Oligodendrocyte precursor cells (OPCs) are a heterogeneous multipotent population in the central nervous system (CNS) that appear during embryogenesis and persist as resident cells in the adult brain parenchyma. OPCs could generate oligodendrocytes to participate in myelination. Recent advances have renewed our knowledge of OPC biology by discovering novel markers of oligodendroglial cells, the myelin-independent roles of OPCs, and the regulatory mechanism of OPC development. In this review, we will explore the updated knowledge on OPC identity, their multifaceted roles in the CNS in health and diseases, as well as the regulatory mechanisms that are involved in their developmental stages, which hopefully would contribute to a further understanding of OPCs and attract attention in the field of OPC biology.
{"title":"A New Acquaintance of Oligodendrocyte Precursor Cells in the Central Nervous System.","authors":"Zexuan Ma, Wei Zhang, Chenmeng Wang, Yixun Su, Chenju Yi, Jianqin Niu","doi":"10.1007/s12264-024-01261-8","DOIUrl":"10.1007/s12264-024-01261-8","url":null,"abstract":"<p><p>Oligodendrocyte precursor cells (OPCs) are a heterogeneous multipotent population in the central nervous system (CNS) that appear during embryogenesis and persist as resident cells in the adult brain parenchyma. OPCs could generate oligodendrocytes to participate in myelination. Recent advances have renewed our knowledge of OPC biology by discovering novel markers of oligodendroglial cells, the myelin-independent roles of OPCs, and the regulatory mechanism of OPC development. In this review, we will explore the updated knowledge on OPC identity, their multifaceted roles in the CNS in health and diseases, as well as the regulatory mechanisms that are involved in their developmental stages, which hopefully would contribute to a further understanding of OPCs and attract attention in the field of OPC biology.</p>","PeriodicalId":19314,"journal":{"name":"Neuroscience bulletin","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11422404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1007/s12264-024-01250-x
Cheng Cheng, Guangjie Zhu, Kaijian Wang, Chuan Bu, Siyu Li, Yue Qiu, Jie Lu, Xinya Ji, Wenli Hao, Junguo Wang, Chengwen Zhu, Ye Yang, Yajun Gu, Xiaoyun Qian, Chenjie Yu, Xia Gao
{"title":"Correction to: Deletion of Luzp2 Does Not Cause Hearing Loss in Mice.","authors":"Cheng Cheng, Guangjie Zhu, Kaijian Wang, Chuan Bu, Siyu Li, Yue Qiu, Jie Lu, Xinya Ji, Wenli Hao, Junguo Wang, Chengwen Zhu, Ye Yang, Yajun Gu, Xiaoyun Qian, Chenjie Yu, Xia Gao","doi":"10.1007/s12264-024-01250-x","DOIUrl":"10.1007/s12264-024-01250-x","url":null,"abstract":"","PeriodicalId":19314,"journal":{"name":"Neuroscience bulletin","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11422339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141875519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01Epub Date: 2024-06-03DOI: 10.1007/s12264-024-01235-w
Run-Zhou Yang, Dian-Dian Wang, Sen-Miao Li, Pei-Pei Liu, Jian-Sheng Kang
Mitochondrial membrane potential (MMP) plays a crucial role in the function of cells and organelles, involving various cellular physiological processes, including energy production, formation of reactive oxygen species (ROS), unfolded protein stress, and cell survival. Currently, there is a lack of genetically encoded fluorescence indicators (GEVIs) for MMP. In our screening of various GEVIs for their potential monitoring MMP, the Accelerated Sensor of Action Potentials (ASAP) demonstrated optimal performance in targeting mitochondria and sensitivity to depolarization in multiple cell types. However, mitochondrial ASAPs also displayed sensitivity to ROS in cardiomyocytes. Therefore, two ASAP mutants resistant to ROS were generated. A double mutant ASAP3-ST exhibited the highest voltage sensitivity but weaker fluorescence. Overall, four GEVIs capable of targeting mitochondria were obtained and named mitochondrial potential indicators 1-4 (MPI-1-4). In vivo, fiber photometry experiments utilizing MPI-2 revealed a mitochondrial depolarization during isoflurane-induced narcosis in the M2 cortex.
{"title":"Development and Application of a Mitochondrial Genetically Encoded Voltage Indicator in Narcosis.","authors":"Run-Zhou Yang, Dian-Dian Wang, Sen-Miao Li, Pei-Pei Liu, Jian-Sheng Kang","doi":"10.1007/s12264-024-01235-w","DOIUrl":"10.1007/s12264-024-01235-w","url":null,"abstract":"<p><p>Mitochondrial membrane potential (MMP) plays a crucial role in the function of cells and organelles, involving various cellular physiological processes, including energy production, formation of reactive oxygen species (ROS), unfolded protein stress, and cell survival. Currently, there is a lack of genetically encoded fluorescence indicators (GEVIs) for MMP. In our screening of various GEVIs for their potential monitoring MMP, the Accelerated Sensor of Action Potentials (ASAP) demonstrated optimal performance in targeting mitochondria and sensitivity to depolarization in multiple cell types. However, mitochondrial ASAPs also displayed sensitivity to ROS in cardiomyocytes. Therefore, two ASAP mutants resistant to ROS were generated. A double mutant ASAP3-ST exhibited the highest voltage sensitivity but weaker fluorescence. Overall, four GEVIs capable of targeting mitochondria were obtained and named mitochondrial potential indicators 1-4 (MPI-1-4). In vivo, fiber photometry experiments utilizing MPI-2 revealed a mitochondrial depolarization during isoflurane-induced narcosis in the M2 cortex.</p>","PeriodicalId":19314,"journal":{"name":"Neuroscience bulletin","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11422539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141200387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bipolar disorder is a highly heritable and functionally impairing disease. The recognition and intervention of BD especially that characterized by early onset remains challenging. Risk biomarkers for predicting BD transition among at-risk youth may improve disease prognosis. We reviewed the more recent clinical studies to find possible pre-diagnostic biomarkers in youth at familial or (and) clinical risk of BD. Here we found that putative biomarkers for predicting conversion to BD include findings from multiple sample sources based on different hypotheses. Putative risk biomarkers shown by perspective studies are higher bipolar polygenetic risk scores, epigenetic alterations, elevated immune parameters, front-limbic system deficits, and brain circuit dysfunction associated with emotion and reward processing. Future studies need to enhance machine learning integration, make clinical detection methods more objective, and improve the quality of cohort studies.
{"title":"Putative Risk Biomarkers of Bipolar Disorder in At-risk Youth.","authors":"Xinyu Meng, Shengmin Zhang, Shuzhe Zhou, Yantao Ma, Xin Yu, Lili Guan","doi":"10.1007/s12264-024-01219-w","DOIUrl":"10.1007/s12264-024-01219-w","url":null,"abstract":"<p><p>Bipolar disorder is a highly heritable and functionally impairing disease. The recognition and intervention of BD especially that characterized by early onset remains challenging. Risk biomarkers for predicting BD transition among at-risk youth may improve disease prognosis. We reviewed the more recent clinical studies to find possible pre-diagnostic biomarkers in youth at familial or (and) clinical risk of BD. Here we found that putative biomarkers for predicting conversion to BD include findings from multiple sample sources based on different hypotheses. Putative risk biomarkers shown by perspective studies are higher bipolar polygenetic risk scores, epigenetic alterations, elevated immune parameters, front-limbic system deficits, and brain circuit dysfunction associated with emotion and reward processing. Future studies need to enhance machine learning integration, make clinical detection methods more objective, and improve the quality of cohort studies.</p>","PeriodicalId":19314,"journal":{"name":"Neuroscience bulletin","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11422403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140865324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stroke, a major cerebrovascular disease, has high morbidity and mortality. Effective methods to reduce the risk and improve the prognosis are lacking. Currently, uric acid (UA) is associated with the pathological mechanism, prognosis, and therapy of stroke. UA plays pro/anti-oxidative and pro-inflammatory roles in vivo. The specific role of UA in stroke, which may have both neuroprotective and damaging effects, remains unclear. There is a U-shaped association between serum uric acid (SUA) levels and ischemic stroke (IS). UA therapy provides neuroprotection during reperfusion therapy for acute ischemic stroke (AIS). Urate-lowering therapy (ULT) plays a protective role in IS with hyperuricemia or gout. SUA levels are associated with the cerebrovascular injury mechanism, risk, and outcomes of hemorrhagic stroke. In this review, we summarize the current research on the role of UA in stroke, providing potential targets for its prediction and treatment.
中风是一种主要的脑血管疾病,发病率和死亡率都很高。目前尚缺乏降低风险和改善预后的有效方法。目前,尿酸(UA)与中风的病理机制、预后和治疗有关。尿酸在体内发挥着促/抗氧化和促炎症的作用。尿酸在中风中的具体作用仍不清楚,它可能同时具有神经保护和损伤作用。血清尿酸(SUA)水平与缺血性中风(IS)之间呈 U 型关系。尿酸治疗可在急性缺血性卒中(AIS)再灌注治疗期间提供神经保护。降尿酸治疗(ULT)对高尿酸血症或痛风的 IS 起保护作用。SUA 水平与出血性卒中的脑血管损伤机制、风险和预后有关。在这篇综述中,我们总结了目前有关 UA 在中风中作用的研究,为其预测和治疗提供了潜在的靶点。
{"title":"A New Perspective on the Prediction and Treatment of Stroke: The Role of Uric Acid.","authors":"Bingrui Zhu, Xiaobin Huang, Jiahao Zhang, Xiaoyu Wang, Sixuan Tian, Tiantong Zhan, Yibo Liu, Haocheng Zhang, Sheng Chen, Cheng Yu","doi":"10.1007/s12264-024-01301-3","DOIUrl":"https://doi.org/10.1007/s12264-024-01301-3","url":null,"abstract":"<p><p>Stroke, a major cerebrovascular disease, has high morbidity and mortality. Effective methods to reduce the risk and improve the prognosis are lacking. Currently, uric acid (UA) is associated with the pathological mechanism, prognosis, and therapy of stroke. UA plays pro/anti-oxidative and pro-inflammatory roles in vivo. The specific role of UA in stroke, which may have both neuroprotective and damaging effects, remains unclear. There is a U-shaped association between serum uric acid (SUA) levels and ischemic stroke (IS). UA therapy provides neuroprotection during reperfusion therapy for acute ischemic stroke (AIS). Urate-lowering therapy (ULT) plays a protective role in IS with hyperuricemia or gout. SUA levels are associated with the cerebrovascular injury mechanism, risk, and outcomes of hemorrhagic stroke. In this review, we summarize the current research on the role of UA in stroke, providing potential targets for its prediction and treatment.</p>","PeriodicalId":19314,"journal":{"name":"Neuroscience bulletin","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
General anesthesia, pivotal for surgical procedures, requires precise depth monitoring to mitigate risks ranging from intraoperative awareness to postoperative cognitive impairments. Traditional assessment methods, relying on physiological indicators or behavioral responses, fall short of accurately capturing the nuanced states of unconsciousness. This study introduces a machine learning-based approach to decode anesthesia depth, leveraging EEG data across different anesthesia states induced by propofol and esketamine in rats. Our findings demonstrate the model’s robust predictive accuracy, underscored by a novel intra-subject dataset partitioning and a 5-fold cross-validation method. The research diverges from conventional monitoring by utilizing anesthetic infusion rates as objective indicators of anesthesia states, highlighting distinct EEG patterns and enhancing prediction accuracy. Moreover, the model’s ability to generalize across individuals suggests its potential for broad clinical application, distinguishing between anesthetic agents and their depths. Despite relying on rat EEG data, which poses questions about real-world applicability, our approach marks a significant advance in anesthesia monitoring.
{"title":"Accurate Machine Learning-based Monitoring of Anesthesia Depth with EEG Recording","authors":"Zhiyi Tu, Yuehan Zhang, Xueyang Lv, Yanyan Wang, Tingting Zhang, Juan Wang, Xinren Yu, Pei Chen, Suocheng Pang, Shengtian Li, Xiongjie Yu, Xuan Zhao","doi":"10.1007/s12264-024-01297-w","DOIUrl":"https://doi.org/10.1007/s12264-024-01297-w","url":null,"abstract":"<p>General anesthesia, pivotal for surgical procedures, requires precise depth monitoring to mitigate risks ranging from intraoperative awareness to postoperative cognitive impairments. Traditional assessment methods, relying on physiological indicators or behavioral responses, fall short of accurately capturing the nuanced states of unconsciousness. This study introduces a machine learning-based approach to decode anesthesia depth, leveraging EEG data across different anesthesia states induced by propofol and esketamine in rats. Our findings demonstrate the model’s robust predictive accuracy, underscored by a novel intra-subject dataset partitioning and a 5-fold cross-validation method. The research diverges from conventional monitoring by utilizing anesthetic infusion rates as objective indicators of anesthesia states, highlighting distinct EEG patterns and enhancing prediction accuracy. Moreover, the model’s ability to generalize across individuals suggests its potential for broad clinical application, distinguishing between anesthetic agents and their depths. Despite relying on rat EEG data, which poses questions about real-world applicability, our approach marks a significant advance in anesthesia monitoring.</p>","PeriodicalId":19314,"journal":{"name":"Neuroscience bulletin","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The looming stimulus-evoked flight response to approaching predators is a defensive behavior in most animals. However, how looming stimuli are detected in the retina and transmitted to the brain remains unclear. Here, we report that a group of GABAergic retinal ganglion cells (RGCs) projecting to the superior colliculus (SC) transmit looming signals from the retina to the brain, mediating the looming-evoked flight behavior by releasing GABA. GAD2-Cre and vGAT-Cre transgenic mice were used in combination with Cre-activated anterograde or retrograde tracer viruses to map the inputs to specific GABAergic RGC circuits. Optogenetic technology was used to assess the function of SC-projecting GABAergic RGCs (scpgRGCs) in the SC. FDIO-DTA (Flp-dependent Double-Floxed Inverted Open reading frame-Diphtheria toxin) combined with the FLP (Florfenicol, Lincomycin & Prednisolone) approach was used to ablate or silence scpgRGCs. In the mouse retina, GABAergic RGCs project to different brain areas, including the SC. ScpgRGCs are monosynaptically connected to parvalbumin-positive SC neurons known to be required for the looming-evoked flight response. Optogenetic activation of scpgRGCs triggers GABA-mediated inhibition in SC neurons. Ablation or silencing of scpgRGCs compromises looming-evoked flight responses without affecting image-forming functions. Our study reveals that scpgRGCs control the looming-evoked flight response by regulating SC neurons via GABA, providing novel insight into the regulation of innate defensive behaviors.
{"title":"GABAergic Retinal Ganglion Cells Projecting to the Superior Colliculus Mediate the Looming-Evoked Flight Response","authors":"Man Yuan, Gao Tan, Danrui Cai, Xue Luo, Kejiong Shen, Qinqin Deng, Xinlan Lei, Wen-Bo Zeng, Min-Hua Luo, Lu Huang, Chaoran Ren, Yin Shen","doi":"10.1007/s12264-024-01295-y","DOIUrl":"https://doi.org/10.1007/s12264-024-01295-y","url":null,"abstract":"<p>The looming stimulus-evoked flight response to approaching predators is a defensive behavior in most animals. However, how looming stimuli are detected in the retina and transmitted to the brain remains unclear. Here, we report that a group of GABAergic retinal ganglion cells (RGCs) projecting to the superior colliculus (SC) transmit looming signals from the retina to the brain, mediating the looming-evoked flight behavior by releasing GABA. <i>GAD2-Cre</i> and <i>vGAT-Cre</i> transgenic mice were used in combination with Cre-activated anterograde or retrograde tracer viruses to map the inputs to specific GABAergic RGC circuits. Optogenetic technology was used to assess the function of SC-projecting GABAergic RGCs (scpgRGCs) in the SC. FDIO-DTA (Flp-dependent Double-Floxed Inverted Open reading frame-Diphtheria toxin) combined with the FLP (Florfenicol, Lincomycin & Prednisolone) approach was used to ablate or silence scpgRGCs. In the mouse retina, GABAergic RGCs project to different brain areas, including the SC. ScpgRGCs are monosynaptically connected to parvalbumin-positive SC neurons known to be required for the looming-evoked flight response. Optogenetic activation of scpgRGCs triggers GABA-mediated inhibition in SC neurons. Ablation or silencing of scpgRGCs compromises looming-evoked flight responses without affecting image-forming functions. Our study reveals that scpgRGCs control the looming-evoked flight response by regulating SC neurons via GABA, providing novel insight into the regulation of innate defensive behaviors.</p>","PeriodicalId":19314,"journal":{"name":"Neuroscience bulletin","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-16DOI: 10.1007/s12264-024-01292-1
Hong Chen, Gang Yang, De-En Xu, Yu-tong Du, Chao Zhu, Hua Hu, Li Luo, Lei Feng, Wenhui Huang, Yan-Yun Sun, Quan-Hong Ma
Oligodendrocyte lineage cells, including oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLs), are essential in establishing and maintaining brain circuits. Autophagy is a conserved process that keeps the quality of organelles and proteostasis. The role of autophagy in oligodendrocyte lineage cells remains unclear. The present study shows that autophagy is required to maintain the number of OPCs/OLs and myelin integrity during brain aging. Inactivation of autophagy in oligodendrocyte lineage cells increases the number of OPCs/OLs in the developing brain while exaggerating the loss of OPCs/OLs with brain aging. Inactivation of autophagy in oligodendrocyte lineage cells impairs the turnover of myelin basic protein (MBP). It causes MBP to accumulate in the cytoplasm as multimeric aggregates and fails to be incorporated into integral myelin, which is associated with attenuated endocytic recycling. Inactivation of autophagy in oligodendrocyte lineage cells impairs myelin integrity and causes demyelination. Thus, this study shows autophagy is required to maintain myelin quality during aging by controlling the turnover of myelin components.
{"title":"Autophagy in Oligodendrocyte Lineage Cells Controls Oligodendrocyte Numbers and Myelin Integrity in an Age-dependent Manner","authors":"Hong Chen, Gang Yang, De-En Xu, Yu-tong Du, Chao Zhu, Hua Hu, Li Luo, Lei Feng, Wenhui Huang, Yan-Yun Sun, Quan-Hong Ma","doi":"10.1007/s12264-024-01292-1","DOIUrl":"https://doi.org/10.1007/s12264-024-01292-1","url":null,"abstract":"<p>Oligodendrocyte lineage cells, including oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLs), are essential in establishing and maintaining brain circuits. Autophagy is a conserved process that keeps the quality of organelles and proteostasis. The role of autophagy in oligodendrocyte lineage cells remains unclear. The present study shows that autophagy is required to maintain the number of OPCs/OLs and myelin integrity during brain aging. Inactivation of autophagy in oligodendrocyte lineage cells increases the number of OPCs/OLs in the developing brain while exaggerating the loss of OPCs/OLs with brain aging. Inactivation of autophagy in oligodendrocyte lineage cells impairs the turnover of myelin basic protein (MBP). It causes MBP to accumulate in the cytoplasm as multimeric aggregates and fails to be incorporated into integral myelin, which is associated with attenuated endocytic recycling. Inactivation of autophagy in oligodendrocyte lineage cells impairs myelin integrity and causes demyelination. Thus, this study shows autophagy is required to maintain myelin quality during aging by controlling the turnover of myelin components.</p>","PeriodicalId":19314,"journal":{"name":"Neuroscience bulletin","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}