| 1. |
- Birney, Ewan, et al.
(författare)
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Prepublication data sharing
- 2009
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 461:7261, s. 168-170
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Tidskriftsartikel (refereegranskat)abstract
- Rapid release of prepublication data has served the field of genomics well. Attendees at a workshop in Toronto recommend extending the practice to other biological data sets.
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| 2. |
- Crittenden, Jill R., et al.
(författare)
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CalDAG-GEFI mediates striatal cholinergic modulation of dendritic excitability, synaptic plasticity and psychomotor behaviors
- 2021
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Ingår i: Neurobiology of Disease. - Maryland Heights, MO, United States : Academic Press. - 0969-9961 .- 1095-953X. ; 158
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Tidskriftsartikel (refereegranskat)abstract
- CalDAG-GEFI (CDGI) is a protein highly enriched in the striatum, particularly in the principal spiny projection neurons (SPNs). CDGI is strongly down-regulated in two hyperkinetic conditions related to striatal dysfunction: Huntingtons disease and levodopa-induced dyskinesia in Parkinsons disease. We demonstrate that genetic deletion of CDGI in mice disrupts dendritic, but not somatic, M1 muscarinic receptors (M1Rs) signaling in indirect pathway SPNs. Loss of CDGI reduced temporal integration of excitatory postsynaptic potentials at dendritic glutamatergic synapses and impaired the induction of activity-dependent long-term potentiation. CDGI deletion selectively increased psychostimulant-induced repetitive behaviors, disrupted sequence learning, and eliminated M1R blockade of cocaine self-administration. These findings place CDGI as a major, but previously unrecognized, mediator of cholinergic signaling in the striatum. The effects of CDGI deletion on the selfadministration of drugs of abuse and its marked alterations in hyperkinetic extrapyramidal disorders highlight CDGIs therapeutic potential.
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| 3. |
- Gaulton, Kyle J, et al.
(författare)
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Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.
- 2015
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:12, s. 1415-1415
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Tidskriftsartikel (refereegranskat)abstract
- We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
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| 4. |
- Gilling, Mette, et al.
(författare)
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Biparental inheritance of chromosomal abnormalities in male twins with non-syndromic mental retardation
- 2011
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Ingår i: European Journal of Medical Genetics. - : Elsevier BV. - 1769-7212. ; 54:4, s. 383-388
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Tidskriftsartikel (refereegranskat)abstract
- In a monozygotic twin couple with mental retardation (MR), we identified a maternally inherited inversion and a paternally inherited translocation: 46,XY,inv(10)(p11.2q21.2)mat,t(9;18)(p22;q21.1) pat. The maternally inherited inv(10) was a benign variant without any apparent phenotypical implications. The translocation breakpoint at 9p was within a cluster of interferon a genes and the 18q21 breakpoint truncated ZBTB7C (zinc finger and BTB containing 7C gene). In addition, analyses with array-CGH revealed a 931 kb maternally inherited deletion on chromosome 8q22 as well as an 875 kb maternally inherited duplication on 5p14. The deletion encompasses the RIM2 (Rab3A-interacting molecule 2), FZD6 (Frizzled homolog 6) and BAALC (Brain and Acute Leukemia Gene, Cytoplasmic) genes and the duplication includes the 5' end of the CDH9 (cadherin 9) gene. Exome sequencing did not reveal any additional mutations that could explain the MR phenotype. The protein products of the above mentioned genes are involved in different aspects of brain development and/or maintenance of the neurons which suggest that accumulation of genetic defects segregating from both parents might be the basis of MR in the twins. This hypothesis was further supported by protein interaction analysis. (C) 2011 Elsevier Masson SAS. All rights reserved.
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| 5. |
- Hudson, Thomas J., et al.
(författare)
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International network of cancer genome projects
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7291, s. 993-998
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Tidskriftsartikel (refereegranskat)abstract
- The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
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| 6. |
- Nielsen, Jakob Toudahl, et al.
(författare)
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In situ high-resolution structure of the baseplate antenna complex in Chlorobaculum tepidum.
- 2016
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Ingår i: Nature Communications. - : Springer Science+Business Media B.V.. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Photosynthetic antenna systems enable organisms harvesting light and transfer the energy to the photosynthetic reaction centre, where the conversion to chemical energy takes place. One of the most complex antenna systems, the chlorosome, found in the photosynthetic green sulfur bacterium Chlorobaculum (Cba.) tepidum contains a baseplate, which is a scaffolding super-structure, formed by the protein CsmA and bacteriochlorophyll a. Here we present the first high-resolution structure of the CsmA baseplate using intact fully functional, light-harvesting organelles from Cba. tepidum, following a hybrid approach combining five complementary methods: solid-state NMR spectroscopy, cryo-electron microscopy, isotropic and anisotropic circular dichroism and linear dichroism. The structure calculation was facilitated through development of new software, GASyCS for efficient geometry optimization of highly symmetric oligomeric structures. We show that the baseplate is composed of rods of repeated dimers of the strongly amphipathic CsmA with pigments sandwiched within the dimer at the hydrophobic side of the helix.
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| 7. |
- Thomsen, Morten Feldtfos, 1983-
(författare)
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Scenes of Writing, Scenes of Looking : Don DeLillo, Claus Beck-Nielsen, and the Politics of the Novel
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cries of the death of the novel and even of literature in general have become cultural commonplaces. In an age seemingly dominated by digital spectacle, many seem to think that traditional print literature has become an almost obsolete cultural practice, bereft of any critical social and political relevance. Combining theories and concepts from such diverse fields as Comparative Literature, Intermedial Studies and Visual Culture Studies, Morten Feldtfos Thomsen argues for the continued cultural relevance of the print novel not only as a form of aesthetic expression and experience, but also as a form of political intervention. Through readings of novels by American author Don DeLillo, and Danish writer and avant-garde artist Claus Beck-Nielsen, he argues that the print novel can engage in a critical and potentially subversive redistribution of what can be seen, said and generally perceived in contemporary society. Following French philosopher Jacques Rancière’s writings on perception as the ground of both aesthetics and politics, as well as W.J.T. Mitchell’s theories on multimodality and mixed media, Scenes of Writing, Scenes of Looking investigates the formal and thematic manifestation in DeLillo’s and Beck-Nielsen’s novels of an imagetext discourse, i.e. an intermingling of images and words, looking and writing. Such strategies insistently interrogate the relationship of mediation and perception to one another as well as the ideological underpinnings thereof. In doing so, the novels participate in the construction and possible disruption of the perceptual field of experience that underpins social order and political engagement. More than merely a self-absorbed play with media and modalities, DeLillo’s and Beck-Nielsen’s insistent mixing of words and images, the verbal and the visual, constitutes a deeply political interrogation of the conditions of possibility that govern our perceptions of the world and our mode of participation and interaction with it.
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| 8. |
- Wuttke, Matthias, et al.
(författare)
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A catalog of genetic loci associated with kidney function from analyses of a million individuals
- 2019
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Ingår i: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 51:6, s. 957-972
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Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
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