Small sample sizes : A big data problem in high-dimensional data analysis

Acknowledgements The authors are grateful to the Editor, Associate Editor and three anonymous referees for their helpful suggestions, which greatly improved the manuscript. Funding The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The research is supported by the German Science Foundation awards number DFG KO 4680/3-2 and PA 2409/3-2.Peer reviewedPublisher PD

Multiplex LA-ICP-MS bio-imaging of brain tissue of a parkinsonian mouse model stained with metal-coded affinity-tagged antibodies and coated with indium-spiked commercial inks as internal standards

SH received financial support by the “Bundesministerium fuer Wirtschaft und Energie, Projektnummer MNPQ 09/10″.Peer reviewedPublisher PD

Solubility of α-synuclein species in the L62 mouse model of synucleinopathy

The authors acknowledge Dr. Silke Frahm for providing the 4D6 immunoblot in Supplementary Fig. S1.Peer reviewe

A Meta-Analysis on Presynaptic Changes in Alzheimer's Disease

This work was funded by TauRx Therapeutics Ltd.,SingaporePeer reviewedPublisher PD

Endothelin-1 overexpression and endothelial nitric oxide synthase knock-out induce different pathological responses in the heart of male and female mice

AbstractAimsThe nitric oxide and endothelin systems are key components of a local paracrine hormone network in the heart. We previously reported that diastolic dysfunction observed in mice lacking the endothelial nitric oxide synthase (eNOS−/−) can be prevented by a genetic overexpression of ET-1. Sexual dimorphisms have been reported in both ET-1 and NO systems. Particularly, eNOS−/− mice present sex related phenotypic differences.Main methodsWe used the ET-1 transgenic (ET+/+), eNOS−/−, and crossbred ET+/+eNOS−/− mice, and wild type controls. We measured cardiac function by heart catheterization. Cardiac ventricles were collected for histological and molecular profiling.Key findingsWe report here that (i) the level of ET-1 expression in eNOS−/− mice was elevated in males but not in females. (ii) Left ventricular end-diastolic blood pressure was higher in male eNOS−/− mice than in females. (ii) eNOS−/− males but not females developed cardiomyocyte hypertrophy. (iv) Perivascular fibrosis of intracardiac arteries developed in female ET+/+ and eNOS−/− mice but not in males. Additionally, (v) the cardiac expression of metalloprotease-9 was higher in eNOS−/− males compared to females. Finally, (vi) cardiac proteome analysis revealed that the protein abundance of the oxidative stress related enzyme superoxide dismutase presented with sexual dimorphism in eNOS−/− and ET+/+ mice.SignificanceThese results indicate that the cardiac phenotypes of ET-1 transgenic mice and eNOS knockout mice are sex specific. Since both systems are key players in the pathogenesis of cardiovascular diseases, our findings might be important in the context of gender differences in patients with such diseases

Proteomic analysis of hydromethylthionine in the line 66 model of frontotemporal dementia demonstrates actions on tau-dependent and tau-independent networks

Funding: This research received no external funding. Acknowledgments: The authors acknowledge Boris Neumann and Karola Lehmann for the excellent support with the proteomics data.Peer reviewedPublisher PD

Glutamatergic transmission and receptor expression in the synucleinopathy h-α-synL62 mouse model : Effects of hydromethylthionine

Acknowledgements The authors acknowledge Dr. Dilyara Lauer and Heide Lueck for the excellent technical support with the administration of drugs, collection of brains and sectioning of brain tissue for immunohistochemistry. Funding This work was funded by TauRx Therapeutics Ltd., Singapore. Z. C. was funded by the Erasmus+ programme of the European Union.Peer reviewedPublisher PD

Hydromethylthionine rescues synaptic SNARE proteins in a mouse model of tauopathies : interference by cholinesterase inhibitors

The authors acknowledge Malgorzata Wydrych and Joanna Lewandowska for the technical support with perfusion of mice and collection of brains, and of Soumya Palliyil Soman for the development of the s1D12 antibody.Peer reviewe

Differential compartmental processing and phosphorylation of pathogenic human tau and native mouse tau in the Line 66 model of frontotemporal dementia

Funding Information: Funding and additional information—This work was supported by EMPIR programme in Research Project 15HLT02 ReMiND cofinanced by the Participating States and the European Union's Horizon 2020 research and innovation programme (to N. L.). Work was also supported by WisTa Laboratories Ltd. (to V. M., D. L., M. M., C. R. H., G. R., C. M. W., F. T., and K. S.). Conflict of interest—This work was sponsored by WisTa Laboratories Ltd., an affiliate of TauRx Therapeutics Ltd. C. R. H. and C. M. W. are employees and officers of TauRx Therapeutics Ltd.Peer reviewedPublisher PD

Increased Cholinergic Response in α-Synuclein Transgenic Mice (h-α-synL62)

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