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4. ”Hallå här, titta lite nyktert på det här” : En kvalitativ studie om normer och föreställningar kopplat till mammor och pappor inom det familjerättsliga området.

Author

Eriksson, Isabella, Westerlund, Marie, Eriksson, Isabella, and Westerlund, Marie

Abstract

This study aimed to examine how gender and gender norms influence custody, residence, and visitation evaluations from a social constructivist perspective. Five qualitative interviews were conducted with social workers within the family law field. The data underwent qualitative content analysis, guided by theoretical frameworks such as Hirdman's gender theory, attachment theory, and Giddens' structuration theory. The results indicated that the majority of the respondents did not experience any difference in which parent files a lawsuit, but variations were observed in the claims submitted by mothers and fathers. Traditional norms associated with mothers and fathers were found to persist, leading to differential assessments of custody, residence, and visitation. Family court officers noted that these differences often revolve around attachment. The findings suggest the prevalence of traditional gender norms within the family court system, albeit with increasing challenges and questioning. This study contributes to understanding how these norms persist and evolve, emphasizing the need for ongoing critical examination of gender-related factors in custody and visitation decisions., Denna studie syftade till att, med en socialkonstruktivistisk utgångspunkt, undersöka upplevelsen hos socionomer inom det familjerättsliga området av hur normer om genus påverkar vårdnad-, boende-, och umgängesutredningar. För att få svar på studiens syfte och frågeställningar genomfördes fem kvalitativa intervjuer med yrkesverksamma socionomer inom det familjerättsliga området. Den insamlade empiriska datan genomgick en kvalitativ innehållsanalys, där tolkningen baserades på Hirdmans genusteori, anknytningsteorin och Giddens struktureringsteori. Tidigare forskning inom ämnet beaktades också i analysen. Resultatet visade att majoriteten av respondenterna inte upplever någon skillnad i vem av föräldrarna som går in med en stämning. Däremot observerades skillnader i vilka yrkanden som lämnades in av mammor och pappor. Respondenterna upplevde även att traditionella normer och föreställningar kopplade till mammor och pappor lever kvar och att det görs skillnad mellan mammor och pappor vid bedömningar av vårdnad, boende och umgänge. Respondenternas upplevelse var att de skillnader som görs ofta är kopplat till anknytning. Sammanfattningsvis tyder resultaten på att traditionella normer rörande genus fortsätter att vara framträdande inom det familjerättsliga området. Dock utmanas och ifrågasätts dessa normer alltmer. Studien bidrar till en djupare förståelse av hur dessa normer överlever och förändras inom familjerätten, och betonar behovet av kontinuerlig kritisk granskning och omvärdering av könsrelaterade faktorer vid beslut om vårdnad och umgänge.

Published
2023

7. Glucocerebrosidase variant T369M is not a risk factor for Parkinson's disease in Sweden.

Author

Ran, Caroline, Brodin, Lovisa, Gellhaar, Sandra, Westerlund, Marie, Fardell, Camilla, Nissbrandt, Hans, Söderkvist, Peter, Sydow, Olof, Markaki, Ioanna, Hertz, Ellen, Wirdefeldt, Karin, Svenningsson, Per, Ran, Caroline, Brodin, Lovisa, Gellhaar, Sandra, Westerlund, Marie, Fardell, Camilla, Nissbrandt, Hans, Söderkvist, Peter, Sydow, Olof, Markaki, Ioanna, Hertz, Ellen, Wirdefeldt, Karin, and Svenningsson, Per

Abstract

INTRODUCTION: Genetic variants in the Beta-glucocerebrosidase gene (GBA1) is a known risk factor for Parkinson's disease. The GBA1 mutations L444P, N370S and many other have been shown to associate with the disease in populations with diverse background. Some GBA1 polymorphisms have a less pronounced effect, and their pathogenicity has been debated. We have previously found associations with L444P, N370S and E326K and Parkinson's disease in Sweden. METHOD: In this study we used pyrosequencing to genotype the T369M variant in a large Swedish cohort consisting of 1,131 patients with idiopathic Parkinson's disease, and 1,594 control subjects to evaluate the possibility of this variant conferring an increased risk for Parkinson's disease. RESULTS: The minor allele frequency was 2.15% in patients and 1.76% in controls. Statistical analysis showed that there was no significant difference in allele frequency between patients and control subjects, p-value 0.37, Odds Ratio 1.23 with a 95% confidence interval of 0.82-1.83. CONCLUSION: Our results suggest that T369M is not a risk factor for Parkinson's disease in the Swedish population., Funding agencies: Swedish Research Council, The Swedish Parkinson Foundation, The Swedish Brain Foundation, Swedish Brain Power and the Karolinska Institutet Foundation and Funds, PS is a Wallenberg Clinical Scholar

Published
2022
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13. A Pan-European Study of the C9orf72 Repeat Associated with FTLD: Geographic Prevalence, Genomic Instability, and Intermediate Repeats

Author

van der Zee, Julie, Gijselinck, Ilse, Dillen, Lubina, Van Langenhove, Tim, Theuns, Jessie, Engelborghs, Sebastiaan, Philtjens, Stéphanie, Vandenbulcke, Mathieu, Sleegers, Kristel, Sieben, Anne, Bäumer, Veerle, Maes, Githa, Corsmit, Ellen, Borroni, Barbara, Padovani, Alessandro, Archetti, Silvana, Perneczky, Robert, Diehl-Schmid, Janine, de Mendonça, Alexandre, Miltenberger-Miltenyi, Gabriel, Pereira, Sónia, Pimentel, José, Nacmias, Benedetta, Bagnoli, Silvia, Sorbi, Sandro, Graff, Caroline, Chiang, Huei-Hsin, Westerlund, Marie, Sanchez-Valle, Raquel, Llado, Albert, Gelpi, Ellen, Santana, Isabel, Almeida, Maria Rosário, Santiago, Beatriz, Frisoni, Giovanni, Zanetti, Orazio, Bonvicini, Cristian, Synofzik, Matthis, Maetzler, Walter, vom Hagen, Jennifer Müller, Schöls, Ludger, Heneka, Michael T., Jessen, Frank, Matej, Radoslav, Parobkova, Eva, Kovacs, Gabor G., Ströbel, Thomas, Sarafov, Stayko, Tournev, Ivailo, Jordanova, Albena, Danek, Adrian, Arzberger, Thomas, Fabrizi, Gian Maria, Testi, Silvia, Salmon, Eric, Santens, Patrick, Martin, Jean-Jacques, Cras, Patrick, Vandenberghe, Rik, De Deyn, Peter Paul, Cruts, Marc, and Van Broeckhoven, Christine

Published
2013
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21. Tillgängligt lärande : Möjligheter och hinder med en dator per elev

Author

Hanneman, Jessica and Westerlund, Marie

Subjects
förändringprocess, Pedagogy, digtalisering, Pedagogik, skolutveckling, Social Sciences, Samhällsvetenskap, Digitala verktyg, Educational Sciences, specialpedagogik, digital kompetens, inkludering kompensatoriska lärverktyg, Utbildningsvetenskap
Abstract

Syftet med den här studien var att beskriva, analysera och problematisera den digitala satsningen 1:1 på högstadiet i en mindre kommun. Vidare fokuserade studien på hur datorsatsningen kunde bidra till att skapa tillgängligt lärande för alla elever och vilken roll specialpedagogen hade i detta. Kvalitativa semistrukturerade intervjuer användes för att kartlägga tjänstepersoners, specialpedagogers och lärares tankar inför satsningen, syn på implementeringen, hur de digitala verktygen användes och vilka utvecklingsbehov som fanns för att skapa tillgängliga lärmiljöer med 1:1. Ur ett sociokulturellt och specialpedagogiskt perspektiv analyserades resultatet. Även en teori om förändringsprocesser användes för analysen. Resultatet visade att satsningen delvis får ses som framgångsrik då det framkom flera lyckade exempel på hur datorsatsningen 1:1 användes i undervisningen och hur den bidrog till inkludering och ökat lärande. Detta framkom bland annat genom att informanterna berättade om spelbaserade plattformar som skapade ökad motivation hos eleverna, förenklade metoder att ge återkoppling och en ökad tillgång till alternativa lärverktyg för elever i behov av särskilt stöd. Det blev dock tydligt att det fanns brister i förändringsprocessen då viktiga aspekter, som exempelvis tydlig plan och utvärderingsbara mål saknades. Övervägande del av både specialpedagoger och lärare ansåg sig sakna tillräcklig kompetens för att kunna nyttja de digitala verktygens fulla potential. Det framkom också att specialpedagogernas kompetens att leda utvecklingsarbeten inte användes. En slutsats av studien var att de intervjuade tjänstepersonerna, specialpedagogerna och lärarna alla var positiva till datorsatsningen. En annan slutsats var att det fanns behov av fortbildning för att ytterligare kunna utveckla den pedagogiska användningen av de digitala verktygen.

Published
2018

22. Genetic Variations and mRNA Expression of NRF2 in Parkinson’s Disease

Author

Ran, Caroline, primary, Wirdefeldt, Karin, additional, Brodin, Lovisa, additional, Ramezani, Mehrafarin, additional, Westerlund, Marie, additional, Xiang, Fengqing, additional, Anvret, Anna, additional, Willows, Thomas, additional, Sydow, Olof, additional, Johansson, Anders, additional, Galter, Dagmar, additional, Svenningsson, Per, additional, and Belin, Andrea Carmine, additional

Published
2017
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23. Bryggarsalen : Underlag för kommande marknadsföringsinsatser

Author

Andersson, Louise and Westerlund, Marie

Subjects
points – of – difference, marketing orientation, Resource – based view, organizational embedded knowledge, Business Administration, Företagsekonomi
Abstract

The purpose of this study is to identify the points-of-difference that should form the basis for Bryggarsalen’s future marketing efforts. Bryggarsalen is a newly established conference business in Stockholm. To be able to identify these points-of-difference, Bryggarsalen’s marketing problems have been studied from the resource-based view, claiming that the source of sustained competitive advantage derive from a firm’s unique bundle of resources. The study proceeded from the assumption that organizational embedded knowledge is a strategic resource that automatically is a source of sustained competitive advantage. In marketing terms we claim that this resource can be considered as a source for finding points-of-difference. However to be considered as points-of-difference, the organizational embedded knowledge must also be seen as valuable to target customer group. Therefore, this study starts by mapping Bryggarsalen’s and its parent company Studiefrämjandet’s organizational embedded knowledge. After that, the identified organizational embedded knowledge is matched with target customer needs. The method used to identify the organizational embedded knowledge is inspired by the technique for causal mapping. To identify target customer needs we have made a trend analysis of the Swedish conference market. Based on our findings following elements in Bryggarsalen’s access to organizational embedded knowledge can be considered as points-of-difference: Studiefrämjandet’s embedded knowledge regarding effective and interactive learning (folkbildningen); Studiefrämjandet’s embedded knowledge regarding keeping courses attractive; Martin Orchidéen’s embedded knowledge regarding cooking and UIf Cronheim’s embedded knowledge regarding event logistics.

Published
2011

24. Association of LRRK2 exonic variants with susceptibility to Parkinson's disease: a case-control study

Author

Ross, Owen A, Soto-Ortolaza, Alexandra I, Brighina, Laura, Riess, Olaf, Klein, Christine, Djarmati, Ana, Hagenah, Johann, Lohmann, Katja, van de Loo, Simone, Abahuni, Nadine, Gispert-Sánchez, Suzana, Hilker, Rüdiger, Auburger, Georg, Van Broeckhoven, Christine, Xiromerisiou, Georgia, Tsimourtou, Vaia, Ralli, Styliani, Kountra, Persa, Markou, Katerina, Patramani, Gianna, Vogiatzi, Christina, Lynch, Tim, Gibson, J Mark, Craig, Dr David, Carr, Jonathan, Valente, Enza Maria, Ferraris, Alessandro, Bentivoglio, Anna Rita, Ialongo, Tamara, Guidubaldi, Arianna, Piano, Carla, Ferrarese, Carlo, Tarantino, Patrizia, Annesi, Ferdinanda, Chartier-Harlin, Marie-Christine, Annesi, Grazia, Quattrone, Aldo, Hattori, Nobutaka, Tomiyama, Hiroyuki, Funayama, Manabu, Yoshino, Hiroyo, Li, Yuanzhe, Imamichi, Yoko, Toda, Tatsushi, Satake, Wataru, Dardiotis, Efthimios, Aasly, J., Opala, Grzegorz, Jasinska-Myga, Barbara, Boczarska-Jedynak, Magdalena, Tan, Eng King, Bardien, Soraya, Jeon, Beom Seok, Park, Sung Sup, Kim, Yun Joong, Dickson, Dennis W, Sohn, Young Ho, Belin, Andrea Carmine, Olson, Lars, Galter, Dagmar, Westerlund, Marie, Sydow, Olof, Pedersen, Nancy L, Wirdefeldt, Karin, Nilsson, Christer, Puschmann, Andreas, Diehl, Nancy N, Wu, Ruey-Meei, Maraganore, Demetrius M, Ahlskog, Eric, de Andrade, Mariza, Lesnick, Timothy G, Rocca, Walter A, Checkoway, Harvey, Farrer, M., Elbaz, Alexis, Heckman, Michael G, Fiske, Brian, Gibson, Rachel, Hadjigeorgiou, Georgios M, Ioannidis, John P A, Jeon, Beom S, Aasly, Jan O, Kruger, Rejko, Kyratzi, Elli, Lesage, Suzanne, Lin, Chin-Hsien, Lynch, Timothy, Mellick, George D, Mutez, Eugénie, Sharma, Manu, Silburn, Peter A, Stefanis, Leonidas, Tadic, Vera, Theuns, Jessie, Uitti, Ryan J, Vassilatis, Demetrios K, Vilariño-Güell, Carles, White, Linda R, Wszolek, Zbigniew K, Farrer, Matthew J, Bacon, Justin A, Disease, Genetic Epidemiology Of Parkinson's, Sutherland, G. T., Siebert, G. A., Nuytemans, Karen, Meeus, Bram, Crosiers, David, Pickut, Barbara, Engelborghs, Sebastiaan, De Deyn, Peter P, Cras, Patrick, Rogaeve, Ekaterina, Destée, A., Agid, Y., Anheim, M., Bonnet, A-M, Borg, M., Bozi, Maria, Brice, A., Broussolle, E., Corvol, J. C., Damier, P., Dürr, A., Durif, F., Lesage, S., Lohmann, E., Pollak, P., Brice, Alexis, Rascol, O., Tison, F., Tranchant, C., Viallet, F., Vidailhet, M., Gasser, Thomas, Krüger, Rejko, Berg, Daniela, Schulte, Claudia, Ross, O, Soto Ortolaza, A, Heckman, M, Aasly, J, Abahuni, N, Annesi, G, Bacon, J, Bardien, S, Bozi, M, Brice, A, Brighina, L, Van Broeckhoven, C, Carr, J, Chartier Harlin, M, Dardiotis, E, Dickson, D, Diehl, N, Elbaz, A, Ferrarese, C, Ferraris, A, Fiske, B, Gibson, J, Gibson, R, Hadjigeorgiou, G, Hattori, N, Ioannidis, J, Jasinska Myga, B, Jeon, B, Kim, Y, Klein, C, Kruger, R, Kyratzi, E, Lesage, S, Lin, C, Lynch, T, Maraganore, D, Mellick, G, Mutez, E, Nilsson, C, Opala, G, Park, S, Puschmann, A, Quattrone, A, Sharma, M, Silburn, P, Sohn, Y, Stefanis, L, Tadic, V, Theuns, J, Tomiyama, H, Uitti, R, Valente, E, van de Loo, S, Vassilatis, D, Vilariño Güell, C, White, L, Wirdefeldt, K, Wszolek, Z, Wu, R, Farrer, M, Engelborghs, Sebastiaan, De Deyn, Peter Paul, Cras, Patrick, Genetic Epidemiology Of Parkinson's Disease (GEO-PD) Consortium, Pathologic Biochemistry and Physiology, and Pollak, Pierre

Subjects
Male, Polymorphism, Single Nucleotide/*genetics, International Cooperation, Ethnic Groups/genetics, Ethnic Group, Genome-wide association study, Protein-Serine-Threonine Kinase, methods [Genome-Wide Association Study], genetics [Ethnic Groups], 0302 clinical medicine, Gene Frequency, genetics [Parkinson Disease], Risk Factors, Exons/genetics, Ethnicity, Parkinson Disease/genetics, Medicine(all), Genetics, Aged, 80 and over, 0303 health sciences, Parkinson Disease, Exons, genetics [Exons], Middle Aged, Polymorphism, Single Nucleotide/genetics, Protein-Serine-Threonine Kinases, LRRK2, 3. Good health, genetics [Polymorphism, Single Nucleotide], Genome-Wide Association Study/methods, Female, Case-Control Studie, Human, Adult, Parkinson Disease/*genetics, Genotype, Adolescent, Protein-Serine-Threonine Kinases/*genetics, Protein-Serine-Threonine Kinases/genetics, Exon, Protein Serine-Threonine Kinases, Biology, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, genetics [Protein-Serine-Threonine Kinases], Polymorphism, Single Nucleotide, 03 medical and health sciences, Young Adult, Humans, Genetic Predisposition to Disease, ddc:610, LRRK2 protein, human, Risk factor, Allele frequency, 030304 developmental biology, Aged, Risk Factor, Case-control study, Exons/*genetics, Odds ratio, nervous system diseases, ddc:616.8, Minor allele frequency, Genetic epidemiology, Case-Control Studies, Neurology (clinical), Human medicine, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

BACKGROUND: Background The leucine-rich repeat kinase 2 gene (LRRK2) harbours highly penetrant mutations that are linked to familial parkinsonism. However, the extent of its polymorphic variability in relation to risk of Parkinson's disease (PD) has not been assessed systematically. We therefore assessed the frequency of LRRK2 exonic variants in individuals with and without PD, to investigate the role of the variants in PD susceptibility. METHODS: LRRK2 was genotyped in patients with PD and controls from three series (white, Asian, and Arab-Berber) from sites participating in the Genetic Epidemiology of Parkinson's Disease Consortium. Genotyping was done for exonic variants of LRRK2 that were identified through searches of literature and the personal communications of consortium members. Associations with PD were assessed by use of logistic regression models. For variants that had a minor allele frequency of 0.5% or greater, single variant associations were assessed, whereas for rarer variants information was collapsed across variants. FINDINGS: 121 exonic LRRK2 variants were assessed in 15 540 individuals: 6995 white patients with PD and 5595 controls, 1376 Asian patients and 962 controls, and 240 Arab-Berber patients and 372 controls. After exclusion of carriers of known pathogenic mutations, new independent risk associations were identified for polymorphic variants in white individuals (M1646T, odds ratio 1.43, 95% CI 1.15-1.78; p=0.0012) and Asian individuals (A419V, 2.27, 1.35-3.83; p=0.0011). A protective haplotype (N551K-R1398H-K1423K) was noted at a frequency greater than 5% in the white and Asian series, with a similar finding in the Arab-Berber series (combined odds ratio 0.82, 0.72-0.94; p=0.0043). Of the two previously reported Asian risk variants, G2385R was associated with disease (1.73, 1.20-2.49; p=0.0026), but no association was noted for R1628P (0.62, 0.36-1.07; p=0.087). In the Arab-Berber series, Y2189C showed potential evidence of risk association with PD (4.48, 1.33-15.09; p=0.012). INTERPRETATION: The results for LRRK2 show that several rare and common genetic variants in the same gene can have independent effects on disease risk. LRRK2, and the pathway in which it functions, is important in the cause and pathogenesis of PD in a greater proportion of patients with this disease than previously believed. These results will help discriminate those patients who will benefit most from therapies targeted at LRRK2 pathogenic activity. FUNDING: Michael J Fox Foundation and National Institutes of Health. Lancet Neurol

Published
2011

25. Övergångar : En studie i hur lärare arbetar med övergångar

Author

Westerlund, Marie-Louise and Wiberg, Sofia

Subjects
ledarskap, observation, kommunikation, grundskola, övergångar, intervju
Abstract

Syftet med denna studie är att ta reda på hur ett urval lärare i årskurs tre arbetar med övergångar mellan olika aktiviteter under en lektion i ämnena matematik och svenska. För att undersöka detta har vi genomfört en empirisk studie med hjälp av två kvalitativa metoder, observation och intervju. I varje ämne har fem lärare ingått i studien. Det insamlade materialet har sammanställts och analyserats utifrån våra teoretiska begrepp som flertalet kommer av Jacob S. Kounin (1977).Vårt resultat visade att det inte fanns så tydliga skillnader i arbetet kring övergångar mellan de två ämnena matematik och svenska vilket gjorde att vi istället la vikt på att se hur alla lärare i vår studie arbetar med övergångar i stort. De resultat vi då fick fram var att lärarna ansåg att det viktigaste för att skapa en smidig övergång var att planera, ha en struktur och fånga elevernas uppmärksamhet för att ha eleverna med sig. De flesta lärarna använde någon form av tecken för att fånga elevernas uppmärksamhet vid övergångarna, de hade god kontroll på eleverna och många hade någon form av struktur. Planering av övergångarna anses vara av stor vikt samtidigt som även flexibiliteten lyfts fram som väsentlig. Kommunikationen som sker till eleverna vid övergångarna är både verbal och icke verbal.

Published
2011

27. Association of a protective paraoxonase 1 (PON1) polymorphism in Parkinson's disease

Author

Belin, Andrea Carmine, Ran, Caroline, Anvret, Anna, Paddock, Silvia, Westerlund, Marie, Håkansson, Anna, Nissbrandt, Hans, Söderkvist, Peter, Dizdar (Dizdar Segrell), Nil, Ahmadi, Ahmad, Anvret, Maria, Willows, Thomas, Sydow, Olof, Galter, Dagmar, Belin, Andrea Carmine, Ran, Caroline, Anvret, Anna, Paddock, Silvia, Westerlund, Marie, Håkansson, Anna, Nissbrandt, Hans, Söderkvist, Peter, Dizdar (Dizdar Segrell), Nil, Ahmadi, Ahmad, Anvret, Maria, Willows, Thomas, Sydow, Olof, and Galter, Dagmar

Abstract

Pesticide exposure has been suggested to increase the risk to develop Parkinson's disease (PD). The arylesterase paraoxonase 1 (PON1) is mainly expressed in the liver and hydrolyzes organophosphates such as pesticides. The polymorphism Leu54Met (rs854560) in PON1, impairing enzyme activity and leading to decreased PON1 expression levels, has been reported to be associated with Parkinson's disease (PD). PON1 is part of a cluster on chromosome 7q21.3 together with PON2 and PON3. We investigated the occurrence of four additional polymorphisms in PON1 and two in PON2 in a Swedish PD case-control material. We found a significant association (p=0.007) with a PON1 promoter polymorphism, rs854571. The minor allele was more common among controls than PD cases which suggest a protective effect. This is strengthened by the fact that rs854571 is in strong linkage disequilibrium with another PON1 promoter polymorphism, rs854572, reported to increase PON1 gene expression. Our findings support the hypothesis that PON1 is involved in the etiology of PD and that higher PON1 levels are reducing the risk for PD., funding agencies|Swedish Research Council||Magnus Bergvall Foundation||Swedish Parkinson Foundation||Swedish Brain Foundation||Swedish Brain Power||Ake Wiberg Foundation||Karolinska Institutet Funds

Published
2012
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28. On the roles of genes in Parkinsons disease

Author

Westerlund, Marie and Westerlund, Marie

Abstract

Parkinson fs disease is a progressive neurodegenerative disorder which affects 1% of the population over the age of 60. In order to identify candidate genes with a potential role in Parkinson fs disease pathology, we investigated genes which are involved in protein aggregation and the ubiquitin ]proteasome system (alpha ]synuclein and ubiquitin carboxy ]terminal hydrolase L1, UCH ]L1), oxidative stress (DJ ]1), mitochondrial function (mitochondrial transcription factor A, TFAM), regulation of drug/toxin levels (multi ]drug resistance 1, MDR1 and alcohol and aldehyde dehydrogenases, ADH and ALDHs), as well as a gene with unknown function, but highly implicated in Parkinson fs disease genetics (leucine ]rich repeat kinase 2, LRRK2). (1) Using in situ hybridization, we characterized the cellular localization of candidate genes in both human and rodent tissues and found marked diversity in terms of areas and intensities of transcriptional activity. Some genes exhibited a widespread neuronal expression (UCH ]L1, DJ ]1, SNCA), one showed a particularly high expression in the dopamine target area striatum (LRRK2), some were expressed also in non ]neuronal tissues (LRRK2, DJ ]1, MDR1), and others exclusively so (ADH1, ADH4). (2) We also searched for genetic variability in a Swedish case ]control sample consisting of 310 Parkinson patients and 315 controls, which resulted in identification of several potential risk factors (LRRK2 G2019S; MDR1 1236C/T; SNCA rs2737029 (A/G) and rs356204 (A/G), as well as protective factors (UCH ]L1 S18Y) for disease. (3) Behavior, gene expression and/or brain neurotransmitter levels were studied in different transgenic and drug ]induced rodent models (Adh4 ]/ ]; alpha ]synuclein over expressing and alpha ]synuclein ]/ ]; Darpp ]32 ]/ ] and Darpp ]32 T34A mutant and MitoPark mice and in 6 ]OHDA treated rats). A possible co ]regulation between Lrrk2 and alpha ]synuclein gene activities was found. Moreover, Adh4 ]/ ] mice displayed alterations in

Published
2008

30. Large-scale replication and heterogeneity in Parkinson disease genetic loci

Author

Sharma, Manu, primary, Ioannidis, John P.A., additional, Aasly, Jan O., additional, Annesi, Grazia, additional, Brice, Alexis, additional, Van Broeckhoven, Christine, additional, Bertram, Lars, additional, Bozi, Maria, additional, Crosiers, David, additional, Clarke, Carl, additional, Facheris, Maurizio, additional, Farrer, Matthew, additional, Garraux, Gaetan, additional, Gispert, Suzana, additional, Auburger, Georg, additional, Vilariño-Güell, Carles, additional, Hadjigeorgiou, Georgios M., additional, Hicks, Andrew A., additional, Hattori, Nobutaka, additional, Jeon, Beom, additional, Lesage, Suzanne, additional, Lill, Christina M., additional, Lin, Juei-Jueng, additional, Lynch, Timothy, additional, Lichtner, Peter, additional, Lang, Anthony E., additional, Mok, Vincent, additional, Jasinska-Myga, Barbara, additional, Mellick, George D., additional, Morrison, Karen E., additional, Opala, Grzegorz, additional, Pramstaller, Peter P., additional, Pichler, Irene, additional, Park, Sung Sup, additional, Quattrone, Aldo, additional, Rogaeva, Ekaterina, additional, Ross, Owen A., additional, Stefanis, Leonidas, additional, Stockton, Joanne D., additional, Satake, Wataru, additional, Silburn, Peter A., additional, Theuns, Jessie, additional, Tan, Eng-King, additional, Toda, Tatsushi, additional, Tomiyama, Hiroyuki, additional, Uitti, Ryan J., additional, Wirdefeldt, Karin, additional, Wszolek, Zbigniew, additional, Xiromerisiou, Georgia, additional, Yueh, Kuo-Chu, additional, Zhao, Yi, additional, Gasser, Thomas, additional, Maraganore, Demetrius, additional, Krüger, Rejko, additional, Boyle, R.S, additional, Sellbach, A, additional, O'Sullivan, J.D., additional, Sutherland, G.T., additional, Siebert, G.A, additional, Dissanayaka, N.N.W, additional, Pickut, Barbara, additional, Engelborghs, Sebastiaan, additional, Meeus, Bram, additional, De Deyn, Peter P., additional, Cras, Patrick, additional, Lang, Anthony E, additional, Agid, Y, additional, Anheim, M, additional, Bonnet, A-M, additional, Borg, M, additional, Brice, A, additional, Broussolle, E, additional, Corvol, JC, additional, Damier, P, additional, Destée, A, additional, Dürr, A, additional, Durif, F, additional, Lesage, S, additional, Lohmann, E, additional, Pollak, P, additional, Rascol, O, additional, Tison, F, additional, Tranchant, C, additional, Viallet, F, additional, Vidailhet, M, additional, Tzourio, Christophe, additional, Amouyel, Philippe, additional, Loriot, Marie-Anne, additional, Mutez, Eugénie, additional, Duflot, Aurélie, additional, Legendre, Jean-Philippe, additional, Waucquier, Nawal, additional, Riess, Olaf, additional, Berg, Daniela, additional, Schulte, Claudia, additional, Klein, Christine, additional, Djarmati, Ana, additional, Hagenah, Johann, additional, Lohmann, Katja, additional, Hilker, Rüdiger, additional, van de Loo, Simone, additional, Dardiotis, Efthimios, additional, Tsimourtou, Vaia, additional, Ralli, Styliani, additional, Kountra, Persa, additional, Patramani, Gianna, additional, Vogiatzi, Cristina, additional, Funayama, Manabu, additional, Yoshino, Hiroyo, additional, Li, Yuanzhe, additional, Imamichi, Yoko, additional, Lynch, Tim, additional, Gibson, J. Mark, additional, Valente, Enza Maria, additional, Ferraris, Alessandro, additional, Dallapiccola, Bruno, additional, Ialongo, Tamara, additional, Brighina, Laura, additional, Corradi, Barbara, additional, Piolti, Roberto, additional, Tarantino, Patrizia, additional, Annesi, Ferdinanda, additional, Jeon, Beom S., additional, Park, Sung-Sup, additional, Aasly, J, additional, Klodowska-Duda, Gabriela, additional, Boczarska-Jedynak, Magdalena, additional, Tan, Eng King, additional, Belin, Andrea Carmine, additional, Olson, Lars, additional, Galter, Dagmar, additional, Westerlund, Marie, additional, Sydow, Olof, additional, Nilsson, Christer, additional, Puschmann, Andreas, additional, Lin, JJ, additional, Maraganore, Demetrius M., additional, Ahlskog, J, Eric, additional, de Andrade, Mariza, additional, Lesnick, Timothy G., additional, Rocca, Walter A., additional, Checkoway, Harvey, additional, Ross, Owen A, additional, and Wszolek, Zbigniew K., additional

Published
2012
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31. Association of a protective paraoxonase 1 (PON1) polymorphism in Parkinson's disease

Author

Belin, Andrea Carmine, primary, Ran, Caroline, additional, Anvret, Anna, additional, Paddock, Silvia, additional, Westerlund, Marie, additional, Håkansson, Anna, additional, Nissbrandt, Hans, additional, Söderkvist, Peter, additional, Dizdar, Nil, additional, Ahmadi, Ahmad, additional, Anvret, Maria, additional, Willows, Thomas, additional, Sydow, Olof, additional, and Galter, Dagmar, additional

Published
2012
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33. Dopaminergic Neuronal Loss, Reduced Neurite Complexity and Autophagic Abnormalities in Transgenic Mice Expressing G2019S Mutant LRRK2

Author

Ramonet, David, primary, Daher, João Paulo L., additional, Lin, Brian M., additional, Stafa, Klodjan, additional, Kim, Jaekwang, additional, Banerjee, Rebecca, additional, Westerlund, Marie, additional, Pletnikova, Olga, additional, Glauser, Liliane, additional, Yang, Lichuan, additional, Liu, Ying, additional, Swing, Deborah A., additional, Beal, M. Flint, additional, Troncoso, Juan C., additional, McCaffery, J. Michael, additional, Jenkins, Nancy A., additional, Copeland, Neal G., additional, Galter, Dagmar, additional, Thomas, Bobby, additional, Lee, Michael K., additional, Dawson, Ted M., additional, Dawson, Valina L., additional, and Moore, Darren J., additional

Published
2011
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34. Altered enzymatic activity and allele frequency of OMI/HTRA2 in Alzheimer's disease

Author

Westerlund, Marie, primary, Behbahani, Homira, additional, Gellhaar, Sandra, additional, Forsell, Charlotte, additional, Belin, Andrea Carmine, additional, Anvret, Anna, additional, Zettergren, Anna, additional, Nissbrandt, Hans, additional, Lind, Charlotta, additional, Sydow, Olof, additional, Graff, Caroline, additional, Ankarcrona, Maria, additional, Galter, Dagmar, additional, and Olson, Lars, additional

Published
2010
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39. Association study of two genetic variants in mitochondrial transcription factor A (TFAM) in Alzheimer's and Parkinson's disease

Author

Belin, Andrea Carmine, primary, Björk, Behnosh F., additional, Westerlund, Marie, additional, Galter, Dagmar, additional, Sydow, Olof, additional, Lind, Charlotta, additional, Pernold, Karin, additional, Rosvall, Lina, additional, Håkansson, Anna, additional, Winblad, Bengt, additional, Nissbrandt, Hans, additional, Graff, Caroline, additional, and Olson, Lars, additional

Published
2007
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42. Altered enzymatic activity and allele frequency of OMI/HTRA2 in Alzheimer's disease.

Author

Westerlund, Marie, Behbahani, Homira, Gellhaar, Sandra, Forsell, Charlotte, Belin, Andrea Carmine, Anvret, Anna, Zettergren, Anna, Nissbrandt, Hans, Lind, Charlotta, Sydow, Olof, Graff, Caroline, Olson, Lars, Ankarcrona, Maria, and Galter, Dagmar

Subjects
*SERINE proteinases, *ALZHEIMER'S disease, *PARKINSON'S disease, *HIPPOCAMPUS (Brain), *ENZYMES, *MESSENGER RNA
Abstract

The serine-protease OMI/HTRA2, required for several cellular processes, including mitochondrial function, autophagy, chaperone activity, and apoptosis, has been implicated in the pathogenesis of both Alzheimer's disease (AD) and Parkinson's disease (PD). Western blot quantification of OMI/HTRA2 in frontal cortex of patients with AD (n10) and control subjects (n10) in two separate materials indicated reduced processed (active, 35 kDa) OMI/HTRA2 levels, whereas unprocessed (50 kDa) enzyme levels were not significantly different between the groups. Interestingly, the specific protease activity of OMI/HTRA2 was found to be significantly increased in patients with AD (n10) compared to matched control subjects (n10) in frontal cortex in two separate materials. Comparison of OMI/HTRA2 mRNA levels in frontal cortex and hippocampus, two brain areas particularly affected by AD, indicated similar levels in patients with AD (n10) and matched control subjects (n10). In addition, we analyzed the occurrence of the OMI/HTRA2 variants A141S and G399S in Swedish case-control materials for AD and PD and found a weak association of A141S with AD, but not with PD. In conclusion, our genetic, histological, and biochemical findings give further support to an involvement of OMI/HTRA2 in the pathology of AD; however, further studies are needed to clarify the role of this gene in neurodegeneration. [ABSTRACT FROM AUTHOR]

Published
2011
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44. Cerebellar α-synuclein levels are decreased in Parkinson's disease and do not correlate with SNCA polymorphisms associated with disease in a Swedish material.

Author

Westerlund, Marie, Belin, Andrea Carmine, Anvret, Anna, Håkansson, Anna, Nissbrandt, Hans, Lind, Charlotta, Sydow, Olof, Olson, Lars, and Galter, Dagmar

Subjects
*PROTEINS, *PARKINSON'S disease, *GENETIC polymorphisms, *CEREBELLUM, *TUBULINS
Abstract

Alterations of brain and plasma α-synuclein levels and SNCA gene variability have been implicated in the pathogenesis of Parkinson's disease (PD). We therefore measured α-synuclein protein levels in postmortem PD and control cerebellum tissue using Western blot and investigated whether the levels correlated to SNCA genotype. We found markedly decreased α-synuclein levels in PD patients (n=16) compared to gender- and age-matched controls (n=14; P=0.004) normalized to α-tubulin. We also performed an association study of the noncoding polymorphisms rs2737029 (A/G) and rs356204 (A/G) (intron 4), and of rs356219 (T/C) (3'-region) of SNCA in a Swedish PD case-control material. Using a two-sided X² test, we found significant association of rs2737029 (P=0.003; X²=9.07) and rs356204 (P=0.048; X²=3.91) with disease, strengthening the involvement of SNCA polymorphisms in sporadic PD. Stratification of the human postmortem brain material by genotype of the three investigated polymorphisms, did not indicate any influence of genotype on α-synuclein protein levels when comparing PD with controls. Taken together, our findings demonstrate that the investigated Parkinson patients have markedly reduced levels of α-synuclein in cerebellum, and that this reduction is general, rather then correlated to the investigated polymorphisms, although two of the polymorphisms also associated with disease in a Swedish material. [ABSTRACT FROM AUTHOR]

Published
2008
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45. Genetic Screening of the Mitochondrial Rho GTPases MIRO1 and MIRO2 in Parkinson's Disease

Author

Anvret, Anna, Ran, Caroline, Westerlund, Marie, Sydow, Olof, Willows, Thomas, Olson, Lars, Galter, Dagmar, and Carmine Belin, Andrea

Abstract

MIRO1 and MIRO2 (mitochondrial Ras homolog gene family, member T1 and T2) also referred to as RHOT1 and RHOT2, belong to the mitochondrial Rho GTPase family and are involved in axonal transport of mitochondria in neu-rons. Because mitochondrial dysfunction is strongly implicated in Parkinson's disease (PD), MIRO1 and MIRO2 can be considered as new candidate genes for PD. We analyzed two non-synonymous polymorphisms and one synonymous polymorphism in MIRO1 and two non-synonymous polymorphisms in MIRO2, in a Swedish Parkinson case-control mate-rial consisting of 241 patients and 307 neurologically healthy controls. None of the analyzed polymorphisms in MIRO1 and MIRO2 were significantly associated with PD. Although we did not find a significant association with PD in our Swedish case-control material, we cannot exclude these Rho GTPases as candidate genes for PD or other neurodegenera-tive disorders.

Published
2012
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46. Mutations are Rare in a Swedish Parkinson Cohort

Author

Anvret, Anna, Blackinton, Jeff G, Westerlund, Marie, Ran, Caroline, Sydow, Olof, Willows, Thomas, Håkansson, Anna, Nissbrandt, Hans, and Belin, Andrea Carmine

Abstract

Mutations in the PARK7 gene, , have been reported to cause early-onset and familial Parkinson’s disease (PD). The function of DJ-1 and how it contributes to the development of the disease is not clear today, but several studies report that DJ-1 is responsive to oxidative stress and important for the maintenance of mitochondria. We have screened three coding regions of (exon 2, 5 and 7) in a Swedish Parkinson cohort. The Swedish PD material consisted of 67 patients with a self reported positive family history of PD and 77 patients with early-onset of disease (≤50 years old). We detected two patients with the previously reported synonymous mutation, Ala167Ala (c.501A>G, rs71653621), in exon 7. No Ala167Ala carriers were identified among 213 neurologically healthy Swedish controls. Mechanisms by which the synonymous Ala167Ala mutation can have consequences are unknown. It may affect the mRNA stability, secondary structure of mRNA, synthesis, turnover, protein folding and function. We could show a 1.3% decrease in mRNA folding energy in the A

Published
2011

47. DJ-1 Mutations are Rare in a Swedish Parkinson Cohort

Author

Anvret, Anna, Blackinton, Jeff G., Westerlund, Marie, Ran, Caroline, Sydow, Olof, Willows, Thomas, Håkansson, Anna, Nissbrandt, Hans, and Carmine Belin, Andrea

Abstract

Mutations in the PARK7 gene, DJ-1, have been reported to cause early-onset and familial Parkinson’s disease (PD). The function of DJ-1 and how it contributes to the development of the disease is not clear today, but several studies report that DJ-1 is responsive to oxidative stress and important for the maintenance of mitochondria. We have screened three coding regions of DJ-1 (exon 2, 5 and 7) in a Swedish Parkinson cohort. The Swedish PD material consisted of 67 patients with a self reported positive family history of PD and 77 patients with early-onset of disease (??50 years old). We detected two patients with the previously reported synonymous mutation, Ala167Ala (c.501AG, rs71653621), in exon 7. No Ala167Ala carriers were identified among 213 neurologically healthy Swedish controls. Mechanisms by which the synonymous Ala167Ala mutation can have consequences are unknown. It may affect the mRNA stability, secondary structure of mRNA, synthesis, turnover, protein folding and function. We could show a 1.3% decrease in DJ-1 mRNA folding energy in the A

Published
2011
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48. Large-scale replication and heterogeneity in Parkinson disease genetic loci

Author

Sharma, Manu, Ioannidis, John P A, Facheris, Maurizio, Klein, Christine, Djarmati, Ana, Hagenah, Johann, Lohmann, Katja, Auburger, Georg, Hilker, Rüdiger, van de Loo, Simone, Dardiotis, Efthimios, Tsimourtou, Vaia, Ralli, Styliani, Farrer, Matthew, Kountra, Persa, Patramani, Gianna, Vogiatzi, Cristina, Hattori, Nobutaka, Tomiyama, Hiroyuki, Funayama, Manabu, Yoshino, Hiroyo, Li, Yuanzhe, Imamichi, Yoko, Toda, Tatsushi, Garraux, Gaetan, Satake, Wataru, Lynch, Tim, Gibson, J Mark, Valente, Enza Maria, Ferraris, Alessandro, Dallapiccola, Bruno, Ialongo, Tamara, Brighina, Laura, Corradi, Barbara, Piolti, Roberto, Gispert, Suzana, Tarantino, Patrizia, Annesi, Ferdinanda, Jeon, Beom S, Park, Sung-Sup, Aasly, J., Opala, Grzegorz, Jasinska-Myga, Barbara, Klodowska-Duda, Gabriela, Boczarska-Jedynak, Magdalena, Tan, Eng King, Belin, Andrea Carmine, Olson, Lars, Galter, Dagmar, Westerlund, Marie, Sydow, Olof, Nilsson, Christer, Puschmann, Andreas, Lin, J. J., Maraganore, Demetrius M, Ahlskog, J Eric, Vilariño-Güell, Carles, de Andrade, Mariza, Lesnick, Timothy G, Rocca, Walter A, Checkoway, Harvey, Ross, Owen A, Wszolek, Zbigniew K, Uitti, Ryan J, Hadjigeorgiou, Georgios M, Hicks, Andrew A, Jeon, Beom, Aasly, Jan O, Lesage, Suzanne, Lill, Christina M, Lin, Juei-Jueng, Lynch, Timothy, Lichtner, Peter, Lang, Anthony E, Mok, Vincent, Mellick, George D, Morrison, Karen E, Annesi, Grazia, Pramstaller, Peter P, Pichler, Irene, Park, Sung Sup, Quattrone, Aldo, Rogaeva, Ekaterina, Stefanis, Leonidas, Stockton, Joanne D, Brice, Alexis, Silburn, Peter A, Theuns, Jessie, Tan, Eng-King, Wirdefeldt, Karin, Wszolek, Zbigniew, Xiromerisiou, Georgia, Yueh, Kuo-Chu, Van Broeckhoven, Christine, Zhao, Yi, Gasser, Thomas, Maraganore, Demetrius, Krüger, Rejko, Consortium, GEO-PD, Boyle, R. S., Sellbach, A., O'Sullivan, J. D., Sutherland, G. T., Siebert, G. A., Bertram, Lars, Dissanayaka, N. N. W., Crosiers, David, Pickut, Barbara, Engelborghs, Sebastiaan, Meeus, Bram, De Deyn, Peter P, Cras, Patrick, Bozi, Maria, Agid, Y., Anheim, M., Bonnet, A-M, Borg, M., Brice, A., Broussolle, E., Corvol, J. C., Damier, P., Destée, A., Dürr, A., Durif, F., Lesage, S., Lohmann, E., Pollak, P., Rascol, O., Tison, F., Tranchant, C., Viallet, F., Vidailhet, M., Clarke, Carl, Tzourio, Christophe, Amouyel, Philippe, Loriot, Marie-Anne, Mutez, Eugénie, Duflot, Aurélie, Legendre, Jean-Philippe, Waucquier, Nawal, Riess, Olaf, Berg, Daniela, Schulte, Claudia, Pathologic Biochemistry and Physiology, Pollak, Pierre, De Deyn, Peter Paul, and GEO-PD Consortium

Subjects
Male, Genotype, Single-nucleotide polymorphism, Genome-wide association study, Case-control studies, Biology, Polymorphism, Single Nucleotide, Gene Frequency, genetics [Parkinson Disease], Humans, Genetic Predisposition to Disease, ddc:610, Allele, Parkinson Disease/genetics, Allele frequency, Alleles, Genetic association, Aged, Genetics, Medicine(all), Case-control study, Parkinson Disease, Odds ratio, Middle Aged, ddc:616.8, Genetic epidemiology, Genetic Loci, Case-Control Studies, Female, Neurology (clinical), Human medicine, Genome-Wide Association Study
Abstract

Objective: Eleven genetic loci have reached genome-wide significance in a recent meta-analysis of genome-wide association studies in Parkinson disease (PD) based on populations of Caucasian descent. The extent to which these genetic effects are consistent across different populations is unknown. Methods: Investigators from the Genetic Epidemiology of Parkinson9s Disease Consortium were invited to participate in the study. A total of 11 SNPs were genotyped in 8,750 cases and 8,955 controls. Fixed as well as random effects models were used to provide the summary risk estimates for these variants. We evaluated between-study heterogeneity and heterogeneity between populations of different ancestry. Results: In the overall analysis, single nucleotide polymorphisms (SNPs) in 9 loci showed significant associations with protective per-allele odds ratios of 0.78–0.87 ( LAMP3 , BST1 , and MAPT ) and susceptibility per-allele odds ratios of 1.14–1.43 ( STK39 , GAK , SNCA , LRRK2 , SYT11 , and HIP1R ). For 5 of the 9 replicated SNPs there was nominally significant between-site heterogeneity in the effect sizes ( I 2 estimates ranged from 39% to 48%). Subgroup analysis by ethnicity showed significantly stronger effects for the BST1 (rs11724635) in Asian vs Caucasian populations and similar effects for SNCA , LRRK2 , LAMP3 , HIP1R , and STK39 in Asian and Caucasian populations, while MAPT rs2942168 and SYT11 rs34372695 were monomorphic in the Asian population, highlighting the role of population-specific heterogeneity in PD. Conclusion: Our study allows insight to understand the distribution of newly identified genetic factors contributing to PD and shows that large-scale evaluation in diverse populations is important to understand the role of population-specific heterogeneity. Neurology ® 2012;79:659–667

49. Effects of a full-body electrostimulation garment application in a cohort of subjects with cerebral palsy, multiple sclerosis, and stroke on upper motor neuron syndrome symptoms.

Author

Hahn A, Moeller S, Schlausch A, Ekmann M, de Chelle G, Westerlund M, Braatz F, and Mayr W

Subjects
Female, Humans, Motor Neurons, Muscle Spasticity therapy, Pain complications, Clothing, Cerebral Palsy therapy, Cerebral Palsy complications, Cerebral Palsy diagnosis, Multiple Sclerosis therapy, Multiple Sclerosis complications, Stroke, Electric Stimulation Therapy methods
Abstract

Objectives: Dysfunction of the central nervous system may inflict spastic movement disorder (SMD). Electrical stimuli were identified as promising therapeutic option. Electrical stimulation provided by a 58-electrode full body garment was investigated based on data from regular trial fittings., Methods: Data from 72 testees were investigated. Age averages 36.6 (19.8) ys with 44 females. The cohort spans infantile cerebral paresis (CP) (n=29), multiple sclerosis (MS) (n=23) and stroke (n=20). Data were stratified by etiology and an entry BBS Score<45., Results: Effect sizes (Cohen`s d) related BBS, TUG, FGA, 10mWT, WMFT, EQ5D5L and Pain. Significance levels are indicated by *: p<0.05, **: p<0.01, ***: p<0.001, (t): p<0.1: CP: 1.64***, 0.29*, 1.59***, 0.76(t), 1.00***, 0.5*, 1.28***; MS: 1.83***, 0.83***, 1.28**, 1.07***, 0.93*, 1,11**, 0.78*; Stroke: 1.28**, 0.78**, 0.89, 0.92**, 0.71, 1.26*, 0.78*., Conclusions: Multi-site transcutaneous electrical stimulation may increase ambulation related skills in subjects with SMD stemming from CP, MS and stroke. The results indicate effects on static and dynamic balance, fall risk, mobility, upper extremity improvement and an overall increase in health utility and a reduction in spasticity related pain. Effects are immediate as well as sustained. These results may inspire individual trial fittings and inform further controlled trials., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

Published
2023
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50. Variations of the CAG trinucleotide repeat in DNA polymerase γ (POLG1) is associated with Parkinson's disease in Sweden.

Author

Anvret A, Westerlund M, Sydow O, Willows T, Lind C, Galter D, and Belin AC

Subjects
Aged, Case-Control Studies, DNA Polymerase gamma, DNA, Mitochondrial genetics, Female, Humans, Male, Middle Aged, Parkinson Disease epidemiology, Sweden epidemiology, DNA-Directed DNA Polymerase genetics, Genetic Variation genetics, Parkinson Disease enzymology, Parkinson Disease genetics, Trinucleotide Repeats genetics
Abstract

DNA polymerase gamma (POLG1) is coding for the catalytic subunit of the heterotrimeric mitochondrial DNA polymerase and involved in replication and repair of mitochondrial DNA. In addition to its 5' to 3' polymerase activity, POLG1 has a 3' to 5' exonuclease activity important in the repair process. Mitochondrial dysfunction has been implicated in neurodegenerative disorders like Parkinson's disease (PD). Dopamine neurons, which degenerate in PD, are believed to be particularly susceptible to mitochondrial dysfunction, which makes POLG1 a possible candidate gene for the disease. POLG1 has a polyglutamine tract (poly-Q) in the N-terminal, encoded by a CAG sequence in exon 2. Most commonly the poly-Q tract comprises 10 repeats (10Q, frequency >80%) or moderately common 11Q (frequency 6-12%); however the composition of poly-Q alleles has been reported to vary from 6Q to 14Q. We analyzed this POLG1 trinucleotide repeat in a Swedish PD case-control material and detected variations from 5Q to 15Q. We report a significant association between the non-10/11Q repeats with PD (p=0.002). In silico analysis of poly-Q length effect on mRNA folding energy show a decrease in energy for <10/11Q mRNA (4.6%) and an increase for >10/11Q mRNA (4.8%) compared to 10/11Q mRNA. Our results strengthen the evidence for involvement of POLG1 and mitochondrial dysfunction in PD., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Published
2010
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