University of Mu Nster

Mu, Germany

University of Mu Nster

Mu, Germany
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Huffmeier U.,Friedrich - Alexander - University, Erlangen - Nuremberg | Bergboer J.G.M.,Radboud University Nijmegen | Becker T.,University of Bonn | Armour J.A.,University of Nottingham | And 11 more authors.
Journal of Investigative Dermatology | Year: 2010

Recently, a deletion of two late cornified envelope (LCE) genes within the epidermal differentiation complex on chromosome 1 was shown to be overrepresented in 1,426 psoriasis vulgaris (PsV) patients of European ancestry. In this study, we report a confirmation of this finding in 1,354 PsV patients and 937 control individuals of German origin. We found an allele frequency of the deletion of 70.9% in PsV patients and of 64.9% in control individuals (X2= 17.44, P2.97 × 10-5, odds ratio (95% confidence interval)1.31 (1.15-1.48)). The overall copy number of the two LCE genes had no influence on the age of onset, but we observed a dosage effect at the genotype level. There was no evidence of statistically significant interaction with copy number of the Β-defensin cluster on 8p23.1 or with an IL-23R pathway variant in a combined data set of German and Dutch individuals, whereas evidence for interaction with the PSORS1 risk allele in German individuals was marginal and did not remain significant after correction for multiple testing. Our study confirms the recently published finding that the deletion of the two LCE genes is a susceptibility factor for PsV with dosage effect, while, because of power limitation, no final conclusion regarding interaction with other PsV risk factors can be made at this stage. © 2010 The Society for Investigative Dermatology.


Borchard F.,University of Mu nster | Buchholz S.,TU Berlin | Helbing F.,University of Mu nster | Fartmann T.,University of Mu nster | Fartmann T.,University of Osnabru ck
Biological Conservation | Year: 2014

Semi-natural habitats such as heathland ecosystems are important for the conservation of biodiversity. Due to land use changes, these valuable ecosystems have become highly threatened. Nowadays, their management and restoration is of special relevance for nature conservation. In this study, we used carabid beetles and spiders as bioindicators to evaluate the success of montane heathland restoration on former spruce forests. We compared three different treatments: (i) montane heathlands (MONHEATH), (ii) restoration (RESSITE) and (iii) control (CONTROL) sites. Four to five years after conducting the restoration measures, all environmental variables, except soil moisture, significantly differed between MONHEATH on one hand and RESSITE and CONTROL on the other. MONHEATH was characterised by a high cover of dwarf shrubs; in contrast, RESSITE/CONTROL had a vegetation rich in herbs/grasses with some bare ground. Both carabid beetle and spider assemblage composition clearly reflected these differences in environmental conditions. Alpha-diversity (Simpson diversity, evenness) and niche positions were, however, only significantly different for spiders. Diversity as well as spider indicator values for shade and moisture were higher for MONHEATH. Due to the cool and wet montane climate and the dense dwarf-shrub stands the carabid beetle and spider species characteristic of MONHEATH are typical woodland species. Four to five years after restoration, RESSITE and CONTROL still represent early successional stages with a low cover of the Ericaceae target dwarf shrubs (Calluna vulgaris, Vaccinium myrtillus and Vaccinium vitis-idaea), but are already home to some typical heathland carabid beetle and spider species that are missing in MONHEATH. © 2014 Elsevier Ltd.


Mathieu-Rivet E.,University of Rouen | Scholz M.,University of Mu Nster | Arias C.,Autonomous University of Madrid | Dardelle F.,University of Rouen | And 13 more authors.
Molecular and Cellular Proteomics | Year: 2013

Chlamydomonas reinhardtii is a green unicellular eukaryotic model organism for studying relevant biological and biotechnological questions. The availability of genomic resources and the growing interest in C. reinhardtii as an emerging cell factory for the industrial production of biopharmaceuticals require an in-depth analysis of protein N-glycosylation in this organism. Accordingly, we used a comprehensive approach including genomic, glycomic, and glycoproteomic techniques to unravel the N-glycosylation pathway of C. reinhardtii. Using mass-spectrometry-based approaches, we found that both endogenous soluble and membrane-bound proteins carry predominantly oligomannosides ranging from Man-2 to Man-5. In addition, minor complex N-linked glycans were identified as being composed of partially 6-Omethylated Man-3 to Man-5 carrying one or two xylose residues. These findings were supported by results from a glycoproteomic approach that led to the identification of 86 glycoproteins. Here, a combination of in-source collision- induced dissodiation (CID) for glycan fragmentation followed by mass tag-triggered CID for peptide sequencing and PNGase F treatment of glycopeptides in the presence of 18O-labeled water in conjunction with CID mass spectrometric analyses were employed. In conclusion, our data support the notion that the biosynthesis and maturation of N-linked glycans in the endoplasmic reticulum and Golgi apparatus occur via a GnT I-independent pathway yielding novel complex N-linked glycans that maturate differently from their counterparts in land plants. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.


Lempert T.,Heubnerweg | Olesen J.,Copenhagen University | Furman J.,University of Pittsburgh | Johnwaterston,Monash University | And 6 more authors.
Revue Neurologique | Year: 2014

This paper presents diagnostic criteria for vestibular migraine, jointly formulated by the Committee for Classification of Vestibular Disorders of the Baany Society and the Migraine Classification Subcommittee of the International Headache Society (IHS). The classification includes vestibular migraine and probable vestibular migraine. Vestibular migraine will appear in an appendix of the third edition of the International Classification of Headache Disorders (ICHD) as a first step for new entities, in accordance with the usual IHS procedures. Probable vestibular migraine may be included in a later version of the ICHD, when further evidence has been accumulated. The diagnosis of vestibular migraine is based on recurrent vestibular symptoms, a history of migraine, a temporal association between vestibular symptoms and migraine symptoms and exclusion of other causes of vestibular symptoms. Symptoms that qualify for a diagnosis of vestibular migraine include various types of vertigo as well as head motion-induced dizziness with nausea. Symptoms must be of moderate or severe intensity. Duration of acute episodes is limited to a window of between 5minutes and 72hours. © 2014 Elsevier Masson SAS. All rights reserved.


Roth W.,University of Leipzig | Kumar V.,University of Leipzig | Beer H.-D.,University of Zürich | Richter M.,University of Leipzig | And 12 more authors.
Journal of Cell Science | Year: 2012

Keratin 1 (KRT1) and its heterodimer partner keratin 10 (KRT10) are major constituents of the intermediate filament cytoskeleton in suprabasal epidermis. KRT1 mutations cause epidermolytic ichthyosis in humans, characterized by loss of barrier integrity and recurrent erythema. In search of the largely unknown pathomechanisms and the role of keratins in barrier formation and inflammation control, we show here that Krt1 is crucial for maintenance of skin integrity and participates in an inflammatory network in murine keratinocytes. Absence of Krt1 caused a prenatal increase in interleukin-18 (IL-18) and the S100A8 and S100A9 proteins, accompanied by a barrier defect and perinatal lethality. Depletion of IL-18 partially rescued Krt-/- mice. IL-18 release was keratinocyte-autonomous, KRT1 and caspase-1 dependent, supporting an upstream role of KRT1 in the pathology. Finally, transcriptome profiling revealed a Krt1-mediated gene expression signature similar to atopic eczema and psoriasis, but different from Krt5 deficiency and epidermolysis bullosa simplex. Our data suggest a functional link between KRT1 and human inflammatory skin diseases. © 2012. Published by The Company of Biologists Ltd.


Kohl T.,Justus Liebig University | Ziemann M.,University of Bonn | Weinbach J.,University of Bonn | Tchatcheva K.,University of Bonn | And 2 more authors.
Journal of Laparoendoscopic and Advanced Surgical Techniques | Year: 2010

Background: Partial amniotic carbon dioxide insufflation (PACI) during fetoscopic interventions greatly improves visualization of intraamniotic contents. The purpose of this study was to assess any histologically discernable effects from this approach on the fetal brain after long-term survival in sheep. Methods: Six pregnant ewes between 63 and 92 days of gestation underwent PACI after fetoscopic intraamniotic access. Insufflation pressures ranged between 7 and 15mm Hg (mean 11.7; median 12.5). Insufflation times ranged between 45 and 80 minutes (mean 55.8 minutes; median 52.5) and depended on the duration of various percutaneous fetoscopic maneuvers (e.g., posturing, fetal transesophageal electrocardiography, and chronic fetal vascular access) that were tested during these studies. After fetal spontaneous delivery between 147 and 150 days of gestation, 5 of the lambs were observed for abnormal neurological symptoms. The last ewe and her sheep were terminated at 133 days of gestation for humane reasons. All six brains were examined for hemorrhage, embolism, infarctions, inflammatory changes, and abnormal cortical maturation. An unoperated sibling was available as a control. Results: The 5 sheep that were spontaneously delivered exhibited no abnormal neurological findings. In all 6 sheep, PACI did not result in any histologically discernable damage to their brain in these long-term studies. Maternal and fetal complications were not observed during or after the approach. Conclusion: The application of PACI during minimally invasive fetoscopic interventions seems safe for the fetal brain. Due to the still limited clinical experience with PACI, continued assessment of its maternal and fetal risks as well as management are required. © 2010 Mary Ann Liebert, Inc.


Stegger L.,University of Tübingen | Stegger L.,University of Mu nster | Martirosian P.,University of Tübingen | Schwenzer N.,University of Tübingen | And 8 more authors.
Acta Radiologica | Year: 2012

Background: Hybrid positron emission tomography/magnetic resonance imaging (PET/MRI) with simultaneous data acquisition promises a comprehensive evaluation of cerebral pathophysiology on a molecular, anatomical, and functional level. Considering the necessary changes to the MR scanner design the feasibility of arterial spin labeling (ASL) is unclear. Purpose: To evaluate whether cerebral blood flow imaging with ASL is feasible using a prototype PET/MRI device. Material and Methods: ASL imaging of the brain with Flow-sensitive Alternating Inversion Recovery (FAIR) spin preparation and true fast imaging in steady precession (TrueFISP) data readout was performed in eight healthy volunteers sequentially on a prototype PET/MRI and a stand-alone MR scanner with 128 128 and 192 192 matrix sizes. Cerebral blood flow values for gray matter, signal-to-noise and contrast-to-noise ratios, and relative signal change were compared. Additionally, the feasibility of ASL as part of a clinical hybrid PET/MRI protocol was demonstrated in five patients with intracerebral tumors. Results: Blood flow maps showed good delineation of gray and white matter with no discernible artifacts. The mean blood flow values of the eight volunteers on the PET/MR system were 51+9 and 51 +7 mL/100 g/min for the 128 128 and 192 192 matrices (stand-alone MR, 57+2 and 55+5, not significant). The value for signal-to-noise (SNR) was significantly higher for the PET/MRI system using the 192 192 matrix size (P, 0.01), the relative signal change (dS) was significantly lower for the 192 192 matrix size (P = 0.02). ASL imaging as part of a clinical hybrid PET/MRI protocol could successfully be accomplished in all patients in diagnostic image quality. Conclusion: ASL brain imaging is feasible with a prototype hybrid PET/MRI scanner, thus adding to the value of this novel imaging technique.


Meyer W.,University of Mu nster | Seiler T.-B.,RWTH Aachen | Schwarzbauer J.,RWTH Aachen | Hollert H.,RWTH Aachen | Achten C.,University of Mu nster
Science of the Total Environment | Year: 2014

Investigations of the bioavailability and toxicity of polycyclic aromatic compounds (PAC) have rarely considered the heterogeneity of coals and the impact of more polar PAC besides polycyclic aromatic hydrocarbons (PAH).Earlier, we investigated the toxicity of eight heterogeneous coals and their extracts. In the present study, the hazard potential with respect to mechanism-specific toxicity of polar fractions of dichloromethane extracts from coals was studied. Polar extract fractions of all coal types except for anthracite induced EROD activity (determined in RTL-W1 cells), independent of coal type (Bio-TEQs between 23 ± 16 and 52 ± 22. ng/g). The polar fractions of all bituminous coal extracts revealed mutagenic activity (determined using the Ames Fluctuation test). No significant mutation induction was detected for the polar extract fractions from the lignite, sub-bituminous coal and anthracite samples, which indicates a higher dependency on coal type for polar PAC here.Additionally, information on bioavailability was derived from a bioaccumulation test using the deposit-feeding oligochaete Lumbriculus variegatus which was exposed for 28. days to ground coal samples. Despite the high toxic potential of most coal extracts and a reduced biomass of Lumbriculus in bituminous coal samples, bioaccumulation of PAH and mortality after 28 days were found to be low. Limited bioaccumulation of PAH (up to 3.6 ± 3.8 mg/kg EPA-PAH) and polar PAC were observed for all coal samples. A significant reduction of Lumbriculus biomass was observed in the treatments containing bituminous coals (from 0.019 ± 0.004. g to 0.046 ± 0.011 g compared to 0.080 ± 0.025 g per replicate in control treatments).We conclude that bioavailability of native PAC from coals including polar PAC is low for all investigated coal types. In comparison to lignite, sub-bituminous coals and anthracite, the bioavailability of PAC from bituminous coals is slightly increased. © 2014 Elsevier B.V.


Jungmann P.M.,University Hospital Freiburg | Mehlhorn A.T.,University Hospital Freiburg | Schmal H.,University Hospital Freiburg | Schillers H.,University of Mu Nster | And 2 more authors.
Tissue Engineering - Part A | Year: 2012

Objectives: Human adipose-derived stem cells (ASCs) show gene expression of chondrogenic markers after three-dimensional cultivation. However, hypertrophy and osteogenic transdifferentiation are still limiting clinical applications. The aim of this study was to investigate the impact of small GTPases (Rac1 and RhoA) on transforming growth factor (TGF)-β1-mediated chondrogenic differentiation of ASCs and compare it with BMP-2-induced hypertrophy, by assessing effects on intracellular and extracellular matrix. Methods: In a novel experimental approach we characterized differentiation of living stem cells by single-cell elasticity measurements using atomic force microscopy. Results were matched with single-cell size measurements (diameter and volume) and quantitative real time-polymerase chain reaction for osteogenic and hypertrophic (alkaline phosphatase [ALP], collagen type X) as well as chondrogenic (collagen type II) gene expression. Intracellular F-actin expression was visualized by phalloidin staining of alginate-embedded ASCs. Statistical analysis was performed using analysis of variance (ANOVA) and two-sided t-test. Results: Nontreated two-dimensional cultured ASCs (2D ASC) showed a significantly lower deformability than chondrocytes (Young's modulus: 294.4 vs. 225.1 Pa; ANOVA: p<0.001). Standard chondrogenic stimulation decreased stem cell elasticity to chondrocyte values (221.7 Pa). All other chondrogenic differentiated ASCs presented intermediate elasticity (BMP-2 stimulation: 269.1 Pa; Rac1 inhibition: 279.8 Pa; RhoA inhibtition: 257.8 Pa; p<0.05 compared to 2D ASC). F-actin fluorescence was visually decreased in Rac1-inhibited cells and increased in BMP-2-stimulated cells. Cell volume of 2D ASCs (6382.3fL; p<0.001) was significantly higher than in all stimulated samples (BMP-2: 3076.7fL; RhoA inhibition: 3126.0fL). Volume of stem cells after standard chondrogenic stimulation (2590.0fL) was not significantly different from chondrocyte volume (2244.9fL). Rac1-Inhibitor reduced stem cell volume significantly below chondrocyte volume (1781.1fL). Regarding mRNA expression, Rac1-Inhibitor reduced late hypertrophic transdifferentiation (collagen type X), while collagen type II production slightly increased (p<0.05). RhoA-Inhibitor increased osteogenesis (ALP) and slightly decreased collagen type II production (p<0.05). Conclusion: Biologically relevant nanomechanical parameters contribute to the evaluation of stem cell differentiation, in view of increased deformability of stem cells after chondrogenic stimulation. Regarding gene expression, Rac1 inhibition reduced hypertrophic chondrogenic differentiation and RhoA inhibition increased osteogenic transdifferentiation. Thus, the control of small GTPases is promising for cartilage tissue engineering purposes of stem cells. © 2012, Mary Ann Liebert, Inc.


PubMed | University of Mu nster
Type: Case Reports | Journal: Neurology | Year: 2012

Progressive multifocal leukoencephalopathy (PML) has become much more common with monoclonal antibody treatment for multiple sclerosis and other immune-mediated disorders.We report 2 patients with severe psoriasis and fatal PML treated for 3 years with efalizumab, a neutralizing antibody to L2-leukointegrin (LFA-1). In one patient, we conducted serial studies of peripheral blood and CSF including analyses of leukocyte phenotypes, migration ex vivo, and CDR3 spectratypes with controls coming from HIV-infected patients with PML. Extensive pathologic and histologic analysis was done on autopsy CNS tissue of both patients.Both patients developed progressive cognitive and motor deficits, and JC virus was identified in CSF. Despite treatment including plasma exchange (PE) and signs of immune reconstitution, both died of PML 2 and 6 months after disease onset. Neuropathologic examination confirmed PML. Efalizumab treatment was associated with reduced transendothelial migration by peripheral T cells in vitro. As expression levels of LFA-1 on peripheral T cells gradually rose after PE, in vitro migration increased. Peripheral and CSF T-cell spectratyping showed CD8+ T-cell clonal expansion but blunted activation, which was restored after PE.From these data we propose that inhibition of peripheral and intrathecal T-cell activation and suppression of CNS effector-phase migration both characterize efalizumab-associated PML. LFA-1 may be a crucial factor in homeostatic JC virus control.

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