Glia and alpha-synuclein in neurodegeneration: A complex interaction

Abstractα-Synucleinopathies (ASP) comprise adult-onset, progressive neurodegenerative disorders such as Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA) that are characterized by α-synuclein (AS) aggregates in neurons or glia. PD and DLB feature neuronal AS-positive inclusions termed Lewy bodies (LB) whereas glial cytoplasmic inclusions (GCIs, Papp–Lantos bodies) are recognized as the defining hallmark of MSA. Furthermore, AS-positive cytoplasmic aggregates may also be seen in astroglial cells of PD/DLB and MSA brains. The glial AS-inclusions appear to trigger reduced trophic support resulting in neuronal loss. Moreover, microgliosis and astrogliosis can be found throughout the neurodegenerative brain and both are key players in the initiation and progression of ASP. In this review, we will highlight AS-dependent alterations of glial function and their impact on neuronal vulnerability thereby providing a detailed summary on the multifaceted role of glia in ASP

Biofunctionalized zinc peroxide (ZnO2) nanoparticles as active oxygen sources and antibacterial agents

Oxygen is one of the most important substances for physiological reactions and metabolisms in biological systems. Through the tailored design of oxygen-releasing materials it might be possible to control different biological processes. In this work we synthesized for the first time zinc peroxide nanoparticles with controlled sizes and biofunctionalized surfaces using a one-step reaction procedure. The zinc peroxide nanoparticles were obtained with tunable sizes (between 4.0 ± 1.2 nm and 9.4 ± 5.2 nm) and were decorated with glucose 1-phosphate (Glc-1P). The specific interaction of the phosphate function of Glc-1P with the nanoparticle surface was monitored by solid state 31P-NMR and zeta-potential measurements. Furthermore, using fluorescence measurements we demonstrated that anchored glucose molecules on the nanoparticle surface are accessible for specific interactions with lectins. It could be shown that these interactions strongly depend on the amount of Glc-1P attached to the nanoparticle surface. Additionally it was demonstrated that the oxygen release from biofunctionalized zinc peroxide nanoparticles could be tuned according to the chemical composition of the nanoparticles and the pH of the aqueous solution. The antibacterial efficiency of the synthesized nanoparticles against Enterococcus faecalis, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Prevotella intermedia was evaluated by determination of minimal bactericidal concentration (MIC)

Autoantibodies to MOG in a distinct subgroup of adult multiple sclerosis

Objectives: To evaluate the presence of antibodies to conformation-intact myelin oligodendrocyte glycoprotein (MOG) in a subgroup of adult patients with clinically definite multiple sclerosis (MS) preselected for a specific clinical phenotype including severe spinal cord, optic nerve, and brainstem involvement. Methods: Antibodies to MOG were investigated using a cell-based assay in 3 groups of patients: 104 preselected patients with MS (group 1), 55 age-and sex-matched, otherwise unselected patients with MS (group 2), and in 22 brain-biopsied patients with demyelinating diseases of the CNS (n = 19 with MS), 4 of whom classified as MS type II (group 3). Recognized epitopes were identified with mutated variants of MOG. Results: Antibodies to MOG were found in about 5%(5/104) of preselected adult patients with MS. In contrast, in groups 2 and 3, none of the patients tested positive for MOG antibodies. Patients with MS with antibodies to MOG predominantly manifested with concomitant severe brainstem and spinal cord involvement and had a severe disease course with high relapse rates and failure to several disease-modifying therapies. Three of them had been treated with plasma exchange with a favorable response. All anti-MOG-positive patients with MS showed typical MS lesions on brain MRI. Longitudinal analysis up to 9 years revealed fluctuations and reappearance of anti-MOG reactivity. Epitope mapping indicated interindividual heterogeneity, yet intraindividual stability of the antibody response. Conclusions: Antibodies to MOG can be found in a distinct subgroup of adult MS with a specific clinical phenotype and may indicate disease heterogeneity

Disease-Free Survival of Patients With Muscle-Invasive Bladder Cancer Treated With Radical Cystectomy Versus Bladder-Preserving Therapy:A Nationwide Study

Purpose: Although level I evidence is lacking that radical cystectomy (RC) is superior to bladder-preserving therapy (BPT), RC is still advocated as the recommended treatment in patients with nonmetastatic muscle-invasive bladder cancer (MIBC). This study sought to compare the survival of patients with MIBC treated with BPT versus those treated with RC. Methods and Materials: All patients with nonmetastatic MIBC diagnoses were identified via the population-based Netherlands Cancer Registry. Only patients treated with BPT or RC were included. The primary endpoint was 2-year disease-free survival (DFS), defined as time from start of treatment until locoregional recurrence, distant metastasis, or death. The secondary endpoint was overall survival (OS). Inverse propensity treatment weighting (IPTW) was used based on propensity scores to adjust for baseline differences between treatment groups. Survival was analyzed with Kaplan-Meier and Cox proportional hazards models. Results: A total of 1432 patients were included, of whom 1101 underwent RC and 331, BPT. Median follow-up was 39 months (range, 27-51 months). The IPTW-adjusted 2-year DFS was 61.5% (95% CI, 53.5%-69.6%) with BPT and 55.3% (95% CI, 51.6%-59.1%) with RC, with an adjusted hazard ratio of 0.84 (95% CI, 0.69-1.05). The adjusted 2-year OS for patients treated with BPT versus RC was 74.0% (95% CI, 67.0%-80.9%) versus 66.0% (95% CI, 62.7%-68.8%), respectively, with an adjusted hazard ratio of 0.80 (95% CI, 0.64-0.98). Conclusions: There was no statistically significant difference between the 2-year DFS of patients treated with BPT and RC. We propose that both RC and BPT should be offered as a curative treatment option to eligible patients with nonmetastatic MIBC.</p

New magnetic phase of the chiral skyrmion material Cu₂OSeO₃

The lack of inversion symmetry in the crystal lattice of magnetic materials gives rise to complex noncollinear spin orders through interactions of a relativistic nature, resulting in interesting physical phenomena, such as emergent electromagnetism. Studies of cubic chiral magnets revealed a universal magnetic phase diagram composed of helical spiral, conical spiral, and skyrmion crystal phases. We report a remarkable deviation from this universal behavior. By combining neutron diffraction with magnetization measurements, we observe a new multidomain state in Cu2OSeO3. Just below the upper critical field at which the conical spiral state disappears, the spiral wave vector rotates away from the magnetic field direction. This transition gives rise to large magnetic fluctuations. We clarify the physical origin of the new state and discuss its multiferroic properties.RST/Neutron and Positron Methods in MaterialsRST/Fundamental Aspects of Materials and Energ