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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Shafik, Andrew M.; Zhang, Feiran; Guo, Zhenxing; Dai, Qing; +9 Authors

    AbstractBackgroundN6-methyladenosine (m6A) modification is known to impact many aspects of RNA metabolism, including mRNA stability and translation, and is highly prevalent in the brain.ResultsWe show that m6A modification displays temporal and spatial dynamics during neurodevelopment and aging. Genes that are temporally differentially methylated are more prone to have mRNA expression changes and affect many pathways associated with nervous system development. Furthermore, m6A shows a distinct tissue-specific methylation profile, which is most pronounced in the hypothalamus. Tissue-specific methylation is associated with an increase in mRNA expression and is associated with tissue-specific developmental processes. During the aging process, we observe significantly more m6A sites as age increases, in both mouse and human. We show a high level of overlap between mouse and human; however, humans at both young and old ages consistently show more m6A sites compared to mice. Differential m6A sites are found to be enriched in alternative untranslated regions of genes that affect aging-related pathways. These m6A sites are associated with a strong negative effect on mRNA expression. We also show that many Alzheimer-related transcripts exhibit decreased m6A methylation in a mouse model of Alzheimer’s disease, which is correlated with reduced protein levels.ConclusionsOur results suggest that m6A exerts a critical function in both early and late brain development in a spatio-temporal fashion. Furthermore, m6A controls protein levels of key genes involved in Alzheimer’s disease-associated pathways, suggesting that m6A plays an important role in aging and neurodegenerative disease.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Europe PubMed Central
    Article . 2021
    Data sources: PubMed Central
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    DOAJ-Articles
    Article . 2021
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    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Genome Biology
    Article . 2021 . Peer-reviewed
    License: CC BY
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    Genome Biology
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      Europe PubMed Central
      Article . 2021
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      DOAJ-Articles
      Article . 2021
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      Genome Biology
      Article . 2021 . Peer-reviewed
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      Genome Biology
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Lingling Zhang; Kuan Hu; Tuo Shao; Lu Hou; +10 Authors

    The 18 kDa translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor, is predominately localized to the outer mitochondrial membrane in steroidogenic cells. Brain TSPO expression is relatively low under physiological conditions, but is upregulated in response to glial cell activation. As the primary index of neuroinflammation, TSPO is implicated in the pathogenesis and progression of numerous neuropsychiatric disorders and neurodegenerative diseases, including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), multiple sclerosis (MS), major depressive disorder (MDD) and obsessive compulsive disorder (OCD). In this context, numerous TSPO-targeted positron emission tomography (PET) tracers have been developed. Among them, several radioligands have advanced to clinical research studies. In this review, we will overview the recent development of TSPO PET tracers, focusing on the radioligand design, radioisotope labeling, pharmacokinetics, and PET imaging evaluation. Additionally, we will consider current limitations, as well as translational potential for future application of TSPO radiopharmaceuticals. This review aims to not only present the challenges in current TSPO PET imaging, but to also provide a new perspective on TSPO targeted PET tracer discovery efforts. Addressing these challenges will facilitate the translation of TSPO in clinical studies of neuroinflammation associated with central nervous system diseases. Graphical abstract The 18 kDa translocator protein (TSPO) expression in the central nervous system is upregulated in response to glial cell activation. There is a great potential for the future application of TSPO radioligands as diagnostic and prognostic tools, as well as for assessing therapeutic interventions for neurologic diseases.Image 1

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    Europe PubMed Central
    Article . 2020 . Peer-reviewed
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    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Acta Pharmaceutica Sinica B
    Article . 2021 . Peer-reviewed
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
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      Europe PubMed Central
      Article . 2020 . Peer-reviewed
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      Acta Pharmaceutica Sinica B
      Article . 2021 . Peer-reviewed
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Liting Chen; Xiaole Fan; Haijun Li; Chenglong Ye; +5 Authors

    Impaired spontaneous regional activity and altered topology of the brain network have been observed in obstructive sleep apnea (OSA). However, the mechanisms of disrupted functional connectivity (FC) and topological reorganization of the default mode network (DMN) in patients with OSA remain largely unknown. We explored whether the FC is altered within the DMN and examined topological changes occur in the DMN in patients with OSA using a graph theory analysis of resting-state functional magnetic resonance imaging data and evaluated the relationship between neuroimaging measures and clinical variables. Resting-state data were obtained from 46 male patients with untreated severe OSA and 46 male good sleepers (GSs). We specifically selected 20 DMN subregions to construct the DMN architecture. The disrupted FC and topological properties of the DMN in patients with OSA were characterized using graph theory. The OSA group showed significantly decreased FC of the anterior–posterior DMN and within the posterior DMN, and also showed increased FC within the DMN. The DMN exhibited small-world topology in both OSA and GS groups. Compared to GSs, patients with OSA showed a decreased clustering coefficient (Cp) and local efficiency, and decreased nodal centralities in the left posterior cingulate cortex and dorsal medial prefrontal cortex, and increased nodal centralities in the ventral medial prefrontal cortex and the right parahippocampal cortex. Finally, the abnormal DMN FC was significantly related to Cp, path length, global efficiency, and Montreal cognitive assessment score. OSA showed disrupted FC within the DMN, which may have contributed to the observed topological reorganization. These findings may provide further evidence of cognitive deficits in patients with OSA.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
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    Europe PubMed Central
    Article . 2018
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    Frontiers in Neurology
    Article . 2018
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    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Frontiers in Neurology
    Article . 2018 . Peer-reviewed
    License: CC BY
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
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      Europe PubMed Central
      Article . 2018
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      Frontiers in Neurology
      Article . 2018
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      Frontiers in Neurology
      Article . 2018 . Peer-reviewed
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Yuanyuan Yin; Shushu He; Jingchen Xu; Wanfang You; +8 Authors

    AbstractChronic pain surrounding the temporomandibular joints and masticatory muscles is often the primary chief complaint of patients with temporomandibular disorders (TMD) seeking treatment. Yet, the neuro-pathophysiological basis underlying it remains to be clarified. Neuroimaging techniques have provided a deeper understanding of what happens to brain structure and function in TMD patients with chronic pain. Therefore, we performed a systematic review of magnetic resonance imaging (MRI) studies investigating structural and functional brain alterations in TMD patients to further unravel the neurobiological underpinnings of TMD-related pain. Online databases (PubMed, EMBASE, and Web of Science) were searched up to August 3, 2019, as complemented by a hand search in reference lists. A total of 622 papers were initially identified after duplicates removed and 25 studies met inclusion criteria for this review. Notably, the variations of MRI techniques used and study design among included studies preclude a meta-analysis and we discussed the findings qualitatively according to the specific neural system or network the brain regions were involved in. Brain changes were found in pathways responsible for abnormal pain perception, including the classic trigemino-thalamo-cortical system and the lateral and medial pain systems. Dysfunction and maladaptive changes were also identified in the default mode network, the top-down antinociceptive periaqueductal gray-raphe magnus pathway, as well as the motor system. TMD patients displayed altered brain activations in response to both innocuous and painful stimuli compared with healthy controls. Additionally, evidence indicates that splint therapy can alleviate TMD-related symptoms by inducing functional brain changes. In summary, MRI research provides important novel insights into the altered neural manifestations underlying chronic pain in TMD.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
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    Europe PubMed Central
    Article . 2020
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    The Journal of Headache and Pain
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    The Journal of Headache and Pain
    Article . 2020 . Peer-reviewed
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
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      Europe PubMed Central
      Article . 2020
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      The Journal of Headache and Pain
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      The Journal of Headache and Pain
      Article . 2020 . Peer-reviewed
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Jing Xiang; Qian Luo; Rupesh Kotecha; Abraham M. Korman; +5 Authors

    Recent studies have revealed the importance of high-frequency brain signals (>70 Hz). One challenge of high-frequency signal analysis is that the size of time-frequency representation of high-frequency brain signals could be larger than 1 terabytes (TB), which is beyond the upper limits of a typical computer workstation’s memory (<196 GB). The aim of the present study is to develop a new method to provide greater sensitivity in detecting high-frequency magnetoencephalography (MEG) signals in a single automated and versatile interface, rather than the more traditional, time-intensive visual inspection methods, which may take up to several days. To address the aim, we developed a new method, accumulated source imaging, defined as the volumetric summation of source activity over a period of time. This method analyzes signals in both low- (1~70 Hz) and high-frequency (70~200 Hz) ranges at source levels. To extract meaningful information from MEG signals at sensor space, the signals were decomposed to channel-cross-channel matrix (CxC) representing the spatiotemporal patterns of every possible sensor-pair. A new algorithm was developed and tested by calculating the optimal CxC and source location-orientation weights for volumetric source imaging, thereby minimizing multi-source interference and reducing computational cost. The new method was implemented in C/C++ and tested with MEG data recorded from clinical epilepsy patients. The results of experimental data demonstrated that accumulated source imaging could effectively summarize and visualize MEG recordings within 12.7 hours by using approximately 10 GB of computer memory. In contrast to the conventional method of visually identifying multi-frequency epileptic activities that traditionally took 2-3 days and used 1-2 TB storage, the new approach can quantify epileptic abnormalities in both low- and high-frequency ranges at source levels, using much less time and computer memory.

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    Europe PubMed Central
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    Frontiers in Neuroinformatics
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    Frontiers in Neuroinformatics
    Article . 2014 . Peer-reviewed
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      Frontiers in Neuroinformatics
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      Frontiers in Neuroinformatics
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    Authors: Shen, Yujun; Sun, Aimin; Wang, Yunhong; Cha, Daqin; +5 Authors

    Abstract Background Mesencephalic astrocyte-derived neurotrophic factor (MANF), a 20 kDa secreted protein, was originally derived from a rat mesencephalic type-1 astrocyte cell line. MANF belongs to a novel evolutionally conserved family of neurotrophic factors along with conserved dopamine neurotrophic factor. In recent years, ever-increasing evidence has shown that both of them play a remarkable protective role against various injuries to neurons in vivo or in vitro. However, the characteristics of MANF expression in the different types of glial cells, especially in astrocytes, remain unclear. Methods The model of focal cerebral ischemia was induced by rat middle cerebral artery occlusion. Double-labeled immunofluorescent staining was used to identify the types of neural cells expressing MANF. Primarily cultured glial cells were used to detect the response of glial cells to endoplasmic reticulum stress stimulation. Propidium iodide staining was used to determine dead cells. Reverse transcription PCR and western blotting were used to detect the levels of mRNA and proteins. Results We found that MANF was predominantly expressed in neurons in both normal and ischemic cortex. Despite its name, MANF was poorly expressed in glial cells, including astrocytes, in normal brain tissue. However, the expression of MANF was upregulated in the glial cells under focal cerebral ischemia, including the astrocytes. This expression was also induced by several endoplasmic reticulum stress inducers and nutrient deprivation in cultured primary glial cells. The most interesting phenomenon observed in this study was the pattern of MANF expression in the microglia. The expression of MANF was closely associated with the morphology and state of microglia, accompanied by the upregulation of BIP/Grp78. Conclusions These results indicate that MANF expression was upregulated in the activated glial cells, which may contribute to the mechanism of ischemia-induced neural injury.

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    Journal of Neuroinflammation
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      Journal of Neuroinflammation
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    Authors: Yijing Zhang; Jinfei Ma; Chi Zhang; Ruosong Chang;

    Abstract With the continuous improvement of automated vehicles, researchers have found that automated driving is more likely to cause insufficient mental workload for the driver, which induces passive fatigue and endangers traffic safety. To explore the impact of automation and scenario complexity on the passive fatigue of the driver, we developed a three-factor, 2 (automated driving, manual driving) × 2 (monotonic condition, engaging condition) × 6 (measurement stage: 1–6) mixed experiment. We collected electroencephalography (EEG), detection-response task (DRT) performance, and the subjective report scores of 48 drivers. We found that in automated driving under monotonic conditions, the topographic map’s activation range of the drivers brain was the smallest in the six stages, and the mental workload of this group continued to maintain the lowest state at each stage; however, the subjectively reported fatigue level was significantly increased; thus, the driver experienced passive fatigue. After simulating a low-load scenario for 40 min, the power of the alpha of the driver’s EEG indicators increased significantly, the accuracy of the detection reaction task decreased, and the reaction time became slower. The EEG sample’s entropy value of the driver’s passive fatigue was 0.243, and the judgement accuracy rate was 0.71. We proved that in automated driving under monotonic conditions, the driver is more prone to passive fatigue owing to insufficient mental workload.

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    https://doi.org/10.21203/rs.3....
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      https://doi.org/10.21203/rs.3....
      Preprint . 2021
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    Authors: Tao Xu; Yun Zhou; Zekai Hou; Wenlan Zhang;

    The brain is a complex and dynamic system, consisting of interacting sets and the temporal evolution of these sets. Electroencephalogram (EEG) recordings of brain activity play a vital role to decode the cognitive process of human beings in learning research and application areas. In the real world, people react to stimuli differently, and the duration of brain activities varies between individuals. Therefore, the length of EEG recordings in trials gathered in the experiment is variable. However, current approaches either fix the length of EEG recordings in each trial which would lose information hidden in the data or use the sliding window which would consume large computation on overlapped parts of slices. In this paper, we propose TOO (Traverse Only Once), a new approach for processing variable-length EEG trial data. TOO is a convolutional quorum voting approach that breaks the fixed structure of the model through convolutional implementation of sliding windows and the replacement of the fully connected layer by the 1 × 1 convolutional layer. Each output cell generated from 1 × 1 convolutional layer corresponds to each slice created by a sliding time window, which reflects changes in cognitive states. Then, TOO employs quorum voting on output cells and determines the cognitive state representing the entire single trial. Our approach provides an adaptive model for trials of different lengths with traversing EEG data of each trial only once to recognize cognitive states. We design and implement a cognitive experiment and obtain EEG data. Using the data collecting from this experiment, we conducted an evaluation to compare TOO with a state-of-art sliding window end-to-end approach. The results show that TOO yields a good accuracy (83.58%) at the trial level with a much lower computation (11.16%). It also has the potential to be used in variable signal processing in other application areas.

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    Complexity
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    Complexity
    Article . 2020 . Peer-reviewed
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    Authors: A. Gaskell; Darren Hight; Joel D Winders; Gabriel Tran; +5 Authors

    Abstract Background The isolated forearm test (IFT) is the gold standard test of connected consciousness (awareness of the environment) during anaesthesia. The frontal alpha-delta EEG pattern (seen in slow wave sleep) is widely held to indicate anaesthetic-induced unconsciousness. A priori we proposed that one responder with the frontal alpha-delta EEG pattern would falsify this concept. Methods Frontal EEG was recorded in a subset of patients from three centres participating in an international multicentre study of IFT responsiveness following tracheal intubation. Raw EEG waveforms were analysed for power–frequency spectra, depth-of-anaesthesia indices, permutation entropy, slow wave activity saturation and alpha-delta amplitude-phase coupling. Results Volitional responses to verbal command occurred in six out of 90 patients. Three responses occurred immediately following intubation in patients (from Sites 1 and 2) exhibiting an alpha-delta dominant (delta power >20 dB, alpha power >10 dB) EEG pattern. The power–frequency spectra obtained during these responses were similar to those of non-responders (P>0.05) at those sites. A further three responses occurred in (Site 3) patients not exhibiting the classic alpha-delta EEG pattern; these responses occurred later relative to intubation, and in patients had been co-administered ketamine and less volatile anaesthetic compared with Site 1 and 2 patients. None of the derived depth-of-anaesthesia indices could robustly discrimate IFT responders and non-responders. Conclusions Connected consciousness can occur in the presence of the frontal alpha-delta EEG pattern during anaesthesia. Frontal EEG parameters do not readily discriminate volitional responsiveness (a marker of connected consciousness) and unresponsiveness during anaesthesia. Clinical trial registration NCT02248623

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    British Journal of Anaesthesia
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    British Journal of Anaesthesia
    Article . 2017 . Peer-reviewed
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      British Journal of Anaesthesia
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      British Journal of Anaesthesia
      Article . 2017 . Peer-reviewed
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Lucy K. Bicks; Lucy K. Bicks; Lucy K. Bicks; Lucy K. Bicks; +19 Authors

    Social dominance hierarchies are a common adaptation to group living and exist across a broad range of the animal kingdom. Social dominance is known to rely on the prefrontal cortex (PFC), a brain region that shows a protracted developmental trajectory in mice. However, it is unknown to what extent the social dominance hierarchy is plastic across postnatal development and how it is regulated. Here we identified a sensitive period for experience-dependent social dominance plasticity in adolescent male mice, which is regulated by mechanisms that affect cortical plasticity. We show that social dominance hierarchies in male mice are already formed at weaning and are highly stable into adulthood. However, one experience of forced losing significantly reduces social dominance during the adolescent period but not in adulthood, suggesting adolescence as a sensitive period for experience-dependent social dominance plasticity. Notably, robust adolescent plasticity can be prolonged into adulthood by genetic deletion of Lynx1, a molecular brake that normally limits cortical plasticity through modulation of cortical nicotinic signaling. This plasticity is associated with increased activation of established nodes of the social dominance network including dorsal medial PFC and medial dorsal thalamus evidenced by increased c-Fos. Pharmacologically mediated elevation of cortical plasticity by valproic acid rapidly destabilizes the hierarchy of adult wildtype animals. These findings provide insight into mechanisms through which increased behavioral plasticity may be achieved to improve therapeutic recovery from psychiatric disorders that are associated with social deficits.

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    Europe PubMed Central
    Article . 2021
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    Frontiers in Neural Circuits
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    Frontiers in Neural Circuits
    Article . 2021 . Peer-reviewed
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      Frontiers in Neural Circuits
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      Frontiers in Neural Circuits
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Shafik, Andrew M.; Zhang, Feiran; Guo, Zhenxing; Dai, Qing; +9 Authors

    AbstractBackgroundN6-methyladenosine (m6A) modification is known to impact many aspects of RNA metabolism, including mRNA stability and translation, and is highly prevalent in the brain.ResultsWe show that m6A modification displays temporal and spatial dynamics during neurodevelopment and aging. Genes that are temporally differentially methylated are more prone to have mRNA expression changes and affect many pathways associated with nervous system development. Furthermore, m6A shows a distinct tissue-specific methylation profile, which is most pronounced in the hypothalamus. Tissue-specific methylation is associated with an increase in mRNA expression and is associated with tissue-specific developmental processes. During the aging process, we observe significantly more m6A sites as age increases, in both mouse and human. We show a high level of overlap between mouse and human; however, humans at both young and old ages consistently show more m6A sites compared to mice. Differential m6A sites are found to be enriched in alternative untranslated regions of genes that affect aging-related pathways. These m6A sites are associated with a strong negative effect on mRNA expression. We also show that many Alzheimer-related transcripts exhibit decreased m6A methylation in a mouse model of Alzheimer’s disease, which is correlated with reduced protein levels.ConclusionsOur results suggest that m6A exerts a critical function in both early and late brain development in a spatio-temporal fashion. Furthermore, m6A controls protein levels of key genes involved in Alzheimer’s disease-associated pathways, suggesting that m6A plays an important role in aging and neurodegenerative disease.

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    Europe PubMed Central
    Article . 2021
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    Article . 2021
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    Genome Biology
    Article . 2021 . Peer-reviewed
    License: CC BY
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    Genome Biology
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      Genome Biology
      Article . 2021 . Peer-reviewed
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Lingling Zhang; Kuan Hu; Tuo Shao; Lu Hou; +10 Authors

    The 18 kDa translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor, is predominately localized to the outer mitochondrial membrane in steroidogenic cells. Brain TSPO expression is relatively low under physiological conditions, but is upregulated in response to glial cell activation. As the primary index of neuroinflammation, TSPO is implicated in the pathogenesis and progression of numerous neuropsychiatric disorders and neurodegenerative diseases, including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), multiple sclerosis (MS), major depressive disorder (MDD) and obsessive compulsive disorder (OCD). In this context, numerous TSPO-targeted positron emission tomography (PET) tracers have been developed. Among them, several radioligands have advanced to clinical research studies. In this review, we will overview the recent development of TSPO PET tracers, focusing on the radioligand design, radioisotope labeling, pharmacokinetics, and PET imaging evaluation. Additionally, we will consider current limitations, as well as translational potential for future application of TSPO radiopharmaceuticals. This review aims to not only present the challenges in current TSPO PET imaging, but to also provide a new perspective on TSPO targeted PET tracer discovery efforts. Addressing these challenges will facilitate the translation of TSPO in clinical studies of neuroinflammation associated with central nervous system diseases. Graphical abstract The 18 kDa translocator protein (TSPO) expression in the central nervous system is upregulated in response to glial cell activation. There is a great potential for the future application of TSPO radioligands as diagnostic and prognostic tools, as well as for assessing therapeutic interventions for neurologic diseases.Image 1

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    Europe PubMed Central
    Article . 2020 . Peer-reviewed
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    Acta Pharmaceutica Sinica B
    Article . 2021 . Peer-reviewed
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      Acta Pharmaceutica Sinica B
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