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Plaisier E.,AP HP | Plaisier E.,French Institute of Health and Medical Research | Plaisier E.,University Pierre and Marie Curie | Chen Z.,French Institute of Health and Medical Research | And 10 more authors.
American Journal of Medical Genetics, Part A | Year: 2010

The COL4A1 gene encodes the α1-chain of type IV collagen, which is ubiquitously expressed in basement membranes. Mutations in COL4A1 have been reported in autosomal-dominant porencephaly and in patients with symptomatic small vessel brain disease, inconstantly associated with eye defects. We have previously reported three COL4A1 mutations associated with a systemic phenotype that we called HANAC (Hereditary Angiopathy, Nephropathy, Aneurysms, and Cramps). We carried out a clinical and genetic study of three families presenting with characteristic features of HANAC syndrome. Common systemic signs included arterial retinal tortuosity and muscle cramps, with a variable combination of small vessel brain disease, Raynaud phenomena, and kidney defects. Three novel COL4A1 missense substitutions are described, which affect highly conserved glycine residues within the collagenous domain of the protein. All six known mutations associated with the HANAC phenotype are localized within the CB3[IV] fragment of COL4A1, which encompasses major integrin-binding sites. Our results confirm that HANAC syndrome is a distinct clinical entity within the COL4A1-related disorders, which is characterized by systemic involvement and usually asymptomatic brain disease. The restricted distribution of COL4A1 mutations within the CB3[IV] region is a characteristic of the reports of patients with HANAC, which suggests that abnormal cell-type IV collagen interactions may underlie the systemic defects observed in this syndrome. © 2010 Wiley-Liss, Inc.

Mark F.E.,Haus Tomis | Vehlow J.,Tubingen | Dresch H.,Zweckverband Abfallwirtschaft Raum Wurzburg ZVAWS | Dima B.,Wurzburger Versorgungs und Verkehrs GmbH WVV | And 2 more authors.
Waste Management and Research | Year: 2015

Hexabromocyclododecane containing polystyrene foam obtained from the building and construction market has been co-incinerated in a full-scale waste incineration plant. The co-feeding of 1 and 2 wt% of polystyrene foam had no influence on the operation of the plant. The bromine content increased the raw gas hydrogen bromide concentration slightly. The air emission, including that of dioxins and bromine, was not altered and so was the quality of the solid residues. The hexabromocyclododecane concentrations in the solid residues were almost identical, regardless of whether or not and how much polystyrene foam was added. The obtained destruction efficiency was >99.999% independent of the amount of added polystyrene foam. This finding indicates a virtually total destruction of hexabromocyclododecane. © The Author(s) 2015.

Schiefer U.,University Hospital of Tuebingen | Schiefer U.,University of Tubingen | Dietzsch J.,University Hospital of Tuebingen | Dietz K.,Tubingen | And 5 more authors.
British Journal of Ophthalmology | Year: 2012

Purpose: To identify the variable with the strongest association between the magnitude of the relative afferent pupillary defect (RAPD) and visual field indices in patients with glaucomatous optic neuropathy. Methods: Seventy-nine consecutive subjects with manifest glaucomatous optic neuropathy at least in one eye were enrolled in this retrospective study. RAPD was assessed with the swinging flashlight test and quantified with a neutral density filter. Perimetry was performed using the fast thresholding strategy German Adaptive Threshold Estimation. The values of the central differential luminance sensitivity (DLS), of the MD (mean defect) and of the 'loss volume' (LVOL) based on the individually modelled 3D hill of vision - the latter two within the eccentricities of 108, 20° and 30°, respectively - were entered into a linear regression model without intercept as a function of RAPD. Results: An absolute value of RAPD of 0.3 log 10 units or more was present in 20 out of 79 glaucoma subjects (25%). The magnitude of RAPD was most closely associated with LVOL-30° (R 2=0.77), followed by MD- 30° (R 2=0.73), MD-20° (R 2=0.71), LVOL-20° (R 2=0.67), MD-10° (R 2=0.58), LVOL-10° (R 2=0.54) and central DLS (R 2=0.04). Conclusions: The prevalence of RAPD in glaucoma patients is comparatively small (25%). The magnitude of RAPD in glaucoma subjects is associated most closely with the LVOL within 30° eccentricity (which is the maximum visual field region tested in this study) and most loosely with central DLS, underscoring the impact of the entire (30°) visual field area on the afferent pupillary system.

Iatsenko I.,Max Planck Institute for Developmental Biology | Boichenko I.,Tubingen | Sommer R.J.,Max Planck Institute for Developmental Biology
Applied and Environmental Microbiology | Year: 2014

Bacillus thuringiensis has been widely used as a biopesticide, primarily for the control of insect pests, but some B. thuringiensis strains specifically target nematodes. However, nematicidal virulence factors of B. thuringiensis are poorly investigated. Here, we describe virulence factors of nematicidal B. thuringiensis DB27 using Caenorhabditis elegans as a model. We show that B. thuringiensis DB27 kills a number of free-living and animal-parasitic nematodes via intestinal damage. Its virulence factors are plasmid- encoded Cry protoxins, since plasmid-cured derivatives do not produce Cry proteins and are not toxic to nematodes. Whole-genome sequencing of B. thuringiensis DB27 revealed multiple potential nematicidal factors, including several Cry-like proteins encoded by different plasmids. Two of these proteins appear to be novel and show high similarity to Cry21Ba1. Named Cry21Fa1 and Cry21Ha1, they were expressed in Escherichia coli and fed to C. elegans, resulting in intoxication, intestinal damage, and death of nematodes. Interestingly, the effects of the two protoxins on C. elegans are synergistic (synergism factor, 1.8 to 2.5). Using purified proteins, we determined the 50% lethal concentrations (LC50s) for Cry21Fa1 and Cry21Ha1 to be 13.6 μg/ml and 23.9 μg/ml, respectively, which are comparable to the LC50 of nematicidal Cry5B. Finally, we found that signaling pathways which protect C. elegans against Cry5B toxin are also required for protection against Cry21Fa1. Thus, B. thuringiensis DB27 produces novel nematicidal protoxins Cry21Fa1 and Cry21Ha1 with synergistic action, which highlights the importance of naturally isolated strains as a source of novel toxins. © 2014, American Society for Microbiology.

Rasini V.,University of Modena and Reggio Emilia | Dominici M.,University of Modena and Reggio Emilia | Kluba T.,Tubingen | Siegel G.,University of Tubingen | And 5 more authors.
Cytotherapy | Year: 2013

Background aims. Mesenchymal stromal/stem cells (MSCs) can be isolated from human bone marrow (BM), expanded ex vivo and identified via numerous surface antigens. Despite the importance of these cells in regenerative therapy programs, it is unclear whether the cell membrane signature defining MSC preparations ex vivo is determined during culture or may reflect an in vivo counterpart. BM-MSC phenotype in vivo requires further investigation. Methods. To characterize cells in their natural BM environment, we performed multi-parametric immunohistochemistry on trabecular bone biopsy specimens from multiple donors and described cells by different morphology and micro-anatomic localization in relationship to a precise pattern of MSC antigen expression. Results. Microscopically examined high-power field marrow sections revealed an overlapping in vivo expression of antigens characterizing ex vivo expanded BM-MSCs, including CD10, CD73, CD140b, CD146, GD2 and CD271. Expanding this panel to proteins associated with pluripotency, such as Oct4, Nanog and SSEA-4, we were able to identify different cellular populations in the human trabecular bone and BM expressing different progenitor cell markers. Conclusions. Targeting several multipotency and pluripotency markers, we found that the BM contains identifiable and distinct progenitor cells further justifying their introduction for a wide range of applications in regenerative medicine. © 2013, International Society for Cellular Therapy.

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