| 1. |
- Kenna, Kevin P., et al.
(författare)
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NEK1 variants confer susceptibility to amyotrophic lateral sclerosis
- 2016
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:9, s. 1037-1042
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Tidskriftsartikel (refereegranskat)abstract
- To identify genetic factors contributing to amyotrophic lateral sclerosis (ALS), we conducted whole-exome analyses of 1,022 index familial ALS (FALS) cases and 7,315 controls. In a new screening strategy, we performed gene-burden analyses trained with established ALS genes and identified a significant association between loss-of-function (LOF) NEK1 variants and FALS risk. Independently, autozygosity mapping for an isolated community in the Netherlands identified a NEK1 p.Arg261 His variant as a candidate risk factor. Replication analyses of sporadic ALS (SALS) cases and independent control cohorts confirmed significant disease association for both p.Arg261 His (10,589 samples analyzed) and NEK1 LOF variants (3,362 samples analyzed). In total, we observed NEK1 risk variants in nearly 3% of ALS cases. NEK1 has been linked to several cellular functions, including cilia formation, DNA-damage response, microtubule stability, neuronal morphology and axonal polarity. Our results provide new and important insights into ALS etiopathogenesis and genetic etiology.
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| 2. |
- Baas, Leo, et al.
(författare)
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Inventing the intervention: how organizations deal with alternative approaches to eco-management
- 2000
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Ingår i: Eco-Management and Auditing. - 0968-9427 .- 1099-0925. ; 7:2, s. 67-73
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Tidskriftsartikel (refereegranskat)abstract
- The concept of translation captures the essence of the way in which innovative ideas diffuse to organizations: rather than being transplanted in the same way in every organization, the idea is reformulated into a shape that fits the adapting organization. For instance, pollution prevention, which consists of a conceptual framework as well as a set of organizational routines, is an idea that is translated by adopting organizations into shapes that can differ substantially. When intervening in organizations to implement the idea of pollution prevention, the intervention strategy should be sensitive to this translation process. In this paper, we will present the cases of two chemical firms who participated in an action research project aimed at diffusing the concept of pollution prevention. The way in which members from each of these organizations (re)acted in this process reveals some important points about organizational change, organizational culture and interventions. In the translation process, organizational members reframe an outside idea into concepts and routines that fit with existing practices. Thus, introducing a radically new concept can result in piecemeal organizational change or even no change at all. Differences in the translation process are not determined by the technologies employed by an organization; it is the organizational culture that seems to be more important. Involving governmental agencies in the intervention strategy complicates the translation process: in addition to the firm, the agencies seek to shape the idea of pollution prevention into concepts and routines that fit their own existing practices.
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| 3. |
- Baas, Leo, et al.
(författare)
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The introduction and dissemination of the industrial symbiosis projects in the Rotterdam Harbour and Industry Complex
- 2007
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Ingår i: International Journal of Environmental Technology and Management. - 1466-2132 .- 1741-511X. ; 7:5-6, s. 551-577
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Tidskriftsartikel (refereegranskat)abstract
- The dissemination and implementation of the Industrial Symbiosis projects in the Rotterdam Harbour and Industry Complex can be characterised by break-through projects on the basis of long-term industrial ecology projects. The first 4-year Industrial Symbiosis programme started in 1994 and generated the basis for 15 projects that were further developed in a second 4-year programme that started in 1999 and merged into a 8-years Sustainable Enterprises programme in 2003. This development at the system level is created through the activities of individual organisation in a dynamic, loosely coupled network. The concept of sustainability capabilities is used to analyse the way in which these activities lead to the development of the system.
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| 4. |
- Boons, Frank, et al.
(författare)
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Mapping the Diversity of Industrial Symbiosis: Comparative analysis of European public and private efforts to develop symbiotic networks
- 2013
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Ingår i: 7th International Society for industrial Ecology Biennial Conference.
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Konferensbidrag (refereegranskat)abstract
- The paper presents ongoing research performed by a network of European researchers on the development and diffusion of industrial symbiosis in European countries. The research has a number of aims:1. To find out the nature of industrial symbiosis by finding out the national peculiarities as well as points of correspondence in countries with varying characteristics in socio-economic institutions;2. To map the process of diffusion of industrial symbiosis within and across European countries;3. To find unique and corresponding elements in the (public and private) efforts to stimulate industrial symbiosis.The paper will present main results from the analysis of our cross-national dataset covering these dimensions. It will show the highly specific nature in which symbiosis is defined and diffuse in each country. This leads to a reflection on the way in which industrial symbiosis research should develop more extended typologies of forms of symbiotic networks that are sensitive to these differences. The paper will also reflect on the methods we used to perform this research, and the learning curve we experienced in doing so. This experience is valuable for future research efforts to extend the comparison to other parts of the world, and compare European with American and Asian developments.
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| 5. |
- Boons, Frank, et al.
(författare)
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Trajectories of greening : The diffusion of green organizational routines in the Netherlands, 1986-1995
- 2000
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Ingår i: International Studies of Management and Organization. - : Routledge. - 0020-8825 .- 1558-0911. ; 30:3, s. 18-40
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Tidskriftsartikel (refereegranskat)abstract
- In the Netherlands. there has been an ongoing effort by business firms and government organizations to deal with the ecological impact of industrial activities. Over the years. the set of organizational routines that firms employ to deal with their ecological impact is changing. In this article, we analyze first of all the change in this set of routines in the period 1986-1995. Then we address the question by what mechanisms these changes are brought about. Institutional theory provides us with three possible mechanisms (i.e., forms of isomorphism) by which such changes occur. Our analysis suggests that, in addition to these three forms, there are two distinct mechanisms of change. We also suggest that each mechanism leads to a certain kind of organizational change. We thus develop the concept of trajectories of change.
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| 6. |
- Eggens, Veerle Rc, et al.
(författare)
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EXOSC3 mutations in pontocerebellar hypoplasia type 1: novel mutations and genotype-phenotype correlations.
- 2014
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Ingår i: Orphanet journal of rare diseases. - : Springer Science and Business Media LLC. - 1750-1172. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Pontocerebellar hypoplasia (PCH) represents a group of neurodegenerative disorders with prenatal onset. Eight subtypes have been described thus far (PCH1-8) based on clinical and genetic features. Common characteristics include hypoplasia and atrophy of the cerebellum, variable pontine atrophy, and severe mental and motor impairments. PCH1 is distinctly characterized by the combination with degeneration of spinal motor neurons. Recently, mutations in the exosome component 3 gene (EXOSC3) have been identified in approximately half of the patients with PCH subtype 1.
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| 7. |
- Jones, Gregory T., et al.
(författare)
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Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci
- 2017
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Ingår i: Circulation Research. - 0009-7330 .- 1524-4571. ; 120:2, s. 341-
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. Objective: To identify additional AAA risk loci using data from all available genome-wide association studies. Methods and Results: Through a meta-analysis of 6 genome-wide association study data sets and a validation study totaling 10 204 cases and 107 766 controls, we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches, we observed no new associations between the lead AAA single nucleotide polymorphisms and coronary artery disease, blood pressure, lipids, or diabetes mellitus. Network analyses identified ERG, IL6R, and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. Conclusions: The 4 new risk loci for AAA seem to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease.
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| 8. |
- Namavar, Yasmin, et al.
(författare)
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Clinical, neuroradiological and genetic findings in pontocerebellar hypoplasia.
- 2011
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Ingår i: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156. ; 134:Pt 1, s. 143-56
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Tidskriftsartikel (refereegranskat)abstract
- Pontocerebellar hypoplasia is a group of autosomal recessive neurodegenerative disorders with prenatal onset. The common characteristics are cerebellar hypoplasia with variable atrophy of the cerebellum and the ventral pons. Supratentorial involvement is reflected by variable neocortical atrophy, ventriculomegaly and microcephaly. Mutations in the transfer RNA splicing endonuclease subunit genes (TSEN54, TSEN2, TSEN34) were found to be associated with pontocerebellar hypoplasia types 2 and 4. Mutations in the mitochondrial transfer RNA arginyl synthetase gene (RARS2) were associated with pontocerebellar hypoplasia type 6. We studied a cohort of 169 patients from 141 families for mutations in these genes, of whom 106 patients tested positive for mutations in one of the TSEN genes or the RARS2 gene. In order to delineate the neuroradiological and clinical phenotype of patients with mutations in these genes, we compared this group with 63 patients suspected of pontocerebellar hypoplasia who were negative on mutation analysis. We found a strong correlation (P < 0.0005) between TSEN54 mutations and a dragonfly-like cerebellar pattern on magnetic resonance imaging, in which the cerebellar hemispheres are flat and severely reduced in size and the vermis is relatively spared. Mutations in TSEN54 are clinically associated with dyskinesia and/or dystonia and variable degrees of spasticity, in some cases with pure generalized spasticity. Nonsense or splice site mutations in TSEN54 are associated with a more severe phenotype of more perinatal symptoms, ventilator dependency and early death. In addition, we present ten new mutations in TSEN54, TSEN2 and RARS2. Furthermore, we show that pontocerebellar hypoplasia type 1 together with elevated cerebrospinal fluid lactate may be caused by RARS2 mutations.
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| 9. |
- Nicolas, Aude, et al.
(författare)
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Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
- 2018
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Ingår i: Neuron. - : Cell Press. - 0896-6273 .- 1097-4199. ; 97:6, s. 1268-1283.e6
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Tidskriftsartikel (refereegranskat)abstract
- To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.
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| 10. |
- Smith, Bradley N., et al.
(författare)
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The C9ORF72 expansion mutation is a common cause of ALS+/-FTD in Europe and has a single founder
- 2013
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Ingår i: European Journal of Human Genetics. - London : Nature Publishing Group. - 1018-4813 .- 1476-5438. ; 21:1, s. 102-108
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Tidskriftsartikel (refereegranskat)abstract
- A massive hexanucleotide repeat expansion mutation (HREM) in C9ORF72 has recently been linked to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here we describe the frequency, origin and stability of this mutation in ALS+/-FTD from five European cohorts (total n = 1347). Single-nucleotide polymorphisms defining the risk haplotype in linked kindreds were genotyped in cases (n = 434) and controls (n = 856). Haplotypes were analysed using PLINK and aged using DMLE+. In a London clinic cohort, the HREM was the most common mutation in familial ALS+/-FTD: C9ORF72 29/112 (26%), SOD1 27/112 (24%), TARDBP 1/112 (1%) and FUS 4/112 (4%) and detected in 13/216 (6%) of unselected sporadic ALS cases but was rare in controls (3/856, 0.3%). HREM prevalence was high for familial ALS+/-FTD throughout Europe: Belgium 19/22 (86%), Sweden 30/41 (73%), the Netherlands 10/27 (37%) and Italy 4/20 (20%). The HREM did not affect the age at onset or survival of ALS patients. Haplotype analysis identified a common founder in all 137 HREM carriers that arose around 6300 years ago. The haplotype from which the HREM arose is intrinsically unstable with an increased number of repeats (average 8, compared with 2 for controls, P<10(-8)). We conclude that the HREM has a single founder and is the most common mutation in familial and sporadic ALS in Europe.
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