Corticomuscular coherence between motor cortex, somatosensory areas and forearm muscles in the monkey

Corticomuscular coherence has previously been reported between primary motor cortex (M1) and contralateral muscles. We examined whether such coherence could also be seen from somatosensory areas. Local field potentials (LFPs) were recorded from primary somatosensory cortex (S1; areas 3a and 2) and posterior parietal cortex (PPC; area 5) simultaneously with M1 LFP and forearm EMG activity in two monkeys during an index finger flexion task. Significant beta-band (∼20 Hz) corticomuscular coherence was found in all areas investigated. Directed coherence (Granger causality) analysis was used to investigate the direction of effects. Surprisingly, the strongest beta-band directed coherence was in the direction from S1/PPC to muscle; it was much weaker in the ascending direction. Examination of the phase of directed coherence provided estimates of the time delay from cortex to muscle. Delays were longer from M1 (∼62 ms for the first dorsal interosseous muscle) than from S1/PPC (∼36 ms). We then looked at coherence and directed coherence between M1 and S1 for clues to this discrepancy. Directed coherence showed large beta-band effects from S1/PPC to M1, with smaller directed coherence in the reverse direction. The directed coherence phase suggested a delay of ∼40 ms from M1 to S1. Corticomuscular coherence from S1/PPC could involve multiple pathways; the most important is probably common input from M1 to S1/PPC and muscles. If correct, this implies that somatosensory cortex receives oscillatory efference copy information from M1 about the motor command. This could allow sensory inflow to be interpreted in the light of its motor context

Dynamic Offloading Design in Time-Varying Mobile Edge Networks with Deep Reinforcement Learning Approach

Mobile edge computing (MEC) is regarded as a promising wireless access architecture to alleviate the intensive computation burden at resource limited mobile terminals (MTs). Allowing the MTs to offload partial tasks to MEC servers could significantly decrease task processing delay. In this study, to minimize the processing delay for a multi-user MEC system, we jointly optimize the local content splitting ratio, the transmission/computation power allocation, and the MEC server selection under a dynamic environment with time-varying task arrivals and wireless channels. The reinforcement learning (RL) technique is utilized to deal with the considered problem. Two deep RL strategies, that is, deep Q-learning network (DQN) and deep deterministic policy gradient (DDPG), are proposed to efficiently learn the offloading policies adaptively. The proposed DQN strategy takes the MEC selection as a unique action while using convex optimization approach to obtain the remaining variables. And the DDPG strategy takes all dynamic variables as actions. Numerical results demonstrates that both proposed strategies perform better than existing schemes. And the DDPG strategy is superior to the DQN strategy as it can learn all variables online although it requires relatively large complexity

ROS/TRPA1/CGRP signaling mediates cortical spreading depression

Abstract Objectives The transient receptor potential ankyrin A 1 (TRPA1) channel and calcitonin gene-related peptide (CGRP) are targets for migraine prophylaxis. This study aimed to understand their mechanisms in migraine by investigating the role of TRPA1 in cortical spreading depression (CSD) in vivo and exploring how reactive oxygen species (ROS)/TRPA1/CGRP interplay in regulating cortical susceptibility to CSD. Methods Immunohistochemistry was used for detecting TRPA1 expression. CSD was induced by K+ on the cerebral cortex, monitored using electrophysiology in rats, and intrinsic optical imaging in mouse brain slices, respectively. Drugs were perfused into contralateral ventricle of rats. Lipid peroxidation (malondialdehyde, MDA) analysis was used for indicating ROS level. Results TRPA1 was expressed in cortical neurons and astrocytes of rats and mice. TRPA1 deactivation by an anti-TRPA1 antibody reduced cortical susceptibility to CSD in rats and decreased ipsilateral MDA level induced by CSD. In mouse brain slices, H2O2 facilitated submaximal CSD induction, which disappeared by the antioxidant, tempol and the TRPA1 antagonist, A-967079; Consistently, TRPA1 activation reversed prolonged CSD latency and reduced magnitude by the antioxidant. Further, blockade of CGRP prolonged CSD latency, which was reversed by H2O2 and the TRPA1 agonist, allyl-isothiocyanate, respectively. Conclusions ROS/TRPA1/CGRP signaling plays a critical role in regulating cortical susceptibility to CSD. Inhibition ROS and deactivation of TRPA1 channels may have therapeutic benefits in preventing stress-triggered migraine via CGRP

Exploring Regulation Genes Involved in the Expression of L-Amino Acid Oxidase in Pseudoalteromonas sp. Rf-1

Bacterial L-amino acid oxidase (LAAO) is believed to play important biological and ecological roles in marine niches, thus attracting increasing attention to understand the regulation mechanisms underlying its production. In this study, we investigated genes involved in LAAO production in marine bacterium Pseudoalteromonas sp. Rf-1 using transposon mutagenesis. Of more than 4,000 mutants screened, 15 mutants showed significant changes in LAAO activity. Desired transposon insertion was confirmed in 12 mutants, in which disrupted genes and corresponding functionswere identified. Analysis of LAAO activity and lao gene expression revealed that GntR family transcriptional regulator, methylase, non-ribosomal peptide synthetase, TonB-dependent heme-receptor family, Na⁺/H⁺ antiporter and related arsenite permease, N-acetyltransferase GCN5, Ketol-acid reductoisomerase and SAM-dependent methytransferase, and their coding genes may be involved in either upregulation or downregulation pathway at transcriptional, posttranscriptional, translational and/or posttranslational level. The nhaD and sdmT genes were separately complemented into the corresponding mutants with abolished LAAO-activity. The complementation of either gene can restore LAAO activity and lao gene expression, demonstrating their regulatory role in LAAO biosynthesis. This study provides, for the first time, insights into the molecular mechanisms regulating LAAO production in Pseudoalteromonas sp. Rf-1, which is important to better understand biological and ecological roles of LAAO

Clinical outcomes of active specific immunotherapy in advanced colorectal cancer and suspected minimal residual colorectal cancer: a meta-analysis and system review

<p>Abstract</p> <p>Background</p> <p>To evaluate the objective clinical outcomes of active specific immunotherapy (ASI) in advanced colorectal cancer (advanced CRC) and suspected minimal residual colorectal cancer (suspected minimal residual CRC).</p> <p>Methods</p> <p>A search was conducted on Medline and Pub Med from January 1998 to January 2010 for original studies on ASI in colorectal cancer (CRC). All articles included in this study were assessed with the application of predetermined selection criteria and were divided into two groups: ASI in advanced CRC and ASI in suspected minimal residual CRC. For ASI in suspected minimal residual CRC, a meta-analysis was executed with results regarding the overall survival (OS) and disease-free survival (DFS). Regarding ASI in advanced colorectal cancer, a system review was performed with clinical outcomes.</p> <p>Results</p> <p>1375 colorectal carcinoma patients with minimal residual disease have been enrolled in Meta-analysis. A significantly improved OS and DFS was noted for suspected minimal residual CRC patients utilizing ASI (For OS: HR = 0.76, P = 0.007; For DFS: HR = 0.76, P = 0.03). For ASI in stage II suspected minimal residual CRC, OS approached significance when compared with control (HR = 0.71, P = 0.09); however, the difference in DFS of ASI for the stage II suspected minimal residual CRC reached statistical significance (HR = 0.66, P = 0.02). For ASI in stage III suspected minimal residual CRC compared with control, The difference in both OS and DFS achieved statistical significance (For OS: HR = 0.76, P = 0.02; For DFS: HR = 0.81, P = 0.03). 656 advanced colorectal patients have been evaluated on ASI in advanced CRC. Eleven for CRs and PRs was reported, corresponding to an overall response rate of 1.68%. No serious adverse events have been observed in 2031 patients.</p> <p>Conclusions</p> <p>It is unlikely that ASI will provide a standard complementary therapeutic approach for advanced CRC in the near future. However, the clinical responses to ASI in patients with suspected minimal residual CRC have been encouraging, and it has become clear that immunotherapy works best in situations of patients with suspected minimal residual CRC.</p

Src family kinases activity is required for transmitting purinergic P2X7 receptor signaling in cortical spreading depression and neuroinflammation

BACKGROUND: Purinergic P2X7 receptor plays an important role in migraine pathophysiology. Yet precise molecular mechanism underlying P2X7R signaling in migraine remains unclear. This study explores the hypothesis that P2X7 receptor transmits signaling to Src family kinases (SFKs) during cortical spreading depression (CSD) and neuroinflammation after CSD. METHODS: CSD was recorded using electrophysiology in rats and intrinsic optical imaging in mouse brain slices. Cortical IL-1β and TNFα mRNA levels were detected using qPCR. Glutamate release from mouse brain slices was detected using glutamate assay. RESULTS: The data showed that deactivation of SFKs by systemic injection of PP2 reduced cortical susceptibility to CSD in rats and CSD-induced IL-1β and TNF-α gene expression in rat ipsilateral cortices. Consistently, in mouse brain slices, inhibition of SFKs activity by saracatinib and P2X7 receptor by A740003 similarly reduced cortical susceptibility to CSD. When the interaction of P2X7 receptor and SFKs was disrupted by TAT-P2X7, a marked reduction of cortical susceptibility to CSD, IL-1β gene expression and glutamate release after CSD induction were observed in mouse brain slices. The reduced cortical susceptibility to CSD by TAT-P2X7 was restored by NMDA, and disrupting the Fyn-NMDA interaction using TAT-Fyn (39-57) but not disrupting Src-NMDA receptor interaction using TAT-Src (40-49) reduced cortical susceptibility to CSD. Furthermore, activation of P2X7 receptor by BzATP restored the TAT-Fyn (39-57)-reduced cortical susceptibility to CSD. CONCLUSION: This study reveals that SFKs activity transmits P2X7 receptor signaling to facilitate CSD propagation via glutamatergic pathway and promote neuroinflammation, which is of particular relevance to migraine

Phylogenetic studies of magnoliids: Advances and perspectives

Magnoliids are the largest flowering plant clades outside of the eudicots and monocots, which are distributed worldwide and have high economic, ornamental and ecological values. Eudicots, monocots and magnoliids are the three major clades of Mesangiospermae, and their phylogenetic relationship is one of the most interesting issues. In recent years, with the continuous accumulation of genomic information, the evolutionary status of magnoliids has become a hot spot in plant phylogenetic research. Although great efforts have been made to study the evolution of magnoliids using molecular data from several representative species such as nuclear genome, plastid genome, mitochondrial genome, and transcriptome, the results of current studies on the phylogenetic status of magnoliids are inconsistent. Here, we systematically describe the current understanding of the molecular research on magnoliid phylogeny and review the differences in the evolutionary state of magnoliids. Understanding the research approaches and limitations of magnoliid phylogeny can guide research strategies to further improve the study of the phylogenetic evolution of magnoliids