Notes

Current improvement throughout near-infrared photoacoustic photo.
Cognitive Multisensory Rehabilitation (CMR) is a promising therapy for upper limb recovery in stroke, but the brain mechanisms are unknown. We previously demonstrated that the parietal operculum (parts OP1/OP4) is activated with CMR exercises. In this exploratory study, we assessed the baseline difference between OP1/OP4 functional connectivity (FC) at rest in stroke versus healthy adults to then explore whether CMR affects OP1/OP4 connectivity and sensorimotor recovery after stroke. We recruited 8 adults with chronic stroke and left hemiplegia/paresis and 22 healthy adults. Resting-state FC with the OP1/OP4 region-of-interest in the affected hemisphere was analysed before and after 6 weeks of CMR. We evaluated sensorimotor function and activities of daily life pre- and post-CMR, and at 1-year post-CMR. At baseline, we found decreased FC between the right OP1/OP4 and 34 areas distributed across all lobes in stroke versus healthy adults. After CMR, only four areas had decreased FC compared to healthy adults. Compared to baseline (pre-CMR), participants improved on motor function (MESUPES arm p = 0.02; MESUPES hand p = 0.03; MESUPES total score p = 0.006); on stereognosis (p = 0.03); and on the Frenchay Activities Index (p = 0.03) at post-CMR and at 1-year follow-up. These results suggest enhanced sensorimotor recovery post-stroke after CMR. Our results justify larger-scale studies.An amendment to this paper has been published and can be accessed via a link at the top of the paper.Diagnostic leukapheresis (DLA) enables to sample larger blood volumes and increases the detection of circulating tumor cells (CTC) significantly. Nevertheless, the high excess of white blood cells (WBC) of DLA products remains a major challenge for further downstream CTC enrichment and detection. To address this problem, we tested the performance of two label-free CTC technologies for processing DLA products. For the testing purposes, we established ficollized buffy coats (BC) with a WBC composition similar to patient-derived DLA products. The mimicking-DLA samples (with up to 400 × 106 WBCs) were spiked with three different tumor cell lines and processed with two versions of a spiral microfluidic chip for label-free CTC enrichment the commercially available ClearCell FR1 biochip and a customized DLA biochip based on a similar enrichment principle, but designed for higher throughput of cells. While the samples processed with FR1 chip displayed with increasing cell load significantly higher WBC backgrounds and decreasing cell recovery, the recovery rates of the customized DLA chip were stable, even if challenged with up to 400 × 106 WBCs (corresponding to around 120 mL peripheral blood or 10% of a DLA product). These results indicate that the further up-scalable DLA biochip has potential to process complete DLA products from 2.5 L of peripheral blood in an affordable way to enable high-volume CTC-based liquid biopsies.Parkinson's disease (PD) is a neurodegenerative disorder for which only symptomatic treatments are available. Repurposing drugs that target α-synuclein aggregation, considered one of the main drivers of PD progression, could accelerate the development of disease-modifying therapies. In this work, we focused on chemically modified tetracycline 3 (CMT-3), a derivative with reduced antibiotic activity that crosses the blood-brain barrier and is pharmacologically safe. We found that CMT-3 inhibited α-synuclein amyloid aggregation and led to the formation of non-toxic molecular species, unlike minocycline. Furthermore, CMT-3 disassembled preformed α-synuclein amyloid fibrils into smaller fragments that were unable to seed in subsequent aggregation reactions. Most interestingly, disaggregated species were non-toxic and less inflammogenic on brain microglial cells. Finally, we modelled the interactions between CMT-3 and α-synuclein aggregates by molecular simulations. In this way, we propose a mechanism for fibril disassembly. Our results place CMT-3 as a potential disease modifier for PD and possibly other synucleinopathies.Measuring biological samples by atom probe tomography (APT) in their natural environment, i.e. aqueous solution, would take this analytical method, which is currently well established for metals, semi-conductive materials and non-metals, to a new level. It would give information about the 3D chemical structure of biological systems, which could enable unprecedented insights into biological systems and processes, such as virus protein interactions. For this future aim, we present as a first essential step the APT analysis of pure water (Milli-Q) which is the main component of biological systems. After Cryo-preparation, nanometric water tips are field evaporated with assistance by short laser pulses. The obtained data sets of several tens of millions of atoms reveal a complex evaporation behavior. Understanding the field evaporation process of water is fundamental for the measurement of more complex biological systems. For the identification of the individual signals in the mass spectrum, DFT calculations were performed to prove the stability of the detected molecules.The magnetic skyrmion is a topological magnetic vortex, and its topological nature is characterized by an index called skyrmion number which is a mapping of the magnetic moments defined on a two-dimensional space to a unit sphere. In three-dimensions, a skyrmion, i.e., a vortex penetrating though the magnet naturally forms a string, which terminates at the surfaces of the magnet or in the bulk. For such a string, the topological indices, which control its topological stability are less trivial. Here, we study theoretically, in terms of numerical simulation, the dynamics of current-driven motion of a skyrmion string in a film sample with the step edges on the surface. α-Conotoxin GI cost In particular, skyrmion-antiskyrmion pair is generated by driving a skyrmion string through the side step with an enough height. We find that the topological indices relevant to the stability are the followings; (1) skyrmion number along the developed surface, and (2) the monopole charge in the bulk defined as the integral over the surface enclosing a singular magnetic configuration.
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