http://hdl.handle.net/10400.18/50 2013-05-17T20:14:59Z 2013-05-17T20:14:59Z Gilling, M. Rasmussen, H.B. Calloe, K. Sequeira, A.F. Barreto, M. Oliveira, G. Almeida, J. Lauritsen, M.B. Ullmann, R. Boonen, S.E. Brondum-Nielsen, K. Kalscheuer, V.M. Tümer, Z. Vicente, A.M. Schmitt, N. Tommerup, N. http://hdl.handle.net/10400.18/1576 2013-04-26T15:00:53Z 2013-04-16T00:00:00Z

Title: Dysfunction of the Heteromeric KV7.3/KV7.5 Potassium Channel is Associated with Autism Spectrum Disorders Authors: Gilling, M.; Rasmussen, H.B.; Calloe, K.; Sequeira, A.F.; Barreto, M.; Oliveira, G.; Almeida, J.; Lauritsen, M.B.; Ullmann, R.; Boonen, S.E.; Brondum-Nielsen, K.; Kalscheuer, V.M.; Tümer, Z.; Vicente, A.M.; Schmitt, N.; Tommerup, N. Abstract: Heterozygous mutations in the KCNQ3 gene on chromosome 8q24 encoding the voltage-gated potassium channel KV7.3 subunit have previously been associated with rolandic epilepsy and idiopathic generalized epilepsy (IGE) including benign neonatal convulsions. We identified a de novo t(3;8) (q21;q24) translocation truncating KCNQ3 in a boy with childhood autism. In addition, we identified a c.1720C > T [p.P574S] nucleotide change in three unrelated individuals with childhood autism and no history of convulsions. This nucleotide change was previously reported in patients with rolandic epilepsy or IGE and has now been annotated as a very rare SNP (rs74582884) in dbSNP. The p.P574S KV7.3 variant significantly reduced potassium current amplitude in Xenopus laevis oocytes when co-expressed with KV7.5 but not with KV7.2 or KV7.4. The nucleotide change did not affect trafficking of heteromeric mutant KV7.3/2, KV7.3/4, or KV7.3/5 channels in HEK 293 cells or primary rat hippocampal neurons. Our results suggest that dysfunction of the heteromeric KV7.3/5 channel is implicated in the pathogenesis of some forms of autism spectrum disorders, epilepsy, and possibly other psychiatric disorders and therefore, KCNQ3 and KCNQ5 are suggested as candidate genes for these disorders.

2013-04-16T00:00:00Z Traylor, M. Farrall, M. Holliday, E.G. Sudlow, C. Hopewell, J.C. Cheng, Y.C. Fornage, M. Ikram, M.A. Malik, R. Bevan, S. Thorsteinsdottir, U. Nalls, M.A. Longstreth, W. Wiggins, K.L. Yadav, S. Parati, E.A. Destefano, A.L. Worrall, B.B. Kittner, S.J. Khan, M.S. Reiner, A.P. Helgadottir, A. Achterberg, S. Fernandez-Cadenas, I. Abboud, S. Schmidt, R. Walters, M. Chen, W.M. Ringelstein, E.B. O'Donnell, M. Ho, W.K. Pera, J. Lemmens, R. Norrving, B. Higgins, P. Benn, M. Sale, M. Kuhlenbäumer, G. Doney, A.S. Vicente, A.M. Delavaran, H. Algra, A. Davies, G. Oliveira, S.A. Palmer, C.N. Deary, I. Schmidt, H. Pandolfo, M. Montaner, J. Carty, C. de Bakker, P.I. Kostulas, K. Ferro, J.M. van Zuydam, N.R, Valdimarsson, E. Nordestgaard, B.G. Lindgren, A. Thijs, V. Slowik, A. Saleheen, D. Paré, G. Berger, K. Thorleifsson, G. Australian Stroke Genetics Collaborative, Wellcome Trust Case Control Consortium 2 (WTCCC2) Hofman, A. Mosley, T.H. Mitchell, B.D. Furie, K. Clarke, R. Levi, C. Seshadri, S. Gschwendtner, A. Boncoraglio, G.B. Sharma, P. Bis, J.C. Gretarsdottir, S. Psaty, B.M. Rothwell, P.M. Rosand, J. Meschia, J.F. Stefansson, K. Dichgans, M. Markus, H.S. International Stroke Genetics Consortium. http://hdl.handle.net/10400.18/1472 2013-02-25T16:35:10Z 2012-10-05T00:00:00Z

Title: Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE collaboration): a meta-analysis of genome-wide association studies Authors: Traylor, M.; Farrall, M.; Holliday, E.G.; Sudlow, C.; Hopewell, J.C.; Cheng, Y.C.; Fornage, M.; Ikram, M.A.; Malik, R.; Bevan, S.; Thorsteinsdottir, U.; Nalls, M.A.; Longstreth, W.; Wiggins, K.L.; Yadav, S.; Parati, E.A.; Destefano, A.L.; Worrall, B.B.; Kittner, S.J.; Khan, M.S.; Reiner, A.P.; Helgadottir, A.; Achterberg, S.; Fernandez-Cadenas, I.; Abboud, S.; Schmidt, R.; Walters, M.; Chen, W.M.; Ringelstein, E.B.; O'Donnell, M.; Ho, W.K.; Pera, J.; Lemmens, R.; Norrving, B.; Higgins, P.; Benn, M.; Sale, M.; Kuhlenbäumer, G.; Doney, A.S.; Vicente, A.M.; Delavaran, H.; Algra, A.; Davies, G.; Oliveira, S.A.; Palmer, C.N.; Deary, I.; Schmidt, H.; Pandolfo, M.; Montaner, J.; Carty, C.; de Bakker, P.I.; Kostulas, K.; Ferro, J.M.; van Zuydam, N.R,; Valdimarsson, E.; Nordestgaard, B.G.; Lindgren, A.; Thijs, V.; Slowik, A.; Saleheen, D.; Paré, G.; Berger, K.; Thorleifsson, G.; Australian Stroke Genetics Collaborative, Wellcome Trust Case Control Consortium 2 (WTCCC2); Hofman, A.; Mosley, T.H.; Mitchell, B.D.; Furie, K.; Clarke, R.; Levi, C.; Seshadri, S.; Gschwendtner, A.; Boncoraglio, G.B.; Sharma, P.; Bis, J.C.; Gretarsdottir, S.; Psaty, B.M.; Rothwell, P.M.; Rosand, J.; Meschia, J.F.; Stefansson, K.; Dichgans, M.; Markus, H.S.; International Stroke Genetics Consortium. Abstract: Various genome-wide association studies (GWAS) have been done in ischaemic stroke, identifying a few loci associated with the disease, but sample sizes have been 3500 cases or less. We established the METASTROKE collaboration with the aim of validating associations from previous GWAS and identifying novel genetic associations through meta-analysis of GWAS datasets for ischaemic stroke and its subtypes.

2012-10-05T00:00:00Z Botelho, Mónica C. Vale, N. Gouveia, M.J. Rinaldi, G. Santos, J. Santos, L.L. Gomes, P. Brindley, P.J. Correia da Costa, José Manuel http://hdl.handle.net/10400.18/1165 2013-01-28T12:04:58Z 2013-01-01T00:00:00Z

Title: Tumour-like phenotypes in urothelial cells after exposure to antigens from eggs of Schistosoma haematobium: an oestrogen-DNA adducts mediated pathway? Authors: Botelho, Mónica C.; Vale, N.; Gouveia, M.J.; Rinaldi, G.; Santos, J.; Santos, L.L.; Gomes, P.; Brindley, P.J.; Correia da Costa, José Manuel Abstract: Chronic infection with the blood fluke, Schistosoma haematobium, is associated with squamous cell carcinoma of the bladder. Previously, it has been shown that soluble extracts of mixed sex adult S. haematobium worms (SWAP) are tumourigenic, both in vitro and in vivo. In addition, oestrogen-related molecules in SWAP of S. haematobium down-regulate oestrogen receptors (ERs) alpha and beta in oestrogen responsive cells. Moreover, schistosome oestrogens occur in sera of persons with schistosomiasis haematobia and repress transcription of ERs in urothelial cells. Given that eggs of S. haematobium are the developmental stage directly responsible for urogenital disease during schistosomiasis haematobia, we suspected that soluble antigens from S. haematobium eggs exhibit similar or more potent tumorigenic capacity. Here we investigated the tumorigenic potential of soluble egg antigens (Sh-SEA) of S. haematobium and the endocrine system in favouring parasitism by schistosomes. The findings confirmed that 6.25μg/ml of Sh-SEA was enough to stimulate cell proliferation, reduce apoptosis and increase oxidative stress of Sh-SEA-exposed urothelial cells. In addition, genotoxic effects of Sh-SEA on these cells were determined by using alkaline single-cell gel electrophoresis (Comet). Furthermore, Liquid Chromatography Diode Array Detection Electron Spray Ionisation Mass Spectrometry indicated the presence of catechol-oestrogens in S. haematobium SEA. A prospective oestrogen-DNA adduct mediated pathway in S. haematobium egg induced bladder cancer is also discussed.

2013-01-01T00:00:00Z Marques, L. Auriac, A. Willemetz, A. Banha, J. Silva, B. Canonne-Hergaux, F. Costa, L. http://hdl.handle.net/10400.18/1106 2012-11-13T02:35:08Z 2012-02-01T00:00:00Z

Title: Immune cells and hepatocytes express glycosylphosphatidylinositol-anchored ceruloplasmin at their cell surface Authors: Marques, L.; Auriac, A.; Willemetz, A.; Banha, J.; Silva, B.; Canonne-Hergaux, F.; Costa, L. Abstract: Ceruloplasmin is a positive acute-phase protein with both anti- and pro-oxidant activities, thus having still unclear physiological functions in inflammatory processes. Importantly, ceruloplasmin has been implicated in iron metabolism due to its ferroxidase activity, assisting ferroportin on cellular iron efflux. Ceruloplasmin can be expressed as a secreted or as a membrane glycosylphosphatidylinositol-anchored protein (GPI-ceruloplasmin), this latter one being reported as expressed mostly in the brain.

2012-02-01T00:00:00Z