Mitochondria and neuroprotection in stroke: Cationic arginine-rich peptides (CARPs) as a novel class of mitochondria-targeted neuroprotective therapeutics

Stroke is the second leading cause of death globally and represents a major cause of devastating long-term disability. Despite sustained efforts to develop clinically effective neuroprotective therapies, presently there is no clinically available neuroprotective agent for stroke. As a central mediator of neurodamaging events in stroke, mitochondria are recognised as a critical neuroprotective target, and as such, provide a focus for developing mitochondrial-targeted therapeutics. In recent years, cationic arginine-rich peptides (CARPs) have been identified as a novel class of neuroprotective agent with several demonstrated mechanisms of action, including their ability to target mitochondria and exert positive effects on the organelle. This review provides an overview on neuronal mitochondrial dysfunction in ischaemic stroke pathophysiology and highlights the potential beneficial effects of CARPs on mitochondria in the ischaemic brain following stroke

Proteomic analysis of cortical neuronal cultures treated with poly-arginine peptide-18 (R18) and exposed to glutamic acid excitotoxicity

Poly-arginine peptide-18 (R18) has recently emerged as a highly effective neuroprotective agent in experimental stroke models, and is particularly efficacious in protecting cortical neurons against glutamic acid excitotoxicity. While we have previously demonstrated that R18 can reduce excitotoxicity-induced neuronal calcium influx, other molecular events associated with R18 neuroprotection are yet to investigated. Therefore, in this study we were particularly interested in protein expression changes in R18 treated neurons subjected to excitotoxicity. Proteomic analysis was used to compare protein expression patterns in primary cortical neuronal cultures subjected to: (i) R18-treatment alone (R18); (ii) glutamic acid excitotoxic injury (Glut); (iii) R18-treatment and glutamic acid injury (R18 + Glut); (iv) no treatment (Cont). Whole cell lysates were harvested 24 h post-injury and subjected to quantitative proteomic analysis (iTRAQ), coupled with liquid chromatography-tandem mass spectrometry (LC-MS/ MS) and subsequent bioinformatic analysis of differentially expressed proteins (DEPs). Relative to control cultures, R18, Glut, and R18 + Glut treatment resulted in the detection of 5, 95 and 14 DEPs respectively. Compared to Glut alone, R18 + Glut revealed 98 DEPs, including 73 proteins whose expression was also altered by treatment with Glut and/or R18 alone, as well as 25 other uniquely regulated proteins. R18 treatment reversed the up- or down-regulation of all 73 Glut-associated DEPs, which included proteins involved in mitochondrial integrity, ATP generation, mRNA processing and protein translation. Analysis of protein-protein interactions of the 73 DEPs showed they were primarily associated with mitochondrial respiration, proteasome activity and protein synthesis, transmembrane trafficking, axonal growth and neuronal differentiation, and carbohydrate metabolism. Identified protein pathways associated with proteostasis and energy metabolism, and with pathways involved in neurodegeneration. Collectively, the findings indicate that R18 neuroprotection following excitotoxicity is associated with preservation of neuronal protein profiles, and differential protein expression that assists in maintaining mitochondrial function and energy production, protein homeostasis, and membrane trafficking

ZyON: Enabling Spike Sorting on APSoC-Based Signal Processors for High-Density Microelectrode Arrays

Multi-Electrode Arrays and High-Density Multi-Electrode Arrays of sensors are a key instrument in neuroscience research. Such devices are evolving to provide ever-increasing temporal and spatial resolution, paving the way to unprecedented results when it comes to understanding the behaviour of neuronal networks and interacting with them. However, in some experimental cases, in-place low-latency processing of the sensor data acquired by the arrays is required. This poses the need for high-performance embedded computing platforms capable of processing in real-time the stream of samples produced by the acquisition front-end to extract higher-level information. Previous work has demonstrated that Field-Programmable Gate Array and All-Programmable System-On-Chip devices are suitable target technology for the implementation of real-time processors of High-Density Multi-Electrode Arrays data. However, approaches available in literature can process a limited number of channels or are designed to execute only the first steps of the neural signal processing chain. In this work, we propose an All-Programmable System-On-Chip based implementation capable of sorting neural spikes acquired by the sensors, to associate the shape of each spike to a specific firing neuron. Our system, implemented on a Xilinx Z7020 All-Programmable System-On-Chip is capable of executing on-line spike sorting up to 5500 acquisition channels, 43x more than state-of-the-art alternatives, supporting 18KHz acquisition frequency. We present an experimental study on a commonly used reference dataset, using on-line refinement of the sorting clusters to improve accuracy up to 82%, with only 4% degradation with respect to off-line analysis

A Bandwidth-Efficient Emulator of Biologically-Relevant Spiking Neural Networks on FPGA

Closed-loop experiments involving biological and artificial neural networks would improve the understanding of neural cells functioning principles and lead to the development of new generation neuroprosthesis. Several technological challenges require to be faced, as the development of real-time spiking neural network emulators which could bear the increasing amount of data provided by new generation High-Density Multielectrode Arrays. This work focuses on the development of a real-time spiking neural network emulator addressing fully-connected neural networks. This work presents a new way to increase the number of synapses supported by real-time neural network accelerators. The proposed solution has been implemented on the Xilinx Zynq 7020 All-Programmable SoC and can emulate fully connected spiking neural networks counting up to 3,098 Izhikevich neurons and 9.6e6 synapses in real-time, with a resolution of 0.1 ms

Poly-arginine peptide R18D reduces neuroinflammation and functional deficits following traumatic brain injury in the Long-Evans rat

We have previously demonstrated that the poly-arginine peptide R18 can improve histological and functional outcomes following traumatic brain injury (TBI) in the Sprague–Dawley rat. Since D-enantiomer peptides are often exploited in pharmacology for their increased stability and potency, the present study compared the effects of R18 and its D-enantiomer, R18D, following TBI in the Long-Evans rat. Following a closed-head impact delivered via a weight-drop apparatus, peptide was administered at a dose of 1000 nmol/kg at 30 min after TBI. Treatment with R18D, but not R18 resulted in significant reductions in sensorimotor (p = 0.026) and vestibulomotor (p = 0.049) deficits as measured by the adhesive tape removal and rotarod tests. Furthermore, treatment with R18 and R18D resulted in a significant reduction in brain protein levels of the astrocytic marker, glial fibrillary acidic protein (p = 0.019 and 0.048, respectively). These results further highlight the beneficial effects of poly-arginine peptides in TBI, however additional studies are required to confirm these positive effects

Bandwidth and accuracy-aware state estimation for smart grids using software defined networks

Smart grid (SG) will be one of the major application domains that will present severe pressures on future communication networks due to the expected huge number of devices that will be connected to it and that will impose stringent quality transmission requirements. To address this challenge, there is a need for a joint management of both monitoring and communication systems, so as to achieve a flexible and adaptive management of the SG services. This is the issue addressed in this paper, which provides the following major contributions. We define a new strategy to optimize the accuracy of the state estimation (SE) of the electric grid based on available network bandwidth resources and the sensing intelligent electronic devices (IEDs) installed in the field. In particular, we focus on phasor measurement units (PMUs) as measurement devices. We propose the use of the software defined networks (SDN) technologies to manage the available network bandwidth, which is then assigned by the controller to the forwarding devices to allow for the flowing of the data streams generated by the PMUs, by considering an optimization routine to maximize the accuracy of the resulting SE. Additionally, the use of SDN allows for adding and removing PMUs from the monitoring architecture without any manual intervention. We also provide the details of our implementation of the SDN solution, which is used to make simulations with an IEEE 14-bus test network in order to show performance in terms of bandwidth management and estimation accuracy

Twenty years of geomagnetic field observations at Mario Zucchelli Station (Antarctica)

During the 1986-87 austral summer a geomagnetic observatory was installed at Terra Nova Bay. During the first years both geomagnetic field time variation monitoring and absolute measurements were carried out only during summer. Since 1991 variometer measurements are automatically performed during the whole year, while absolute measurements are still performed only during summer. In spite of this, interesting observations were obtained during the life (quite long for Antarctica) of the geomagnetic observatory. In particular in this paper some of the most relevant results are briefly presented: studies about secular variation, daily variation (and its dependence from solar cycle and seasons) and geomagnetic higher frequency variations, such as geomagnetic pulsations

Twenty years of geomagnetic field observations at Mario Zucchelli Station (Antarctica)

During the 1986-87 austral summer a geomagnetic observatory was installed at Terra Nova Bay. During the first years both geomagnetic field time variation monitoring and absolute measurements were carried out only during summer. Since 1991 variometer measurements are automatically performed throughout the year, while absolute measurements are still performed only during summer. In spite of this, interesting observations were obtained during the life (quite long for Antarctica) of the geomagnetic observatory. In particular, this paper briefly presents some of the most important results: studies on secular variation, daily variation (and its dependence from solar cycle and seasons) and geomagnetic higher frequency variations, such as geomagnetic pulsations

Structure and Thermodynamic Stability of the OsC and OsC2 Molecules by Theoretical Calculations and by Knudsen Cell Mass Spectrometry

Knudsen cell mass spectrometric equilibrium measurements together with theoretical computations have been employed to gain structural and thermodynamic information of the OsC and OsC[sub 2] molecules. Several levels of theory have been applied to determine the structures, molecular parameters, and physico-chemical properties of OsC(g) and OsC[sub 2](g), and their singly charged ions. Complete active space self-consistent field (CASSCF) calculations were performed on the apparent [sup 3]Σ[sup -] ground state and first [sup 3]Δ excited state of OsC. From the analyzed gaseous equilibria and the thermal functions calculated from the computed molecular parameters, the following atomization enthalpies, Δ[sub a]H[sub 0][sup o](OsC,g) and Δ[sub a]H[sub 0][sup o](OsC[sub 2],g), and enthalpies of formation, Δ[sub f]H[sub 298.15][sup o](OsC,g) and Δ[sub f]H[sub 298.15][sup o](OsC[sub 2],g), in kJ mol-1, have been obtained: OsC, 605.6±14.0 and 895.4±14.0; OsC[sub 2], 1154.6±18.0 and 1059.5±18.0. The results have been compared with those for the other platinum metal carbides and oxides

Use of plastic-based analytical device, smartphone and chemometric tools to discriminate amines

Amine-based volatile compounds released bymicroorganisms offer an alternative diagnostic approach for the identification of foodborne pathogens. Our objective has been to solvent cast cellulose acetate membranes to immobilise dyes and to use the resultant membranes as a plastic device to discriminate between different types of amines (triethylamine, isobutylamine, isopentylamine). The plastic device consisted of an array of membranes with five pH indicators (namely alizarin, bromophenol blue, chlorophenol red, methyl red and thymol blue). To analyse the data using a portable instrument, we used an iPhone (R) to obtain images and to extract red, green and blue colours (RGB) using in-house software before and after contact with each individual amine. All the RGB values extracted for each analyte allowed us to generate a unique colour pattern, which was used as input for non-supervised pattern recognition methods. Based on this analysis, it was possible to clearly discriminate between the amines studied without any misclassification, demonstrating that the device is well-suited for large-scale applications such as non-destructive methods to discriminate amines and, in future, for smart packaging applications in order to give early warning of rotting food that may lead to food poisoning. Additionally, a semi-quantitative analysis was performed and we have demonstrated that it is possible to quantify concentrations of amines down to 1 ppm