Effects of in vitro Brevetoxin Exposure on Apoptosis and Cellular Metabolism in a Leukemic T Cell Line (Jurkat)

Harmful algal blooms (HABs) of the toxic dinoflagellate, Karenia brevis, produce red tide toxins, or brevetoxins. Significant health effects associated with red tide toxin exposure have been reported in sea life and in humans, with brevetoxins documented within immune cells from many species. The objective of this research was to investigate potential immunotoxic effects of brevetoxins using a leukemic T cell line (Jurkat) as an in vitro model system. Viability, cell proliferation, and apoptosis assays were conducted using brevetoxin congeners PbTx-2, PbTx-3, and PbTx-6. The effects of in vitro brevetoxin exposure on cell viability and cellular metabolism or proliferation were determined using trypan blue and MTT (1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan), respectively. Using MTT, cellular metabolic activity was decreased in Jurkat cells exposed to 5 – 10 μg/ml PbTx-2 or PbTx-6. After 3 h, no significant effects on cell viability were observed with any toxin congener in concentrations up to 10 μg/ml. Viability decreased dramatically after 24 h in cells treated with PbTx-2 or -6. Apoptosis, as measured by caspase-3 activity, was significantly increased in cells exposed to PbTx-2 or PbTx-6. In summary, brevetoxin congeners varied in effects on Jurkat cells, with PbTx-2 and PbTx-6 eliciting greater cellular effects compared to PbTx-3

Optically pumped magnetometers: From quantum origins to multi-channel magnetoencephalography

Optically Pumped Magnetometers (OPMs) have emerged as a viable and wearable alternative to cryogenic, superconducting MEG systems. This new generation of sensors has the advantage of not requiring cryogenic cooling and as a result can be flexibly placed on any part of the body. The purpose of this review is to provide a neuroscience audience with the theoretical background needed to understand the physical basis for the signal observed by OPMs. Those already familiar with the physics of MRI and NMR should note that OPMs share much of the same theory as the operation of OPMs rely on magnetic resonance. This review establishes the physical basis for the signal equation for OPMs. We re-derive the equations defining the bounds on OPM performance and highlight the important trade-offs between quantities such as bandwidth, sensor size and sensitivity. These equations lead to a direct upper bound on the gain change due to cross-talk for a multi-channel OPM system

Balanced, bi-planar magnetic field and field gradient coils for field compensation in wearable magnetoencephalography

To allow wearable magnetoencephalography (MEG) recordings to be made on unconstrained subjects the spatially inhomogeneous remnant magnetic field inside the magnetically shielded room (MSR) must be nulled. Previously, a large bi-planar coil system which produces uniform fields and field gradients was used for this purpose. Its construction presented a significant challenge, six distinct coils were wound on two 1.6 x 1.6 m2 planes. Here, we exploit shared coil symmetries to produce coils simultaneously optimised to generate homogenous fields and gradients. We show nulling performance comparable to that of a sixcoil system is achieved with this three-coil system, decreasing the strongest field component Bx by a factor of 53, and the strongest gradient dBx/dz by a factor of 7. To allow the coils to be used in environments with temporally-varying magnetic interference a dynamic nulling system was developed with a shielding factor of 40 dB at 0.01 Hz. Reducing the number of coils required and incorporating dynamic nulling should allow for greater take-up of this technology. Interactions of the coils with the high-permeability walls of the MSR were investigated using a method of images approach. Simulations show a degrading of field uniformity which was broadly consistent with measured values. These effects should be incorporated into future designs

Magnetic Field Mapping and Correction for Moving OP-MEG

Background: Optically pumped magnetometers (OPMs) have made moving, wearable magnetoencephalography (MEG) possible. The OPMs typically used for MEG require a low background magnetic field to operate, which is achieved using both passive and active magnetic shielding. However, the background magnetic field is never truly zero Tesla, and so the field at each of the OPMs changes as the participant moves. This leads to position and orientation dependent changes in the measurements, which manifest as low frequency artefacts in MEG data. Objective: We model the spatial variation in the magnetic field and use the model to predict the movement artefact found in a dataset. Methods: We demonstrate a method for modelling this field with a triaxial magnetometer, then show that we can use the same technique to predict the movement artefact in a real OPM-based MEG (OP-MEG) dataset. Results: Using an 86-channel OP-MEG system, we found that this modelling method maximally reduced the power spectral density of the data by 27.8 ± 0.6 dB at 0 Hz, when applied over 5 s non-overlapping windows. Conclusion: The magnetic field inside our state-of-the art magnetically shielded room can be well described by low-order spherical harmonic functions. We achieved a large reduction in movement noise when we applied this model to OP-MEG data. Significance: Real-time implementation of this method could reduce passive shielding requirements for OP-MEG recording and allow the measurement of low-frequency brain activity during natural participant movement

Mouth magnetoencephalography: A unique perspective on the human hippocampus

Traditional magnetoencephalographic (MEG) brain imaging scanners consist of a rigid sensor array surrounding the head; this means that they are maximally sensitive to superficial brain structures. New technology based on optical pumping means that we can now consider more flexible and creative sensor placement. Here we explored the magnetic fields generated by a model of the human hippocampus not only across scalp but also at the roof of the mouth. We found that simulated hippocampal sources gave rise to dipolar field patterns with one scalp surface field extremum at the temporal lobe and a corresponding maximum or minimum at the roof of the mouth. We then constructed a fitted dental mould to accommodate an Optically Pumped Magnetometer (OPM). We collected data using a previously validated hippocampal-dependant task to test the empirical utility of a mouth-based sensor, with an accompanying array of left and right temporal lobe OPMs. We found that the mouth sensor showed the greatest task-related theta power change. We found that this sensor had a mild effect on the reconstructed power in the hippocampus (~10% change) but that coherence images between the mouth sensor and reconstructed source images showed a global maximum in the right hippocampus. We conclude that augmenting a scalp-based MEG array with sensors in the mouth shows unique promise for both basic scientists and clinicians interested in interrogating the hippocampus

A lightweight magnetically shielded room with active shielding

Magnetically shielded rooms (MSRs) use multiple layers of materials such as MuMetal to screen external magnetic fields that would otherwise interfere with high precision magnetic field measurements such as magnetoencephalography (MEG). Optically pumped magnetometers (OPMs) have enabled the development of wearable MEG systems which have the potential to provide a motion tolerant functional brain imaging system with high spatiotemporal resolution. Despite significant promise, OPMs impose stringent magnetic shielding requirements, operating around a zero magnetic field resonance within a dynamic range of ± 5 nT. MSRs developed for OPM-MEG must therefore effectively shield external sources and provide a low remnant magnetic field inside the enclosure. Existing MSRs optimised for OPM-MEG are expensive, heavy, and difficult to site. Electromagnetic coils are used to further cancel the remnant field inside the MSR enabling participant movements during OPM-MEG, but present coil systems are challenging to engineer and occupy space in the MSR limiting participant movements and negatively impacting patient experience. Here we present a lightweight MSR design (30% reduction in weight and 40–60% reduction in external dimensions compared to a standard OPM-optimised MSR) which takes significant steps towards addressing these barriers. We also designed a ‘window coil’ active shielding system, featuring a series of simple rectangular coils placed directly onto the walls of the MSR. By mapping the remnant magnetic field inside the MSR, and the magnetic field produced by the coils, we can identify optimal coil currents and cancel the remnant magnetic field over the central cubic metre to just |B|= 670 ± 160 pT. These advances reduce the cost, installation time and siting restrictions of MSRs which will be essential for the widespread deployment of OPM-MEG

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements