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

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

Radio-microanalytical particle measurements method and application to Fukushima aerosols collected in Japan

A nondestructive analytical method based on autoradiography and gamma spectrometry was developed to perform activity distribution analysis for particulate samples. This was applied to aerosols collected in Fukushima Japan, 40 km north of the Daiichi nuclear power plant for a 6 week period beginning shortly after the March 2011 tsunami. For an activity distribution of 990 “hot particles” from a small filter area, the hottest particle was nearly one Bq[superscript 137+134]Cs but most of the activity in the filter was produced by particles having <50 mBq each. [superscript 134]Cs/[superscript 137]Cs activity ratios corrected to March 20, 2011 ranged from 0.68 (u[subscript c] = 28 %) to 1.3 (u[subscript c] = 15 %). The average ratio for a large quantity of particles was 0.92 (u[subscript c] = 4 %). Virtually all activity collected was beta and not alpha, suggesting little if any direct fuel debris was present at this site and time. These findings are expected to assist with separate efforts to better understand the emission events, radionuclide transport and potential environmental or biological uptake. The methods should be applicable to general environmental, radiotoxicological and similar studies for which activity distribution and particle chemistry are of importance

Incorporating usability evaluation into iterative development of an online platform to support research participation in Parkinson\u27s disease: A mixed methods protocol

\ua9 Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. Introduction Many people with Parkinson\u27s (PwP) are not given the opportunity or do not have adequate access to participate in clinical research. To address this, we have codeveloped with users an online platform that connects PwP to clinical studies in their local area. It enables site staff to communicate with potential participants and aims to increase the participation of the Parkinson\u27s community in research. This protocol outlines the mixed methods study protocol for the usability testing of the platform. Methods and analysis We will seek user input to finalise the platform\u27s design, which will then be deployed in a limited launch for beta testing. The beta version will be used as a recruitment tool for up to three studies with multiple UK sites. Usability data will be collected from the three intended user groups: PwP, care partners acting on their behalf and site study coordinators. Usability questionnaires and website analytics will be used to capture user experience quantitatively, and a purposive sample of users will be invited to provide further feedback via semistructured interviews. Quantitative data will be analysed using descriptive statistics, and a thematic analysis undertaken for interview data. Data from this study will inform future platform iterations. Ethics and dissemination Ethical approval was obtained from the University of Plymouth (3291; 3 May 2022). We will share our findings via a \u27Latest News\u27 section within the platform, presentations, conference meetings and national PwP networks

Δ9-TETRAHYDROCANNABINOL IS PROTECTIVE THROUGH PPARγ DEPENDENT MITOCHONDRIAL BIOGENESIS IN A CELL CULTURE MODEL OF PARKINSON'S DISEASE.

Cannabinoids such as Δ9-tetrahydrocannabinol (Δ9-THC) are neuroprotective in animal and cell culture models of Parkinson's disease (PD). In a PD cell culture model we recently demonstrated that Δ9-THC is neuroprotective through activation of the nuclear receptor peroxisomal proliferator-activated receptor γ (PPARγ). Furthermore, activation by specific agonists rosiglitazone and pioglitazone, has also been found neuroprotective. PPARγ is a nuclear receptor whose activation can lead to the expression of proteins involved in the de novo synthesis of mitochondria. One such protein is the PPARγ co-activator 1 α (PGC1α) as it co-activates NRF-1 mediated gene expression which is essential for the production of nuclear encoded, mitochondrial proteins. Here we investigate the effect of Δ9-THC and pioglitazone on mitochondrial biogenesis

Pinning and hysteresis in the field dependent diameter evolution of skyrmions in Pt/Co/Ir superlattice stacks

We have imaged N\'eel skyrmion bubbles in perpendicularly magnetised polycrystalline multilayers patterned into 1 \mu m diameter dots, using scanning transmission x-ray microscopy. The skyrmion bubbles can be nucleated by the application of an external magnetic field and are stable at zero field with a diameter of 260 nm. Applying an out of plane field that opposes the magnetisation of the skyrmion bubble core moment applies pressure to the bubble and gradually compresses it to a diameter of approximately 100 nm. On removing the field the skyrmion bubble returns to its original diameter via a hysteretic pathway where most of the expansion occurs in a single abrupt step. This contradicts analytical models of homogeneous materials in which the skyrmion compression and expansion are reversible. Micromagnetic simulations incorporating disorder can explain this behaviour using an effective thickness modulation between 10 nm grains

Diameter-independent skyrmion Hall angle observed in chiral magnetic multilayers

Magnetic skyrmions are topologically non-trivial nanoscale objects. Their topology, which originates in their chiral domain wall winding, governs their unique response to a motion inducing force. When subjected to an electrical current, the chiral winding of the spin texture leads to a deflection of the skyrmion trajectory, characterised by an angle with respect to the applied force direction. This skyrmion Hall angle is predicted to be skyrmion diameter dependent. In contrast, our experimental study finds that the skyrmion Hall angle is diameter independent for skyrmions with diameters ranging from 35 to 825 nm. At an average velocity of 6 ± 1 ms−1, the average skyrmion Hall angle was measured to be 9° ± 2°. In fact, the skyrmion dynamics is dominated by the local energy landscape such as materials defects and the local magnetic configuration

Extensive degeneracy, Coulomb phase and magnetic monopoles in an artificial realization of the square ice model

Artificial spin ice systems have been introduced as a possible mean to investigate frustration effects in a well-controlled manner by fabricating lithographically-patterned two-dimensional arrangements of interacting magnetic nanostructures. This approach offers the opportunity to visualize unconventional states of matter, directly in real space, and triggered a wealth of studies at the frontier between nanomagnetism, statistical thermodynamics and condensed matter physics. Despite the strong efforts made these last ten years to provide an artificial realization of the celebrated square ice model, no simple geometry based on arrays of nanomagnets succeeded to capture the macroscopically degenerate ground state manifold of the corresponding model. Instead, in all works reported so far, square lattices of nanomagnets are characterized by a magnetically ordered ground state consisting of local flux-closure configurations with alternating chirality. Here, we show experimentally and theoretically, that all the characteristics of the square ice model can be observed if the artificial square lattice is properly designed. The spin configurations we image after demagnetizing our arrays reveal unambiguous signatures of an algebraic spin liquid state characterized by the presence of pinch points in the associated magnetic structure factor. Local excitations, i.e. classical analogues of magnetic monopoles, are found to be free to evolve in a massively degenerated, divergence-free vacuum. We thus provide the first lab-on-chip platform allowing the investigation of collective phenomena, including Coulomb phases and ice-like physics.Comment: 26 pages, 10 figure

Deterministic Field-Free Skyrmion Nucleation at a Nanoengineered Injector Device

Magnetic skyrmions are topological solitons promising for applications as encoders for digital information. A number of different skyrmion-based memory devices have been recently proposed. In order to demonstrate a viable skyrmion-based memory device, it is necessary to reliably and reproducibly nucleate, displace, detect, and delete the magnetic skyrmions, possibly in the absence of external applied magnetic fields, which would needlessly complicate the device design. While the skyrmion displacement and detection have both been thoroughly investigated, much less attention has been dedicated to the study of the skyrmion nucleation process and its sub-nanosecond dynamics. In this study, we investigate the nucleation of magnetic skyrmions from a dedicated nanoengineered injector, demonstrating the reliable magnetic skyrmion nucleation at the remnant state. The sub-nanosecond dynamics of the skyrmion nucleation process were also investigated, allowing us to shine light on the physical processes driving the nucleation