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Appropriate response to others is necessary for social interactions. Yet little is known about how neurotransmitters regulate attractive and repulsive social cues. Using genetic and pharmacological manipulations in Drosophila melanogaster, we show that dopamine is contributing the response to others in a social group, specifically, social spacing, but not the avoidance of odours released by stressed flies (dSO). Interestingly, this dopamine-mediated behaviour is prominent only in the day-time, and its effect varies depending on tissue, sex and type of manipulation. Furthermore, alteration of dopamine levels has no effect on dSO avoidance regardless of sex, which suggests that a different neurotransmitter regulates this response. DA_Social_PaperRaw social space data in cm, dSO performance index and locomotion (numbers of lines crossed in 1 min. All details of how the data were obtained can be found in the material and methods of the paper.

Axial Image with 4-element PTX coil in suppression modeAxial slice through center of phantom obtained with GRE sequence (TR = 2000 ms, TE = 40 ms, slice thickness = 10 mm, in-plane resolution = 256x256, FOV = 24 cm) with 4-Element PTX operating in suppression mode (phase shifts of 40, 16, 200 and 301 degrees). Dicom file for image shown in manuscript.AxialGREwPTX.dcmCoil GeometryContains specs about the geometry of the coil configurations (including capacitance values) for the simulations.CoilGeometry.txtBirdcage HeatingTemperature probe measurements for heating at tip of wire 12 cm long copper wire in a polyacrylic acid cylindrical phantom (radius = 9 cm, height = 24 cm) using FRFSE sequence (TR = 559 ms, TE = 100 ms, echo train length = 24, 1 slice, imaging time = 4:08). Excitation with transmit/receive GE birdcage coil with transmit gain of 153.PTx Quadrature HeatingTemperature probe measurements for heating at tip of wire 12 cm long copper wire in a polyacrylic acid cylindrical phantom (radius = 9 cm, height = 24 cm) using FRFSE sequence (TR = 559 ms, TE = 100 ms, echo train length = 24, 1 slice, imaging time = 4:08). Excitation with 4-element parallel transmit coil with phase shifts of 0, 90, 180 and 270 degrees between elements with transmit gain of 195PTx Quad Heating Test 1 TX195.txtPTx Suppression Heating Test 1Temperature probe measurements for heating at tip of wire 12 cm long copper wire in a polyacrylic acid cylindrical phantom (radius = 9 cm, height = 24 cm) using FRFSE sequence (TR = 559 ms, TE = 100 ms, echo train length = 24, 1 slice, imaging time = 4:08). Excitation with 4-element parallel transmit coil with phase shifts of 40, 16, 200 and 301 degrees (suppression mode) with a transmit gain of 190PTx Suppression Heating Test 2Temperature probe measurements for heating at tip of wire 12 cm long copper wire in a polyacrylic acid cylindrical phantom (radius = 9 cm, height = 24 cm) using FRFSE sequence (TR = 559 ms, TE = 100 ms, echo train length = 24, 1 slice, imaging time = 4:08). Excitation with 4-element parallel transmit coil with phase shifts of 40, 16, 200 and 301 degrees (suppression mode) with a transmit gain of 187. Second measurement.E-field increase as function of wire positionFolder containing two files with % increase in E-field magnitude at tip of wire vs minimum in field of view for varying radial position (RposRatio.csv) and z position (ZposRatio.csv)WirePos.zipSimulation data for wire at r = 2.5 cm, z = 0 cm (E-field and H-field)Contains simulation data for wire positions r = 2.5 cm, z = 0 cm. Includes data for a 16-rung birdcage coil operating in quadrature mode and a 2-element PTX coil, 4-element PTX coil and 8-element PTX operating in suppression mode (amplitudes and phases found in manuscript). Each folder contains a folder named 'XY plane' corresponding to data in the z = 0 cm plane, x = -10 cm to x = 10 cm, y = -10 cm to 10 cm and 'YZ plane' corresponding to data in the x = 0 cm plane, z = -12 cm to 1 cm, y = -10 cm to 10 cm. Each file is named: _.txt. The files are space delimited. Header of 15 lines.Leadat25mm.zipSimulation data for wire at r = 8 cm, z = 2 cm (E-field and H-field)Contains simulation data for wire positions r = 8 cm, z = 2 cm. Includes data for a 16-rung birdcage coil operating in quadrature mode and a 2-element PTX coil, 4-element PTX coil and 8-element PTX operating in suppression mode (amplitudes and phases found in manuscript). Each folder contains a folder named 'XY plane' corresponding to data in the z = 0 cm plane, x = -10 cm to x = 10 cm, y = -10 cm to 10 cm and 'YZ plane' corresponding to data in the x = 0 cm plane, z = -12 cm to 1 cm, y = -10 cm to 10 cm. Each file is named: _.txt. The files are space delimited. Header of 15 linesLeadat80mmz2cm.zipSimulation data for wire at r = 7.5 cm, z = 0 cm (E-field and H-field)Contains simulation data for wire positions r = 7.5 cm, z = 0 cm. Includes data for a 16-rung birdcage coil operating in quadrature mode and a 2-element PTX coil, 4-element PTX coil and 8-element PTX operating in suppression mode (amplitudes and phases found in manuscript). Each folder contains a folder named 'XY plane' corresponding to data in the z = 0 cm plane, x = -10 cm to x = 10 cm, y = -10 cm to 10 cm and 'YZ plane' corresponding to data in the x = 0 cm plane, z = -12 cm to 1 cm, y = -10 cm to 10 cm. Each file is named: _.txt. The files are space delimited. Header of 15 linesLeatat75mm.zip Deep Brain Stimulation (DBS) is increasingly used to treat a variety of brain diseases by sending electrical impulses to deep brain nuclei through long, electrically conductive leads. Magnetic resonance imaging (MRI) of patients pre- and post-implantation is desirable to target and position the implant, to evaluate possible side-effects and to examine DBS patients who have other health conditions. Although MRI is the preferred modality for pre-operative planning, MRI post-implantation is limited due to the risk of high local power deposition, and therefore tissue heating, at the tip of the lead. The localized power deposition arises from currents induced in the leads caused by coupling with the radiofrequency (RF) transmission field during imaging. In the present work, parallel RF transmission (pTx) is used to tailor the RF electric field to suppress coupling effects. Electromagnetic simulations were performed for three pTx coil configurations with 2, 4, and 8-elements, respectively. Optimal input voltages to minimize coupling, while maintaining RF magnetic field homogeneity, were determined for all configurations using a Nelder-Mead optimization algorithm. Resulting electric and magnetic fields were compared to that of a 16-rung birdcage coil. Experimental validation was performed with a custom-built 4-element pTx coil. In simulation, 95-99% reduction of the electric field at the tip of the lead was observed between the various pTx coil configurations and the birdcage coil. Maximal reduction in E-field was obtained with the 8-element pTx coil. Magnetic field homogeneity was comparable to the birdcage coil for the 4- and 8-element pTx configurations. In experiment, a temperature increase of 2±0.15°C was observed at the tip of the wire using the birdcage coil, whereas negligible increase (0.2±0.15°C) was observed with the optimized pTx system. Although further research is required, these initial results suggest that the concept of optimizing pTx to reduce DBS heating effects holds considerable promise.

Objective: To investigate the efficacy and safety of aceneuramic acid extended-release (Ace-ER), a treatment intended to replace deficient sialic acid, in patients with GNE myopathy. Methods: UX001-CL301 was a Phase 3, double-blind, placebo-controlled, randomized, international study evaluating the efficacy and safety of Ace-ER in patients with GNE Myopathy. Participants who could walk ≥200 meters in a 6-minute walk test at screening were randomized 1:1, and stratified by sex, to receive Ace-ER 6g/day or placebo for 48 weeks and assessed every 8 weeks. The primary endpoint was change in muscle strength over 48 weeks measured by Upper Extremity Composite (UEC) score. Key secondary endpoints included change in Lower Extremity Composite (LEC) score, knee extensor strength, and GNE myopathy-Functional Activity Scale (GNEM-FAS) mobility domain score. Safety assessments included adverse events (AEs), vital signs, and clinical laboratory results. Results: Eighty-nine patients were randomized (Ace-ER n = 45; Placebo n = 44). Change from baseline to week 48 for UEC score between treatments did not differ (least square mean [LSM] Ace-ER -2.25 kg vs Placebo -2.99 kg; LSM difference (confidence interval [CI]) 0.74 (-1.61, 3.09); p = 0.5387). At week 48, there was no significant difference between treatments for the change in key secondary endpoints: LEC LSM difference (CI) -1.49 (-5.83, 2.86); knee extension strength -0.40 (-2.38, 1.58); and GNEM-FAS mobility domain score -0.72 (-2.01, 0.57). Gastrointestinal events were the most common AEs. Conclusions: Ace-ER was not superior to placebo in improving muscle strength and function in patients with GNE myopathy. Lochmuller et al UX001 CL301 MS supp materials protocol 13Dec2018Supplemental Material for Lochmuller et al Neurology: Table e-1. Change from Baseline to Week 48 in UEC and LEC Individual Muscle Groups with Hand-Held Dynamometry; Figure e-1. UX001-CL301 CONSORT Flow Diagram; UX001-CL301 Protocol

Magnetic resonance imaging (MRI) is a non-destructive technique that is capable of localizing pathologies and assessing other anatomical features (e.g., tissue volume, microstructure, and white matter connectivity) in postmortem, ex vivo human brains. However, when brains are removed from the skull and cerebrospinal fluid (i.e., their normal in vivo magnetic environment), air bubbles and air–tissue interfaces typically cause magnetic susceptibility artifacts that severely degrade the quality of ex vivo MRI data. In this report, we describe a relatively simple and cost-effective experimental setup for acquiring artifact-free ex vivo brain images using a clinical MRI system with standard hardware. In particular, we outline the necessary steps, from collecting an ex vivo human brain to the MRI scanner setup, and have also described changing the formalin (as might be necessary in longitudinal postmortem studies). Finally, we share some representative ex vivo MRI images that have been acquired using the proposed setup in order to demonstrate the efficacy of this approach. We hope that this protocol will provide both clinicians and researchers with a straight-forward and cost-effective solution for acquiring ex vivo MRI data from whole postmortem human brains.

The cardiac nervous system continuously controls cardiac function whether or not pathology is present. While myocardial infarction typically has a major and catastrophic impact, population studies have shown that longer-term risk for recurrent myocardial infarction and the related potential for sudden cardiac death depends mainly upon standard atherosclerotic variables and autonomic nervous system maladaptations. Investigative neurocardiology has demonstrated that autonomic control of cardiac function includes local circuit neurons for networked control within the peripheral nervous system. The structural and adaptive characteristics of such networked interactions define the dynamics and a new normal for cardiac control that results in the aftermath of recurrent myocardial infarction and/or unstable angina that may or may not precipitate autonomic derangement. These features are explored here via a mathematical model of cardiac regulation. A main observation is that the control environment during pathology is an extrapolation to a setting outside prior experience. Although global bounds guarantee stability, the resulting closed-loop dynamics exhibited while the network adapts during pathology are aptly described as ‘free-floating’ in order to emphasize their dependence upon details of the network structure. The totality of the results provide a mechanistic reasoning that validates the clinical practice of reducing sympathetic efferent neuronal tone while aggressively targeting autonomic derangement in the treatment of ischemic heart disease. Networked Mathematical ModelThe mathematical model is stored in a zip file. The model is written in JAVA. There is a readme file that explains how to compile and run the file. If there are any questions please contact the first author and full assistance will be supplied.DryadRepository.zip