Etablierung eines neuartigen zellulären Models zur Erforschung der Tumorheterogenität in Myxofibrosarkomen

This paper shows the development of a new magnetic resonance imaging (MRI)-compatible guide wire made from fiber-reinforced plastics. The basic material of the developed guide wire is manufactured using a specially developed micro-pullwinding technology, which allows the adjustment of tensile, bending, and torsional stiffness independent from each other. Additionally, the micro-pullwinding technology provides the possibility to vary the stiffness along the length of the guide wire in a continuous process. With the possibilities of this technology, the mechanical properties of the guide wire were precisely adjusted for the intended usage in MRI-guided interventions. The performance of the guide wire regarding the mechanical properties was investigated. It could be shown, that the mechanical properties could be changed independently from each other by varying the process parameters. Especially, the torsional stiffness could be significantly improved with only a minor infl uence on bending and tensile properties. The precise influence of the variation of the winding angle on the mechanical and geometrical properties has to be further investigated. The usability of the guide wire as well as its visibility in MRI was investigated by radiologists. With the micro-pullwinding technology, a continuous manufacturing technique for highly stressable, MRI-safe profiles is available and can be the trigger for a new class of medical devices

Turn plasticity distinguishes different modes of amyloid-beta aggregation.

Pathogenesis of Alzheimer's disease (AD) is associated with aggregation of the amyloid-beta (A beta) peptide into oligomeric and fibrillar assemblies; however, little is known about the molecular basis of aggregation of A beta into distinct assembly states. Here we demonstrate that phosphorylation at serine 26 (S26) impairs A beta fibrillization while stabilizing its monomers and nontoxic soluble assemblies of nonfibrillar morphology. NMR spectroscopy and replica-exchange molecular dynamics indicate that introduction of a phosphate group or phosphomimetic at position 26 diminishes A beta's propensity to form a beta-hairpin, rigidifies the region around the modification site, and interferes with formation of a fibril-specific salt bridge between aspartic acid 23 and lysine 28. The combined data demonstrate that phosphorylation of S26 prevents a distinct conformational rearrangement that is required for progression of A beta aggregation toward fibrils and provide a basis for a possible role of phosphorylation at serine 26 in AD

Induction of α-synuclein aggregate formation by CSF exosomes from patients with Parkinson's disease and dementia with Lewy bodies

Extracellular α-synuclein has been proposed as a crucial mechanism for induction of pathological aggregate formation in previously healthy cells. In vitro, extracellular α-synuclein is partially associated with exosomal vesicles. Recently, we have provided evidence that exosomal α-synuclein is present in the central nervous system in vivo. We hypothesized that exosomal α-synuclein species from patients with α-synuclein related neurodegeneration serve as carriers for interneuronal disease transmission. We isolated exosomes from cerebrospinal fluid from patients with Parkinson’s disease, dementia with Lewy bodies, progressive supranuclear palsy as a non-α-synuclein related disorder that clinically overlaps with Parkinson’s disease, and neurological controls. Cerebrospinal fluid exosome numbers, α-synuclein protein content of cerebrospinal fluid exosomes and their potential to induce oligomerization of α-synuclein were analysed. The quantification of cerebrospinal fluid exosomal α-synuclein showed distinct differences between patients with Parkinson’s disease and dementia with Lewy bodies. In addition, exosomal α-synuclein levels correlated with the severity of cognitive impairment in cross-sectional samples from patients with dementia with Lewy bodies. Importantly, cerebrospinal fluid exosomes derived from Parkinson’s disease and dementia with Lewy bodies induce oligomerization of α-synuclein in a reporter cell line in a dose-dependent manner. Our data suggest that cerebrospinal fluid exosomes from patients with Parkinson’s disease and dementia with Lewy bodies contain a pathogenic species of α-synuclein, which could initiate oligomerization of soluble α-synuclein in target cells and confer disease pathology