| 1. |
- Pulit, S. L., et al.
(författare)
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Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes
- 2018
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Ingår i: Neurology-Genetics. - : Ovid Technologies (Wolters Kluwer Health). - 2376-7839. ; 4:6
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Tidskriftsartikel (refereegranskat)abstract
- Objective We sought to assess whether genetic risk factors for atrial fibrillation (AF) can explain cardioembolic stroke risk. We evaluated genetic correlations between a previous genetic study of AF and AF in the presence of cardioembolic stroke using genome-wide genotypes from the Stroke Genetics Network (N = 3,190 AF cases, 3,000 cardioembolic stroke cases, and 28,026 referents). We tested whether a previously validated AF polygenic risk score (PRS) associated with cardioembolic and other stroke subtypes after accounting for AF clinical risk factors. We observed a strong correlation between previously reported genetic risk for AF, AF in the presence of stroke, and cardioembolic stroke (Pearson r = 0.77 and 0.76, respectively, across SNPs with p < 4.4 x 10(-4) in the previous AF meta-analysis). An AF PRS, adjusted for clinical AF risk factors, was associated with cardioembolic stroke (odds ratio [OR] per SD = 1.40, p = 1.45 x 10(-48)), explaining similar to 20% of the heritable component of cardioembolic stroke risk. The AF PRS was also associated with stroke of undetermined cause (OR per SD = 1.07,p = 0.004), but no other primary stroke subtypes (all p > 0.1). Genetic risk of AF is associated with cardioembolic stroke, independent of clinical risk factors. Studies are warranted to determine whether AF genetic risk can serve as a biomarker for strokes caused by AF.
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| 2. |
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| 3. |
- Marini, S., et al.
(författare)
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Association of Apolipoprotein E With Intracerebral Hemorrhage Risk by Race/Ethnicity A Meta-analysis
- 2019
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Ingår i: Jama Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:4, s. 480-491
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Genetic studies of intracerebral hemorrhage (ICH) have focused mainly on white participants, but genetic risk may vary or could be concealed by differing nongenetic coexposures in nonwhite populations. Transethnic analysis of risk may clarify the role of genetics in ICH risk across populations. OBJECTIVE To evaluate associations between established differences in ICH risk by race/ethnicity and the variability in the risks of apolipoprotein E (APOE) epsilon 4 alleles, the most potent genetic risk factor for ICH. DESIGN, SETTING, AND PARTICIPANTS This case-control study of primary ICH meta-analyzed the association of APOE allele status on ICH risk, applying a 2-stage clustering approach based on race/ethnicity and stratified by a contributing study. A propensity score analysis was used to model the association of APOE with the burden of hypertension across race/ethnic groups. Primary ICH cases and controls were collected from 3 hospital- and population-based studies in the United States and 8 in European sites in the International Stroke Genetic Consortium. Participants were enrolled from January 1, 1999, to December 31, 2017. Participants with secondary causes of ICH were excluded from enrollment. Controls were regionally matched within each participating study. MAIN OUTCOMES AND MEASURES Clinical variables were systematically obtained from structured interviews within each site. APOE genotype was centrally determined for all studies. RESULTS In total, 13 124 participants (7153 [54.5%] male with a median [interquartile range] age of 66 [56-76] years) were included. In white participants, APOE epsilon 2 (odds ratio [OR], 1.49; 95% CI, 1.24-1.80; P < .001) and APOE epsilon 4 (OR, 1.51; 95% CI, 1.23-1.85; P < .001) were associated with lobar ICH risk; however, within self-identified Hispanic and black participants, no associations were found. After propensity score matching for hypertension burden, APOE epsilon 4 was associated with lobar ICH risk among Hispanic (OR, 1.14; 95% CI, 1.03-1.28; P = .01) but not in black (OR, 1.02; 95% CI, 0.98-1.07; P = .25) participants. APOE epsilon 2 and epsilon 4 did not show an association with nonlobar ICH risk in any race/ethnicity. CONCLUSIONS AND RELEVANCE APOE epsilon 4 and epsilon 2 alleles appear to affect lobar ICH risk variably by race/ethnicity, associations that are confirmed in white individuals but can be shown in Hispanic individuals only when the excess burden of hypertension is propensity score-matched; further studies are needed to explore the interactions between APOE alleles and environmental exposures that vary by race/ethnicity in representative populations at risk for ICH.
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| 4. |
- Shellock, R. J., et al.
(författare)
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Building leaders for the UN Ocean Science Decade : a guide to supporting early career women researchers within academic marine research institutions
- 2023
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Ingår i: ICES Journal of Marine Science. - : Oxford University Press (OUP). - 1054-3139 .- 1095-9289. ; 80:1, s. 56-75
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Tidskriftsartikel (refereegranskat)abstract
- Diverse and inclusive marine research is paramount to addressing ocean sustainability challenges in the 21st century, as envisioned by the UN Decade of Ocean Science for Sustainable Development. Despite increasing efforts to diversify ocean science, women continue to face barriers at various stages of their career, which inhibits their progression to leadership within academic institutions. In this perspective, we draw on the collective experiences of thirty-four global women leaders, bolstered by a narrative review, to identify practical strategies and actions that will help empower early career women researchers to become the leaders of tomorrow. We propose five strategies: (i) create a more inclusive culture, (ii) ensure early and equitable career development opportunities for women ECRs, (iii) ensure equitable access to funding for women ECRs, (iv) offer mentoring opportunities and, (v) create flexible, family-friendly environments. Transformational, meaningful, and lasting change will only be achieved through commitment and collaborative action across various scales and by multiple stakeholders.
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| 5. |
- Gau, Rémi, et al.
(författare)
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Brainhack : Developing a culture of open, inclusive, community-driven neuroscience
- 2021
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Ingår i: Neuron. - : Elsevier. - 0896-6273 .- 1097-4199. ; 109:11, s. 1769-1775
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Tidskriftsartikel (refereegranskat)abstract
- Brainhack is an innovative meeting format that promotes scientific collaboration and education in an open, inclusive environment. This NeuroView describes the myriad benefits for participants and the research community and how Brainhacks complement conventional formats to augment scientific progress.
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| 6. |
- Gron, K. L., et al.
(författare)
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The association of fatigue, comorbidity burden, disease activity, disability and gross domestic product in patients with rheumatoid arthritis. : Results from 34 countries participating in the Quest-RA programme
- 2014
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Ingår i: Clinical and Experimental Rheumatology. - 0392-856X .- 1593-098X. ; 32:6, s. 869-877
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Tidskriftsartikel (refereegranskat)abstract
- Objective The aim is to assess the prevalence of comorbidities and to further analyse to which degree fatigue can be explained by comorbidity burden, disease activity, disability and gross domestic product (GDP) in patients with rheumatoid arthritis (RA). Methods Nine thousands eight hundred seventy-four patients from 34 countries, 16 with high GDP (>24.000 US dollars [USD] per capita) and 18 low-GDP countries (<24.000 USD) participated in the Quantitative Standard monitoring of Patients with RA (QUEST-RA) study. The prevalence of 31 comorbid conditions, fatigue (0-10 cm visual analogue scale [VAS] [10 worst]), disease activity in 28 joints (DAS28), and physical disability (Health Assessment Questionnaire score MAW) were assessed. Univariate and multivariate linear regression analyses were performed to assess the association between fatigue and comorbidities, disease activity, disability and GDP. Results Overall, patients reported a median of 2 comorbid conditions of which hypertension (31.5%), osteoporosis (17.6%), osteoarthritis (15.5%) and hyperlipidaemia (14.2%) were the most prevalent. The majority of comorbidities were more common in high-GDP countries. The median fatigue score was 4.4 (4.8 in low-GDP countries and 3.8 in high-GDP countries, p<0.001). In low-GDP countries 25.4% of the patients had a high level of fatigue (>6.6) compared with 23.0% in high-GDP countries (p<0.001). In univariate analysis, fatigue increased with increasing number of comorbidities, disease activity and disability in both high- and low-GDP countries. In multivariate analysis of all countries, these 3 variables explained 29.4% of the variability, whereas GDP was not significant. Conclusion Fatigue is a widespread problem associated with high comorbidity burden, disease activity and disability regardless of GDP.
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| 7. |
- Alsoghier, H. M., et al.
(författare)
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NMR spectroscopic investigation of benzothiazolylacetonitrile azo dyes : CR7 substitution effect and semiempirical study
- 2021
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Ingår i: RESULTS IN CHEMISTRY. - : Elsevier. - 2211-7156. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Ebead et al. had reported in the synthesis and the UV-Visible solvatochromism combined with semiempirical calculations to study the tautomerism of 1,3-benzothiazol-2-ylacetonitrile azo dyes [1]. In this study, 1,3-ben zothiazol-2-ylacetonitrile azo dyes (1-6) have been resynthesized, one and two dimensional H-1 and C-13 NMR, as well as absorption and emission spectra, were collected and interpreted. The obtained results were used to clarify the tautomerization phenomenon of these dyes. Predominantly, these dyes exist in Z-hydrazone form reinforced through intramolecular hydrogen bonding in deuterated chloroform. Substituents (R) in carbon7 (CR7) are the key player of the changes in H-1 and C-13 NMR chemical shifts, also in the absorption and emission wavelengths of benzothiazole azo dyes. Also, the relative photoluminescence quantum yields (PL QY) of these dyes (1-6) were estimated and related to the nature of substituents. Finally, PM6 semiempirical calculations were employed to confirm the preferred geometric structure and experimental NMR, absorption, and emission results.
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| 8. |
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| 9. |
- Anderson, Christopher D., et al.
(författare)
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Common Variants Within Oxidative Phosphorylation Genes Influence Risk of Ischemic Stroke and Intracerebral Hemorrhage
- 2013
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Ingår i: Stroke: a journal of cerebral circulation. - 1524-4628. ; 44:3, s. 612-619
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose-Previous studies demonstrated association between mitochondrial DNA variants and ischemic stroke (IS). We investigated whether variants within a larger set of oxidative phosphorylation (OXPHOS) genes encoded by both autosomal and mitochondrial DNA were associated with risk of IS and, based on our results, extended our investigation to intracerebral hemorrhage (ICH). Methods-This association study used a discovery cohort of 1643 individuals, a validation cohort of 2432 individuals for IS, and an extension cohort of 1476 individuals for ICH. Gene-set enrichment analysis was performed on all structural OXPHOS genes, as well as genes contributing to individual respiratory complexes. Gene-sets passing gene-set enrichment analysis were tested by constructing genetic scores using common variants residing within each gene. Associations between each variant and IS that emerged in the discovery cohort were examined in validation and extension cohorts. Results-IS was associated with genetic risk scores in OXPHOS as a whole (odds ratio [OR], 1.17; P=0.008) and complex I (OR, 1.06; P=0.050). Among IS subtypes, small vessel stroke showed association with OXPHOS (OR, 1.16; P=0.007), complex I (OR, 1.13; P=0.027), and complex IV (OR, 1.14; P=0.018). To further explore this small vessel association, we extended our analysis to ICH, revealing association between deep hemispheric ICH and complex IV (OR, 1.08; P=0.008). Conclusions-This pathway analysis demonstrates association between common genetic variants within OXPHOS genes and stroke. The associations for small vessel stroke and deep ICH suggest that genetic variation in OXPHOS influences small vessel pathobiology. Further studies are needed to identify culprit genetic variants and assess their functional consequences. (Stroke. 2013;44:612-619.)
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| 10. |
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| 11. |
- Rannikmaee, Kristiina, et al.
(författare)
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Common variation in COL4A1/COL4A2 is associated with sporadic cerebral small vessel disease
- 2015
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Ingår i: Neurology. - 1526-632X. ; 84:9, s. 918-926
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Tidskriftsartikel (refereegranskat)abstract
- Objectives:We hypothesized that common variants in the collagen genes COL4A1/COL4A2 are associated with sporadic forms of cerebral small vessel disease.Methods:We conducted meta-analyses of existing genotype data among individuals of European ancestry to determine associations of 1,070 common single nucleotide polymorphisms (SNPs) in the COL4A1/COL4A2 genomic region with the following: intracerebral hemorrhage and its subtypes (deep, lobar) (1,545 cases, 1,485 controls); ischemic stroke and its subtypes (cardioembolic, large vessel disease, lacunar) (12,389 cases, 62,004 controls); and white matter hyperintensities (2,733 individuals with ischemic stroke and 9,361 from population-based cohorts with brain MRI data). We calculated a statistical significance threshold that accounted for multiple testing and linkage disequilibrium between SNPs (p < 0.000084).Results:Three intronic SNPs in COL4A2 were significantly associated with deep intracerebral hemorrhage (lead SNP odds ratio [OR] 1.29, 95% confidence interval [CI] 1.14-1.46, p = 0.00003; r(2) > 0.9 between SNPs). Although SNPs associated with deep intracerebral hemorrhage did not reach our significance threshold for association with lacunar ischemic stroke (lead SNP OR 1.10, 95% CI 1.03-1.18, p = 0.0073), and with white matter hyperintensity volume in symptomatic ischemic stroke patients (lead SNP OR 1.07, 95% CI 1.01-1.13, p = 0.016), the direction of association was the same. There was no convincing evidence of association with white matter hyperintensities in population-based studies or with non-small vessel disease cerebrovascular phenotypes.Conclusions:Our results indicate an association between common variation in the COL4A2 gene and symptomatic small vessel disease, particularly deep intracerebral hemorrhage. These findings merit replication studies, including in ethnic groups of non-European ancestry.
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| 12. |
- van Putten, E. I., et al.
(författare)
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History matters : societal acceptance of deep-sea mining and incipient conflicts in Papua New Guinea
- 2023
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Ingår i: Maritime Studies. - : Springer Berlin/Heidelberg. - 1872-7859 .- 2212-9790. ; 22:3
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Tidskriftsartikel (refereegranskat)abstract
- New marine industries that develop and grow in response to the changing demand for their products have the potential to exert pressure on fragile marine environments. These emerging industries can benefit local communities but equally can have negative environmental and socio-cultural impacts. The development of new and emerging industries, like deep seabed mining (DSM), requires the acceptance and involvement of local communities. Yet, the history of marine exploitation is imbued with conflicts between industries and local communities. This paper presents a DSM case study in Papua New Guinea (PNG) to stimulate debate around the potential for conflict in the pursuit of resource extraction from the deep sea and the social and environmental harm that these extractions can cause. We do so by first presenting a timeline of local and extra-local events and enabling conditions that form the development background for the DSM Solwara 1 project in PNG. We then undertake a media narrative analysis to consider the contribution of aspects of social acceptability to this highly complex and multi-scale conflict. We find that the lack of (or a decrease in) social acceptability contributed to the conflict situation and ultimately the demise of the Solwara 1 project. Extra-locally, the initial development was positively framed around solutions for decarbonisation using new technology. Over time, actions by international NGOs, financial issues related to foreign companies, and asymmetry in the power balance between the Pacific Island nation and global businesses played a role in growing negative perceptions of acceptability. Historical experiences with prior environmental mining disasters, together with sea tenure governance challenges, and a lack of community and stakeholder acceptance also contributed to the demise of the project. Untangling and debating these complex interactions provides context and reasons for the tension between the lack of societal acceptance at a local scale and the perceived need for DSM products in the global North for innovative technologies and decarbonising societies. Better understanding these interactions and tensions can help emerging industries navigate a future blue economy.
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| 13. |
- Hagag, Naglaa M., et al.
(författare)
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Molecular Epidemiology and Evolutionary Analysis of Avian Influenza A(H5) Viruses Circulating in Egypt, 2019-2021
- 2022
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Ingår i: Viruses. - : MDPI AG. - 1999-4915. ; 14:8
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Tidskriftsartikel (refereegranskat)abstract
- The highly pathogenic avian influenza (HPAI) H5N8 virus was first detected in Egypt in late 2016. Since then, the virus has spread rapidly among different poultry sectors, becoming the dominant HPAI H5 subtype reported in Egypt. Different genotypes of the HPAI H5N8 virus were reported in Egypt; however, the geographic patterns and molecular evolution of the Egyptian HPAI H5N8 viruses are still unclear. Here, extensive epidemiological surveillance was conducted, including more than half a million samples collected from different poultry sectors (farms/backyards/live bird markets) from all governorates in Egypt during 2019-2021. In addition, genetic characterization and evolutionary analyses were performed using 47 selected positive H5N8 isolates obtained during the same period. The result of the conducted surveillance showed that HPAI H5N8 viruses of clade 2.3.4.4b continue to circulate in different locations in Egypt, with an obvious seasonal pattern, and no further detection of the HPAI H5N1 virus of clade 2.2.1.2 was observed in the poultry population during 2019-2021. In addition, phylogenetic and Bayesian analyses revealed that two major genotypes (G5 and G6) of HPAI H5N8 viruses were continually expanding among the poultry sectors in Egypt. Notably, molecular dating analysis suggested that the Egyptian HPAI H5N8 virus is the potential ancestral viruses of the European H5N8 viruses of 2020-2021. In summary, the data of this study highlight the current epidemiology, diversity, and evolution of HPAI H5N8 viruses in Egypt and call for continuous monitoring of the genetic features of the avian influenza viruses in Egypt.
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| 14. |
- Leard, Lorriana E., et al.
(författare)
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Consensus document for the selection of lung transplant candidates: An update from the International Society for Heart and Lung Transplantation
- 2021
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Ingår i: Journal of Heart and Lung Transplantation. - : Elsevier BV. - 1053-2498 .- 1557-3117. ; 40, s. 1349-1379
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Tidskriftsartikel (refereegranskat)abstract
- Tens of thousands of patients with advanced lung diseases may be eligible to be considered as potential candidates for lung transplant around the world each year. The timing of referral, evaluation, determination of candidacy, and listing of candidates continues to pose challenges and even ethical dilemmas. To address these challenges, the International Society for Heart and Lung Transplantation appointed an international group of members to review the literature, to consider recent advances in the management of advanced lung diseases, and to update prior consensus documents on the selection of lung transplant candidates. The purpose of this updated consensus document is to assist providers throughout the world who are caring for patients with pulmonary disease to identify potential candidates for lung transplant, to optimize the timing of the referral of these patients to lung transplant centers, and to provide transplant centers with a framework for evaluating and selecting candidates. In addition to addressing general considerations and providing disease specific recommendations for referral and listing, this updated consensus document includes an ethical framework, a recognition of the variability in acceptance of risk between transplant centers, and establishes a system to account for how a combination of risk factors may be taken into consideration in candidate selection for lung transplantation.
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| 15. |
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| 16. |
- Shellock, Rebecca J., et al.
(författare)
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Breaking down barriers : The identification of actions to promote gender equality in interdisciplinary marine research institutions
- 2022
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Ingår i: One Earth. - : Elsevier BV. - 2590-3330 .- 2590-3322. ; 5:6, s. 687-708
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Tidskriftsartikel (refereegranskat)abstract
- Interdisciplinary research is paramount to addressing ocean sustainability challenges in the 21st century. However, women leaders have been underrepresented in interdisciplinary marine research, and there is little guidance on how to achieve the conditions that will lead to an increased proportion of women scientists in positions of leadership. Here, we conduct in-depth qualitative research to explore the main barriers and enablers to women’s leadership in an academic interdisciplinary marine research context. We found that interdisciplinarity can present unique and additional barriers to women leaders (e.g., complexity and lack of value attributed to interdisciplinary research) and are exacerbated by existing gender-specific issues that women experience (e.g., isolation and underrepresentation and stereotyping). Together these barriers overlap forming the “glass obstacle course”—which is particularly challenging for women in minoritized groups. Here, we provide a list of concrete, ambitious, and actionable enablers that can promote and support women’s leadership in academic interdisciplinary marine research.
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| 19. |
- van Kuilenburg, André B P, et al.
(författare)
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ß-ureidopropionase deficiency : phenotype, genotype and protein structural consequences in 16 patients
- 2012
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Ingår i: Biochimica et Biophysica Acta. - : Elsevier BV. - 0006-3002 .- 1878-2434. ; 1822:7, s. 1096-108
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Tidskriftsartikel (refereegranskat)abstract
- ß-ureidopropionase is the third enzyme of the pyrimidine degradation pathway and catalyzes the conversion of N-carbamyl-ß-alanine and N-carbamyl-ß-aminoisobutyric acid to ß-alanine and ß-aminoisobutyric acid, ammonia and CO(2). To date, only five genetically confirmed patients with a complete ß-ureidopropionase deficiency have been reported. Here, we report on the clinical, biochemical and molecular findings of 11 newly identified ß-ureidopropionase deficient patients as well as the analysis of the mutations in a three-dimensional framework. Patients presented mainly with neurological abnormalities (intellectual disabilities, seizures, abnormal tonus regulation, microcephaly, and malformations on neuro-imaging) and markedly elevated levels of N-carbamyl-ß-alanine and N-carbamyl-ß-aminoisobutyric acid in urine and plasma. Analysis of UPB1, encoding ß-ureidopropionase, showed 6 novel missense mutations and one novel splice-site mutation. Heterologous expression of the 6 mutant enzymes in Escherichia coli showed that all mutations yielded mutant ß-ureidopropionase proteins with significantly decreased activity. Analysis of a homology model of human ß-ureidopropionase generated using the crystal structure of the enzyme from Drosophila melanogaster indicated that the point mutations p.G235R, p.R236W and p.S264R lead to amino acid exchanges in the active site and therefore affect substrate binding and catalysis. The mutations L13S, R326Q and T359M resulted most likely in folding defects and oligomer assembly impairment. Two mutations were identified in several unrelated ß-ureidopropionase patients, indicating that ß-ureidopropionase deficiency may be more common than anticipated.
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