WorldWideScience

Sample records for htt ivar jaek

  1. Koputajate kaitseks! / Ivar Tallo

    Index Scriptorium Estoniae

    Tallo, Ivar, 1964-

    2003-01-01

    Politoloog Ivar Tallo arvates võiks Riigikogu välja tulla initsiatiiviga luua ühiskonna esindajate osavõtul vigade ja pettuste paljastajate kaitse seadus. Küsimusele, kust läheb politseiametniku sõnavabaduse piir vastavad Ain Seppik, Tarmo Loodus ja Jaanus Rahumägi. Indrek Sirgi juhtum

  2. Ivar Giaever, Tunneling, and Superconductors

    Science.gov (United States)

    dropdown arrow Site Map A-Z Index Menu Synopsis Ivar Giaever, Tunneling, and Superconductors Resources with in Superconductors Measured by Electron Tunneling; Physical Review Letters, Vol. 5 Issue 4: 147 - 148 ; August 15, 1960 Electron Tunneling Between Two Superconductors; Physical Review Letters, Vol. 5 Issue 10

  3. DVD-plaatide hind langeb / Ivar Sild

    Index Scriptorium Estoniae

    Sild, Ivar

    2003-01-01

    DVD (Digital Versatile Disk = digitaalne mitmekülgne plaat) kui ka juba Eestis videolindiga edukalt konkureeriv audiovisuaalse info kandja. Ivar Vendelin firmast V&K Holding loodab jõuda DVDga massidesse

  4. Ivar Tallo : Meie Nokia on paindlik riik / Ivar Tallo ; interv. Kai Simson

    Index Scriptorium Estoniae

    Tallo, Ivar, 1964-

    2005-01-01

    e-Riigi Akadeemia Sihtasutuse direktor Ivar Tallo kõrgemate riigiametnike koolitamisest info- ja kommunikatsioonitehnoloogia kasutamiseks ja edendamiseks avalikus halduses. Kogemusi jagatakse Kesk-Aasias, Kaukaasias ja Balkanimaades

  5. Ole Ivar Lovaas--His Life, Merits and Legacy

    Science.gov (United States)

    Özerk, Kamil; Vea, Gunvor Dalby; Eikeseth, Svein; Özerk, Meral

    2016-01-01

    Ole Ivar Lovaas (1927-2010) is known worldwide for his research within the field of Applied Behavior Analysis, and is probably the most influential researcher within the field of treatment of children with autism. In the first part of this biographically oriented paper, we inform the readers about his family background, childhood, elementary and…

  6. Ivar Tallo : e-riigi toimimiseks on vaja mõtteviisi muutust / Ivar Tallo ; interv. Silvia Lotman

    Index Scriptorium Estoniae

    Tallo, Ivar, 1964-

    2005-01-01

    e-Riigi Akadeemia Sihtasutuse direktor räägib infoühiskonna arengust Eestis, koostööprojektidest välispartneritega, infoühiskonna keskkonnamõõtest ja e-Riigi Akadeemia tulevikuplaanidest. Lisa: Ivar Tallo CV

  7. HTT-DB: horizontally transferred transposable elements database.

    Science.gov (United States)

    Dotto, Bruno Reis; Carvalho, Evelise Leis; Silva, Alexandre Freitas; Duarte Silva, Luiz Fernando; Pinto, Paulo Marcos; Ortiz, Mauro Freitas; Wallau, Gabriel Luz

    2015-09-01

    Horizontal transfer of transposable (HTT) elements among eukaryotes was discovered in the mid-1980s. As then, >300 new cases have been described. New findings about HTT are revealing the evolutionary impact of this phenomenon on host genomes. In order to provide an up to date, interactive and expandable database for such events, we developed the HTT-DB database. HTT-DB allows easy access to most of HTT cases reported along with rich information about each case. Moreover, it allows the user to generate tables and graphs based on searches using Transposable elements and/or host species classification and export them in several formats. This database is freely available on the web at http://lpa.saogabriel.unipampa.edu.br:8080/httdatabase. HTT-DB was developed based on Java and MySQL with all major browsers supported. Tools and software packages used are free for personal or non-profit projects. bdotto82@gmail.com or gabriel.wallau@gmail.com. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  8. Rolling Bearing Fault Diagnosis Based on an Improved HTT Transform.

    Science.gov (United States)

    Pang, Bin; Tang, Guiji; Tian, Tian; Zhou, Chong

    2018-04-14

    When rolling bearing failure occurs, vibration signals generally contain different signal components, such as impulsive fault feature signals, background noise and harmonic interference signals. One of the most challenging aspects of rolling bearing fault diagnosis is how to inhibit noise and harmonic interference signals, while enhancing impulsive fault feature signals. This paper presents a novel bearing fault diagnosis method, namely an improved Hilbert time-time (IHTT) transform, by combining a Hilbert time-time (HTT) transform with principal component analysis (PCA). Firstly, the HTT transform was performed on vibration signals to derive a HTT transform matrix. Then, PCA was employed to de-noise the HTT transform matrix in order to improve the robustness of the HTT transform. Finally, the diagonal time series of the de-noised HTT transform matrix was extracted as the enhanced impulsive fault feature signal and the contained fault characteristic information was identified through further analyses of amplitude and envelope spectrums. Both simulated and experimental analyses validated the superiority of the presented method for detecting bearing failures.

  9. iVAR: a program for imputing missing data in multivariate time series using vector autoregressive models.

    Science.gov (United States)

    Liu, Siwei; Molenaar, Peter C M

    2014-12-01

    This article introduces iVAR, an R program for imputing missing data in multivariate time series on the basis of vector autoregressive (VAR) models. We conducted a simulation study to compare iVAR with three methods for handling missing data: listwise deletion, imputation with sample means and variances, and multiple imputation ignoring time dependency. The results showed that iVAR produces better estimates for the cross-lagged coefficients than do the other three methods. We demonstrate the use of iVAR with an empirical example of time series electrodermal activity data and discuss the advantages and limitations of the program.

  10. Ole Ivar Lovaas - His Life, Merits and Legacy

    Directory of Open Access Journals (Sweden)

    Kamil ÖZERK

    2016-12-01

    Full Text Available Ole Ivar Lovaas (1927-2010 is known worldwide for his research within the field of Applied Behavior Analysis, and is probably the most influential researcher within the field of treatment of children with autism. In the first part of this biographically oriented paper, we inform the readers about his family background, childhood, elementary and secondary school years, and his adolescent years during World War II in his first homeland, Norway, based on archival research and interviews. In the second part, we describe his life, academic studies, research and successes in his second home country, the United States. Finally, we briefly recount the impact Lovaas has had on the field of Applied Behavior Analysis and the treatment of and services for children with autism spectrum disorders in Norway and in the North America.

  11. Chaperone protein HYPK interacts with the first 17 amino acid region of Huntingtin and modulates mutant HTT-mediated aggregation and cytotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Choudhury, Kamalika Roy [Crystallography and Molecular Biology Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064 (India); Centre for Neuroscience, Indian Institute of Science, Bangalore 560012 (India); Bhattacharyya, Nitai P., E-mail: nitai_sinp@yahoo.com [Biomedical Genomics Centre, PG Polyclinic Building, 5, Suburbun Hospital Road, Kolkata 700020 (India)

    2015-01-02

    Highlights: • HYPK reduces mutant HTT-mediated aggregate formation and cytotoxicity. • Interaction of HYPK with HTT requires N-terminal 17 amino acid of HTT (HTT-N17). • Deletion of HTT-N17 leads to SDS-soluble, smaller, nuclear aggregates. • These smaller aggregates do not associate with HYPK and are more cytotoxic. • Maybe, interaction of HYPK with amphipathic HTT-N17 block HTT aggregate formation. - Abstract: Huntington’s disease is a polyglutamine expansion disorder, characterized by mutant HTT-mediated aggregate formation and cytotoxicity. Many reports suggests roles of N-terminal 17 amino acid domain of HTT (HTT-N17) towards subcellular localization, aggregate formation and subsequent pathogenicity induced by N-terminal HTT harboring polyQ stretch in pathogenic range. HYPK is a HTT-interacting chaperone which can reduce N-terminal mutant HTT-mediated aggregate formation and cytotoxicity in neuronal cell lines. However, how HYPK interacts with N-terminal fragment of HTT remained unknown. Here we report that specific interaction of HYPK with HTT-N17 is crucial for the chaperone activity of HYPK. Deletion of HTT-N17 leads to formation of tinier, SDS-soluble nuclear aggregates formed by N-terminal mutant HTT. The increased cytotoxicity imparted by these tiny aggregates might be contributed due to loss of interaction with HYPK.

  12. [The value of 5-HTT gene polymorphism for the assessment and prediction of male adolescence violence].

    Science.gov (United States)

    Yu, Yue; Liu, Xiang; Yang, Zhen-xing; Qiu, Chang-jian; Ma, Xiao-hong

    2012-08-01

    To establish an adolescent violence crime prediction model, and to assess the value of serotonin transporter (5-HTT) gene polymorphism for the assessment and prediction of violent crime. Investigative tools were used to analyze the difference in personality dimensions, social support, coping styles, aggressiveness, impulsivity, and family condition scale between 223 adolescents with violence behavior and 148 adolescents without violence behavior. The distribution of 5-HTT gene polymorphisms (5-HTTLPR and 5-HTTVNTR) was compared between the two groups. The role of 5-HTT gene polymorphism on adolescent personality, impulsion and aggression scale also was also analyzed. Stepwise logistic regression was used to establish a predictive model for adolescent violent crime. Significant difference was found between the violence group and the control group on multiple dimensions of psychology and environment scales. However, no statistical difference was found with regard to the 5-HTT genotypes and alleles between adolescents with violent behaviors and normal controls. The rate of prediction accuracy was not significantly improved when 5-HTT gene polymorphism was taken into the model. The violent crime of adolescents was closely related with social and environmental factors. No association was found between 5-HTT polymorphisms and adolescent violence criminal behavior.

  13. The personality trait openness is related to cerebral 5-HTT levels

    DEFF Research Database (Denmark)

    Kalbitzer, Jan; Frøkjær, Vibe G.; Erritzøe, David

    2009-01-01

    Potentiation of serotonergic transmission increases cognitive flexibility, but can in other circumstances increase sensitivity to stressful environmental cues. The personality trait Openness to Experience reflects and is also associated with an increased risk for mood disorders. We hypothesized...... that the personality trait has an association with a biomarker of serotonergic transmission, the plasma membrane serotonin transporter (5-HTT). In 50 healthy volunteers, we tested for correlations between scores on the NEO-PI-R scale Openness to Experience and its subscales, and cerebral binding of the 5-HTT selective...... in openness scores. Thus, high scores in personality facets indicative of cognitive flexibility and openness to change are associated with lower [11C]DASB binding. Lower abundance of 5-HTT sites may result in potentiation of serotonergic signaling, which occurs during treatment with SSRIs. We speculate...

  14. Aggression and 5HTT polymorphism in females: study of synchronized swimming and control groups.

    Science.gov (United States)

    Sysoeva, Olga V; Maluchenko, Natalia V; Timofeeva, Marina A; Portnova, Galina V; Kulikova, Maria A; Tonevitsky, Alexandr G; Ivanitsky, Alexey M

    2009-05-01

    Aggression is a heterogeneous heritable psychological trait, also influenced by environmental factors. Previous studies, mostly conducted on male population, have found some associations of the aggression with the polymorphisms of genes, regulating the activity of serotonin (5-HT) in the brain. However, psychological as well as biochemical manifestations of the aggression are different in males and females. Our study aimed to investigate the association of 5-HTT gene polymorphism with different facets of aggression (BDHI) in females. Two groups: the synchronized swimming and non-athlete control, - were examined to study the possible modulation effect of sport on the association between 5-HTT gene polymorphism and aggression. It was found that in both groups the low-active 5-HTT polymorphism (SS) was associated with increased scores on Indirect Hostility scale and decreased scores on Negativism scale, compared to LL genotype. No interaction effect between sport and 5-HTT polymorphism was found. The higher percentage of LL-carriers and lower of LS-carriers in the synchronized swimming group compared to the control one was observed. This may be the sign of the importance of LL polymorphism of 5-HTT gene, previously associated with higher resistance to stress factors, for being an athlete, although this result has to be taken cautiously keeping in mind the stratification problem. Synchronized swimmers had lower scores on Assault, Negativism, Irritability and Verbal Hostility compared to age-matched control girls (in general and for each 5-HTT genotype separately), suggesting that they may have more matured emotional system (older control group has also lower scores on these scales).

  15. Normal and mutant HTT interact to affect clinical severity and progression in Huntington disease

    DEFF Research Database (Denmark)

    Aziz, N A; Jurgens, C K; Landwehrmeyer, G B

    2009-01-01

    OBJECTIVE: Huntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by a CAG repeat expansion in the HD gene (HTT). We aimed to assess whether interaction between CAG repeat sizes in the mutant and normal allele could affect disease severity and progression. METHODS: Using...... with less severe symptoms and pathology. CONCLUSIONS: Increasing CAG repeat size in normal HTT diminishes the association between mutant CAG repeat size and disease severity and progression in Huntington disease. The underlying mechanism may involve interaction of the polyglutamine domains of normal...

  16. [Relationship between genetic polymorphisms of 3 SNP loci in 5-HTT gene and paranoid schizophrenia].

    Science.gov (United States)

    Xuan, Jin-Feng; Ding, Mei; Pang, Hao; Xing, Jia-Xin; Sun, Yi-Hua; Yao, Jun; Zhao, Yi; Li, Chun-Mei; Wang, Bao-Jie

    2012-12-01

    To investigate the population genetic data of 3 SNP loci (rs25533, rs34388196 and rs1042173) of 5-hydroxytryptamine transporter (5-HTT) gene and the association with paranoid schizophrenia. Three SNP loci of 5-HTT gene were examined in 132 paranoid schizophrenia patients and 150 unrelated healthy individuals of Northern Chinese Han population by PCR-RFLP technique. The Hardy-Weinberg equilibrium test was performed using the chi-square test and the data of haplotype frequency and population genetics parameters were statistically analyzed. Among these three SNP loci, four haplotypes were obtained. There were no statistically significant differences between the patient group and the control group (P > 0.05). The DP values of the 3 SNP loci were 0.276, 0.502 and 0.502. The PIC of them were 0.151, 0.281 and 0.281. The PE of them were 0.014, 0.072 and 0.072. The three SNP loci and four haplotypes of 5-HTT gene have no association with paranoid schizophrenia, while the polymorphism still have high potential application in forensic practice.

  17. A SNP in the HTT promoter alters NF-κB binding and is a bidirectional genetic modifier of Huntington disease.

    Science.gov (United States)

    Bečanović, Kristina; Nørremølle, Anne; Neal, Scott J; Kay, Chris; Collins, Jennifer A; Arenillas, David; Lilja, Tobias; Gaudenzi, Giulia; Manoharan, Shiana; Doty, Crystal N; Beck, Jessalyn; Lahiri, Nayana; Portales-Casamar, Elodie; Warby, Simon C; Connolly, Colúm; De Souza, Rebecca A G; Tabrizi, Sarah J; Hermanson, Ola; Langbehn, Douglas R; Hayden, Michael R; Wasserman, Wyeth W; Leavitt, Blair R

    2015-06-01

    Cis-regulatory variants that alter gene expression can modify disease expressivity, but none have previously been identified in Huntington disease (HD). Here we provide in vivo evidence in HD patients that cis-regulatory variants in the HTT promoter are bidirectional modifiers of HD age of onset. HTT promoter analysis identified a NF-κB binding site that regulates HTT promoter transcriptional activity. A non-coding SNP, rs13102260:G > A, in this binding site impaired NF-κB binding and reduced HTT transcriptional activity and HTT protein expression. The presence of the rs13102260 minor (A) variant on the HD disease allele was associated with delayed age of onset in familial cases, whereas the presence of the rs13102260 (A) variant on the wild-type HTT allele was associated with earlier age of onset in HD patients in an extreme case-based cohort. Our findings suggest a previously unknown mechanism linking allele-specific effects of rs13102260 on HTT expression to HD age of onset and have implications for HTT silencing treatments that are currently in development.

  18. Negative social acts and pain: evidence of a workplace bullying and 5-HTT genotype interaction.

    Science.gov (United States)

    Jacobsen, Daniel Pitz; Nielsen, Morten Birkeland; Einarsen, Ståle; Gjerstad, Johannes

    2018-05-01

    Objectives Long-term exposure to systematic negative acts at work, usually labeled workplace bullying, is a prevalent problem at many workplaces. The adverse effects of such exposure may range from psychological symptoms, such as depression and anxiety to somatic ailments like cardiovascular disease and musculoskeletal complaints. In this study, we examined the relationships among exposure to negative acts, genetic variability in the 5-HTT gene SLC6A4 and pain. Methods The study was based on a nationally representative survey of 987 Norwegian employees drawn from the Norwegian Central Employee Register by Statistics Norway. Exposure to bullying in the workplace was measured with the 9-item version of the Negative Acts Questionnaire - Revised (NAQ-R) inventory. Pain was rated using an 11-point (0-10) numeric rating scale (NRS). Genotyping with regard to SLC6A4 was carried out using a combination of gel-electrophoresis and TaqMan assay. Results The data revealed a significant interaction between exposure to negative acts and the SLC6A4 genotype with regard to pain (linear regression with 5000 resamples; age, sex, tobacco use and education were included as covariates). The relationship between negative acts and pain intensity was significantly stronger for subjects with the LALA genotype than for subjects with the SLA/LALG/SLG genotype. No significant difference between subjects with the LALA genotype and SS genotype was observed. Conclusions Our data demonstrated that the relationship between bullying and pain was modified by the 5-HTT genotype, ie, genetic variation in SLC6A4. The association between negative acts and health among vulnerable individuals appeared more potent than previously reported.

  19. Hydrothermal Treatment (HTT) of Microalgae: Evaluation of the Process As Conversion Method in an Algae Biorefinery Concept

    NARCIS (Netherlands)

    Garcia Alba, Laura; Torri, C.; Samori, C.; van der Spek, J.J.; Fabbri, D.; Kersten, Sascha R.A.; Brilman, Derk Willem Frederik

    2012-01-01

    The hydrothermal treatment (HTT) technology is evaluated for its potential as a process to convert algae and algal debris into a liquid fuel, within a sustainable algae biorefinery concept in which, next to fuels (gaseous and liquid), high value products are coproduced, nutrients and water are

  20. A polymorphism in the 5'-flanking region of the serotonin transporter (5-HTT) gene affects fear-related behaviors of adult domestic chickens.

    Science.gov (United States)

    Krause, E Tobias; Kjaer, Joergen B; Lüders, Carolin; van, Loc Phi

    2017-07-14

    The neural serotonin (5-HT)/serotonin transporter (5-HTT) system is involved in the regulation of physiological processes and emotional states. In humans, the short (S) allele in the 5-HTT gene-linked polymorphic region, which decreases 5-HTT expression, has been shown to be associated with behavioral changes including an increased level of anxiety. Also in birds a polymorphism in the 5-HTT gene is described, a deletion (D) has been found to have functional consequences on growth and locomotion. Furthermore, the D-allele leads to an increased 5-HTT expression compared to the wild type (W), a feature which is linked to lower levels of fear in mammalian species. Thus, we aimed here to test whether the polymorphism in the chicken 5-HTT gene also leads to respective alternations of fear-related behaviors. We tested 268 hens of three genotypes (W/W, W/D, D/D) in two behavioral paradigms (open field, light-dark test) to assess fear-related behavior. Both tests revealed that hens possessing the D-allele showed lower levels of fear than those having the W-allele. These similar outcomes in fear-related behaviors in an avian and a mammalian species are associated with an increased 5-HTT expression. In the human 5-HTT gene, the long (L) allele is linked to such increased expression, whereas in chickens it is the D-allele. Thus, increased 5-HTT expression causing decreased fear may be a general mechanism in vertebrates. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. 5-HT2C Receptor Desensitization Moderates Anxiety in 5-HTT Deficient Mice: From Behavioral to Cellular Evidence

    Science.gov (United States)

    Martin, Cédric BP; Martin, Vincent S.; Trigo, José M.; Chevarin, Caroline; Maldonado, Rafael; Fink, Latham H.; Cunningham, Kathryn A.; Hamon, Michel; Lanfumey, Laurence

    2015-01-01

    Background: Desensitization and blockade of 5-HT2C receptors (5-HT2CR) have long been thought to be central in the therapeutic action of antidepressant drugs. However, besides behavioral pharmacology studies, there is little in vivo data documenting antidepressant-induced 5-HT2CR desensitization in specific brain areas. Methods: Mice lacking the 5-HT reuptake carrier (5-HTT-/-) were used to model the consequences of chronic 5-HT reuptake inhibition with antidepressant drugs. The effect of this mutation on 5-HT2CR was evaluated at the behavioral (social interaction, novelty-suppressed feeding, and 5-HT2CR–induced hypolocomotion tests), the neurochemical, and the cellular (RT-qPCR, mRNA editing, and c-fos–induced expression) levels. Results: Although 5-HTT-/- mice had an anxiogenic profile in the novelty-suppressed feeding test, they displayed less 5-HT2CR–mediated anxiety in response to the agonist m-chlorophenylpiperazine in the social interaction test. In addition, 5-HT2CR–mediated inhibition of a stress-induced increase in 5-HT turnover, measured in various brain areas, was markedly reduced in 5-HTT-/- mutants. These indices of tolerance to 5-HT2CR stimulation were associated neither with altered levels of 5-HT2CR protein and mRNA nor with changes in pre-mRNA editing in the frontal cortex. However, basal c-fos mRNA production in cells expressing 5-HT2CR was higher in 5-HTT-/- mutants, suggesting an altered basal activity of these cells following sustained 5-HT reuptake carrier inactivation. Furthermore, the increased c-fos mRNA expression in 5-HT2CR–like immune-positive cortical cells observed in wild-type mice treated acutely with the 5-HT2CR agonist RO-60,0175 was absent in 5-HTT-/- mutants. Conclusions: Such blunted responsiveness of the 5-HT2CR system, observed at the cell signaling level, probably contributes to the moderation of the anxiety phenotype in 5-HTT-/- mice. PMID:25522398

  2. Pre-clinical evaluation of AAV5-miHTT gene therapy of Huntington´s disease

    Czech Academy of Sciences Publication Activity Database

    Konstantinová, P.; Miniarikova, J.; Blits, B.; Zimmer, V.; Spoerl, A.; Southwell, A.; Hayden, M.; van Deventer, S.; Deglon, N.; Motlík, Jan; Juhás, Štefan; Juhásová, Jana; Richard, Ch.; Petry, H.

    2015-01-01

    Roč. 78, Supl 2 (2015), s. 8-8 ISSN 1210-7859. [Conference on Animal Models for neurodegenerative Diseases /3./. 08.11.2015-10.11.2015, Liblice] R&D Projects: GA MŠk ED2.1.00/03.0124 Institutional support: RVO:67985904 Keywords : Huntington ´s disease * gene therapy * AAV5-miHTT Subject RIV: EB - Genetics ; Molecular Biology

  3. Generation of KCL028 research grade human embryonic stem cell line carrying a mutation in the HTT gene

    Directory of Open Access Journals (Sweden)

    Laureen Jacquet

    2016-03-01

    Full Text Available The KCL028 human embryonic stem cell line was derived from an embryo donated for research that carried an autosomal dominant mutation affecting one allele of the HTT gene encoding huntingtin (43 trinucleotide repeats; 21 for the normal allele. The ICM was isolated using laser microsurgery and plated on γ-irradiated human foreskin fibroblasts. Both the derivation and cell line propagation were performed in an animal product-free environment. Pluripotent state and differentiation potential were confirmed by in vitro and in vivo assays.

  4. Serotonin Transporter (5-HTT) and gamma-Aminobutyric Acid Receptor Subunit beta3 (GABRB3) Gene Polymorphisms are not Associated with Autism in the IMGSA Families

    DEFF Research Database (Denmark)

    Maestrini, E.; Lai, C.; Marlow, A.

    1999-01-01

    Previous studies have suggested that the serotonin transporter (5-HTT) gene and the gamma-aminobutyric acid receptor subunit beta3 (GABRB3) gene, or other genes in the 15q11-q13 region, are possibly involved in susceptibility to autism. To test this hypothesis we performed an association study on...

  5. A SNP in the HTT promoter alters NF-κB binding and is a bidirectional genetic modifier of Huntington disease

    DEFF Research Database (Denmark)

    Bečanović, Kristina; Nørremølle, Anne; Neal, Scott J

    2015-01-01

    Cis-regulatory variants that alter gene expression can modify disease expressivity, but none have previously been identified in Huntington disease (HD). Here we provide in vivo evidence in HD patients that cis-regulatory variants in the HTT promoter are bidirectional modifiers of HD age of onset....

  6. Impact of Institutional Care on Attachment Disorganization and Insecurity of Ukrainian Preschoolers: Protective Effect of the Long Variant of the Serotonin Transporter Gene (5HTT)

    Science.gov (United States)

    Bakermans-Kranenburg, Marian J.; Dobrova-Krol, Natasha; van IJzendoorn, Marinus

    2012-01-01

    Institutional care has been shown to lead to insecure and disorganized attachments and indiscriminate friendliness. Some children, however, are surprisingly resilient to the adverse environment. Here the protective role of the long variant of the serotonin receptor gene (5HTT) is explored in a small hypothesis-generating study of 37 Ukrainian…

  7. Tartu meeriks pürgijad pakuvad - mis tooks ülikoolile Nobeli preemia / Ivar Tallo, Teet Jagomägi, Jüri Kumar, Malle Salupere...[jt.

    Index Scriptorium Estoniae

    2002-01-01

    Tartu linnapeakandidaadid Ivar Tallo, Teet Jagomägi, Jüri Kumar, Malle Salupere, Tõni Kauba, Tõnis Lukas ja Andrus Ansip vastavad küsimustele : Tartu Ülikooli arenguvõimalustest ja -vajadustest, konkurentsivõime suurendamisest / vahendasid Sander Silm, Priit Rajalo, Ivi Drikkit

  8. "en este aff ösel" in Visby : Ösel and Estland in the Gotlandic account books of Ivar Axelsson Tott 1585-87 and Sören Norby 1524-25 / Jan-Christian Schlüter

    Index Scriptorium Estoniae

    Schlüter, Jan-Christian, 1979-

    2008-01-01

    Ojamaa ja Saaremaa kontaktidest on vähe teada perioodist Saksa ordu ja Rootsi kuningate valitsemisaja vahel. Ivar Axelsson Totti ja Sören Nörby arveraamatutes mainitud kohanimede seas on Eestiga seotud nimedel küllalt suur osakaal. Ka esineb kaptenite palgaarvetel Eestist pärit isikute nimesid

  9. ADHD and Disruptive behavior scores – associations with MAO-A and 5-HTT genes and with platelet MAO-B activity in adolescents

    Directory of Open Access Journals (Sweden)

    Larsson Jan-Olov

    2008-04-01

    Full Text Available Abstract Background Pharmacological and genetic studies suggest the importance of the dopaminergic, serotonergic, and noradrenergic systems in the pathogenesis of Attention Deficit Hyperactivity Disorder (ADHD and Disruptive Behavior Disorder (DBD. We have, in a population-based sample, studied associations between dimensions of the ADHD/DBD phenotype and Monoamine Oxidase B (MAO-B activity in platelets and polymorphisms in two serotonergic genes: the Monoamine Oxidase A Variable Number of Tandem Repeats (MAO-A VNTR and the 5-Hydroxytryptamine Transporter gene-Linked Polymorphic Region (5-HTT LPR. Methods A population-based sample of twins, with an average age of 16 years, was assessed for ADHD/DBD with a clinical interview; Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL. Blood was drawn from 247 subjects and analyzed for platelet MAO-B activity and polymorphisms in the MAO-A and 5-HTT genes. Results We found an association in girls between low platelet MAO-B activity and symptoms of Oppositional Defiant Disorder (ODD. In girls, there was also an association between the heterozygote long/short 5-HTT LPR genotype and symptoms of conduct disorder. Furthermore the heterozygote 5-HTT LPR genotype in boys was found to be associated with symptoms of Conduct Disorder (CD. In boys, hemizygosity for the short MAO-A VNTR allele was associated with disruptive behavior. Conclusion Our study suggests that the serotonin system, in addition to the dopamine system, should be further investigated when studying genetic influences on the development of Disruptive Behavior Disorders.

  10. 2305-7432. htt

    African Journals Online (AJOL)

    Peter Berglez

    film actor Hope Chisanu expressing the feeling commonly shared in the country about ... David Kerr's Dance, Media, Entertainment and Performance in south east Africa (Kerr, ... Africanus Aveh in the Rise of video film industry & its social .... commonly known as adventures of Sam Mperu (Magalasi, personal experience).

  11. Ideaalteatri realavastus / Ivar Põllu

    Index Scriptorium Estoniae

    2004-01-01

    W. Shakespeare'i "Romeo ja Julia" moderniseeritud versioon "Julia", instseneerija, lavastaja ja muusikaline kujundaja T. Ojasoo, kaasinstseneerija ja kunstnik E.-L. Semper. Esietendus Eesti Draamateatris 8. okt

  12. Sons & Lumieres / Ivar Jung

    Index Scriptorium Estoniae

    Jung, Ivar

    2004-01-01

    Näitus "Hääl ja valgus" Pariisi Pompidou keskuses 22. IX 2004-3. I 2005. Väljas on 99 kunstniku (Paul Klee, Frantishek Kupka, Vassili Kandinsky, Laszlo Moholy-Nagy, Raoul Hausmann, Bill Viola, Robert Rauschenberg, Joseph Beuys, Rodney Graham jne.) tööd ajavahemikust 1910-2004. Kuraatorid Sophie Duplaix ja Marcella Lista

  13. Eetikakompassi vajadus / Ivar Tallo

    Index Scriptorium Estoniae

    Tallo, Ivar, 1964-

    2007-01-01

    Autori arvates vähendavad meedias levitatavad süüdistused president Toomas Hendrik Ilvese Ärma talu ümber toimuva suhtes presidendi väga olulist võimet eetika teemadel sõna võtta. Riigile oleks vajalik eetikakoja loomine, kuhu saaksid pöörduda need, kelle tegevusele hinnangu andmine on põhjustanud kriisi avalikus arvamuses

  14. Life satisfaction in the new country: a multilevel longitudinal analysis of effects of culture and 5-HTT allele frequency distribution in country of origin.

    Science.gov (United States)

    Kashima, Emiko S; Kent, Stephen; Kashima, Yoshihisa

    2015-01-01

    Life satisfaction of migrants to Australia from 17 countries, assessed at 4-5 months, 16-17 months and 3½ years after arrival, was analyzed with a longitudinal, multilevel analysis. The results indicated that migrants were more satisfied, if the national average life satisfaction was higher in their country of origin, after adjustment for individual-level income, age, and sex and a linear temporal trend. Simultaneously, the migrants were also happier if people in their country of origin had a higher frequency of 5-HTT long allele, a genotype known to be associated with resilience under life stresses. These two relationships were independent, suggesting that both culture and gene matter in international transitions. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  15. Influence of 5-HTT variation, childhood trauma and self-efficacy on anxiety traits: a gene-environment-coping interaction study.

    Science.gov (United States)

    Schiele, Miriam A; Ziegler, Christiane; Holitschke, Karoline; Schartner, Christoph; Schmidt, Brigitte; Weber, Heike; Reif, Andreas; Romanos, Marcel; Pauli, Paul; Zwanzger, Peter; Deckert, Jürgen; Domschke, Katharina

    2016-08-01

    Environmental vulnerability factors such as adverse childhood experiences in interaction with genetic risk variants, e.g., the serotonin transporter gene linked polymorphic region (5-HTTLPR), are assumed to play a role in the development of anxiety and affective disorders. However, positive influences such as general self-efficacy (GSE) may exert a compensatory effect on genetic disposition, environmental adversity, and anxiety traits. We, thus, assessed childhood trauma (Childhood Trauma Questionnaire, CTQ) and GSE in 678 adults genotyped for 5-HTTLPR/rs25531 and their interaction on agoraphobic cognitions (Agoraphobic Cognitions Questionnaire, ACQ), social anxiety (Liebowitz Social Anxiety Scale, LSAS), and trait anxiety (State-Trait Anxiety Inventory, STAI-T). The relationship between anxiety traits and childhood trauma was moderated by self-efficacy in 5-HTTLPR/rs25531 LALA genotype carriers: LALA probands maltreated as children showed high anxiety scores when self-efficacy was low, but low anxiety scores in the presence of high self-efficacy despite childhood maltreatment. Our results extend previous findings regarding anxiety-related traits showing an interactive relationship between 5-HTT genotype and adverse childhood experiences by suggesting coping-related measures to function as an additional dimension buffering the effects of a gene-environment risk constellation. Given that anxiety disorders manifest already early in childhood, this insight could contribute to the improvement of psychotherapeutic interventions by including measures strengthening self-efficacy and inform early targeted preventive interventions in at-risk populations, particularly within the crucial time window of childhood and adolescence.

  16. Festival nimega Mono / Ivar Sakk

    Index Scriptorium Estoniae

    Sakk, Ivar, 1962-

    2015-01-01

    Haapsalu graafilise disaini festival Haapsalu Linnagaleriis: sisaldab ülevaate- ja teemanäitust ning väikest sümpoosioni. Temaatilise aastanäituse motiiv on "MONO". Plakateid on ka välismaa tegijatelt. Kuraator Marko Kekishev

  17. Tundmatu eesti disain / Ivar Sakk

    Index Scriptorium Estoniae

    Sakk, Ivar, 1962-

    2006-01-01

    Eesti disainist, selle teadvustamisest, disainiajaloo puudumisest. Eesti keraamika ajaloost on kirjutanud Leo Rohlin, klaasikunsti ajaloost Maie-Ann Raun, sisearhitektuuri ajaloost Krista Kodres. Kai Lobjakas on kirjutanud ülevaate "Märkmeid eesti disainist". Saksa disaineri Serge Rompza ja ameerika disainiteoreetiku Victor Margolini arvamusest näituse "Ajast ees" kohta

  18. Euro on teel / Ivar Jung

    Index Scriptorium Estoniae

    Jung, Ivar

    2005-01-01

    Reet Varblase kureeritud näitus "Oma raha" Tallinna Kunstihoone galeriis 12. XI-4. XII. Gints Gabransi videotest, Jaan Jaanisoo masin-installatsioonist, Siim-Tanel Annuse tööst. 2. XII galeriis toimunud kunstnike, kultuurihuviliste ja rahamaailma esindajate (Eesti Panga asepresident Rein Minka, endine president Vahur Kraft, rahandusministri nõuniku kt Veiko Valkiainen) kohtumisest

  19. Uue tantsu Superinimene / Ivar Põllu

    Index Scriptorium Estoniae

    Põllu, Ivar

    2007-01-01

    Festivalil "Uue tantsu nädal Tartus " esitatud viiest autorilavastusest : Katrin Essensoni "Manusega mõtted", Renate Valme "Mesta", Mart Kangro "Start. Based on a True Story", Kaja Kannu "There are Laika Dogs living in Estonia" ja Marten Spangbergi "Heja Sverige"

  20. Differentiating for loyalty / Ivar Soone

    Index Scriptorium Estoniae

    Soone, Ivar, 1975-

    2004-01-01

    Autor väidab, et kui on suudetud tekitada tarbija seotus ja sellel põhinev lojaalsus, saab turundaja võtta kasumit seda enam, mida kõrgema astme lojaalsusega on tegemist. Selline kasumi juhtimine muutub jätkusuutlikkuse ning konkurentsieelise hoidmisel üha olulisemaks. Graafikud. Tabelid

  1. Vorst ja poliitika / Ivar Tallo

    Index Scriptorium Estoniae

    Tallo, Ivar, 1964-

    2002-01-01

    Siiani on lahendamata erakondade rahastamise küsimus, samuti on reguleerimata, kes ja missuguses vormis tohib lobby teha ja kuidas peavad avaliku võimu esindajad sellisesse huvide esindamisse suhtuma. Autor: Rahvaerakond Mõõdukad

  2. Rahaga kleebit suu / Ivar Tallo

    Index Scriptorium Estoniae

    Tallo, Ivar, 1964-

    2009-01-01

    Ametnike politiseerimisest ja selle põhjusest. Autor on arvamusel, et sotsiaalminister Maret Maripuu valis endale 2007. a. kantsleriks inimese, kellel puudus ametnikuelu kogemus. See, et sotsiaalministeeriumi kantsler vabastatakse ja minister jätkab ametis, meenutab autori sõnul pigem monarhiat, kus monarh ei saanud eksida ja keegi alamatest pidi süü endale võtma

  3. Tõrvapott ja meetilgad / Ivar Tallo

    Index Scriptorium Estoniae

    Tallo, Ivar, 1964-

    2002-01-01

    Ilmunud ka: Põhjarannik ; Severnoje Poberezhje 2. oktoober lk. 2. Riigikogu liikmete palgast ja ametihüvedest. Autor: Rahvaerakond Mõõdukad. Vt. samas küsitlus Kuidas suhtute Riigikogu liikmete peaaegu kontrollimatutesse hüvitistesse? Vastavad: Eri Klas, Jaak Mae, Kuno Pajula, Mati Unt

  4. Musta pesu pesemine / Ivar Tallo

    Index Scriptorium Estoniae

    Tallo, Ivar, 1964-

    2005-01-01

    Valitsuse korruptsioonivastase asjatundjate komisjoni juht aastatel 2002-2003 on seisukohal, et ajakirjandus on ainult üks võimalikest vahenditest tõe tuvastamisel ning lõpliku tõe Edgar Savisaare ja Ain Hanschmidti jt seotud skandaalide kohta peavad selgitama võimuinstitutsioonid

  5. Silmaklapid julgeoleku tagatis? / Ivar Tallo

    Index Scriptorium Estoniae

    Tallo, Ivar, 1964-

    2009-01-01

    Riigikogus lugemisel olevast avaliku teabe seaduse eelnõust, milles nähakse ette võimalus, et internetis veebilehtedel olevaid andmeid riigiasutuste kohta võib riigi julgeoleku huvides hakata varjama

  6. Takistusriba avalikule teabele / Ivar Tallo

    Index Scriptorium Estoniae

    Tallo, Ivar, 1964-

    2004-01-01

    Autori arvates on riiklike registrite poolt jagatava teabe eest tasu võtmine avaliku teabe seadusega vastuolus ega vasta kaasaegsetele infotehnoloogilistele lahendustele. Vastuseks vt.Viljar Peep. Registritest 6.aug. Postimees lk. 10

  7. Sõrmuse uus retk / Ivar Laus

    Index Scriptorium Estoniae

    Laus, Ivar

    2002-01-01

    Peter Jacksoni esimene film J.R.R. Tolkieni triloogia "Sõrmuste isand" alusel - "Sõrmuse vennaskond", "The Lord of the Rings : The Fellowship of the Ring" : Uus-Meremaa, Ameerika Ühendriigid 2001. Erinev elamus DVD vaatamisest kinoekraanil nähtuga võrreldes

  8. Evidence for the Association of a Deleted Variant in the 5′-Flanking Region of the Chicken serotonin transporter (5-HTT Gene with a Temporary Increase in Feed Intake and Growth Rate

    Directory of Open Access Journals (Sweden)

    Joergen B. Kjaer

    2016-10-01

    Full Text Available The serotonergic system has been shown to be implicated in the regulation of mood and feeding behavior. Previous studies have identified a polymorphism in the 5′-flanking region of the serotonin transporter ( 5 - HTT gene of Lohmann Brown (LB laying hens. The deleted variant D was found to be associated with increased body weight. The objective of this study was to address whether the increased body weight may be due to an increased feed intake. After hatching, hens were kept under ad libitum feeding conditions, and their body weight and feed intake were weekly determined. From 5 weeks of age, the body weight of hens with the D/D and W/D genotypes was significantly greater than that of W/W carrying hens. Interestingly, we found that the feed intake of D/D carrying hens, relative to body weight, was transiently increased only between 4 and 7 weeks of age ( p < 0.05, leading to a higher growth rate ( p < 0.05, compared with that of W/W carrying hens. These results suggest that the presence of variant D may be correlated with a transiently increased appetite of D/D carrying hens.

  9. (Online & Print): 2305-7432. htt

    African Journals Online (AJOL)

    Peter Berglez

    could afford after working for a good five years in the public service as a teacher. ... image of the Life President, the Malawi Congress Party and the Ngwazi's diplomatic friends. Note that ... too close to be bribed and corrupted by that friendship.

  10. ELi institutsioonide ja juhtimise reform / Ivar Raig

    Index Scriptorium Estoniae

    Raig, Ivar, 1953-

    2003-01-01

    Kuna Eestist võib 2004. aasta mais saada EL-i liige, siis on vaja kujundada seisukoht, milline EL-i institutsioonide ja juhtimise reform oleks kõige vastuvõetavam Eesti kui erilise majanduspoliitikaga väikeriigi huvidest lähtuvalt. Märkused valitsuse sellekohaste seisukohtade suhtes ja ettepanekud nende muutmiseks või täiendamiseks

  11. Millennium breakthrough : North goes west / Ivar Leimus

    Index Scriptorium Estoniae

    Leimus, Ivar, 1953-

    2009-01-01

    Kaubandusest Kasaari ja Volga-Bulgari riigi keskustes. Saksa idamisjonist ja Põhjala misjonist. Ebaõnnestunud misjonist Kiievi-Venes. Inglise misjonist Rootsis ja Taanis. Seosest misjonitegevuse ja mündiekspordi lähtealade vahel. Euroopa orientatsioonile üleminekust paar sajandit enne Eesti vägivaldset hõivamist

  12. Kaklus andmekaitse ümber / Ivar Tallo

    Index Scriptorium Estoniae

    Tallo, Ivar, 1964-

    2006-01-01

    Vt. ka Postimees : na russkom jazõke 27. juuni lk. 7. Autor leiab, et andmekaitse kohta käivad otsused peavad olema põhjalikult läbi mõeldud ning samas peaksid ka kodanikud andmete avalikustamisest rohkem teadma

  13. Staatuspalga eelnõu / Ivar Tallo

    Index Scriptorium Estoniae

    Tallo, Ivar, 1964-

    2009-01-01

    Kõrgemate riigiteenijate palgakorraldusest ja vastavast seaduseelnõust. Lisatud: riigiteenijate palga muutus. Tabelis on toodud andmed ka presidendi palga kohta. Vt. ka juhtkiri lk. 2: Palgad jälle tõusevad

  14. Värviline revolutsioon Eestis? / Ivar Tallo

    Index Scriptorium Estoniae

    Tallo, Ivar, 1964-

    2009-01-01

    Autor viitab kohalike valimiste tulemustele järgnenud valulikule reaktsioonile avalikus meediaruumis. Järgmist, valimistevahelist aastat tuleb kasutada ühiskonna lepitamiseks ja ratsionaalse poliitikakäitumise edendamiseks

  15. Aukartus võimu ees / Ivar Tallo

    Index Scriptorium Estoniae

    Tallo, Ivar, 1964-

    2004-01-01

    Autori arvates valitseb Eestis olukord, kus tegelikke otsuseid langetatakse väljaspool otsustamise mehhanisme ning otsuste formaalsed tegijad ja nende eest vastutajad on erinevad inimesed. Erakondlik poliitika ja poliitikud

  16. Dr. Arthur Puksovi Fondi teadaanne / Ivar Nippak

    Index Scriptorium Estoniae

    Nippak, Ivar

    2005-01-01

    1975. aastal asutatud fondi eesmärgiks on innustada Eesti vanema ajaloo teaduslikku uurimist ja vastavate tööde kirjastamist. 2004. aastal tunnistati I auhinna vääriliseks Tiiu Reimo monograafia "Raamatukultuur Tallinnas 18. saj. teisel poolel" (2001); II auhinna sai Aivar Põldvee monograafia "Pakri rootslaste kaebused Karl XI-le 1684. aastal: muutuste aeg Harju-Madise ja Risti kihelkonnas" (2001) ja pikema artikli "Talurahvakoolid Eesti- ja Liivimaal 17. sajandi viimasel veerandil" (2002) eest. 2005. aastal fond auhindu ei andnud. Auhinnavõistlus 2006. aastaks on välja kuulutatud

  17. Millenniumi murrang : North goes West / Ivar Leimus

    Index Scriptorium Estoniae

    Leimus, Ivar, 1953-

    2007-01-01

    Enamiku muinasaja lõpu hõbeaarete rahadest moodustavad Kesk-Aasia mündid. Kaubandusest Kasaari ja Volga-Bulgari riigi keskustes, mis vahendasid kaubandust Idamaadega. Saksa idamisjonist ja Põhjala misjonist, ebaõnnestunud misjonist Kiievi-Venes. Inglise misjonist Rootsis ja Taanis. Seosest misjonitegevuse ja mündiekspordi lähtealade vahel. Euroopa orientatsioonile üleminekust paar sajandit enne Eesti vägivaldset hõlvamist

  18. Kirja teekond rahvusliku vormi otsinguil / Ivar Sakk

    Index Scriptorium Estoniae

    Sakk, Ivar, 1962-

    2010-01-01

    Kunstnikud kirja joonistamas. Trükikojad kujundavad Eesti kirjapilti. Art deco kui rahvuslikkuse manifestatsioon. Kirjandus räägib kirjast. Ruunikiri : Eesti oma kiri. Natsi-šrift ja Eesti traditsioon.

  19. "Agent Sinikael" aasta parim film / Ivar Sild

    Index Scriptorium Estoniae

    Sild, Ivar

    2003-01-01

    Eesti Filmiajakirjanike Ühing andis kümnendat korda välja auhinda Aasta film 2002. Parimaks filmiks tunnistati mängufilm "Agent Sinikael" : režissöör Marko Raat. Viimane sai preemiaks Neitsi Maali kuju ja 12 000 krooni

  20. Baselist Californiasse ja sealt Tallinna / Ivar Sakk

    Index Scriptorium Estoniae

    Sakk, Ivar, 1962-

    2011-01-01

    Ameerika iseõppinud disaineri David Carsoni, šveitsi tüpograafi Wolfgang Weingarti ja eesti disaineri ja graafiku Villu Järmuti loomingu kõrvutamine. Graafilise disaini areng Euroopas, nn. Baseli koolkond, "uus laine" (New Wave)

  1. Arusaamatu optimism / Ivar Tammemäe

    Index Scriptorium Estoniae

    Tammemäe, Ivar

    2010-01-01

    Intrum Justitia maksekultuuri-uuringust selgub, et vaid iga viienda Eesti ettevõtja arvates on kaupa või teenust krediiti müüa lähema aasta jooksul riskantsem kui praegu. Enamik Kreeka, Belgia, Saksamaa, Prantsusmaa ja Iirimaa jt. äri- ja finantsjuhte arvab, et riskid suurenevad. Intrum Justitia tegevdirektor viitab, et Eestis on keskmise makseviivituse aeg pikenenud, kasvanud on üle 3 kuu pikkused võlad, krediidikahjud on kasvanud 14%

  2. Kolm ilmarada ja jumalat / Ivar Sild

    Index Scriptorium Estoniae

    Sild, Ivar

    2002-01-01

    Arvustus: Kompus, Marko. Make love not love. Põlgaste ; Soodoma ; Kanepi : Erakkond, 2001; Mathura [Lattik, Margus]. Poeesia valgel taustal. Tln. : Erakkond, 2001; Sommer, Lauri. Raagraamis poiss. Tartu : EYS Veljesto, 2001

  3. Riik, ohuallikad ja inimeste hirmud / Ivar Aimre

    Index Scriptorium Estoniae

    Aimre, Ivar, 1941-2009

    2005-01-01

    Autori hinnangul tähendab turvalisuse tootmine hirmude asjatu suurendamise ärahoidmist, ohtudest ja õnnetustest õigeaegset ning efektiivset teavitamist, nende puhul tõhusat tegutsemist ning sootsiumile sellekohase info edastamist

  4. Integration and Validation of Avian Radars (IVAR)

    Science.gov (United States)

    2011-07-01

    TrackViewer Workstation UAV Unmanned Aerial Vehicle USDA United States Department of Agriculture USFWS United States Fish & Wildlife Service...hovering above water, with the hope that they are feeding on fish below. Many marine radars in fact have a “bird” setting on the setup and installation...the current position (yellow blob ) of the target (in this case, a flock of Mallards), while a straight line of blue blobs denoting returns from the

  5. Loss aversion and 5HTT gene variants in adolescent anxiety.

    Science.gov (United States)

    Ernst, Monique; Plate, Rista C; Carlisi, Christina O; Gorodetsky, Elena; Goldman, David; Pine, Daniel S

    2014-04-01

    Loss aversion, a well-documented behavioral phenomenon, characterizes decisions under risk in adult populations. As such, loss aversion may provide a reliable measure of risky behavior. Surprisingly, little is known about loss aversion in adolescents, a group who manifests risk-taking behavior, or in anxiety disorders, which are associated with risk-avoidance. Finally, loss aversion is expected to be modulated by genotype, particularly the serotonin transporter (SERT) gene variant, based on its role in anxiety and impulsivity. This genetic modulation may also differ between anxious and healthy adolescents, given their distinct propensities for risk taking. The present work examines the modulation of loss aversion, an index of risk-taking, and reaction-time to decision, an index of impulsivity, by the serotonin-transporter-gene-linked polymorphisms (5HTTLPR) in healthy and clinically anxious adolescents. Findings show that loss aversion (1) does manifest in adolescents, (2) does not differ between healthy and clinically anxious participants, and (3), when stratified by SERT genotype, identifies a subset of anxious adolescents who are high SERT-expressers, and show excessively low loss-aversion and high impulsivity. This last finding may serve as preliminary evidence for 5HTTLPR as a risk factor for the development of comorbid disorders associated with risk-taking and impulsivity in clinically anxious adolescents. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Loss aversion and 5HTT gene variants in adolescent anxiety

    Directory of Open Access Journals (Sweden)

    Monique Ernst

    2014-04-01

    Full Text Available Loss aversion, a well-documented behavioral phenomenon, characterizes decisions under risk in adult populations. As such, loss aversion may provide a reliable measure of risky behavior. Surprisingly, little is known about loss aversion in adolescents, a group who manifests risk-taking behavior, or in anxiety disorders, which are associated with risk-avoidance. Finally, loss aversion is expected to be modulated by genotype, particularly the serotonin transporter (SERT gene variant, based on its role in anxiety and impulsivity. This genetic modulation may also differ between anxious and healthy adolescents, given their distinct propensities for risk taking. The present work examines the modulation of loss aversion, an index of risk-taking, and reaction-time to decision, an index of impulsivity, by the serotonin-transporter-gene-linked polymorphisms (5HTTLPR in healthy and clinically anxious adolescents. Findings show that loss aversion (1 does manifest in adolescents, (2 does not differ between healthy and clinically anxious participants, and (3, when stratified by SERT genotype, identifies a subset of anxious adolescents who are high SERT-expressers, and show excessively low loss-aversion and high impulsivity. This last finding may serve as preliminary evidence for 5HTTLPR as a risk factor for the development of comorbid disorders associated with risk-taking and impulsivity in clinically anxious adolescents.

  7. Unistuste õhuloss juustumaal Šveitsis / Ivar-Kristjan Hein

    Index Scriptorium Estoniae

    Hein, Ivar-Kristjan

    2002-01-01

    New Yorgi arhitektide Elizabeth Dilleri (46) ja Ricardo Scofidio (65) looming Neuchateli järvel - kunstlik pilv, kuhu saab siseneda. Arhitektid eksperimenteerivad ruumikasutuse erinevate võimalustega

  8. Läti koduloomade huvitav elu / Ivar Jung

    Index Scriptorium Estoniae

    Jung, Ivar

    2006-01-01

    Eesti, Läti ja Sloveenia koostööfilm "Koer, lennuk ja laulupidu" ("The Hostage") : režissöör ja stsenarist Laila Pakalnina : operaator ja üks produtsentidest Arko Okk : Eesti (Acuba Film) - Läti (Casablanca Film Production) 2006

  9. Naistepäev ikka hinnas / Ivar Jung

    Index Scriptorium Estoniae

    Jung, Ivar

    2003-01-01

    Kunstihoone galeriis Ivika Kivi ja Dagmar Kase näituse "ID 2002" taustal 8. III toimunud Reet Varblase organiseeritud seminarist "Naised, ühiskond, ilu ja hügieen". Linnagaleriis lõpetas Meiu Mündi maalinäituse Oksana Titova tantsuetendus. 9. III Pärnus Taave Tuutma kureeritud tegevuskunstipäev

  10. Estonský styl = estonian style / Ivar Sakk

    Index Scriptorium Estoniae

    Sakk, Ivar, 1962-

    2009-01-01

    Eesti graafilise disaini rahvuslikust eripärast ja arengust 20. sajandil. Teiste riikide (Rootsi, Venemaa, Saksamaa) mõjust eesti graafilise disaini kujunemisele. Lähemalt Günther Reindorffi, Paul Luhteina tegevusest

  11. Kas uus teerull või uus poliitika? / Ivar Tallo

    Index Scriptorium Estoniae

    Tallo, Ivar, 1964-

    2003-01-01

    Autor küsib, kas koalitsioonileppe näol on tegemist ühiste väärtuste deklaratsiooni, järgmiste aastate riigivalitsemise tegevuskava või kohtade jaotusega riigi juhtimiseks. Riigieelarve teadliku vähendamise probleemist

  12. Tagurpidi pööratud poliitika / Ivar Tallo

    Index Scriptorium Estoniae

    Tallo, Ivar, 1964-

    2009-01-01

    Autor näeb vastuolu seoses vaidlusega kaitseväelaste õiguse üle määrata enda hukkumishüvitise saaja: konservatiivse IRL-i minister Jaak Aaviksoo kaitseb sõdurite valikuvabadust ning liberaalist Reformierakonna minister Jürgen Ligi tahaks sõdurite eest otsustada

  13. Kas tõmbame vee peale? / Ivar Tallo

    Index Scriptorium Estoniae

    Tallo, Ivar, 1964-

    2007-01-01

    Autori hinnangul on riigi uuendamise teema jäänud viimase kolme valitsuse tähelepanu alt täiesti kõrvale - nagu oleks Eesti riik valmis saanud. Tema sõnul oleks e-riigi arendamisega võimalik Eesti murenevat positiivset mainet püsti hoida

  14. Poliitikat ja vorsti ei tehta ühtemoodi / Ivar Tallo

    Index Scriptorium Estoniae

    Tallo, Ivar, 1964-

    2006-01-01

    Tallinna linnavolikogus puhkenud lindiskandaalist. Autori arvates näitab järjekordne skandaal, et poliitikutel puudub elementaarne vastutustunne oma tegevuse tulemuste suhtes ning poliitika puhastumisprotsess Eestis alles kestab

  15. Euroopa hiliskeskaja suur depressioon - kas ka Liivimaal? / Ivar Leimus

    Index Scriptorium Estoniae

    Leimus, Ivar, 1953-

    2005-01-01

    Elutarbekaupade enam kui kolmekordse kallinemise tõenäoliseks põhjuseks Liivimaal 15. saj. esimesel kolmandikul võib pidada tootjate (maaelanike) arvu märgatavat vähenemist. Järgneva reaalhindade languse põhjustas arvatavasti münditoodangu järsk vähenemine alates 1440. aastatest. Pöördepunkt Liivimaa majanduses saabus 15. saj. viimasel veerandil, mil elavnes müntimine ja raha jätkus nii ehitustöödeks kui hinnaliste altarite muretsemiseks

  16. Kellogg's - identiteedi või 7 toitaine allikas? / Ivar Soone

    Index Scriptorium Estoniae

    Soone, Ivar, 1975-

    2003-01-01

    Strateegia, mille abil Kellogg's on loonud unikaalse identiteedi, mis on segu füüsilistest hoomatavatest ja psühholoogilistest hüvedest, on toonud ettevõttele edu aastakümneid ja toob ka edaspidi, leiab autor. Skeem: Pakendi kui esmase kommunikatsioonikanali osade funktsioonid. Kommenteerib Elar Killumets. Lisa: Paul Twivy: Brändid peavad täitma oma lubadused

  17. Kaks soome-ugri keeleõppe projekti / Ivar Sinimets

    Index Scriptorium Estoniae

    Sinimets, Ivar

    2010-01-01

    Kahest ungari keele õpetamisele keskendunud projektist "survival.hu" ja "TeLeHu", mille eesmärgiks oli õppematerjalide valmistamine, õpetajate täiendamine ning ka hindamisaluste väljatöötamine ja ungari keele õpetajate infovõrgustiku loomine

  18. Unikaalne leid Tallinna lahest / Ivar Leimus, Krista Sarv

    Index Scriptorium Estoniae

    Leimus, Ivar, 1953-

    2012-01-01

    Hobisukelduja Andrei Ossiptšuki poolt augustis 2011 leitud keskaegsest reisikastist, mis sisaldas münte, klappkaalud koos vihikomplektiga ,nugade katkeid. Tõenäoliselt kuulus kast 13. sajandi lõpu kaupmehele. Noatuppede ornamentikast. Sarnasusest Inglismaa ja Iirimaa vastava leiumaterjaliga

  19. Ivar Vigla. Mees, keda pole / Gert D Hankewitz

    Index Scriptorium Estoniae

    Hankewitz, Gert D

    2007-01-01

    Teleprodutsent. Teised temast : "Toomas Lepp : kahepalgeline mees", "Erki Berends : veenmisjõuline mees", "Jan Uuspõld : usalduisväärne mees", "Andrus Nilk : omaette mõtleja". Lisaks "Kuidas vimkast tõusis paanika"

  20. How did mintmaster Leinhart Pauwermann die? / Ivar Leimus

    Index Scriptorium Estoniae

    Leimus, Ivar, 1953-

    2011-01-01

    Leinhart Pauwermann on väheseid nimepidi teada mündimeistreid keskaegsest Soomest. Tallinna bürgermeistri Jacob Richerdesi ettepanekul alustati öörodi jt. müntide vermimist 1523. aastal. 1524. aastal jätkus tegevus Tallinnas. Liivimaa ordumeister Wolter von Plettenberg keelas illegaalse tegevuse ja Pauermanni rahad kuulutati keelatuks Valmiera maapäeval 1525. Seda lugu käsitleb ka hiljuti leitud 1860ndaltel aastatel ajaloolase Eduard Pabsti poolt tehtud väljakirjutus Suure Gildi materjalidest. Väljakirjutuse tekst ja ligikaudne tõlge

  1. Ivar Tallo: presidendi erakorteris käinud peod mainet ei kahjusta / Ivar Tallo ; interv. Sigrid Laev

    Index Scriptorium Estoniae

    Tallo, Ivar, 1964-

    2006-01-01

    Noortepeod Kadrioru presidendilossis. Avaliku halduse spetsialist vastab küsimustele, kuidas jaguneb Kadrioru lossis era- ja avalik ruum, kas on õigustatud presidendi kantselei taotlus registreerida kõik, ka erakülalised ning kas juhtunu võib kahjustada presidendi mainet. Kaart, skeem: sissepääsud. Vt. samas. Presidendipaar palus vabandust ; Politsei kogub Kadrioru lastepidude kohta infot. Tallinna Vanalinna hariduskolleegiumi põhikooli juhataja Alar Saare kommentaar ; Garel Püüa. Kärmas: tegu ei ole poliitilise vandenõuga

  2. Ivar Tallo : presidendi erakorteris käinud peod mainet ei kahjusta / Ivar Tallo ; interv. Sigrid Laev

    Index Scriptorium Estoniae

    Tallo, Ivar, 1964-

    2006-01-01

    Avaliku halduse spetsialist vastab küsimustele, kuidas jaguneb Kadrioru lossis era- ja avalik ruum, kas on õigustatud presidendi kantselei taotlus registreerida kõik, ka erakülalised ning kas juhtunu võib kahjustada presidendi mainet. Kaart, skeem: Sissepääsud. Kommenteerivad Andrus Ansip, Villu Reiljan, Andrus Saar. Vt. samas: Presidendipaar palus vabandust; Garel Püüa. Kärmas: tegu ei ole vandenõuga

  3. Effect of hydrothermal treatment of coal on the oxidation susceptibility and electrical resistivity of HTT coke

    Energy Technology Data Exchange (ETDEWEB)

    Sarkar, N.B.; Sarkar, P.; Choudhury, A. [Central Fuel Research Institute, P.O. FRI, Dhanbad-828108, Jharkhand (India)

    2005-02-25

    The influence of hydrothermal treatment of coal prior to carbonization, on the oxidation susceptibility of resultant coke/char, calcined at 1350, 1800 and 2200 {sup o}C has been investigated. The non-isothermal thermogravimetric analysis technique has been employed, and parameters such as onset, DTG peak temperatures, and cumulative oxidation loss (wt.%) at different temperatures have been utilized to compare proneness to oxidation with respective untreated samples apart from electrical resistivity. Data suggest that all the cokes/chars samples produced from hydrothermally treated coals are less reactive and more electrically conductive (less resistive) than their respective untreated counterparts. But the extent of improvement of oxidation resistance and electrical conductivity appears to be coal-specific. The kinetic parameters obtained by non-linear regression analysis on multi-curve reveal that the n{sup th} order reaction model (where 'n' was found to vary from 0.9 to 1.3) is the best-fitted model. The higher activation energy values observed for hydrothermally treated coke samples are in agreement with the observation of TG analysis data. Overall results indicate the importance of introducing a hydrothermal treatment step for the improvement of oxidation resistance as well as electrical conductivity of the coke samples.

  4. Amotz Zahavi - mees, kes leidis raiskamisele evolutsioonilise seletuse / Peeter Hõrak, Ivar Puuura

    Index Scriptorium Estoniae

    Hõrak, Peeter, 1963-

    2009-01-01

    Septembri alguses esineb Tartus loengutega Tel-Avivi ülikooli emeriitprofessor Amotz Zahavi. Ta on uurinud looduslikku valikut ning leidnud seal palju raiskamist ja pillamist, mis on omane inimühiskonnalegi

  5. Andrei Koroli kohtuasi - kindlad võitjad on advokaat ja kaebaja / Ivar Soopan

    Index Scriptorium Estoniae

    Soopan, Ivar, 1971-

    2006-01-01

    Araabia Ühendemiraatides vahistatud Eesti kaitseväelase Andrei Koroli advokaat Hesham Al Naswani räägib A. Koroli ja egiptlannast politseiniku Mirvati tunnistustest. Vt. samas: Dubai ajalehe reporter: see on ilmselt väljapressimine

  6. Pärnumaal koolitati välisernalasi / Erik Reinhold ; interv. Ivar Jõesaar

    Index Scriptorium Estoniae

    Reinhold, Erik

    2004-01-01

    Kaitseliidu Pärnumaa maleva pealik kapten Erik Reinhold räägib Pärnumaal toimunud patrullvõistluse Erna retk 2004 ettevalmistuslaagrist, milles Eesti, Saksamaa ja Türgi võistkonnad läbisid väljaõppeprogrammi

  7. Maandatud pinged igavas provintsiriigis - Arnold Rüütli viis aastat Kadriorus / Ivar Tallo

    Index Scriptorium Estoniae

    Tallo, Ivar, 1964-

    2006-01-01

    Avaliku halduse ekspert analüüsib president Arnold Rüütli tegevust. Võrdlus president Lennart Meriga. Presidendi kantseleist. Vt. samas: Eesti Vabariigi president on meie põhiseaduse järgi Eesti riigipea, kellel on 20 konkreetset ametiülesannet. Lisa: President Rüütli tähtsamad abilised esimesel ametiajal

  8. Tallo: IT-ala vajab arhitekti kätt / Ivar Tallo ; intervjueerinud Rein Sikk

    Index Scriptorium Estoniae

    Tallo, Ivar, 1964-

    2010-01-01

    Autor analüüsib ebaõnnestumisi avaliku sektori IT-projektides ning ütleb, et kõige suurem kaotus on olnud usalduse kaotus uute e-lahenduste vastu. Riigis peaks olema üks inimene, kes vastutaks kogu avaliku sektori IT eest

  9. Hizbollah lubab : "Me tahame ameeriklastega häid suhteid" / Mohamad Afif ; interv. Ivar Soopan

    Index Scriptorium Estoniae

    Afif, Mohamad

    2005-01-01

    Liibanoni shiiitide organisatsiooni Hizbollah meediasuhete direktor ütleb, et Hizbollah ei ole terroriorganisatsioon. Religioosse ja poliitilise grupina tahab Hizbollah häid suhteid teistega kõikjal maailmas, kuid probleem on poliitikas, selles, kuidas USA suhtub nende regiooni, tõekspidamistesse

  10. Faktooring käibevahendite finantseerimise vahendina / Ivar Sikk, Kaido Kallas

    Index Scriptorium Estoniae

    Sikk, Ivar

    2002-01-01

    Faktooring on väga paindlik käibevahendite finantseerimise vahend, mis sobib kõikidele ettevõtetele, kes pakuvad või soovivad pakkuda oma kauba või teenuse ostjatele maksetähtaega. Tabelid. Joonised

  11. Die spätmittelalterliche grosse Wirtschaftskrise in Europa - war auch Livland davon betroffen? / Ivar Leimus

    Index Scriptorium Estoniae

    Leimus, Ivar, 1953-

    2005-01-01

    Oluliste kaupade kallinemiseest, mille põhjustas tõenäoliselt (maaelanike) arvu märgatav vähenemine. Järgnenud reaalhindade languse põhjustas arvatavasti münditootmise oluline vähenemine. Pöördepunkt Liivimaa majanduses saabus 15. saj. viimasel veerandil

  12. E.E.L.K. Peapiiskopi valimised / Thomas Vaga, Ivar Nippak

    Index Scriptorium Estoniae

    Vaga, Thomas, 1938-

    2007-01-01

    21. detsembril teatas häältelugemiskomisjon, et kaks enam hääli saanud kandidaati on Thomas Vaga ja Andres Taul. Samade kandidaatide vahel toimub korduv hääletus. Uued valimismaterjalid saadetakse välja 2007. aasta jaanuaris

  13. Puud pillavad koort, kirjanikud tekste : Michel Butor Oklahomas / Ivar Ivask ; tõlkinud Mart Kuldkepp

    Index Scriptorium Estoniae

    Ivask, Ivar, 1927-1992

    2010-01-01

    Michel Butor külastas 1971-1981 Oklahoma Ülikooli kolmel korral: 1971 esines loengutega, 1974 kuulus Neustadti kirjandusauhinna žüriisse ning 1981 toimus ülikoolis tema loomingule pühendatud Puterbaugh' konverents

  14. Majandusvabadusi kujundav majanduspoliitika Eestis ja selle perspektiivid Euroopa Liidus / Ivar Raig

    Index Scriptorium Estoniae

    Raig, Ivar, 1953-

    2004-01-01

    Lühiülevaade majandusvabadusi kujundavast majanduspoliitikast taasiseseisvunud Eestis, EL-i mõju Eesti majanduspoliitikale, uuringu tulemustest majandusvabaduste kohta Eesti erinevates majandussektorites. Tabel

  15. Kodusandi märk - tõend vaestehoolekandest Tallinnas 16. sajandil / Ivar Leimus

    Index Scriptorium Estoniae

    Leimus, Ivar, 1953-

    2008-01-01

    Oleviste majavaese märgist. Oleviste kiriku juurde vaeste fondi asutanud Lutke van Oyteni elukäigust. Tõus vallaslapsest linna eliiti polnud hiliskeskajal tavaline saatus. Kahjuks polnud tema loodud fondil õnne. Laekumiste lakkamine sõjaajal ja inflatsioon sõid selle nelja aastakümne jooksul peaaegu olematuks

  16. Kaitseväelase ja kaitseliitlase uue sajandi sõjavarustus / Ivar Jõesaar

    Index Scriptorium Estoniae

    Jõesaar, Ivar, 1960-

    2005-01-01

    Tutvustav ülevaade kaitseväelaste ja -liitlaste uuest vormiriietusest, relvastusest ning muust lahinguvarustusest, mis on vastavuses 21. sajandil NATO liikmesriigi sõjaväele esitatavate nõuetega ning kavandatud kaitsejõudude arenguplaanis aastani 2010

  17. Tagasiviitavad tõendid: teine pilk pilditeadusele / Beat Wyss ; intervjueerinud Ivar-Kristjan Hein

    Index Scriptorium Estoniae

    Wyss, Beat, 1947-

    2011-01-01

    Intervjuus Karlsruhe kunsti- ja disainiülikooli kunstiajaloo ja meediateooria professori Beat Wyssiga on teemaks Zürichis tema juhitav uurimisprojekt, mille keskmes on Venezia biennaal Ida-Euroopa riikide positsioonilt, tema EKA Kunstiteaduse Instituudi doktorantidele peetud seminar "Tagasiviitavad tõendid. Teine pilk pilditeadusele", tema kaasaegse kunsti universaalsed põhimõtted

  18. Baselist Californiasse ja sealt Tallinna = From Basel to Califonia and from there to Tallinn / Ivar Sakk

    Index Scriptorium Estoniae

    Sakk, Ivar, 1962-

    2001-01-01

    Ameerika iseõppinud disaineri David Carsoni, šveitsi tüpograafi Wolfgang Weingarti ja eesti disaineri ja graafiku Villu Järmuti loomingu kõrvutamine. Graafilise disaini areng Euroopas, nn. Baseli koolkond, "uus laine" (New Wave)

  19. Eestimaa Kirjanduse Ühingu mündikogu kujunemisest / Ivar Leimus

    Index Scriptorium Estoniae

    Leimus, Ivar, 1953-

    2013-01-01

    Eesti Kirjanduse Ühingu mündikogu oli vanem kui muuseum ja asutati 1844. aastal. Mündikogu oli ühingu kõige kiiremini kasvavaid kollektsioone. Kogu haruldustest. Algusest peale oli EKÜ numismaatikakogu kaasaegse Europa tasemel või sellest isegi eespool

  20. Alex Miller, Knesseti liige : Iisrael mõtleb oma kodanikele / Alex Miller ; interv. Ivar Soopan

    Index Scriptorium Estoniae

    Miller, Alex

    2007-01-01

    Iisraeli parlamendiliikme sõnul ei ole läbirääkimised Palestiinaga vastuvõetavad, kui valitsuses on Hamas. Iisraeli-Palestiina konflikt ei ole tema sõnul mitte territoriaalprobleem, vaid tsivilisatsioonidevaheline konflikt. Parlamendiliige vastab küsimustele, mis puudutavad Palestiinale kuuluva 600 miljoni dollari maksuraha kinnihoidmist ning 40 Palestiina parlamendiliikme vangistamist, samuti Liibanoni ründamist eelmisel aastal

  1. Erikontrollil on tellija nägu / Ivar Kiigemägi

    Index Scriptorium Estoniae

    Kiigemägi, Ivar, 1974-

    2011-01-01

    Vastukaja artiklitele: Esse, Fredy-Edwin. Aivar Pilv: Arco erikontrollis paljud küsimused vastuseta (aripaev.ee, 20.09.2011) ; Esse, Fredy-Edwin.Arco erikontrolli raport koosneb avalikust infost (aripaev.ee, 20.09.2011)

  2. Palestiinlaste katastroof : Iisraeli asundused ja äärmuslik Hamas / Ivar Soopan

    Index Scriptorium Estoniae

    Soopan, Ivar, 1971-

    2007-01-01

    Äärmusrühmituse Hamas võit 2006. aastal Palestiina parlamendivalimistel näitas, et rahvas oli väsinud korrumpeerunud võimust, samas ei pööratud tähelepanu sellele, et Hamas kasutab oma eesmärkide saavutamiseks vägivalda. Palestiina teabeminister Mustafa Barghout taunib, et Iisrael ei võta Palestiina valitsust kui ühtset võimu, vaid teeb vahet Hamasi ja teiste poliitiliste jõudude ministritel. Palestiinlane Ala Shehadeh palestiinlaste intifadadest, juudi asunduste probleemist. Vt. samas: Miks Palestiinas elatakse nagu sada aastat tagasi?

  3. Hertsog Magnus, tema võlad ja võlausaldajad / Ivar Leimus

    Index Scriptorium Estoniae

    Leimus, Ivar, 1953-

    2008-01-01

    Lisa : Nimekiri hertsog Magnuse võlgadest (tõenäoliselt koostatud 1561. aastal). Hertsog Magnuse võlausaldajateks olid kohalikud aadlikud, kaupmehed. Tohutute võlgade katteks annetas Magnus maavaldusi, mis tähendas aga sissetulekuallikate vähenemist.

  4. Interaction of child maltreatment and 5-HTT polymorphisms: suicidal ideation among children from low-SES backgrounds.

    Science.gov (United States)

    Cicchetti, Dante; Rogosch, Fred A; Sturge-Apple, Melissa; Toth, Sheree L

    2010-06-01

    To investigate whether genotypic variation of the serotonin transporter gene-linked promoter region (5-HTTLPR) moderates the effect of maltreatment on suicidal ideation in school-aged children. Eight hundred and fifty low-income children (478 maltreated; 372 non-maltreated) provided DNA samples and self-reported depressive and suicidal symptoms. Genotypes of 5-HTTLPR (s/s or s/l vs. l/l) were determined by fragment analyses. Higher suicidal ideation was found among maltreated than non-maltreated children; the groups did not differ in 5-HTTLPR genotype frequencies. Children with one to two maltreatment subtypes and s/s or s/l genotypes had higher suicidal ideation than those with the l/l genotype; suicidal ideation did not differ in non-maltreated children or children with three to four maltreatment subtypes based on 5-HTTLPR variation. The results were applicable to emotionally maltreated/neglected and to physically/sexually abused children. Gene-environment interaction was not found for depressive symptoms. The protective effect of the 5-HTTLPR l/l genotype on suicidal ideation was limited to maltreated children experiencing fewer subtypes.

  5. Convergent genetic modulation of the endocrine stress response involves polymorphic variations of 5-HTT, COMT and MAOA

    NARCIS (Netherlands)

    Jabbi, M.; Korf, J.; Kema, I. P.; Hartman, C.; van der Pompe, G.; Minderaa, R. B.; Ormel, J.; den Boer, J. A.

    Highly prevalent stress-related disorders such as major depression ( MD) are characterised by a dysregulation of the neuroendocrine system. Although heritability for these disorders is high, the role of genes in the underlying pathophysiology is poorly understood. Here, we show that polymorphic

  6. Iraagi hall kardinal usub uude riiki / Muhsen Naif Al-Faisal Al-Jarba ; interv. Ivar Soopan

    Index Scriptorium Estoniae

    Al-Jarba, Muhsen Naif Al-Faisal

    2004-01-01

    Iraagi presidendi ja peaministri nõuniku sõnul tahab Iraak üles ehitada tõelise armee, politsei, piirivalve. Pärast seda koalitsiooniarmeed enam ei vajata. Rahu kogu Lähis-Idas sõltub Iisraelist, ütleb nõunik. Vt. samas: Kuidas ma tutvusin sheigiga

  7. Ivar Andenæs: Medier i sjokk og sorg. Pressens møde med terroren 22. juli 2011

    DEFF Research Database (Denmark)

    Andersen, Michael Bruun

    2013-01-01

    Anmeldelse af bog om norske journalisters vurdering af norske mediers dækning af Breivik-massakren.......Anmeldelse af bog om norske journalisters vurdering af norske mediers dækning af Breivik-massakren....

  8. Väliskülalistele jäi silma eestlaste suur armastus oma teatri vastu / Ivar Põllu

    Index Scriptorium Estoniae

    Põllu, Ivar, 1974-

    2005-01-01

    10. sept. lõppenud festivali "Draama 2005" laureaatidest. Parima lavastuse auhinna pälvis T. Ojasoo ja E.-L. Semperi "Julia" ja väliskriitikute eriauhinna E. Nüganeni "Tõde ja õigus. Teine osa". Lisatud laureaatide nimekiri. Vt. ka lk..2 "Draama läbi. Draamata"

  9. Iura christianorum - Läti Henriku sõnakõlks või nõks paganate alistamiseks? / Ivar Leimus

    Index Scriptorium Estoniae

    Leimus, Ivar, 1953-

    2011-01-01

    Kristlikust õigusest kui paganlike normide ja käitumisviisi asendajast. Korduvalt nimetab oma kroonikas kristlikku õigust Läti Henrik. Tavaliselt käisid ristimine ja kristlik seadus käsikäes. Kümnis oli kristliku õigussüsteemi osa, mis kohati asendati vakamõõduga. Ristimine oli mitte ainult religioosne, vaid poliitiliselt oluline akt. Kristliku õiguse ilmalik osa tähendas kohustust osaleda sakslaste sõjaretkedel, kirikute ehitamisel jne. Kuid kristlaste õiguse omaksvõtt ei tähendanud veel maaomandi kaotamist. Ristisõdijate lepingutest kohalike hõimudega. Mõiste "iura christianorum" omas kindlat sisu, mille ümber vallutajad ehitasid kogu uue sotsiaalse võrgustiku ja läänekristlusel põhineva feodaalsüsteemi

  10. Ainult hulludele : [ultra-võistluste sarjast Haanja100 Neliküritus] / Ivar Tupp aka Dr Holden

    Index Scriptorium Estoniae

    Tupp, Ivar

    2011-01-01

    Tartu üliõpilaste looduskaitseringi Lumeilvese matkadest ehk Eesti 20 kõrgeima mäetipu vallutamisest, millest kasvas välja haanjamatkad.ee, mis korraldab ka ülipika distantsiga spordivõistluste sarja Haanja neliküritus. Lisa: Matk üle mägede

  11. Plasmodium falciparum i>var genes expressed in children with severe malaria encode CIDRα1 domains

    DEFF Research Database (Denmark)

    Jespersen, Jakob S.; Wang, Christian W.; Mkumbaye, Sixbert I.

    2016-01-01

    Most severe Plasmodium falciparum infections are experienced by young children. Severe symptoms are precipitated by vascular sequestration of parasites expressing a particular subset of the polymorphic P. falciparum erythrocyte membrane protein 1 (PfEMP1) adhesion molecules. Parasites binding hum...... the hypothesis that the CIDRα1-EPCR interaction is key to the pathogenesis of severe malaria and strengthen the rationale for pursuing a vaccine or adjunctive treatment aiming at inhibiting or reducing the damaging effects of this interaction....

  12. Enesessetõmbumine ehk Ungari välispoliitika argipäevad / Anita Orban ; tõlk. Ivar Sinimets

    Index Scriptorium Estoniae

    Orban, Anita

    2006-01-01

    Autor leiab, et Ungari välispoliitika on toodud sisepoliitikale ohvriks ja seetõttu suudetakse saavutada ainult murdosake sellest, mida tegelikult tuleks ja saaks teha. Ungari diplomaatia pole võimeline pärast liitumisläbirääkimisi ELiga välja töötama või ellu viima Ungari huve hõlmavat kontseptsiooni. Ülevaade riigi poliitilisest olukorrast

  13. Alkoholi tootmine ja turg : [2002-2004] / Katrin Karolin

    Index Scriptorium Estoniae

    Karolin, Katrin

    2005-01-01

    Ilmunud ka: Agriculture and the development of rural life : overview 2004/2005. - Tallinn, 2005, lk. 45-47. 2004. a. 9 kuu alkoholi jaekäive ulatus 2,2 mld kroonini, mis on 13% suurem kui eelmise aasta samal perioodil. Tabelid: Alkohoolsete jookide tootmine Eestis (9 kuud 2002-2004); Alkoholi tarbimine elanike hinnangute alusel

  14. Digital Load Control Applied to Full-Scale Airframe Fatigue Tests

    Science.gov (United States)

    1979-05-01

    77 ’ iELT A19 AFFDL-TR-79-3011 The zero steady-state error is consistent with the model even with the bias, i.e.: REF KpS + Ki K C The response of...console operator has the following functions available: U Disk read or write R Read Slave common table W Write to Slave common table G Start a job L...IVAR IVAR = 1 XNIT ARRAY TO SLAVE IVAR = 2 RECEIVE ARRAY FROM SLAVE IVAR = 3 WRITE OUT COMMON TO DISK IVAR = 4 READ IN OLD COM4ON FROM DISK IVAR = 5

  15. 25. XI esitleti Viviann Napi galeriis...

    Index Scriptorium Estoniae

    2004-01-01

    Esitleti Berliinis elava kunstniku Ivar Kaasiku raamatut "Camera obscura, Ivar Kaasiku õlimaalid 2001-2004". Sissejuhatavad ja tõlgendavad tekstid on kirjutanud Harry Liivrand, Jaan Elken ja Raivo Kelomees

  16. Association of the 5-HTT gene-linked promoter region (5-HTTLPR polymorphism with psychiatric disorders: review of psychopathology and pharmacotherapy

    Directory of Open Access Journals (Sweden)

    Kenna GA

    2012-01-01

    Full Text Available George A Kenna1, Nick Roder-Hanna2, Lorenzo Leggio3, William H Zywiak4, James Clifford5, Steven Edwards3, John A Kenna6, Jessica Shoaff1, Robert M Swift11Center for Alcohol and Addiction Studies, Department of Psychiatry and Human Behavior, Brown University, Providence; 2College of Pharmacy, University of Rhode Island, Kingston; 3Center for Alcohol and Addiction Studies, Department of Community Health, Brown University, Providence; 4Butler Hospital, Providence, RI; 5Virginia Institute for Psychiatric and Behavior Genetics, Virginia Commonwealth University, Richmond, VA; 6College of Nursing, University of Rhode Island, Kingston, RI, USAAbstract: Serotonin (5-HT regulates important biological and psychological processes including mood, and may be associated with the development of several psychiatric disorders. An association between psychopathology and genes that regulate 5-HT neurotransmission is a robust area of research. Identification of the genes responsible for the predisposition, development, and pharmacological response of various psychiatric disorders is crucial to the advancement of our understanding of their underlying neurobiology. This review highlights research investigating 5-HT transporter (5-HTTLPR polymorphism, because studies investigating the impact of the 5-HTTLPR polymorphism have demonstrated significant associations with many psychiatric disorders. Decreased transcriptional activity of the S allele (“risk allele” may be associated with a heightened amygdala response leading to anxiety-related personality traits, major depressive disorder, suicide attempts, and bipolar disorder. By contrast, increased transcriptional activity of the L allele is considered protective for depression but is also associated with completed suicide, nicotine dependence, and attention deficit hyperactivity disorder. For some disorders, such as post-traumatic stress disorder and major depressive disorder, the research suggests that treatment response may vary by allele (such as an enhanced response to serotonin specific reuptake inhibitors in patients with major depressive disorder and post-traumatic stress disorder with L alleles, and for alcohol dependence, the association and treatment for S or L alleles may vary with alcoholic subtype. While some studies suggest that 5-HTTLPR polymorphism can moderate the response to pharmacotherapy, the association between 5-HTTLPR alleles and therapeutic outcomes is inconsistent. The discovery of triallelic 5-HTTLPR alleles (LA/LG/S may help to explain some of the conflicting results of many past association studies, while concurrently providing more meaningful data in the future. Studies assessing 5-HTTLPR as the solitary genetic factor contributing to the etiology of psychiatric disorders continue to face the challenges of statistically small effect sizes and limited replication.Keywords: 5-HTTLPR, SCC6A4, 5-HT, serotonin, genetics, alleles, triallele, psychiatric, polymorphisms, pharmacotherapy, psychopathology

  17. Polimorfismo del gen del transportador de serotonina (5-HTT y trastorno de depresión mayor en pacientes en Bogotá, Colombia

    Directory of Open Access Journals (Sweden)

    Isabel Pérez-Olmos

    2016-06-01

    Conclusiones. El genotipo SL se asoció con el trastorno de depresión mayor en pacientes de todas las edades. El alelo S se asoció significativamente con el trastorno de depresión mayor en pacientes menores de 37 años al ajustar por trastornos concomitantes de ansiedad.

  18. Association of polymorphisms in 5-HTT (SLC6A4) and MAOA genes with measures of obesity in young adults of Portuguese origin.

    Science.gov (United States)

    Dias, Helena; Muc, Magdalena; Padez, Cristina; Manco, Licínio

    2016-01-01

    To investigate the association of polymorphisms in SLC6A4 and MAOA genes with overweight (including obesity). Young adults (n = 535) of Portuguese origin were genotyped for the SLC6A4 polymorphisms 5-HTTLPR and STin2 and a MAOA VNTR. BMI and body fat percentage were measured and a questionnaire was used to assess individual's sport practicing habits. In whole study sample, haplotype-based analysis revealed significant association with overweight/obesity for the individual 5-HTTLPR/Stin2 haplotype L10 (p = 0.04). In men, the MAOA 3R genotype was nominally associated with body fat (p = 0.04). In inactive individuals, overweight/obesity was found significantly associated with 5-HTTLPR L-allele (p = 0.01) and nominally associated with STin2 10-allele (p = 0.03). A significant association was also found testing for all haplotype effects (χ(2 )= 8.7; p = 0.03). We found some evidences for the association of SLC6A4 and MAOA genes with measures of obesity. Our results suggest physical inactivity accentuates the influence of SLC6A4 polymorphisms on obesity risk.

  19. Nõrk või tugev raha? : mündireformid ja nende põhjused Euroopas 15. sajandi alguses / Ivar Leimus

    Index Scriptorium Estoniae

    Leimus, Ivar, 1953-

    2014-01-01

    Saksa Ordu majanduslikust pankrotist Tannenbergi lahingu järel. Katsetest olukorda lahendada. Danzigi veriselt maha surutud mündimässust, misjärel kõrgmeistril tuli siiski loobuda reformist algselt mõeldud kujul. Mündireform toimus 15. sajandi alguses ka Liivimaal. Küsimuseks jääb kuivõrd mõjutas seda kõrgmeistrile osutatud rahalinae abi. Suurem kriis Liivimaa mündinduses näib olevat alanud alles 1415. aastal. 15. sajandi algul halvenes raha peaaegu kõikjal Euroopas, kuid selle põhjused ja käik olid erinevad

  20. Kolonel Peeter Läns: tark personalipoliitika on kaitseväes ülemate võimalus / Peeter Läns ; intervjueerinud Ivar Jõesaar

    Index Scriptorium Estoniae

    Läns, Peeter

    2013-01-01

    Kaitseväe Peastaabi personaliosakonna ülem hindab kaitseväe personalipoliitikat lähtudes uuest kaitseväeteenistuse seadusest, avaliku teenistuse seadusest ja riigikaitse arengukavast aastateks 2013-2022

  1. Iisraeli-Palestiina vastasseis : kahe tõe võitlus määrib mõlemad verega / Ivar Soopan

    Index Scriptorium Estoniae

    Soopan, Ivar, 1971-

    2007-01-01

    Iisraeli-Palestiina konflikt alates 1967. aastast. Vt. samas: Minister kurdab apartheidi. Palestiina teabeminister Mustafa Barghouti ütles intervjuus ajalehele Palestine Times, et vastasseis Iisraeliga laheneks, kui Iisrael tunnistaks, et palestiinlased ja iisraellased on võrdsed inimesed võrdsete õigustega ja neil peaksid olema võrdsed võimalused. Tema sõnul on okupatsioon loonud Palestiinas apartheidi

  2. The new era of cyber marketing / interv. Alina Lisina

    Index Scriptorium Estoniae

    2005-01-01

    Vestlusringis internetireklaamist osalesid Juris Mendzinsh, Linda Saulite, Ilze Taurina, Daina Misina, Edgars Rozentals, Gatis Veikshins, Reinis Zitmanis, Agris Strautnieks, Jurijs Zarinsh, Ivars Bauls, Martinsh Labans ja Vents Dorinsh

  3. Johann Christoph Brotze ja ajalugu akvarellides / Teet Veispak

    Index Scriptorium Estoniae

    Veispak, Teet, 1955-

    2006-01-01

    Kirjastuselt Estopol ilmus 2006. a. raamat "Estonica" Riias tegutsenud baltisaksa kultuuriloolase Eestit puudutavatest akvarellidest ja joonistustest. Koostajad Ants Hein, Ivar Leimus, Raimo Pullat ja Ants Viires

  4. Brotze väljaande filoloogilisi probleeme / Mati Hint

    Index Scriptorium Estoniae

    Hint, Mati

    2007-01-01

    Rets. rmt. : Johann Christoph Brotze. Estonica. Koostanud / Herausgegeben von Ants Hein, Ivar Leimus, Raimo Pullat, Ants Viires. Projektijuht ja vastutav toimetaja : Raimo Pullat. tõlge eesti keelde: Tõnis Liibek, Ivar Leimus, tõlge saksa keelde: Aigi Heero, Ene Rõngelep. Kujundus: Andres Tali. Tallinn : Estopol OÜ, 2006. XXXVI, 619 lk. Teoses esinevaid keele- ja kohanimeprobleeme

  5. Full-length huntingtin levels modulate body weight by influencing insulin-like growth factor 1 expression

    DEFF Research Database (Denmark)

    Pouladi, Mahmoud A; Xie, Yuanyun; Skotte, Niels Henning

    2010-01-01

    of the IGF-1 pathway in mediating the effect of htt on body weight. IGF-1 expression was examined in transgenic mouse lines expressing different levels of FL wild-type (WT) htt (YAC18 mice), FL mutant htt (YAC128 and BACHD mice) and truncated mutant htt (shortstop mice). We demonstrate that htt influences...... body weight by modulating the IGF-1 pathway. Plasma IGF-1 levels correlate with body weight and htt levels in the transgenic YAC mice expressing human htt. The effect of htt on IGF-1 expression is independent of CAG size. No effect on body weight is observed in transgenic YAC mice expressing...... and decreases the body weight of YAC128 animals to WT levels. Furthermore, given the ubiquitous expression of IGF-1 within the central nervous system, we also examined the impact of FL htt levels on IGF-1 expression in different regions of the brain, including the striatum, cerebellum of YAC18, YAC128...

  6. Nord Streami keskkonnamõjude aruanne jätab tähelepanuta Läänemere eripära / Madis Filippov ; kommenteerinud Ivar Puura, Tarmo Soomere, Endel Lippmaa

    Index Scriptorium Estoniae

    Filippov, Madis

    2009-01-01

    Teadlastes tekitavad ärevust Vene-Saksa ühisfirma Nord-Streami poolt Läänemerre kavandatava gaasitoru keskkonnamõjud. Artiklis on juttu ka Eesti Teaduste Akadeemia kirjast president Toomas Hendrik Ilvesele ja peaminister Andrus Ansipile sooviga moodustada professionaalne komisjon, mis töötaks läbi Nord Streami gaasijuhtme keskkonnamõju hindamise materjalid. Vt. samas: Dioksiinide kontsentratsioon setetes; Nord Streami gaasijuhe

  7. [Ose, Ieva. Livonijas pilu attēli no marķīza Pauluči albuma - Abbildungen der livländischen Burgen im Album des Marquis Paulucci] / Ivar Leimus

    Index Scriptorium Estoniae

    Leimus, Ivar, 1953-

    2011-01-01

    Arvustus: Livonijas pilu attēli no marķīza Pauluči albuma = Abbildungen der livländischen Burgen im Album des Marquis Paulucci. LU Latvijas vēstures institūts; Latvijas Akadēmiska biblioteka. (Rīga, 2008.) Kuramaa, Liivimaa ja Eestimaa pildialbumitest, mis tõenäoliselt on valminud aastatel 1827-1830, mis on nüüd välja antud ühiste kaante vahel. Tekst tõlgitud saksa keelde

  8. Preventing mutant huntingtin proteolysis and intermittent fasting promote autophagy in models of Huntington disease.

    Science.gov (United States)

    Ehrnhoefer, Dagmar E; Martin, Dale D O; Schmidt, Mandi E; Qiu, Xiaofan; Ladha, Safia; Caron, Nicholas S; Skotte, Niels H; Nguyen, Yen T N; Vaid, Kuljeet; Southwell, Amber L; Engemann, Sabine; Franciosi, Sonia; Hayden, Michael R

    2018-03-06

    Huntington disease (HD) is caused by the expression of mutant huntingtin (mHTT) bearing a polyglutamine expansion. In HD, mHTT accumulation is accompanied by a dysfunction in basal autophagy, which manifests as specific defects in cargo loading during selective autophagy. Here we show that the expression of mHTT resistant to proteolysis at the caspase cleavage site D586 (C6R mHTT) increases autophagy, which may be due to its increased binding to the autophagy adapter p62. This is accompanied by faster degradation of C6R mHTT in vitro and a lack of mHTT accumulation the C6R mouse model with age. These findings may explain the previously observed neuroprotective properties of C6R mHTT. As the C6R mutation cannot be easily translated into a therapeutic approach, we show that a scheduled feeding paradigm is sufficient to lower mHTT levels in YAC128 mice expressing cleavable mHTT. This is consistent with a previous model, where the presence of cleavable mHTT impairs basal autophagy, while fasting-induced autophagy remains functional. In HD, mHTT clearance and autophagy may become increasingly impaired as a function of age and disease stage, because of gradually increased activity of mHTT-processing enzymes. Our findings imply that mHTT clearance could be enhanced by a regulated dietary schedule that promotes autophagy.

  9. Potent and selective antisense oligonucleotides targeting single-nucleotide polymorphisms in the Huntington disease gene / allele-specific silencing of mutant huntingtin

    DEFF Research Database (Denmark)

    Carroll, Jeffrey B; Warby, Simon C; Southwell, Amber L

    2011-01-01

    Huntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by CAG-expansion in the huntingtin gene (HTT) that results in a toxic gain of function in the mutant huntingtin protein (mHTT). Reducing the expression of mHTT is therefore an attractive therapy for HD. However, wild...

  10. Frequency of nuclear mutant huntingtin inclusion formation in neurons and glia is cell-type-specific

    NARCIS (Netherlands)

    Jansen, Anne H. P.; van Hal, Maurik; Op den Kelder, Ilse C.; Meier, Romy T.; de Ruiter, Anna-Aster; Schut, Menno H.; Smith, Donna L.; Grit, Corien; Brouwer, Nieske; Kamphuis, Willem; Boddeke, H. W. G. M.; den Dunnen, Wilfred F. A.; van Roon, Willeke M. C.; Bates, Gillian P.; Hol, Elly M.; Reits, Eric A.

    2017-01-01

    Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disorder that is caused by a CAG expansion in the Huntingtin (HTT) gene, leading to HTT inclusion formation in the brain. The mutant huntingtin protein (mHTT) is ubiquitously expressed and therefore nuclear inclusions

  11. Frequency of Nuclear Mutant Huntingtin Inclusion Formation in Neurons and Glia is Cell-Type-Specific

    NARCIS (Netherlands)

    Jansen, Anne H P; van Hal, Maurik; op den Kelder, Ilse C.; Meier, Romy T.; de Ruiter, Anna-Aster; Schut, Menno H.; Smith, Donna L.; Grit, Corien; Brouwer, Nieske; Kamphuis, Willem; Boddeke, H. W. G. M.; den Dunnen, Wilfred F. A.; van Roon, Willeke M. C.; Bates, Gillian P.; Hol, Elly M.; Reits, Eric A.

    Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disorder that is caused by a CAG expansion in the Huntingtin (HTT) gene, leading to HTT inclusion formation in the brain. The mutant huntingtin protein (mHTT) is ubiquitously expressed and therefore nuclear inclusions

  12. Valimised 2002 : Tartu linnapeakandidaadid prioriteetidest linna arengus : kolm esimest ülesannet

    Index Scriptorium Estoniae

    2002-01-01

    Artiklite autorid: Andrus Ansip Reformierakonnast, Tõnu Kauba Keskerakonnast, Jüri Kumar ERL-ist, Ivar Tallo Mõõdukatest, Tõnis Lukas Isamaaliidust, Teet Jagomägi Res Publicast. Parlamendisaadik

  13. Godovshtshina bez eiforii / Aleksei Klepikov

    Index Scriptorium Estoniae

    Klepikov, Aleksei

    2005-01-01

    EL-i ja NATO-ga liitumise mõjudest Baltimaade elanike turvatundele ning majandusele. Arvamust avaldavad Tiit Matsulevitsh, Ivar Sikk, Toivo Kuldkepp jt. Toimetuse kommentaar. Diagramm: Inflatsioonimäärad Ida-Euroopa riikides

  14. Ajutine juht - jube kallis, aga see-eest väga kasu(m)lik / Irja Rae

    Index Scriptorium Estoniae

    Rae, Irja

    2005-01-01

    Ajutise juhi (interim manager) ehk üleminekujuhi palkamisest ettevõttes. Vt. samas: Kus teda näha võib. Kommenteerib juhtimiskonsultatsioonide firma PW Partnersi vanemkonsultant Jana Võrk. Vt. samas: Keskpaik, Ivar. Eesti tuntuim üleminekujuht

  15. TiSSA eelkonverents doktorantidele Tallinnas / Koidu Saame

    Index Scriptorium Estoniae

    Saame, Koidu

    2010-01-01

    Tallinna Ülikoolis toimunud TiSSA doktorantide eelkonverentsist 22.-24. aug. 2010.a. Doktorantide ettekannetest. Esinesid: Hans-Uwe Otto, Andriy Yuryev, Tiina Naarits, Ivar Tröner, Koidu Saame, Maija Jäppinen, Janissa Miettinen

  16. Täna kell 17.30 on Tartu Kunstimuuseumis...

    Index Scriptorium Estoniae

    2004-01-01

    Läti kunstniku Ilmars Blumbergsi ja kunstiteadlase Ivars Runkovskise happening-kohtumisõhtu. 4. II Peeter Linnapi filmiõhtu "Autoritarismi fikseerimise 3 palet. Leni Riefenstahl. Ülo Sooster. Pink Floyd"

  17. Kirjanduslik orgia?! Tänan, ei! / Raul Sulbi

    Index Scriptorium Estoniae

    Sulbi, Raul

    2002-01-01

    Arkaadia järjejutt (juuni - august 2002, autorid Wimberg, Veiko Märka, Urmas Vadi, Jürgen Rooste, Aapo Ilves, Aarne Ruben, Matt Barker, Hedda Maurer, Ivar Sild, Karen Orlau, Indrek Hargla, Jan Kaus, Mehis Heinsaar)

  18. Rector's office as of 31 December 2006

    Index Scriptorium Estoniae

    2007-01-01

    Rektor prof. Jaak Aaviksoo, teadusprorektor prof. Ain Heinaru, õppeprorektor prof. Birute Klaas, administratsioonidirektor prof. Mihkel Pärnoja, finantsdirektor Taimo saan, haldusdirektor Riho Illak, akadeemiline sekretär Ivar-Igor Saarniit

  19. Rector's office as of 31 December 2005

    Index Scriptorium Estoniae

    2006-01-01

    TÜ rektoraadi koosseis: rektor prof. Jaak Aaviksoo, teadusprorektor prof. Ain Heinaru, õppeprorektor prof. Tõnu Lehtsaar, prorektor prof. Jaak Kangilaski; administratsioonidirektor Mihkel Pärnoja, finantsdirektor Taimo Saan, haldusdirektor Riho Illak, akadeemiline sekretär Ivar-Igor Saarniit

  20. Eesti ajalugu Vene-Liivimaa sõjast Põhjasõjani / Lea Kõiv

    Index Scriptorium Estoniae

    Kõiv, Lea, 1961-

    2014-01-01

    Arvustus: Enn Küng, Margus Laidre, Ivar Leimus, Aivar Põldvee, Anti Selart, Marten Seppel, Kai Tafenau, Ülle Tarkiainen, Enn Tarvel. Eesti ajalugu III: Vene-Liivimaa sõjast Põhjasõjani. Tartu, 2013

  1. Kinnisvaraäri ajas Pärnu linnajuhid omavahel tülli / Eno-Gerrit Link

    Index Scriptorium Estoniae

    Link, Eno-Gerrit

    2008-01-01

    Pärnu linnavolikogu esimees Ahti Kõo peab ebaeetiliseks linnapea Mart Viisitamme ja spordiseltsi Põhjakotkas juhatuse esimehe Ivar Hallopi vahel sõlmitud ühtse kavatsuse protokolli. Ilmunud ka Pärnu Postimees 17. nov. lk. 1

  2. Poliitikud või eksperdid ? / Aarne Ruben

    Index Scriptorium Estoniae

    Ruben, Aarne, 1971-

    2009-01-01

    ETV saates "Foorum" esinesid 21. jaanuaril Indrek Neivelt, Erik Terk, Ivar Raig ja Raivo Vare, kes avaldasid arvamust, et valitsuses oleks vaja rohkem majandusharidusega inimesi. Autori arvates on erialast kõrgharidust vaja kõikjal riigiametites

  3. Eesti disainerid maailma tüpograafiakonverentsil

    Index Scriptorium Estoniae

    2005-01-01

    Helsingis toimunud tüpograafiakonverentsil esinesid ettekannetega Ivar Sakk ja Mart Anderson. Soome disainimuuseumis avatud näitusel "Souvenir" osalesid oma uusi kirju esitlevate plakatitega Mart Anderson, Asko Künnap, Anton Koovit jt

  4. Poor man status awaits if Estonia adopts euro too soon

    Index Scriptorium Estoniae

    2009-01-01

    Akadeemia Nord Euroopa uuringute instituudi juhataja professor Ivar Raig leiab, et eurole üleminek tekitab veel rohkem probleeme Eesti majanduses ning et Eesti vajab uut majanduspoliitikat. Tema sõnul peaks euroga liituma aastatel 2016-2018

  5. SHORT COMMUNICATION REMOVAL OF LEAD IONS FROM ...

    African Journals Online (AJOL)

    a

    manufacturing and battery manufacturing industries is an important pathway for entry of metals ... ion exchange [12], membrane separation methods [13] and electro-remediation methods [14] .... Zhongming, L.I.; Weie Y.J.; Ivars, N. Environ. Sci.

  6. Coaching näitab töötajast hoolimist / Urve Vilk

    Index Scriptorium Estoniae

    Vilk, Urve

    2012-01-01

    Konverentsil "Arengukompass 2012: uue ajastu organisatsiooni arendusvahendid" esinenud juhtimiskoolitaja ja sertifitseeritud coach'i Ivar Lukki, Elioni tehnoloogiadirektori Kalev Reiljani ja superviisori Katrin Aava Tallinna Ülikoolist sõnavõttudest

  7. Sundelevitsh, Kaasik, Tali / Harry Liivrand

    Index Scriptorium Estoniae

    Liivrand, Harry, 1961-

    2007-01-01

    Ilja Sundelevitshi fotonäitus "Lahemaa Lobi" Tallinna Kunstihoones. Ivar Kaasiku maalinäitus "Over the rainbow" Ühispanga galeriis. Näitus "Andres Tali loeb Byroni luuletust 1. mail 2007" Tallinna Linnagaleriis

  8. Kui palju tuleb juhitöös tegeleda "pean" ja "tahan" tegevustega?

    Index Scriptorium Estoniae

    2003-01-01

    Vastavad Fontes Grupi Nõukogu esimees Tõnis Arro, Aeroc AS-i juhatuse esimees Ivar Paplavskis, Eesti Ehitusettevõtjate Liidu tegevdirektor Tarmo Lige, American Toursi tegevdirektor Anu Eha ja Esmofoni juhatuse esimees Aivar Sirelpuu

  9. Rektoraat seisuga 31.12. 2005

    Index Scriptorium Estoniae

    2006-01-01

    TÜ rektoraadi koosseis: rektor prof. Jaak Aaviksoo, teadusprorektor prof. Ain Heinaru, õppeprorektor prof. Tõnu Lehtsaar, prorektor prof. Jaak Kangilaski; administratsioonidirektor Mihkel Pärnoja, finantsdirektor Taimo Saan, haldusdirektor Riho Illak, akadeemiline sekretär Ivar-Igor Saarniit

  10. Rektoraat seisuga 31.12.2006

    Index Scriptorium Estoniae

    2007-01-01

    Rektor prof. Jaak Aaviksoo, teadusprorektor prof. Ain Heinaru, õppeprorektor prof. Birute Klaas, administratsioonidirektor prof. Mihkel Pärnoja, finantsdirektor Taimo saan, haldusdirektor Riho Illak, akadeemiline sekretär Ivar-Igor Saarniit

  11. Kivikuulide saladus / Marielle Liivet, Peeter Ernits

    Index Scriptorium Estoniae

    Liivet, Marielle

    2001-01-01

    Costa Rica dzunglitesse peitunud hiiglaslikke kivikuule kasutati ilmselt meremeeste koolitamisel. Costa Rica ülikooli õppejõud eestlane Ivar Zapp on kirjutanud neist raamatu "Atlantis in America". Joonis : Orientiirid meresõitjatele

  12. Eesti täispikad dokumentaalfilmid 2005. aastal / Marianne Kõrver

    Index Scriptorium Estoniae

    Kõrver, Marianne, 1980-

    2006-01-01

    Portreefilmid : Priit Pärnast "Pärnograafia" (Hardi Volmer), Ivar Heinmaast "Kutse" (Peep Puks), Veljo Tormisest "Tormise regi" (Sulev Keedus), Rein Tammikust "Teekond ruudulisel laudlinal" (Peeter Urbla), "Afanassi" (Liina Trishkina) ; probleemfilmid : "Parema elu nimel" (Märt Sildvee), "Piisa torn" (Arko Okk) ; sõjateemalised dokumentaalid : "Afganistani armid" (Ivar Heinmaa), "Hauka grupp" (Rene Vilbre), "Tõrjutud mälestused" (Imbi Paju) ; loodusfilm "Eesti kotkad" (Rein Maran)

  13. Huntingtin Protein is Essential for Mitochondrial Metabolism, Bioenergetics and Structure in Murine Embryonic Stem Cells

    Science.gov (United States)

    Ismailoglu, Ismail; Chen, Qiuying; Popowski, Melissa; Yang, Lili; Gross, Steven S.; Brivanlou, Ali H.

    2014-01-01

    Mutations in the Huntington locus (htt) have devastating consequences. Gain-of-poly-Q repeats in Htt protein causes Huntington's disease (HD), while htt-/- mutants display early embryonic lethality. Despite its importance, the function of Htt remains elusive. To address this, we compared more than 3,700 compounds in three syngeneic mouse embryonic stem cell (mESC) lines: htt-/-, extended poly-Q (Htt-Q140/7), and wildtype mESCs (Htt-Q7/7) using untargeted metabolite profiling. While Htt-Q140/7 cells, did not show major differences in cellular bioenergetics, we find extensive metabolic aberrations in htt-/- mESCs, including: (i) complete failure of ATP production despite preservation of the mitochondrial membrane potential; (ii) near-maximal glycolysis, with little or no glycolytic reserve; (iii) marked ketogenesis; (iv) depletion of intracellular NTPs; (v) accelerated purine biosynthesis and salvage; and (vi) loss of mitochondrial structural integrity. Together, our findings reveal that Htt is necessary for mitochondrial structure and function from the earliest stages of embryogenesis, providing a molecular explanation for htt-/- early embryonic lethality. PMID:24780625

  14. Huntingtin coordinates the dynein-mediated dynamic positioning of endosomes and lysosomes

    Science.gov (United States)

    Caviston, Juliane P.; Zajac, Allison L.; Tokito, Mariko; Holzbaur, Erika L.F.

    2011-01-01

    Huntingtin (Htt) is a membrane-associated scaffolding protein that interacts with microtubule motors as well as actin-associated adaptor molecules. We examined a role for Htt in the dynein-mediated intracellular trafficking of endosomes and lysosomes. In HeLa cells depleted of either Htt or dynein, early, recycling, and late endosomes (LE)/lysosomes all become dispersed. Despite altered organelle localization, kinetic assays indicate only minor defects in intracellular trafficking. Expression of full-length Htt is required to restore organelle localization in Htt-depleted cells, supporting a role for Htt as a scaffold that promotes functional interactions along its length. In dynein-depleted cells, LE/lysosomes accumulate in tight patches near the cortex, apparently enmeshed by cortactin-positive actin filaments; Latrunculin B-treatment disperses these patches. Peripheral LE/lysosomes in dynein-depleted cells no longer colocalize with microtubules. Htt may be required for this off-loading, as the loss of microtubule association is not seen in Htt-depleted cells or in cells depleted of both dynein and Htt. Inhibition of kinesin-1 relocalizes peripheral LE/lysosomes induced by Htt depletion but not by dynein depletion, consistent with their detachment from microtubules upon dynein knockdown. Together, these data support a model of Htt as a facilitator of dynein-mediated trafficking that may regulate the cytoskeletal association of dynamic organelles. PMID:21169558

  15. A series of N-terminal epitope tagged Hdh knock-in alleles expressing normal and mutant huntingtin: their application to understanding the effect of increasing the length of normal huntingtin’s polyglutamine stretch on CAG140 mouse model pathogenesis

    Directory of Open Access Journals (Sweden)

    Zheng Shuqiu

    2012-08-01

    Full Text Available Abstract Background Huntington’s disease (HD is an autosomal dominant neurodegenerative disease that is caused by the expansion of a polyglutamine (polyQ stretch within Huntingtin (htt, the protein product of the HD gene. Although studies in vitro have suggested that the mutant htt can act in a potentially dominant negative fashion by sequestering wild-type htt into insoluble protein aggregates, the role of the length of the normal htt polyQ stretch, and the adjacent proline-rich region (PRR in modulating HD mouse model pathogenesis is currently unknown. Results We describe the generation and characterization of a series of knock-in HD mouse models that express versions of the mouse HD gene (Hdh encoding N-terminal hemaglutinin (HA or 3xFlag epitope tagged full-length htt with different polyQ lengths (HA7Q-, 3xFlag7Q-, 3xFlag20Q-, and 3xFlag140Q-htt and substitution of the adjacent mouse PRR with the human PRR (3xFlag20Q- and 3xFlag140Q-htt. Using co-immunoprecipitation and immunohistochemistry analyses, we detect no significant interaction between soluble full-length normal 7Q- htt and mutant (140Q htt, but we do observe N-terminal fragments of epitope-tagged normal htt in mutant htt aggregates. When the sequences encoding normal mouse htt’s polyQ stretch and PRR are replaced with non-pathogenic human sequence in mice also expressing 140Q-htt, aggregation foci within the striatum, and the mean size of htt inclusions are increased, along with an increase in striatal lipofuscin and gliosis. Conclusion In mice, soluble full-length normal and mutant htt are predominantly monomeric. In heterozygous knock-in HD mouse models, substituting the normal mouse polyQ and PRR with normal human sequence can exacerbate some neuropathological phenotypes.

  16. Hyalinizing trabecular tumor of the thyroid: Diagnosed of a rare tumor using ultrasonography, cytology, and intraoperative frozen sections

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Hyun Sik; Kim, Eun Kyung; Kwak, Jin Young; Moon, Hee Jung; Yoon, Jung Hyun [Dept. of Radiology, Severance Hospital, Research Institute of Radiological Science, Yonsei University, College of Medicine, Seoul (Korea, Republic of); Park, Cheol Keun; Son, Eun Ju [Gangnam Severance Hospital, Yonsei University, College of Medicine, Seoul (Korea, Republic of)

    2016-03-15

    The goal of this study was to evaluate the clinicopathological and imaging features of thyroid nodules surgically diagnosed as hyaline trabecular tumor (HTT), and to assess the role of cytology and frozen sections (FS) in the diagnosis of HTT. This study included 21 thyroid nodules in 21 patients treated from August 2005 to March 2015 (mean age, 53.3 years) who were either diagnosed as HTT or had HTT suggested as a possible diagnosis based on cytology, FS, or the final pathology report. Patients' medical records were retrospectively reviewed for cytopathologic results and outcomes during the course of follow-up. Sonograms were reviewed and categorized. Twelve nodules from 12 patients were surgically confirmed as HTT. Ultrasonography (US)-guided fine needle aspiration (FNA) was performed on 11 nodules, of which six (54.5%) were papillary thyroid carcinoma (PTC) or suspicious for PTC and three (27.3%) were HTT or suspicious for HTT. Intraoperative FS suggested the possibility of HTT in seven nodules, of which four (57.1%) were confirmed as HTT. US-FNA suggested the diagnosis of HTT in 10 nodules, of which three (30.0%) were confirmed as HTT. Common US features of the 12 pathologically confirmed cases of HTT were hypoechogenicity or marked hypoechogenicity (83.4%), absence of calcifications (91.7%), parallel shape (100.0%), presence of vascularity (75.0%), and probable benignity (58.3%). HTT should be included in the differential diagnosis of solid tumors with hypoechogenicity or marked hypoechogenicity and otherwise benign US features that have been diagnosed as PTC through cytology.

  17. Hyalinizing trabecular tumor of the thyroid: Diagnosed of a rare tumor using ultrasonography, cytology, and intraoperative frozen sections

    International Nuclear Information System (INIS)

    Jang, Hyun Sik; Kim, Eun Kyung; Kwak, Jin Young; Moon, Hee Jung; Yoon, Jung Hyun; Park, Cheol Keun; Son, Eun Ju

    2016-01-01

    The goal of this study was to evaluate the clinicopathological and imaging features of thyroid nodules surgically diagnosed as hyaline trabecular tumor (HTT), and to assess the role of cytology and frozen sections (FS) in the diagnosis of HTT. This study included 21 thyroid nodules in 21 patients treated from August 2005 to March 2015 (mean age, 53.3 years) who were either diagnosed as HTT or had HTT suggested as a possible diagnosis based on cytology, FS, or the final pathology report. Patients' medical records were retrospectively reviewed for cytopathologic results and outcomes during the course of follow-up. Sonograms were reviewed and categorized. Twelve nodules from 12 patients were surgically confirmed as HTT. Ultrasonography (US)-guided fine needle aspiration (FNA) was performed on 11 nodules, of which six (54.5%) were papillary thyroid carcinoma (PTC) or suspicious for PTC and three (27.3%) were HTT or suspicious for HTT. Intraoperative FS suggested the possibility of HTT in seven nodules, of which four (57.1%) were confirmed as HTT. US-FNA suggested the diagnosis of HTT in 10 nodules, of which three (30.0%) were confirmed as HTT. Common US features of the 12 pathologically confirmed cases of HTT were hypoechogenicity or marked hypoechogenicity (83.4%), absence of calcifications (91.7%), parallel shape (100.0%), presence of vascularity (75.0%), and probable benignity (58.3%). HTT should be included in the differential diagnosis of solid tumors with hypoechogenicity or marked hypoechogenicity and otherwise benign US features that have been diagnosed as PTC through cytology

  18. A novel humanized mouse model of Huntington disease for preclinical development of therapeutics targeting mutant huntingtin alleles

    DEFF Research Database (Denmark)

    Southwell, Amber L; Skotte, Niels H; Villanueva, Erika B

    2017-01-01

    transgenes in Hu128/21 mice match the human HTT exon 1 reference sequence. Conversely, the BACHD transgene carries a floxed, synthetic exon 1 sequence. Hu128/21 mice will be useful for investigations of human HTT that cannot be addressed in Hu97/18 mice, for developing therapies targeted to exon 1......Huntington disease (HD) is a neurodegenerative disease caused by a mutation in the huntingtin (HTT) gene. HTT is a large protein, interacts with many partners and is involved in many cellular pathways, which are perturbed in HD. Therapies targeting HTT directly are likely to provide the most global......-length, genomic human HTT transgenes heterozygous for the HD mutation and polymorphisms associated with HD in populations of East Asian descent and in a minority of patients from other ethnic groups. Hu128/21 mice display a wide variety of HD-like phenotypes that are similar to YAC128 mice. Additionally, both...

  19. Ensiling and hydrothermal pretreatment of grass: Consequences for enzymatic biomass conversion and total monosaccharide yields

    DEFF Research Database (Denmark)

    Ambye-Jensen, Morten; Johansen, Katja Salomon; Didion, Thomas

    2014-01-01

    Ensiling may act as a pretreatment of fresh grass biomass and increase the enzymatic conversion of structural carbohydrates to fermentable sugars. However, ensiling does not provide sufficient severity to be a standalone pretreatment method. Here, ensiling of grass is combined with hydrothermal...... treatment (HTT) with the aim of improving the enzymatic biomass convertibility and decrease the required temperature of the HTT. Results: Grass silage (Festulolium Hykor) was hydrothermally treated at temperatures of 170, 180, and 190°C for 10 minutes. Relative to HTT treated dry grass, ensiling increased...... convertibility). The effect of ensiling of grass prior to HTT improved the enzymatic conversion of cellulose for HTT at 170 and 180°C, but the increased glucose release did not make up for the loss of water soluble carbohydrates (WSC) during ensiling. Overall, sugar yields (C6 + C5) were similar for HTT of grass...

  20. Expression analysis for inverted effects of serotonin transporter inactivation

    International Nuclear Information System (INIS)

    Ichikawa, Manabu; Okamura-Oho, Yuko; Shimokawa, Kazuro; Kondo, Shinji; Nakamura, Sakiko; Yokota, Hideo; Himeno, Ryutaro; Lesch, Klaus-Peter; Hayashizaki, Yoshihide

    2008-01-01

    Inactivation of serotonin transporter (HTT) by pharmacologically in the neonate or genetically increases risk for depression in adulthood, whereas pharmacological inhibition of HTT ameliorates symptoms in depressed patients. The differing role of HTT function during early development and in adult brain plasticity in causing or reversing depression remains an unexplained paradox. To address this we profiled the gene expression of adult Htt knockout (Htt KO) mice and HTT inhibitor-treated mice. Inverted profile changes between the two experimental conditions were seen in 30 genes. Consistent results of the upstream regulatory element search and the co-localization search of these genes indicated that the regulation may be executed by Pax5, Pax7 and Gata3, known to be involved in the survival, proliferation, and migration of serotonergic neurons in the developing brain, and these factors are supposed to keep functioning to regulate downstream genes related to serotonin system in the adult brain

  1. Cystathionine γ-lyase deficiency mediates neurodegeneration in Huntington’s disease

    OpenAIRE

    Paul, Bindu D.; Sbodio, Juan I.; Xu, Risheng; Vandiver, M. Scott; Cha, Jiyoung Y.; Snowman, Adele M.; Snyder, Solomon H.

    2014-01-01

    Huntington’s disease is an autosomal dominant disease associated with a mutation in the gene encoding huntingtin (Htt) leading to expanded polyglutamine repeats of mutant Htt (mHtt) that elicit oxidative stress, neurotoxicity, and motor and behavioural changes1. Huntington’s disease is characterized by highly selective and profound damage to the corpus striatum, which regulates motor function. Striatal selectivity of Huntington’s disease may reflect the striatally selective small G protein Rh...

  2. Scalable production in human cells and biochemical characterization of full-length normal and mutant huntingtin.

    Directory of Open Access Journals (Sweden)

    Bin Huang

    Full Text Available Huntingtin (Htt is a 350 kD intracellular protein, ubiquitously expressed and mainly localized in the cytoplasm. Huntington's disease (HD is caused by a CAG triplet amplification in exon 1 of the corresponding gene resulting in a polyglutamine (polyQ expansion at the N-terminus of Htt. Production of full-length Htt has been difficult in the past and so far a scalable system or process has not been established for recombinant production of Htt in human cells. The ability to produce Htt in milligram quantities would be a prerequisite for many biochemical and biophysical studies aiming in a better understanding of Htt function under physiological conditions and in case of mutation and disease. For scalable production of full-length normal (17Q and mutant (46Q and 128Q Htt we have established two different systems, the first based on doxycycline-inducible Htt expression in stable cell lines, the second on "gutless" adenovirus mediated gene transfer. Purified material has then been used for biochemical characterization of full-length Htt. Posttranslational modifications (PTMs were determined and several new phosphorylation sites were identified. Nearly all PTMs in full-length Htt localized to areas outside of predicted alpha-solenoid protein regions. In all detected N-terminal peptides methionine as the first amino acid was missing and the second, alanine, was found to be acetylated. Differences in secondary structure between normal and mutant Htt, a helix-rich protein, were not observed in our study. Purified Htt tends to form dimers and higher order oligomers, thus resembling the situation observed with N-terminal fragments, although the mechanism of oligomer formation may be different.

  3. The cryo-electron microscopy structure of huntingtin

    Science.gov (United States)

    Guo, Qiang; Bin Huang; Cheng, Jingdong; Seefelder, Manuel; Engler, Tatjana; Pfeifer, Günter; Oeckl, Patrick; Otto, Markus; Moser, Franziska; Maurer, Melanie; Pautsch, Alexander; Baumeister, Wolfgang; Fernández-Busnadiego, Rubén; Kochanek, Stefan

    2018-03-01

    Huntingtin (HTT) is a large (348 kDa) protein that is essential for embryonic development and is involved in diverse cellular activities such as vesicular transport, endocytosis, autophagy and the regulation of transcription. Although an integrative understanding of the biological functions of HTT is lacking, the large number of identified HTT interactors suggests that it serves as a protein-protein interaction hub. Furthermore, Huntington’s disease is caused by a mutation in the HTT gene, resulting in a pathogenic expansion of a polyglutamine repeat at the amino terminus of HTT. However, only limited structural information regarding HTT is currently available. Here we use cryo-electron microscopy to determine the structure of full-length human HTT in a complex with HTT-associated protein 40 (HAP40; encoded by three F8A genes in humans) to an overall resolution of 4 Å. HTT is largely α-helical and consists of three major domains. The amino- and carboxy-terminal domains contain multiple HEAT (huntingtin, elongation factor 3, protein phosphatase 2A and lipid kinase TOR) repeats arranged in a solenoid fashion. These domains are connected by a smaller bridge domain containing different types of tandem repeats. HAP40 is also largely α-helical and has a tetratricopeptide repeat-like organization. HAP40 binds in a cleft and contacts the three HTT domains by hydrophobic and electrostatic interactions, thereby stabilizing the conformation of HTT. These data rationalize previous biochemical results and pave the way for improved understanding of the diverse cellular functions of HTT.

  4. Maintenance of Chronic Fatigue Syndrome (CFS in Young CFS Patients Is Associated with the 5-HTTLPR and SNP rs25531 A > G Genotype.

    Directory of Open Access Journals (Sweden)

    Benedicte Meyer

    Full Text Available Earlier studies have shown that genetic variability in the SLC6A4 gene encoding the serotonin transporter (5-HTT may be important for the re-uptake of serotonin (5-HT in the central nervous system. In the present study we investigated how the 5-HTT genotype i.e. the short (S versus long (L 5-HTTLPR allele and the SNP rs25531 A > G affect the physical and psychosocial functioning in patients with chronic fatigue syndrome (CFS. All 120 patients were recruited from The Department of Paediatrics at Oslo University Hospital, Norway, a national referral center for young CFS patients (12-18 years. Main outcomes were number of steps per day obtained by an accelerometer and disability scored by the Functional Disability Inventory (FDI. Patients with the 5-HTT SS or SLG genotype had a significantly lower number of steps per day than patients with the 5-HTT LALG, SLA or LALA genotype. Patients with the 5-HTT SS or SLG genotype also had a significantly higher FDI score than patients with the 5-HTT LALG, SLA or LALA genotype. Thus, CFS patients with the 5-HTT SS or SLG genotype had worse 30 weeks outcome than CFS patients with the 5-HTT LALG, SLA or LALA genotype. The present study suggests that the 5-HTT genotype may be a factor that contributes to maintenance of CFS.

  5. Midbrain serotonin transporter binding potential measured with [11C]DASB is affected by serotonin transporter genotype

    International Nuclear Information System (INIS)

    Reimold, M.; Bares, R.; Reischl, G.; Solbach, C.; Machulla, H.-J.; Smolka, M.N.; Mann, K.; Schumann, G.; Zimmer, A.; Wrase, J.; Hu, X.-Z.; Goldman, D.; Heinz, A.

    2007-01-01

    Homozygote carriers of two long (L) alleles of the serotonin transporter (5-HTT) regulatory region displayed in vitro a twofold increase in 5-HTT expression compared with carriers of one or two short (S) alleles. However, in vivo imaging studies yielded contradictory results. Recently, an A > G exchange leading to differential transcriptional activation of 5-HTT mRNA in lymphobalstoid cell lines was discovered in the 5-HTT regulatory region. In vitro and in vivo evidence suggests that [ 11 C]DASB, a new 5-HTT ligand offers some advantages over the ligands used in previous studies in measuring 5-HTT density independent of synaptic levels of serotonin. We assessed 5-HTT binding potential (BP 2) in the midbrain of 19 healthy subjects with positron emission tomography and [ 11 C]DASB. Accounting for the hypothesized functional similarity of L G and S in driving 5-HTT transcription, we assessed whether L A L A homozygotes display increased midbrain BP 2 compared with carriers of at least one S allele. BP 2 in the midbrain was significantly increased in L A L A homozygotes compared with carriers of at least one S allele. Interestingly, the genotype effect on the midbrain was significantly different from that on the thalamus and the amygdala where no group differences were detected. This in vivo study provides further evidence that subjects homozygous for the L A allele display increased expression of 5-HTT in the midbrain, the origin of central serotonergic projections. (author)

  6. El equívoco de la literatura infantil

    Directory of Open Access Journals (Sweden)

    Claudia Cadena Silva

    1991-05-01

    Full Text Available Torta de cumpleaños: Historias de Eusebio, I. Ivar da Coll. Ilustraciones del autor. Carlos Valencia Editores, Bogotá, 1989, 28 págs. Tengo miedo: Historias de Eusebio, II. Ivar da Coll. Ilustraciones del autor. Carlos Valencia Editores, Bogotá, 1989, 36 págs. Garabato: Historias de Eusebio, III. Ivar da Coll. Ilustraciones del autor. Carlos Valencia Editores, Bogotá, 1990, 32 págs. Isabel en invierno. Antonio Caballero. Ilustraciones del autor. Carlos Valencia Editores, Bogotá, 1989, 24 págs. Pégale duro, Joey. Beatriz Caballero. Ilustraciones de Ernesto Díaz. Carlos Valencia Editores, Bogotá, 20 págs. Conjuros y sortilegios. Irene Vasco, Cristina López. Ilustraciones de Cristina López. Carlos Valencia Editores, Bogotá, 1990, 24 págs.

  7. Calcium Handling by Endoplasmic Reticulum and Mitochondria in a Cell Model of Huntington’s Disease

    Science.gov (United States)

    De Mario, Agnese; Scarlatti, Chiara; Costiniti, Veronica; Primerano, Simona; Lopreiato, Raffaele; Calì, Tito; Brini, Marisa; Giacomello, Marta; Carafoli, Ernesto

    2016-01-01

    Huntington disease (HD) is caused by the CAG (Q) expansion in exon 1 of the IT15 gene encoding a polyglutamine (poly-Q) stretch of the Huntingtin protein (Htt). In the wild type protein, the repeats specify a stretch of up 34 Q in the N-terminal portion of Htt. In the pathological protein (mHtt) the poly-Q tract is longer. Proteolytic cleavage of the protein liberates an N-terminal fragment containing the expanded poly-Q tract becomes harmful to cells, in particular to striatal neurons. The fragments cause the transcriptional dysfunction of genes that are essential for neuronal survival. Htt, however, could also have non-transcriptional effects, e.g. it could directly alter Ca2+ homeostasis and/or mitochondrial morphology and function. Ca2+ dyshomeostasis and mitochondrial dysfunction are considered important in the molecular aetiology of the disease. Here we have analyzed the effect of the overexpression of Htt fragments (18Q, wild type form, wtHtt and 150Q mutated form, mHtt) on Ca2+ homeostasis in striatal neuronal precursor cells (Q7/7). We have found that the transient overexpression of the Htt fragments increases Ca2+ transients in the mitochondria of cells stimulated with Ca2+-mobilizing agonists. The bulk Ca2+ transients in the cytosol were unaffected, but the Ca2+ content of the endoplasmic reticulum was significantly decreased in the case of mHtt expression. To rule out possible transcriptional effects due to the presence of mHtt, we have measured the mRNA level of a subunit of the respiratory chain complex II, whose expression is commonly altered in many HD models. No effects on the mRNA level was found suggesting that, in our experimental condition, transcriptional action of Htt is not occurring and that the effects on Ca2+ homeostasis were dependent to non-transcriptional mechanisms. PMID:26819834

  8. Calcium Handling by Endoplasmic Reticulum and Mitochondria in a Cell Model of Huntington's Disease.

    Science.gov (United States)

    De Mario, Agnese; Scarlatti, Chiara; Costiniti, Veronica; Primerano, Simona; Lopreiato, Raffaele; Calì, Tito; Brini, Marisa; Giacomello, Marta; Carafoli, Ernesto

    2016-01-06

    Huntington disease (HD) is caused by the CAG (Q) expansion in exon 1 of the IT15 gene encoding a polyglutamine (poly-Q) stretch of the Huntingtin protein (Htt). In the wild type protein, the repeats specify a stretch of up 34 Q in the N-terminal portion of Htt. In the pathological protein (mHtt) the poly-Q tract is longer. Proteolytic cleavage of the protein liberates an N-terminal fragment containing the expanded poly-Q tract becomes harmful to cells, in particular to striatal neurons. The fragments cause the transcriptional dysfunction of genes that are essential for neuronal survival. Htt, however, could also have non-transcriptional effects, e.g. it could directly alter Ca2+ homeostasis and/or mitochondrial morphology and function. Ca2+ dyshomeostasis and mitochondrial dysfunction are considered important in the molecular aetiology of the disease. Here we have analyzed the effect of the overexpression of Htt fragments (18Q, wild type form, wtHtt and 150Q mutated form, mHtt) on Ca2+ homeostasis in striatal neuronal precursor cells (Q7/7). We have found that the transient overexpression of the Htt fragments increases Ca2+ transients in the mitochondria of cells stimulated with Ca2+-mobilizing agonists. The bulk Ca2+ transients in the cytosol were unaffected, but the Ca2+ content of the endoplasmic reticulum was significantly decreased in the case of mHtt expression. To rule out possible transcriptional effects due to the presence of mHtt, we have measured the mRNA level of a subunit of the respiratory chain complex II, whose expression is commonly altered in many HD models. No effects on the mRNA level was found suggesting that, in our experimental condition, transcriptional action of Htt is not occurring and that the effects on Ca2+ homeostasis were dependent to non-transcriptional mechanisms.

  9. A new model for separation between brain dopamine and serotonin transporters in {sup 123}I-{beta}-CIT SPECT measurements: normal values and sex and age dependence

    Energy Technology Data Exchange (ETDEWEB)

    Ryding, Erik; Rosen, Ingmar [Department of Clinical Neurophysiology, University Hospital, Lund (Sweden); Lindstroem, Mats; Bosson, Peter; Traeskman-Bendz, Lil [Department of Psychiatry, University Hospital, Lund (Sweden); Braadvik, Bjoern; Grabowski, Martin [Department of Neurology, University Hospital, Lund (Sweden)

    2004-08-01

    {sup 123}I-{beta}-CIT is a radioactive ligand for single-photon emission computed tomography (SPECT) imaging of the pre-synaptic (transporter) re-uptake sites for dopamine (DAT) and serotonin (5HTT), and it is widely used to visualize monoamine turnover. Since {sup 123}I-{beta}-CIT uptake occurs at 5HTT and DAT sites in conjunction with the presence of freely soluble {sup 123}I-{beta}-CIT in brain tissue, adequate separation of these three components is necessary. However, only partial separation is possible with current methods. Two main strategies have previously been used for {sup 123}I-{beta}-CIT component separation, based on the following considerations: (1) the faster uptake rate for 5HTT compared with DAT enables temporal separation by performing 5HTT imaging at 1-2 h and DAT imaging at 20-24 h; (2) blocking the 5HTT re-uptake with citalopram renders {sup 123}I-{beta}-CIT imaging DAT (non-5HTT) specific. In a new analytical model, we combined these two approaches with methods to isolate the passively dissolved {sup 123}I-{beta}-CIT in brain tissue from the monoamine transporter uptake, and to correct the 5HTT and DAT values for concomitant uptake. The new analytical model was used to study brain 5HTT and DAT in 23 normal subjects, with the aim of clarifying the effect of age and sex. A significant correlation between 5HTT and DAT values was found only in the thalamus, indicating successful component separation. Negative correlations between age and DAT were found for basal ganglia, thalami, brain stem and temporal lobes, but not for the frontal, parietal or occipital regions. No correlation with age was found for 5HTT. We found no sex difference for 5HTT or DAT. (orig.)

  10. Head First Object-Oriented Analysis and Design

    CERN Document Server

    McLaughlin, Brett D; West, David

    2006-01-01

    "Head First Object Oriented Analysis and Design is a refreshing look at subject of OOAD. What sets this book apart is its focus on learning. The authors have made the content of OOAD accessible, usable for the practitioner." Ivar Jacobson, Ivar Jacobson Consulting "I just finished reading HF OOA&D and I loved it! The thing I liked most about this book was its focus on why we do OOA&D-to write great software!" Kyle Brown, Distinguished Engineer, IBM "Hidden behind the funny pictures and crazy fonts is a serious, intelligent, extremely well-crafted presentation of OO Analysis and Design

  11. President tunnustab Pärnumaad kümne riikliku autasuga / Eno-Gerrit Link

    Index Scriptorium Estoniae

    Link, Eno-Gerrit

    2007-01-01

    Pärnumaalt saavad iseseisvuspäeva puhul riikliku autasu kümme inimest. Vt. samas: Ester Vilgats. Ivar Kaldasaunal on alati kollektiiviga vedanud; Vello Lahtvee kolmkümmend aastat kohtunikuna. Teenetemärgi pälvinute seas on Lääne-Eesti päästekeskuse direktor Ivar Kaldasaun ja Pärnu maakohtu kohtunik Vello Lahtvee. Vt. ka juhtkiri lk. 15: Vilgats, Kalev. Ebaõigluse visa vastupanu. Rüütliristi kavaler Harald Nugiseks jäi taas teenetemärgist ilma

  12. Genetic variation in 5-hydroxytryptamine transporter expression causes adaptive changes in 5-HT4 receptor levels

    DEFF Research Database (Denmark)

    Jennings, Katie Ann; Licht, Cecilie Löe; Bruce, Aynsley

    2012-01-01

    +/+ mice in all brain regions. Compared to wild-type (WT) littermate controls, 5-HTT OE mice had increased 5-HT4 binding density across all brain regions, except amygdala (118-164% of WT) and this difference between genotypes was reduced by the 5-HTT inhibitor, fluoxetine (20 mg/kg twice daily, 3 d...

  13. Hydrothermal emergence model for ripgut brome (Bromus diandrus)

    Science.gov (United States)

    A model that describes the emergence of ripgut brome (Bromus diandrus) was developed using a two-season data set from a no-tilled field in northeastern Spain. The relationship between cumulative emergence and hydrothermal time (HTT) was described by a sigmoid growth function (Chapman equation). HTT ...

  14. Discovery of novel isoforms of huntingtin reveals a new hominid-specific exon.

    Directory of Open Access Journals (Sweden)

    Albert Ruzo

    Full Text Available Huntington's disease (HD is a devastating neurological disorder that is caused by an expansion of the poly-Q tract in exon 1 of the Huntingtin gene (HTT. HTT is an evolutionarily conserved and ubiquitously expressed protein that has been linked to a variety of functions including transcriptional regulation, mitochondrial function, and vesicle transport. This large protein has numerous caspase and calpain cleavage sites and can be decorated with several post-translational modifications such as phosphorylations, acetylations, sumoylations, and palmitoylations. However, the exact function of HTT and the role played by its modifications in the cell are still not well understood. Scrutiny of HTT function has been focused on a single, full length mRNA. In this study, we report the discovery of 5 novel HTT mRNA splice isoforms that are expressed in normal and HTT-expanded human embryonic stem cell (hESC lines as well as in cortical neurons differentiated from hESCs. Interestingly, none of the novel isoforms generates a truncated protein. Instead, 4 of the 5 new isoforms specifically eliminate domains and modifications to generate smaller HTT proteins. The fifth novel isoform incorporates a previously unreported additional exon, dubbed 41b, which is hominid-specific and introduces a potential phosphorylation site in the protein. The discovery of this hominid-specific isoform may shed light on human-specific pathogenic mechanisms of HTT, which could not be investigated with current mouse models of the disease.

  15. Discovery of Novel Isoforms of Huntingtin Reveals a New Hominid-Specific Exon

    Science.gov (United States)

    Popowski, Melissa; Haremaki, Tomomi; Croft, Gist F.; Deglincerti, Alessia; Brivanlou, Ali H.

    2015-01-01

    Huntington’s disease (HD) is a devastating neurological disorder that is caused by an expansion of the poly-Q tract in exon 1 of the Huntingtin gene (HTT). HTT is an evolutionarily conserved and ubiquitously expressed protein that has been linked to a variety of functions including transcriptional regulation, mitochondrial function, and vesicle transport. This large protein has numerous caspase and calpain cleavage sites and can be decorated with several post-translational modifications such as phosphorylations, acetylations, sumoylations, and palmitoylations. However, the exact function of HTT and the role played by its modifications in the cell are still not well understood. Scrutiny of HTT function has been focused on a single, full length mRNA. In this study, we report the discovery of 5 novel HTT mRNA splice isoforms that are expressed in normal and HTT-expanded human embryonic stem cell (hESC) lines as well as in cortical neurons differentiated from hESCs. Interestingly, none of the novel isoforms generates a truncated protein. Instead, 4 of the 5 new isoforms specifically eliminate domains and modifications to generate smaller HTT proteins. The fifth novel isoform incorporates a previously unreported additional exon, dubbed 41b, which is hominid-specific and introduces a potential phosphorylation site in the protein. The discovery of this hominid-specific isoform may shed light on human-specific pathogenic mechanisms of HTT, which could not be investigated with current mouse models of the disease. PMID:26010866

  16. Assessment of motor function, sensory motor gating and recognition memory in a novel BACHD transgenic rat model for Huntington disease

    NARCIS (Netherlands)

    Abada, Yah-se K.; Nguyen, Huu Phuc; Schreiber, Rudy; Ellenbroek, Bart

    2013-01-01

    Rationale: Huntington disease (HD) is frequently first diagnosed by the appearance of motor symptoms; the diagnosis is subsequently confirmed by the presence of expanded CAG repeats (> 35) in the HUNTINGTIN (HTT) gene. A BACHD rat model for HD carrying the human full length mutated HTT with 97

  17. Hydrothermal time models for conidial germination and mycelial growth of the seed pathogen Pyrenophora semeniperda

    Science.gov (United States)

    Connor W. Barth; Susan E. Meyer; Julie Beckstead; Phil S. Allen

    2015-01-01

    Population-based threshold models using hydrothermal time (HTT) have been widely used to model seed germination. We used HTT to model conidial germination and mycelial growth for the seed pathogen Pyrenophora semeniperda in a novel approach to understanding its interactions with host seeds. Germination time courses and mycelial growth rates for P.semeniperda were...

  18. Reduced availability of serotonin transporters in obsessive-compulsive disorder correlates with symptom severity - a [11C]DASB PET study

    International Nuclear Information System (INIS)

    Reimold, M.; Smolka, M.N.; Zimmer, A.

    2007-01-01

    Reduced availability of brainstem serotonin transporters (5-HTT) has been observed in vivo in obsessive-compulsive disorder (OCD). However, results vary and may be influenced by competition with endogenous serotonin. Using positron emission tomography (PET) and [ 11 C]DASB, a specific 5-HTT ligand that showed no competition with serotonin for 5-HTT binding in vitro, we tested the hypothesis that 5-HTT availability is reduced in OCD patients and correlated with OCD severity. 5-HTT availability in the thalamus and the midbrain was measured in nine drug-free OCD patients and compared with 19 healthy controls, matched for the individual combination of 5-HTT genotype, gender and smoking status. OCD severity was assessed with the Yale-Brown obsessive compulsive scale (Y-BOCS). 5-HTT availability was significantly reduced in the thalamus and midbrain of OCD patients. Age and 5-HTT in the thalamus explained 83 % of OCD severity in patients that were drug-free for at least 1 year. This PET study confirms a central role of the serotonergic system, particularly the thalamus in the pathogenesis of obsessive compulsive disorder. (author)

  19. Normal aging modulates the neurotoxicity of mutant huntingtin.

    Directory of Open Access Journals (Sweden)

    Elsa Diguet

    Full Text Available Aging likely plays a role in neurodegenerative disorders. In Huntington's disease (HD, a disorder caused by an abnormal expansion of a polyglutamine tract in the protein huntingtin (Htt, the role of aging is unclear. For a given tract length, the probability of disease onset increases with age. There are mainly two hypotheses that could explain adult onset in HD: Either mutant Htt progressively produces cumulative defects over time or "normal" aging renders neurons more vulnerable to mutant Htt toxicity. In the present study, we directly explored whether aging affected the toxicity of mutant Htt in vivo. We studied the impact of aging on the effects produced by overexpression of an N-terminal fragment of mutant Htt, of wild-type Htt or of a beta-Galactosidase (beta-Gal reporter gene in the rat striatum. Stereotaxic injections of lentiviral vectors were performed simultaneously in young (3 week and old (15 month rats. Histological evaluation at different time points after infection demonstrated that the expression of mutant Htt led to pathological changes that were more severe in old rats, including an increase in the number of small Htt-containing aggregates in the neuropil, a greater loss of DARPP-32 immunoreactivity and striatal neurons as assessed by unbiased stereological counts.The present results support the hypothesis that "normal" aging is involved in HD pathogenesis, and suggest that age-related cellular defects might constitute potential therapeutic targets for HD.

  20. The Role of Heat Tolerance Testing in Recovery and Return to Duty

    Science.gov (United States)

    2008-10-01

    CV diseases Hyperthyroidism Pheochromocytoma Infectious diseases Diabetes mellitus Psychiatric illness Parkinsonism Congenital abnormalities: CF...environments. To assess the heat tolerance status of prior heat stroke patient. Heat tolerance test (HTT) “HTT was effective in evaluating the heat tolerance

  1. Huntingtin gene repeat size variations affect risk of lifetime depression

    DEFF Research Database (Denmark)

    Gardiner, Sarah L.; van Belzen, Martine J.; Boogaard, Merel W.

    2017-01-01

    Huntington disease (HD) is a severe neuropsychiatric disorder caused by a cytosine-adenine-guanine (CAG) repeat expansion in the HTT gene. Although HD is frequently complicated by depression, it is still unknown to what extent common HTT CAG repeat size variations in the normal range could affect...

  2. Korralik inimene ostab jõulukingid raamatupoest / Valner Valme, Rebekka Lotman, Merit Kask

    Index Scriptorium Estoniae

    Valme, Valner, 1970-

    2007-01-01

    Peatselt ilmuvatest raamatutest: Kareva, Doris. Lõige : [luuletused] ; Rowling, Joanne Kathleen. Harry Potter ja surma vägised ; Sild, Ivar. Tantsiv linn ; Lee, Maria. Äramõte ; Christensen, Lars Saabye. Modell / tõlkinud Eha Vain ; Murakami, Haruki. Kafka mererannas / tõlkinud Kati Lindström

  3. Tartu Postimehe küsitlus

    Index Scriptorium Estoniae

    2002-01-01

    Vastus küsimusele: mis on see, mis aitaks teil olukorras, kus Andrus Ansipit toetab 64% tartlastest, tõusta Tartu meeritoolile? Vastavad Ivar Tallo, Malle Salupere, Jüri Kumar, Tõnu Kauba, Teet Jagomägi, Tõnis Lukas. Parlamendisaadik

  4. Tammsaare ja piltlugu

    Index Scriptorium Estoniae

    2006-01-01

    Anton Hansen Tammsaare muuseumi korraldatud koomiksivõistlusest "Teistmoodi Tammsaare", žürii koosseis. Esimese koha pälvis Joonas Sildre koomiks "Kuningal on külm", teise koha Elina Sildre töö "Koolis", kolmanda koha soomlase Jyrki Heikkineni töö "Soo peal". Kommenteerivad Tõnu Kaalep, Maarja Lõhmus, Ivar Laus, Meelik Mallene, Mari Laaniste

  5. Selgusid Betti Alveri preemia nominendid

    Index Scriptorium Estoniae

    2005-01-01

    Betti Alveri kirjandusauhinna nominendid: Sass Henno "Mina olin siin", Andrei Hvostovi "Lombakas Achilleus", Mart Kanguri, Jaak Ranna ja Ivar Ravi "Jaak Rand ja teisi jutte", Diana Leesalu "2 grammi hämaruseni", Jaan Pehki "Sisukord", Linnar Priimäe "Kelle tee on varjul", Leo de Sixtuse "Skarabeuse tsivilisatsioon". Vt. ka Eesti Päevaleht, 16. nov., lk. 15

  6. Betti Alveri sünniaastapäeval kuulutatakse välja järjekordne Alveri kirjandusauhinna saaja...

    Index Scriptorium Estoniae

    2005-01-01

    Kirjandusauhinna nominendid: Sass Henno. Mina olin siin ; Andrei Hvostov. Lombakas Achilleus ; Mart Kangur, Jaak Rand ja Ivar Ravi. Jaak Rand ja teisi jutte ; Diana Leesalu. 2 grammi hämaruseni ; Jaan Pehk. Sisukord ; Linnar Priimägi. Kelle tee on varjul ; Leo de Sixtus. Skarabeuse tsivilisatsioon

  7. Dilemmas in SEA application

    DEFF Research Database (Denmark)

    Lyhne, Ivar

    Dilemmas in SEA Application: The DK Energy SectorIvar Lyhne - lyhne@plan.aau.dk. Based on three years of collaborative research, this paper outlines dilemmas in the application of SEA in the strategic development of the Danish energy sector. The dilemmas are based on concrete examples from practice...

  8. Heroines & Superheroines

    DEFF Research Database (Denmark)

    Raahauge, Kirsten Marie

    2010-01-01

    Med udgangspunkt i billedkunstneren Ivar Tønsbergs værker, der under titlen Heroines & Superheroines udstilles ved Dronninglund Kunstcenter 6.6.-1.8.2010, diskuterer denne tekst til udstillingskataloget kvinder og magt, fremstillingsformer og ansigtsaflæsninger. Motivet for værkerne er kvindelige...

  9. Põhjalik koguteos Rootsi võidust / Kaarel Vanamölder

    Index Scriptorium Estoniae

    Vanamölder, Kaarel, 1981-

    2015-01-01

    Arvustus: Enn Küng, Margus Laidre, Ivar Leimus, Aivar Põldvee, Anti Selart, Marten Seppel, Kai Tafenau, Ülle Tarkiainen, Enn Tarvel. Eesti ajalugu III: Vene-Liivimaa sõjast Põhjasõjani. Tartu : Tartu Ülikooli Ajaloo ja arheoloogia instituut, 2013

  10. Keelesümpoosion arutas Põhjamaade mõistet / Ülo Ignats ; fotod: Ülo Ignats

    Index Scriptorium Estoniae

    Ignats, Ülo, 1951-2011

    2006-01-01

    Stockholmis Riigipäeva teise koja saalis teemal "Kuivõrd põhjamaine on Baltikum". Ettekannetega esinesid: Kristel Zilmer, Battail, Jean-Francois Battail, Torkel Jansson, Madis Kanarbik, Stig Örjan Ohlsson, Ivars Orehovs, Erika Sausverde, Thomas Lundén, Katrin Maandi, Kristel Kääramees

  11. Propagaçăo vegetativa de pupunheira (Bactris gasipaes H.B.K.) a partir de perfilhos /

    OpenAIRE

    Tracz, Anderson Luiz Augusto

    2005-01-01

    Orientador: Marguerite Quoirin Co-orientador: Ivar Wendling Dissertaçăo (mestrado) - Universidade Federal do Paraná, Setor de Cięncias Agrárias, Programa de Pós-Graduaçăo em Agronomia. Defesa: Curitiba, 2005 Inclui bibliografia e anexos Área de concentraçăo: Produçăo vegetal

  12. Tartu Tervishoiu Kõrgkool = Tartu Health Care College

    Index Scriptorium Estoniae

    2015-01-01

    Tartu Tervishoiu Kõrgkool Nooruse tänav 5, valminud 2011. Arhitektid Indrek Peil, Siiri Vallner (Kavakava), kaasautorid Johannes Feld, Sten-Mark Mändmaa, Andro Mänd, Ragnar Põllukivi. Sisearhitekt Tarmo Piirmets (Pink). Konstruktorid Ivar Muuk, Andres Hirve (Pike)

  13. Kanepikasvatajate unine suvi / Jüri Ehlvest

    Index Scriptorium Estoniae

    Ehlvest, Jüri, 1967-2006

    2002-01-01

    Arkaadia järjejutust, ilmus juuni - august 2002 Eesti Päevalehes, autorid: Wimberg, Veiko Märka, Urmas Vadi, Jürgen Rooste, Aapo Ilves, Aarne Ruben, Matt Barker, Hedda Maurer, Ivar Sild, Karen Orlau, Indrek Hargla, Jan Kaus, Mehis Heinsaar

  14. Rahvalik ehitus : galeriimaja Harjumaal Peetris Uusmaa tee 1, 3, 5 = Construction for the people : gallery-accessed building in Peetri, Harju County / Triin Ojari

    Index Scriptorium Estoniae

    Ojari, Triin, 1974-

    2008-01-01

    Projekteerija: Arhitektuuribüroo Emil Urbel. Autorid: Emil Urbel, Ainar Luik, Ivar Lubjak. Konstruktor: OÜ Printsiip. Ehitaja: KMG Ehitus. Projekt: 2006, valmis: 2007. Emil Urbel ja Ainar Luik hoone arhitektuursest lahendusest, ehitusmaterjalidest, ökonoomsusest, ehitusest. Asendiplaan, I-III korruse plaan, 7 värv. välisvaadet

  15. [Eesti ajalugu III: Vene-Liivimaa sõjast Põhjasõjani] / Kalle Kroon

    Index Scriptorium Estoniae

    Kroon, Kalle, 1966-

    2014-01-01

    Arvustus. Enn Küng, Margus Laidre, Ivar Leimus, Aivar Põldvee, Anti Selart, Marten Sepepl, Kai Tafenau, Ülle Tarkiainen, Enn Tarvel. Eesti ajalugu III: Vene-Liivimaa sõjast Põhjasõjani. Tartu: Tartu Ülikooli Ajaloo ja Arheoloogia Instituut, 2013

  16. 13.-20. IV viiakse Kütioru Avatud Ateljees läbi metsakunsti projekt

    Index Scriptorium Estoniae

    2005-01-01

    Osalevad "isekasvava arhitektuuri" (evolutionary architecture) teooria rajaja John Frazer Londonist ning Hollandi arhitektuuribürood S333 ja Onix. Käsitletakse Eesti metsade võsastumise temaatikat. 19. IV Eesti Kunstiakadeemias seminar, lisaks väliskülalistele esinevad Marek Strandberg, Ivar Puura jt.

  17. Eesti Maanteemuuseumi välialad : avalik maastikuarhitektuuri ideekonkurss = Public Landscape Architectural Idea Competition "Outdoor Spaces of the Estonian Highway Museum" / Toomas Muru

    Index Scriptorium Estoniae

    Muru, Toomas, 1970-

    2004-01-01

    Põlvamaal, endises Varbuse hobupostijaamas avatava Eesti Maanteemuuseumi välialade konkursi eesmärgist, tingimustest, žürii koosseisust, premeeritud töödest. Preemiad: I - Margit Kärner, II - Karli Luik, Ralf Lõoke ja Maarja Kask, III - Taavi Kuningas, Andrus Padu ja Martin Prommik, ergutuspreemiad - Piret Looveer ja Remi Kübar ning Maria Pukk ja Ivar Lubjak

  18. Surnuist üles äratamine = Reviving the dead / David Crowley

    Index Scriptorium Estoniae

    Crowley, David, 1966-

    2012-01-01

    Eesti ekspositsioonist "Kui pikk on ühe maja elu?" 13. Venezia arhitektuuribiennaalil "Common Ground" (kuraator David Chipperfield). Tallinna Linnahalli minevikust ja praegusest olukorrast. Kuraator Tüüne-Kristin Vaikla, näituse autorid Urmo Vaikla, Tüüne-Kristin Vaikla, Ingel Vaikla, Maria Pukk, Ivar Lubjak, Veronika Valk. Saksa paviljoni näitusest "Reduce, reuse, recycle"

  19. Igual que en un circo pobre

    Directory of Open Access Journals (Sweden)

    Rodrigo Pérez Gil

    2005-09-01

    Full Text Available Los casibandidos que casi ruban el sol. Triunfo Arciniegas. Fondo de Cultura Económica, México, 2003. 39 págs., il. Balada peluda. Ivar da Coll. Fondo de Cuhura Económica. México, 2004, 38 págs., il.

  20. Unista. Taju. Kohane. Toida. Linnahalli 5 visiooni = Dream. Sense. Adapt. Feed. 5 visions for Linnahall

    Index Scriptorium Estoniae

    2012-01-01

    Tallinna Linnahalli visiooni töötuba Eesti Kunstiakadeemia, Eesti Maaülikooli ja Tallinna Ülikooli Balti Filmi- ja Meediakooli üliõpilastele 28.05.-01.06.2012. Juhendasid Maria Pukk, Ivar Lubjak ja Veronika Valk

  1. Lahkunud maailmaparandaja Robert Lepikson jäi igavesti otsijaks / Kai Kalamees

    Index Scriptorium Estoniae

    Kalamees, Kai

    2006-01-01

    Ülevaade riigikogu liikme, endise siseministri, Tallinna linnapea ja Võru maavanema Robert Lepiksoni elukäigust, meenutused tuntud ühiskonnategelastelt. Lisad: Robert Lepikson; Kõva sõnaga mees. Vt. samas: Turvavaatleja vastutusrikas töö viimasel rallil; Ivar Raidam: Lepiksoni panus autosporti oli tohutu; Hans H. Luik: Respect, Robert!

  2. "Ird, K." sai Riias preemia

    Index Scriptorium Estoniae

    2011-01-01

    7. Balti teatrifestivalil Riias sai Tartu Uue Teatri juht Ivar Põllu auhinna lavastuse "Ird, K." kontseptsiooni ja helikujunduse eest ning näitleja Nero Urke Kaarel Irdi rolli eest. Von Krahli Teatri truppi hinnati aja ja ruumi loova käsitluse eest lavastuses "The End"

  3. Театр хочет быть авторским / Борис Тух

    Index Scriptorium Estoniae

    Тух, Борис, 1946-

    2011-01-01

    7. Balti teatrifestivalist Riias (СКАТС-2011), lavastustest. Eestit esindanud Tartu Uue Teatri juht Ivar Põllu sai auhinna lavastuse "Ird, K." kontseptsiooni ja helikujunduse eest, näitleja Nero Urke Kaarel Irdi rolli eest samas lavastuses. Von Krahli Teatri truppi hinnati aja ja ruumi loova käsitluse eest lavastuses "The End"

  4. Villa Vision

    DEFF Research Database (Denmark)

    1994-01-01

    Præsentation af det højteknologiske fremtidshus i Høje Taastrup tegnet af Ivar Moltke og Flemming Skude. Huset er stort set selvforsynende med energi til eludstyr og opvarmning ligesom det renser sit grå og sorte spildevand. Konceptet bygger på passiv solvarme, aerodynamisk form og materialeoplev...

  5. Savisaare jõuluime taustaks on valimiseelne leping Kruudaga / Hannes Krause

    Index Scriptorium Estoniae

    Krause, Hannes

    2005-01-01

    Keskerakonna esimehele Edgar Savisaarele Keila-Joal asuva suvila müümisest alla turuhinna. Kommenteerivad Ivar Tallo ja Margus Leivo. Lisad: Savisaare majatehing; Tehing; Savisaarel teine majaskandaal. Vt. samas: Hannes Krause, Jaanus Piirsalu. Aruanne võib näidata maja õiget hinda; Hannes Krause, Kristjan Jõevere. Savisaare omaga sarnane maja müügis 3 miljoniga

  6. Arnold Rüütel alustas oma Valgamaa visiiti Tõrvas ja Otepääl / Urve Sinisalu

    Index Scriptorium Estoniae

    Sinisalu, Urve, 1945-

    2002-01-01

    President Arnold Rüütli visiidist Valgamaale. Kohtumisest Tõrva Gümnaasiumi direktori Ivar Hanvere ja Tõrva linnapea Väino Tõemetsaga, külaskäigust Ants Tauli torupillitallu. Kommenteerib Ingrid Rüütel. Maakonnavisiit Valgamaale 23.-24.09.2002

  7. 26. V võõrustas Läti suursaadik Edgars Skuja Tallinnas Tõnismäel Liivimaa aja- ja kultuuriloo huvilist üldsust... / Aili Künstler

    Index Scriptorium Estoniae

    Künstler, Aili

    2005-01-01

    Antakse välja Riias tegutsenud baltisaksa kultuuriloolase Johann Christoph Brotze (1742-1823) siinset arhitektuuri, eluolu, inimtüüpe, maastikku, linnavaateid jms. kujutava materjaliga köide. J. Chr. Brotze joonistuste hulgast teevad valiku ja tema saksakeelset teksti kommenteerivad peatoimetaja Raimo Pullat, Ivar Leimus, Ants Hein, Ants Viires, Lauri Suurmaa ja Tõnis Liibek

  8. Patarei ja Lennusadama ala planeering = Plan for the Patarei Fort and Lennusadam Port Area

    Index Scriptorium Estoniae

    2007-01-01

    Patarei ja Lennusadama ala mahulise planeerimise rahvusvaheline ideevõistlus 2007. aastal. Võistlustööd "Kolm õuna" (I preemia - Sverre Laanjärv, Ivar Lubjak), "Põhi" (II preemia - Tõnu Laanemäe, Jaak-Adam Looveer, Toomas Paaver, kaasautorid Indrek Järve ja Lauri Saar) ja "Kompass" (III preemia - Ott Kadarik ja Villem Tomiste, AB Kosmos)

  9. Rahvusvaheline naer läbi pisarate kunstihoones / Riin Kübarsepp

    Index Scriptorium Estoniae

    Kübarsepp, Riin, 1978-

    2008-01-01

    Näitus "Halb nali" Tallinna Kunstihoones, kuraator Johannes Saar. Eksponeeritakse Nathalie Djurberg'i (Rootsi), Peter Finnemore' (Wales), Ivars Gravlejs'i (Läti), Tsui Kuang-Yu (Taiwan), Marko Mäetamme (Eesti), Jüri Ojaveri (Eesti) jt. kunstnike töid

  10. Halb nali. Oma viga? / Maria-Kristiina Soomre

    Index Scriptorium Estoniae

    Soomre, Maria-Kristiina, 1978-

    2007-01-01

    Näitus "Halb nali" Tallinna Kunstihoones kuni 6. I 2008. Kuraator Johannes Saar, kunstnikud: Tamy Ben-Tor, Nathalie Djurberg, Peter Finnemore, Paul Granjon, Ivars Gravlejs, Igor Grubic, Zlatko Kopljar, Tsui Kuang-Yu, Marko Mäetamm, Jüri Ojaver, Julian Rosefeldt, Tommi Toija

  11. Functional Analysis: Entering Hilbert Space

    DEFF Research Database (Denmark)

    Hansen, Vagn Lundsgaard

    in a new chapter on Fredholm theory (Chapter 6). Fredholm theory originates in pioneering work of the Swedish mathematician Erik Ivar Fred-holm on integral equations, which inspired the study of a new class of bounded linear operators, known as Fredholm operators. Chapter 6 presents the basic elements...

  12. Gallup : kirjandus, kirjanik, kriitika ja kriitik : [küsitlus

    Index Scriptorium Estoniae

    2005-01-01

    Küsimustele vastavad: Jan Kaus, Arne Merilai, Aarne Ruben, Peeter Sauter, Asta Põldmäe, Aare Pilv, Arvo Valton, Lauri Sommer, Mari Laaniste, Toomas Raudam, Ivar Sild, Olev Remsu, Kalle Kurg, Fagira D Morti, Eeva Park, Neeme Lopp, Valle-Sten Maiste, Sirli Ojaste, Ene-Reet Soovik, Märt Väljataga, Indrek Mesikepp

  13. Eestis on juba puudu üle 400 IT-spetsialisti / Kai Simson

    Index Scriptorium Estoniae

    Simson, Kai

    2006-01-01

    Cisco Systemsi poolt 31 Ida- ja Lääne-Euroopa riigis tehtud uuringu kohaselt on Eesti IT-spetsialistidega varustatuse paremusjärjestuses alles 28. kohal. Vt. samas lühiintervjuud e-Riigi Akadeemia direktori Ivar Talloga

  14. Disainiöös on asju / Karin Paulus

    Index Scriptorium Estoniae

    Paulus, Karin, 1975-

    2016-01-01

    Tallinna Disainiöö 12.-18. septembrini 2016. Uuest kodumaisest disainist (näiteid Marta Mooratsi, Tarmo Luisu, Veiko Liisi, Urmas Lüüsi, Ivar Kaasiku, Krista Leesi, Mariana Laane, Margot Holtsi, Jan Plaani, Pille Ernesaksa loomingust)

  15. Taani ristisõjad Läänemere ääres / Linda Kaljundi

    Index Scriptorium Estoniae

    Kaljundi, Linda

    2007-01-01

    Raamatututvustus: Taani ristisõjad - sõda ja misjon Läänemere ääres / John H. Lind, Carsten Selch Jensen, Kurt Villads Jensen, Ane L. Bysted ; tõlkijad Ivar Rüütli ja Kalle Kroon ; teaduslik toimetaja ja järelsõna: Linda Kaljundi. Tallinn : Argo, 2007

  16. Kalev Spa : Aia tn. 18, Tallinn = Kalev Spa : Aia St. 18, Tallinn / Henry Kuningas

    Index Scriptorium Estoniae

    Kuningas, Henry

    2006-01-01

    "Kalevi" ujula ümberehitus. Projekteerija: AB Emil Urbel OÜ. Autorid: Emil Urbel, Ivar Lubjak. Sisekujundaja: Taavi Aunre (OÜ Boom.ee). Konstruktor: Margus Allik (MG Inseneribüroo OÜ). Projekt ja valmis: 2005. Ill.: I korruse plaan, 4 värv. vaadet

  17. Kas Mustjõe kasvab linnaks? / Tõnu Laigu

    Index Scriptorium Estoniae

    Laigu, Tõnu

    2002-01-01

    Tallinna Mustjõe asumi korterelamu ja puhkeala ruumilise planeerimise ideevõistlusest. Preemiad: I - Ott Kadarik, Villem Tomiste, Mihkel Tüür (büroo Kosmos), II - Margit Mutso (büroo Eek & Mutso), III - Veronika Valk, ostupreemia - Sverre Laanjärv, Ivar Lubjak

  18. Studying biosphere-atmosphere exchange of CO2 through Carbon-13 stable isotopes

    NARCIS (Netherlands)

    Velde, van der I.R.

    2015-01-01

    Summary Thesis ‘Studying biosphere-atmosphere exchange of CO2 through

    carbon-13 stable isotopes’

    Ivar van der Velde

    Making predictions of future climate is difficult, mainly due to large uncertainties in the carbon cycle. The rate at which carbon is stored in the oceans and

  19. [Raamat] / Elisa Loopealne

    Index Scriptorium Estoniae

    Loopealne, Elisa

    2007-01-01

    Tutvustus: Bristol, Piret. Nöörist ja seebist. Pärnu : Jumalikud Ilmutused, 2006. (Ji) ; Kivisildnik. Vägistatud jäämägi. Pärnu : Jumalikud Ilmutused, 2006. (Ji) ; Sild, Ivar. Spermaga ja puha. Pärnu : Jumalikud Ilmutused, 2006. (Ji) ; Meiel, Kaupo. Polügrafisti käsiraamat, 2006

  20. M-A-G-I-C viis marsruuti, viis pilku meie Euroopale

    Index Scriptorium Estoniae

    2006-01-01

    10. juunil Eesti Rahvusraamatukogus etendunud teatrivõrgustiku Magic Net (organisatsioon, mis ühendab 14 Euroopa teatrit) ühislavastusest "Peidetud lood" (Projekti juht Dirk Neldner). Arvustavad teatrikriitikud Rait Avestik, Madis Kolk, Ivar Põllu, Andres Keil ja üliõpilane Uku Uusberg

  1. Ärimees ootab annetuse eest Keskerakonnalt vastuteenet / Dannar Leitmaa, Erik Rand, Milan Bališ

    Index Scriptorium Estoniae

    Leitmaa, Dannar, 1982-

    2009-01-01

    Slovakkia ärimehed annetasid Eesti Keskerakonnale 1,4 mln. krooni, avaliku teenistuse eetikakoodeksi autor Ivar Tallo peab välismaistelt annetajatelt raha saamist taunitavaks. Annetustest teistele erakondadele I kvartalis. Vt. samas lühiintervjuud Milan Bališiga

  2. Täna selgub aasta film 2005

    Index Scriptorium Estoniae

    2006-01-01

    Eesti Filmiajakirjanike Ühing kuulutab välja Neitsi Maali filmiauhinna võitja. Nominendid on : "Afganistani armid" (rezh. Ivar Heinmaa), "Kuum külm sõda : Haukka grupp" (rezh. Rene Vilbre), "Kohtumine tundmatuga" (rezh. Jaak Kilmi), "Libahundi needus" (rezh. Rainer Sarnet), "Mees animatsioonist" (rezh. Hardi Volmer)

  3. Vaatamisest teateni / Margot Kask

    Index Scriptorium Estoniae

    Kask, Margot

    2006-01-01

    Maastiku mõiste arengust läbi kunstiajaloo ning nägemise ja kujutamise vastastikustest seostest. Reimo Võsa Tangsoo (sünd. 1976), Eve Kiileri (sünd. 1962), Ivar Veermäe (sünd. 1982) ja Taavi Suitsu maastikufotodest

  4. President Toomas Hendrik Ilvese avaldus seoses sündmustega Gruusias / Toomas Hendrik Ilves

    Index Scriptorium Estoniae

    Ilves, Toomas Hendrik, 1953-

    2008-01-01

    Vt. samas: President Ilves sõitis Thbilisisse. President Toomas Hendrik Ilves sõitis koos Poola riigipea Lech Kaczynski, Leedu riigipea Valdas Adamkuse, Ukraina riigipea Viktor Jushtshenko ning Läti peaministri Ivars Godmanisega Gruusiasse. Vabariigi President töövisiidil Gruusias 12.-13.08.2008. Ilmunud ka: Postimees : na russkom jazõke 13. aug, lk. 2

  5. Normalitet og afvigelse

    DEFF Research Database (Denmark)

    Holst, Jesper

    2009-01-01

    Anmeldelse ad Ivar Morkens bog:" Normalitet og afvigelse", der tager udgangspunkt i kontrasten mellem visionerne om inklusion, empowerment og anerkendelse og de faktiske forhold, hvor menneskelig afvig stadig diagnosticeres. Kontrasterne defineres og forsøges imødegået med forskellige former for ...

  6. Norma Maja astub kindlalt tulevikku / Ain Alvela

    Index Scriptorium Estoniae

    Alvela, Ain, 1967-

    2000-01-01

    AS Norma Maja saavutas kõrged kasumi ja kasumi kasvu näitajad töötajate koondamisega. Tabel: Norma Maja valdused, AS Norma Maja areng, AS ETK Majad areng. Arvamused: Ero Toom, Ivar Lahi ja Rein Loo

  7. "Hey Russia hands off Georgia"

    Index Scriptorium Estoniae

    2008-01-01

    Eesti presidendi Toomas Hendrik Ilvese, Leedu presidendi Valdas Adamkuse, Poola presidendi Lech Kaczynski ning Läti peaministri Ivars Godmanise toetusvisiidist Gruusiasse. Balti riikide juhid mõistsid Venemaa-Gruusia konflikti hukka ning pälvisid sellega Venemaa kriitika. Vabariigi President töövisiidil Gruusias 12.-13.08.2008

  8. Post-ideology and post-conceptual architecture and urbanism in (Eastern) Europe / Marina Gržinić

    Index Scriptorium Estoniae

    Gržinić, Marina, 1958-

    2012-01-01

    Essee on kirjutatud Eesti ekspositsiooni "Kui pikk on ühe maja elu?" (näituse komissar Ülar Mark, kuraator Tüüne-Kristin Vaikla, autorid Tüüne-Kristin Vaikla, Urmo Vaikla, Ingel Vaikla, Maria Pukk. Ivar Lubjak, Veronika Valk) jaoks 13. Venezia arhitektuuribiennaalil "Common Ground" 2012. aastal

  9. SUMO-2 and PIAS1 Modulate Insoluble Mutant Huntingtin Protein Accumulation

    Directory of Open Access Journals (Sweden)

    Jacqueline Gire O’Rourke

    2013-07-01

    Full Text Available A key feature in Huntington disease (HD is the accumulation of mutant Huntingtin (HTT protein, which may be regulated by posttranslational modifications. Here, we define the primary sites of SUMO modification in the amino-terminal domain of HTT, show modification downstream of this domain, and demonstrate that HTT is modified by the stress-inducible SUMO-2. A systematic study of E3 SUMO ligases demonstrates that PIAS1 is an E3 SUMO ligase for both HTT SUMO-1 and SUMO-2 modification and that reduction of dPIAS in a mutant HTT Drosophila model is protective. SUMO-2 modification regulates accumulation of insoluble HTT in HeLa cells in a manner that mimics proteasome inhibition and can be modulated by overexpression and acute knockdown of PIAS1. Finally, the accumulation of SUMO-2-modified proteins in the insoluble fraction of HD postmortem striata implicates SUMO-2 modification in the age-related pathogenic accumulation of mutant HTT and other cellular proteins that occurs during HD progression.

  10. Loss of Huntingtin stimulates capture of retrograde dense-core vesicles to increase synaptic neuropeptide stores.

    Science.gov (United States)

    Bulgari, Dinara; Deitcher, David L; Levitan, Edwin S

    2017-08-01

    The Huntington's disease protein Huntingtin (Htt) regulates axonal transport of dense-core vesicles (DCVs) containing neurotrophins and neuropeptides. DCVs travel down axons to reach nerve terminals where they are either captured in synaptic boutons to support later release or reverse direction to reenter the axon as part of vesicle circulation. Currently, the impact of Htt on DCV dynamics in the terminal is unknown. Here we report that knockout of Drosophila Htt selectively reduces retrograde DCV flux at proximal boutons of motoneuron terminals. However, initiation of retrograde transport at the most distal bouton and transport velocity are unaffected suggesting that synaptic capture rate of these retrograde DCVs could be altered. In fact, tracking DCVs shows that retrograde synaptic capture efficiency is significantly elevated by Htt knockout or knockdown. Furthermore, synaptic boutons contain more neuropeptide in Htt knockout larvae even though bouton size, single DCV fluorescence intensity, neuropeptide release in response to electrical stimulation and subsequent activity-dependent capture are unaffected. Thus, loss of Htt increases synaptic capture as DCVs travel by retrograde transport through boutons resulting in reduced transport toward the axon and increased neuropeptide in the terminal. These results therefore identify native Htt as a regulator of synaptic capture and neuropeptide storage. Copyright © 2017 Elsevier GmbH. All rights reserved.

  11. Cardiac mTORC1 Dysregulation Impacts Stress Adaptation and Survival in Huntington’s Disease

    Directory of Open Access Journals (Sweden)

    Daniel D. Child

    2018-04-01

    Full Text Available Summary: Huntington’s disease (HD is a dominantly inherited neurological disorder caused by CAG-repeat expansion in exon 1 of Huntingtin (HTT. But in addition to the neurological disease, mutant HTT (mHTT, which is ubiquitously expressed, impairs other organ systems. Indeed, epidemiological and animal model studies suggest higher incidence of and mortality from heart disease in HD. Here, we show that the protein complex mTORC1 is dysregulated in two HD mouse models through a mechanism that requires intrinsic mHTT expression. Moreover, restoring cardiac mTORC1 activity with constitutively active Rheb prevents mortality and relieves the mHTT-induced block to hypertrophic adaptation to cardiac stress. Finally, we show that chronic mTORC1 dysregulation is due in part to mislocalization of endogenous Rheb. These data provide insight into the increased cardiac-related mortality of HD patients, with cardiac mHTT expression inhibiting mTORC1 activity, limiting heart growth, and decreasing the heart’s ability to compensate to chronic stress. : Child et al. demonstrate that mTORC1 dysregulation is a key molecular mechanism in the Huntington’s disease (HD heart phenotype. Impaired cardiac mTORC1 activity in HD mouse models requires intrinsic mHTT expression and explains the limited adaptation to cardiac stress. Keywords: Huntington’s disease, heart, mTOR, Rheb

  12. Highly purified, multi-wall carbon nanotubes induce light-chain 3B expression in human lung cells

    International Nuclear Information System (INIS)

    Tsukahara, Tamotsu; Matsuda, Yoshikazu; Usui, Yuki; Haniu, Hisao

    2013-01-01

    Highlights: •HTT2800-treated BEAS-2B cells induced LC3B in a time-dependent manner. •HTT2800-treated BEAS-2B cells showed decreased cell proliferation that was both time- and dose-dependent. •Addition of 3-MA, LC3B-II protein and mRNA levels were significantly decreased. •3-MA and E64-d + pepstatin A, but not brefeldin A, provided protection against HTT2800-induced cell death. •These results suggest that HTT2800 predominantly causes autophagy rather than apoptotic cell death in BEAS-2B cells. -- Abstract: Bronchial epithelial cells are targets of inhalation and play a critical role in the maintenance of mucosal integrity as mechanical barriers against various particles. Our previous result suggest that vapor-grown carbon fiber, HTT2800, which is one of the most highly purified multi-wall carbon nanotubes (MWCNT) showed cellular uptake of the carbon nanotube, increased cell death, enhanced DNA damage, and induced cytokine release. Increasing evidence suggests that autophagy may critically influence vital cellular processes such as apoptosis, cell proliferation and inflammation and thereby may play a critical role in pulmonary diseases. Autophagy was recently recognized as a critical cell death pathway, and autophagosome accumulation has been found to be associated with the exposure of various nanoparticles. In this study, the authors focus on the autophagic responses of HTT2800 exposure. The HTT2800-exposed cells induced LC3B expression and induced cell growth inhibition

  13. Highly purified, multi-wall carbon nanotubes induce light-chain 3B expression in human lung cells

    Energy Technology Data Exchange (ETDEWEB)

    Tsukahara, Tamotsu, E-mail: ttamotsu@kanazawa-med.ac.jp [Department of Hematology and Immunology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293 (Japan); Matsuda, Yoshikazu [Clinical Pharmacology Educational Center, Nihon Pharmaceutical University, Ina-machi, Saitama 362-0806 (Japan); Usui, Yuki [Research Center for Exotic Nanocarbons, Shinshu University, 4-17-1 Wakasato, Nagano-shi, Nagano 380-8553 (Japan); Haniu, Hisao [Department of Orthopaedic Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621 (Japan)

    2013-10-18

    Highlights: •HTT2800-treated BEAS-2B cells induced LC3B in a time-dependent manner. •HTT2800-treated BEAS-2B cells showed decreased cell proliferation that was both time- and dose-dependent. •Addition of 3-MA, LC3B-II protein and mRNA levels were significantly decreased. •3-MA and E64-d + pepstatin A, but not brefeldin A, provided protection against HTT2800-induced cell death. •These results suggest that HTT2800 predominantly causes autophagy rather than apoptotic cell death in BEAS-2B cells. -- Abstract: Bronchial epithelial cells are targets of inhalation and play a critical role in the maintenance of mucosal integrity as mechanical barriers against various particles. Our previous result suggest that vapor-grown carbon fiber, HTT2800, which is one of the most highly purified multi-wall carbon nanotubes (MWCNT) showed cellular uptake of the carbon nanotube, increased cell death, enhanced DNA damage, and induced cytokine release. Increasing evidence suggests that autophagy may critically influence vital cellular processes such as apoptosis, cell proliferation and inflammation and thereby may play a critical role in pulmonary diseases. Autophagy was recently recognized as a critical cell death pathway, and autophagosome accumulation has been found to be associated with the exposure of various nanoparticles. In this study, the authors focus on the autophagic responses of HTT2800 exposure. The HTT2800-exposed cells induced LC3B expression and induced cell growth inhibition.

  14. Synthesis, radiolabeling and baboon SPECT imaging of 2{beta}-carbomethoxy-3{beta}-(3'-[{sup 123}I]iodophenyl)tropane ([{sup 123}I]YP256) as a serotonin transporter radiotracer

    Energy Technology Data Exchange (ETDEWEB)

    Bois, Frederic; Baldwin, Ronald M.; Amici, Louis; Al-Tikriti, Mohammed S. [Yale University, School of Medicine, VA Connecticut HCS (116A2), West Haven, CT 06516 (United States); Kula, Nora; Baldessarini, Ross [Department of Psychiatry and Neuroscience Program, Harvard Medical School, Mailman Research Center McLean Division of Massachusetts General Hospital, Belmont, MA 02478 (United States); Innis, Robert B.; Staley, Julie K. [Yale University, School of Medicine, VA Connecticut HCS (116A2), West Haven, CT 06516 (United States); Tamagnan, Gilles D. [Yale University, School of Medicine, VA Connecticut HCS (116A2), West Haven, CT 06516 (United States); Institute for Neurodegenerative Disorders, New Haven, CT 06510 (United States)], E-mail: gtamagnan@indd.org

    2008-01-15

    To develop a potential SPECT probe to evaluate the integrity of the serotoninergic system (5-HTT) whose dysfunction is linked to several disease conditions such as Parkinson's disease, Alzheimer's disease and depression, we report the synthesis, radiolabeling and in vivo baboon imaging of 2{beta}-carbomethoxy-3{beta}-(3'-[{sup 123}I]iodophenyl) tropane (YP256, ). The radiolabeling was performed by iododestannylation using sodium [{sup 123}I]iodide and peracetic acid. Although the ligand displayed high selectivity for 5-HTT over dopamine transporter in vitro, SPECT imaging in baboons did not reveal selective 5-HTT accumulation in brain in vivo.

  15. Synthesis, radiolabeling and baboon SPECT imaging of 2β-carbomethoxy-3β-(3'-[123I]iodophenyl)tropane ([123I]YP256) as a serotonin transporter radiotracer

    International Nuclear Information System (INIS)

    Bois, Frederic; Baldwin, Ronald M.; Amici, Louis; Al-Tikriti, Mohammed S.; Kula, Nora; Baldessarini, Ross; Innis, Robert B.; Staley, Julie K.; Tamagnan, Gilles D.

    2008-01-01

    To develop a potential SPECT probe to evaluate the integrity of the serotoninergic system (5-HTT) whose dysfunction is linked to several disease conditions such as Parkinson's disease, Alzheimer's disease and depression, we report the synthesis, radiolabeling and in vivo baboon imaging of 2β-carbomethoxy-3β-(3'-[ 123 I]iodophenyl) tropane (YP256, ). The radiolabeling was performed by iododestannylation using sodium [ 123 I]iodide and peracetic acid. Although the ligand displayed high selectivity for 5-HTT over dopamine transporter in vitro, SPECT imaging in baboons did not reveal selective 5-HTT accumulation in brain in vivo

  16. CTG repeat-targeting oligonucleotides for down-regulating Huntingtin expression

    DEFF Research Database (Denmark)

    Zaghloul, Eman M; Gissberg, Olof; Moreno, Pedro M D

    2017-01-01

    Huntington's disease (HD) is a fatal, neurodegenerative disorder in which patients suffer from mobility, psychological and cognitive impairments. Existing therapeutics are only symptomatic and do not significantly alter the disease progression or increase life expectancy. HD is caused by expansion....... Thus, reduction of both muHTT mRNA and protein levels would ideally be the most useful therapeutic option. We herein present a novel strategy for HD treatment using oligonucleotides (ONs) directly targeting the HTT trinucleotide repeat DNA. A partial, but significant and potentially long-term, HTT...

  17. BDNF val66met association with serotonin transporter binding in healthy humans

    DEFF Research Database (Denmark)

    Fisher, P. M.; Ozenne, B.; Svarer, C.

    2017-01-01

    The serotonin transporter (5-HTT) is a key feature of the serotonin system, which is involved in behavior, cognition and personality and implicated in neuropsychiatric illnesses including depression. The brain-derived neurotrophic factor (BDNF) val66met and 5-HTTLPR polymorphisms have predicted......-carriers have increased subcortical 5-HTT binding. The small difference suggests limited statistical power may explain previously reported null effects. Our finding adds to emerging evidence that BDNF val66met contributes to differences in the human brain serotonin system, informing how variability in the 5-HTT...

  18. Helmet Sensor - Transfer Function and Model Development

    Science.gov (United States)

    2010-09-01

    that helmets be examined forensically when estimating the impact direction and location and the electronic HMSS data not be used in that determination... forensic analysis of the helmet itself is therefore recommended to determine the direction and severity of the ballistic impact 5. The helmet shell does...ot83 HTI l ot 8J HT1 lot S ,HTt IOt S , HTI l otiH HTt lotSS HTt l vt85 HTI l o)t 85 HT1 Front Level Acceleration ~~,--~----~--,30’p~g

  19. Brain Networks Implicated in Seasonal Affective Disorder

    DEFF Research Database (Denmark)

    Nørgaard, Martin; Ganz, Melanie; Svarer, Claus

    2017-01-01

    , patients with SAD fail to globally downregulate their cerebral serotonin transporter (5-HTT) in winter, and that this effect seemed to be particularly pronounced in female S-carriers of the 5-HTTLPR genotype. The purpose of this study was to identify a 5-HTT brain network that accounts for the adaption...... without SAD; it included the right superior frontal gyrus, brainstem, globus pallidus (bilaterally) and the left hippocampus. Across seasons, female S' carriers without SAD showed nominally higher 5-HTT levels in these regions compared to female S' carriers with SAD, but the group difference was only...... winter compared to female S' carriers without SAD. Limitations: The study is preliminary and limited by small sample size in the SAD group (N = 6). Conclusions: These findings provide novel exploratory evidence for a wintertime state-dependent difference in 5-HTT levels that may leave SAD females...

  20. Acute inescapable stress alleviates fear extinction recall deficits caused by serotonin transporter abolishment.

    Science.gov (United States)

    Schipper, Pieter; Henckens, Marloes J A G; Lopresto, Dora; Kozicz, Tamas; Homberg, Judith R

    2018-07-02

    Life stress increases risk for developing post-traumatic stress disorder (PTSD), and more prominently so in short-allele carriers of the serotonin transporter linked polymorphic region (5-HTTLPR). Serotonin transporter knockout (5-HTT -/- ) rats show compromised extinction (recall) of conditioned fear, which might mediate the increased risk for PTSD and reduce the therapeutic efficacy of exposure therapy. Here, we assessed whether acute inescapable stress (IS) differentially affects fear extinction and extinction recall in 5-HTT -/- rats and wildtype controls. Surprisingly, IS experience improved fear extinction recall in 5-HTT -/- rats to the level of wildtype animals, while wildtypes were unaffected by this IS. Thus, whereas 5-HTT -/- rats evidently were more responsive to the stressor, the behavioral consequences presented themselves as adaptive. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  1. Perseverative instrumental and Pavlovian responding to conditioned stimuli in serotonin transporter knockout rats

    NARCIS (Netherlands)

    Nonkes, L.J.P.; Homberg, J.R.

    2013-01-01

    Environmental stimuli can influence behavior via the process of Pavlovian conditioning. Recent genetic research suggests that some individuals are more sensitive to environmental stimuli for behavioral guidance than others. One important mediator of this effect is serotonin transporter (5-HTT)

  2. File list: His.Dig.50.AllAg.Intestine,_Small [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Dig.50.AllAg.Intestine,_Small hg19 Histone Digestive tract Intestine, Small htt...p://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Dig.50.AllAg.Intestine,_Small.bed ...

  3. Stemcell Information: SKIP000385 [SKIP Stemcell Database[Archive

    Lifescience Database Archive (English)

    Full Text Available Teratoma formation ... Yes ... Yes ... National Research Institute for Child Health and Development htt...p://www.ncbi.nlm.nih.gov/geo/ Akihiro Umezawa 梅澤 明弘 Available National Research Institute for Child Health a

  4. ROCK and PRK-2 Mediate the Inhibitory Effect of Y-27632 on Polyglutamine Aggregation

    Science.gov (United States)

    Shao, Jieya; Welch, William J.; Diamond, Marc I.

    2009-01-01

    Polyglutamine expansion in huntingtin (Htt) and the androgen receptor (AR) causes untreatable neurodegenerative diseases. Y-27632, a therapeutic lead, reduces Htt and AR aggregation in cultured cells, and Htt-induced neurodegeneration in Drosophila. Y-27632 inhibits both Rho-associated kinases ROCK and PRK-2, making its precise intracellular target uncertain. Over-expression of either kinase increases Htt and AR aggregation. Three ROCK inhibitors (Y-27632, H-1077, HA-1152), and a specific ROCK inhibitory peptide reduce polyglutamine protein aggregation, as does knockdown of ROCK or PRK-2 by RNAi. RNAi also indicates that each kinase is required for the inhibitory effects of Y-27632 to manifest fully. These two actin regulatory kinases are thus involved in polyglutamine aggregation, and their simultaneous inhibition may be an important therapeutic goal. PMID:18423405

  5. File list: Unc.Kid.50.AllAg.Nephrectomy_sample [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Kid.50.AllAg.Nephrectomy_sample hg19 Unclassified Kidney Nephrectomy sample htt...p://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Kid.50.AllAg.Nephrectomy_sample.bed ...

  6. File list: Unc.Kid.10.AllAg.Nephrectomy_sample [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Kid.10.AllAg.Nephrectomy_sample hg19 Unclassified Kidney Nephrectomy sample htt...p://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Kid.10.AllAg.Nephrectomy_sample.bed ...

  7. File list: Unc.Kid.20.AllAg.Nephrectomy_sample [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Kid.20.AllAg.Nephrectomy_sample hg19 Unclassified Kidney Nephrectomy sample htt...p://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Kid.20.AllAg.Nephrectomy_sample.bed ...

  8. Anorexigen-induced pulmonary hypertension and the serotonin (5-HT hypothesis: lessons for the future in pathogenesis

    Directory of Open Access Journals (Sweden)

    Adnot Serge

    2002-01-01

    Full Text Available Abstract Epidemiological studies have established that fenfluramine, D-fenfluramine, and aminorex, but not other appetite suppressants, increase the risk of primary pulmonary hypertension (PH. One current hypothesis suggests that fenfluramine-like medications may act through interactions with the serotonin (5-hydroxytryptamine [5-HT] transporter (5-HTT located on pulmonary artery smooth muscle cells and responsible for the mitogenic action of 5-HT. Anorexigens may contribute to PH by boosting 5-HT levels in the bloodstream, directly stimulating smooth muscle cell growth, or altering 5-HTT expression. We suggest that individuals with a high basal level of 5-HTT expression related to the presence of the long 5-HTT gene promoter variant may be particularly susceptible to one or more of these potential mechanisms of appetite-suppressant-related PH.

  9. Temperament, character and serotonin activity in the human brain

    DEFF Research Database (Denmark)

    Tuominen, L; Salo, J; Hirvonen, J

    2013-01-01

    The psychobiological model of personality by Cloninger and colleagues originally hypothesized that interindividual variability in the temperament dimension 'harm avoidance' (HA) is explained by differences in the activity of the brain serotonin system. We assessed brain serotonin transporter (5-HTT...

  10. Prior fear conditioning does not impede enhanced active avoidance in serotonin transporter knockout rats.

    Science.gov (United States)

    Schipper, Pieter; Henckens, Marloes J A G; Borghans, Bart; Hiemstra, Marlies; Kozicz, Tamas; Homberg, Judith R

    2017-05-30

    Stressors can be actively or passively coped with, and adequate adaption of the coping response to environmental conditions can reduce their potential deleterious effects. One major factor influencing stress coping behaviour is serotonin transporter (5-HTT) availability. Abolishment of 5-HTT is known to impair fear extinction but facilitates acquisition of signalled active avoidance (AA), a behavioural task in which an animal learns to avoid an aversive stimulus that is predicted by a cue. Flexibility in adapting coping behaviour to the nature of the stressor shapes resilience to stress-related disorders. Therefore, we investigated the relation between 5-HTT expression and ability to adapt a learned coping response to changing environmental conditions. To this end, we first established and consolidated a cue-conditioned passive fear response in 5-HTT -/- and wildtype rats. Next, we used the conditioned stimulus (CS) to signal oncoming shocks during signalled AA training in 5-HTT -/- and wildtype rats to study their capability to acquire an active coping response to the CS following fear conditioning. Finally, we investigated the behavioural response to the CS in a novel environment and measured freezing, exploration and self-grooming, behaviours reflective of stress coping strategy. We found that fear conditioned and sham conditioned 5-HTT -/- animals acquired the signalled AA response faster than wildtypes, while prior conditioning briefly delayed AA learning similarly in both genotypes. Subsequent exposure to the CS in the novel context reduced freezing and increased locomotion in 5-HTT -/- compared to wildtype rats. This indicates that improved AA performance in 5-HTT -/- rats resulted in a weaker residual passive fear response to the CS in a novel context. Fear conditioning prior to AA training did not affect freezing upon re-encountering the CS, although it did reduce locomotion in 5-HTT -/- rats. We conclude that independent of 5-HTT signalling, prior fear

  11. Central serotonin transporter availability in highly obese individuals compared with non-obese controls: A [11C] DASB positron emission tomography study

    International Nuclear Information System (INIS)

    Hesse, Swen; Sabri, Osama; Rullmann, Michael; Luthardt, Julia; Becker, Georg-Alexander; Bresch, Anke; Patt, Marianne; Meyer, Philipp M.; Winter, Karsten; Hankir, Mohammed K.; Zientek, Franziska; Reissig, Georg; Drabe, Mandy; Regenthal, Ralf; Schinke, Christian; Arelin, Katrin; Lobsien, Donald; Fasshauer, Mathias; Fenske, Wiebke K.; Stumvoll, Michael; Blueher, Matthias

    2016-01-01

    The role of the central serotonin (5-hydroxytryptamine, 5-HT) system in feeding has been extensively studied in animals with the 5-HT family of transporters (5-HTT) being identified as key molecules in the regulation of satiety and body weight. Aberrant 5-HT transmission has been implicated in the pathogenesis of human obesity by in vivo positron emission tomography (PET) and single-photon emission computed tomography (SPECT) imaging techniques. However, results obtained thus far from studies of central 5-HTT availability have been inconsistent, which is thought to be brought about mainly by the low number of individuals with a high body mass index (BMI) previously used. The aim of this study was therefore to assess 5-HTT availability in the brains of highly obese otherwise healthy individuals compared with non-obese healthy controls. We performed PET using the 5-HTT selective radiotracer [ 11 C] DASB on 30 highly obese (BMI range between 35 and 55 kg/m 2 ) and 15 age- and sex-matched non-obese volunteers (BMI range between 19 and 27 kg/m 2 ) in a cross-sectional study design. The 5-HTT binding potential (BP ND ) was used as the outcome parameter. On a group level, there was no significant difference in 5-HTT BP ND in various cortical and subcortical regions in individuals with the highest BMI compared with non-obese controls, while statistical models showed minor effects of age, sex, and the degree of depression on 5-HTT BP ND . The overall finding of a lack of significantly altered 5-HTT availability together with its high variance in obese individuals justifies the investigation of individual behavioral responses to external and internal cues which may further define distinct phenotypes and subgroups in human obesity. (orig.)

  12. Genetic variation in the serotonin transporter gene (5-HTTLPR, rs25531) influences the analgesic response to the short acting opioid Remifentanil in humans

    OpenAIRE

    Schalling Martin; Lonsdorf Tina B; Jensen Karin B; Kosek Eva; Ingvar Martin

    2009-01-01

    Abstract Background There is evidence from animal studies that serotonin (5-HT) can influence the antinociceptive effects of opioids at the spinal cord level. Therefore, there could be an influence of genetic polymorphisms in the serotonin system on individual variability in response to opioid treatment of pain. The serotonin transporter (5-HTT) is a key regulator of serotonin metabolism and availability and its gene harbors several known polymorphisms that are known to affect 5-HTT expressio...

  13. Central serotonin transporter availability in highly obese individuals compared with non-obese controls: A [{sup 11}C] DASB positron emission tomography study

    Energy Technology Data Exchange (ETDEWEB)

    Hesse, Swen; Sabri, Osama [University of Leipzig, Department of Nuclear Medicine, Leipzig (Germany); Integrated Research and Treatment Centre Adiposity Diseases Leipzig, Leipzig (Germany); Rullmann, Michael [University of Leipzig, Department of Nuclear Medicine, Leipzig (Germany); Integrated Research and Treatment Centre Adiposity Diseases Leipzig, Leipzig (Germany); Max Planck Institute for Human Cognitive and Brain Sciences Leipzig, Leipzig (Germany); Luthardt, Julia; Becker, Georg-Alexander; Bresch, Anke; Patt, Marianne; Meyer, Philipp M. [University of Leipzig, Department of Nuclear Medicine, Leipzig (Germany); Winter, Karsten [University of Leipzig, Centre for Translational Regenerative Medicine, Leipzig (Germany); University of Leipzig, Institute for Medical Informatics, Statistics, and Epidemiology, Leipzig (Germany); Hankir, Mohammed K.; Zientek, Franziska; Reissig, Georg; Drabe, Mandy [Integrated Research and Treatment Centre Adiposity Diseases Leipzig, Leipzig (Germany); Regenthal, Ralf [University of Leipzig, Division of Clinical Pharmacology, Rudolf Boehm Institute of Pharmacology and Toxicology, Leipzig (Germany); Schinke, Christian [University of Leipzig, Department of Neurology, Leipzig (Germany); Arelin, Katrin [Max Planck Institute for Human Cognitive and Brain Sciences Leipzig, Leipzig (Germany); University of Leipzig, Day Clinic for Cognitive Neurology, Leipzig (Germany); Lobsien, Donald [University of Leipzig, Department of Neuroradiology, Leipzig (Germany); Fasshauer, Mathias; Fenske, Wiebke K.; Stumvoll, Michael [Integrated Research and Treatment Centre Adiposity Diseases Leipzig, Leipzig (Germany); University of Leipzig, Medical Department III, Leipzig (Germany); Blueher, Matthias [University of Leipzig, Medical Department III, Leipzig (Germany); University of Leipzig, Collaborative Research Centre 1052 Obesity Mechanisms, Leipzig (Germany)

    2016-06-15

    The role of the central serotonin (5-hydroxytryptamine, 5-HT) system in feeding has been extensively studied in animals with the 5-HT family of transporters (5-HTT) being identified as key molecules in the regulation of satiety and body weight. Aberrant 5-HT transmission has been implicated in the pathogenesis of human obesity by in vivo positron emission tomography (PET) and single-photon emission computed tomography (SPECT) imaging techniques. However, results obtained thus far from studies of central 5-HTT availability have been inconsistent, which is thought to be brought about mainly by the low number of individuals with a high body mass index (BMI) previously used. The aim of this study was therefore to assess 5-HTT availability in the brains of highly obese otherwise healthy individuals compared with non-obese healthy controls. We performed PET using the 5-HTT selective radiotracer [{sup 11}C] DASB on 30 highly obese (BMI range between 35 and 55 kg/m{sup 2}) and 15 age- and sex-matched non-obese volunteers (BMI range between 19 and 27 kg/m{sup 2}) in a cross-sectional study design. The 5-HTT binding potential (BP{sub ND}) was used as the outcome parameter. On a group level, there was no significant difference in 5-HTT BP{sub ND} in various cortical and subcortical regions in individuals with the highest BMI compared with non-obese controls, while statistical models showed minor effects of age, sex, and the degree of depression on 5-HTT BP{sub ND}. The overall finding of a lack of significantly altered 5-HTT availability together with its high variance in obese individuals justifies the investigation of individual behavioral responses to external and internal cues which may further define distinct phenotypes and subgroups in human obesity. (orig.)

  14. Analysis of proteolytic processes and enzymatic activities in the generation of huntingtin n-terminal fragments in an HEK293 cell model.

    Directory of Open Access Journals (Sweden)

    Andrew T N Tebbenkamp

    Full Text Available N-terminal fragments of mutant huntingtin (htt that terminate between residues 90-115, termed cleavage product A or 1 (cp-A/1, form intracellular and intranuclear inclusion bodies in the brains of patients with Huntington's disease (HD. These fragments appear to be proteolytic products of the full-length protein. Here, we use an HEK293 cell culture model to investigate huntingtin proteolytic processing; previous studies of these cells have demonstrated cleavage of htt to cp-A/1 like htt fragments.Recombinant N-terminal htt fragments, terminating at residue 171 (also referred to as cp-B/2 like, were efficiently cleaved to produce cp-A/1 whereas fragments representing endogenous caspase, calpain, and metalloproteinase cleavage products, terminating between residues 400-600, were inefficiently cleaved. Using cysteine-labeling techniques and antibody binding mapping, we localized the C-terminus of the cp-A/1 fragments produced by HEK293 cells to sequences minimally limited by cysteine 105 and an antibody epitope composed of residues 115-124. A combination of genetic and pharmacologic approaches to inhibit potential proteases, including γ-secretase and calpain, proved ineffective in preventing production of cp-A/1.Our findings indicate that HEK293 cells express a protease that is capable of efficiently cleaving cp-B/2 like fragments of htt with normal or expanded glutamine repeats. For reasons that remain unclear, this protease cleaves longer htt fragments, with normal or expanded glutamine expansions, much less efficiently. The protease in HEK293 cells that is capable of generating a cp-A/1 like htt fragment may be a novel protease with a high preference for a cp-B/2-like htt fragment as substrate.

  15. The Human Terrain System: Achieving a Competitive Advantage Through Enhanced Population-Centric Knowledge Flows

    Science.gov (United States)

    2008-09-01

    of behavior ( Fetterman , 1998, p. 35). Moreover, the goal of the participating observer is to internalize fundamental “beliefs, fears, hopes and...expectations of the people under study” ( Fetterman , 1998, p. 35). Additionally, HTT members frequently conduct informal interviews (open ended casual...techniques, and questionnaires ( Fetterman , 1998, p. 35). The third principle method HTT members use to learn the population is the semi- structured

  16. Modulation of Human Serotonin Transporter Expression by 5-HTTLPR in Colon Cells

    Directory of Open Access Journals (Sweden)

    Tewin Tencomnao

    2011-10-01

    Full Text Available Serotonin (5-HT is a monoamine neurotransmitter and plays important roles in several of the human body’s systems. Known as a primary target for psychoactive drug development, the 5-HT transporter (5-HTT, SERT plays a critical role in the regulation of serotonergic function by reuptaking 5-HT. The allelic variation of 5-HTT expression is caused by functional gene promoter polymorphism with two principal variant alleles, 5-HTT gene-linked polymorphic region (5-HTTLPR. It has been demonstrated that 5-HTTLPR is associated with numerous neuropsychiatric disorders. The functional roles of 5-HTTLPR have been reported in human choriocarcinoma (JAR, lymphoblast and raphe cells. To date, the significance of 5-HTTLPR in gastrointestinal tract-derived cells has never been elucidated. Thus, the impact of 5-HTTLPR on 5-HTT transcription was studied in SW480 human colon carcinoma cells, which were shown to express 5-HTT. We found 42-bp fragment in long (L allele as compared to short (S allele, and this allelic difference resulted in 2-fold higher transcriptional efficiency of L allele (P < 0.05 as demonstrated using a functional reporter gene assay. Nevertheless, the transcriptional effect of estrogen and glucocorticoid on 5-HTT expression via 5-HTTLPR was not found in this cell line. Our study was the first to demonstrate the molecular role of this allelic variation in gastrointestinal tract cells.

  17. Cystathionine γ-lyase deficiency mediates neurodegeneration in Huntington’s disease

    Science.gov (United States)

    Paul, Bindu D.; Sbodio, Juan I.; Xu, Risheng; Vandiver, M. Scott; Cha, Jiyoung Y.; Snowman, Adele M.; Snyder, Solomon H.

    2015-01-01

    Huntington’s disease is an autosomal dominant disease associated with a mutation in the gene encoding huntingtin (Htt) leading to expanded polyglutamine repeats of mutant Htt (mHtt) that elicit oxidative stress, neurotoxicity, and motor and behavioural changes1. Huntington’s disease is characterized by highly selective and profound damage to the corpus striatum, which regulates motor function. Striatal selectivity of Huntington’s disease may reflect the striatally selective small G protein Rhes binding to mHtt and enhancing its neurotoxicity2. Specific molecular mechanisms by which mHtt elicits neurodegeneration have been hard to determine. Here we show a major depletion of cystathionine γ-lyase (CSE), the biosynthetic enzyme for cysteine, in Huntington’s disease tissues, which may mediate Huntington’s disease pathophysiology. The defect occurs at the transcriptional level and seems to reflect influences of mHtt on specificity protein 1, a transcriptional activator for CSE. Consistent with the notion of loss of CSE as a pathogenic mechanism, supplementation with cysteine reverses abnormalities in cultures of Huntington’s disease tissues and in intact mouse models of Huntington’s disease, suggesting therapeutic potential. PMID:24670645

  18. Ser46 phosphorylation and prolyl-isomerase Pin1-mediated isomerization of p53 are key events in p53-dependent apoptosis induced by mutant huntingtin.

    Science.gov (United States)

    Grison, Alice; Mantovani, Fiamma; Comel, Anna; Agostoni, Elena; Gustincich, Stefano; Persichetti, Francesca; Del Sal, Giannino

    2011-11-01

    Huntington disease (HD) is a neurodegenerative disorder caused by a CAG repeat expansion in the gene coding for huntingtin protein. Several mechanisms have been proposed by which mutant huntingtin (mHtt) may trigger striatal neurodegeneration, including mitochondrial dysfunction, oxidative stress, and apoptosis. Furthermore, mHtt induces DNA damage and activates a stress response. In this context, p53 plays a crucial role in mediating mHtt toxic effects. Here we have dissected the pathway of p53 activation by mHtt in human neuronal cells and in HD mice, with the aim of highlighting critical nodes that may be pharmacologically manipulated for therapeutic intervention. We demonstrate that expression of mHtt causes increased phosphorylation of p53 on Ser46, leading to its interaction with phosphorylation-dependent prolyl isomerase Pin1 and consequent dissociation from the apoptosis inhibitor iASPP, thereby inducing the expression of apoptotic target genes. Inhibition of Ser46 phosphorylation by targeting homeodomain-interacting protein kinase 2 (HIPK2), PKCδ, or ataxia telangiectasia mutated kinase, as well as inhibition of the prolyl isomerase Pin1, prevents mHtt-dependent apoptosis of neuronal cells. These results provide a rationale for the use of small-molecule inhibitors of stress-responsive protein kinases and Pin1 as a potential therapeutic strategy for HD treatment.

  19. Sequestration of Sup35 by aggregates of huntingtin fragments causes toxicity of [PSI+] yeast.

    Science.gov (United States)

    Zhao, Xiaohong; Park, Yang-Nim; Todor, Horia; Moomau, Christine; Masison, Daniel; Eisenberg, Evan; Greene, Lois E

    2012-07-06

    Expression of huntingtin fragments with 103 glutamines (HttQ103) is toxic in yeast containing either the [PIN(+)] prion, which is the amyloid form of Rnq1, or [PSI(+)] prion, which is the amyloid form of Sup35. We find that HttQP103, which has a polyproline region at the C-terminal end of the polyQ repeat region, is significantly more toxic in [PSI(+)] yeast than in [PIN(+)], even though HttQP103 formed multiple aggregates in both [PSI(+)] and [PIN(+)] yeast. This toxicity was only observed in the strong [PSI(+)] variant, not the weak [PSI(+)] variant, which has more soluble Sup35 present than the strong variant. Furthermore, expression of the MC domains of Sup35, which retains the C-terminal domain of Sup35, but lacks the N-terminal prion domain, almost completely rescued HttQP103 toxicity, but was less effective in rescuing HttQ103 toxicity. Therefore, the toxicity of HttQP103 in yeast containing the [PSI(+)] prion is primarily due to sequestration of the essential protein, Sup35.

  20. Technology demonstration of space intravehicular automation and robotics

    Science.gov (United States)

    Morris, A. Terry; Barker, L. Keith

    1994-01-01

    Automation and robotic technologies are being developed and capabilities demonstrated which would increase the productivity of microgravity science and materials processing in the space station laboratory module, especially when the crew is not present. The Automation Technology Branch at NASA Langley has been working in the area of intravehicular automation and robotics (IVAR) to provide a user-friendly development facility, to determine customer requirements for automated laboratory systems, and to improve the quality and efficiency of commercial production and scientific experimentation in space. This paper will describe the IVAR facility and present the results of a demonstration using a simulated protein crystal growth experiment inside a full-scale mockup of the space station laboratory module using a unique seven-degree-of-freedom robot.

  1. TWRS engineering bibliography software listing

    International Nuclear Information System (INIS)

    Husa, E.I.

    1995-01-01

    This document contains the computer software listing for Engineering Bibliography software, developed by E. Ivar Husa. This software is in the working prototype stage of development. The code has not been tested to requirements. TWRS Engineering created this software for engineers to share bibliographic references across the Hanford site network (HLAN). This software is intended to store several hundred to several thousand references (a compendium with limited range). Coded changes are needed to support the larger number of references

  2. Sadamaala konkurss : Tallinna kesklinnaga piirneva mereäärse ala parima linnaehitusliku kontseptsiooni saamiseks korraldatud arhitektuurivõistlus / Andres Alver, Margus Koot, Arvo Rikkinen...[jt.] ; interv. Triin Ojari

    Index Scriptorium Estoniae

    2000-01-01

    Zürii liikmed konkursist, premeeritud töödest. Preemiad: I - Villem Tomiste, Veronika Valk; II - Illimar Truverk, Indrek Järve, Mattias Agabus, Tiit Sild, Karri Tiigisoon ning Toomas Paaver, Lauri Saar; III - Ivar Lubjak, Maria Pukk; ostud: Ott Kadarik, Rene Valner ning Siiri Vallner, Indrek Peil; täiendav ost (Muinsuskaitseamaet): Nikolai Serebrjakov, Leonid Tozil, Sergei Sevtsenko, Sulev Roosmaa. 6 illustratsiooni

  3. Basel II - mis, milleks ja milliste mõjudega laenuvõtjatele?

    Index Scriptorium Estoniae

    2006-01-01

    Ilmunud ka: Finansovõi Menedzhment : infovõpusk nr. 10 dets. lk. 6-7. Pankade kapitali adekvaatsuse uue raamistiku Basel II tulemuseks võiksid teoreetiliselt olla soodsamad intressid ja laenutingimused, suureneb turudistsipliini roll. Vt. samas: USA ei kiirusta Basel IIga; Mida muudab Basel II panga äriklientide jaoks? Küsimusele vastavad Sampo Panga finantsdirektor Ivar Pae ja SEB Ühispanga krediidi arenduse ja koolituse osakonna juhataja Jaanus Leemets; Kui palju omakapitali vajab pank laenukliendi krediidiriski katteks?

  4. Mitigating the Tyranny, a Moral Responsibility

    Science.gov (United States)

    2009-12-01

    to their society they must be physically and emotionally equipped to handle life outside the warzone; it is, therefore, the military’s obligation...Moral Responsibilities of Victors in War, Warfare studies AY10 Coursebook , edited by Sharon McBride, (Maxwell AFB, Al: Air University Press, October... Coursebook , edited by Sharon McBride, page156-167. Maxwell AFB, AL [or Ala.]: Air University Press, October 2009. Myhr, Kjell-Ivar. ―Norsk F-16 pilot

  5. Eesti proosa 2007 - kultuuri ja tsivilisatsiooni vahel / Peeter Helme

    Index Scriptorium Estoniae

    Helme, Peeter, 1978-

    2010-01-01

    2007. a. ilmunud proosaraamatutest: Tiina Laanemi "Väikesed vanamehed", Ene Mihkelsoni "Katkuhaud", Toomas Vindi "Mäluauguga naine", Vahur Afanasjevi "Kaadrid otsustavad", Armin Kõomäe "Nägu, mis jäi üle" (ilmus 2006. a.), Jaan Kaplinski "Seesama jõgi", Tõnu Õnnepalu "Flandria päevik", Maimu Bergi "Unustatud inimesed", Mehis Heinsaare "Rändaja õnn", Mihkel Muti "Siseemigrant", Aarne Biini "Linna valitsemine", Ivar Silla "Tantsiv linn" ja Epp Annuse "Sina, Matilda"

  6. Vikergallup : eesti kirjandus 2000 : [vastused Vikerkaare küsimustele

    Index Scriptorium Estoniae

    2001-01-01

    Aut.: Epp Annus, Andres Aule, Veiko Belials, Jan Kaus, Andrus Kivirähk, Leo Luks, Hedda Maurer, Anneli Mihkelev, Marko Mägi, Aare Pilv, Jürgen Rooste, Aarne Ruben, Mihkel Samarüütel, François Serpent, Ivar Sild, Karl Martin Sinijärv, Jaak Urmet. 2000. a. parimaks uudisraamatuks tunnistati Andrus Kivirähu "Rehepapp ehk November" ja parimaks esikraamatuks Wimbergi [Jaak Urmet] "Maaaraamat"

  7. Tartu spordimaja võitis parima terasehitise tiitli / Aivar Õepa

    Index Scriptorium Estoniae

    Õepa, Aivar, 1967-

    2006-01-01

    Eesti Teraskonstruktsiooniühing valis viimase viie aasta parimaks teraskonstruktsiooniga tervikehitiseks Tartu spordihoone A. Le Coq Sport (arhitekt Eero Palm, konstruktsioonide autor Randväli & Karema AS). Parima insenerilahenduse auhinna sai eestlaste teostatud Läti jäähalli Arena Riga katusekonstruktsioon. Parima arhitektuurse lahenduse auhinna sai Eesti Panga siseõue galerii, mille projekteeris arhitektuuribüroo Urban Mark. Kommenteerib Ivar Talvik

  8. Vigour Health: the ASC-Series launch in Canada

    OpenAIRE

    Danielsen, David M.; Fredriksen, Joakim; Nordli, Espen; Nøstberg, Bjørn R.

    2008-01-01

    This report is part of the authors’ bachelor degree in International Marketing and analyzes the Canadian vitamins and dietary supplements (VDS) industry. Based on this analysis, the authors will be proposing how Vigour can enter the market. Vigour Health was founded in 2006 by Omar Paulsen Bekheet and John Ivar Andre and the goal was to introduce a new lifestyle concept that should be inventive in its approach. Vigour utilizes raw materials from the northern parts of Norway, an...

  9. Läti sakslane Brotze ja Eesti ajalugu / Anne Untera

    Index Scriptorium Estoniae

    Untera, Anne, 1951-

    2006-01-01

    Näitus "Johann Christoph Brotze joonistusi ja käsikirju Eesti- ja Liivimaast Läti Akadeemilise Raamatukogu kogudest" Kuressaare lossis kuni 30. IV. Eesti ainestikuga eriköide Brotze pärandist valmib Eesti-Läti uurijate koostöös ja ilmub Tallinnas. Väljaande peatoimetaja on Raimo Pullat, alajaotuste toimetajad Ants Hein, Ivar Leimus, Ants Viires

  10. Eesti identiteedi kasv ja kasvatus 2006. aastal - Kumust Brotzeni / Mati Hint

    Index Scriptorium Estoniae

    Hint, Mati, 1937-

    2006-01-01

    Tallinna Ülikooli emeriitprofessori loetletud tippsündmused Eesti kunsti ja ajaloo valdkonnas 2006. a. - Kumu Kunstimuuseumi avamine, Kristjan ja Paul Raua näitus Kumus ning Riias tegutsenud baltisaksa kultuuriloolase Johann Christoph Brotze joonistuste kogumiku "Johann Christoph Brotze. Estonica." Koostanud Ants Hein, Ivar Leimus, Raimo Pullat, Ants Viires. Estopol OÜ 2006, ilmumine Tallinnas, peatoimetaja Raimo Pullat. Pikemalt eesti nüüdisaegsest kunstist Kumus ja rahvuslikust identiteedist

  11. Eestis on üle tuhande lõvi : [Lions-liikumisest] / Vello Talviste, Olev Saluveer, Jaan Palumets...[jt.

    Index Scriptorium Estoniae

    2009-01-01

    Lions-liikumisega on ühinenud ka koolidirektorid. Küsimustele - mis ajendas neid seda tegema, mida lõvid ette võtavad ning kui aktuaalne on heategevuse temaatika koolis, vastavad Paide Gümnaasiumi direktor Vello Talviste, Ülenurme Gümnaasiumi direktor Olev Saluveer, Saue Gümnaasiumi direktor Jaan Palumets, Tõrva Gümnaasiumi direktor Ivar Hanvere ja Tabivere Gümnaasiumi direktor Toivo Punga

  12. Folding Landscape of Mutant Huntingtin Exon1: Diffusible Multimers, Oligomers and Fibrils, and No Detectable Monomer.

    Directory of Open Access Journals (Sweden)

    Bankanidhi Sahoo

    Full Text Available Expansion of the polyglutamine (polyQ track of the Huntingtin (HTT protein above 36 is associated with a sharply enhanced risk of Huntington's disease (HD. Although there is general agreement that HTT toxicity resides primarily in N-terminal fragments such as the HTT exon1 protein, there is no consensus on the nature of the physical states of HTT exon1 that are induced by polyQ expansion, nor on which of these states might be responsible for toxicity. One hypothesis is that polyQ expansion induces an alternative, toxic conformation in the HTT exon1 monomer. Alternative hypotheses posit that the toxic species is one of several possible aggregated states. Defining the nature of the toxic species is particularly challenging because of facile interconversion between physical states as well as challenges to identifying these states, especially in vivo. Here we describe the use of fluorescence correlation spectroscopy (FCS to characterize the detailed time and repeat length dependent self-association of HTT exon1-like fragments both with chemically synthesized peptides in vitro and with cell-produced proteins in extracts and in living cells. We find that, in vitro, mutant HTT exon1 peptides engage in polyQ repeat length dependent dimer and tetramer formation, followed by time dependent formation of diffusible spherical and fibrillar oligomers and finally by larger, sedimentable amyloid fibrils. For expanded polyQ HTT exon1 expressed in PC12 cells, monomers are absent, with tetramers being the smallest molecular form detected, followed in the incubation time course by small, diffusible aggregates at 6-9 hours and larger, sedimentable aggregates that begin to build up at 12 hrs. In these cell cultures, significant nuclear DNA damage appears by 6 hours, followed at later times by caspase 3 induction, mitochondrial dysfunction, and cell death. Our data thus defines limits on the sizes and concentrations of different physical states of HTT exon1 along the

  13. I am the smartest man I know a Nobel laureate's difficult journey

    CERN Document Server

    Giaever, Ivar

    2016-01-01

    A unique individual with a fascinating life story, Ivar Giaever is a scientist who won the Nobel Prize in Experimental Physics in 1973. In his own words, Giaever relates an absorbing tale of how important luck and good fortune have been in shaping his life. He narrates the story of an ordinary childhood in Norway and an unremarkable undergraduate career at university. After finishing his engineering degree, he served in the Norwegian army and married his childhood sweetheart, Inger Skramstad. His desire to make a better life for his new family led Ivar to Canada and then to the United States. Even without an advanced degree in a scientific field, Ivar was given the opportunity to work with cutting-edge scientific researchers at General Electric R&D in Schenectady, New York. While there, he completed his PhD at Rensselaer Polytechnic Institute — one of the nation's oldest technological universities. His work on superconductivity led to worldwide recognition and the Nobel Prize. This memoire is more than ...

  14. CAG Expansions Are Genetically Stable and Form Nontoxic Aggregates in Cells Lacking Endogenous Polyglutamine Proteins

    Directory of Open Access Journals (Sweden)

    Ashley A. Zurawel

    2016-09-01

    Full Text Available Proteins containing polyglutamine (polyQ regions are found in almost all eukaryotes, albeit with various frequencies. In humans, proteins such as huntingtin (Htt with abnormally expanded polyQ regions cause neurodegenerative diseases such as Huntington’s disease (HD. To study how the presence of endogenous polyQ aggregation modulates polyQ aggregation and toxicity, we expressed polyQ expanded Htt fragments (polyQ Htt in Schizosaccharomyces pombe. In stark contrast to other unicellular fungi, such as Saccharomyces cerevisiae, S. pombe is uniquely devoid of proteins with more than 10 Q repeats. We found that polyQ Htt forms aggregates within S. pombe cells only with exceedingly long polyQ expansions. Surprisingly, despite the presence of polyQ Htt aggregates in both the cytoplasm and nucleus, no significant growth defect was observed in S. pombe cells. Further, PCR analysis showed that the repetitive polyQ-encoding DNA region remained constant following transformation and after multiple divisions in S. pombe, in contrast to the genetic instability of polyQ DNA sequences in other organisms. These results demonstrate that cells with a low content of polyQ or other aggregation-prone proteins can show a striking resilience with respect to polyQ toxicity and that genetic instability of repetitive DNA sequences may have played an important role in the evolutionary emergence and exclusion of polyQ expansion proteins in different organisms.

  15. Fluorinated Nucleotide Modifications Modulate Allele Selectivity of SNP-Targeting Antisense Oligonucleotides

    Directory of Open Access Journals (Sweden)

    Michael E. Østergaard

    2017-06-01

    Full Text Available Antisense oligonucleotides (ASOs have the potential to discriminate between subtle RNA mismatches such as SNPs. Certain mismatches, however, allow ASOs to bind at physiological conditions and result in RNA cleavage mediated by RNase H. We showed that replacing DNA nucleotides in the gap region of an ASO with other chemical modification can improve allele selectivity. Herein, we systematically substitute every position in the gap region of an ASO targeting huntingtin gene (HTT with fluorinated nucleotides. Potency is determined in cell culture against mutant HTT (mtHTT and wild-type HTT (wtHTT mRNA and RNase H cleavage intensities, and patterns are investigated. This study profiled five different fluorinated nucleotides and showed them to have predictable, site-specific effects on RNase H cleavage, and the cleavage patterns were rationalized from a published X-ray structure of human RNase H1. The results herein can be used as a guide for future projects where ASO discrimination of SNPs is important.

  16. Prevalence of Huntington's disease gene CAG trinucleotide repeat alleles in patients with bipolar disorder.

    Science.gov (United States)

    Ramos, Eliana Marisa; Gillis, Tammy; Mysore, Jayalakshmi S; Lee, Jong-Min; Alonso, Isabel; Gusella, James F; Smoller, Jordan W; Sklar, Pamela; MacDonald, Marcy E; Perlis, Roy H

    2015-06-01

    Huntington's disease is a neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms that are caused by huntingtin gene (HTT) CAG trinucleotide repeat alleles of 36 or more units. A greater than expected prevalence of incompletely penetrant HTT CAG repeat alleles observed among individuals diagnosed with major depressive disorder raises the possibility that another mood disorder, bipolar disorder, could likewise be associated with Huntington's disease. We assessed the distribution of HTT CAG repeat alleles in a cohort of individuals with bipolar disorder. HTT CAG allele sizes from 2,229 Caucasian individuals diagnosed with DSM-IV bipolar disorder were compared to allele sizes in 1,828 control individuals from multiple cohorts. We found that HTT CAG repeat alleles > 35 units were observed in only one of 4,458 chromosomes from individuals with bipolar disorder, compared to three of 3,656 chromosomes from control subjects. These findings do not support an association between bipolar disorder and Huntington's disease. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Early life stress predicts negative urgency through brooding, depending on 5-HTTLPR genotype: A pilot study with 6-month follow-up examining suicide ideation.

    Science.gov (United States)

    Valderrama, Jorge; Miranda, Regina

    2017-12-01

    The present study examined the interaction between early life stress and 5-HTT genotypes in predicting two risk factors for suicidal behavior - the brooding subtype of rumination and impulsivity, in the form of negative urgency - over time. Furthermore, we examined early life stress, brooding, and impulsivity as predictors of suicidal ideation over time. Participants with and without a history of early life stress were genotyped for the 5-HTTLPR polymorphism and completed assessments assessing brooding and negative urgency at baseline and 6-month follow up. Early life emotional abuse was associated with negative urgency at follow-up. We found an indirect effect of early life emotional abuse on negative urgency through brooding among individuals with 5-HTT low expressing genotypes but not among individuals with 5-HTT high expressing genotypes. Further, a logistic regression analysis revealed that negative urgency was associated with higher odds (O.R. = 16.2) of reporting suicide ideation (versus no ideation) at follow-up. Our findings suggest that brooding and negative urgency may result from the interaction between early life emotional abuse and 5-HTT low expressing genotypes. Further research is necessary to understand how early life stress interacts with 5-HTT genotypes to confer risk for suicidal behavior through psychological mechanisms. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Intravitreal administration of HA-1077, a ROCK inhibitor, improves retinal function in a mouse model of huntington disease.

    Directory of Open Access Journals (Sweden)

    Mei Li

    Full Text Available Huntington disease (HD is an inherited neurodegenerative disease that affects multiple brain regions. It is caused by an expanded polyglutamine tract in huntingtin (Htt. The development of therapies for HD and other neurodegenerative diseases has been hampered by multiple factors, including the lack of clear therapeutic targets, and the cost and complexity of testing lead compounds in vivo. The R6/2 HD mouse model is widely used for pre-clinical trials because of its progressive and robust neural dysfunction, which includes retinal degeneration. Profilin-1 is a Htt binding protein that inhibits Htt aggregation. Its binding to Htt is regulated by the rho-associated kinase (ROCK, which phosphorylates profilin at Ser-137. ROCK is thus a therapeutic target in HD. The ROCK inhibitor Y-27632 reduces Htt toxicity in fly and mouse models. Here we characterized the progressive retinopathy of R6/2 mice between 6-19 weeks of age to determine an optimal treatment window. We then tested a clinically approved ROCK inhibitor, HA-1077, administered intravitreally via liposome-mediated drug delivery. HA-1077 increased photopic and flicker ERG response amplitudes in R6/2 mice, but not in wild-type littermate controls. By targeting ROCK with a new inhibitor, and testing its effects in a novel in vivo model, these results validate the in vivo efficacy of a therapeutic candidate, and establish the feasibility of using the retina as a readout for CNS function in models of neurodegenerative disease.

  19. Impaired heat shock response in cells expressing full-length polyglutamine-expanded huntingtin.

    Directory of Open Access Journals (Sweden)

    Sidhartha M Chafekar

    Full Text Available The molecular mechanisms by which polyglutamine (polyQ-expanded huntingtin (Htt causes neurodegeneration in Huntington's disease (HD remain unclear. The malfunction of cellular proteostasis has been suggested as central in HD pathogenesis and also as a target of therapeutic interventions for the treatment of HD. We present results that offer a previously unexplored perspective regarding impaired proteostasis in HD. We find that, under non-stress conditions, the proteostatic capacity of cells expressing full length polyQ-expanded Htt is adequate. Yet, under stress conditions, the presence of polyQ-expanded Htt impairs the heat shock response, a key component of cellular proteostasis. This impaired heat shock response results in a reduced capacity to withstand the damage caused by cellular stress. We demonstrate that in cells expressing polyQ-expanded Htt the levels of heat shock transcription factor 1 (HSF1 are reduced, and, as a consequence, these cells have an impaired a heat shock response. Also, we found reduced HSF1 and HSP70 levels in the striata of HD knock-in mice when compared to wild-type mice. Our results suggests that full length, non-aggregated polyQ-expanded Htt blocks the effective induction of the heat shock response under stress conditions and may thus trigger the accumulation of cellular damage during the course of HD pathogenesis.

  20. A new Caenorhabditis elegans model of human huntingtin 513 aggregation and toxicity in body wall muscles.

    Directory of Open Access Journals (Sweden)

    Amy L Lee

    Full Text Available Expanded polyglutamine repeats in different proteins are the known determinants of at least nine progressive neurodegenerative disorders whose symptoms include cognitive and motor impairment that worsen as patients age. One such disorder is Huntington's Disease (HD that is caused by a polyglutamine expansion in the human huntingtin protein (htt. The polyglutamine expansion destabilizes htt leading to protein misfolding, which in turn triggers neurodegeneration and the disruption of energy metabolism in muscle cells. However, the molecular mechanisms that underlie htt proteotoxicity have been somewhat elusive, and the muscle phenotypes have not been well studied. To generate tools to elucidate the basis for muscle dysfunction, we engineered Caenorhabditis elegans to express a disease-associated 513 amino acid fragment of human htt in body wall muscle cells. We show that this htt fragment aggregates in C. elegans in a polyglutamine length-dependent manner and is toxic. Toxicity manifests as motor impairment and a shortened lifespan. Compared to previous models, the data suggest that the protein context in which a polyglutamine tract is embedded alters aggregation propensity and toxicity, likely by affecting interactions with the muscle cell environment.

  1. Mitochondrial fragmentation in neuronal degeneration: Toward an understanding of HD striatal susceptibility

    International Nuclear Information System (INIS)

    Cherubini, Marta; Ginés, Silvia

    2017-01-01

    Huntington's disease (HD) is an autosomal-dominant progressive neurodegenerative disorder that primarily affects medium spiny neurons within the striatum. HD is caused by inheritance of an expanded CAG repeat in the HTT gene, resulting in a mutant huntingtin (mHtt) protein containing extra glutamine residues. Despite the advances in understanding the molecular mechanisms involved in HD the preferential vulnerability of the striatum remains an intriguing question. This review discusses current knowledge that links altered mitochondrial dynamics with striatal susceptibility in HD. We also highlight how the modulation of mitochondrial function may constitute an attractive therapeutic approach to reduce mHtt-induced toxicity and therefore prevent the selective striatal neurodegeneration. - Highlights: • Mitochondrial dynamics is unbalanced towards fission in HD. • Excessive mitochondrial fragmentation plays a critical role in the selective vulnerability of the striatum in HD. • Therapeutic approaches aimed to inhibit mitochondrial fission could contribute to prevent striatal neurodegeneration in HD.

  2. Electrochemical reversibility of reticulated vitreous carbon electrodes heat treated at different carbonization temperatures

    Directory of Open Access Journals (Sweden)

    Emerson Sarmento Gonçalves

    2006-06-01

    Full Text Available Electrochemical response of ferri/ferrocyanide redox couple is discussed for a system that uses reticulated vitreous carbon (RVC three dimensional electrodes prepared at five different Heat Treatment Temperatures (HTT in the range of 700 °C to 1100 °C. Electrical resistivity, scanning electron microscopy and X ray Diffraction analyses were performed for all prepared samples. It was observed that the HTT increasing promotes an electrical conductivity increasing while the Bragg distance d002 decreases. The correlation between reversibility behavior of ferri/ferrocyanide redox couple and both surface morphology and chemical properties of the RVC electrodes demonstrated a strong dependence on the HTT used to prepare the RVC.

  3. How the cerebral serotonin homeostasis predicts environmental changes

    DEFF Research Database (Denmark)

    Kalbitzer, Jan; Kalbitzer, Urs; Knudsen, Gitte Moos

    2013-01-01

    Molecular imaging studies with positron emission tomography have revealed that the availability of serotonin transporter (5-HTT) in the human brain fluctuates over the course of the year. This effect is most pronounced in carriers of the short allele of the 5-HTT promoter region (5-HTTLPR), which...... has in several previous studies been linked to an increased risk to develop mood disorders. We argue that long-lasting fluctuations in the cerebral serotonin transmission, which is regulated via the 5-HTT, are responsible for mediating responses to environmental changes based on an assessment...... of cerebral serotonin transmission to seasonal and other forms of environmental change imparts greater behavioral flexibility, at the expense of increased vulnerability to stress. This model may explain the somewhat higher prevalence of the s-allele in some human populations dwelling at geographic latitudes...

  4. AAV-mediated delivery of the transcription factor XBP1s into the striatum reduces mutant Huntingtin aggregation in a mouse model of Huntington’s disease

    International Nuclear Information System (INIS)

    Zuleta, Amparo; Vidal, Rene L.; Armentano, Donna; Parsons, Geoffrey; Hetz, Claudio

    2012-01-01

    Highlights: ► The contribution of ER stress to HD has not been directly addressed. ► Expression of XBP1s using AAVs decreases Huntingtin aggregation in vivo. ► We describe a new in vivo model of HD based on the expression of a large fragment of mHtt-RFP. -- Abstract: Huntington’s disease (HD) is caused by mutations that expand a polyglutamine region in the amino-terminal domain of Huntingtin (Htt), leading to the accumulation of intracellular inclusions and progressive neurodegeneration. Recent reports indicate the engagement of endoplasmic reticulum (ER) stress responses in human HD post mortem samples and animal models of the disease. Adaptation to ER stress is mediated by the activation of the unfolded protein response (UPR), an integrated signal transduction pathway that attenuates protein folding stress by controlling the expression of distinct transcription factors including X-Box binding protein 1 (XBP1). Here we targeted the expression of XBP1 on a novel viral-based model of HD. We delivered an active form of XBP1 locally into the striatum of adult mice using adeno-associated vectors (AAVs) and co-expressed this factor with a large fragment of mutant Htt as a fusion protein with RFP (Htt588 Q95 -mRFP) to directly visualize the accumulation of Htt inclusions in the brain. Using this approach, we observed a significant reduction in the accumulation of Htt588 Q95 -mRFP intracellular inclusion when XBP1 was co-expressed in the striatum. These results contrast with recent findings indicating a protective effect of XBP1 deficiency in neurodegeneration using knockout mice, and suggest a potential use of gene therapy strategies to manipulate the UPR in the context of HD.

  5. Huntingtin gene repeat size variations affect risk of lifetime depression.

    Science.gov (United States)

    Gardiner, Sarah L; van Belzen, Martine J; Boogaard, Merel W; van Roon-Mom, Willeke M C; Rozing, Maarten P; van Hemert, Albert M; Smit, Johannes H; Beekman, Aartjan T F; van Grootheest, Gerard; Schoevers, Robert A; Oude Voshaar, Richard C; Roos, Raymund A C; Comijs, Hannie C; Penninx, Brenda W J H; van der Mast, Roos C; Aziz, N Ahmad

    2017-12-11

    Huntington disease (HD) is a severe neuropsychiatric disorder caused by a cytosine-adenine-guanine (CAG) repeat expansion in the HTT gene. Although HD is frequently complicated by depression, it is still unknown to what extent common HTT CAG repeat size variations in the normal range could affect depression risk in the general population. Using binary logistic regression, we assessed the association between HTT CAG repeat size and depression risk in two well-characterized Dutch cohorts─the Netherlands Study of Depression and Anxiety and the Netherlands Study of Depression in Older Persons─including 2165 depressed and 1058 non-depressed persons. In both cohorts, separately as well as combined, there was a significant non-linear association between the risk of lifetime depression and HTT CAG repeat size in which both relatively short and relatively large alleles were associated with an increased risk of depression (β = -0.292 and β = 0.006 for the linear and the quadratic term, respectively; both P < 0.01 after adjustment for the effects of sex, age, and education level). The odds of lifetime depression were lowest in persons with a HTT CAG repeat size of 21 (odds ratio: 0.71, 95% confidence interval: 0.52 to 0.98) compared to the average odds in the total cohort. In conclusion, lifetime depression risk was higher with both relatively short and relatively large HTT CAG repeat sizes in the normal range. Our study provides important proof-of-principle that repeat polymorphisms can act as hitherto unappreciated but complex genetic modifiers of depression.

  6. Msh2 acts in medium-spiny striatal neurons as an enhancer of CAG instability and mutant huntingtin phenotypes in Huntington's disease knock-in mice.

    Directory of Open Access Journals (Sweden)

    Marina Kovalenko

    Full Text Available The CAG trinucleotide repeat mutation in the Huntington's disease gene (HTT exhibits age-dependent tissue-specific expansion that correlates with disease onset in patients, implicating somatic expansion as a disease modifier and potential therapeutic target. Somatic HTT CAG expansion is critically dependent on proteins in the mismatch repair (MMR pathway. To gain further insight into mechanisms of somatic expansion and the relationship of somatic expansion to the disease process in selectively vulnerable MSNs we have crossed HTT CAG knock-in mice (HdhQ111 with mice carrying a conditional (floxed Msh2 allele and D9-Cre transgenic mice, in which Cre recombinase is expressed specifically in MSNs within the striatum. Deletion of Msh2 in MSNs eliminated Msh2 protein in those neurons. We demonstrate that MSN-specific deletion of Msh2 was sufficient to eliminate the vast majority of striatal HTT CAG expansions in HdhQ111 mice. Furthermore, MSN-specific deletion of Msh2 modified two mutant huntingtin phenotypes: the early nuclear localization of diffusely immunostaining mutant huntingtin was slowed; and the later development of intranuclear huntingtin inclusions was dramatically inhibited. Therefore, Msh2 acts within MSNs as a genetic enhancer both of somatic HTT CAG expansions and of HTT CAG-dependent phenotypes in mice. These data suggest that the selective vulnerability of MSNs may be at least in part contributed by the propensity for somatic expansion in these neurons, and imply that intervening in the expansion process is likely to have therapeutic benefit.

  7. Environmental enrichment reduces innate anxiety with no effect on depression-like behaviour in mice lacking the serotonin transporter.

    Science.gov (United States)

    Rogers, Jake; Li, Shanshan; Lanfumey, Laurence; Hannan, Anthony J; Renoir, Thibault

    2017-08-14

    Along with being the main target of many antidepressant medications, the serotonin transporter (5-HTT) is known to be involved in the pathophysiology of depression and anxiety disorders. In line with this, mice with varying 5-HTT genotypes are invaluable tools to study depression- and anxiety-like behaviours as well as the mechanisms mediating potential therapeutics. There is clear evidence that both genetic and environmental factors play a role in the aetiology of psychiatric disorders. In that regard, housing paradigms which seek to enhance cognitive stimulation and physical activity have been shown to exert beneficial effects in animal models of neuropsychiatric disorders. In the present study, we examined the effects of environmental enrichment on affective-like behaviours and sensorimotor gating function of 5-HTT knock-out (KO) mice. Using the elevated-plus maze and the light-dark box, we found that environmental enrichment ameliorated the abnormal innate anxiety of 5-HTT KO mice on both tests. In contrast, environmental enrichment did not rescue the depression-like behaviour displayed by 5-HTT KO mice in the forced-swim test. Finally, measuring pre-pulse inhibition, we found no effect of genotype or treatment on sensorimotor gating. In conclusion, our data suggest that environmental enrichment specifically reduces innate anxiety of 5-HTT KO mice with no amelioration of the depression-like behaviour. This has implications for the current use of clinical interventions for patients with symptoms of both anxiety and depression. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Short G-rich oligonucleotides as a potential therapeutic for Huntington's Disease

    Directory of Open Access Journals (Sweden)

    Parekh-Olmedo Hetal

    2006-10-01

    Full Text Available Abstract Background Huntington's Disease (HD is an inherited autosomal dominant genetic disorder in which neuronal tissue degenerates. The pathogenesis of the disease appears to center on the development of protein aggregates that arise initially from the misfolding of the mutant HD protein. Mutant huntingtin (Htt is produced by HD genes that contain an increased number of glutamine codons within the first exon and this expansion leads to the production of a protein that misfolds. Recent studies suggest that mutant Htt can nucleate protein aggregation and interfere with a multitude of normal cellular functions. Results As such, efforts to find a therapy for HD have focused on agents that disrupt or block the mutant Htt aggregation pathway. Here, we report that short guanosine monotonic oligonucleotides capable of adopting a G-quartet structure, are effective inhibitors of aggregation. By utilizing a biochemical/immunoblotting assay as an initial screen, we identified a 20-mer, all G-oligonucleotide (HDG as an active molecule. Subsequent testing in a cell-based assay revealed that HDG was an effective inhibitor of aggregation of a fusion protein, comprised of a mutant Htt fragment and green fluorescent protein (eGFP. Taken together, our results suggest that a monotonic G-oligonucleotide, capable of adopting a G-quartet conformation is an effective inhibitor of aggregation. This oligonucleotide can also enable cell survival in PC12 cells overexpressing a mutant Htt fragment fusion gene. Conclusion Single-stranded DNA oligonucleotides capable of forming stable G-quartets can inhibit aggregation of the mutant Htt fragment protein. This activity maybe an important part of the pathogenecity of Huntington's Disease. Our results reveal a new class of agents that could be developed as a therapeutic approach for Huntington's Disease.

  9. Desorption of cesium ions from vermiculite with sea water by hydrothermal process

    International Nuclear Information System (INIS)

    Yin, Xiangbiao; Takahashi, Hideharu; Inaba, Yusuke; Takeshita, Kenji

    2016-01-01

    Cesium ions (Cs + ) strongly intercalated in vermiculite clay (Verm) had been effectively removed using sea water for its free utility, totally environmental friendly feature, and within containing numerous salt by the hydrothermal treatment process (HTT), which can help significantly promote desorption by the cation-exchange mechanism in subcritical condition. >74-100% removal was achieved to the interacted Cs + for a loading capacity of 4.8-50 mg g −1 . XRD results indicated that cation exchange proceeded between the intercalated Cs + and various cations in sea water during HTT. (author)

  10. First molecular modeling report on novel arylpyrimidine kynurenine monooxygenase inhibitors through multi-QSAR analysis against Huntington's disease: A proposal to chemists!

    Science.gov (United States)

    Amin, Sk Abdul; Adhikari, Nilanjan; Jha, Tarun; Gayen, Shovanlal

    2016-12-01

    Huntington's disease (HD) is caused by mutation of huntingtin protein (mHtt) leading to neuronal cell death. The mHtt induced toxicity can be rescued by inhibiting the kynurenine monooxygenase (KMO) enzyme. Therefore, KMO is a promising drug target to address the neurodegenerative disorders such as Huntington's diseases. Fiftysix arylpyrimidine KMO inhibitors are structurally explored through regression and classification based multi-QSAR modeling, pharmacophore mapping and molecular docking approaches. Moreover, ten new compounds are proposed and validated through the modeling that may be effective in accelerating Huntington's disease drug discovery efforts. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. The role of polyglutamine expansion and protein context in disease-related huntingtin/lipid interactions

    Science.gov (United States)

    Burke, Kathleen Anne

    Huntington's Disease (HD) is a neurodegenerative disorder that is defined by the accumulation of nanoscale aggregates comprised of the huntingtin (htt) protein. Aggregation is directly caused by an expanded polyglutamine (polyQ) domain in htt, leading to a diverse population of aggregate species, such as oligomers, fibrils, and annular aggregates. Furthermore, the length of this polyQ domain is directly related to onset and severity of disease. The first 17 amino acids on the N-terminus (N17) and the polyproline domain on the C-terminal side of the polyQ domain have been shown to further modulate the aggregation process. Additionally, N17 appears to have lipid binding properties as htt interacts with a variety of membrane-containing structures present in cells, such as organelles, and interactions with these membrane surfaces may further modulate htt aggregation. To investigate the interaction between htt exon1 and lipid bilayers, in situ atomic force microscopy (AFM) was used to directly monitor the aggregation of htt exon1 constructs with varying Q-length (35Q, 46Q, 51Q, and myc- 53Q) or synthetic peptides with different polyQ domain flanking sequences (KK-Q35-KK, KK-Q 35-P10-KK, N17-Q35-KK, and N 17-Q35-P10-KK) on supported lipid membranes comprised of total brain lipid extract. The exon1 fragments accumulated on the lipid membranes, causing disruption of the membrane, in a polyQ dependent manner. By adding N-terminal tags to the htt exon1 fragments, the interaction with the lipid bilayer was impeded. The KK-Q35-KK and KK-Q 35-P10-KK peptides had no appreciable interaction with lipid bilayers. Interestingly, polyQ peptides with the N17 flanking sequence interacted with the bilayer. N17-Q35-KK formed discrete aggregates on the bilayer, but there was minimal membrane disruption. The N17-Q35-P10-KK peptide interacted more aggressively with the lipid bilayer in a manner reminiscent of the htt exon1 proteins.

  12. Jevrorealistõ stshitajut variantõ prognoza / Eteri Kekelidze

    Index Scriptorium Estoniae

    Kekelidze, Eteri, 1944-

    2006-01-01

    Professor Ivar Raig analüüsib, kuidas on mõjutanud ja mõjutab Eesti majandust liitumine EL-iga. Tema arvates on juba märke, et majanduskasv lähematel aastatel väheneb. Euroskeptikud on seisukohal, et eurot ei saa kasutusele võtta ilma põhiseadust muutmata. Professori väitel ei ole Eesti valitsusel vastust küsimustele, millisena näeb Eesti EL-i tulevikku ja kellelga ta EL-is koostööd hakkab tegema

  13. Merks kisti Lätis skandaali / Hille Tressum, Lemmi Kann

    Index Scriptorium Estoniae

    Tressum, Hille

    2008-01-01

    Ilmunud ka: Delovõje Vedomosti 9. apr. lk. 10. Läti meedia tõmbas Merko Ehituse tütarfirma Merksi korruptsiooniskandaali, väites, et altkäemaksu võtmises kahtlustatuna vahistatud Riia linna arendusosakonna eksjuht Vilnis Shtrams oli lähedastes suhetes nii Merksi juhi Ivars Geidansi kui ka Merko Ehituse juhi Toomas Annusega. Vt. samas: Merko: see on laimukampaania; Merks tegi miljard krooni odavama pakkumise; Merks on Riias ehitanud mitu kaalukat objekti; Valguse Lossi hanget ihaldavad paljud

  14. Eesti proosa 2007 - kultuuri ja tsivilisatsiooni vahel / Peeter Helme

    Index Scriptorium Estoniae

    Helme, Peeter, 1978-

    2008-01-01

    Ülevaade 2007. aasta eesti proosast. Käsitletakse järgimisi autoreid ja nende teoseid: Ene Mihkelson "Katkuhaud", Jaan Kaplinski "Seesama jõgi", Toomas Vint "Mäluauguga naine", Mehis Heinsaar "Rändaja õnn", Maimu Berg "Unustatud inimesed", Mihkel Mutt "Siseemigrant", Vahur Afanasjev "Kaadrid otsustavad", Epp Annus "Sina, Matilda", Ivar Sild "Tantsiv linn", Tiina Laanem "Väikesed vanamehed", Olle Lauli "Niguliste õpilased", Aarne Biin "Linna valitsemine", Jaan Aps ja Joonas Sildre "Hinglõõm". Ka Armin Kõomäe loomingust. Artikli aluseks on Eesti Kirjanduse Seltsi 2007. a. eesti kirjanduse ülevaatekoosolekul peetud ettekanne

  15. Vikergallup : eesti kirjandus 2001 : [vastused Vikerkaare küsitlusele

    Index Scriptorium Estoniae

    2002-01-01

    Aut.: Vahur Afanasjev, Veiko Belials, Piret Jaaks, Jan Kaus, Janek Kraavi, Priit Kruus, Leo Luks, Ilona Martson, Hedda Maurer, Anneli Mihkelev, Jürgen Rooste, Aarne Ruben, Mihkel Samarüütel, François Serpent, Ivar Sild, Karl Martin Sinijärv, Lauri Sommer, Jaak Urmet, Berk Vaher. 2001. a. parima uudisraamatu tiitlit jagasid Mehis Heinsaare "Härra Pauli kroonikad", Jan Kausi "Maailm ja mõni" ning Ene Mihkelsoni "Ahasveeruse uni"; parimaks esikraamatuks valiti Mehis Heinsaare "Vanameeste näppaja"

  16. E-kursuste konkursi tulemused / Reelyka Läheb

    Index Scriptorium Estoniae

    Läheb, Reelyka

    2004-01-01

    01.09.-31.10. 2003 toimus Tallinna Pedagoogikaülikoolis konkurss "Eesti e-Ülikooli toetus e-õppe kursustele, sügis 2003" eesmärgiga töötada välja uusi veebipõhiseid kursuseid. Konkursile laekunud 10 tööst otsustati ellu rakendada kõik. Projekti täitmiseks määrati toetused Hindrek Lootusele, Leif Kalevile, Anu Tootsile, Raivo Vetikule, Tiiu Reimole, Ivar Pornile, Sirje Pihtile, Kai Randrüütile ja Reelyka Lähebile

  17. Reactor pressure vessel embrittlement: Insights from neural network modelling

    Science.gov (United States)

    Mathew, J.; Parfitt, D.; Wilford, K.; Riddle, N.; Alamaniotis, M.; Chroneos, A.; Fitzpatrick, M. E.

    2018-04-01

    Irradiation embrittlement of steel pressure vessels is an important consideration for the operation of current and future light water nuclear reactors. In this study we employ an ensemble of artificial neural networks in order to provide predictions of the embrittlement using two literature datasets, one based on US surveillance data and the second from the IVAR experiment. We use these networks to examine trends with input variables and to assess various literature models including compositional effects and the role of flux and temperature. Overall, the networks agree with the existing literature models and we comment on their more general use in predicting irradiation embrittlement.

  18. SSBRP Communication & Data System Development using the Unified Modeling Language (UML)

    Science.gov (United States)

    Windrem, May; Picinich, Lou; Givens, John J. (Technical Monitor)

    1998-01-01

    The Unified Modeling Language (UML) is the standard method for specifying, visualizing, and documenting the artifacts of an object-oriented system under development. UML is the unification of the object-oriented methods developed by Grady Booch and James Rumbaugh, and of the Use Case Model developed by Ivar Jacobson. This paper discusses the application of UML by the Communications and Data Systems (CDS) team to model the ground control and command of the Space Station Biological Research Project (SSBRP) User Operations Facility (UOF). UML is used to define the context of the system, the logical static structure, the life history of objects, and the interactions among objects.

  19. Graafikatriennaali grand prix Korea kunstnikule

    Index Scriptorium Estoniae

    1998-01-01

    Tallinna XI graafikatriennaali rahvusvaheline žürii andis grand prix korea kunstnikule Chung¡Sang-Gonile, kolm võrdset preemiat - soome kunstnikele Anita Jensenile ja Tapani Mikkonenile ning jaapani kunstnikule Estuko Obatale. Eesti Kunstimuuseumi preemia - Wendy Swallow. Tallinna linna preemia ja Ivar Luki sponsoripreemia - Walter Jule. Sponsoripreemiad : Paletti Eesti AS preemia - Inga Heamägi; Rannila Profiili preemia - Mojca Zlokarnik; UNDP preemia - Andrea Juan. Rotermanni soolalao arhitektuuri- ja kunstikeskuse diplom - Lis Ingram, Heli Päivikki Kurunsaari, Randi Strand, Wendy Swallow

  20. Unistused muudavad maailma / Enn Tammearu

    Index Scriptorium Estoniae

    Tammearu, Enn

    2000-01-01

    Rocca al Mare koolimaja ehitamisest, AS KGM Ehitus meeskonnast ja juhatuse esimehest Tiit Nurklikust. Projekti autor: AB Urbel & Peil. Arhitektid Emil Urbel, Indrek Erm, sisearhitekt Taso Mähar, projektijuht Ivar Aus. Konstruktiivne osa: E-Inseneribüroo. Kooli direktori Rein Rebase, I. Ausi, I. Ermi ja T. Nurkliku kommentaarid. Nr. 11, lk. 4-6: Rocca al Mare koolile 2000. a. parima betoonehitise tiitel. Akustik Linda Madalik. Monoliitbetoonitööd: AS Roxor Ehitus. Arvamust avaldavad: T. Nurklik, I. Erm, OÜ Roxoe Ehituse tehniline juht Kalev Ramjalg, žürii esimees Aadu Kana

  1. Mål, utfordringer og muligheter for omdømmehåndtering i offentlig sektor: Fra identitet via ekspressivitet og transparens til autokommunikasjon?

    OpenAIRE

    Solbakk, Marianne N

    2015-01-01

    Artikkel nummer 1 og nummer 3 i avhandlingen er ikke tilgjengelig i Munin: 1. Wæraas, Arild and Marianne Nikolaisen Solbakk: «Defining the essence of a university: lessons from higher education branding.» Higher Education, 57(4), 2009, s. 449-462. Available at http://doi.org/10.1007/s10734-008-9155-z 3. Solbakk, Marianne Nikolaisen: «Omdømmehåndtering i sykehussektoren. Hvorfor og hvordan?1» I: Arild Wæraas; Haldor Byrkjeflot og Svein Ivar Angell (red.): Substans og Framtreden: Omdømmeh...

  2. Ehte järelkasv ja klassikud laegast täitmas / Ketli Tiitsar

    Index Scriptorium Estoniae

    Tiitsar, Ketli

    2004-01-01

    Ede Kurreli 95. sünniaastapäevale pühendatud Eesti Metallikunstnike Liidu ja Eesti Kunstiakadeemia ehte- ja sepakunsti eriala ühisnäitus "Laegas" Eesti Tarbekunsti- ja Disainimuuseumis kuni 17. X. Ede Kurreli, Arseni Möldri, Leili Kuldkepi, Kadri Mälgu, rühmituse ÕhuLoss, Birgit Marjundi, Risto Tali, Bruno Lillemetsa, Tõnis Bergi, Mart Reino, Adolfas Shaulyse, Mari Relo-Shaulyse, parima üliõpilastöö autori Kertu Tubergi ja 2004. a. Ede Kurreli preemia saanud Anneli Tammiku töödest, Maria Puki ja Ivar Lubjaku näitusekujundusest

  3. Paris-Princeton Lectures on Mathematical Finance

    CERN Document Server

    Carmona, René A; Kohatsu-Higa, Arturo; Lasry, Jean-Michel; Lions, Pierre-Louis; Pham, Huyên; Taflin, Erik

    2007-01-01

    The Paris-Princeton Lectures in Financial Mathematics, of which this is the third volume, will, on an annual basis, publish cutting-edge research in self-contained, expository articles from outstanding - established or upcoming! - specialists. The aim is to produce a series of articles that can serve as an introductory reference for research in the field. It arises as a result of frequent exchanges between the finance and financial mathematics groups in Paris and Princeton. The present volume sets standards with articles by René Carmona, Ivar Ekeland/Erik Taflin, Arturo Kohatsu-Higa, Pierre-Louis Lions/Jean-Michel Lasry, and Hyuên Pham.

  4. Meie nominendid

    Index Scriptorium Estoniae

    2005-01-01

    Areeni kultuuripreemia žürii tutvustab nominente: kunstikoguja Jaan Manitski, fotograaf Peeter Laurits, lavastaja Ain Mäeots, maalikunstnik Peeter Mudist, fotograaf Tiit Lepp, graafik Kristjan Mändmaa, metallikunstnik Ivar Kaasik, arhitekt Arne Maasik, PÖFFi korraldaja Tiina Lokk, tantsumanager Priit Raud, teatrijuht, lavastaja Peeter Jalakas, režissöör Mark Soosaar, lavastaja Tiit Ojasoo, kirjanikud Jaan Kaplinski, Hando Runnel, ajaloolane Magnus Ilmjärv, muusik Aivar Tõnso, disainer Lazer, helilooja Rein Fuks, hip hop ansambel Toe Tag

  5. President Ilves Tbilisis : Gruusia rahvale kuulub meie kindel toetus / Kristel Peterson

    Index Scriptorium Estoniae

    Peterson, Kristel

    2008-01-01

    Eesti president Toomas Hendrik Ilves, Läti peaminister Ivars Godmanis, Leedu president Valdas Adamkus, Poola president Lech Kaczynski ja Ukraina president Viktor Jushtshenko külastasid Gruusia pealinna Tbilisit, et näidata oma toetust Gruusia rahva demokraatlikule valikule ja avaldada tunnustust Gruusia otsusele mitte alistuda Venemaa agressioonile. Riigijuhid kohtusid ka Tbilisisse saabunud Prantsusmaa presidendi Nicolaz Sarkozy'ga. Ingl. k. ilmunud ka: Vaba Eesti Sõna 14. aug. 2008, lk. 12, pealk.: President Ilves in Tbilisi: the Georgian people have our firm support. Vabariigi President töövisiidil Gruusias 12.-13.08.2008

  6. Hüpped modernismi poole II : 20. sajandi eesti kirjandusteadus Euroopa kirjandusteaduse taustal : 17. loeng : pagulasaastad III. Hilisem kirjandusuurimine Rootsis ja kirjanduslood / Tiit Hennoste

    Index Scriptorium Estoniae

    Hennoste, Tiit, 1953-

    2009-01-01

    1970.-1980. aastatel ilmunud rootsieesti uurijate töödest ja kirjanduslugudest eesti kirjanduse kohta. Pikemalt Herbert Salu, Bernard Kangro, Valter Uibopuu, Ilmar Talve, Ilmar Laabani, Ivar Grünthali ja Ilmar Mikiveri uurimustest. Võõrkeelsetest ülevaadetest käsitletakse Jüri Kurmani, Raimond Kolga, Arvo Mägi ja Mall Jürma töid. Samuti on juttu eesti kirjandust uurinud välismaiste uurijate Friedrich Scholzi, Erik Thomsoni ja Ernest Howard Harrise töödest

  7. Aaviku fenomen = The Aaviku Phenomenon / Andres Kurg

    Index Scriptorium Estoniae

    Kurg, Andres, 1975-

    2003-01-01

    Aaviku elamurajoonist, kus on 67 maja, 6 erinevat tüüpi, ühe- ja kahekorruselised, 84-144 mø suured, hindadega vahemikus 760000-1200000 krooni. Projekteerija: Arhitektuuribüroo Emil Urbel. Autorid Emil Urbel ja Indrek Erm. Konstruktor Otto Pukk (OMK Inseneribüroo). Haljastus: Maria Pukk, Ivar Lubjak (Oaas Arhitektid). Projekt 2000-2001, valmis 2001-2003. Tüüpprojekti S-5 I ja II korruse plaan, tüüpprojekti V-2 põhiplaan, sisevaade, 5 välisvaadet

  8. Turunduse tulevik algab täna / Christopher Vollmer, John Frelinghuysen, Randall Rothenberg ; tõlk. Kadi Tarand

    Index Scriptorium Estoniae

    Vollmer, Christopher

    2006-01-01

    Järg nr. 8 okt. lk. 12-13. Ameerika Ühendriikides nähakse uusi digitaalseid meediavahendeid, eelkõige Internetti, üha enam potentsiaalse turunduskeskkonnana, mis tõrjub tahaplaanile traditsioonilised levikanalid. Uued võimalused sunnivad ka ettevõtete turundusosakondi muutma oma müügistrateegiaid tarbijakesksemaks. Kommenteerivad Maurice Saatchi, Robin, Gurney. Diagrammid: Autoreklaami meediakulud; Reklaamiandjate ootused; Ootused uue meedia suhtes; Reklaamikulutused Eestis. Skeem: Nn ostulehter - meedia hindamise süteem. Nr. 8 kommenteerivad Margo Veskimägi ja Ivar Soone

  9. Ma tean, mida sa näitad end olevat teinud läinud suvel / Laura Kuusk

    Index Scriptorium Estoniae

    Kuusk, Laura, 1982-

    2006-01-01

    Kuraator Marco Laimre juhendamisel valminud Eesti Kunstiakadeemia III kursuse fotograafiaüliõpilaste suvepraktika tööde näitus "Ma tean, mida sa tegid läinud suvel / I know what you did last summer" Eesti Kunstiakadeemia galeriis kuni 3. X. Helina Kõrmi, Dmitri Gerassimovi, Kristjan-Jaak Tammiksaare, Anne-Mai Pällo, Tuuli Antsovi, Terje Ugandi, Ivar Veermäe, Riika Tauriaineni, Kätly Kaibaldi, Raul Viitungi ja Andrus Kaursoni töödest

  10. Ilves : lisaks välisele julgeolekule on sama oluline sisejulgeolek / Toomas Hendrik Ilves ; interv. Erkki Bahovski

    Index Scriptorium Estoniae

    Ilves, Toomas Hendrik, 1953-

    2008-01-01

    President räägib Euroopa julgeoleku paradigma muutumisest seoses Gruusia ja Venemaa konfliktiga, NATO tähtsuse kasvust Euroopa julgeolekut tagava organisatsioonina, Eesti kaitsevõimest ja sisejulgeolekust, Eesti-Vene suhetest ja piirilepingust, Lissaboni leppest, NATO ja Euroopa Liidu võimalustest Gruusia abistamisel, NATO baaside Eestisse toomise võimalusest, Sotši olümpiamängude ja Eurovisooni lauluvõistluse boikoteerimisest. Juuresoleval fotol Gruusia president Mikheil Saakashvili, Eesti president T. H. Ilves, Poola president Lech Kaczynski, Leedu president Valdas Adamkus ja Läti peaminister Ivars Godmanis Thbilisis 13. augustil 2008. Vt. ka juhtkiri lk. 2: Muutunud maailm

  11. Production of 2nd generation Bioethanol from Lucerne - Optimization of Hydrothermal Pretreatment

    DEFF Research Database (Denmark)

    Thomsen, Sune Tjalfe; Jensen, Morten; Schmidt, Jens Ejbye

    2012-01-01

    Lucerne (Medicago sativa) has many qualities associated with sustainable agriculture such as nitrogen fixation and high biomass yield. Therefore, there is interest in whether lucerne is a suitable biomass substrate for bioethanol production, and if hydrothermal pretreatment (HTT) of lucerne impro...

  12. File list: Oth.NoD.10.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.NoD.10.Epitope_tags.AllCell hg19 TFs and others Epitope tags No description htt...p://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.NoD.10.Epitope_tags.AllCell.bed ...

  13. File list: Oth.NoD.50.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.NoD.50.Epitope_tags.AllCell hg19 TFs and others Epitope tags No description htt...p://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.NoD.50.Epitope_tags.AllCell.bed ...

  14. File list: Oth.NoD.05.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.NoD.05.Epitope_tags.AllCell hg19 TFs and others Epitope tags No description htt...p://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.NoD.05.Epitope_tags.AllCell.bed ...

  15. File list: Oth.NoD.20.Epitope_tags.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.NoD.20.Epitope_tags.AllCell hg19 TFs and others Epitope tags No description htt...p://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.NoD.20.Epitope_tags.AllCell.bed ...

  16. Haplotype-based stratification of Huntington's disease.

    Science.gov (United States)

    Chao, Michael J; Gillis, Tammy; Atwal, Ranjit S; Mysore, Jayalakshmi Srinidhi; Arjomand, Jamshid; Harold, Denise; Holmans, Peter; Jones, Lesley; Orth, Michael; Myers, Richard H; Kwak, Seung; Wheeler, Vanessa C; MacDonald, Marcy E; Gusella, James F; Lee, Jong-Min

    2017-11-01

    Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by expansion of a CAG trinucleotide repeat in HTT, resulting in an extended polyglutamine tract in huntingtin. We and others have previously determined that the HD-causing expansion occurs on multiple different haplotype backbones, reflecting more than one ancestral origin of the same type of mutation. In view of the therapeutic potential of mutant allele-specific gene silencing, we have compared and integrated two major systems of HTT haplotype definition, combining data from 74 sequence variants to identify the most frequent disease-associated and control chromosome backbones and revealing that there is potential for additional resolution of HD haplotypes. We have used the large collection of 4078 heterozygous HD subjects analyzed in our recent genome-wide association study of HD age at onset to estimate the frequency of these haplotypes in European subjects, finding that common genetic variation at HTT can distinguish the normal and CAG-expanded chromosomes for more than 95% of European HD individuals. As a resource for the HD research community, we have also determined the haplotypes present in a series of publicly available HD subject-derived fibroblasts, induced pluripotent cells, and embryonic stem cells in order to facilitate efforts to develop inclusive methods of allele-specific HTT silencing applicable to most HD patients. Our data providing genetic guidance for therapeutic gene-based targeting will significantly contribute to the developments of rational treatments and implementation of precision medicine in HD.

  17. A dual-process account of auditory change detection.

    Science.gov (United States)

    McAnally, Ken I; Martin, Russell L; Eramudugolla, Ranmalee; Stuart, Geoffrey W; Irvine, Dexter R F; Mattingley, Jason B

    2010-08-01

    Listeners can be "deaf" to a substantial change in a scene comprising multiple auditory objects unless their attention has been directed to the changed object. It is unclear whether auditory change detection relies on identification of the objects in pre- and post-change scenes. We compared the rates at which listeners correctly identify changed objects with those predicted by change-detection models based on signal detection theory (SDT) and high-threshold theory (HTT). Detected changes were not identified as accurately as predicted by models based on either theory, suggesting that some changes are detected by a process that does not support change identification. Undetected changes were identified as accurately as predicted by the HTT model but much less accurately than predicted by the SDT models. The process underlying change detection was investigated further by determining receiver-operating characteristics (ROCs). ROCs did not conform to those predicted by either a SDT or a HTT model but were well modeled by a dual-process that incorporated HTT and SDT components. The dual-process model also accurately predicted the rates at which detected and undetected changes were correctly identified.

  18. Locus - ASTRA | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available switchLanguage; BLAST Search Image Search Home About Archive Update History Data ...URL: ftp://ftp.biosciencedbc.jp/archive/astra/LATEST/astra_locus.zip File size: 887 KB Simple search URL htt...icing type (ex. cassette) About This Database Database Description Download License Update History of This Database Site Policy | Contact Us Locus - ASTRA | LSDB Archive ...

  19. File list: InP.NoD.05.Input_control.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.NoD.05.Input_control.AllCell dm3 Input control Input control No description htt...p://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/InP.NoD.05.Input_control.AllCell.bed ...

  20. File list: InP.NoD.20.Input_control.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.NoD.20.Input_control.AllCell dm3 Input control Input control No description htt...p://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/InP.NoD.20.Input_control.AllCell.bed ...

  1. Understanding the Biology and Technology of ToxCast and Tox21 Assays

    Science.gov (United States)

    The ToxCast high-throughput toxicity (HTT) testing methods have been developed to evaluate the hazard potential of diverse environmental, industrial and consumer product chemicals. The main goal is prioritizing the compounds of greatest concern for more detailed toxicological stu...

  2. The development of high-temperature reactors in the Federal Republic of Germany

    International Nuclear Information System (INIS)

    Engelmann, P.; Krings, F.

    1980-01-01

    The principal features of high-temperature reactors are recalled, then the current state of technology of the line in the Federal Republic of Germany is described. Reference is made to the experience of operating the AVR reactor, the construction of the THTR-300 reactor as well as the HTT and PNP projects [fr

  3. Looking on the bright side of serotonin transporter gene variation.

    NARCIS (Netherlands)

    Homberg, J.R.; Lesch, K.P.

    2011-01-01

    Converging evidence indicates an association of the short (s), low-expressing variant of the repeat length polymorphism, serotonin transporter-linked polymorphic region (5-HTTLPR), in the human serotonin transporter gene (5-HTT, SERT, SLC6A4) with anxiety-related traits and increased risk for

  4. Phenotype-gene: 454 [Arabidopsis Phenome Database[Archive

    Lifescience Database Archive (English)

    Full Text Available stance in response to organism biotroph for AT5G60600 Gil M Jos辿 et al. 2005 Oct. Plant J. 44(1):155-66. htt...p://metadb.riken.jp/db/SciNetS_ria224i/cria224u4ria224u16167903i increased resistance in response to organism biotroph

  5. Phenotype-gene: 399 [Arabidopsis Phenome Database[Archive

    Lifescience Database Archive (English)

    Full Text Available rescence for quantity of chlorophyll for AT5G51545 Ma Jinfang et al. 2007 Jun. Plant Cell 19(6):1980-93. htt...p://metadb.riken.jp/db/SciNetS_ria224i/cria224u4ria224u17601825i increased fluorescence for quantity of chloroph

  6. File list: DNS.Emb.10.AllAg.Pre-somitic_mesoderm [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Emb.10.AllAg.Pre-somitic_mesoderm mm9 DNase-seq Embryo Pre-somitic mesoderm htt...p://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Emb.10.AllAg.Pre-somitic_mesoderm.bed ...

  7. File list: DNS.Emb.20.AllAg.Pre-somitic_mesoderm [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Emb.20.AllAg.Pre-somitic_mesoderm mm9 DNase-seq Embryo Pre-somitic mesoderm htt...p://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Emb.20.AllAg.Pre-somitic_mesoderm.bed ...

  8. File list: DNS.Emb.50.AllAg.Pre-somitic_mesoderm [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Emb.50.AllAg.Pre-somitic_mesoderm mm9 DNase-seq Embryo Pre-somitic mesoderm htt...p://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Emb.50.AllAg.Pre-somitic_mesoderm.bed ...

  9. File list: DNS.Emb.05.AllAg.Pre-somitic_mesoderm [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Emb.05.AllAg.Pre-somitic_mesoderm mm9 DNase-seq Embryo Pre-somitic mesoderm htt...p://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Emb.05.AllAg.Pre-somitic_mesoderm.bed ...

  10. The effects of smoking and nicotine ingestion on exercise heat tolerance.

    Science.gov (United States)

    Druyan, Amit; Atias, Danit; Ketko, Itay; Cohen-Sivan, Yoav; Heled, Yuval

    2017-03-01

    Smoking has a thermogenic effect and is associated with low physical performance. Nevertheless, a direct, quantitative effect of acute smoking on exercise heat tolerance has not been reported. Sixteen healthy young male volunteers, eight cigarette smokers, and eight non-smokers participated in the study. All subjects performed a maximal oxygen consumption test (VO2max) and a standardized heat tolerance test (HTT) after at least 12 h without smoking under the following conditions: no nicotine exposure, 10 min after nicotine exposure (2 mg nicotine lozenge), and 10 min after smoking two cigarettes (0.8 mg nicotine in each cigarette, smokers only). There was no significant effect of nicotine exposure on physiological performance and heat tolerance in the non-smokers group. In the smokers group, cigarette smoking, but not nicotine ingestion, resulted with higher heart rate (by 9±9 bpm) at the end of the HTT (psmoking and nicotine ingestion increased smokers' rectal temperature at the end of the HTT (by 0.24±0.16°C and 0.21±0.26°C, respectively, psmoking in the smokers group compared with no exposure (2.13±2.57 and 2.48±2.76, respectively, psmoking and nicotine ingestion increase the physiological strain during a HTT in smokers. Acute smoking may, therefore, increase heat intolerance and the risk to heat injuries.

  11. Phenotype abnormality: 251 [Arabidopsis Phenome Database[Archive

    Lifescience Database Archive (English)

    Full Text Available lant flowering stage in environment of long day length regimen in environment of long day length regimen htt... 251 http://metadb.riken.jp/db/SciNetS_ria224i/cria224u1ria224u757i delayed whole p

  12. Large normal-range TBP and ATXN7 CAG repeat lengths are associated with increased lifetime risk of depression

    DEFF Research Database (Denmark)

    Gardiner, S. L.; van Belzen, M. J.; Boogaard, M. W.

    2017-01-01

    Depression is one of the most prevalent and debilitating psychiatric disorders worldwide. Recently, we showed that both relatively short and relatively long cytosine–adenine–guanine (CAG) repeats in the huntingtin gene (HTT) are associated with an increased risk of lifetime depression. However, t...

  13. Dopaminergic, Serotonergic, and Oxytonergic Candidate Genes Associated with Infant Attachment Security and Disorganization? In Search of Main and Interaction Effects

    Science.gov (United States)

    Luijk, Maartje P. C. M.; Roisman, Glenn I.; Haltigan, John D.; Tiemeier, Henning; Booth-LaForce, Cathryn; van IJzendoorn, Marinus H.; Belsky, Jay; Uitterlinden, Andre G.; Jaddoe, Vincent W. V.; Hofman, Albert; Verhulst, Frank C.; Tharner, Anne; Bakermans-Kranenburg, Marian J.

    2011-01-01

    Background and methods: In two birth cohort studies with genetic, sensitive parenting, and attachment data of more than 1,000 infants in total, we tested main and interaction effects of candidate genes involved in the dopamine, serotonin, and oxytocin systems ("DRD4", "DRD2", "COMT", "5-HTT", "OXTR") on attachment security and disorganization.…

  14. 20180416 - Understanding the Biology and Technology of ToxCast and Tox21 Assays (SETAC Durham NC)

    Science.gov (United States)

    The ToxCast high-throughput toxicity (HTT) testing methods have been developed to evaluate the hazard potential of diverse environmental, industrial and consumer product chemicals. The main goal is prioritizing the compounds of greatest concern for more detailed toxicological stu...

  15. When cytokinin, a plant hormone, meets the adenosine A2A receptor: a novel neuroprotectant and lead for treating neurodegenerative disorders?

    Directory of Open Access Journals (Sweden)

    Yi-Chao Lee

    Full Text Available It is well known that cytokinins are a class of phytohormones that promote cell division in plant roots and shoots. However, their targets, biological functions, and implications in mammalian systems have rarely been examined. In this study, we show that one cytokinin, zeatin riboside, can prevent pheochromocytoma (PC12 cells from serum deprivation-induced apoptosis by acting on the adenosine A(2A receptor (A(2A-R, which was blocked by an A(2A-R antagonist and a protein kinase A (PKA inhibitor, demonstrating the functional ability of zeatin riboside by mediating through A(2A-R signaling event. Since the A(2A-R was implicated as a therapeutic target in treating Huntington's disease (HD, a cellular model of HD was applied by transfecting mutant huntingtin in PC12 cells. By using filter retardation assay and confocal microscopy we found that zeatin riboside reversed mutant huntingtin (Htt-induced protein aggregations and proteasome deactivation through A(2A-R signaling. PKA inhibitor blocked zeatin riboside-induced suppression of mutant Htt aggregations. In addition, PKA activated proteasome activity and reduced mutant Htt protein aggregations. However, a proteasome inhibitor blocked both zeatin riboside-and PKA activator-mediated suppression of mutant Htt aggregations, confirming mediation of the A(2A-R/PKA/proteasome pathway. Taken together, zeatin riboside might have therapeutic potential as a novel neuroprotectant and a lead for treating neurodegenerative disorders.

  16. File list: InP.Oth.20.AllAg.Pancreas_and_brain [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Oth.20.AllAg.Pancreas_and_brain mm9 Input control Others Pancreas and brain htt...p://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Oth.20.AllAg.Pancreas_and_brain.bed ...

  17. File list: InP.Oth.50.AllAg.Pancreas_and_brain [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Oth.50.AllAg.Pancreas_and_brain mm9 Input control Others Pancreas and brain htt...p://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Oth.50.AllAg.Pancreas_and_brain.bed ...

  18. File list: InP.Oth.10.AllAg.Pancreas_and_brain [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Oth.10.AllAg.Pancreas_and_brain mm9 Input control Others Pancreas and brain htt...p://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Oth.10.AllAg.Pancreas_and_brain.bed ...

  19. Hoare type theory, polymorphism and separation

    DEFF Research Database (Denmark)

    Nanevski, Alexandar; Morrisett, J. Gregory; Birkedal, Lars

    2008-01-01

    We consider the problem of reconciling a dependently typed functional language with imperative features such as mutable higher-order state, pointer aliasing, and nontermination. We propose Hoare type theory (HTT), which incorporates Hoare-style specifications into types, making it possible to sta...

  20. File list: DNS.Lng.10.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Lng.10.AllAg.Carcinoma,_Lewis_Lung mm9 DNase-seq Lung Carcinoma, Lewis Lung htt...p://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Lng.10.AllAg.Carcinoma,_Lewis_Lung.bed ...

  1. File list: DNS.Lng.50.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Lng.50.AllAg.Carcinoma,_Lewis_Lung mm9 DNase-seq Lung Carcinoma, Lewis Lung htt...p://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Lng.50.AllAg.Carcinoma,_Lewis_Lung.bed ...

  2. File list: DNS.Lng.20.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Lng.20.AllAg.Carcinoma,_Lewis_Lung mm9 DNase-seq Lung Carcinoma, Lewis Lung htt...p://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Lng.20.AllAg.Carcinoma,_Lewis_Lung.bed ...

  3. Association between a genetic variant in the serotonin transporter gene (SLC6A4) and suicidal behavior in patients with schizophrenia

    DEFF Research Database (Denmark)

    Lindholm Carlstrom, Eva; Saetre, Peter; Rosengren, Anders

    2012-01-01

    ABSTRACT: BACKGROUND: The serotonin (5-hydroxytryptamin; 5-HT) system has a central role in the circuitry of cognition and emotions. Multiple lines of evidence suggest that genetic variation in the serotonin transporter gene (SLC6A4; 5-HTT) is associated with schizophrenia and suicidal behavior. ...

  4. Experiment list: SRX1084162 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available 0 GSM1811344: P2 HA ChIPSeq; Drosophila melanogaster; ChIP-Seq source_name=Female whole animal_paraquat || tissue=whole animal || gen...der=female || age=1-3 days || genotype=k6801/k6801;gHA-KDM5 || chip antibody=HA htt

  5. OF MICE, RATS AND MEN: REVISITING THE QUINOLINIC ACID HYPOTHESIS OF HUNTINGTON’S DISEASE

    Science.gov (United States)

    Schwarcz, R.; Guidetti, P.; Sathyasaikumar, K. V.; Muchowski, P. J.

    2009-01-01

    The neurodegenerative disease Huntington’s Disease (HD) is caused by an expanded polyglutamine (polyQ) tract in the protein huntingtin (htt). Although the gene encoding htt was identified and cloned more than 15 years ago, and in spite of impressive efforts to unravel the mechanism(s) by which mutant htt induces nerve cell death, these studies have so far not led to a good understanding of pathophysiology or an effective therapy. Set against a historical background, we review data supporting the idea that metabolites of the kynurenine pathway (KP) of tryptophan degradation provide a critical link between mutant htt and the pathophysiology of HD. New studies in HD brain and genetic model organisms suggest that the disease may in fact be causally related to early abnormalities in KP metabolism, favoring the formation of two neurotoxic metabolites, 3-hydroxykynurenine and quinolinic acid, over the related neuroprotective agent kynurenic acid. These findings not only link the excitotoxic hypothesis of HD pathology to an impairment of the KP but also define new drug targets and therefore have direct therapeutic implications. Thus, pharmacological normalization of the imbalance in brain KP metabolism may provide clinical benefits, which could be especially effective in the early stages of the disease. PMID:19394403

  6. Waste-to-energy: Dehalogenation of plastic-containing wastes.

    Science.gov (United States)

    Shen, Yafei; Zhao, Rong; Wang, Junfeng; Chen, Xingming; Ge, Xinlei; Chen, Mindong

    2016-03-01

    The dehalogenation measurements could be carried out with the decomposition of plastic wastes simultaneously or successively. This paper reviewed the progresses in dehalogenation followed by thermochemical conversion of plastic-containing wastes for clean energy production. The pre-treatment method of MCT or HTT can eliminate the halogen in plastic wastes. The additives such as alkali-based metal oxides (e.g., CaO, NaOH), iron powders and minerals (e.g., quartz) can work as reaction mediums and accelerators with the objective of enhancing the mechanochemical reaction. The dehalogenation of waste plastics could be achieved by co-grinding with sustainable additives such as bio-wastes (e.g., rice husk), recyclable minerals (e.g., red mud) via MCT for solid fuels production. Interestingly, the solid fuel properties (e.g., particle size) could be significantly improved by HTT in addition with lignocellulosic biomass. Furthermore, the halogenated compounds in downstream thermal process could be eliminated by using catalysts and adsorbents. Most dehalogenation of plastic wastes primarily focuses on the transformation of organic halogen into inorganic halogen in terms of halogen hydrides or salts. The integrated process of MCT or HTT with the catalytic thermal decomposition is a promising way for clean energy production. The low-cost additives (e.g., red mud) used in the pre-treatment by MCT or HTT lead to a considerable synergistic effects including catalytic effect contributing to the follow-up thermal decomposition. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. File list: DNS.Emb.20.AllAg.Embryonic_trunk [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Emb.20.AllAg.Embryonic_trunk mm9 DNase-seq Embryo Embryonic trunk SRX191030 htt...p://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Emb.20.AllAg.Embryonic_trunk.bed ...

  8. File list: NoD.Adl.50.AllAg.Adult_male_fatbody [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Adl.50.AllAg.Adult_male_fatbody dm3 No description Adult Adult male fatbody htt...p://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/NoD.Adl.50.AllAg.Adult_male_fatbody.bed ...

  9. File list: Oth.Adl.20.AllAg.Adult_male_fatbody [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Adl.20.AllAg.Adult_male_fatbody dm3 TFs and others Adult Adult male fatbody htt...p://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/Oth.Adl.20.AllAg.Adult_male_fatbody.bed ...

  10. File list: Pol.Adl.50.AllAg.Adult_male_fatbody [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Adl.50.AllAg.Adult_male_fatbody dm3 RNA polymerase Adult Adult male fatbody htt...p://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/Pol.Adl.50.AllAg.Adult_male_fatbody.bed ...

  11. File list: NoD.Adl.05.AllAg.Adult_male_fatbody [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Adl.05.AllAg.Adult_male_fatbody dm3 No description Adult Adult male fatbody htt...p://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/NoD.Adl.05.AllAg.Adult_male_fatbody.bed ...

  12. File list: Pol.Adl.10.AllAg.Adult_male_fatbody [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Adl.10.AllAg.Adult_male_fatbody dm3 RNA polymerase Adult Adult male fatbody htt...p://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/Pol.Adl.10.AllAg.Adult_male_fatbody.bed ...

  13. File list: Oth.Adl.05.AllAg.Adult_male_fatbody [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Adl.05.AllAg.Adult_male_fatbody dm3 TFs and others Adult Adult male fatbody htt...p://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/Oth.Adl.05.AllAg.Adult_male_fatbody.bed ...

  14. File list: NoD.Adl.20.AllAg.Adult_male_fatbody [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Adl.20.AllAg.Adult_male_fatbody dm3 No description Adult Adult male fatbody htt...p://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/NoD.Adl.20.AllAg.Adult_male_fatbody.bed ...

  15. File list: Oth.Adl.10.AllAg.Adult_male_fatbody [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Adl.10.AllAg.Adult_male_fatbody dm3 TFs and others Adult Adult male fatbody htt...p://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/Oth.Adl.10.AllAg.Adult_male_fatbody.bed ...

  16. File list: NoD.Adl.10.AllAg.Adult_male_fatbody [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Adl.10.AllAg.Adult_male_fatbody dm3 No description Adult Adult male fatbody htt...p://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/NoD.Adl.10.AllAg.Adult_male_fatbody.bed ...

  17. File list: Pol.Adl.20.AllAg.Adult_male_fatbody [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Adl.20.AllAg.Adult_male_fatbody dm3 RNA polymerase Adult Adult male fatbody htt...p://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/Pol.Adl.20.AllAg.Adult_male_fatbody.bed ...

  18. File list: InP.NoD.50.Input_control.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.NoD.50.Input_control.AllCell dm3 Input control Input control No description htt...p://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/InP.NoD.50.Input_control.AllCell.bed ...

  19. File list: InP.NoD.20.Input_control.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.NoD.20.Input_control.AllCell mm9 Input control Input control No description htt...p://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.NoD.20.Input_control.AllCell.bed ...

  20. File list: InP.NoD.05.Input_control.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.NoD.05.Input_control.AllCell mm9 Input control Input control No description htt...p://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.NoD.05.Input_control.AllCell.bed ...

  1. File list: InP.NoD.10.Input_control.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.NoD.10.Input_control.AllCell dm3 Input control Input control No description htt...p://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/InP.NoD.10.Input_control.AllCell.bed ...

  2. Cellular cytotoxic response induced by highly purified multi-wall carbon nanotube in human lung cells.

    Science.gov (United States)

    Tsukahara, Tamotsu; Haniu, Hisao

    2011-06-01

    Carbon nanotubes, a promising nanomaterial with unique characteristics, have applications in a variety of fields. The cytotoxic effects of carbon nanotubes are partially due to the induction of oxidative stress; however, the detailed mechanisms of nanotube cytotoxicity and their interaction with cells remain unclear. In this study, the authors focus on the acute toxicity of vapor-grown carbon fiber, HTT2800, which is one of the most highly purified multi-wall carbon nanotubes (MWCNT) by high-temperature thermal treatment. The authors exposed human bronchial epithelial cells (BEAS-2B) to HTT2800 and measured the cellular uptake, mitochondrial function, cellular LDH release, apoptotic signaling, reactive oxygen species (ROS) generation and pro-inflammatory cytokine release. The HTT2800-exposed cells showed cellular uptake of the carbon nanotube, increased cell death, enhanced DNA damage, and induced cytokine release. However, the exposed cells showed no obvious intracellular ROS generation. These cellular and molecular findings suggest that HTT2800 could cause a potentially adverse inflammatory response in BEAS-2B cells.

  3. Serotonin Transporter Knockout Rats Show Improved Strategy Set-Shifting and Reduced Latent Inhibition

    Science.gov (United States)

    Nonkes, Lourens J. P.; van de Vondervoort, Ilse I. G. M.; de Leeuw, Mark J. C.; Wijlaars, Linda P.; Maes, Joseph H. R.; Homberg, Judith R.

    2012-01-01

    Behavioral flexibility is a cognitive process depending on prefrontal areas allowing adaptive responses to environmental changes. Serotonin transporter knockout (5-HTT[superscript -/-]) rodents show improved reversal learning in addition to orbitofrontal cortex changes. Another form of behavioral flexibility, extradimensional strategy set-shifting…

  4. Early life adversity and serotonin transporter gene variation interact to affect DNA methylation of the corticotropin-releasing factor gene promoter region in the adult rat brain

    NARCIS (Netherlands)

    Doelen, R.H.A. van der; Arnoldussen, I.A.C.; Ghareh, H.; Och, L. van; Homberg, J.R.; Kozicz, L.T.

    2015-01-01

    The interaction between childhood maltreatment and the serotonin transporter (5-HTT) gene linked polymorphic region has been associated with increased risk to develop major depression. This Gene x Environment interaction has furthermore been linked with increased levels of anxiety and glucocorticoid

  5. Early life adversity and serotonin transporter gene variation interact at the level of the adrenal gland to affect the adult hypothalamo-pituitary-adrenal axis

    NARCIS (Netherlands)

    Doelen, R.H.A. van der; Deschamps, W.; D'Annibale, C.; Peeters, D.; Wevers, R.A.; Zelena, D.; Homberg, J.R.; Kozicz, L.T.

    2014-01-01

    The short allelic variant of the serotonin transporter (5-HTT) promoter-linked polymorphic region (5-HTTLPR) has been associated with the etiology of major depression by interaction with early life stress (ELS). Furthermore, 5-HTTLPR has been associated with abnormal functioning of the

  6. 5-HTTLPR modulates the recognition accuracy and exploration of emotional facial expressions

    Directory of Open Access Journals (Sweden)

    Sabrina eBoll

    2014-07-01

    Full Text Available Individual genetic differences in the serotonin transporter-linked polymorphic region (5-HTTLPR have been associated with variations in the sensitivity to social and emotional cues as well as altered amygdala reactivity to facial expressions of emotion. Amygdala activation has further been shown to trigger gaze changes towards diagnostically relevant facial features. The current study examined whether altered socio-emotional reactivity in variants of the 5-HTTLPR promoter polymorphism reflects individual differences in attending to diagnostic features of facial expressions. For this purpose, visual exploration of emotional facial expressions was compared between a low (n=39 and a high (n=40 5-HTT expressing group of healthy human volunteers in an eye tracking paradigm. Emotional faces were presented while manipulating the initial fixation such that saccadic changes towards the eyes and towards the mouth could be identified. We found that the low versus the high 5-HTT group demonstrated greater accuracy with regard to emotion classifications, particularly when faces were presented for a longer duration. No group differences in gaze orientation towards diagnostic facial features could be observed. However, participants in the low 5-HTT group exhibited more and faster fixation changes for certain emotions when faces were presented for a longer duration and overall face fixation times were reduced for this genotype group. These results suggest that the 5-HTT gene influences social perception by modulating the general vigilance to social cues rather than selectively affecting the pre-attentive detection of diagnostic facial features.

  7. Reversal learning and associative memory impairments in a BACHD rat model for Huntington disease

    NARCIS (Netherlands)

    Abada, Yah-se K.; Nguyen, Huu Phuc; Ellenbroek, Bart; Schreiber, Rudy

    2013-01-01

    Chorea and psychiatric symptoms are hallmarks of Huntington disease (HD), a neurodegenerative disorder, genetically characterized by the presence of expanded CAG repeats (>35) in the HUNTINGTIN (HTT) gene. HD patients present psychiatric symptoms prior to the onset of motor symptoms and we recently

  8. Experiment list: SRX122491 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ntibody=Atf3 || treatment=LPS || time=60 min || chip antibody manufacturer 1=Santa Cruz || chip antibody cat...alog number 1=sc-188 || chip antibody manufacturer 2=Abcam || chip antibody catalog number 2=ab70005-100 htt

  9. Experiment list: SRX122468 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available antibody=Rela || treatment=LPS || time=0 min || chip antibody manufacturer 1=Bethyl || chip antibody catalo...g number 1=A301-824A || chip antibody manufacturer 2=Santa Cruz || chip antibody catalog number 2=sc-372 htt

  10. Experiment list: SRX122551 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available antibody=Stat1 || treatment=LPS || time=0 min || chip antibody manufacturer 1=Santa Cruz || chip antibody ca...talog number 1=sc-346 || chip antibody manufacturer 2=Bethyl || chip antibody catalog number 2=A302-753A htt

  11. Experiment list: SRX122409 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ip antibody=Irf1 || treatment=LPS || time=60 min || chip antibody manufacturer 1=Abcam || chip antibody cata...log number 1=ab52520 || chip antibody manufacturer 2=Santa Cruz || chip antibody catalog number 2=sc-640 htt

  12. Experiment list: SRX122490 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ntibody=Atf3 || treatment=LPS || time=30 min || chip antibody manufacturer 1=Santa Cruz || chip antibody cat...alog number 1=sc-188 || chip antibody manufacturer 2=Abcam || chip antibody catalog number 2=ab70005-100 htt

  13. Experiment list: SRX122492 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ntibody=Atf3 || treatment=LPS || time=60 min || chip antibody manufacturer 1=Santa Cruz || chip antibody cat...alog number 1=sc-188 || chip antibody manufacturer 2=Abcam || chip antibody catalog number 2=ab70005-100 htt

  14. Dysregulation of gene expression in the striatum of BACHD rats expressing full-length mutant huntingtin and associated abnormalities on molecular and protein levels.

    Science.gov (United States)

    Yu-Taeger, Libo; Bonin, Michael; Stricker-Shaver, Janice; Riess, Olaf; Nguyen, Hoa Huu Phuc

    2017-05-01

    Huntington disease (HD) is an autosomal dominantly inherited neurodegenerative disorder caused by a CAG repeat expansion in the gene coding for the huntingtin protein (HTT). Mutant HTT (mHTT) has been proposed to cause neuronal dysfunction and neuronal loss through multiple mechanisms. Transcriptional changes may be a core pathogenic feature of HD. Utilizing the Affymetrix platform we performed a genome-wide RNA expression analysis in two BACHD transgenic rat lines (TG5 and TG9) at 12 months of age, both of which carry full-length human mHTT but with different expression levels. By defining the threshold of significance at p < 0.01, we found 1608 genes and 871 genes differentially expressed in both TG5 and TG9 rats when compared to the wild type littermates, respectively. We only chose the highly up-/down-regulated genes for further analysis by setting an additional threshold of 1.5 fold change. Comparing gene expression profiles of human HD brains and BACHD rats revealed a high concordance in both functional and IPA (Ingenuity Pathway Analysis) canonical pathways relevant to HD. In addition, we investigated the causes leading to gene expression changes at molecular and protein levels in BACHD rats including the involvement of polyQ-containing transcription factors TATA box-binding protein (TBP), Sp1 and CBP as well as the chromatin structure. We demonstrate that the BACHD rat model recapitulates the gene expression changes of the human disease supporting its role as a preclinical research animal model. We also show for the first time that TFIID complex formation is reduced, while soluble TBP is increased in an HD model. This finding suggests that mHTT is a competitor instead of a recruiter of polyQ-containing transcription factors in the transcription process in HD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Correlations of behavioral deficits with brain pathology assessed through longitudinal MRI and histopathology in the R6/1 mouse model of Huntington's disease.

    Directory of Open Access Journals (Sweden)

    Ivan Rattray

    Full Text Available Huntington's disease (HD is caused by the expansion of a CAG repeat in the huntingtin (HTT gene. The R6 mouse models of HD express a mutant version of exon 1 HTT and typically develop motor and cognitive impairments, a widespread huntingtin (HTT aggregate pathology and brain atrophy. Unlike the more commonly used R6/2 mouse line, R6/1 mice have fewer CAG repeats and, subsequently, a less rapid pathological decline. Compared to the R6/2 line, fewer descriptions of the progressive pathologies exhibited by R6/1 mice exist. The association between the molecular and cellular neuropathology with brain atrophy, and with the development of behavioral phenotypes remains poorly understood in many models of HD. In attempt to link these factors in the R6/1 mouse line, we have performed detailed assessments of behavior and of regional brain abnormalities determined through longitudinal, in vivo magnetic resonance imaging (MRI, as well as an end-stage, ex vivo MRI study and histological assessment. We found progressive decline in both motor and non-motor related behavioral tasks in R6/1 mice, first evident at 11 weeks of age. Regional brain volumes were generally unaffected at 9 weeks, but by 17 weeks there was significant grey matter atrophy. This age-related brain volume loss was validated using a more precise, semi-automated Tensor Based morphometry assessment. As well as these clear progressive phenotypes, mutant HTT (mHTT protein, the hallmark of HD molecular pathology, was widely distributed throughout the R6/1 brain and was accompanied by neuronal loss. Despite these seemingly concomitant, robust pathological phenotypes, there appeared to be little correlation between the three main outcome measures: behavioral performance, MRI-detected brain atrophy and histopathology. In conclusion, R6/1 mice exhibit many features of HD, but the underlying mechanisms driving these clear behavioral disturbances and the brain volume loss, still remain unclear.

  16. The Unexpected Effects of Beneficial and Adverse Social Experiences during Adolescence on Anxiety and Aggression and Their Modulation by Genotype

    Science.gov (United States)

    Meyer, Neele; Richter, S. Helene; Schreiber, Rebecca S.; Kloke, Vanessa; Kaiser, Sylvia; Lesch, Klaus-Peter; Sachser, Norbert

    2016-01-01

    Anxiety and aggression are part of the behavioral repertoire of humans and animals. However, in their exaggerated form both can become maladaptive and result in psychiatric disorders. On the one hand, genetic predisposition has been shown to play a crucial modulatory role in anxiety and aggression. On the other hand, social experiences have been implicated in the modulation of these traits. However, so far, mainly experiences in early life phases have been considered crucial for shaping anxiety-like and aggressive behavior, while the phase of adolescence has largely been neglected. Therefore, the aim of the present study was to elucidate how levels of anxiety-like and aggressive behavior are shaped by social experiences during adolescence and serotonin transporter (5-HTT) genotype. For this purpose, male mice of a 5-HTT knockout mouse model including all three genotypes (wildtype, heterozygous and homozygous 5-HTT knockout mice) were either exposed to an adverse social situation or a beneficial social environment during adolescence. This was accomplished in a custom-made cage system where mice experiencing the adverse environment were repeatedly introduced to the territory of a dominant opponent but had the possibility to escape to a refuge cage. Mice encountering beneficial social conditions had free access to a female mating partner. Afterwards, anxiety-like and aggressive behavior was assessed in a battery of tests. Surprisingly, unfavorable conditions during adolescence led to a decrease in anxiety-like behavior and an increase in exploratory locomotion. Additionally, aggressive behavior was augmented in animals that experienced social adversity. Concerning genotype, homozygous 5-HTT knockout mice were more anxious and less aggressive than heterozygous 5-HTT knockout and wildtype mice. In summary, adolescence is clearly an important phase in which anxiety-like and aggressive behavior can be shaped. Furthermore, it seems that having to cope with challenge during

  17. Application of hybrid organic/inorganic polymers as coatings on metallic substrates

    Science.gov (United States)

    Augustinho, T. R.; Motz, G.; Ihlow, S.; Machado, R. A. F.

    2016-09-01

    Acrylic polymers, particularly poly (methyl methacrylate) (PMMA), have certain specific properties, such as good film formation, transparency, and good mechanical properties, which have been widely used in paints, coatings and adhesives. However, the limited chemical and physical stability of these pure polymers limits their applications when exposed to hostile conditions, as in ship hulls, for example. A suitable way to enhance PMMA properties is the addition of silicon polymers with very good protective characteristics. In this study, a PMMA and HTT 1800 (commercial silazane) copolymer were applied on metallic substrate and compared to pure PMMA and HTT 1800. All the materials were applied as coatings. They were applied on stainless steel via dip-coating to investigate the coating properties. Thermal cycling was employed to analyze coating durability at high temperatures (50 °C to 600 °C). Optical microscopy (OM) and scanning electron microscopy (SEM) were used to characterize the coated surfaces, and the adhesion of pure PMMA, pure HTT 1800 and PMMA/HTT 1800 coatings on metallic substrate was investigated by Cross-Cut-Test (ASTM D 3359). The sessile drop method was used to determine the contact angle. PMMA coatings presented complete degradation from 250 °C, while hybrid coatings of PMMA and HTT 1800 have good protection until 400 °C. The adherence of the coating on metallic substrate showed improvement in all synthesized materials when compared to pure PMMA, obtaining the best adherence possible. The contact angle test showed that the hydrophobicity of the hybrid coatings is higher than that of the pure coatings.

  18. Functions of huntingtin in germ layer specification and organogenesis.

    Directory of Open Access Journals (Sweden)

    Giang D Nguyen

    Full Text Available Huntington's disease (HD is a neurodegenerative disease caused by abnormal polyglutamine expansion in the huntingtin protein (Htt. Although both Htt and the HD pathogenic mutation (mHtt are implicated in early developmental events, their individual involvement has not been adequately explored. In order to better define the developmental functions and pathological consequences of the normal and mutant proteins, respectively, we employed embryonic stem cell (ESC expansion, differentiation and induction experiments using huntingtin knock-out (KO and mutant huntingtin knock-in (Q111 mouse ESC lines. In KO ESCs, we observed impairments in the spontaneous specification and survival of ectodermal and mesodermal lineages during embryoid body formation and under inductive conditions using retinoic acid and Wnt3A, respectively. Ablation of BAX improves cell survival, but failed to correct defects in germ layer specification. In addition, we observed ensuing impairments in the specification and maturation of neural, hepatic, pancreatic and cardiomyocyte lineages. These developmental deficits occurred in concert with alterations in Notch, Hes1 and STAT3 signaling pathways. Moreover, in Q111 ESCs, we observed differential developmental stage-specific alterations in lineage specification and maturation. We also observed changes in Notch/STAT3 expression and activation. Our observations underscore essential roles of Htt in the specification of ectoderm, endoderm and mesoderm, in the specification of neural and non-neural organ-specific lineages, as well as cell survival during early embryogenesis. Remarkably, these developmental events are differentially deregulated by mHtt, raising the possibility that HD-associated early developmental impairments may contribute not only to region-specific neurodegeneration, but also to non-neural co-morbidities.

  19. The unexpected effects of beneficial and adverse social experiences during adolescence on anxiety and aggression and their modulation by genotype.

    Directory of Open Access Journals (Sweden)

    Neele eMeyer

    2016-05-01

    Full Text Available Anxiety and aggression are part of the behavioral repertoire of humans and animals. However, in their exaggerated form both can become maladaptive and result in psychiatric disorders. On the one hand, genetic predisposition has been shown to play a crucial modulatory role in anxiety and aggression. On the other hand, social experiences have been implicated in the modulation of these traits. However, so far, mainly experiences in early life phases have been considered crucial for shaping anxiety-like and aggressive behavior while the phase of adolescence has mainly been neglected. Therefore, the aim of the present study was to elucidate how levels of anxiety-like and aggressive behavior are shaped by social experiences during adolescence and serotonin transporter (5-HTT genotype. For this purpose, male mice of a 5-HTT knockout mouse model including all three genotypes (wildtype, heterozygous and homozygous 5-HTT knockout mice were either exposed to an adverse social situation or a beneficial social environment during adolescence. This was accomplished in a custom-made cage system where mice experiencing the adverse environment were repeatedly introduced to the territory of a dominant opponent but had the possibility to escape to a refuge cage. Mice encountering beneficial social conditions had free access to a female mating partner. Afterwards, anxiety-like and aggressive behavior was assessed in a battery of tests. Surprisingly, unfavorable conditions during adolescence led to a decrease in anxiety-like behavior and an increase in exploratory locomotion. Additionally, aggressive behavior was augmented in animals that experienced social adversity. Concerning genotype, homozygous 5-HTT knockout mice were more anxious and less aggressive than heterozygous 5-HTT knockout and wildtype mice. In summary, adolescence is clearly an important phase in which anxiety-like and aggressive behavior can be shaped. Furthermore, it seems that having to cope with

  20. Huntingtin interacting proteins are genetic modifiers of neurodegeneration.

    Directory of Open Access Journals (Sweden)

    Linda S Kaltenbach

    2007-05-01

    Full Text Available Huntington's disease (HD is a fatal neurodegenerative condition caused by expansion of the polyglutamine tract in the huntingtin (Htt protein. Neuronal toxicity in HD is thought to be, at least in part, a consequence of protein interactions involving mutant Htt. We therefore hypothesized that genetic modifiers of HD neurodegeneration should be enriched among Htt protein interactors. To test this idea, we identified a comprehensive set of Htt interactors using two complementary approaches: high-throughput yeast two-hybrid screening and affinity pull down followed by mass spectrometry. This effort led to the identification of 234 high-confidence Htt-associated proteins, 104 of which were found with the yeast method and 130 with the pull downs. We then tested an arbitrary set of 60 genes encoding interacting proteins for their ability to behave as genetic modifiers of neurodegeneration in a Drosophila model of HD. This high-content validation assay showed that 27 of 60 orthologs tested were high-confidence genetic modifiers, as modification was observed with more than one allele. The 45% hit rate for genetic modifiers seen among the interactors is an order of magnitude higher than the 1%-4% typically observed in unbiased genetic screens. Genetic modifiers were similarly represented among proteins discovered using yeast two-hybrid and pull-down/mass spectrometry methods, supporting the notion that these complementary technologies are equally useful in identifying biologically relevant proteins. Interacting proteins confirmed as modifiers of the neurodegeneration phenotype represent a diverse array of biological functions, including synaptic transmission, cytoskeletal organization, signal transduction, and transcription. Among the modifiers were 17 loss-of-function suppressors of neurodegeneration, which can be considered potential targets for therapeutic intervention. Finally, we show that seven interacting proteins from among 11 tested were able to

  1. Electron spin resonance and its application to heat treated carbonaceous materials

    International Nuclear Information System (INIS)

    Emmerich, Francisco Guilherme

    1993-01-01

    This work presents the basic characteristics of the electron spin resonance technique, also called paramagnetic resonance, being discussed its application to heat treated carbonaceous materials. In the low heat treatment temperature (HTT) range (below 700 deg C) the organic free radical are the predominant unpaired spin center, which play a key role in the process of carbonization and meso phase formation. At higher temperatures, it is possible to make correlations between the low H T T range and the high HTT range (above 130 deg C), where the predominant unpaired spin center are the free charge carriers (free electrons) of the graphite like crystallites of the material, which are formed by the carbonization process. (author)

  2. Glucose transportation in the brain and its impairment in Huntington disease: one more shade of the energetic metabolism failure?

    Science.gov (United States)

    Morea, Veronica; Bidollari, Eris; Colotti, Gianni; Fiorillo, Annarita; Rosati, Jessica; De Filippis, Lidia; Squitieri, Ferdinando; Ilari, Andrea

    2017-07-01

    Huntington's disease (HD) or Huntington's chorea is the most common inherited, dominantly transmitted, neurodegenerative disorder. It is caused by increased CAG repeats number in the gene coding for huntingtin (Htt) and characterized by motor, behaviour and psychiatric symptoms, ultimately leading to death. HD patients also exhibit alterations in glucose and energetic metabolism, which result in pronounced weight loss despite sustained calorie intake. Glucose metabolism decreases in the striatum of all the subjects with mutated Htt, but affects symptom presentation only when it drops below a specific threshold. Recent evidence points at defects in glucose uptake by the brain, and especially by neurons, as a relevant component of central glucose hypometabolism in HD patients. Here we review the main features of glucose metabolism and transport in the brain in physiological conditions and how these processes are impaired in HD, and discuss the potential ability of strategies aimed at increasing intracellular energy levels to counteract neurological and motor degeneration in HD patients.

  3. Simvastatin mitigates functional and structural impairment of lung and right ventricle in a rat model of cigarette smoke-induced COPD.

    Science.gov (United States)

    Wang, Yajie; Jiang, Xue; Zhang, Lihai; Wang, Lihong; Li, Zhu; Sun, Wuzhuang

    2014-01-01

    This study is conducted to investigate an effect of simvastatin on cigarette smoke-induced COPD. Rats were exposed to air (control) and cigarette smoke (smoking) in presence and absence of simvastatin. Heart and lung tissues were harvested for histopathologic and morphometric analysis. Body weight of rat, mean liner intercept (MLI), mean alveolar number (MAN), lung function test, mean pulmonary artery pressure (mPAP), right ventricular hypertrophy index (RVHI) and 5-HTT level in serum and BALF were examined in experimental rats, respectively. Application of simvastatin mitigated peribronchiolar inflammation and pulmonary bullae formed in the smoke-exposed lungs with weight gain as compared to the smoking rats (P reversal of lung function decline (all P reverses lung function decline and attenuates structural impairments of lung and right ventricle possibly through reducing 5-HTT content in the model of COPD.

  4. Interaction between genetic polymorphisms and stressful life events in first episode depression

    DEFF Research Database (Denmark)

    Bukh, Jens Drachmann; Bock, Camilla; Vinberg, Maj

    2009-01-01

    of depression among participants. METHOD: We applied a case-only design, including 290 ethnically homogeneous patients suffering exclusively from first episode depression. Psychiatric mo-morbidity, personality traits and disorders and stressful life events in a six months period preceding onset of depression......BACKGROUND: A polymorphism in the serotonin transporter (5-HTT) gene seems to moderate the influence of stressful life events on depression. However, the results from previous studies of gene-environment interactions in depression are inconsistent and might be confounded by the history......A, 2A, and 2C. RESULTS: The low activity variants of the 5-HTT-linked polymorphic region in the serotonin transporter gene and the Met-allele of a single nucleotide polymorphism (Val66Met) in the gene encoding brain derived neurotrophic factor were independently associated with the presence...

  5. A probabilistic approach to delineating functional brain regions

    DEFF Research Database (Denmark)

    Kalbitzer, Jan; Svarer, Claus; Frokjaer, Vibe G

    2009-01-01

    The purpose of this study was to develop a reliable observer-independent approach to delineating volumes of interest (VOIs) for functional brain regions that are not identifiable on structural MR images. The case is made for the raphe nuclei, a collection of nuclei situated in the brain stem known...... to be densely packed with serotonin transporters (5-hydroxytryptaminic [5-HTT] system). METHODS: A template set for the raphe nuclei, based on their high content of 5-HTT as visualized in parametric (11)C-labeled 3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile PET images, was created for 10...... healthy subjects. The templates were subsequently included in the region sets used in a previously published automatic MRI-based approach to create an observer- and activity-independent probabilistic VOI map. The probabilistic map approach was tested in a different group of 10 subjects and compared...

  6. Thermal conductivity improvement in carbon nanoparticle doped PAO oil: An experimental study

    Science.gov (United States)

    Shaikh, S.; Lafdi, K.; Ponnappan, R.

    2007-03-01

    The present work involves a study on the thermal conductivity of nanoparticle-oil suspensions for three types of nanoparticles, namely, carbon nanotubes (CNTs), exfoliated graphite (EXG), and heat treated nanofibers (HTT) with PAO oil as the base fluid. To accomplish the above task, an experimental analysis is performed using a modern light flash technique (LFA 447) for measuring the thermal conductivity of the three types of nanofluids, for different loading of nanoparticles. The experimental results show a similar trend as observed in literature for nanofluids with a maximum enhancement of approximately 161% obtained for the CNT-PAO oil suspension. The overall percent enhancements for different volume fractions of the nanoparticles are highest for the CNT-based nanofluid, followed by the EXG and the HTT. The findings from this study for the three different types of carbon nanoparticles can have great potential in the field of thermal management.

  7. Electron spin resonance and its application to heat treated carbonaceous materials; A ressonancia de spin eletronico e sua aplicacao aos materiais carbonosos tratados termicamente

    Energy Technology Data Exchange (ETDEWEB)

    Emmerich, Francisco Guilherme [Espirito Santo Univ., Vitoria, ES (Brazil). Laboratorio de Materiais Carbonosos e Plasma Termico

    1994-12-31

    This work presents the basic characteristics of the electron spin resonance technique, also called paramagnetic resonance, being discussed its application to heat treated carbonaceous materials. In the low heat treatment temperature (HTT) range (below 700 deg C) the organic free radical are the predominant unpaired spin center, which play a key role in the process of carbonization and meso phase formation. At higher temperatures, it is possible to make correlations between the low H T T range and the high HTT range (above 130 deg C), where the predominant unpaired spin center are the free charge carriers (free electrons) of the graphite like crystallites of the material, which are formed by the carbonization process. (author) 10 refs., 3 figs.

  8. Tics as an initial manifestation of juvenile Huntington's disease: case report and literature review.

    Science.gov (United States)

    Cui, Shi-Shuang; Ren, Ru-Jing; Wang, Ying; Wang, Gang; Chen, Sheng-Di

    2017-08-08

    Huntington's disease (HD) is an autosomal dominant disorder, typically characterized by chorea due to a trinucleotide repeat expansion in the HTT gene, although the clinical manifestations of patients with juvenile HD (JHD) are atypical. A 17-year-old boy with initial presentation of tics attended our clinic and his DNA analysis demonstrated mutation in the HTT gene (49 CAG repeats). After treatment, his symptoms improved. Furthermore, we performed literature review through searching the databases and summarized clinical features in 33 JHD patients. The most prevalent symptoms are ataxia, and two cases reported that tics as initial and prominent manifestation in JHD. Among them, 88% patients carried CAG repeats beyond 60 and most of them have family history. This case here illustrates the variable range of clinical symptoms of JHD and the necessity of testing for the HD mutation in young patients with tics with symptoms unable to be explained by Tourette's syndrome (TS).

  9. Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

    OpenAIRE

    Hensman Moss, Davina J; Pardinas, Antonio; Langbehn, Douglas; Lo, Kitty; Leavitt, Blair R; Roos, Raymund; Durr, Alexandra; Mead, Simon; Holmans, Peter; Jones, Lesley; Tabrizi, Sarah J; Coleman, A; Santos, R Dar; Decolongon, J; Sturrock, A

    2017-01-01

    Background\\ud \\ud Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure.\\ud \\ud Methods\\ud \\ud We generated a progression score on the basis of principal ...

  10. Exploring Anthropology’s Value to Military Strategy Since 2000

    Science.gov (United States)

    2014-04-01

    anthropological study of military culture, MA2 : anthropological study for the military, in endeavors such as the Human Terrain System concept, where teams of...Anthropology The AAA has judged MA2 as the least ethical category of military anthropology by means of its code of ethics, CEAUSSIC reports, and...open debates on its blog. The lighting rod system most associated with MA2 is the Human Terrain Team, (HTT) employed under the Human Terrain System

  11. PPARGC1A/PGC-1α, TFEB and enhanced proteostasis in Huntington disease: Defining regulatory linkages between energy production and protein–organelle quality control

    OpenAIRE

    La Spada, Albert R.

    2012-01-01

    Huntington disease (HD) results from CAG repeats that encode expanded polyglutamine tracts in the HTT/huntingtin protein. HD belongs to a large category of inherited and sporadic neurodegenerative disorders in which production of a misfolded protein initiates the pathogenic cascade. Previous studies have shown that misfolded proteins become resistant to cellular protein turnover pathways by eluding and disabling the ubiquitin-proteasome system (UPS) and autophagy-lysosome pathway. Based upon ...

  12. Inhibition of serotonin but not norepinephrine transport during development produces delayed, persistent perturbations of emotional behaviors in mice.

    Science.gov (United States)

    Ansorge, Mark S; Morelli, Emanuela; Gingrich, Jay A

    2008-01-02

    Serotonin (5-HT) acts as a neurotransmitter, but also modulates brain maturation during early development. The demonstrated influence of genetic variants on brain function, personality traits, and susceptibility to neuropsychiatric disorders suggests a critical importance of developmental mechanisms. However, little is known about how and when developmentally perturbed 5-HT signaling affects circuitry and resulting behavior. The 5-HT transporter (5-HTT) is a key regulator of extracellular 5-HT levels and we used pharmacologic strategies to manipulate 5-HTT function during development and determine behavioral consequences. Transient exposure to the 5-HTT inhibitors fluoxetine, clomipramine, and citalopram from postnatal day 4 (P4) to P21 produced abnormal emotional behaviors in adult mice. Similar treatment with the norepinephrine transporter (NET) inhibitor, desipramine, did not adversely affect adult behavior, suggesting that 5-HT and norepinephrine (NE) do not share the same effects on brain development. Shifting our period of treatment/testing to P90/P185 failed to mimic the effect of earlier exposure, demonstrating that 5-HT effects on adult behavior are developmentally specific. We have hypothesized that early-life perturbations of 5-HT signaling affect corticolimbic circuits that do not reach maturity until the peri-adolescent period. In support of this idea, we found that abnormal behaviors resulting from postnatal fluoxetine exposure have a post-pubescent onset and persist long after reaching adult age. A better understanding of the underlying 5-HT sensitive circuits and how they are perturbed should lead to new insights into how various genetic polymorphisms confer their risk to carriers. Furthermore, these studies should help determine whether in utero exposure to 5-HTT blocking drugs poses a risk for behavioral abnormalities in later life.

  13. 2009 Biometrics Conference

    Science.gov (United States)

    2009-01-28

    gov/fpkia/crosscert htm. . . – Verisign – Wells Fargo CSPs on Other Bridges at eAuth-4 (Certipath only today) htt // ti th / ki t htp : www.cer pa .com...Center (TEDAC) provided latent fingerprints recovered from an Improvised Explosive Device (IED) to BFC BFC manually processed latent prints...to original fingerprint. If no match manual review; may not test , . Other action may be taken. Copyright© 2009, Graduate Management Admission

  14. Stemcell Information: SKIP000389 [SKIP Stemcell Database[Archive

    Lifescience Database Archive (English)

    Full Text Available +5ng/ml human bFGF ... Riken BioResource Center 理化学研究所バイオリソースセンター Riken BioResource Center 理化学...研究所バイオリソースセンター Available Riken BioResource Center 理化学研究所バイオリソースセンター htt

  15. Inhibition of serotonin transporters disrupts the enhancement of fear memory extinction by 3,4-methylenedioxymethamphetamine (MDMA).

    Science.gov (United States)

    Young, Matthew B; Norrholm, Seth D; Khoury, Lara M; Jovanovic, Tanja; Rauch, Sheila A M; Reiff, Collin M; Dunlop, Boadie W; Rothbaum, Barbara O; Howell, Leonard L

    2017-10-01

    3,4-Methylenedioxymethamphetamine (MDMA) persistently improves symptoms of post-traumatic stress disorder (PTSD) when combined with psychotherapy. Studies in rodents suggest that these effects can be attributed to enhancement of fear memory extinction. Therefore, MDMA may improve the effects of exposure-based therapy for PTSD, particularly in treatment-resistant patients. However, given MDMA's broad pharmacological profile, further investigation is warranted before moving to a complex clinical population. We aimed to inform clinical research by providing a translational model of MDMA's effect, and elucidating monoaminergic mechanisms through which MDMA enhances fear extinction. We explored the importance of monoamine transporters targeted by MDMA to fear memory extinction, as measured by reductions in conditioned freezing and fear-potentiated startle (FPS) in mice. Mice were treated with selective inhibitors of individual monoamine transporters prior to combined MDMA treatment and fear extinction training. MDMA enhanced the lasting extinction of FPS. Acute and chronic treatment with a 5-HT transporter (5-HTT) inhibitor blocked MDMA's effect on fear memory extinction. Acute inhibition of dopamine (DA) and norepinephrine (NE) transporters had no effect. 5-HT release alone did not enhance extinction. Blockade of MDMA's effect by 5-HTT inhibition also downregulated 5-HT 2A -mediated behavior, and 5-HT 2A antagonism disrupted MDMA's effect on extinction. We validate enhancement of fear memory extinction by MDMA in a translational behavioral model, and reveal the importance of 5-HTT and 5-HT 2A receptors to this effect. These observations support future clinical research of MDMA as an adjunct to exposure therapy, and provide important pharmacological considerations for clinical use in a population frequently treated with 5-HTT inhibitors.

  16. Use of anti-depressants and the risk of fracture of the hip or femur.

    Science.gov (United States)

    van den Brand, M W M; Pouwels, S; Samson, M M; van Staa, T P; Thio, B; Cooper, C; Leufkens, H G M; Egberts, A C G; Verhaar, H J J; de Vries, F

    2009-10-01

    Anti-depressants are used largely, but have serious side effects. We show that both selective serotonin re-uptake inhibitors (SSRIs) and tricyclic anti-depressants (TCAs) increase the risk of hip/femur fracture and that this risk is time related and depends on the degree of serotonin transporter inhibition. This should be considered when prescribing anti-depressants to patients. Anti-depressants are known to have serious side effects. We examined the association between the use of anti-depressants and the risk of hip/femur fractures with a special focus on the relation with the degree of 5-hydroxytryptamine transporter (5-HTT) inhibition and the duration of use. A case-control study was conducted within the Dutch PHARMO-RLS database. Cases (n = 6,763) were adult patients with a first hip/femur fracture during the study period. For each case, four controls (n = 26341) were matched by age, gender and geographic region. The risk of hip/femur fracture increased with current use of SSRIs (adjusted odds ratio (OR(adj)) 2.35 [95% confidence interval (CI) 1.94-2.84]) and TCAs (ORadj 1.76 [95% CI 1.45-2.15]). The risk of hip/femur fracture declined rapidly after discontinuation of use. The risk of hip/femur fracture increased as the degree of 5-HTT inhibition of all anti-depressants increased from OR(adj) 1.64 [95% CI 1.14-2.35] for drugs with low 5-HTT inhibition to OR(adj) 2.31 [95% CI 1.94-2.76] for those with high 5-HTT inhibiting properties. Current use of both SSRIs and TCAs increase hip/femur fracture risk. Further studies are needed to elucidate the mechanistic pathways and the relation with the underlying pathophysiology. Until then, the elevated fracture risk should be considered when prescribing anti-depressants.

  17. Human glia can both induce and rescue aspects of disease phenotype in Huntington disease

    DEFF Research Database (Denmark)

    Benraiss, Abdellatif; Wang, Su; Herrlinger, Stephanie

    2016-01-01

    The causal contribution of glial pathology to Huntington disease (HD) has not been heavily explored. To define the contribution of glia to HD, we established human HD glial chimeras by neonatally engrafting immunodeficient mice with mutant huntingtin (mHTT)-expressing human glial progenitor cells...... chimeras are hyperexcitable. Conversely, normal glia can ameliorate disease phenotype in transgenic HD mice, as striatal transplantation of normal glia rescues aspects of electrophysiological and behavioural phenotype, restores interstitial potassium homeostasis, slows disease progression and extends...

  18. Pathophysiology and molecular basis of selected metabolic abnormalities in Huntington’s disease

    Directory of Open Access Journals (Sweden)

    Jolanta Krzysztoń-Russjan

    2016-12-01

    Full Text Available Huntington’s disease (HD is an incurable, devastating neurodegenerative disease with a known genetic background and autosomally dominant inheritance pattern. HTT gene mutation (mHTT is associated with polymorphic fragment elongation above 35 repeats of the CAG triplet. The mHTT product is an altered protein with a poly-Q elongated fragment, with the highest expression determined in the central nervous system (CNS and with differentiated expression outside the CNS. A drastic loss of striatal and deeper layers of the cerebral cortex neurons was determined in the CNS, but muscle and body weight mass loss with dysfunction of many organs was also observed. HD symptoms include neurological disturbances, such as choreal movements with dystonia, speech and swallowing impairments, and additionally a variety of psychiatric and behavioral symptoms with cognitive decline have been described.They are the result of disturbances of several cellular pathways related to signal transmission, mitochondrial dysfunction and energy metabolism impairment shown by gene and protein expression and alteration of their functions. Impairment of energy processes demonstrated by a decrease of ATP production and increase of oxidative stress markers was determined in- and outside of the CNS in glycolysis, the Krebs cycle and the electron transport chain. A correlation between the increase of energy metabolism impairment level and the increase in number of CAG repeats in HTT has often been described. The energy metabolism study is an initial stage of sensitive biomarkers and a new therapeutic investigative option for early application in order to inhibit pathological processes in HD.Identification of pathological changes outside the CNS requires a reevaluation of diagnostic and therapeutic rules in HD.

  19. Pathophysiology and molecular basis of selected metabolic abnormalities in Huntington's disease.

    Science.gov (United States)

    Krzysztoń-Russjan, Jolanta

    2016-12-30

    Huntington's disease (HD) is an incurable, devastating neurodegenerative disease with a known genetic background and autosomally dominant inheritance pattern. HTT gene mutation (mHTT) is associated with polymorphic fragment elongation above 35 repeats of the CAG triplet. The mHTT product is an altered protein with a poly-Q elongated fragment, with the highest expression determined in the central nervous system (CNS) and with differentiated expression outside the CNS. A drastic loss of striatal and deeper layers of the cerebral cortex neurons was determined in the CNS, but muscle and body weight mass loss with dysfunction of many organs was also observed. HD symptoms include neurological disturbances, such as choreal movements with dystonia, speech and swallowing impairments, and additionally a variety of psychiatric and behavioral symptoms with cognitive decline have been described. They are the result of disturbances of several cellular pathways related to signal transmission, mitochondrial dysfunction and energy metabolism impairment shown by gene and protein expression and alteration of their functions. Impairment of energy processes demonstrated by a decrease of ATP production and increase of oxidative stress markers was determined in- and outside of the CNS in glycolysis, the Krebs cycle and the electron transport chain. A correlation between the increase of energy metabolism impairment level and the increase in number of CAG repeats in HTT has often been described. The energy metabolism study is an initial stage of sensitive biomarkers and a new therapeutic investigative option for early application in order to inhibit pathological processes in HD. Identification of pathological changes outside the CNS requires a reevaluation of diagnostic and therapeutic rules in HD.

  20. The study of genetic polymorphisms related to serotonin in Alzheimer's disease: a new perspective in a heterogenic disorder

    Directory of Open Access Journals (Sweden)

    Oliveira J.R.M.

    1999-01-01

    Full Text Available Genetic and environmental factors have been implicated in the development of Alzheimer's disease (AD, the most common form of dementia in the elderly. Mutations in 3 genes mapped on chromosomes 21, 14 and 1 are related to the rare early onset forms of AD while the e4 allele of the apolipoprotein E (APOE gene (on chromosome 19 is the major susceptibility locus for the most common late onset AD (LOAD. Serotonin (5-hydroxytryptamine or 5-HT is a key neurotransmitter implicated in the control of mood, sleep, appetite and a variety of traits and behaviors. Recently, a polymorphism in the transcriptional control region upstream of the 5-HT transporter (5-HTT gene has been studied in several psychiatric diseases and personality traits. It has been demonstrated that the short variant(s of this 5-HTT gene-linked polymorphic region (5-HTTLPR is associated with a different transcriptional efficiency of the 5-HTT gene promoter resulting in decreased 5-HTT expression and 5-HT uptake in lymphocytes. An increased frequency of this 5-HTTLPR short variant polymorphism in LOAD was recently reported. In addition, another common polymorphic variation in the 5-HT2A and 5-HT2C serotonin receptor genes previously analyzed in schizophrenic patients was associated with auditory and visual hallucinations in AD. These observations suggest that the involvement of the serotonin pathway might provide an explanation for some aspects of the affective symptoms commonly observed in AD patients. In summary, research on genetic polymorphisms related to AD and involved in receptors, transporter proteins and the enzymatic machinery of serotonin might enhance our understanding of this devastating neurodegenerative disorder.

  1. Transcriptomic study to understand thermal adaptation in a high temperature-tolerant strain of Pyropia haitanensis.

    Science.gov (United States)

    Wang, Wenlei; Teng, Fei; Lin, Yinghui; Ji, Dehua; Xu, Yan; Chen, Changsheng; Xie, Chaotian

    2018-01-01

    Pyropia haitanensis, a high-yield commercial seaweed in China, is currently undergoing increasing levels of high-temperature stress due to gradual global warming. The mechanisms of plant responses to high temperature stress vary with not only plant type but also the degree and duration of high temperature. To understand the mechanism underlying thermal tolerance in P. haitanensis, gene expression and regulation in response to short- and long-term temperature stresses (SHS and LHS) was investigated by performing genome-wide high-throughput transcriptomic sequencing for a high temperature tolerant strain (HTT). A total of 14,164 differential expression genes were identified to be high temperature-responsive in at least one time point by high-temperature treatment, representing 41.10% of the total number of unigenes. The present data indicated a decrease in the photosynthetic and energy metabolic rates in HTT to reduce unnecessary energy consumption, which in turn facilitated in the rapid establishment of acclimatory homeostasis in its transcriptome during SHS. On the other hand, an increase in energy consumption and antioxidant substance activity was observed with LHS, which apparently facilitates in the development of resistance against severe oxidative stress. Meanwhile, ubiquitin-mediated proteolysis, brassinosteroids, and heat shock proteins also play a vital role in HTT. The effects of SHS and LHS on the mechanism of HTT to resist heat stress were relatively different. The findings may facilitate further studies on gene discovery and the molecular mechanisms underlying high-temperature tolerance in P. haitanensis, as well as allow improvement of breeding schemes for high temperature-tolerant macroalgae that can resist global warming.

  2. EMQN/CMGS best practice guidelines for the molecular genetic testing of Huntington disease

    OpenAIRE

    Losekoot, Monique; van Belzen, Martine J; Seneca, Sara; Bauer, Peter; Stenhouse, Susan A R; Barton, David E

    2012-01-01

    Huntington disease (HD) is caused by the expansion of an unstable polymorphic trinucleotide (CAG)n repeat in exon 1 of the HTT gene, which translates into an extended polyglutamine tract in the protein. Laboratory diagnosis of HD involves estimation of the number of CAG repeats. Molecular genetic testing for HD is offered in a wide range of laboratories both within and outside the European community. In order to measure the quality and raise the standard of molecular genetic testing in these ...

  3. Perturbation with intrabodies reveals that calpain cleavage is required for degradation of huntingtin exon 1.

    Directory of Open Access Journals (Sweden)

    Amber L Southwell

    2011-01-01

    Full Text Available Proteolytic processing of mutant huntingtin (mHtt, the protein that causes Huntington's disease (HD, is critical for mHtt toxicity and disease progression. mHtt contains several caspase and calpain cleavage sites that generate N-terminal fragments that are more toxic than full-length mHtt. Further processing is then required for the degradation of these fragments, which in turn, reduces toxicity. This unknown, secondary degradative process represents a promising therapeutic target for HD.We have used intrabodies, intracellularly expressed antibody fragments, to gain insight into the mechanism of mutant huntingtin exon 1 (mHDx-1 clearance. Happ1, an intrabody recognizing the proline-rich region of mHDx-1, reduces the level of soluble mHDx-1 by increasing clearance. While proteasome and macroautophagy inhibitors reduce turnover of mHDx-1, Happ1 is still able to reduce mHDx-1 under these conditions, indicating Happ1-accelerated mHDx-1 clearance does not rely on these processes. In contrast, a calpain inhibitor or an inhibitor of lysosomal pH block Happ1-mediated acceleration of mHDx-1 clearance. These results suggest that mHDx-1 is cleaved by calpain, likely followed by lysosomal degradation and this process regulates the turnover rate of mHDx-1. Sequence analysis identifies amino acid (AA 15 as a potential calpain cleavage site. Calpain cleavage of recombinant mHDx-1 in vitro yields fragments of sizes corresponding to this prediction. Moreover, when the site is blocked by binding of another intrabody, V(L12.3, turnover of soluble mHDx-1 in living cells is blocked.These results indicate that calpain-mediated removal of the 15 N-terminal AAs is required for the degradation of mHDx-1, a finding that may have therapeutic implications.

  4. Assembly of Huntingtin headpiece into α-helical bundles.

    Science.gov (United States)

    Ozgur, Beytullah; Sayar, Mehmet

    2017-05-24

    Protein aggregation is a hallmark of neurodegenerative disorders. In this group of brain-related disorders, a disease-specific "host" protein or fragment misfolds and adopts a metastatic, aggregate-prone conformation. Often, this misfolded conformation is structurally and thermodynamically different from its native state. Intermolecular contacts, which arise in this non-native state, promote aggregation. In this regard, understanding the molecular principles and mechanisms that lead to the formation of such a non-native state and further promote the formation of the critical nucleus for fiber growth is essential. In this study, the authors analyze the aggregation propensity of Huntingtin headpiece (htt NT ), which is known to facilitate the polyQ aggregation, in relation to the helix mediated aggregation mechanism proposed by the Wetzel group. The authors demonstrate that even though htt NT displays a degenerate conformational spectrum on its own, interfaces of macroscopic or molecular origin can promote the α-helix conformation, eliminating all other alternatives in the conformational phase space. Our findings indicate that htt NT molecules do not have a strong orientational preference for parallel or antiparallel orientation of the helices within the aggregate. However, a parallel packed bundle of helices would support the idea of increased polyglutamine concentration, to pave the way for cross-β structures.

  5. Characterisation of the ruminal fermentation and microbiome in lambs supplemented with hydrolysable and condensed tannins.

    Science.gov (United States)

    Salami, Saheed A; Valenti, Bernardo; Bella, Marco; O'Grady, Michael N; Luciano, Giuseppe; Kerry, Joseph P; Jones, Eleanor; Priolo, Alessandro; Newbold, Charles J

    2018-05-01

    This study characterised the response of ruminal fermentation and the rumen microbiome in lambs fed commercial vegetal sources of hydrolysable tannins (HT) and condensed tannins (CT). Forty-four lambs (19.56 ± 2.06 kg) were randomly assigned to either a concentrate diet (CON, n = 8) or CON supplemented with 4% of two HT [chestnut (Castanea sativa, HT-c) and tara (Caesalpinia spinosa, HT-t)] and CT [mimosa (Acacia negra, CT-m) and gambier (Uncaria gambir, CT-g)] extracts (all, n = 9) for 75 days pre-slaughter. Tannin supplementation did not influence ruminal fermentation traits. Quantitative PCR demonstrated that tannins did not affect the absolute abundance of ruminal bacteria or fungi. However, CT-m (-12.8%) and CT-g (-11.5%) significantly reduced the abundance of methanogens, while HT-t (-20.7%) and CT-g (-20.8%) inhibited protozoal abundance. Ribosomal amplicon sequencing revealed that tannins caused changes in the phylogenetic structure of the bacterial and methanogen communities. Tannins inhibited the fibrolytic bacterium, Fibrobacter and tended to suppress the methanogen genus, Methanosphaera. Results demonstrated that both HT and CT sources could impact the ruminal microbiome when supplemented at 4% inclusion level. HT-t, CT-m and CT-g extracts displayed specific antimicrobial activity against methanogens and protozoa without compromising ruminal fermentation in a long-term feeding trial.

  6. Sensitivity and Specificity of Clinical and Laboratory Otolith Function Tests.

    Science.gov (United States)

    Kumar, Lokesh; Thakar, Alok; Thakur, Bhaskar; Sikka, Kapil

    2017-10-01

    To evaluate clinic based and laboratory tests of otolith function for their sensitivity and specificity in demarcating unilateral compensated complete vestibular deficit from normal. Prospective cross-sectional study. Tertiary care hospital vestibular physiology laboratory. Control group-30 healthy adults, 20-45 years age; Case group-15 subjects post vestibular shwannoma excision or post-labyrinthectomy with compensated unilateral complete audio-vestibular loss. Otolith function evaluation by precise clinical testing (head tilt test-HTT; subjective visual vertical-SVV) and laboratory testing (headroll-eye counterroll-HR-ECR; vesibular evoked myogenic potentials-cVEMP). Sensitivity and specificity of clinical and laboratory tests in differentiating case and control subjects. Measurable test results were universally obtained with clinical otolith tests (SVV; HTT) but not with laboratory tests. The HR-ECR test did not indicate any definitive wave forms in 10% controls and 26% cases. cVEMP responses were absent in 10% controls.HTT test with normative cutoff at 2 degrees deviations from vertical noted as 93.33% sensitive and 100% specific. SVV test with normative cutoff at 1.3 degrees noted as 100% sensitive and 100% specific. Laboratory tests demonstrated poorer specificities owing primarily to significant unresponsiveness in normal controls. Clinical otolith function tests, if conducted with precision, demonstrate greater ability than laboratory testing in discriminating normal controls from cases with unilateral complete compensated vestibular dysfunction.

  7. Hydrothermal treatment and enzymatic hydrolysis of Tamarix ramosissima: evaluation of the process as a conversion method in a biorefinery concept.

    Science.gov (United States)

    Xiao, Ling-Ping; Shi, Zheng-Jun; Xu, Feng; Sun, Run-Cang

    2013-05-01

    The present work investigated the effects of hydrothermal treatment (HTT) of Tamarix ramosissima by determination of sugar and inhibitor formation in the liquid fraction, and chemical and morphological changes of the pretreated solid material coupled with an evaluation of enzymatic hydrolysis. HTT was carried out in a batch reactor system at a maximal temperature (TMAX 180-240 °C) and evaluated for severities logRo ranging from 2.40 to 4.17. The liquid fractions were analyzed by HPLC, GPC, and GC-MS. The morphology and composition of the solid residues were characterized using an array of techniques, such as SEM, XRD, BET surface area, and CP/MAS (13)C NMR. Using a variety of tools, we have developed a better understanding of how HTT process affects biomass structure and cellulose properties that impact on its digestibility. These results provided new insights into the factors limiting enzymatic digestibility and mechanism of biomass deconstruction during hydrothermal process. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

  8. Modulating Neurotrophin Receptor Signaling as a Therapeutic Strategy for Huntington’s Disease

    Science.gov (United States)

    Simmons, Danielle A.

    2017-01-01

    Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder caused by CAG repeat expansions in the IT15 gene which encodes the huntingtin (HTT) protein. Currently, no treatments capable of preventing or slowing disease progression exist. Disease modifying therapeutics for HD would be expected to target a comprehensive set of degenerative processes given the diverse mechanisms contributing to HD pathogenesis including neuroinflammation, excitotoxicity, and transcription dysregulation. A major contributor to HD-related degeneration is mutant HTT-induced loss of neurotrophic support. Thus, neurotrophin (NT) receptors have emerged as therapeutic targets in HD. The considerable overlap between NT signaling networks and those dysregulated by mutant HTT provides strong theoretical support for this approach. This review will focus on the contributions of disrupted NT signaling in HD-related neurodegeneration and how targeting NT receptors to augment pro-survival signaling and/or to inhibit degenerative signaling may combat HD pathologies. Therapeutic strategies involving NT delivery, peptidomimetics, and the targeting of specific NT receptors (e.g., Trks or p75NTR), particularly with small molecule ligands, are discussed. PMID:29254102

  9. The Wnt receptor Ryk reduces neuronal and cell survival capacity by repressing FOXO activity during the early phases of mutant huntingtin pathogenicity.

    Directory of Open Access Journals (Sweden)

    Cendrine Tourette

    2014-06-01

    Full Text Available The Wnt receptor Ryk is an evolutionary-conserved protein important during neuronal differentiation through several mechanisms, including γ-secretase cleavage and nuclear translocation of its intracellular domain (Ryk-ICD. Although the Wnt pathway may be neuroprotective, the role of Ryk in neurodegenerative disease remains unknown. We found that Ryk is up-regulated in neurons expressing mutant huntingtin (HTT in several models of Huntington's disease (HD. Further investigation in Caenorhabditis elegans and mouse striatal cell models of HD provided a model in which the early-stage increase of Ryk promotes neuronal dysfunction by repressing the neuroprotective activity of the longevity-promoting factor FOXO through a noncanonical mechanism that implicates the Ryk-ICD fragment and its binding to the FOXO co-factor β-catenin. The Ryk-ICD fragment suppressed neuroprotection by lin-18/Ryk loss-of-function in expanded-polyQ nematodes, repressed FOXO transcriptional activity, and abolished β-catenin protection of mutant htt striatal cells against cell death vulnerability. Additionally, Ryk-ICD was increased in the nucleus of mutant htt cells, and reducing γ-secretase PS1 levels compensated for the cytotoxicity of full-length Ryk in these cells. These findings reveal that the Ryk-ICD pathway may impair FOXO protective activity in mutant polyglutamine neurons, suggesting that neurons are unable to efficiently maintain function and resist disease from the earliest phases of the pathogenic process in HD.

  10. A broad phenotypic screen identifies novel phenotypes driven by a single mutant allele in Huntington's disease CAG knock-in mice.

    Directory of Open Access Journals (Sweden)

    Sabine M Hölter

    Full Text Available Huntington's disease (HD is an autosomal dominant neurodegenerative disorder caused by the expansion of a CAG trinucleotide repeat in the HTT gene encoding huntingtin. The disease has an insidious course, typically progressing over 10-15 years until death. Currently there is no effective disease-modifying therapy. To better understand the HD pathogenic process we have developed genetic HTT CAG knock-in mouse models that accurately recapitulate the HD mutation in man. Here, we describe results of a broad, standardized phenotypic screen in 10-46 week old heterozygous HdhQ111 knock-in mice, probing a wide range of physiological systems. The results of this screen revealed a number of behavioral abnormalities in HdhQ111/+ mice that include hypoactivity, decreased anxiety, motor learning and coordination deficits, and impaired olfactory discrimination. The screen also provided evidence supporting subtle cardiovascular, lung, and plasma metabolite alterations. Importantly, our results reveal that a single mutant HTT allele in the mouse is sufficient to elicit multiple phenotypic abnormalities, consistent with a dominant disease process in patients. These data provide a starting point for further investigation of several organ systems in HD, for the dissection of underlying pathogenic mechanisms and for the identification of reliable phenotypic endpoints for therapeutic testing.

  11. Coordination preference and magnetic properties of FeII assemblies with a bis-azole bearing 1,2,4-triazole and tetrazole

    Science.gov (United States)

    Naik, Anil D.; Railliet, Antoine P.; Dîrtu, Marinela M.; Garcia, Yann

    2012-03-01

    With a new bis-azole molecular fragment ( Htt) bearing 1,2,4-triazole and tetrazole, a mononuclear complex [Fe(tt)2(H2O)4]·2H2O ( 1), a trinuclear complex [Fe3(tt)6(H2O)6]·2H2O ( 2) and a 1D coordination polymer [Fe(tt)(Htt)2]BF4·2CH3OH ( 3) were obtained by varying reaction conditions. Htt acts either as an anionic or neutral ligand depending upon the reaction medium and pH. Thermal variation of spin states of 1- 3 were investigated in the range 77-300 K by 57Fe Mössbauer spectroscopy. 1 totally remains in high-spin state over the entire temperature range whereas no spin crossover was evidenced in 2. Nearly 1:1 high-spin and low-spin population ratio is found in 3, which remains constant over the entire temperature range investigated.

  12. Genetic exchange in eukaryotes through horizontal transfer: connected by the mobilome.

    Science.gov (United States)

    Wallau, Gabriel Luz; Vieira, Cristina; Loreto, Élgion Lúcio Silva

    2018-01-01

    All living species contain genetic information that was once shared by their common ancestor. DNA is being inherited through generations by vertical transmission (VT) from parents to offspring and from ancestor to descendant species. This process was considered the sole pathway by which biological entities exchange inheritable information. However, Horizontal Transfer (HT), the exchange of genetic information by other means than parents to offspring, was discovered in prokaryotes along with strong evidence showing that it is a very important process by which prokaryotes acquire new genes. For some time now, it has been a scientific consensus that HT events were rare and non-relevant for evolution of eukaryotic species, but there is growing evidence supporting that HT is an important and frequent phenomenon in eukaryotes as well. Here, we will discuss the latest findings regarding HT among eukaryotes, mainly HT of transposons (HTT), establishing HTT once and for all as an important phenomenon that should be taken into consideration to fully understand eukaryotes genome evolution. In addition, we will discuss the latest development methods to detect such events in a broader scale and highlight the new approaches which should be pursued by researchers to fill the knowledge gaps regarding HTT among eukaryotes.

  13. Length and sequence dependence in the association of Huntingtin protein with lipid membranes

    Science.gov (United States)

    Jawahery, Sudi; Nagarajan, Anu; Matysiak, Silvina

    2013-03-01

    There is a fundamental gap in our understanding of how aggregates of mutant Huntingtin protein (htt) with overextended polyglutamine (polyQ) sequences gain the toxic properties that cause Huntington's disease (HD). Experimental studies have shown that the most important step associated with toxicity is the binding of mutant htt aggregates to lipid membranes. Studies have also shown that flanking amino acid sequences around the polyQ sequence directly affect interactions with the lipid bilayer, and that polyQ sequences of greater than 35 glutamine repeats in htt are a characteristic of HD. The key steps that determine how flanking sequences and polyQ length affect the structure of lipid bilayers remain unknown. In this study, we use atomistic molecular dynamics simulations to study the interactions between lipid membranes of varying compositions and polyQ peptides of varying lengths and flanking sequences. We find that overextended polyQ interactions do cause deformation in model membranes, and that the flanking sequences do play a role in intensifying this deformation by altering the shape of the affected regions.

  14. Establishing whether the structural feature controlling the mechanical properties of starch films is molecular or crystalline.

    Science.gov (United States)

    Li, Ming; Xie, Fengwei; Hasjim, Jovin; Witt, Torsten; Halley, Peter J; Gilbert, Robert G

    2015-03-06

    The effects of molecular and crystalline structures on the tensile mechanical properties of thermoplastic starch (TPS) films from waxy, normal, and high-amylose maize were investigated. Starch structural variations were obtained through extrusion and hydrothermal treatment (HTT). The molecular and crystalline structures were characterized using size-exclusion chromatography and X-ray diffractometry, respectively. TPS from high-amylose maize showed higher elongation at break and tensile strength than those from normal maize and waxy maize starches when processed with 40% plasticizer. Within the same amylose content, the mechanical properties were not affected by amylopectin molecular size or the crystallinity of TPS prior to HTT. This lack of correlation between the molecular size, crystallinity and mechanical properties may be due to the dominant effect of the plasticizer on the mechanical properties. Further crystallization of normal maize TPS by HTT increased the tensile strength and Young's modulus, while decreasing the elongation at break. The results suggest that the crystallinity from the remaining ungelatinized starch granules has less significant effect on the mechanical properties than that resulting from starch recrystallization, possibly due to a stronger network from leached-out amylose surrounding the remaining starch granules. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Possible association between serotonin transporter promoter region polymorphism and extremely violent crime in Chinese males.

    Science.gov (United States)

    Liao, Ding-Lieh; Hong, Chen-Jee; Shih, Hao-Ling; Tsai, Shih-Jen

    2004-01-01

    The neurotransmitter, serotonin, has been implicated in aggressive behavior. The serotonin transporter (5-HTT), which reuptakes serotonin into the nerve terminal, plays a critical role in the regulation of serotonergic function. Previous western reports have demonstrated that the low-activity short (S) allele of the 5-HTT gene-linked polymorphic-region (5-HTTLPR) polymorphism is associated with aggressive behavior and associated personality traits. In the present study, we investigated this 5-HTTLPR genetic polymorphism in a group of Chinese males who had been convicted for extremely violent crime (n = 135) and a normal control group (n = 111). The proportion of S-allele carriers was significantly higher in the criminal group than in the controls (p = 0.006). A significant association was not demonstrated for the relationship between the 5-HTTLPR polymorphism and antisocial personality disorder, substance abuse or alcohol abuse in the criminal group. Our findings demonstrate that carriage of the low-activity S allele is associated with extremely violent criminal behavior in Chinese males, and suggests that the 5-HTT may be implicated in the mechanisms underlying violent behaviors.

  16. Inhibition of PIP4Kγ ameliorates the pathological effects of mutant huntingtin protein.

    Science.gov (United States)

    Al-Ramahi, Ismael; Panapakkam Giridharan, Sai Srinivas; Chen, Yu-Chi; Patnaik, Samarjit; Safren, Nathaniel; Hasegawa, Junya; de Haro, Maria; Wagner Gee, Amanda K; Titus, Steven A; Jeong, Hyunkyung; Clarke, Jonathan; Krainc, Dimitri; Zheng, Wei; Irvine, Robin F; Barmada, Sami; Ferrer, Marc; Southall, Noel; Weisman, Lois S; Botas, Juan; Marugan, Juan Jose

    2017-12-26

    The discovery of the causative gene for Huntington's disease (HD) has promoted numerous efforts to uncover cellular pathways that lower levels of mutant huntingtin protein (mHtt) and potentially forestall the appearance of HD-related neurological defects. Using a cell-based model of pathogenic huntingtin expression, we identified a class of compounds that protect cells through selective inhibition of a lipid kinase, PIP4Kγ. Pharmacological inhibition or knock-down of PIP4Kγ modulates the equilibrium between phosphatidylinositide (PI) species within the cell and increases basal autophagy, reducing the total amount of mHtt protein in human patient fibroblasts and aggregates in neurons. In two Drosophila models of Huntington's disease, genetic knockdown of PIP4K ameliorated neuronal dysfunction and degeneration as assessed using motor performance and retinal degeneration assays respectively. Together, these results suggest that PIP4Kγ is a druggable target whose inhibition enhances productive autophagy and mHtt proteolysis, revealing a useful pharmacological point of intervention for the treatment of Huntington's disease, and potentially for other neurodegenerative disorders.

  17. Horizontal transfer of transposons between and within crustaceans and insects.

    Science.gov (United States)

    Dupeyron, Mathilde; Leclercq, Sébastien; Cerveau, Nicolas; Bouchon, Didier; Gilbert, Clément

    2014-01-29

    Horizontal transfer of transposable elements (HTT) is increasingly appreciated as an important source of genome and species evolution in eukaryotes. However, our understanding of HTT dynamics is still poor in eukaryotes because the diversity of species for which whole genome sequences are available is biased and does not reflect the global eukaryote diversity. In this study we characterized two Mariner transposable elements (TEs) in the genome of several terrestrial crustacean isopods, a group of animals particularly underrepresented in genome databases. The two elements have a patchy distribution in the arthropod tree and they are highly similar (>93% over the entire length of the element) to insect TEs (Diptera and Hymenoptera), some of which were previously described in Ceratitis rosa (Crmar2) and Drosophila biarmipes (Mariner-5_Dbi). In addition, phylogenetic analyses and comparisons of TE versus orthologous gene distances at various phylogenetic levels revealed that the taxonomic distribution of the two elements is incompatible with vertical inheritance. We conclude that the two Mariner TEs each underwent at least three HTT events. Both elements were transferred once between isopod crustaceans and insects and at least once between isopod crustacean species. Crmar2 was also transferred between tephritid and drosophilid flies and Mariner-5 underwent HT between hymenopterans and dipterans. We demonstrate that these various HTTs took place recently (most likely within the last 3 million years), and propose iridoviruses and/or Wolbachia endosymbionts as potential vectors of these transfers.

  18. Short outlines of books by Estonian authors / Janika Kronberg, Rutt Hinrikus

    Index Scriptorium Estoniae

    Kronberg, Janika, 1963-

    2004-01-01

    Tutvustus: Baturin, Nikolai. Kentaur. Tallinn : Eesti Raamat, 2003 ; Kaplinski, Jaan. Isale. Tallinn : Varrak, 2003 ; Jaks, Ilmar. Pimedus. Tartu : Ilmamaa, 2003 ; Ivask, Ivar. Tähtede tähendust tunda. Tartu : Ilmamaa, 2003 ; Vint, Toomas. Minu abielu prostituudiga. Tallinn : Eesti Keele Sihtasutus, 2003 ; Ehin, Kristiina. Luigeluulinn. Tallinn : Huma, 2004 ; Kivisildnik. Päike, mida sa õhtul teed? Tallinn : Perioodika, 2003 ; Kivisildnik. Rahvuseepos Kalevipoeg ehk armastus. Tallinn : Tuum, 2003 ; Veidemann, Rein. Lastekodu. Tallinn : Eesti Keele Sihtasutus, 2003 ; Park, Eeva. Lõks lõpmatuses. Tallinn : Tänapäev, 2003 ; Traat, Mats. Islandi suvi. Tartu : Ilmamaa, 2003 ; Kauksi Ülle. Uibu. Tartu : Kauksi Ülle Mänedsment, 2003 ; Kross, Jaan. Kallid kaasteelised. Tallinn : Eesti Keele Sihtasutus, 2003 ; Undusk, Jaan. Quevedo. Tallinn : Perioodika, 2003

  19. Лабораторные работы / Борис Тух ; иллюстрация: Cheng Chu

    Index Scriptorium Estoniae

    Тух, Борис, 1946-

    2013-01-01

    5.-6. okt. 2013 toimus Tallinnas Vene Teatris, Teatris NO99 ja Von Krahli Teatris uue vene dramaturgia laboratoorium ("Лаборатория современной российской драматургии"). Kavas olid järgmised lavastuseskiisid: Ivan Võrõpajevi "Illusioonid" (lav. Pavel Zobnin), Pavel Prjažko "Alukad" (lav. Anton Malikov), Pavel Prjažko "Põld" (lav. Ivar Põllu), Mihhail Durnenkovi "(Kõige) lihtsam meetod suitsetamisest loobumiseks" (lav. Ivan Strelkin). Näidendid ja lavastajad valis Vene Teatri peanäitejuht Marat Katsalov

  20. Short outlines of books by Estonian authors / Janika Kronberg, Rutt Hinrikus

    Index Scriptorium Estoniae

    Kronberg, Janika, 1963-

    2008-01-01

    Arvustus: Afanasjev, Vahur. Kosmos. Tallinn : Jutulind, 2008 ; Hvostov, Andrei. Võõrad lood. Tallinn : Tänapäev, 2008 ; Lauli, Olle. Niguliste õpilased. Tallinn : Verb, 2007 ; Rooste, Jürgen. Tavaline eesti idioot. Pärnu : Ji, 2008 ; Talvet, Jüri. Silmad peksavad une seinu. Tartu : Ilmamaa, 2008 ; Beekman, Aimée. Proovielu. Tallinn : Varrak, 2008 ; Kivi, Aita. Lähedal. Tallinn : Ajakirjade Kirjastus, 2008 ; Beekman, Vladimir. Alles see oli. Tallinn : Tänapäev, 2008 ; Viiding, Elo. Püha Maama. Tallinn : Tuum, 2008 ; Nõu, Helga. Peaaegu geenius ehk Schrödingeri kassi otsimas. Tallinn : Atlex, 2008 ; Unt, Lii. Parim näitleja linnas. Varanasi päevaraamat. Tallinn : Eesti Ekspressi Kirjastus, 2007 ; Sild, Ivar. Tantsiv linn. Tallinn : Tuum, 2007

  1. Pilte ja kõnelusi : Eesti näitekirjandus 2008 / Heidi Aadma

    Index Scriptorium Estoniae

    Aadma, Heidi, 1976-

    2009-01-01

    Ülevaade 2008. aasta eesti näitekirjandusest. Pikemalt käsitletakse järgmisi autoreid ja nende näidendeid/näidendikogumikke: Mart Kivastik "Meie isa, kes sa oled...", Jaan Tätte "Näidendid II", Urmas Vadi "Kohtumine tundmatuga", Andrus Kivirähk "Voldemar", Juhan Saar "Valge tee kutse ja teisi lavatekste 1980-2005", Maimu Berg "Vene rulett ; Euroopasse! Euroopasse! : kaks näidendit", Peeter Sauter "Keldris", Madis Kõiv "Lõputu kohvijoomine", Merle Karusoo "Kui ruumid on täis", Enn Vetemaa, Erki Aule ja Merle Karusoo "Sigma Tau-C705", Martin Algus "Janu", Jaan Undusk "Boulgakoff", Ott Aardam "Poks", Aapo Ilves ja Olavi Ruitlane "Pristan", Ivar Põllu "Endspiel", Loone Ots "Koidula veri", Toomas Suuman "Linnapea", Urmas Lennuk "Päeva lõpus", Kris Moor "Homefucking is killing prostitution"

  2. Mid-infrared spectrometry of milk for dairy metabolomics: a comparison of two sampling techniques and effect of homogenization.

    Science.gov (United States)

    Aernouts, Ben; Polshin, Evgeny; Saeys, Wouter; Lammertyn, Jeroen

    2011-10-31

    Milk production is a dominant factor in the metabolism of dairy cows involving a very intensive interaction with the blood circulation. As a result, the extracted milk contains valuable information on the metabolic status of the cow. On-line measurement of milk components during milking two or more times a day would promote early detection of systemic and local alterations, thus providing a great input for strategic and management decisions. The objective of this study was to investigate the potential of mid-infrared (mid-IR) spectroscopy to measure the milk composition using two different measurement modes: micro attenuated total reflection (μATR) and high throughput transmission (HTT). Partial least squares (PLS) regression was used for prediction of fat, crude protein, lactose and urea after preprocessing IR data and selecting the most informative wavenumber variables. The prediction accuracies were determined separately for raw and homogenized copies of a wide range of milk samples in order to estimate the possibility for on-line analysis of the milk. In case of fat content both measurement modes resulted in an excellent prediction for homogenized samples (R(2)>0.92) but in poor results for raw samples (R(2)protein and lactose with both μATR and HTT, and urea with μATR spectroscopy. Excellent results were obtained for prediction of crude protein, lactose and urea content (R(2)>0.99, 0.98 and 0.86 respectively) in raw and homogenized milk using μATR IR spectroscopy. These results were significantly better than those obtained by HTT IR spectroscopy. However, the prediction performance of HTT was still good for crude protein and lactose content (R(2)>0.86 and 0.78 respectively) in raw and homogenized samples. However, the detection of urea in milk with HTT spectroscopy was significantly better (R(2)=0.69 versus 0.16) after homogenization of the milk samples. Based on these observations it can be concluded that μATR approach is most suitable for rapid at line

  3. Serotonin Transporter Gene 5-HTTLPR Polymorphism as a Protective Factor Against the Progression of Post-Stroke Depression.

    Science.gov (United States)

    Zhao, Qiang; Guo, Yi; Yang, Dong; Yang, Tiansong; Meng, Xianghui

    2016-04-01

    Polymorphisms in the 5-HTT and BDNF genes are shown to affect their function at the molecular and serum level. Prior work has tried to correlate the polymorphisms with post-stroke depression (PSD), the results nevertheless remain indefinitive. A plausible reason accounting for the uncertainty relates to the small sample of each published trial. In this study, we have performed a comprehensive meta-analysis in order to evaluate the effects of 5-HTT and BDNF polymorphisms (5-HTTLPR, STin2 VNTR, 5-HTR2a 102 T/C, Val66Met) on genetic risk of PSD. Human case-control trials were identified by computer-assisted and manual searches. The article search was performed until October 2014. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the fixed effects meta-analysis to measure the effects 5-HTT and BDNF polymorphisms exerted on PSD. We also performed test of heterogeneity, test of publication bias, and sensitivity analysis to examine the reliability and stability of combined effects. 5-HTTLPR was clearly associated with genetic risk of PSD. The association seemed to be more pronounced in the homozygous model (OR = 0.34, 95% CI = 0.23-0.51, P(Q-test) = 0.63). Both the heterozygous model and the recessive model showed 50% decreased risk of PSD (OR = 0.50, 95% CI = 0.37-0.67, P(Q-test) = 0.91; OR = 0.50, 95% CI = 0.36-0.70, P(Q-test) = 0.43, respectively). Such significant association was also detected for Caucasian and Asian. These results were reliable and stable based on related analyses. Taken together, 5-HTTLPR polymorphism of the 5-HTT gene seems to protect against the occurrence of PSD. Small sample size for the polymorphisms within 5-HTT and BDNF genes may have caused underestimated associations, and a larger study is required to further assess the relations.

  4. Size distribution of carbon layer planes in biochar from different plant type of feedstock with different heating temperatures.

    Science.gov (United States)

    Lu, Guan-Yang; Ikeya, Kosuke; Watanabe, Akira

    2016-11-01

    Biochar application to soil is a strategy to decelerate the increase in the atmospheric carbon concentration. The composition of condensed aromatic clusters appears to be an important determinant of the degradation rate of char in soil. The objective of the present study was to determine the size distribution of carbon layer planes in biochars produced from different types of feedstock (a broadleaf and a coniferous tree and two herbs) using different heating treatment temperatures (HTT; 400 °C-800 °C) using X-ray diffraction 11 band profile analysis. (13)C nuclear magnetic resonance with the phase-adjusted spinning side bands of the chars indicated different spectral features depending on the HTT and similar carbon composition among the plant types at each HTT. Both the content and composition of carbon layer planes in biochar produced using the same HTT were also similar among the plant types. The carbon layer plane size in the 400 °C and 600 °C chars was distributed from 0.24 to 1.68 or 1.92 nm (corresponding to 37 or 52 rings) with the mean size of 0.79-0.92 and 0.80-1.14 nm, respectively. The carbon layer planes in the 800 °C chars ranged from 0.72-0.96 nm (7-14 rings) to 2.64-3.60 nm (91-169 rings) and the mean values were 1.47-1.89 nm. The relative carbon layer plane content in the 600 °C and 800 °C chars was typically 2 and 3 times that in the 400 °C chars. These results indicate the progression of the formation and/or the size development of graphite-like structures, suggesting that a char produced at a higher HTT would have better carbon sequestrating characteristics. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. The association study between the interaction of serotonin and norepinephrine transporter gene polymorphisms and the effects of selective serotonin reuptake inhibitors%5-羟色胺和去甲肾上腺素转运体基因多态性的交互作用与重性抑郁障碍临床疗效的关联研究

    Institute of Scientific and Technical Information of China (English)

    孟亚琴; 孙宁; 王彦芳; 段慧君; 李素萍; 彭菊意; 杜巧荣; 张克让

    2013-01-01

    Objective To explore the relevance of the interaction of serotonin and norepinephrine transporter gene polymorphisms and the effects of selective serotonin reuptake inhibitors.Methods The subjects comprised 246 patients according to the diagnostic and statistical manual of mental disorders in the fourth edition (DSM-Ⅳ) criterion for major depressive disorder(MDD).The clinical efficacy were assessed by using 17 Hamilton depression quantity (HAMD) scale after selective serotonin reuptake inhibitors(SSRIs) citalopram (20 to 60 mg/d) or paroxetine (20 to 60 mg/d) were used randomly for 1,2,4,6 weeks.Polymerase chain reaction(PCR),sodium dodecyl sulfate polyacrylamide gel electrophoresis(SDS-PAGE)and DNA sequencing analysis were used to detect the genotype of 5-HTT gene single nucleotide polymorphisms (SNP) of VNTR and LPR and SNPs at rs2242446 and rs5569 of NET.SPSS13.0 software were used for statistical analysis.Results (1) An association between 5-HTT LPR and the efficacy of SSRIs was found after 6 weeks in these samples (P =0.023).The clinical efficiency of LL genotype was higher than SS + LS genotype(OR =2.225,OR 95% CI=1.118,4.427).(2) The interaction of 5-HTT LPR and NET rs5569 and the SSRIs antidepressant effects was statistical significance (P =0.01).Conclusion Preliminary study found that the interaction of 5-HTT LPR and NET rs5569 may be related to SSRIs antidepressant effects in China' s patients with MDD.%目的 探讨5-羟色胺和去甲肾上腺素转运体基因多态性的交互作用与选择性5-羟色胺再摄取抑制剂临床疗效的关联研究.方法 收集符合美国精神障碍诊断与统计手册第四版(DSM-Ⅳ)重性抑郁障碍(MDD)诊断标准的患者246例,给予选择性5-羟色胺再摄取抑制剂(SSRIs)西酞普兰(20~ 60mg/d)或帕罗西汀(20 ~ 60 mg/d),在治疗后1,2,4,6周运用17项汉密尔顿抑郁量表(HAMD)评定临床疗效;应用聚合酶链反应技术(PCR)、聚丙烯酰胺凝胶电

  6. Early-onset sleep defects in Drosophila models of Huntington's disease reflect alterations of PKA/CREB signaling

    Science.gov (United States)

    Gonzales, Erin D.; Tanenhaus, Anne K.; Zhang, Jiabin; Chaffee, Ryan P.; Yin, Jerry C.P.

    2016-01-01

    Huntington's disease (HD) is a progressive neurological disorder whose non-motor symptoms include sleep disturbances. Whether sleep and activity abnormalities are primary molecular disruptions of mutant Huntingtin (mutHtt) expression or result from neurodegeneration is unclear. Here, we report Drosophila models of HD exhibit sleep and activity disruptions very early in adulthood, as soon as sleep patterns have developed. Pan-neuronal expression of full-length or N-terminally truncated mutHtt recapitulates sleep phenotypes of HD patients: impaired sleep initiation, fragmented and diminished sleep, and nighttime hyperactivity. Sleep deprivation of HD model flies results in exacerbated sleep deficits, indicating that homeostatic regulation of sleep is impaired. Elevated PKA/CREB activity in healthy flies produces patterns of sleep and activity similar to those in our HD models. We were curious whether aberrations in PKA/CREB signaling were responsible for our early-onset sleep/activity phenotypes. Decreasing signaling through the cAMP/PKA pathway suppresses mutHtt-induced developmental lethality. Genetically reducing PKA abolishes sleep/activity deficits in HD model flies, restores the homeostatic response and extends median lifespan. In vivo reporters, however, show dCREB2 activity is unchanged, or decreased when sleep/activity patterns are abnormal, suggesting dissociation of PKA and dCREB2 occurs early in pathogenesis. Collectively, our data suggest that sleep defects may reflect a primary pathological process in HD, and that measurements of sleep and cAMP/PKA could be prodromal indicators of disease, and serve as therapeutic targets for intervention. PMID:26604145

  7. Graphitization kinetics of fluidized-bed pyrolytic carbons

    International Nuclear Information System (INIS)

    Beatty, R.L.

    1975-08-01

    Graphitization of 12 fluidized-bed pyrocarbons was studied as a function of heat-treatment time and temperature (1350 to 3000 0 C) to investigate the effect of initial microstructure on the graphitization process. The term ''graphitization'' is defined to include any thermally induced structural change, whether or not any layer stacking order is attained. A broad range of CVD microstructures was prepared at temperatures from 1150 to 1900 0 C and various propylene and methane concentrations. The twelve carbons spanned a wide range of graphitizabilities, primarily as a function of deposition temperature. Hydrocarbon concentration was of much less importance except for deposition at 1900 0 C. Hydrogen content of the as-deposited carbons decreased with increasing temperature of deposition, and initial graphitization behavior of the low-temperature carbons appeared to be related to hydrogen content and evolution. Rates of change in the parameters varied widely throughout the range of heat-treatment times (HTt) and temperatures (HTT) for the different carbons showing differences between the more graphitizable or ''soft'' carbons from the nongraphitizing or ''hard'' carbons. ΔH for nongraphitizing carbons was 175 +- 15 kcal below 1950 0 C, 240 +- 35 kcal at 1950 to 2700 0 C, and 330 +- 20 kcal above 2700 0 C. For graphitizing carbons deposited at 1150 0 C, values near 245 kcal were obtained from anti chi data for the HTT range 1350 to 1650 0 C, while densification data yielded values of about 160 kcal in the same range. The behaviors observed for graphitizable carbons above 2000 0 C are consistent with literature. Different kinetic behaviors below 2000 0 C were shown to be due to different initial microstructures as well as to different parameters measured. (U.S.)

  8. Association of Anxiety-Related Polymorphisms with Sports Performance in Chilean Long Distance Triathletes: A Pilot Study

    Science.gov (United States)

    Sanhueza, Jorge A.; Zambrano, Tomás; Bahamondes-Avila, Carlos; Salazar, Luis A.

    2016-01-01

    Different factors affecting athletic performance are well established: intensity and type of training, anthropometric characteristics as well as an important psychological component. However, the contribution of the genetic background has been less investigated. The aim of the present study was to investigate the influence of polymorphisms within genes associated with stress and anxiety (5HTT, CRH2R, ACE, NK1R, 5HT1AR and CRF-BP) on the physical capability and sports performance in triathletes. One hundred and ninety two (192) unrelated Chilean triathletes who participated in the 2014 70.3 Pucón city triathlon were divided into opposite subgroups of sports performance according to their time results. We identified significant associations for five polymorphisms (5HTT 5-HTTLPR, ACE I/D, NK1R rs6715729, 5HT1AR -1019C>G and CRF-BP CRF-BPs11) with athletic performance. Our results indicate that these polymorphisms are associated with differential sports performance in Chilean triathletes, establishing an initial background for better understanding the relationship between physical performance, genetics and anxiety disorders. Key points Genetic factors influencing sports performance in the Chilean population are unknown. Differential outcomes from athletes who completed a triathlon competition were associated with five polymorphisms (5HTT 5-HTTLPR, ACE I/D, NK1R rs6715729, 5HT1AR -1019C>G and CRF-BP CRF-BPs11). We show that genetic variants within stress- and anxiety-related genes affect athletic performance. PMID:27928199

  9. A modifier of Huntington's disease onset at the MLH1 locus.

    Science.gov (United States)

    Lee, Jong-Min; Chao, Michael J; Harold, Denise; Abu Elneel, Kawther; Gillis, Tammy; Holmans, Peter; Jones, Lesley; Orth, Michael; Myers, Richard H; Kwak, Seung; Wheeler, Vanessa C; MacDonald, Marcy E; Gusella, James F

    2017-10-01

    Huntington's disease (HD) is a dominantly inherited neurodegenerative disease caused by an expanded CAG repeat in HTT. Many clinical characteristics of HD such as age at motor onset are determined largely by the size of HTT CAG repeat. However, emerging evidence strongly supports a role for other genetic factors in modifying the disease pathogenesis driven by mutant huntingtin. A recent genome-wide association analysis to discover genetic modifiers of HD onset age provided initial evidence for modifier loci on chromosomes 8 and 15 and suggestive evidence for a locus on chromosome 3. Here, genotyping of candidate single nucleotide polymorphisms in a cohort of 3,314 additional HD subjects yields independent confirmation of the former two loci and moves the third to genome-wide significance at MLH1, a locus whose mouse orthologue modifies CAG length-dependent phenotypes in a Htt-knock-in mouse model of HD. Both quantitative and dichotomous association analyses implicate a functional variant on ∼32% of chromosomes with the beneficial modifier effect that delays HD motor onset by 0.7 years/allele. Genomic DNA capture and sequencing of a modifier haplotype localize the functional variation to a 78 kb region spanning the 3'end of MLH1 and the 5'end of the neighboring LRRFIP2, and marked by an isoleucine-valine missense variant in MLH1. Analysis of expression Quantitative Trait Loci (eQTLs) provides modest support for altered regulation of MLH1 and LRRFIP2, raising the possibility that the modifier affects regulation of both genes. Finally, polygenic modification score and heritability analyses suggest the existence of additional genetic modifiers, supporting expanded, comprehensive genetic analysis of larger HD datasets. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. Genetic variation in the serotonin transporter gene (5-HTTLPR, rs25531) influences the analgesic response to the short acting opioid Remifentanil in humans.

    Science.gov (United States)

    Kosek, Eva; Jensen, Karin B; Lonsdorf, Tina B; Schalling, Martin; Ingvar, Martin

    2009-07-01

    There is evidence from animal studies that serotonin (5-HT) can influence the antinociceptive effects of opioids at the spinal cord level. Therefore, there could be an influence of genetic polymorphisms in the serotonin system on individual variability in response to opioid treatment of pain. The serotonin transporter (5-HTT) is a key regulator of serotonin metabolism and availability and its gene harbors several known polymorphisms that are known to affect 5-HTT expression (e.g. 5-HTTLPR, rs25531). The aim of this study was to investigate if the triallelic 5-HTTLPR influences pain sensitivity or the analgesic effect of opioids in humans. 43 healthy volunteers (12 men, 31 women, mean age 26 years) underwent heat pain stimulations before and after intravenous injection of Remifentanil; a rapid and potent opioid drug acting on micro-type receptors. Subjects rated their perceived pain on a visual analogue scale (VAS). All participants were genotyped for the 5-HTTLPR and the rs25531 polymorphism. We recruited by advertising, with no history of drug abuse, chronic pain or psychiatric disorders. At baseline, there was no difference in pain ratings for the different triallelic 5-HTTLPR genotype groups. However, the opiod drug had a differential analgesic effect depending on the triallelic 5-HTTLPR genotype. Remifentanil had a significantly better analgesic effect in individuals with a genotype coding for low 5-HTT expression (SA/SA and SA/LG) as compared to those with high expression(LA/LA), p desensitization of 5-HT1 receptors have an increased analgesic response to opioids during acute pain stimuli, but may still be at increased risk of developing chronic pain conditions.

  11. Electrochemical performance of DVB-modified SiOC and SiCN polymer-derived negative electrodes for lithium-ion batteries

    International Nuclear Information System (INIS)

    Liu, Guanwei; Kaspar, Jan; Reinold, Lukas Mirko; Graczyk-Zajac, Magdalena; Riedel, Ralf

    2013-01-01

    Highlights: • Polymer-derived SiCN and SiOC ceramics are studied as anode for Li-ion batteries. • Ceramic precursors are modified in order to increase the carbon content. • Ceramic matrix stabilizes free carbon phase. • Stabilizing role is lost once the amount of carbon exceeds a threshold value. -- Abstract: Chemical modification of commercially available polyorganosilazane (HTT1800) and polyorganosiloxane (Polyramic RD-684a) with divinylbenzene (DVB) is accomplished via hydrosilylation reaction. The incorporation of DVB leads to an increase of the free carbon amount after pyrolysis within the corresponding SiCN and SiOC ceramics. The modification is carried out with lower, equal and higher stoichiometric ratios of the Si-H to C=C groups present in the Si-based polymer and DVB. FTIR results indicate a complete consumption of the Si-H bonds in the case of the stoichiometric amount of DVB and polymer RD-684a, while for HTT1800 neither the stoichiometric ratio nor DVB excess leads to a complete consumption of the Si-H groups. For both SiCN and SiOC ceramics the carbon content is found to increase with the amount of DVB. However, the most significant increase in free carbon content is registered for SiCN samples, namely of ca. 40%. The carbon content changed from 9.9 wt.% in the pure HTT1800-derived material up to 49.3 wt.% for the SiCN ceramic obtained with the highest amount of DVB addition. Accordingly, Li-ion storage and therefore charge storage capacity are simultaneously increased, for the first cycle from 136 to 574 mAh g −1 , while columbic efficiency is raised by 10% up to 60.4%

  12. Architecture of polyglutamine-containing fibrils from time-resolved fluorescence decay.

    Science.gov (United States)

    Röthlein, Christoph; Miettinen, Markus S; Borwankar, Tejas; Bürger, Jörg; Mielke, Thorsten; Kumke, Michael U; Ignatova, Zoya

    2014-09-26

    The disease risk and age of onset of Huntington disease (HD) and nine other repeat disorders strongly depend on the expansion of CAG repeats encoding consecutive polyglutamines (polyQ) in the corresponding disease protein. PolyQ length-dependent misfolding and aggregation are the hallmarks of CAG pathologies. Despite intense effort, the overall structure of these aggregates remains poorly understood. Here, we used sensitive time-dependent fluorescent decay measurements to assess the architecture of mature fibrils of huntingtin (Htt) exon 1 implicated in HD pathology. Varying the position of the fluorescent labels in the Htt monomer with expanded 51Q (Htt51Q) and using structural models of putative fibril structures, we generated distance distributions between donors and acceptors covering all possible distances between the monomers or monomer dimensions within the polyQ amyloid fibril. Using Monte Carlo simulations, we systematically scanned all possible monomer conformations that fit the experimentally measured decay times. Monomers with four-stranded 51Q stretches organized into five-layered β-sheets with alternating N termini of the monomers perpendicular to the fibril axis gave the best fit to our data. Alternatively, the core structure of the polyQ fibrils might also be a zipper layer with antiparallel four-stranded stretches as this structure showed the next best fit. All other remaining arrangements are clearly excluded by the data. Furthermore, the assessed dimensions of the polyQ stretch of each monomer provide structural evidence for the observed polyQ length threshold in HD pathology. Our approach can be used to validate the effect of pharmacological substances that inhibit or alter amyloid growth and structure. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Insulin and IGF-1 improve mitochondrial function in a PI-3K/Akt-dependent manner and reduce mitochondrial generation of reactive oxygen species in Huntington's disease knock-in striatal cells.

    Science.gov (United States)

    Ribeiro, Márcio; Rosenstock, Tatiana R; Oliveira, Ana M; Oliveira, Catarina R; Rego, A Cristina

    2014-09-01

    Oxidative stress and mitochondrial dysfunction have been described in Huntington's disease, a disorder caused by expression of mutant huntingtin (mHtt). IGF-1 was previously shown to protect HD cells, whereas insulin prevented neuronal oxidative stress. In this work we analyzed the role of insulin and IGF-1 in striatal cells derived from HD knock-in mice on mitochondrial production of reactive oxygen species (ROS) and related antioxidant and signaling pathways influencing mitochondrial function. Insulin and IGF-1 decreased mitochondrial ROS induced by mHtt and normalized mitochondrial SOD activity, without affecting intracellular glutathione levels. IGF-1 and insulin promoted Akt phosphorylation without changing the nuclear levels of phosphorylated Nrf2 or Nrf2/ARE activity. Insulin and IGF-1 treatment also decreased mitochondrial Drp1 phosphorylation, suggesting reduced mitochondrial fragmentation, and ameliorated mitochondrial function in HD cells in a PI-3K/Akt-dependent manner. This was accompanied by increased total and phosphorylated Akt, Tfam, and mitochondrial-encoded cytochrome c oxidase II, as well as Tom20 and Tom40 in mitochondria of insulin- and IGF-1-treated mutant striatal cells. Concomitantly, insulin/IGF-1-treated mutant cells showed reduced apoptotic features. Hence, insulin and IGF-1 improve mitochondrial function and reduce mitochondrial ROS caused by mHtt by activating the PI-3K/Akt signaling pathway, in a process independent of Nrf2 transcriptional activity, but involving enhanced mitochondrial levels of Akt and mitochondrial-encoded complex IV subunit. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. A gene-environment investigation on personality traits in two independent clinical sets of adult patients with personality disorder and attention deficit/hyperactive disorder.

    Science.gov (United States)

    Jacob, Christian P; Nguyen, Thuy Trang; Dempfle, Astrid; Heine, Monika; Windemuth-Kieselbach, Christine; Baumann, Katarina; Jacob, Florian; Prechtl, Julian; Wittlich, Maike; Herrmann, Martin J; Gross-Lesch, Silke; Lesch, Klaus-Peter; Reif, Andreas

    2010-06-01

    While an interactive effect of genes with adverse life events is increasingly appreciated in current concepts of depression etiology, no data are presently available on interactions between genetic and environmental (G x E) factors with respect to personality and related disorders. The present study therefore aimed to detect main effects as well as interactions of serotonergic candidate genes (coding for the serotonin transporter, 5-HTT; the serotonin autoreceptor, HTR1A; and the enzyme which synthesizes serotonin in the brain, TPH2) with the burden of life events (#LE) in two independent samples consisting of 183 patients suffering from personality disorders and 123 patients suffering from adult attention deficit/hyperactivity disorder (aADHD). Simple analyses ignoring possible G x E interactions revealed no evidence for associations of either #LE or of the considered polymorphisms in 5-HTT and TPH2. Only the G allele of HTR1A rs6295 seemed to increase the risk of emotional-dramatic cluster B personality disorders (p = 0.019, in the personality disorder sample) and to decrease the risk of anxious-fearful cluster C personality disorders (p = 0.016, in the aADHD sample). We extended the initial simple model by taking a G x E interaction term into account, since this approach may better fit the data indicating that the effect of a gene is modified by stressful life events or, vice versa, that stressful life events only have an effect in the presence of a susceptibility genotype. By doing so, we observed nominal evidence for G x E effects as well as main effects of 5-HTT-LPR and the TPH2 SNP rs4570625 on the occurrence of personality disorders. Further replication studies, however, are necessary to validate the apparent complexity of G x E interactions in disorders of human personality.

  15. Characterization of neurophysiological and behavioral changes, MRI brain volumetry and 1H MRS in zQ175 knock-in mouse model of Huntington's disease.

    Directory of Open Access Journals (Sweden)

    Taneli Heikkinen

    Full Text Available Huntington's disease (HD is an autosomal neurodegenerative disorder, characterized by severe behavioral, cognitive, and motor deficits. Since the discovery of the huntingtin gene (HTT mutation that causes the disease, several mouse lines have been developed using different gene constructs of Htt. Recently, a new model, the zQ175 knock-in (KI mouse, was developed (see description by Menalled et al, [1] in an attempt to have the Htt gene in a context and causing a phenotype that more closely mimics HD in humans. Here we confirm the behavioral phenotypes reported by Menalled et al [1], and extend the characterization to include brain volumetry, striatal metabolite concentration, and early neurophysiological changes. The overall reproducibility of the behavioral phenotype across the two independent laboratories demonstrates the utility of this new model. Further, important features reminiscent of human HD pathology are observed in zQ175 mice: compared to wild-type neurons, electrophysiological recordings from acute brain slices reveal that medium spiny neurons from zQ175 mice display a progressive hyperexcitability; glutamatergic transmission in the striatum is severely attenuated; decreased striatal and cortical volumes from 3 and 4 months of age in homo- and heterozygous mice, respectively, with whole brain volumes only decreased in homozygotes. MR spectroscopy reveals decreased concentrations of N-acetylaspartate and increased concentrations of glutamine, taurine and creatine + phosphocreatine in the striatum of 12-month old homozygotes, the latter also measured in 12-month-old heterozygotes. Motor, behavioral, and cognitive deficits in homozygotes occur concurrently with the structural and metabolic changes observed. In sum, the zQ175 KI model has robust behavioral, electrophysiological, and histopathological features that may be valuable in both furthering our understanding of HD-like pathophyisology and the evaluation of potential therapeutic

  16. Granular model, percolation-resistivity, ESR and elastic modulus of carbonaceous materials application to the babassu endocarp heat treated up to 22000C

    International Nuclear Information System (INIS)

    Emmerich, F.G.

    1987-01-01

    A microscopic model (granular model) is presented to study heat treated carbons. A granular structure is defined in the carbon matrix, composed of turbostratic graphite-like microcrystallites, cross-linkings and micropores. A general expression is developed to calculate the volume fraction X of the conducting phase of the granular structure as a function of structural parameters obtained from X-ray diffraction small angle X-ray scattering. The granular model and the percolation theory are used to explain the electrical resistivity behaviour with the heat treatment temperature (HTT), where X is the fundamental parameter. An electron spin resonance (ESR) study of the low and high HTT ranges is presented, including the transition range (700-1300 0 C). The elucitation of the spin center nature in this range and the liking with the two adjacent ranges has been pursued. An expression to calculate the elastic modulus (Young's modulus), based on the microscopic granular model with the fundamental participation of the cross-linkings, is derived to account for the behavior of the modulus with the HTT. The granular model with the expression of X, the percolation-resistivity theory, the ESR study, and the expression of the elastic modulus are applied to the babassu endocarp carbon heat treated up to 2200 0 C. This material can be classified as a tipical non-graphitic carbon, being useful to search the validity of the model and the proposed expressions. It is observed that the theoretical expressions describe with reasonable accuracy the respective experimental behaviours. The measurements of physical and chemical parameters of the babassu endocarp treated up to 2200 0 C area also included. (author) [pt

  17. Asking for an extra photon in Higgs production at the LHC and beyond

    Energy Technology Data Exchange (ETDEWEB)

    Gabrielli, Emidio [Dipartimento di Fisica Teorica, Università di Trieste,Strada Costiera 11, I-34151 Trieste (Italy); INFN, Sezione di Trieste,Via Valerio 2, I-34127 Trieste (Italy); National Institute Of Chemical Physics And Biophysics (NICPB),Ravala 10, Tallinn 10143 (Estonia); Mele, Barbara [INFN, Sezione di Roma, c/o Dipartimento di Fisica, “Sapienza' Università di Roma, P.le Aldo Moro 2, I-00185 Rome (Italy); Piccinini, Fulvio [INFN, Sezione di Pavia,Via A. Bassi 6, I-27100 Pavia (Italy); Pittau, Roberto [Departamento de Física Teórica y del Cosmos and CAFPE, Universidad de Granada, Campus Fuentenueva s.n., E-18071 Granada (Spain)

    2016-07-01

    We study the inclusive production of a Higgs boson in association with a high-p{sub T} photon at the LHC, detailing the leading-order features of the main processes contributing to the Hγ final state. Requiring an extra hard photon in Higgs production upsets the cross-section hierarchy for the dominant channels. The Hγ inclusive production comes mainly from photons radiated in vector-boson fusion (VBF), which accounts for about 2/3 of the total rate, for p{sub T}{sup γ,j}>30 GeV, at leading order. On the other hand, radiating a high-p{sub T} photon in the main top-loop Higgs channel implies an extra parton in the final state, which suppresses the production rate by a further α{sub S} power. As a result, the Hγ production via top loops at the LHC has rates comparable with the ones arising from either the Htt̄ production or the HW(Z)γ associated production. Then, in order of decreasing cross section, comes the single-top-plus-Higgs channel, followed in turn by the heavy-flavor fusion processes bb̄→Hγ and cc̄→Hγ. The Hγ production via electroweak loops has just a minor role. At larger c.m. energies, the Htt̄γ channel surpasses the total contribution of top-loop processes. In particular, requiring p{sub T}{sup γ,j}>30 GeV at √S≃100 TeV, Htt̄γ accounts for about 1/4 of the inclusive Hγ production at leading order, about half of the total being due to VBF production.

  18. A Qualitative Data Collection Strategy for Africa

    Science.gov (United States)

    2013-02-01

    ini on da ta wo rld wi de an d ha s t hr ee an aly sts de dic ate d t o s ub - Sa ha ra n A fric a. Qu an tita tiv e a nd qu ali tat ive da...Int er sta te an d e xtr as tat e w ar s a nd lin ks to oth er qu an tita tiv e i nte rn ati on al re lat ion s da ta. htt p:/ /w ww

  19. CISSP Study Guide

    CERN Document Server

    Conrad, Eric; Feldman, Joshua

    2010-01-01

    The CISSP Study Guide is aligned to cover all of the material included in the exam, complete with special attention to recent updates. The 10 domains are covered completely and as concisely as possible with an eye to passing the exam thr first time. Each of the 10 domains has its own chapter that includes specially-designed pedagogy to aid you in passing the exam. Clearly Stated Exam Objectives Unique Terms / Definitions Exam Warnings Helpful Notes Learning By Example Stepped Chapter Ending Questions Self Test Appendix Detailed Glossary Web Site (htt

  20. Psychiatric and cognitive symptoms in Huntington's disease are modified by polymorphisms in catecholamine regulating enzyme genes

    DEFF Research Database (Denmark)

    Vinther-Jensen, T; Nielsen, Troels Tolstrup; Budtz-Jørgensen, E

    2016-01-01

    Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disorder characterized by motor, psychiatric, and cognitive manifestations. HD is caused by a CAG repeat expansion in the Huntingtin (HTT) gene but the exact pathogenesis remains unknown. Dopamine imbalance has......-described cohort of Danish HD gene-expansion carriers. We show that cognitive impairment and psychiatric symptoms in HD are modified by polymorphisms in the monoamine oxidase A (MAOA) and catechol-O-methyltransferase (COMT) genes and by the 4p16.3 B haplotype. These results support the theory of dopamine imbalance...

  1. Generation of induced pluripotent stem cell line, CSSi004-A (2962, from a patient diagnosed with Huntington's disease at the presymptomatic stage

    Directory of Open Access Journals (Sweden)

    Eris Bidollari

    2018-04-01

    Full Text Available Huntington's disease (HD is an incurable, autosomal dominant, hereditary neurodegenerative disorder that typically manifests itself in midlife. This pathology is linked to the deregulation of multiple, as yet unknown, cellular processes starting before HD onset. A human iPS cell line was generated from skin fibroblasts of a subject at the presymptomatic life stage, carrying a polyglutamine expansion in HTT gene codifying Huntingtin protein. The iPSC line contained the expected CAG expansion, expressed the expected pluripotency markers, displayed in vivo differentiation potential to the three germ layers and had a normal karyotype.

  2. Functional polymorphisms in the interleukin-6 and serotonin transporter genes, and depression and fatigue induced by interferon-alpha and ribavirin treatment.

    LENUS (Irish Health Repository)

    Bull, S J

    2009-12-01

    Depression and fatigue are frequent side effects of interferon-alpha (IFN-alpha) treatment, and there is compelling evidence that the inflammatory response system (including interleukin-6, IL-6) and the serotonergic system is important in the pathophysiology of such symptoms. Functional polymorphisms in the promoter region of the IL-6 gene (rs1800795) and serotonin transporter gene (5-HTTLPR) have been identified as regulating these systems. The present study aimed to determine if these polymorphisms were associated with the development of depression and fatigue during IFN-alpha and ribavirin treatment. Ninety-eight Caucasian patients receiving pegylated IFN-alpha and ribavirin treatment for chronic hepatitis C virus at King\\'s College Hospital, London, and Emory University Hospital, Atlanta, participated in this prospective cohort study. Symptoms of depression and fatigue were measured before treatment and at weeks 4, 8, 12 and 24 during treatment. The \\'low IL-6\\' synthesizing genotype (CC) was associated with significantly fewer symptoms of depression (effect size = 0.7 at week 24; F = 9.4, d.f. = 436, P = 0.002). The \\'high transcription\\' serotonin transporter (5-HTT) genotype (LL) was also associated with significantly fewer symptoms of depression, but with a much smaller effect (effect size = 0.2 at week 24; F = 4.5, d.f. = 436, P = 0.03). Neither polymorphisms were associated with symptoms of fatigue (IL-6: F = 1.2, d.f. = 430, P = 0.2; 5-HTT: F = 0.5, d.f. = 430, P = 0.5). The smaller effects of the 5-HTT polymorphism on depression may be explained by an interaction between the genes (F = 5.0, d.f. = 434, P = 0.02): the \\'protective\\' effect of the 5-HTTLPR polymorphism was evident only in the presence of the \\'low IL-6\\' genotype (F = 5.4, d.f. = 64, P = 0.02), not in the presence of the \\'high IL-6\\' genotype (F = 2.2, d.f. = 369, P = 0.1). The association between the IL-6 polymorphism and reduced risk of depressive symptoms confirms the role

  3. Oligonucleic Acid Drug List: monrd0010 [Oligonucleic Acid Drug Database[Archive

    Lifescience Database Archive (English)

    Full Text Available ciparum Malaria has been initiated. ... https://www.clinicaltrialsregister.eu/ctr-se...arch/trial/2004-003813-18/GB, https://www.clinicaltrialsregister.eu/ctr-search/trial/2004-004686-15/DE, https:...//www.clinicaltrialsregister.eu/ctr-search/trial/2004-004684-30/DE, https://www.clinicaltrialsregister.eu/...ctr-search/trial/2007-005389-11/GB, https://www.clinicaltrialsregister.eu/ctr-search/search?query=CpG, htt...ps://www.clinicaltrialsregister.eu/ctr-search/trial/2005-004557-10/results, https:/

  4. Derivation of Huntington Disease affected Genea046 human embryonic stem cell line

    Directory of Open Access Journals (Sweden)

    Biljana Dumevska

    2016-03-01

    Full Text Available The Genea046 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying HTT gene CAG expansion of 45 repeats, indicative of Huntington Disease. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female Allele pattern. The hESC line had pluripotent cell morphology, 85% of cells expressed Nanog, 92% Oct4, 75% Tra1–60 and 99% SSEA4 and demonstrated Alkaline Phosphatase activity. The cell line was negative for Mycoplasma and visible contamination.

  5. Experiment list: SRX144528 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available -Seq source_name=IgG ChIP SFN treated || biomaterial_provider=Coriell; http://ccr....coriell.org/Sections/Search/Search.aspx?PgId=165&q=GM06993 || biomaterial_provider=Coriell; http://ccr.cori...ell.org/Sections/Search/Search.aspx?PgId=165&q=GM07000 || biomaterial_provider=Coriell; http://ccr.coriell.o...rg/Sections/Search/Search.aspx?PgId=165&q=GM11882 || biomaterial_provider=Coriell...; http://ccr.coriell.org/Sections/Search/Search.aspx?PgId=165&q=GM11992 || biomaterial_provider=Coriell; htt

  6. Taxonomy Icon Data: Ptychodera flava Eschscholtz (Acorn worm) [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available Ptychodera flava Eschscholtz (Acorn worm) Ptychodera flava Hemichordata Ptychodera_flava_L.png Ptycho...dera_flava_NL.png Ptychodera_flava_S.png Ptychodera_flava_NS.png http://biosciencedbc.jp/t...axonomy_icon/icon.cgi?i=Ptychodera+flava&t=L http://biosciencedbc.jp/taxonomy_icon/icon.cgi?i=Ptychodera+fla...va&t=NL http://biosciencedbc.jp/taxonomy_icon/icon.cgi?i=Ptychodera+flava&t=S htt...p://biosciencedbc.jp/taxonomy_icon/icon.cgi?i=Ptychodera+flava&t=NS http://togodb.biosciencedbc.jp/togodb/view/taxonomy_icon_comment_en?species_id=161 ...

  7. Quantitative fluorescence loss in photobleaching for analysis of protein transport and aggregation

    Directory of Open Access Journals (Sweden)

    Wüstner Daniel

    2012-11-01

    Full Text Available Abstract Background Fluorescence loss in photobleaching (FLIP is a widely used imaging technique, which provides information about protein dynamics in various cellular regions. In FLIP, a small cellular region is repeatedly illuminated by an intense laser pulse, while images are taken with reduced laser power with a time lag between the bleaches. Despite its popularity, tools are lacking for quantitative analysis of FLIP experiments. Typically, the user defines regions of interest (ROIs for further analysis which is subjective and does not allow for comparing different cells and experimental settings. Results We present two complementary methods to detect and quantify protein transport and aggregation in living cells from FLIP image series. In the first approach, a stretched exponential (StrExp function is fitted to fluorescence loss (FL inside and outside the bleached region. We show by reaction–diffusion simulations, that the StrExp function can describe both, binding/barrier–limited and diffusion-limited FL kinetics. By pixel-wise regression of that function to FL kinetics of enhanced green fluorescent protein (eGFP, we determined in a user-unbiased manner from which cellular regions eGFP can be replenished in the bleached area. Spatial variation in the parameters calculated from the StrExp function allow for detecting diffusion barriers for eGFP in the nucleus and cytoplasm of living cells. Polyglutamine (polyQ disease proteins like mutant huntingtin (mtHtt can form large aggregates called inclusion bodies (IB’s. The second method combines single particle tracking with multi-compartment modelling of FL kinetics in moving IB’s to determine exchange rates of eGFP-tagged mtHtt protein (eGFP-mtHtt between aggregates and the cytoplasm. This method is self-calibrating since it relates the FL inside and outside the bleached regions. It makes it therefore possible to compare release kinetics of eGFP-mtHtt between different cells and

  8. Oligonucleic Acid Drug List: monrd0030 [Oligonucleic Acid Drug Database[Archive

    Lifescience Database Archive (English)

    Full Text Available u/ema/index.jsp?curl=pages/medicines/human/medicines/000711/human_med_000806.jsp&mid=WC0b01ac058001d124, htt...nes/human/medicines/000711/human_med_000806.jsp&mid=WC0b01ac058001d124, http://www.kegg.jp/dbget-bin/www_bget?D05216 ... P10415 1G5M ...c_assessment_report/human/000711/WC500070766.pdf, http://www.ema.europa.eu/ema/index.jsp?curl=pages/medici

  9. Taxonomy Icon Data: Anopheles stephensi [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available Anopheles stephensi Anopheles stephensi Arthropoda Anopheles_stephensi_L.png Anopheles_stephen...si_NL.png Anopheles_stephensi_S.png Anopheles_stephensi_NS.png http://biosciencedbc.jp/taxonomy_i...con/icon.cgi?i=Anopheles+stephensi&t=L http://biosciencedbc.jp/taxonomy_icon/icon.cgi?i=Anopheles+stephensi&...t=NL http://biosciencedbc.jp/taxonomy_icon/icon.cgi?i=Anopheles+stephensi&t=S htt...p://biosciencedbc.jp/taxonomy_icon/icon.cgi?i=Anopheles+stephensi&t=NS http://togodb.biosciencedbc.jp/togodb/view/taxonomy_icon_comment_en?species_id=149 ...

  10. Genetic variation in the serotonin transporter gene (5-HTTLPR, rs25531 influences the analgesic response to the short acting opioid Remifentanil in humans

    Directory of Open Access Journals (Sweden)

    Schalling Martin

    2009-07-01

    Full Text Available Abstract Background There is evidence from animal studies that serotonin (5-HT can influence the antinociceptive effects of opioids at the spinal cord level. Therefore, there could be an influence of genetic polymorphisms in the serotonin system on individual variability in response to opioid treatment of pain. The serotonin transporter (5-HTT is a key regulator of serotonin metabolism and availability and its gene harbors several known polymorphisms that are known to affect 5-HTT expression (e.g. 5-HTTLPR, rs25531. The aim of this study was to investigate if the triallelic 5-HTTLPR influences pain sensitivity or the analgesic effect of opioids in humans. 43 healthy volunteers (12 men, 31 women, mean age 26 years underwent heat pain stimulations before and after intravenous injection of Remifentanil; a rapid and potent opioid drug acting on μ-type receptors. Subjects rated their perceived pain on a visual analogue scale (VAS. All participants were genotyped for the 5-HTTLPR and the rs25531 polymorphism. We recruited by advertising, with no history of drug abuse, chronic pain or psychiatric disorders. Results At baseline, there was no difference in pain ratings for the different triallelic 5-HTTLPR genotype groups. However, the opiod drug had a differential analgesic effect depending on the triallelic 5-HTTLPR genotype. Remifentanil had a significantly better analgesic effect in individuals with a genotype coding for low 5-HTT expression (SA/SA and SA/LG as compared to those with high expression(LA/LA, p Conclusion This is the first report showing an influence of the triallelic 5-HTTLPR on pain sensitivity or the analgesic effect of opioids in humans. Previously the 5-HTTLPR s-allele has been associated with higher risk of developing chronic pain conditions but in this study we show that the genotype coding for low 5-HTT expression is associated with a better analgesic effect of an opioid. The s-allele has been associated with downregulation of

  11. Serotonin transporter evolution and impact of polymorphic transcriptional regulation

    DEFF Research Database (Denmark)

    Søeby, Karen; Larsen, Svend Ask; Olsen, Line

    2005-01-01

    The serotonin transporter (SERT) is the primary drug target in the current antidepressant therapy. A functional polymorphism in the 2nd intron of the 5HTT gene encoding the SERT has been identified and associated with susceptibility to affective disorders and treatment response to antidepressants...... in the VNTRs of all mammalian SERT genes. The number of these putative binding sites varies proportionally to the length of the VNTR. We propose that the intronic VNTR have been selectively targeted through mammalian evolution to finetune transcriptional regulation of the serotonin expression....

  12. Serotonin transporter evolution and impact of polymorphic transcriptional regulation

    DEFF Research Database (Denmark)

    Søeby, Karen; Larsen, Svend Ask; Olsen, Line

    2005-01-01

    The serotonin transporter (SERT) is the primary drug target in the current antidepressant therapy. A functional polymorphism in the 2nd intron of the 5HTT gene encoding the SERT has been identified and associated with susceptibility to affective disorders and treatment response to antidepressants....... This study addresses the possible impact of the variable number of tandem repeats (VNTR) to behavior and disease by examining the evolutionary origin and mechanisms of differential transcriptional regulation of SERT. We trace the evolutionary origin of the VNTR and show that it is present and varies...

  13. A Physically Based Correlation of Irradiation-Induced Transition Temperature Shifts for RPV Steels

    Energy Technology Data Exchange (ETDEWEB)

    Eason, Ernest D. [Modeling and Computing Services, LLC; Odette, George Robert [UCSB; Nanstad, Randy K [ORNL; Yamamoto, Takuya [ORNL

    2007-11-01

    data. It contains two terms, corresponding to the best-understood radiation damage features, matrix damage and copper-rich precipitates, although the empirical calibration will ensure that all other damage processes that are occurring are also reflected in those terms. Effects of material chemical composition, product form, and radiation exposure are incorporated, such that all effects are supported by findings of statistical significance, physical understanding, or comparison with independent data from controlled experiments, such as the Irradiation Variable (IVAR) Program. In most variable effects, the model is supported by two or three of these different forms of evidence. The key variable trends, such as the neutron fluence dependence and copper-nickel dependence in the new TTS model, are much improved over RG1.99/2 and are well supported by independent data and the current understanding of embrittlement mechanisms. The new model includes the variables copper, nickel, and fluence that are in RG1.99/2, but also includes effects of irradiation temperature, neutron flux, phosphorus, and manganese. The calibrated model is a good fit, with no significant residual error trends in any of the variables used in the model or several additional variables and variable interactions that were investigated. The report includes a chapter summarizing the current understanding of embrittlement mechanisms and one comparing the IVAR database with the TTS model predictions. Generally good agreement is found in that quantitative comparison, providing independent confirmation of the predictive capability of the TTS model. The key new insight in the TTS modeling effort, that flux effects are evident in both low (or no) copper and higher copper materials, is supported by the IVAR data. The slightly simplified version of the TTS model presented in Section 7.3 of this report is recommended for applications.

  14. Physical Characterization of Warm Spitzer-observed Near-Earth Objects

    Science.gov (United States)

    Thomas, Cristina A.; Emery, Joshua P.; Trilling, David E.; Delbo, Marco; Hora, Joseph L.; Mueller, Michael

    2014-01-01

    Near-infrared spectroscopy of Near-Earth Objects (NEOs) connects diagnostic spectral features to specific surface mineralogies. The combination of spectroscopy with albedos and diameters derived from thermal infrared observations can increase the scientific return beyond that of the individual datasets. For instance, some taxonomic classes can be separated into distinct compositional groupings with albedo and different mineralogies with similar albedos can be distinguished with spectroscopy. To that end, we have completed a spectroscopic observing campaign to complement the ExploreNEOs Warm Spitzer program that obtained albedos and diameters of nearly 600 NEOs (Trilling et al., 2010). The spectroscopy campaign included visible and near-infrared observations of ExploreNEOs targets from various observatories. Here we present the results of observations using the low-resolution prism mode (approx. 0.7-2.5 microns) of the SpeX instrument on the NASA Infrared Telescope Facility (IRTF). We also include near-infrared observations of Explore-NEOs targets from the MIT-UH-IRTF Joint Campaign for Spectral Reconnaissance. Our dataset includes near-infrared spectra of 187 ExploreNEOs targets (125 observations of 92 objects from our survey and 213 observations of 154 objects from the MIT survey). We identify a taxonomic class for each spectrum and use band parameter analysis to investigate the mineralogies for the S-, Q-, and V-complex objects. Our analysis suggests that for spectra that contain near-infrared data but lack the visible wavelength region, the Bus-DeMeo system misidentifies some S-types as Q-types. We find no correlation between spectral band parameters and ExploreNEOs albedos and diameters. We investigate the correlations of phase angle with band area ratio and near-infrared spectral slope. We find slightly negative Band Area Ratio (BAR) correlations with phase angle for Eros and Ivar, but a positive BAR correlation with phase angle for Ganymed.The results of our

  15. Mastimännid ja muu mets : mitmekülgsuse võlu Eesti proosast aastal 2007 / Sirje Olesk

    Index Scriptorium Estoniae

    Olesk, Sirje, 1954-

    2008-01-01

    Ülevaade 2007. aasta eesti proosast. Käsitletakse järgimisi autoreid ja nende teoseid: Ene Mihkelson "Katkuhaud", Andrus Kivirähk "Mees, kes teadis ussisõnu", Jaan Kaplinski "Seesama jõgi", Tõnu Õnnepalu "Flandria päevik", Toomas Vint "Mäluauguga naine", Indrek Hargla "French ja Koulu Tarbatus", Kalle Käsper "Buridanid IV", Jaan Tooming "Teekond mäe südamesse", Ustav Mikelsaar "Tunnimehed", Henn Mikelsaar "Teema variatsioonidega", Reet Kudu "Pidupäevad võõrsil", Mara Maret Aronovich "Tagasikäiguga edasi", Aimée Beekman "Proovielu", Valentine Nõlvak "Ellujääja : mälestused", Mehis Heinsaar "Rändaja õnn", Maimu Berg "Unustatud inimesed", Mats Traat "Sarviku armastus : valik kultuuriloolisi novelle", Mihkel Mutt "Siseemigrant : novellid Rui taevalike kommentaaridega", Paavo Kivine "Kaks kavaleri", Kärt Hellerma "Ma armastasin David Copperfieldi", Piret Bristol "Paralleelmeri", Imre Siil "Mereröövlite loss", Kalju Saaber "Issanda loomaaed. Viru sektor", Veiko Märka "Lendas üle marmortahvli", Vahur Afanasjev "Kaadrid otsustavad, ehk, Sööbik ja Pisik seiklevad jälle, ehk, Eesti rahva lühike, kuid õnnelik ajalugu, Ehk kirjalik komejant tühjusest", Aarne Ruuben "Lugusid Anveltist ja Kingissepast", Epp Annus "Sina, Matilda", Peeter Helme "Puudutus", Ivar Sild "Tantsiv linn", Tui Hirv "Tähe tänav. Per musica ad astra", Tiina Laanem "Väikesed vanamehed", Angela Hofberg (pseud.) "Päev nagu elu", Marion Andra "Vähemalt...", Olle Lauli "Niguliste õpilased", Aarne Biin "Linna valitsemine", Erik Tohvri "Mürgiliblikas", Riina Kangur "Elisa", Kerttu Rakke "Küpsiseparadiis", Epp Petrone ja Dagmar Reintam "Õun ära süüa?", Elme Väljaste "Päriselu Proletariaadi puiesteel", Ketlin Priilinn "Hõbeingel", Ira Lember "Kohvik pärnade all", Paul Pajos "Krimijutud edasijõudnuile", Andres Anvelt "Punane elavhõbe", Klaara ja Kaarel Kivi "Mõrvasügis", Tiit Sepa "Hommik ühele", Lembit Uustulnd "Ruutuemanda sündroom : rahvusvaheline

  16. Widespread AAV1- and AAV2-mediated transgene expression in the nonhuman primate brain: implications for Huntington's disease

    Directory of Open Access Journals (Sweden)

    Piotr Hadaczek

    2016-01-01

    Full Text Available Huntington's disease (HD is caused by a toxic gain-of-function associated with the expression of the mutant huntingtin (htt protein. Therefore, the use of RNA interference to inhibit Htt expression could represent a disease-modifying therapy. The potential of two recombinant adeno-associated viral vectors (AAV, AAV1 and AAV2, to transduce the cortico-striatal tissues that are predominantly affected in HD was explored. Green fluorescent protein was used as a reporter in each vector to show that both serotypes were broadly distributed in medium spiny neurons in the striatum and cortico-striatal neurons after infusion into the putamen and caudate nucleus of nonhuman primates (NHP, with AAV1-directed expression being slightly more robust than AAV2-driven expression. This study suggests that both serotypes are capable of targeting neurons that degenerate in HD, and it sets the stage for the advanced preclinical evaluation of an RNAi-based therapy for this disease.

  17. Effect of flomoxef on blood coagulation and alcohol metabolism.

    Science.gov (United States)

    Uchida, K; Matsubara, T

    1991-01-01

    The effect of flomoxef, a newly developed oxacephem antibiotic with an N-hydroxyethyltetrazolethiol (HTT) side chain, on blood coagulation and alcohol metabolism was compared with that of a series of cephalosporin antibiotics with N-methyltetrazolethiol (NMTT), thiadiazolethiol (TDT) or methylthiadiazolethiol (MTDT) side chains in position 3' of the cephalosporin nucleus known to cause hypoprothrombinemia and bleeding in patients who are malnourished, debilitated and/or of high age. A disulfiram-like effect caused by inhibition of aldehyde dehydrogenase was observed for NMTT-containing antibiotics. Studies were carried out on healthy volunteers and on rats. Eight-day treatment with 2 g flomoxef i.v. once or twice daily in five and six healthy male volunteers, respectively, did not cause any significant changes in prothrombin time (PT), coagulation factors II, VII, IX or X, in hepaplastin values or fibrinogen levels, activated partial thromboplastin time (APTT), platelet counts, bleeding time, or collagen- and ADP-induced platelet aggregation. Inhibition of vitamin K epoxide reductase was observed in rats treated with flomoxef, yet to a much lesser extent than observed for cephalosporins with NMTT, TDT or MTDT side chains. This defect was quickly normalized by vitamin K injection. There were no differences between oxacephem (1-O) and cephem (1-S) compounds with respect to effects on blood clotting and platelet aggregation. Flomoxef and its side chain HTT showed no influence on alcohol metbolism.

  18. High Protein Diet and Huntington's Disease

    Science.gov (United States)

    Wu, Yih-Ru; Chen, Pei; Tsai, Fuu-Jen; Yang, Chueh-Lien; Tsao, Ya-Tzu; Chang, Wen; Hsieh, I-Shan; Chern, Yijuang; Soong, Bing-Wen

    2015-01-01

    Huntington’s disease (HD) is a neurodegenerative disorder caused by the huntingtin (HTT) gene with expanded CAG repeats. In addition to the apparent brain abnormalities, impairments also occur in peripheral tissues. We previously reported that mutant Huntingtin (mHTT) exists in the liver and causes urea cycle deficiency. A low protein diet (17%) restores urea cycle activity and ameliorates symptoms in HD model mice. It remains unknown whether the dietary protein content should be monitored closely in HD patients because the normal protein consumption is lower in humans (~15% of total calories) than in mice (~22%). We assessed whether dietary protein content affects the urea cycle in HD patients. Thirty HD patients were hospitalized and received a standard protein diet (13.7% protein) for 5 days, followed by a high protein diet (HPD, 26.3% protein) for another 5 days. Urea cycle deficiency was monitored by the blood levels of citrulline and ammonia. HD progression was determined by the Unified Huntington’s Disease Rating Scale (UHDRS). The HPD increased blood citrulline concentration from 15.19 μmol/l to 16.30 μmol/l (p = 0.0378) in HD patients but did not change blood ammonia concentration. A 2-year pilot study of 14 HD patients found no significant correlation between blood citrulline concentration and HD progression. Our results indicated a short period of the HPD did not markedly compromise urea cycle function. Blood citrulline concentration is not a reliable biomarker of HD progression. PMID:25992839

  19. High Protein Diet and Huntington's Disease.

    Directory of Open Access Journals (Sweden)

    Chiung-Mei Chen

    Full Text Available Huntington's disease (HD is a neurodegenerative disorder caused by the huntingtin (HTT gene with expanded CAG repeats. In addition to the apparent brain abnormalities, impairments also occur in peripheral tissues. We previously reported that mutant Huntingtin (mHTT exists in the liver and causes urea cycle deficiency. A low protein diet (17% restores urea cycle activity and ameliorates symptoms in HD model mice. It remains unknown whether the dietary protein content should be monitored closely in HD patients because the normal protein consumption is lower in humans (~15% of total calories than in mice (~22%. We assessed whether dietary protein content affects the urea cycle in HD patients. Thirty HD patients were hospitalized and received a standard protein diet (13.7% protein for 5 days, followed by a high protein diet (HPD, 26.3% protein for another 5 days. Urea cycle deficiency was monitored by the blood levels of citrulline and ammonia. HD progression was determined by the Unified Huntington's Disease Rating Scale (UHDRS. The HPD increased blood citrulline concentration from 15.19 μmol/l to 16.30 μmol/l (p = 0.0378 in HD patients but did not change blood ammonia concentration. A 2-year pilot study of 14 HD patients found no significant correlation between blood citrulline concentration and HD progression. Our results indicated a short period of the HPD did not markedly compromise urea cycle function. Blood citrulline concentration is not a reliable biomarker of HD progression.

  20. An experimental investigation into the formation of polycyclic-aromatic hydrocarbons (PAH) from pyrolysis of biomass materials

    Energy Technology Data Exchange (ETDEWEB)

    McGrath, T.; Sharma, R.; Hajaligol, M. [Philip Morris USA, Richmond, VA (United States). Research Center

    2001-10-09

    The formation of polycyclic-aromatic hydrocarbons (PAH) from the pyrolysis of cellulose, pectin and chlorogenic acid was studied. The primary product, mostly primary volatile tar, was exposed to a higher thermal severity i.e. high temperatures and long residence times. The reactor setup consisted of a quartz tube with two zones, zone I and II, each heated and controlled separately. Zone I was used to first pyrolyse the substrate at 300{degree}C to produce a low temperature tar (LTT) as well as to pyrolyse the product char at 600{degree}C to produce a high temperature tar (HTT). The LTT and HTT were then subjected to a high thermal severity in the second zone (zone II) where the temperature was varied between 700 and 850{degree}C. The residence time of the volatiles in zone II was varied between ca. 90 and 1400 ms (calculated at 800{degree}C). The results show that the yield of most PAHs increased with temperature, except in a few cases where the yield of two- and three-ring PAHs exhibited a maximum. PAHs yields also generally increased as the residence time was increased from 90 to 1400 ms at 800{degree}C. 19 refs., 9 figs., 2 tabs.

  1. Potentiometric application of boron- and phosphorus-doped glassy carbon electrodes

    Directory of Open Access Journals (Sweden)

    ZORAN V. LAUSEVIC

    2001-03-01

    Full Text Available Acomparative study was carried out of the potentiometric application of boronand phosphorus-doped and undoped glassy carbon samples prepared at the same heat treatment temperature (HTT 1000°C. The electrochemical activities of the obtained electrode materials were investigated on the example of argentometric titrations. It was found that the electrochemical behaviour of the doped glassy carbon samples are very similar to a Sigri (undoped glassy carbon sample (HTT 2400°C. The experiments showed that the potentiometric response depends on the polarization mode, the nature of the sample, the pretreatment of the electrode surface, and the nature of the supporting electrolyte. The amounts of iodide, bromide, and of chloridewere determined to be 1.27 mg, 0.80 mg and 0.54 mg, respectively, with a maximum relative standard deviation of less than 1.1%. The obtained results are in good agreement with the results of comparative potentiometric titrations using a silver indicator electrode. The titrationmethod was applied to the indirect determination of pyridoxine hydrochloride, i.e., vitamin B6.

  2. Testing differential susceptibility: Plasticity genes, the social environment, and their interplay in adolescent response inhibition.

    Science.gov (United States)

    Richards, Jennifer S; Arias Vásquez, Alejandro; van Rooij, Daan; van der Meer, Dennis; Franke, Barbara; Hoekstra, Pieter J; Heslenfeld, Dirk J; Oosterlaan, Jaap; Faraone, Stephen V; Hartman, Catharina A; Buitelaar, Jan K

    2017-06-01

    Impaired inhibitory control is a key feature of attention-deficit/hyperactivity disorder (ADHD). We investigated gene-environment interaction (GxE) as a possible contributing factor to response inhibition variation in context of the differential susceptibility theory. This states individuals carrying plasticity gene variants will be more disadvantaged in negative, but more advantaged in positive environments. Behavioural and neural measures of response inhibition were assessed during a Stop-signal task in participants with (N = 197) and without (N = 295) ADHD, from N = 278 families (age M = 17.18, SD =3.65). We examined GxE between candidate plasticity genes (DAT1, 5-HTT, DRD4) and social environments (maternal expressed emotion, peer affiliation). A DRD4 × Positive peer affiliation interaction was found on the right fusiform gyrus (rFG) activation during successful inhibition. Further, 5-HTT short allele carriers showed increased rFG activation during failed inhibitions. Maternal warmth and positive peer affiliation were positively associated with right inferior frontal cortex activation during successful inhibition. Deviant peer affiliation was positively related to the error rate. While a pattern of differential genetic susceptibility was found, more clarity on the role of the FG during response inhibition is warranted before firm conclusions can be made. Positive and negative social environments were related to inhibitory control. This extends previous research emphasizing adverse environments.

  3. Effects of 2450 MHz microwave radiation on meiosis and reproduction in male mice

    International Nuclear Information System (INIS)

    Manikowska-Czerska, E.; Czerski, P.; Leach, W.M.

    1988-01-01

    A series of studies to examine effects od continuous wave 2450 MHz radiation on meiosis and on chromosomes of germ cells in male CBA/CAY or ICR mice, by means of the spermatocyte (SCT), heritable translocation (HTT) and dominant lethal (DLT) tests is presented. Animals were exposed in an environmentally controlled waveguide system during two consecutive weeks, 30 minutes daily, six days a week. Specific absorption rates (SAR) were used in the range from 0.05 to 20 W/kg. With the SCT, it was demonstrated that chromosomal translocations can be induced by exposure during the first meiotic prophase, particularly during initial and early pachytene stages. The HTT results demonstrated that balanced translocations may be recovered among offspring of exposed males. The DLT provided confirmatory data on effects during prophase and indicated that chromosomal damage may be also induced by exposure of spermatids, during the maturation stage, and of spermatozoa. No changes were observed in spermatogonia. Thus, the effects of exposure were limited to one spermatogenic cycle. Genetically significant effects were induced at an SAR of 2 W/kg in the testes. For comparison, an SAR of 0.4 W/kg is used commonly as a basis for occupational exposure limits

  4. Contamination of liquid oxygen by pressurized gaseous nitrogen

    Science.gov (United States)

    Zuckerwar, Allan J.; King, Tracy K.; Ngo, Kim Chi

    1989-01-01

    The penetration of pressurized gaseous nitrogen (GN2) into liquid oxygen (LOX) was investigated experimentally in the 7-inch High Temperature Tunnel, the pilot tunnel for the 8-foot High Temperature Tunnel (8'HTT) at Langley Research Center. A preliminary test using a nuclear monitor revealed the extent of the liquid nitrogen (LN2) build-up at the LOX interface as a function of GN2 pressure. Then an adaptation of the differential flash vaporization technique was used to determine the binary diffusivity of the LOX-LN2 system at a temperature of 90.2 K. The measured value D equals 0.000086 sq cm/s + or - 25 percent together with two prior measurements at lower temperatures revealed an excellent fit to the Arrhenius equation, yielding a pre-exponential factor D sub 0 equals 0.0452 sq cm/s and an activation enthalpy H equals 1.08 kcal/mol. At a pressure of 1700 psi and holding time of 15 min, the penetration of LN2 into LOX (to a 1 percent contamination level) was found to be 0.9 cm, indicating but minimal impact upon 8'HTT operations.

  5. Pitfalls in the detection of cholesterol in Huntington’s disease models

    Science.gov (United States)

    Marullo, Manuela; Valenza, Marta; Leoni, Valerio; Caccia, Claudio; Scarlatti, Chiara; De Mario, Agnese; Zuccato, Chiara; Di Donato, Stefano; Carafoli, Ernesto; Cattaneo, Elena

    2012-01-01

    Background Abnormalities in brain cholesterol homeostasis have been reported in Huntington’s disease (HD), an adult-onset neurodegenerative disorder caused by an expansion in the number of CAG repeats in the huntingtin (HTT) gene. However, the results have been contradictory with respect to whether cholesterol levels increase or decrease in HD models. Biochemical and mass spectrometry methods show reduced levels of cholesterol precursors and cholesterol in HD cells and in the brains of several HD animal models. Abnormal brain cholesterol homeostasis was also inferred from studies in HD patients. In contrast, colorimetric and enzymatic methods indicate cholesterol accumulation in HD cells and tissues. Here we used several methods to investigate cholesterol levels in cultured cells in the presence or absence of mutant HTT protein. Results Colorimetric and enzymatic methods with low sensitivity gave variable results, whereas results from a sensitive analytical method, gas chromatography-mass spectrometry, were more reliable. Sample preparation, high cell density and cell clonality also influenced the detection of intracellular cholesterol. Conclusions Detection of cholesterol in HD samples by colorimetric and enzymatic assays should be supplemented by detection using more sensitive analytical methods. Care must be taken to prepare the sample appropriately. By evaluating lathosterol levels using isotopic dilution mass spectrometry, we confirmed reduced cholesterol biosynthesis in knock-in cells expressing the polyQ mutation in a constitutive or inducible manner. *Correspondence should be addressed to Elena Cattaneo: elena.cattaneo@unimi.it PMID:23145355

  6. Pitfalls in the detection of cholesterol in Huntington's disease models.

    Science.gov (United States)

    Marullo, Manuela; Valenza, Marta; Leoni, Valerio; Caccia, Claudio; Scarlatti, Chiara; De Mario, Agnese; Zuccato, Chiara; Di Donato, Stefano; Carafoli, Ernesto; Cattaneo, Elena

    2012-10-11

    Background Abnormalities in brain cholesterol homeostasis have been reported in Huntington's disease (HD), an adult-onset neurodegenerative disorder caused by an expansion in the number of CAG repeats in the huntingtin (HTT) gene. However, the results have been contradictory with respect to whether cholesterol levels increase or decrease in HD models. Biochemical and mass spectrometry methods show reduced levels of cholesterol precursors and cholesterol in HD cells and in the brains of several HD animal models. Abnormal brain cholesterol homeostasis was also inferred from studies in HD patients. In contrast, colorimetric and enzymatic methods indicate cholesterol accumulation in HD cells and tissues. Here we used several methods to investigate cholesterol levels in cultured cells in the presence or absence of mutant HTT protein. Results Colorimetric and enzymatic methods with low sensitivity gave variable results, whereas results from a sensitive analytical method, gas chromatography-mass spectrometry, were more reliable. Sample preparation, high cell density and cell clonality also influenced the detection of intracellular cholesterol. Conclusions Detection of cholesterol in HD samples by colorimetric and enzymatic assays should be supplemented by detection using more sensitive analytical methods. Care must be taken to prepare the sample appropriately. By evaluating lathosterol levels using isotopic dilution mass spectrometry, we confirmed reduced cholesterol biosynthesis in knock-in cells expressing the polyQ mutation in a constitutive or inducible manner. *Correspondence should be addressed to Elena Cattaneo: elena.cattaneo@unimi.it.

  7. Perceived discrimination, serotonin transporter linked polymorphic region status, and the development of conduct problems.

    Science.gov (United States)

    Brody, Gene H; Beach, Steven R H; Chen, Yi-Fu; Obasi, Ezemenari; Philibert, Robert A; Kogan, Steven M; Simons, Ronald L

    2011-05-01

    This study examined the prospective relations of adolescents' perceptions of discrimination and their genetic status with increases in conduct problems. Participants were 461 African American youths residing in rural Georgia (Wave 1 mean age = 15.5 years) who provided three waves of data and a saliva sample from which a polymorphism in the SCL6A4 (serotonin transporter [5-HTT]) gene polymorphism known as the 5-HTT linked promoter region (5-HTTLPR) was genotyped. Data analyses using growth curve modeling indicated that perceived discrimination was significantly related to the slope of conduct problems. As hypothesized, interactions between perceived discrimination and genetic status emerged for male but not female youths. Compared with those carrying two copies of the long allele variant of 5-HTTLPR, male youths carrying one or two copies of its short allele variant evinced higher rates of conduct problems over time when they perceived high levels of racial discrimination. These findings are consistent with resilience and differential susceptibility propositions stating that genes can both foster sensitivity to adverse events and confer protection from those events.

  8. Fission gas behavior during fast thermal transients

    International Nuclear Information System (INIS)

    Esteves, R.G.

    1976-01-01

    The behavior of non-equilibrium fission in fuel elements undergoing fast thermal transients is analyzed. To facilitate the analysis, a new variable, the equilibrium variable (EV) is defined. This variable, together with bubble radius, completely specifies a bubble with respect to its size and equilibrium condition. The analysis is coded using a two-variable (radius and EV) multigroup numerical approximation that accepts as input the time-temperature history, the time-fission rate history, and the time-thermal gradient history of the fuel element. Studies were performed to test the code for convergence with respect to the time interval and the number of groups chosen. For a series of transient simulation studies, the measurements obtained at HEDL (microscopic examination of intragranular porosity in oxide fuel transient-tested in TREAT) are used. Two different transient histories were selected; the first, a high-temperature transient (HTT) with a peak at 2477 0 K and the second, a low-temperature transient (LTT) with a peak-temperature at 2000 0 K. The LTT was simulated for three different conditions: Bubbles were allowed to move via (a) only biased migration, (b) via random migration, and (c) via both mechanisms. The HTT was also run for both mechanisms. The agreement with HEDL microscopic observations was fair for bubbles smaller than 964 A in diameter, and poor for larger bubbles. Bubbles that grew during the heat-up part of the transient were frozen at a larger size during the cool down

  9. Polymorphisms of genes related to the hypothalamic-pituitary-adrenal axis influence the cortisol awakening response as well as self-perceived stress.

    Science.gov (United States)

    Li-Tempel, Ting; Larra, Mauro F; Winnikes, Ulrike; Tempel, Tobias; DeRijk, Roel H; Schulz, André; Schächinger, Hartmut; Meyer, Jobst; Schote, Andrea B

    2016-09-01

    The hypothalamus-pituitary-adrenal (HPA) axis is a crucial endocrine system for coping with stress. A reliable and stable marker for the basal state of that system is the cortisol awakening response (CAR). We examined the influence of variants of four relevant candidate genes; the mineralocorticoid receptor gene (MR), the glucocorticoid receptor gene (GR), the serotonin transporter gene (5-HTT) and the gene encoding the brain-derived neurotrophic factor (BDNF) on CAR and self-perceived stress in 217 healthy subjects. We found that polymorphisms of GR influenced both, the basal state of the HPA axis as well as self-perceived stress. MR only associated with self-perceived stress and 5-HTT only with CAR. BDNF did not affected any of the investigated indices. In summary, we suggest that GR variants together with the CAR and supplemented with self reports on perceived stress might be useful indicators for the basal HPA axis activity. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Epigenetic and epistatic interactions between serotonin transporter and brain-derived neurotrophic factor genetic polymorphism: insights in depression.

    Science.gov (United States)

    Ignácio, Z M; Réus, G Z; Abelaira, H M; Quevedo, J

    2014-09-05

    Epidemiological studies have shown significant results in the interaction between the functions of brain-derived neurotrophic factor (BDNF) and 5-HT in mood disorders, such as major depressive disorder (MDD). The latest research has provided convincing evidence that gene transcription of these molecules is a target for epigenetic changes, triggered by stressful stimuli that starts in early childhood and continues throughout life, which are subsequently translated into structural and functional phenotypes culminating in depressive disorders. The short variants of 5-HTTLPR and BDNF-Met are seen as forms which are predisposed to epigenetic aberrations, which leads individuals to a susceptibility to environmental adversities, especially when subjected to stress in early life. Moreover, the polymorphic variants also feature epistatic interactions in directing the functional mechanisms elicited by stress and underlying the onset of depressive disorders. Also emphasized are works which show some mediators between stress and epigenetic changes of the 5-HTT and BDNF genes, such as the hypothalamic-pituitary-adrenal (HPA) axis and the cAMP response element-binding protein (CREB), which is a cellular transcription factor. Both the HPA axis and CREB are also involved in epistatic interactions between polymorphic variants of 5-HTTLPR and Val66Met. This review highlights some research studying changes in the epigenetic patterns intrinsic to genes of 5-HTT and BDNF, which are related to lifelong environmental adversities, which in turn increases the risks of developing MDD. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  11. Human Neural Stem Cell Transplantation Rescues Functional Deficits in R6/2 and Q140 Huntington's Disease Mice

    Directory of Open Access Journals (Sweden)

    Jack C. Reidling

    2018-01-01

    Full Text Available Huntington's disease (HD is an inherited neurodegenerative disorder with no disease-modifying treatment. Expansion of the glutamine-encoding repeat in the Huntingtin (HTT gene causes broad effects that are a challenge for single treatment strategies. Strategies based on human stem cells offer a promising option. We evaluated efficacy of transplanting a good manufacturing practice (GMP-grade human embryonic stem cell-derived neural stem cell (hNSC line into striatum of HD modeled mice. In HD fragment model R6/2 mice, transplants improve motor deficits, rescue synaptic alterations, and are contacted by nerve terminals from mouse cells. Furthermore, implanted hNSCs are electrophysiologically active. hNSCs also improved motor and late-stage cognitive impairment in a second HD model, Q140 knockin mice. Disease-modifying activity is suggested by the reduction of aberrant accumulation of mutant HTT protein and expression of brain-derived neurotrophic factor (BDNF in both models. These findings hold promise for future development of stem cell-based therapies.

  12. A Study of the Standard Model Higgs Boson Decaying to a Pair of Tau Leptons with the CMS Detector at the LHC

    CERN Document Server

    AUTHOR|(INSPIRE)INSPIRE-00398807; Smith, Wesley H.; Herndon, Matthew F.

    This thesis presents a 5.5 standard deviation observation of the Higgs boson decaying to fermions using the data collected at the LHC at 13\\TeV center-of-mass energy. The studied dataset corresponds to an integrated luminosity of 35.9\\fbinv. The best fit signal strength for the $\\htt$ process is measured to be $\\mu = 1.24 ^{+0.29} _{-0.27}$, consistent with standard model predictions. Unique event categories are used targeting the leading Higgs boson production processes, gluon fusion, vector boson fusion, and associated production. This provides signal regions sensitive to Higgs boson couplings to both fermions and vector bosons. These two Higgs boson couplings are measured and are consistent with standard model predictions within one standard deviation. This 5.5 standard deviation observation of the $\\htt$ process and the consistency of the Higgs boson couplings with the standard model provide confirmation of the Higgs boson Yukawa couplings to fermions. This is evidence that the Higgs field provides mass f...

  13. Assessment of motor function, sensory motor gating and recognition memory in a novel BACHD transgenic rat model for huntington disease.

    Science.gov (United States)

    Abada, Yah-Se K; Nguyen, Huu Phuc; Schreiber, Rudy; Ellenbroek, Bart

    2013-01-01

    Huntington disease (HD) is frequently first diagnosed by the appearance of motor symptoms; the diagnosis is subsequently confirmed by the presence of expanded CAG repeats (> 35) in the HUNTINGTIN (HTT) gene. A BACHD rat model for HD carrying the human full length mutated HTT with 97 CAG-CAA repeats has been established recently. Behavioral phenotyping of BACHD rats will help to determine the validity of this model and its potential use in preclinical drug discovery studies. The present study seeks to characterize the progressive emergence of motor, sensorimotor and cognitive deficits in BACHD rats. Wild type and transgenic rats were tested from 1 till 12 months of age. Motor tests were selected to measure spontaneous locomotor activity (open field) and gait coordination. Sensorimotor gating was assessed in acoustic startle response paradigms and recognition memory was evaluated in an object recognition test. Transgenic rats showed hyperactivity at 1 month and hypoactivity starting at 4 months of age. Motor coordination imbalance in a Rotarod test was present at 2 months and gait abnormalities were seen in a Catwalk test at 12 months. Subtle sensorimotor changes were observed, whereas object recognition was unimpaired in BACHD rats up to 12 months of age. The current BACHD rat model recapitulates certain symptoms from HD patients, especially the marked motor deficits. A subtle neuropsychological phenotype was found and further studies are needed to fully address the sensorimotor phenotype and the potential use of BACHD rats for drug discovery purposes.

  14. Enhancing the gene-environment interaction framework through a quasi-experimental research design: evidence from differential responses to September 11.

    Science.gov (United States)

    Fletcher, Jason M

    2014-01-01

    This article uses a gene-environment interaction framework to examine the differential responses to an objective external stressor based on genetic variation in the production of depressive symptoms. This article advances the literature by utilizing a quasi-experimental environmental exposure design, as well as a regression discontinuity design, to control for seasonal trends, which limit the potential for gene-environment correlation and allow stronger causal claims. Replications are attempted for two prominent genes (5-HTT and MAOA), and three additional genes are explored (DRD2, DRD4, and DAT1). This article provides evidence of a main effect of 9/11 on reports of feelings of sadness and fails to replicate a common finding of interaction using 5-HTT but does show support for interaction with MAOA in men. It also provides new evidence that variation in the DRD4 gene modifies an individual's response to the exposure, with individuals with no 7-repeats found to have a muted response.

  15. Common variations in 4p locus are related to male completed suicide.

    Science.gov (United States)

    Must, Anne; Kõks, Sulev; Vasar, Eero; Tasa, Gunnar; Lang, Aavo; Maron, Eduard; Väli, Marika

    2009-01-01

    Suicidal behavior is a multifactorial phenomenon, with a significant genetic predisposition. To assess the contribution of genes in the 4p region to suicide risk, we genotyped 36 single nucleotide polymorphisms from a 49Mb region on the chromosome arm 4p11-16 in a total of 288 male suicide victims and 327 healthy male volunteers. The nonsynonymous variants rs1383180 in EVC gene, rs6811863 in TBC1D1 gene, rs362272 in HTT gene, and rs734312 in WFS1 gene were associated to the male completed suicide. However, only EVC polymorphism remained significant after correcting for multiple comparisons (P < .05 after 10 K permutations). The function of these genes is not clear yet. WFS1 and HTT are related to the unfolded protein response and endoplasmic reticulum stress, and TBC1D1 is a GTPase activator. EVC is a protein with transmembrane and leucine zipper domains, its function has not been elucidated yet. Further studies are required in order to reveal the role of these four polymorphisms in the pathoetiology of suicide.

  16. The POLARBEAR Experiment: Design and Characterization

    Science.gov (United States)

    Kermish, Zigmund David

    We present the design and characterization of the POLARBEAR experiment. POLARBEAR is a millimeter-wave polarimeter that will measure the Cosmic Microwave Background (CMB) polarization. It was designed to have both the sensitivity and angular resolution to detect the expected B-mode polarization due to gravitational lensing at small angular scales while still enabling a search for the degree scale B-mode polarization caused by inflationary gravitational waves. The instrument utilizes the Huan Tran Telescope (HTT), a 2.5-meter primary mirror telescope, coupled to a unique focal plane of 1,274 antenna-coupled transition-edge sensor (TES) detectors to achieve unprecedented sensitivity from angular scales of the experiment's 4 arcminute beam to several degrees. This dissertation focuses on the design, integration and characterization of the cryogenic receiver for the POLARBEAR instrument. The receiver cools the ˜20 cm focal plane to 0.25 Kelvin, with detector readout provided by a digital frequency-multiplexed SQUID system. The POLARBEAR receiver was been successfully deployed on the HTT for an engineering run in the Eastern Sierras of California and is currently deployed on Cerro Toco in the Atacama Dessert of Chile. We present results from lab tests done to characterize the instrument, from the engineering run and preliminary results from Chile.

  17. Association of Anxiety-Related Polymorphisms with Sports Performance in Chilean Long Distance Triathletes: A Pilot Study.

    Science.gov (United States)

    Sanhueza, Jorge A; Zambrano, Tomás; Bahamondes-Avila, Carlos; Salazar, Luis A

    2016-12-01

    Different factors affecting athletic performance are well established: intensity and type of training, anthropometric characteristics as well as an important psychological component. However, the contribution of the genetic background has been less investigated. The aim of the present study was to investigate the influence of polymorphisms within genes associated with stress and anxiety ( 5HTT , CRH2R , ACE , NK1R , 5HT1AR and CRF-BP ) on the physical capability and sports performance in triathletes. One hundred and ninety two (192) unrelated Chilean triathletes who participated in the 2014 70.3 Pucón city triathlon were divided into opposite subgroups of sports performance according to their time results. We identified significant associations for five polymorphisms ( 5HTT 5-HTTLPR, ACE I/D, NK1R rs6715729, 5HT1AR -1019C>G and CRF-BP CRF-BPs11) with athletic performance. Our results indicate that these polymorphisms are associated with differential sports performance in Chilean triathletes, establishing an initial background for better understanding the relationship between physical performance, genetics and anxiety disorders.

  18. Association of Anxiety-Related Polymorphisms with Sports Performance in Chilean Long Distance Triathletes: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Jorge A. Sanhueza, Tomás Zambrano, Carlos Bahamondes-Avila, Luis A. Salazar

    2016-12-01

    Full Text Available Different factors affecting athletic performance are well established: intensity and type of training, anthropometric characteristics as well as an important psychological component. However, the contribution of the genetic background has been less investigated. The aim of the present study was to investigate the influence of polymorphisms within genes associated with stress and anxiety (5HTT, CRH2R, ACE, NK1R, 5HT1AR and CRF-BP on the physical capability and sports performance in triathletes. One hundred and ninety two (192 unrelated Chilean triathletes who participated in the 2014 70.3 Pucón city triathlon were divided into opposite subgroups of sports performance according to their time results. We identified significant associations for five polymorphisms (5HTT 5-HTTLPR, ACE I/D, NK1R rs6715729, 5HT1AR -1019C>G and CRF-BP CRF-BPs11 with athletic performance. Our results indicate that these polymorphisms are associated with differential sports performance in Chilean triathletes, establishing an initial background for better understanding the relationship between physical performance, genetics and anxiety disorders.

  19. Correlations of Behavioral Deficits with Brain Pathology Assessed through Longitudinal MRI and Histopathology in the HdhQ150/Q150 Mouse Model of Huntington's Disease.

    Directory of Open Access Journals (Sweden)

    Ivan Rattray

    Full Text Available A variety of mouse models have been developed that express mutant huntingtin (mHTT leading to aggregates and inclusions that model the molecular pathology observed in Huntington's disease. Here we show that although homozygous HdhQ150 knock-in mice developed motor impairments (rotarod, locomotor activity, grip strength by 36 weeks of age, cognitive dysfunction (swimming T maze, fear conditioning, odor discrimination, social interaction was not evident by 94 weeks. Concomitant to behavioral assessments, T2-weighted MRI volume measurements indicated a slower striatal growth with a significant difference between wild type (WT and HdhQ150 mice being present even at 15 weeks. Indeed, MRI indicated significant volumetric changes prior to the emergence of the "clinical horizon" of motor impairments at 36 weeks of age. A striatal decrease of 27% was observed over 94 weeks with cortex (12% and hippocampus (21% also indicating significant atrophy. A hypothesis-free analysis using tensor-based morphometry highlighted further regions undergoing atrophy by contrasting brain growth and regional neurodegeneration. Histology revealed the widespread presence of mHTT aggregates and cellular inclusions. However, there was little evidence of correlations between these outcome measures, potentially indicating that other factors are important in the causal cascade linking the molecular pathology to the emergence of behavioral impairments. In conclusion, the HdhQ150 mouse model replicates many aspects of the human condition, including an extended pre-manifest period prior to the emergence of motor impairments.

  20. Genetic Contributors to Intergenerational CAG Repeat Instability in Huntington's Disease Knock-In Mice.

    Science.gov (United States)

    Neto, João Luís; Lee, Jong-Min; Afridi, Ali; Gillis, Tammy; Guide, Jolene R; Dempsey, Stephani; Lager, Brenda; Alonso, Isabel; Wheeler, Vanessa C; Pinto, Ricardo Mouro

    2017-02-01

    Huntington's disease (HD) is a neurodegenerative disorder caused by the expansion of a CAG trinucleotide repeat in exon 1 of the HTT gene. Longer repeat sizes are associated with increased disease penetrance and earlier ages of onset. Intergenerationally unstable transmissions are common in HD families, partly underlying the genetic anticipation seen in this disorder. HD CAG knock-in mouse models also exhibit a propensity for intergenerational repeat size changes. In this work, we examine intergenerational instability of the CAG repeat in over 20,000 transmissions in the largest HD knock-in mouse model breeding datasets reported to date. We confirmed previous observations that parental sex drives the relative ratio of expansions and contractions. The large datasets further allowed us to distinguish effects of paternal CAG repeat length on the magnitude and frequency of expansions and contractions, as well as the identification of large repeat size jumps in the knock-in models. Distinct degrees of intergenerational instability were observed between knock-in mice of six background strains, indicating the occurrence of trans-acting genetic modifiers. We also found that lines harboring a neomycin resistance cassette upstream of Htt showed reduced expansion frequency, indicative of a contributing role for sequences in cis, with the expanded repeat as modifiers of intergenerational instability. These results provide a basis for further understanding of the mechanisms underlying intergenerational repeat instability. Copyright © 2017 by the Genetics Society of America.

  1. Early Detection of Apathetic Phenotypes in Huntington's Disease Knock-in Mice Using Open Source Tools.

    Science.gov (United States)

    Minnig, Shawn; Bragg, Robert M; Tiwana, Hardeep S; Solem, Wes T; Hovander, William S; Vik, Eva-Mari S; Hamilton, Madeline; Legg, Samuel R W; Shuttleworth, Dominic D; Coffey, Sydney R; Cantle, Jeffrey P; Carroll, Jeffrey B

    2018-02-02

    Apathy is one of the most prevalent and progressive psychiatric symptoms in Huntington's disease (HD) patients. However, preclinical work in HD mouse models tends to focus on molecular and motor, rather than affective, phenotypes. Measuring behavior in mice often produces noisy data and requires large cohorts to detect phenotypic rescue with appropriate power. The operant equipment necessary for measuring affective phenotypes is typically expensive, proprietary to commercial entities, and bulky which can render adequately sized mouse cohorts as cost-prohibitive. Thus, we describe here a home-built, open-source alternative to commercial hardware that is reliable, scalable, and reproducible. Using off-the-shelf hardware, we adapted and built several of the rodent operant buckets (ROBucket) to test Htt Q111/+ mice for attention deficits in fixed ratio (FR) and progressive ratio (PR) tasks. We find that, despite normal performance in reward attainment in the FR task, Htt Q111/+ mice exhibit reduced PR performance at 9-11 months of age, suggesting motivational deficits. We replicated this in two independent cohorts, demonstrating the reliability and utility of both the apathetic phenotype, and these ROBuckets, for preclinical HD studies.

  2. microRNA-128a dysregulation in transgenic Huntington’s disease monkeys

    Science.gov (United States)

    2014-01-01

    Background Huntington’s Disease (HD) is a progressive neurodegenerative disorder with a single causal mutation in the Huntingtin (HTT) gene. MicroRNAs (miRNAs) have recently been implicated as epigenetic regulators of neurological disorders, however, their role in HD pathogenesis is not well defined. Here we study transgenic HD monkeys (HD monkeys) to examine miRNA dysregulation in a primate model of the disease. Results In this report, 11 miRNAs were found to be significantly associated (P value monkeys. We further focused on one of those candidates, miR-128a, due to the corresponding disruption in humans and mice with HD as well as its intriguing lists of gene targets. miR-128a was downregulated in our HD monkey model by the time of birth. We then confirmed that miR-128a was also downregulated in the brains of pre-symptomatic and post-symptomatic HD patients. Additionally, our studies confirmed a panel of canonical HD signaling genes regulated by miR-128a, including HTT and Huntingtin Interaction Protein 1 (HIP1). Conclusion Our studies found that miR-128a may play a critical role in HD and could be a viable candidate as a therapeutic or biomarker of the disease. PMID:24929669

  3. An extension of hypotheses regarding rapid-acting, treatment-refractory, and conventional antidepressant activity of dextromethorphan and dextrorphan.

    Science.gov (United States)

    Lauterbach, Edward C

    2012-06-01

    It was previously hypothesized that dextromethorphan (DM) and dextrorphan (DX) may possess antidepressant properties, including rapid and conventional onsets of action and utility in treatment-refractory depression, based on pharmacodynamic similarities to ketamine. These similarities included sigma-1 (σ(1)) agonist and NMDA antagonist properties, calcium channel blockade, muscarinic binding, serotonin transporter (5HTT) inhibition, and μ receptor potentiation. Here, six specific hypotheses are developed in light of additional mechanisms and evidence. Comparable potencies to ketamine for DM and DX are detailed for σ(1) (DX>DM>ketamine), NMDA PCP site (DX>ketamine>DM), and muscarinic (DX>ketamine>DM) receptors, 5HTT (DM>DX≫ketamine), and NMDA antagonist potentiation of μ receptor stimulation (DM>ketamine). Rapid acting antidepressant properties of DM include NMDA high-affinity site, NMDR-2A, and functional NMDR-2B receptor antagonism, σ(1) stimulation, putative mTOR activation (by σ(1) stimulation, μ potentiation, and 5HTT inhibition), putative AMPA receptor trafficking (by mTOR activation, PCP antagonism, σ(1) stimulation, μ potentiation, and 5HTT inhibition), and dendritogenesis, spinogenesis, synaptogenesis, and neuronal survival by NMDA antagonism and σ(1) and mTOR signaling. Those for dextrorphan include NMDA high-affinity site and NMDR-2A antagonism, σ(1) stimulation, putative mTOR activation (by σ(1) stimulation and ß adrenoreceptor stimulation), putative AMPA receptor trafficking (by mTOR activation, PCP antagonism, σ(1) stimulation, ß stimulation, and μ antagonism), and dendritogenesis, spinogenesis, synaptogenesis, and neuronal survival by NMDA antagonism and σ(1) and mTOR signaling. Conventional antidepressant properties for dextromethorphan and dextrorphan include 5HTT and norepinephrine transporter inhibition, σ(1) stimulation, NMDA and PCP antagonism, and possible serotonin 5HT1b/d receptor stimulation. Additional properties for

  4. From X-Rays to MRI: Physics in GE

    Science.gov (United States)

    Schmitt, Roland W.

    2004-03-01

    The GE Research Laboratory, founded in 1900, became the first laboratory of scientific research in U.S. industry. William Coolidge, a physicist, joined the laboratory in 1905 and produced two advances of immense importance. The first, ductile tungsten, is still the heart of every incandescent light bulb. The second, the "Coolidge" X-Ray tube, remains an essential tool of modern medicine. In the process, Coolidge explored two main approaches of physics in industry. One addresses a commercial problem or opportunity (better light bulbs) and finds interesting physics. The other explores interesting physics (X-rays) and creates a commercial opportunity. This paper addresses the mix of these approaches during GE's years as an "electric" (and therefore physics-based) company. Episodes include the following: the work of Irving Langmuir (1932 Nobel laureate in chemistry, but as much physicist as chemist); the post-World War II "golden age of industrial physics" when the endless frontier offered opportunities from nuclear power to diamond making to superconductivity; the Nobel-prize winning work of Ivar Giaever; and interdisciplinary efforts that enabled GE to become a world business leader in two medical diagnostic technologies it did not invent: computed tomography and magnetic resonance imaging. I will speculate on whether this mix of problem-driven and opportunity-driven effort is as relevant to the 21st century as it was to the 20th.

  5. Linnulennult 2008. aasta lastekirjandusest / Mare Müürsepp

    Index Scriptorium Estoniae

    Müürsepp, Mare, 1958-

    2009-01-01

    Lühidalt on iseloomustatud järgmisi 2008. a. ilmunud lasteraamatuid: Raud, Piret. Printsess Luluu ja härra Kere (Tänapäev) ; Vilep, Heiki. Horlok ja Ürgvärava võti (A-Disain) ; Reinaus, Reeli. Saladuslik päevik (Tänapäev) ; Kumberg, Krista. Autopõnn Anto läheb seiklema (Koolibri) ; Ausman, Piia. Kaptenid avastavad maailma (Haus Galerii) ; Selli, Tiia. Neletriin ja Kapi-Kaarup (Tänapäev) ; Samuel, Evelin. Ükskord, kui sadas vihma (Ajakirjade Kirjastus) ; Pervik, Aino. Presidendilood (Tänapäev) ; Vainola, Kätlin. Mia, Konrad ja avanevad uksed (Tänapäev) ; Smitt, Katri. Varesejalakiri (Ilo) ; Käo, Henno. Mina, emme ja teised (Tänapäev) ; Saarna, Meelike. Mattias ja mamma (Tänapäev) ; Hinrikus, Kadri. Miia ja Friida (Eesti Ekspressi Kirjastus) ; Soopan, Ivar. Kõik poisid ei saa suureks (Eesti Päevaleht) ; Kutsar, Kuulo. Mõmmikute telerihaigus (Ilo)

  6. Neurosurgical strategies for Gilles de la Tourette’s syndrome

    Directory of Open Access Journals (Sweden)

    Karim Mukhida

    2008-09-01

    Full Text Available Karim Mukhida1,2, Matthew Bishop2, Murray Hong2, Ivar Mendez21Division of Neurosurgery, University of Toronto, Toronto, Ontario, Canada; 2Departments, of Anatomy and Neurobiology and Surgery (Neurosurgery, Dalhousie University, Halifax, Nova Scotia, CanadaAbstract: Tourette’s syndrome (TS is a neurological disorder characterized by motor and vocal tics that typically begin in childhood and often are accompanied by psychiatric comorbidities. Symptoms of TS may be socially disabling and cause secondary medical complications. Pharmacological therapies remain the mainstay of symptom management. For the subset of patients in whom TS symptoms are medically recalcitrant and do not dissipate by adulthood, neurosurgery may offer an alternative treatment strategy. Greater understanding of the neuroanatomic and pathophysiologic basis of TS has facilitated the development of surgical procedures that aim to ameliorate TS symptoms by lesions or deep brain stimulation of cerebral structures. Herein, the rationale for the surgical management of TS is discussed and neurosurgical experiences since the 1960s are reviewed. The necessity for neurosurgical strategies to be performed with appropriate ethical considerations is highlighted.Keywords: tourette’s syndrome, neurosurgery, deep brain stimulation, thalamus

  7. Lastekirjandus 2008 kurja kriitiku pilgu läbi / Ilona Martson

    Index Scriptorium Estoniae

    Martson, Ilona, 1970-

    2009-01-01

    Ülevaade 2008. aasta eesti lastekirjandusest. Pikemalt käsitletakse järgmisi autoreid ja nende teoseid: Piret Raud "Printsess Luluu", Aino Pervik "Presidendilood", Kristiina Kass "Petra lood", Kätlin Vainola "Mia, Konrad ja avanevad uksed", Kerttu Soans "Külaline vannis", Wimberg "Härra Padakonn", Leelo Tungal "Seltsimees laps", Kadri Hinrikus "Miia ja Friida", Ivar Soopan "Kõik poisid ei saa suureks", Siiri Laidla "Raamatukogunõid Rosaalie", Siiri Laidla "Armas hunt", Reeli Reinaus "Saladuslik päevik", Tiia Selli "Neletriin ja Kapi-Kaarup", Markus Saksatamm "Võlur Sinku-Vinku ja nõiatrall", Evelin Samuel "Ükskord, kui sadas vihma", Mikä Keränen "Varastatud oranž jalgratas", Ivo Parbus "Draakon Rudolf", Urmas Nemvalts "Väikeste meeste lennumasinajutud", Lehte Hainsalu "Väike valge", Jaan Tangsoo "Mina ja minu pere", Aidi Vallik "Pints ja Tutsik", Heiki Vilep "Horlok ja Ürgvärava võti", Evelin Samuel "Hiigelsoojad pilvelambad", Sulev Oll "Hea tuju kuju", Paul-Eerik Rummo "Kui lähed teele koidu eel", Heljo Mänd "Suve suurmüük", Heljo Mänd "Sügise süda", Heljo Mänd "Kevade reklaam", Heljo Mänd "Talve Top", Ülo Pikkov. Presidendi torukübar

  8. Mr Bjarne Mork-Eidem, Director General, Norwegian State Audit

    CERN Multimedia

    Maximilien Brice

    2003-01-01

    Photos 01,02: Mr Bjarne Mørk-Eidem, Auditor General of Norway (centre) visiting the ATLAS assembly hall in building 180, with from left to right: Prof. Steinar Stapnes, University of Oslo ; Mr Per Ivar Lied, Permanent Mission of Norway, Geneva ; Prof. Egil Lillestøl, University of Bergen and Mr Jan Otto Jøranli, Office of the Auditor General of Norway, May 2003. Photo 03: Mr Bjarne Mørk-Eidem, Auditor General of Norway (left) visiting the ATLAS assembly hall in building 180, with from left to right: Mr Jan Otto Jøranli, Office of the Auditor General of Norway ; Prof. Steinar Stapnes, University of Oslo and Prof. Egil Lillestøl, University of Bergen, May 2003. Photo 04: Mr Bjarne Mørk-Eidem, Auditor General of Norway, during his visit of the ATLAS assembly hall in building 180, May 2003. Photo 05: From left to right: Mr Jan Otto Jøranli, Office of the Auditor General of Norway ; Mr Bjarne Mørk-Eidem, Auditor General of Norway; Prof. Egil Lillestøl, University of Bergen and Prof. Steinar Stapnes, Univ...

  9. Association study of serotonin transporter and monoamine oxidase A genes polymorphisms with antisocial personality disorder in Han Chinese male%5-羟色胺转运体基因和单胺氧化酶A基因多态性与汉族男性反社会人格障碍患者的关联分析

    Institute of Scientific and Technical Information of China (English)

    茆正洪; 谭钊安; 柯晓燕; 郑大同; 曾彦英; 张建平; 李树明

    2010-01-01

    目的 探讨5-羟色胺转运体基因(5-HTT)第2内含子的一个可变数串联重复序列(Stin2.VNTR)和单胺氧化酶A(MAOA)基因14外显子上的一种限制性片段长度多态性(EcoRV-RFLP)与汉族男性反社会人格障碍(APD),尤其是具有高度冲动性APD的遗传易感性的关系.方法 (1)APD组:对南京地区某监狱男性服刑人员进行人格诊断问卷(PDQ-4+)调查,在PDQ得分为阳性的可疑人群中由临床医师以美国精神障碍诊断与统计手册第4版(DSM-Ⅳ)关于APD诊断标准进一步确诊,入组118例;全部进行Barratt冲动量表(BIS-11)评分,以冲动总分中位值为界,划分为高冲动APD组和低冲动APD组.(2)监狱对照组:经PDQ排除人格障碍的250名服刑人员作为监狱内对照.(3)正常对照组:同时期医院健康体检者300名设为正常对照.取所有人员血液标本提取DNA,应用聚合酶链反应(PCR)和限制性片段长度多态性方法,对等位基因频率和基因型频率进行对比分析.结果 (1)APD组与正常对照组比较,5-HTT-VNTR基因型多态、MAOA-EcoRV-RFLP多态差异无统计学意义(x2=2.819,P=0.244;x2=2.347,P=0.126).(2)高冲动APD组与正常对照组比较,5-HTT-VNTR基因型多态差异有统计学意义(x2=7.422,P=0.024),MAOA-EcoRV-RFLP的等位基因频率有统计学意义(x2=5.478,P=0.019).(3)2个位点的联合分析中,APD组和高冲动APD组分别与对照组比较,12/12/-多倍体型的差异均有统计学意义(x2=7.164,P=0.007;x2=9.590,P=0.002);12/10/+仅在高冲动APD组与正常对照组间差异有统计学意义(x2=5.378,P=0.020).结论 5-HTT基因第2内含子VNTR多态、MAOA基因EcoRV-RFLP多态与具有高冲动的APD关联,12/12/-多倍体型与中国汉族男性APD发病风险可能有关.%Objective To investigate whether the 5-HTT-VNTR, the EcoRV polymorphism of MAOA gene was associated with antisocial personality disorder (APD) in Han Chinese male criminal offenders. Method In a prison in Jiangsu, the male

  10. Mismatch repair genes Mlh1 and Mlh3 modify CAG instability in Huntington's disease mice: genome-wide and candidate approaches.

    Science.gov (United States)

    Pinto, Ricardo Mouro; Dragileva, Ella; Kirby, Andrew; Lloret, Alejandro; Lopez, Edith; St Claire, Jason; Panigrahi, Gagan B; Hou, Caixia; Holloway, Kim; Gillis, Tammy; Guide, Jolene R; Cohen, Paula E; Li, Guo-Min; Pearson, Christopher E; Daly, Mark J; Wheeler, Vanessa C

    2013-10-01

    The Huntington's disease gene (HTT) CAG repeat mutation undergoes somatic expansion that correlates with pathogenesis. Modifiers of somatic expansion may therefore provide routes for therapies targeting the underlying mutation, an approach that is likely applicable to other trinucleotide repeat diseases. Huntington's disease Hdh(Q111) mice exhibit higher levels of somatic HTT CAG expansion on a C57BL/6 genetic background (B6.Hdh(Q111) ) than on a 129 background (129.Hdh(Q111) ). Linkage mapping in (B6x129).Hdh(Q111) F2 intercross animals identified a single quantitative trait locus underlying the strain-specific difference in expansion in the striatum, implicating mismatch repair (MMR) gene Mlh1 as the most likely candidate modifier. Crossing B6.Hdh(Q111) mice onto an Mlh1 null background demonstrated that Mlh1 is essential for somatic CAG expansions and that it is an enhancer of nuclear huntingtin accumulation in striatal neurons. Hdh(Q111) somatic expansion was also abolished in mice deficient in the Mlh3 gene, implicating MutLγ (MLH1-MLH3) complex as a key driver of somatic expansion. Strikingly, Mlh1 and Mlh3 genes encoding MMR effector proteins were as critical to somatic expansion as Msh2 and Msh3 genes encoding DNA mismatch recognition complex MutSβ (MSH2-MSH3). The Mlh1 locus is highly polymorphic between B6 and 129 strains. While we were unable to detect any difference in base-base mismatch or short slipped-repeat repair activity between B6 and 129 MLH1 variants, repair efficiency was MLH1 dose-dependent. MLH1 mRNA and protein levels were significantly decreased in 129 mice compared to B6 mice, consistent with a dose-sensitive MLH1-dependent DNA repair mechanism underlying the somatic expansion difference between these strains. Together, these data identify Mlh1 and Mlh3 as novel critical genetic modifiers of HTT CAG instability, point to Mlh1 genetic variation as the likely source of the instability difference in B6 and 129 strains and suggest that MLH1

  11. A new drug design targeting the adenosinergic system for Huntington's disease.

    Directory of Open Access Journals (Sweden)

    Nai-Kuei Huang

    Full Text Available BACKGROUND: Huntington's disease (HD is a neurodegenerative disease caused by a CAG trinucleotide expansion in the Huntingtin (Htt gene. The expanded CAG repeats are translated into polyglutamine (polyQ, causing aberrant functions as well as aggregate formation of mutant Htt. Effective treatments for HD are yet to be developed. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report a novel dual-function compound, N(6-(4-hydroxybenzyladenine riboside (designated T1-11 which activates the A(2AR and a major adenosine transporter (ENT1. T1-11 was originally isolated from a Chinese medicinal herb. Molecular modeling analyses showed that T1-11 binds to the adenosine pockets of the A(2AR and ENT1. Introduction of T1-11 into the striatum significantly enhanced the level of striatal adenosine as determined by a microdialysis technique, demonstrating that T1-11 inhibited adenosine uptake in vivo. A single intraperitoneal injection of T1-11 in wildtype mice, but not in A(2AR knockout mice, increased cAMP level in the brain. Thus, T1-11 enters the brain and elevates cAMP via activation of the A(2AR in vivo. Most importantly, addition of T1-11 (0.05 mg/ml to the drinking water of a transgenic mouse model of HD (R6/2 ameliorated the progressive deterioration in motor coordination, reduced the formation of striatal Htt aggregates, elevated proteasome activity, and increased the level of an important neurotrophic factor (brain derived neurotrophic factor in the brain. These results demonstrate the therapeutic potential of T1-11 for treating HD. CONCLUSIONS/SIGNIFICANCE: The dual functions of T1-11 enable T1-11 to effectively activate the adenosinergic system and subsequently delay the progression of HD. This is a novel therapeutic strategy for HD. Similar dual-function drugs aimed at a particular neurotransmitter system as proposed herein may be applicable to other neurotransmitter systems (e.g., the dopamine receptor/dopamine transporter and the serotonin receptor

  12. Mismatch repair genes Mlh1 and Mlh3 modify CAG instability in Huntington's disease mice: genome-wide and candidate approaches.

    Directory of Open Access Journals (Sweden)

    Ricardo Mouro Pinto

    2013-10-01

    Full Text Available The Huntington's disease gene (HTT CAG repeat mutation undergoes somatic expansion that correlates with pathogenesis. Modifiers of somatic expansion may therefore provide routes for therapies targeting the underlying mutation, an approach that is likely applicable to other trinucleotide repeat diseases. Huntington's disease Hdh(Q111 mice exhibit higher levels of somatic HTT CAG expansion on a C57BL/6 genetic background (B6.Hdh(Q111 than on a 129 background (129.Hdh(Q111 . Linkage mapping in (B6x129.Hdh(Q111 F2 intercross animals identified a single quantitative trait locus underlying the strain-specific difference in expansion in the striatum, implicating mismatch repair (MMR gene Mlh1 as the most likely candidate modifier. Crossing B6.Hdh(Q111 mice onto an Mlh1 null background demonstrated that Mlh1 is essential for somatic CAG expansions and that it is an enhancer of nuclear huntingtin accumulation in striatal neurons. Hdh(Q111 somatic expansion was also abolished in mice deficient in the Mlh3 gene, implicating MutLγ (MLH1-MLH3 complex as a key driver of somatic expansion. Strikingly, Mlh1 and Mlh3 genes encoding MMR effector proteins were as critical to somatic expansion as Msh2 and Msh3 genes encoding DNA mismatch recognition complex MutSβ (MSH2-MSH3. The Mlh1 locus is highly polymorphic between B6 and 129 strains. While we were unable to detect any difference in base-base mismatch or short slipped-repeat repair activity between B6 and 129 MLH1 variants, repair efficiency was MLH1 dose-dependent. MLH1 mRNA and protein levels were significantly decreased in 129 mice compared to B6 mice, consistent with a dose-sensitive MLH1-dependent DNA repair mechanism underlying the somatic expansion difference between these strains. Together, these data identify Mlh1 and Mlh3 as novel critical genetic modifiers of HTT CAG instability, point to Mlh1 genetic variation as the likely source of the instability difference in B6 and 129 strains and suggest

  13. Clues to γ-secretase, huntingtin and Hirano body normal function using the model organism Dictyostelium discoideum

    Directory of Open Access Journals (Sweden)

    Myre Michael A

    2012-04-01

    Full Text Available Abstract Many neurodegenerative disorders, although related by their destruction of brain function, display remarkable cellular and/or regional pathogenic specificity likely due to a deregulated functionality of the mutant protein. However, neurodegenerative disease genes, for example huntingtin (HTT, the ataxins, the presenilins (PSEN1/PSEN2 are not simply localized to neurons but are ubiquitously expressed throughout peripheral tissues; it is therefore paramount to properly understand the earliest precipitating events leading to neuronal pathogenesis to develop effective long-term therapies. This means, in no unequivocal terms, it is crucial to understand the gene's normal function. Unfortunately, many genes are often essential for embryogenesis which precludes their study in whole organisms. This is true for HTT, the β-amyloid precursor protein (APP and presenilins, responsible for early onset Alzheimer's disease (AD. To better understand neurological disease in humans, many lower and higher eukaryotic models have been established. So the question arises: how reasonable is the use of organisms to study neurological disorders when the model of choice does not contain neurons? Here we will review the surprising, and novel emerging use of the model organism Dictyostelium discoideum, a species of soil-living amoeba, as a valuable biomedical tool to study the normal function of neurodegenerative genes. Historically, the evidence on the usefulness of simple organisms to understand the etiology of cellular pathology cannot be denied. But using an organism without a central nervous system to understand diseases of the brain? We will first introduce the life cycle of Dictyostelium, the presence of many disease genes in the genome and how it has provided unique opportunities to identify mechanisms of disease involving actin pathologies, mitochondrial disease, human lysosomal and trafficking disorders and host-pathogen interactions. Secondly, I will

  14. Xyloketal-derived small molecules show protective effect by decreasing mutant Huntingtin protein aggregates in Caenorhabditis elegans model of Huntington’s disease

    Directory of Open Access Journals (Sweden)

    Zeng YX

    2016-04-01

    Full Text Available Yixuan Zeng,1,2,* Wenyuan Guo,1,* Guangqing Xu,3 Qinmei Wang,4 Luyang Feng,1,2 Simei Long,1 Fengyin Liang,1 Yi Huang,1 Xilin Lu,1 Shichang Li,5 Jiebin Zhou,5 Jean-Marc Burgunder,6 Jiyan Pang,5 Zhong Pei1,2 1Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Disease, The First Affiliated Hospital, Sun Yat-sen University, 2Guangzhou Center, Chinese Huntington’s Disease Network, 3Department of Rehabilitation, The First Affiliated Hospital, 4Key laboratory on Assisted Circulation, Ministry of Health, Department of Cardiovascular Medicine of the First Affiliated Hospital, 5School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 6Swiss Huntington’s Disease Center, Department of Neurology, University of Bern, Bern, Switzerland *These authors contributed equally to this work Abstract: Huntington’s disease is an autosomal-dominant neurodegenerative disorder, with chorea as the most prominent manifestation. The disease is caused by abnormal expansion of CAG codon repeats in the IT15 gene, which leads to the expression of a glutamine-rich protein named mutant Huntingtin (Htt. Because of its devastating disease burden and lack of valid treatment, development of more effective therapeutics for Huntington’s disease is urgently required. Xyloketal B, a natural product from mangrove fungus, has shown protective effects against toxicity in other neurodegenerative disease models such as Parkinson’s and Alzheimer’s diseases. To identify potential neuroprotective molecules for Huntington’s disease, six derivatives of xyloketal B were screened in a Caenorhabditis elegans Huntington’s disease model; all six compounds showed a protective effect. Molecular docking studies indicated that compound 1 could bind to residues GLN369 and GLN393 of the mutant Htt protein, forming a

  15. Enhanced Store-Operated Calcium Entry Leads to Striatal Synaptic Loss in a Huntington's Disease Mouse Model.

    Science.gov (United States)

    Wu, Jun; Ryskamp, Daniel A; Liang, Xia; Egorova, Polina; Zakharova, Olga; Hung, Gene; Bezprozvanny, Ilya

    2016-01-06

    In Huntington's disease (HD), mutant Huntingtin (mHtt) protein causes striatal neuron dysfunction, synaptic loss, and eventual neurodegeneration. To understand the mechanisms responsible for synaptic loss in HD, we developed a corticostriatal coculture model that features age-dependent dendritic spine loss in striatal medium spiny neurons (MSNs) from YAC128 transgenic HD mice. Age-dependent spine loss was also observed in vivo in YAC128 MSNs. To understand the causes of spine loss in YAC128 MSNs, we performed a series of mechanistic studies. We previously discovered that mHtt protein binds to type 1 inositol (1,4,5)-trisphosphate receptor (InsP3R1) and increases its sensitivity to activation by InsP3. We now report that the resulting increase in steady-state InsP3R1 activity reduces endoplasmic reticulum (ER) Ca(2+) levels. Depletion of ER Ca(2+) leads to overactivation of the neuronal store-operated Ca(2+) entry (nSOC) pathway in YAC128 MSN spines. The synaptic nSOC pathway is controlled by the ER resident protein STIM2. We discovered that STIM2 expression is elevated in aged YAC128 striatal cultures and in YAC128 mouse striatum. Knock-down of InsP3R1 expression by antisense oligonucleotides or knock-down or knock-out of STIM2 resulted in normalization of nSOC and rescue of spine loss in YAC128 MSNs. The selective nSOC inhibitor EVP4593 was identified in our previous studies. We now demonstrate that EVP4593 reduces synaptic nSOC and rescues spine loss in YAC128 MSNs. Intraventricular delivery of EVP4593 in YAC128 mice rescued age-dependent striatal spine loss in vivo. Our results suggest EVP4593 and other inhibitors of the STIM2-dependent nSOC pathway as promising leads for HD therapeutic development. In Huntington's disease (HD) mutant Huntingtin (mHtt) causes early corticostriatal synaptic dysfunction and eventual neurodegeneration of medium spine neurons (MSNs) through poorly understood mechanisms. We report here that corticostriatal cocultures prepared from

  16. Identification of genetic variants associated with Huntington's disease progression

    DEFF Research Database (Denmark)

    Hensman Moss, Davina J; Pardiñas, Antonio F; Langbehn, Douglas

    2017-01-01

    indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008-11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers...... in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression......BACKGROUND: Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate...

  17. Henkin and Hybrid Logic

    DEFF Research Database (Denmark)

    Blackburn, Patrick Rowan; Huertas, Antonia; Manzano, Maria

    2014-01-01

    Leon Henkin was not a modal logician, but there is a branch of modal logic that has been deeply influenced by his work. That branch is hybrid logic, a family of logics that extend orthodox modal logic with special proposition symbols (called nominals) that name worlds. This paper explains why...... Henkin’s techniques are so important in hybrid logic. We do so by proving a completeness result for a hybrid type theory called HTT, probably the strongest hybrid logic that has yet been explored. Our completeness result builds on earlier work with a system called BHTT, or basic hybrid type theory...... is due to the first-order perspective, which lies at the heart of Henin’s best known work and hybrid logic....

  18. Analysis list: E2f4 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available E2f4 Blood,Embryonic fibroblast,Liver,Muscle,Pluripotent stem cell + mm9 http://dba...rchive.biosciencedbc.jp/kyushu-u/mm9/target/E2f4.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/E2f4....5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/E2f4.10.tsv http://dbarchive.biosciencedbc....jp/kyushu-u/mm9/colo/E2f4.Blood.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/E2f4....Embryonic_fibroblast.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/E2f4.Liver.tsv,htt

  19. Comparison of Different Pretreatment Strategies for Ethanol Production of West African Biomass

    DEFF Research Database (Denmark)

    Thomsen, Sune Tjalfe; Gonzalez Londono, Jorge Enrique; Schmidt, Jens Ejbye

    2015-01-01

    husks, cocoa pods, maize cobs, maize stalks, rice straw, groundnut straw and oil palm empty fruit bunches. It was found that four biomass’ (plantain peelings, plantain trunks, maize cobs and maize stalks) were most promising for production of cellulosic ethanol with profitable enzymatic conversion......Pretreating lignocellulosic biomass for cellulosic ethanol production in a West African setting requires smaller scale and less capital expenditure compared to current state of the art. In the present study, three low-tech methods applicable for West African conditions, namely Boiling Pretreatment...... (BP), Soaking in Aqueous Ammonia (SAA) and White Rot Fungi pretreatment (WRF), were compared to the high-tech solution of hydrothermal pretreatment (HTT). The pretreatment methods were tested on 11 West African biomasses, i.e. cassava stalks, plantain peelings, plantain trunks, plantain leaves, cocoa...

  20. Optimal Time Allocation in Backscatter Assisted Wireless Powered Communication Networks

    Science.gov (United States)

    Lyu, Bin; Yang, Zhen; Gui, Guan; Sari, Hikmet

    2017-01-01

    This paper proposes a wireless powered communication network (WPCN) assisted by backscatter communication (BackCom). This model consists of a power station, an information receiver and multiple users that can work in either BackCom mode or harvest-then-transmit (HTT) mode. The time block is mainly divided into two parts corresponding to the data backscattering and transmission periods, respectively. The users first backscatter data to the information receiver in time division multiple access (TDMA) during the data backscattering period. When one user works in the BackCom mode, the other users harvest energy from the power station. During the data transmission period, two schemes, i.e., non-orthogonal multiple access (NOMA) and TDMA, are considered. To maximize the system throughput, the optimal time allocation policies are obtained. Simulation results demonstrate the superiority of the proposed model. PMID:28587171