Neural correlates of noun and verb production

Fonologische representatie

Lipidomic analysis of fibroblasts from Zellweger spectrum disorder patients identifies disease-specific phospholipid ratios

Peroxisomes are subcellular organelles involved in various metabolic processes, including fatty acid and phospholipid homeostasis. The Zellweger spectrum disorders (ZSDs) represent a group of diseases caused by a defect in the biogenesis of peroxisomes. Accordingly, cells from ZSD patients are expected to have an altered composition of fatty acids and phospholipids. Using an LC/MS-based lipidomics approach, we show that the phospholipid composition is characteristically altered in cultured primary skin fibroblasts from ZSD patients when compared with healthy controls. We observed a marked overall increase of phospholipid species containing very long-chain fatty acids, and a decrease of phospholipid species with shorter fatty acid species in ZSD patient fibroblasts. In addition, we detected a distinct phosphatidylcholine profile in ZSD patients with a severe and mild phenotype when compared with control cells. Based on our data, we present a set of specific phospholipid ratios for fibroblasts that clearly discriminate between mild and severe ZSD patients, and those from healthy controls. Our findings will aid in the diagnosis and prognosis of ZSD patients, including an increasing number of mild patients in whom hardly any abnormalities are observed in biochemical parameters commonly used for diagnosis

Functional characterisation of peroxisomal β-oxidation disorders in fibroblasts using lipidomics

Peroxisomes play an important role in a variety of metabolic pathways, including the α‐ and β‐oxidation of fatty acids, and the biosynthesis of ether phospholipids. Single peroxisomal enzyme deficiencies (PEDs) are a group of peroxisomal disorders in which either a peroxisomal matrix enzyme or a peroxisomal membrane transporter protein is deficient. To investigate the functional consequences of specific enzyme deficiencies on the lipidome, we performed lipidomics using cultured skin fibroblasts with different defects in the β‐oxidation of very long‐chain fatty acids, including ABCD1‐ (ALD), acyl‐CoA oxidase 1 (ACOX1)‐, D‐bifunctional protein (DBP)‐, and acyl‐CoA binding domain containing protein 5 (ACBD5)‐deficient cell lines. Ultra‐high performance liquid chromatography coupled with high‐resolution mass spectrometry revealed characteristic changes in the phospholipid composition in fibroblasts with different fatty acid β‐oxidation defects. Remarkably, we found that ether phospholipids, including plasmalogens, were decreased. We defined specific phospholipid ratios reflecting the different enzyme defects, which can be used to discriminate the PED fibroblasts from healthy control cells

Cities for citizens! Public value spheres for understanding conflicts in urban planning

Identifying the diverse and often competing values of citizens, and resolving the consequent public value conflicts, are of significant importance for inclusive and integrated urban development. Scholars have highlighted that relational, value-laden urban space gives rise to many diverse conflicts that vary both spatially and temporally. Although notions of public value conflicts have been conceived in theory, there are few empirical studies that identify such values and their conflicts in urban space. Building on public value theory and using a case-study mixed-methods approach, this paper proposes a new approach to empirically investigate public value conflicts in urban space. Using unstructured participatory data of 4528 citizen contributions from a Public Participation Geographic Information Systems in Hamburg, Germany, natural language processing and spatial clustering techniques are used to identify areas of potential value conflicts. Four expert interviews assess and interpret these quantitative findings. By integrating quantitative assessments with the qualitative findings of the interviews, we identify 19 general public values and nine archetypical conflicts. On the basis of these results, this paper proposes a new conceptual model of ‘Public Value Spheres’ that extends the understanding of public value conflicts and helps to further account for the value-laden nature of urban space.Spatial Planning and StrategyUrban StudiesSystem EngineeringPolicy Analysi

Radiation-induced late effects in two affected individuals of the Lilo radiation accident.

Radiation exposure leads to a risk for long-term deterministic and stochastic late effects. Two individuals exposed to protracted photon radiation in the radiological accident at the Lilo Military site in Georgia in 1997 received follow-up treatment and resection of several chronic radiation ulcers in the Bundeswehr Hospital Ulm, Germany, in 2003. Multi-parameter analysis revealed that spermatogenetic arrest and serum hormone levels in both patients had recovered compared to the status in 1997. However, we observed a persistence of altered T-cell ratios, increased ICAM1 and beta1-integrin expression, and aberrant bone marrow cells and lymphocytes with significantly increased translocations 6 years after the accident. This investigation thus identified altered end points still detectable years after the accident that suggest persistent genomic damage as well as epigenetic effects in these individuals, which may be associated with an elevated risk for the development of further late effects. Our observations further suggest the development of a chronic radiation syndrome and indicate follow-up parameters in radiation victims