Measuring activity of the subthalamic nucleus in acute slices using multi electrode arrays

The symptoms of Parkinson’s disease (a.o.: tremor, rigidity) can be suppressed by electrical stimulation of the basal ganglia. The most common target nucleus of this so called Deep Brain Stimulation (DBS) is the subthalamic nucleus (STN). Good clinical results are obtained by the application of pulses of 200 s, 1-3 V amplitude at a constant rate of about 130 Hz. However, the mechanism(s) responsible for the clinical improvements are not yet elucidated.\ud The use of acute brain slices as a model is widely used, despite the inevitable loss of many connections. Accurate (i.e. subthreshold) measurements of single neuron and multiple neuron (up to ~3, for practical reasons) membrane potentials are obtained by patch-clamp technique. We propose to use arrays of microelectrodes in slice recordings of STN. We present here our first results

Increased bradykinesia in Parkinson’s disease with increased movement complexity: elbow flexion-extension movements

The present research investigates factors contributing to bradykinesia in the control of simple and complex voluntary limb movement in Parkinson’s disease (PD) patients. The functional scheme of the basal ganglia (BG)–thalamocortical circuit was described by a mathematical model based on the mean firing rates of BG nuclei. PD was simulated as a reduction in dopamine levels, and a loss of functional segregation between two competing motor modules. In order to compare model simulations with performed movements, flexion and extension at the elbow joint is taken as a test case. Results indicated that loss of segregation contributed to bradykinesia due to interference between competing modules and a reduced ability to suppress unwanted movements. Additionally, excessive neurotransmitter depletion is predicted as a possible mechanism for the increased difficulty in performing complex movements. The simulation results showed that the model is in qualitative agreement with the results from movement experiments on PD patients and healthy subjects. Furthermore, based on changes in the firing rate of BG nuclei, the model demonstrated that the effective mechanism of Deep Brain Stimulation (DBS) in STN may result from stimulation induced inhibition of STN, partial synaptic failure of efferent projections, or excitation of inhibitory afferent axons even though the underlying methods of action may be quite different for the different mechanisms

First Detection of Mid-Infrared Variability from an Ultraluminous X-Ray Source Holmberg II X-1

We present mid-infrared (IR) light curves of the Ultraluminous X-ray Source (ULX) Holmberg II X-1 from observations taken between 2014 January 13 and 2017 January 5 with the \textit{Spitzer Space Telescope} at 3.6 and 4.5 $\mu$m in the \textit{Spitzer} Infrared Intensive Transients Survey (SPIRITS). The mid-IR light curves, which reveal the first detection of mid-IR variability from a ULX, is determined to arise primarily from dust emission rather than from a jet or an accretion disk outflow. We derived the evolution of the dust temperature ($T_\mathrm{d}\sim600 - 800$ K), IR luminosity ($L_\mathrm{IR}\sim3\times10^4$ $\mathrm{L}_\odot$), mass ($M_\mathrm{d}\sim1-3\times10^{-6}$ $\mathrm{M}_\odot$), and equilibrium temperature radius ($R_\mathrm{eq}\sim10-20$ AU). A comparison of X-1 with a sample spectroscopically identified massive stars in the Large Magellanic Cloud on a mid-IR color-magnitude diagram suggests that the mass donor in X-1 is a supergiant (sg) B[e]-star. The sgB[e]-interpretation is consistent with the derived dust properties and the presence of the [Fe II] ($\lambda=1.644$ $\mu$m) emission line revealed from previous near-IR studies of X-1. We attribute the mid-IR variability of X-1 to increased heating of dust located in a circumbinary torus. It is unclear what physical processes are responsible for the increased dust heating; however, it does not appear to be associated with the X-ray flux from the ULX given the constant X-ray luminosities provided by serendipitous, near-contemporaneous X-ray observations around the first mid-IR variability event in 2014. Our results highlight the importance of mid-IR observations of luminous X-ray sources traditionally studied at X-ray and radio wavelengths.Comment: 9 page, 4 figures, 1 table, Accepted to ApJ Letter

Oscillations in subthalamic nucleus measured by multi electrode arrays

The subthalamic nucleus (STN) of the basal ganglia, is involved in the generation of Parkinsonian symptoms and forms one of the main targets for Deep Brain Stimulation (DBS). Effective frequencies of DBS are around 130 Hz. The effect of such stimuli in the STN is largely unknown but has been hypothesized to result in neuronal block, interrupting the pathophysiological oscillatory behavior which is observed in the Parkinsionian basal ganglia. Modelling studies suggest that synchronized oscillation at tremor (4-8 Hz) or beta (14-30 Hz) frequencies may occur. To study synchronicity of the STN in detail, we record action-potential activity from rat brain slices using multi electrode arrays (MEAs). These arrays consist of 60 recording sites and thus allow the study of spatio-temporal activity patterns. Here we show the characteristics of spike trains which we recorded in the STN

Searching for the Donor Stars of ULX Pulsars

We report on our search for the optical counterparts of two ultraluminous X-ray pulsars with known orbital periods, M82 X-2 and NGC 5907 X-1, in new and archival HST observations, in an effort to characterize the donor stars in these systems. We detect five near-infrared sources consistent with the position of M82 X-2 that are too bright to be single stars. We also detect seven sources in the WFC3/UVIS F336W image whose photometry matches that of 10-15 M$_\odot$ stars turning off the main sequence. Such stars have densities consistent with the properties of the donor star of M82 X-2 as inferred from X-ray timing analysis, although it is also possible that the donor is a lower mass star below our detection limit or that there is a significant contribution from the accretion disc to the optical emission. We detect three candidate counterparts to NGC 5907 X-1 in the near-infrared. All of these are too bright to be the donor star of the ULX, which based on its orbital period is a red giant. The high background at the location of NGC 5907 X-1 precludes us from detecting this expected donor star. The recently discovered NGC 5907 ULX-2 also falls within the field of view of the near-infrared imaging; we detect four sources in the error circle, with photometry that matches AGB stars. The star suggested to be the counterpart of NGC 5907 ULX-2 by Pintore et al. (2018) falls outside our 2-$\sigma$ error circle.Comment: 10 pages, 3 figures, accepted for publication in Ap

Inhaled vaccine delivery in the combat against respiratory viruses:A 2021 overview of recent developments and implications for COVID-19

Introduction: As underlined by the late 2019 outbreak of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), vaccination remains the cornerstone of global health-care. Although vaccines for SARS-CoV-2 are being developed at a record-breaking pace, the majority of those that are licensed or currently registered in clinical trials are formulated as an injectable product, requiring a tightly regulated cold-chain infrastructure, and primarily inducing systemic immune responses.Areas covered: Here, we shed light on the status of inhaled vaccines against viral pathogens, providing background to the role of the mucosal immune system and elucidating what factors determine an inhalable vaccine's efficacy. We also discuss whether the development of an inhalable powder vaccine formulation against SARS-CoV-2 could be feasible. The review was conducted using relevant studies from PubMed, Web of Science and Google Scholar.Expert opinion: We believe that the scope of vaccine research should be broadened toward inhalable dry powder formulations since dry vaccines bear several advantages. Firstly, their dry state can tremendously increase vaccine stability and shelf-life. Secondly, they can be inhaled using disposable inhalers, omitting the need for trained health-care personnel and, therefore, facilitating mass-vaccination campaigns. Thirdly, inhalable vaccines may provide improved protection since they can induce an IgA-mediated mucosal immune response

Neural activity in the rat basal ganglia

Objectives: Pathological oscillations in the beta frequencies (8-30Hz) have been found in the local field potentials of Parkinson's disease (PD) patients and non-human primate models of PD1. In particular, these synchronizations appear in the subthalamic nucleus (STN), a common target for deep brain stimulation (DBS) for medically intractable PD2. DBS and dopamine replacement therapy have been shown to reduce these oscillations and ameliorate the motor symptoms of PD. To better understand the origin and mechanisms of these synchronizations, we performed in vitro multielectrode recordings from the rat basal ganglia that support the detection of synchronous activity from numerous neurons. Methods: 300-400 μm basal ganglia slices were obtained from Wistar rats (postnatal days 15-60) using a vibratome and warmed up to room temperature in a holding chamber. The slices were transferred onto a 3D multielectrode array (Ayanda Systems) for recording and continuously perfused with carbogenated artificial cerebral spinal fluid at 36 °C. Neural signals were measured and filtered with a 60 channel amplifier (Multichannel Systems GmbH) and visualized in LabView. Action potentials were detected from the extracellular signal using a 5 standard deviation voltage threshold and sorted into different neuronal units using principal component analysis. Further signal analysis was performed in Matlab to analyze the neuronal firing patterns and measure the extent of synchronous firing. Results: Our preliminary results identified three distinct firing patterns in the STN and substantia nigra. Most neurons exhibited regular spike trains (60%) while others were random (30%) or bursty (10%). The addition of dopamine however reduced the percentage of cells with bursty and random firing patterns. Additionally, we found a very low incidence of synchronizations. Taken together, these results form the basis with which to compare firing patterns in an animal model of PD. Conclusions: Multi-electrode array recordings from the basal ganglia can reveal changes in their neurophysiological properties and measure the amount of synchronization between different neurons. We intend to use this technique to investigate pathological firing patterns in the basal ganglia in a rotenone rat model of PD. Using a combination of chemical and electrical stimulation, we will explore contributions from different nuclei of the basal ganglia to the network behavior. This would allow us to build more realistic models of the basal ganglia and lead to better therapies for PD

Melatonin in neuropaediatric MRI:a retrospective study of efficacy in a general hospital setting

Background: Melatonin may offer a safe and cheap alternative to general anaesthesia and sedatives in neuropaediatric MRI. The purpose of our study was to evaluate its efficacy during a daily scanning programme and to assess its financial benefit. Methods: Neuro-MRI scans, performed in a general hospital setting after administration of melatonin in 64 children aged 10 months–5 years, were retrospectively reassessed by an experienced paediatric neuroradiologist, rating them as diagnostically contributing or as failed. The financial benefit was calculated. Results: 49/64 scans (77%) were diagnostically contributing, in 11 (22%) no movement artefact was seen in any sequence; 15/64 scans failed (23%), in 3/15 because of serious movement artefacts, in 12/15 the scan was not started. Repeat scans under general anaesthesia were performed in 17 cases (27%): in the 15 failed cases and in 2 cases initially assessed as failed, but were considered diagnostically contributing in the present study. The financial benefit at the time the scans were made was approximately 13,360 Euro. Conclusions: In this retrospective study, the use of melatonin in neuropaediatric MRI, made during a daily scanning programme with a remote waiting room, was associated with a high success rate in infants and young children. A minority of scans had no movement artefacts, indicating most children were not asleep. The sleep-inducing effect of melatonin could therefore not be proven, but the high success rate may be attributed to the sedative and/or anxiolytic effect of melatonin. Only a minority of scans had to be repeated under general anesthesia, leading to a reduction of scan related costs

Combining Hydrophilic and Hydrophobic Materials in 3D Printing for Fabricating Microfluidic Devices with Spatial Wettability

The fabrication of microfluidic flow cells via projection micro-stereolithography (PμSL) has excited researchers in recent years. However, due to the inherent process properties of most commercial PμSL, microfluidic devices are fabricated in a monolithic fashion with uniform material properties across a flow cell. Yet, the large surface-to-volume ratio in microfluidics demands to tailor microchannel surface properties—particularly in planar microchannel arrangements—with spatial control and micron-scale resolution to form a desired flow profile, e.g., emulsion droplets. Here, the fabrication of planar microfluidic devices by PμSLbased 3D printing with spatial control over surface properties is presented. For that, homemade photopolymer formulations being either hydrophilic or hydrophobic are designed. Adding acrylic acid to a resin containing poly(ethylene glycol) diacrylate lowers the contact angle down to 0° against water creating a superhydrophilic surface. By utilizing 1H,1H,2H,2H-perfluorodecyl acrylate, a photopolymer formulation allowing for 3D-printing a hydrophobic microchannel surface with a contact angle >120° against water is obtained. Combining these two materials, microfluidic flow cells with spatially defined wettability are 3D-printed for emulsion formation. Finally, the resin vat of the commercial PμSL printer is switched during the printing process for fabricating multimaterial geometries, as exemplarily applied for realizing a hydrophobic-hydrophilic-hydrophobic device for forming O/W/O double emulsions

Quantum transport theory for nanostructures with Rashba spin-orbital interaction

We report on a general theory for analyzing quantum transport through devices in the Metal-QD-Metal configuration where QD is a quantum dot or the device scattering region which contains Rashba spin-orbital and electron-electron interactions. The metal leads may or may not be ferromagnetic, they are assumed to weakly couple to the QD region. Our theory is formulated by second quantizing the Rashba spin-orbital interaction in spectral space (instead of real space), and quantum transport is then analyzed within the Keldysh nonequilibrium Green's function formalism. The Rashba interaction causes two main effects to the Hamiltonian: (i) it gives rise to an extra spin-dependent phase factor in the coupling matrix elements between the leads and the QD; (ii) it gives rise to an inter-level spin-flip term but forbids any intra-level spin-flips. Our formalism provides a starting point for analyzing many quantum transport issues where spin-orbital effects are important. As an example, we investigate transport properties of a Aharnov-Bohm ring in which a QD having Rashba spin-orbital and e-e interactions is located in one arm of the ring. A substantial spin-polarized conductance or current emerges in this device due to a combined effect of a magnetic flux and the Rashba interaction. The direction and strength of the spin-polarization are shown to be controllable by both the magnetic flux and a gate voltage.Comment: 12 pages, 8 figure