Additional file 1: of Inflammation and neuronal death in the motor cortex of the wobbler mouse, an ALS animal model

Comparison between Iba-1-labeled microglial cells in the motor cortex of WT mice and intense symptomatic WR mice 60 d.p.n. (A–C) Relation of activated microglial cells (red) and neurons labeled with neuronal nuclei antibody (green) in brain tissue of WT mice. (D–F) Relation of activated microglial cells (red) and neurons labeled with neuronal nuclei antibody (green) in the brain tissue of severely symptomatic WR mice. (Scale bar = 20 μm). (TIF 10223 kb

Additional file 2: of Inflammation and neuronal death in the motor cortex of the wobbler mouse, an ALS animal model

Visualization of the weak staining of Iba-1- and TNF-α-labeled microglial and caspase 3-positive neuronal cells in motor cortex tissue of WR mice 20 d.p.n. (A–C) Relation of activated microglial cells (red) and neurons labeled with neuronal nuclei antibody (green) in brain tissue of non-symptomatic WR mice. (D–F) Iba-1-labeled microglial cells (red) synthesizing the cytokine TNF-α (green). (G–H) Caspase 3-positive (red) neurons labeled with NeuN (neuronal nuclei antibody) (green). (Scale bar = 20 μm). (TIF 15107 kb

Image2_Innovative in vivo rat model for global cerebral hypoxia: a new approach to investigate therapeutic and preventive drugs.JPEG

Introduction: Severe acute global cerebral hypoxia can lead to significant disability in humans. Although different animal models have been described to study hypoxia, there is no endogenous model that considers hypoxia and its effect on the brain as an independent factor. Thus, we developed a minimally invasive rat model, which is based on the non-depolarizing muscle blocking agent rocuronium in anesthetized animals. This drug causes respiratory insufficiency by paralysis of the striated muscles.Methods: In this study, 14 rats underwent 12 min of hypoxemia with an oxygen saturation of approximately 60% measured by pulse oximetry; thereafter, animals obtained sugammadex to antagonize rocuronium immediately.Results: Compared to controls (14 rats, anesthesia only), hypoxic animals demonstrated significant morphological alterations in the hippocampus (cell decrease in the CA 1 region) and the cerebellum (Purkinje cell decrease), as well as significant changes in hypoxia markers in blood (Hif2α, Il1β, Tgf1β, Tnfα, S100b, cspg2, neuron-specific enolase), hippocampus (Il1β, Tnfα, S100b, cspg2, NSE), and cerebellum (Hif1α, Tnfα, S100b, cspg2, NSE). Effects were more pronounced in females than in males.Discussion: Consequently, this model is suitable to induce hypoxemia with consecutive global cerebral hypoxia. As significant morphological and biochemical changes were proven, it can be used to investigate therapeutic and preventive drugs for global cerebral hypoxia.</p

Image1_Innovative in vivo rat model for global cerebral hypoxia: a new approach to investigate therapeutic and preventive drugs.JPEG

Introduction: Severe acute global cerebral hypoxia can lead to significant disability in humans. Although different animal models have been described to study hypoxia, there is no endogenous model that considers hypoxia and its effect on the brain as an independent factor. Thus, we developed a minimally invasive rat model, which is based on the non-depolarizing muscle blocking agent rocuronium in anesthetized animals. This drug causes respiratory insufficiency by paralysis of the striated muscles.Methods: In this study, 14 rats underwent 12 min of hypoxemia with an oxygen saturation of approximately 60% measured by pulse oximetry; thereafter, animals obtained sugammadex to antagonize rocuronium immediately.Results: Compared to controls (14 rats, anesthesia only), hypoxic animals demonstrated significant morphological alterations in the hippocampus (cell decrease in the CA 1 region) and the cerebellum (Purkinje cell decrease), as well as significant changes in hypoxia markers in blood (Hif2α, Il1β, Tgf1β, Tnfα, S100b, cspg2, neuron-specific enolase), hippocampus (Il1β, Tnfα, S100b, cspg2, NSE), and cerebellum (Hif1α, Tnfα, S100b, cspg2, NSE). Effects were more pronounced in females than in males.Discussion: Consequently, this model is suitable to induce hypoxemia with consecutive global cerebral hypoxia. As significant morphological and biochemical changes were proven, it can be used to investigate therapeutic and preventive drugs for global cerebral hypoxia.</p

Image3_Innovative in vivo rat model for global cerebral hypoxia: a new approach to investigate therapeutic and preventive drugs.JPEG

Introduction: Severe acute global cerebral hypoxia can lead to significant disability in humans. Although different animal models have been described to study hypoxia, there is no endogenous model that considers hypoxia and its effect on the brain as an independent factor. Thus, we developed a minimally invasive rat model, which is based on the non-depolarizing muscle blocking agent rocuronium in anesthetized animals. This drug causes respiratory insufficiency by paralysis of the striated muscles.Methods: In this study, 14 rats underwent 12 min of hypoxemia with an oxygen saturation of approximately 60% measured by pulse oximetry; thereafter, animals obtained sugammadex to antagonize rocuronium immediately.Results: Compared to controls (14 rats, anesthesia only), hypoxic animals demonstrated significant morphological alterations in the hippocampus (cell decrease in the CA 1 region) and the cerebellum (Purkinje cell decrease), as well as significant changes in hypoxia markers in blood (Hif2α, Il1β, Tgf1β, Tnfα, S100b, cspg2, neuron-specific enolase), hippocampus (Il1β, Tnfα, S100b, cspg2, NSE), and cerebellum (Hif1α, Tnfα, S100b, cspg2, NSE). Effects were more pronounced in females than in males.Discussion: Consequently, this model is suitable to induce hypoxemia with consecutive global cerebral hypoxia. As significant morphological and biochemical changes were proven, it can be used to investigate therapeutic and preventive drugs for global cerebral hypoxia.</p

Cyber-physical system design with sensor networking technologies

This book describes how wireless sensor networking technologies can help in establishing and maintaining seamless communications between the physical and cyber systems to enable efficient, secure, reliable acquisition, management, and routing of data

Overlapping coalition formation games in wireless communication networks

This brief introduces overlapping coalition formation games (OCF games), a novel mathematical framework from cooperative game theory that can be used to model, design and analyze cooperative scenarios in future wireless communication networks. The concepts of OCF games are explained, and several algorithmic aspects are studied. In addition, several major application scenarios are discussed. These applications are drawn from a variety of fields that include radio resource allocation in dense wireless networks, cooperative spectrum sensing for cognitive radio networks, and resource management for crowd sourcing. For each application, the use of OCF games is discussed in detail in order to show how this framework can be used to solve relevant wireless networking problems. Overlapping Coalition Formation Games in Wireless Communication Networks provides researchers, students and practitioners with a concise overview of existing works in this emerging area, exploring the relevant fundamental theories, key techniques, and significant applications.

GluA1 function is increased by SGK3 and PIKfyve.

<p>(<b>A</b>) Representative current traces measured in <i>Xenopus</i> oocytes in response to superfusion with 300 µM glutamate plus 100 µM cyclo-thiacide. All currents were measured at −70 mV. Vertical scale-bar, 0,5 µA; horizontal bar, 4 s. (<b>B</b>) GluA1 current amplitudes in oocytes expressing GluA1, or combinations of GluA1 with SGK3, the inactive form of PIKfyve (PIKfyve(S318A)), or wild type PIKfyve. Numbers of oocytes are n = 20–30. Significant changes (p<0.001) are indicated by *** (p = 0.00049; 0.00036; 0.000073, respectively). (<b>C</b>) Representative samples including controls from uninjected oocytes were biotinylated to isolate plasma membrane GluA1, then separated on an SDS gel, Western-blotted and probed with a primary rabbit anti-GluA1 antibody. The GluA1 protein has an apparent molecular weight of ∼105 kDa. (<b>D</b>) Bar graph showing relative abundance of GluA1 plasma membrane protein. The band intensity was quantified by densitometric analysis using the software Scion image.</p

PIKfyve expression, phosphorylation, and function.

<p>(<b>A</b>) PIKfyve is phosphorylated at Ser318 by SGK3 and at Ser318 by PKB. Purified recombinant GST-tagged wild-type (WT) or S318A mutant (SA) of PIKfyve was subjected to Western blotting. Blots were incubated with rabbit anti-GST antibody (PIKfyve; lower panel), followed by stripping and reprobing with a rabbit anti-PIKfyve antibody specific for phosphoserine 318 (apS318; top panel). (<b>B</b>) RT-PCR demonstrating that PIKfyve is expressed in hippocampus. Lane 1: cDNA from hippocampus, the two primers bind in exons 19 and 20, respectively, and amplify a 315 bp fragment of PIKfyve; lane 2: control reaction to exclude genomic contamination; lane 3: control reaction without reverse transcriptase; lane 4: control reaction without cDNA. (<b>C</b>) The PIKfyve inhibitor YM201636 and SGK inhibitor EMD638683 suppress the upregulating effect of SGK3 on GluA1 currents. GluA1 current amplitudes in oocytes expressing GluA1. Acute injection of purified active SGK3 protein led to an increase in GluA1 currents. The effects of YM201636 and EMD638683 on GluA1 currents were measured in oocytes before and after acute injection of SGK3 protein. Significant change to GluA1 control (p = 0.013) is indicated by *. Numbers of oocytes were n = 7–36.</p

List of oligonucleotides used for mRNA expression analyses in retinas of control animals, ischemic animals, and animals treated with ranibizumab after ischemia by quantitative real-time PCR.

<p>The housekeeping gene <i>β-actin</i> served as the gene for normalization and relative quantification. The gene accession number, predicted amplicon size as well as the primer efficiency is indicated for each oligonucleotide pair. Abbreviations: bp = base pairs, F = forward, R = reverse.</p