Emerging Chirality in Artificial Spin Ice

Artificial spin ice, made up of planar nanostructured arrays of simple ferromagnetic bars, is a playground for rich physics associated with the spin alignment of the bars and spin texture associated with the magnetic frustration at the bar vertices. The phase diagram is exotic, showing magnetic monopole-like defects and liquid and solid phases of spins arranged in loop states with predicted chiral order. We show that magnetotransport measurements in connected honeycomb structures yield the onset of an anomalous Hall signal at 50 kelvin. The temperature scale can be attributed to the long-range dipolar ice phase. The topological Hall signal arises because chiral loops form at the sample edges, indicating a generic route to exotic states via nanoarray edge structure

An International Multi-Stakeholder Delphi Survey Study on the Design of Disease Modifying Parkinson’s Disease Trials

Background: Design of disease modification (DM) trials for Parkinson’s disease (PD) is challenging. Successful delivery requires a shared understanding of priorities and practicalities. Objective: To seek stakeholder consensus on phase 3 trials’ overall goals and structure, inclusion criteria, outcome measures, and trial delivery and understand where perspectives differ. Methods: An international expert panel comprising people with Parkinson’s (PwP), care partners (CP), clinical scientists, representatives from industry, funders and regulators participated in a survey-based Delphi study. Survey items were informed by a scoping review of DM trials and PwP input. Respondents scored item agreement over 3 rounds. Scores and reasoning were summarized by participant group each round until consensus, defined as≥70% of at least 3 participant groups falling within the same 3-point region of a 9-point Likert scale. Results: 92/121 individuals from 13 countries (46/69 PwP, 13/18 CP, 20/20 clinical scientists, representatives from 8/8 companies, 4/5 funders, and 1/1 regulator) completed the study. Consensus was reached on 14/31 survey items: 5/8 overall goals and structure, 1/8 Eligibility criteria, 7/13 outcome measures, and 1/2 trial delivery items. Extent of stakeholder endorsement for 428 reasons for scores was collated across items. Conclusions: This is the first systematic multi-stakeholder consultation generating a unique repository of perspectives on pivotal aspects of DM trial design including those of PwP and CP. The panel endorsed outcomes that holistically measure PD and the importance of inclusive trials with hybrid delivery models. Areas of disagreement will inform mitigating strategies of researchers to ensure successful delivery of future trials

An International Multi-Stakeholder Delphi Survey Study on the Design of Disease Modifying Parkinson\u27s Disease Trials

\ua9 2023 - The authors. Published by IOS Press. Background: Design of disease modification (DM) trials for Parkinson\u27s disease (PD) is challenging. Successful delivery requires a shared understanding of priorities and practicalities. Objective: To seek stakeholder consensus on phase 3 trials\u27 overall goals and structure, inclusion criteria, outcome measures, and trial delivery and understand where perspectives differ. Methods: An international expert panel comprising people with Parkinson\u27s (PwP), care partners (CP), clinical scientists, representatives from industry, funders and regulators participated in a survey-based Delphi study. Survey items were informed by a scoping review of DM trials and PwP input. Respondents scored item agreement over 3 rounds. Scores and reasoning were summarized by participant group each round until consensus, defined as≥70% of at least 3 participant groups falling within the same 3-point region of a 9-point Likert scale. Results: 92/121 individuals from 13 countries (46/69 PwP, 13/18 CP, 20/20 clinical scientists, representatives from 8/8 companies, 4/5 funders, and 1/1 regulator) completed the study. Consensus was reached on 14/31 survey items: 5/8 overall goals and structure, 1/8 Eligibility criteria, 7/13 outcome measures, and 1/2 trial delivery items. Extent of stakeholder endorsement for 428 reasons for scores was collated across items. Conclusions: This is the first systematic multi-stakeholder consultation generating a unique repository of perspectives on pivotal aspects of DM trial design including those of PwP and CP. The panel endorsed outcomes that holistically measure PD and the importance of inclusive trials with hybrid delivery models. Areas of disagreement will inform mitigating strategies of researchers to ensure successful delivery of future trials

Delta-9-tetrahydrocannabinol protects against MPP+ toxicity in SH-SY5Y cells by restoring proteins involved in mitochondrial biogenesis

This project was supported through a studentship awarded by the Plymouth University Peninsula Schools of Medicine and Dentistry.Proliferator-activated receptor γ (PPARγ) activation can result in transcription of proteins involved in oxidative stress defence and mitochondrial biogenesis which could rescue mitochondrial dysfunction in Parkinson's disease (PD).The PPARγ agonist pioglitazone is protective in models of PD; however side effects have limited its clinical use. The cannabinoid Δ9-tetrahydrocannabinol (Δ9-THC) may have PPARγ dependent anti-oxidant properties. Here we investigate the effects of Δ9-THC and pioglitazone on mitochondrial biogenesis and oxidative stress. Differentiated SH-SY5Y neuroblastoma cells were exposed to the PD relevant mitochondrial complex 1 inhibitor 1-methyl- 4-phenylpyridinium iodide (MPP+). We found that only Δ9-THC was able to restore mitochondrial content in MPP+ treated SH-SY5Y cells in a PPARγ dependent manner by increasing expression of the PPARγ co-activator 1a (PGC-1a), the mitochondrial transcription factor (TFAM) as well as mitochondrial DNA content. Co-application of Δ9- THC with pioglitazone further increased the neuroprotection against MPP+ toxicity as compared to pioglitazone treatment alone. Furthermore, using lentiviral knock down of the PPARγ receptor we showed that, unlike pioglitazone, Δ9-THC resulted in a PPARγ dependent reduction of MPP+ induced oxidative stress. We therefore suggest that, in contrast to pioglitazone, Δ9-THC mediates neuroprotection via PPARγ-dependent restoration of mitochondrial content which may be beneficial for PD treatment.Publisher PDFPeer reviewe

The non-random walk of chiral magnetic charge carriers in artificial spin ice

The flow of magnetic charge carriers (dubbed magnetic monopoles) through frustrated spin ice lattices, governed simply by Coulombic forces, represents a new direction in electromagnetism. Artificial spin ice nanoarrays realise this effect at room temperature, where the magnetic charge is carried by domain walls. Control of domain wall path is one important element of utilizing this new medium. By imaging the transit of domain walls across different connected 2D honeycomb structures we contribute an important aspect which will enable that control to be realized. Although apparently equivalent paths are presented to a domain wall as it approaches a Y-shaped vertex from a bar parallel to the field, we observe a stark non-random path distribution, which we attribute to the chirality of the magnetic charges. These observations are supported by detailed statistical modelling and micromagnetic simulations. The identification of chiral control to magnetic charge path selectivity invites analogy with spintronics

Limitations in artificial spin ice path selectivity: the challenges beyond topological control

Magnetic charge is carried through nanowire networks by domain walls, and the micromagnetic structure of a domain wall provides an opportunity to manipulate its movement. We have shown previously that magnetic monopole defects exist in artificial spin ice (ASI) and result from two bar switching at a vertex. To create and manipulate monopole defects and indeed magnetic charge in general, path selectivity of the domain wall at a vertex is required. We have recently shown that in connected ASI structures, transverse wall chirality (or topology) determines wall path direction, but a mechanism known as Walker breakdown, where a wall mutates into a wall of opposite chirality partially destroys selectivity. Recently it has been claimed that in isolated Y-shaped junctions that support vortex walls, selectivity is entirely determined by chirality (or topology), the suggestion being that vortex wall chirality is robust in the Walker breakdown process. Here we demonstrate that in Y-shaped junctions, magnetic switching in the important topologically protected regime exists only for a narrow window of field and bar geometry, and that it will be challenging to access this regime in field-driven ASI. This work has implications for the wider field of magnetic charge manipulation for high density memory storage

Dynamic imaging of the delay- and tilt-free motion of Néel domain walls in perpendicularly magnetized superlattices

We report on the time-resolved investigation of current- and field-induced domain wall motion in the flow regime in perpendicularly magnetized microwires exhibiting anti-symmetric exchange interaction by means of scanning transmission x-ray microscopy using a time step of 200 ps. The sub-ns time step of the dynamical images allowed us to observe the absence of incubation times for the motion of the domain wall within an uncertainty of 200 ps, together with indications for a negligible inertia of the domain wall. Furthermore, we observed that, for short current and magnetic field pulses, the magnetic domain walls do not exhibit a tilting during its motion, providing a mechanism for the fast, tilt-free, current-induced motion of magnetic domain walls

Changes in iron-regulatory gene expression occur in human cell culture models of Parkinson's disease.

BACKGROUND: Neuronal iron accumulation is thought to be relevant to the pathogenesis of Parkinson's disease (PD), although the mechanism remains elusive. We hypothesized that neuronal iron uptake may be stimulated by functional mitochondrial iron deficiency. OBJECTIVE: To determine firstly whether the mitochondrial toxin, 1-methyl-4-phenylpyridinium iodide (MPP(+)), results in upregulation of iron-import proteins and transporters of iron into the mitochondria, and secondly whether similar changes in expression are induced by toxins with different mechanisms of action. METHODS: We used quantitative PCR and Western blotting to investigate expression of the iron importers, divalent metal transporter, transferrin receptor 1 and 2 (TfR1 and TfR2) and mitoferrin-2 and the iron exporter ferroportin in differentiated SH-SY5Y cells exposed to three different toxins relevant to PD, MPP(+), paraquat (a free radical generator) and lactacystin (an inhibitor of the ubiquitin-proteasome system (UPS)). RESULTS: MPP(+) resulted in increased mRNA and protein levels of genes involved in cellular iron import and transport into the mitochondria. Similar changes occurred following exposure to paraquat, another inducer of oxidative stress. Lactacystin also resulted in increased TfR1 mRNA levels, although the other changes were not found. CONCLUSION: Our results support the hypothesis of a functional mitochondrial iron deficit driving neuronal iron uptake but also suggest that differences exist in neuronal iron handling induced by different toxins