomere at birth may increase the risk of age-related problems. Telomere length (TL is highly heritable, and a shorter telomere at birth may increase the risk of age-related problems. Additionally, a shorter TL may represent a biomarker of chronic stress and has been associated with psychiatric disorders. However, no study has explored whether there is an association between TL and the symptoms of one of the most common neurodevelopmental disorders in childhood: Attention Deficit/Hyperactive Disorder (ADHD. We evaluated 61 (range, 6-16 years ADHD children and their parents between 2012 and 2014. Telomere length was measured with a quantitative polymerase chain reaction method with telomere signal normalized to the signal from a single copy gene (36B4 to generate a T/S ratio. Family data was processed through a GEE model to determine the effect of parental TL on children TL. Inattentive and hyperactive-impulsive symptoms were also evaluated in relation to TL. For the first time, we found general heritability to be the major mechanism explaining interindividual telomere length variation in ADHD (father-child: 95%CI=0.35/0.91, p0.05. The ADHD inattentive dimension was not significant associated with TL in this study (p>0.05. TL was shown to be a potential biomarker of the ADHD symptoms burden in families affected by this neurodevelopmental disorder. However, it is crucial that future studies investigating the rate of telomere attrition in relation to psychiatric problems to consider the strong determination of telomere length at birth by inheritance.