Differentiation最新文献

{"title":"Lens placode modulates extracellular matrix formation during early eye development","authors":"Cecília G. De Magalhães ,&nbsp;Ales Cvekl ,&nbsp;Ruy G. Jaeger ,&nbsp;C.Y. Irene Yan","doi":"10.1016/j.diff.2024.100792","DOIUrl":"10.1016/j.diff.2024.100792","url":null,"abstract":"<div><p>The role extracellular matrix (ECM) in multiple events of morphogenesis has been well described, little is known about its specific role in early eye development. One of the first morphogenic events in lens development is placodal thickening, which converts the presumptive lens ectoderm from cuboidal to pseudostratified epithelium. This process occurs in the anterior pre-placodal ectoderm when the optic vesicle approaches the cephalic ectoderm and is regulated by transcription factor Pax6 and secreted BMP4. Since cells and ECM have a dynamic relationship of interdependence and modulation, we hypothesized that the ECM evolves with cell shape changes during lens placode formation. This study investigates changes in optic ECM including both protein distribution deposition, extracellular gelatinase activity and gene expression patterns during early optic development using chicken and mouse models. In particular, the expression of <em>Timp2</em>, a metalloprotease inhibitor, corresponds with a decrease in gelatinase activity within the optic ECM. Furthermore, we demonstrate that optic ECM remodeling depends on BMP signaling in the placode. Together, our findings suggest that the lens placode plays an active role in remodeling the optic ECM during early eye development.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141472143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Generation of a Wt1 conditional deletion, nuclear red fluorescent protein reporter allele in the mouse","authors":"Jace A. Aloway ,&nbsp;E. Cristy Ruteshouser ,&nbsp;Vicki Huff ,&nbsp;Richard R. Behringer","doi":"10.1016/j.diff.2024.100791","DOIUrl":"10.1016/j.diff.2024.100791","url":null,"abstract":"<div><p>A <em>Wt1</em> conditional deletion, nuclear red fluorescent protein (RFP) reporter allele was generated in the mouse by gene targeting in embryonic stem cells. Upon Cre-mediated recombination, a deletion allele is generated that expresses RFP in a <em>Wt1</em>-specific pattern. RFP expression was detected in embryonic and adult tissues known to express <em>Wt1</em>, including the kidney, mesonephros, and testis. In addition, RFP expression and WT1 co-localization was detected in the adult uterine stroma and myometrium, suggesting a role in uterine function. Crosses with <em>Wnt7a-Cre</em> transgenic mice that express <em>Cre</em> in the Müllerian duct epithelium activate <em>Wt1</em>-directed RFP expression in the epithelium of the oviduct but not the stroma and myometrium of the uterus. This new mouse strain should be a useful resource for studies of <em>Wt1</em> function and marking <em>Wt1</em>-expressing cells.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141472142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of the zebrafish gabra1sa43718/sa43718 germline loss of function allele confirms a function for Gabra1 in motility and nervous system development","authors":"Nayeli G. Reyes-Nava ,&nbsp;David Paz ,&nbsp;Briana E. Pinales,&nbsp;Isaiah Perez,&nbsp;Claudia B. Gil,&nbsp;Annalise V. Gonzales,&nbsp;Brian I. Grajeda ,&nbsp;Igor L. Estevao ,&nbsp;Cameron C. Ellis ,&nbsp;Victoria L. Castro,&nbsp;Anita M. Quintana","doi":"10.1016/j.diff.2024.100790","DOIUrl":"10.1016/j.diff.2024.100790","url":null,"abstract":"<div><p>Mutation of the <em>GABRA1</em> gene is associated with neurodevelopmental defects and epilepsy. <em>GABRA1</em> encodes for the α1 subunit of the γ-aminobutyric acid type A receptor (GABA_AR), which regulates the fast inhibitory impulses of the nervous system. Multiple model systems have been developed to understand the function of <em>GABRA1</em>, but these models have produced complex and, at times, incongruent data. Thus, additional model systems are required to validate and substantiate previous results. We sought to provide initial phenotypic analysis of a novel germline mutant allele. Our analysis provides a solid foundation for the future use of this allele to characterize <em>gabra1</em> functionally and pharmacologically using zebrafish. We investigated the behavioral swim patterns associated with a nonsense mutation of the zebrafish <em>gabra1</em> (<em>sa43718</em> allele) gene. The <em>sa43718</em> allele causes a decrease in <em>gabra1</em> mRNA expression, which is associated with light induced hypermotility, one phenotype previously associated with seizure like behavior in zebrafish. Mutation of <em>gabra1</em> was accompanied by decreased mRNA expression of <em>gabra2, gabra3, and gabra5,</em> indicating a reduction in the expression of additional α sub-units of the GABA_AR. Although multiple sub-units were decreased, larvae continued to respond to pentylenetetrazole (PTZ), indicating that a residual GABA_AR exists in the <em>sa43718</em> allele. Proteomics analysis demonstrated that mutation of <em>gabra1</em> is associated with abnormal expression of proteins that regulate synaptic vesicle fusion, vesicle transport, synapse development, and mitochondrial protein complexes. These data support previous studies performed in a zebrafish nonsense allele created by CRISPR/Cas9 and validate that loss of function mutations in the <em>gabra1</em> gene result in seizure-like phenotypes with abnormal development of the GABA synapse. Our results add to the existing body of knowledge as to the function of GABRA1 during development and validate that zebrafish can be used to provide complete functional characterization of the gene.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141407482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the impact of osteoprotegerin on osteoclast and precursor fusion: Mechanisms and modulation by ATP","authors":"Yunwen Peng ,&nbsp;Hongyan Zhao ,&nbsp;Sinan Hu ,&nbsp;Yonggang Ma ,&nbsp;Tao Han ,&nbsp;Chuang Meng ,&nbsp;Xishuai Tong ,&nbsp;Hui Zou ,&nbsp;Zongping Liu ,&nbsp;Ruilong Song","doi":"10.1016/j.diff.2024.100789","DOIUrl":"10.1016/j.diff.2024.100789","url":null,"abstract":"<div><p>Osteoclast (OC) differentiation, vital for bone resorption, depends on osteoclast and precursor fusion. Osteoprotegerin (OPG) inhibits osteoclast differentiation. OPG's influence on fusion and mechanisms is unclear. Osteoclasts and precursors were treated with OPG alone or with ATP. OPG significantly reduced OC number, area and motility and ATP mitigated OPG's inhibition. However, OPG hardly affected the motility of precusors. OPG downregulated fusion-related molecules (CD44, CD47, DC-STAMP, ATP6V0D2) in osteoclasts, reducing only CD47 in precursors. OPG reduced Connexin43 phosphorylated forms (P1 and P2) in osteoclasts, affecting only P2 in precursors. OPG disrupted subcellular localization of CD44, CD47, DC-STAMP, ATP6V0D2, and Connexin43 in both cell types. Findings underscore OPG's multifaceted impact, inhibiting multinucleated osteoclast and mononuclear precursor fusion through distinct molecular mechanisms. Notably, ATP mitigates OPG's inhibitory effect, suggesting a potential regulatory role for the ATP signaling pathway. This study enhances understanding of intricate processes in osteoclast differentiation and fusion, offering insights into potential therapeutic targets for abnormal bone metabolism.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141393992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The ciliary protein C2cd3 is required for mandibular musculoskeletal tissue patterning","authors":"Evan C. Brooks ,&nbsp;Simon J.Y. Han ,&nbsp;Christian Louis Bonatto Paese ,&nbsp;Amya A. Lewis ,&nbsp;Megan Aarnio-Peterson ,&nbsp;Samantha A. Brugmann","doi":"10.1016/j.diff.2024.100782","DOIUrl":"10.1016/j.diff.2024.100782","url":null,"abstract":"<div><p>The mandible is composed of several musculoskeletal tissues including bone, cartilage, and tendon that require precise patterning to ensure structural and functional integrity. Interestingly, most of these tissues are derived from one multipotent cell population called cranial neural crest cells (CNCCs). How CNCCs are properly instructed to differentiate into various tissue types remains nebulous. To better understand the mechanisms necessary for the patterning of mandibular musculoskeletal tissues we utilized the avian mutant <em>talpid</em>^<em>2</em> (<em>ta</em>^<em>2</em>) which presents with several malformations of the facial skeleton including dysplastic tendons, mispatterned musculature, and bilateral ectopic cartilaginous processes extending off Meckel's cartilage. We found an ectopic epithelial BMP signaling domain in the <em>ta</em>^<em>2</em> mandibular prominence (MNP) that correlated with the subsequent expansion of <em>SOX9</em>+ cartilage precursors. These findings were validated with conditional murine models suggesting an evolutionarily conserved mechanism for CNCC-derived musculoskeletal patterning. Collectively, these data support a model in which cilia are required to define epithelial signal centers essential for proper musculoskeletal patterning of CNCC-derived mesenchyme.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0301468124000380/pdfft?md5=5f039bdd425a7be72f18daf3f8a996ae&pid=1-s2.0-S0301468124000380-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141176790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pax6 isoforms shape eye development: Insights from developmental stages and organoid models","authors":"Shih-Shun Hung ,&nbsp;Po-Sung Tsai ,&nbsp;Ching-Wen Po ,&nbsp;Pei-Shan Hou","doi":"10.1016/j.diff.2024.100781","DOIUrl":"https://doi.org/10.1016/j.diff.2024.100781","url":null,"abstract":"<div><p>Pax6 is a critical transcription factor involved in the development of the central nervous system. However, in humans, mutations in Pax6 predominantly result in iris deficiency rather than neurological phenotypes. This may be attributed to the distinct functions of Pax6 isoforms, <em>Pax6a</em> and <em>Pax6b</em>. In this study, we investigated the spatial and temporal expression patterns of Pax6 isoforms during different stages of mouse eye development. We observed a strong correlation between <em>Pax6a</em> expression and the neuroretina gene <em>Sox2</em>, while <em>Pax6b</em> showed a high correlation with iris-component genes, including the mesenchymal gene <em>Foxc1</em>. During early patterning from E10.5, <em>Pax6b</em> was expressed in the hinge of the optic cup and neighboring mesenchymal cells, whereas <em>Pax6a</em> was absent in these regions. At E14.5, both <em>Pax6a</em> and <em>Pax6b</em> were expressed in the future iris and ciliary body, coinciding with the integration of mesenchymal cells and <em>Mitf</em>-positive cells in the outer region. From E18.5, Pax6 isoforms exhibited distinct expression patterns as lineage genes became more restricted. To further validate these findings, we utilized ESC-derived eye organoids, which recapitulated the temporal and spatial expression patterns of lineage genes and Pax6 isoforms. Additionally, we found that the spatial expression patterns of <em>Foxc1</em> and <em>Mitf</em> were impaired in <em>Pax6b</em>-mutant ESC-derived eye organoids. This in vitro eye organoids model suggested the involvement of <em>Pax6b</em>-positive local mesodermal cells in iris development. These results provide valuable insights into the regulatory roles of Pax6 isoforms during iris and neuroretina development and highlight the potential of ESC-derived eye organoids as a tool for studying normal and pathological eye development.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0301468124000379/pdfft?md5=8e67d792469eac5c4ece7d22329136d5&pid=1-s2.0-S0301468124000379-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140555556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fibroblast Growth Factor 6","authors":"Jennelle Smith ,&nbsp;Loydie A. Jerome-Majewska","doi":"10.1016/j.diff.2024.100780","DOIUrl":"https://doi.org/10.1016/j.diff.2024.100780","url":null,"abstract":"<div><p>Fibroblast Growth Factor 6 (<em>FGF6</em>), also referred to as <em>HST2</em> or <em>HBGF6</em>, is a member of the Fibroblast Growth Factor (FGF), the Heparin Binding Growth Factor (HBGF) and the Heparin Binding Secretory Transforming Gene (HST) families. The genomic and protein structure of FGF6 is highly conserved among varied species, as is its expression in muscle and muscle progenitor cells. Like other members of the FGF family, <em>FGF6</em> regulates cell proliferation, differentiation, and migration. Specifically, it plays key roles in myogenesis and muscular regeneration, angiogenesis, along with iron transport and lipid metabolism. Similar to others from the FGF family, <em>FGF6</em> also possesses oncogenic transforming activity, and as such is implicated in a variety of cancers.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0301468124000367/pdfft?md5=cfbe55726f20d1e1270ee44f3c9772ab&pid=1-s2.0-S0301468124000367-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140552481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell cycle perturbation uncouples mitotic progression and invasive behavior in a post-mitotic cell","authors":"Michael A.Q. Martinez ,&nbsp;Chris Z. Zhao ,&nbsp;Frances E.Q. Moore ,&nbsp;Callista Yee ,&nbsp;Wan Zhang ,&nbsp;Kang Shen ,&nbsp;Benjamin L. Martin ,&nbsp;David Q. Matus","doi":"10.1016/j.diff.2024.100765","DOIUrl":"10.1016/j.diff.2024.100765","url":null,"abstract":"<div><p>The acquisition of the post-mitotic state is crucial for the execution of many terminally differentiated cell behaviors during organismal development. However, the mechanisms that maintain the post-mitotic state in this context remain poorly understood. To gain insight into these mechanisms, we used the genetically and visually accessible model of <em>C. elegans</em> anchor cell (AC) invasion into the vulval epithelium. The AC is a terminally differentiated uterine cell that normally exits the cell cycle and enters a post-mitotic state before initiating contact between the uterus and vulva through a cell invasion event. Here, we set out to identify the set of negative cell cycle regulators that maintain the AC in this post-mitotic, invasive state. Our findings revealed a critical role for CKI-1 (p21^CIP1/p27^KIP1) in redundantly maintaining the post-mitotic state of the AC, as loss of CKI-1 in combination with other negative cell cycle regulators—including CKI-2 (p21^CIP1/p27^KIP1), LIN-35 (pRb/p107/p130), FZR-1 (Cdh1/Hct1), and LIN-23 (β-TrCP)—resulted in proliferating ACs. Remarkably, time-lapse imaging revealed that these ACs retain their ability to invade. Upon examination of a node in the gene regulatory network controlling AC invasion, we determined that proliferating, invasive ACs do so by maintaining aspects of pro-invasive gene expression. We therefore report that the requirement for a post-mitotic state for invasive cell behavior can be bypassed following direct cell cycle perturbation.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140148321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Type 1 collagen: Synthesis, structure and key functions in bone mineralization","authors":"Vimalraj Selvaraj ,&nbsp;Saravanan Sekaran ,&nbsp;Anuradha Dhanasekaran ,&nbsp;Sudha Warrier","doi":"10.1016/j.diff.2024.100757","DOIUrl":"10.1016/j.diff.2024.100757","url":null,"abstract":"<div><p>Collagen is a highly abundant protein in the extracellular matrix of humans and mammals, and it plays a critical role in maintaining the body's structural integrity. Type I collagen is the most prevalent collagen type and is essential for the structural integrity of various tissues. It is present in nearly all connective tissues and is the main constituent of the interstitial matrix. Mutations that affect collagen fiber formation, structure, and function can result in various bone pathologies, underscoring the significance of collagen in sustaining healthy bone tissue. Studies on type 1 collagen have revealed that mutations in its encoding gene can lead to diverse bone diseases, such as osteogenesis imperfecta, a disorder characterized by fragile bones that are susceptible to fractures. Knowledge of collagen's molecular structure, synthesis, assembly, and breakdown is vital for comprehending embryonic and foetal development and several aspects of human physiology. In this review, we summarize the structure, molecular biology of type 1 collagen, its biomineralization and pathologies affecting bone.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140009594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxidative-stress induced Bmp2-Smad1/5/8 signaling dependent differentiation of early cardiomyocytes from embryonic and adult epicardial cells","authors":"Madhurima Ghosh ,&nbsp;Riffat Khanam ,&nbsp;Arunima Sengupta ,&nbsp;Santanu Chakraborty","doi":"10.1016/j.diff.2024.100756","DOIUrl":"10.1016/j.diff.2024.100756","url":null,"abstract":"<div><p>Heart failure has become a major life-threatening cause affecting millions globally, characterized by the permanent loss of adult functional cardiomyocytes leading to fibrosis which ultimately deprives the heart of its functional efficacy. Here we investigated the reparative property of embryonic and adult epicardial cells towards cardiomyocyte differentiation under oxidative stress-induced conditions along with the identification of a possible molecular signaling pathway. Isolated epicardial cells from embryonic chick hearts subjected to oxidative stress and hypoxia induction. Initial assessment of successful injury induction reveals hypertrophy of isolated epicardial cells. Detailed marker gene expression analyses and inhibitor studies reveal Bone morphogenic protein (Bmp)2-Smad1/5/8 signaling dependent cardiomyocyte lineage specification via epithelial to mesenchymal transition (EMT) post-injury. EMT is further confirmed by increased proliferation, migration, and differentiation towards cardiomyocyte lineage. We have also established an <em>in-vivo</em> model in adult male rats using Isoproterenol. Successful oxidative stress-mediated injury induction in adult heart was marked by increased activated fibroblasts followed by apoptosis of adult cardiomyocytes. The detailed characterization of adult epicardial cells reveals similar findings to our avian <em>in-vitro</em> data. Both <em>in-vitro</em> and <em>in-vivo</em> results show a significant increase in the expression of cardiomyocyte specific markers indicative of lineage specificity and activation of epicardial cells post oxidative stress mediated injury. Our findings suggest an EMT-induced reactivation of epicardial cells and early cardiomyocyte lineage specification following oxidative stress in a Bmp2- Smad1/5/8 dependent manner. Overall, this regulatory mechanism of cardiomyocyte differentiation induced by oxidative stress may contribute to the field of cardiac repair and regenerative therapeutics.</p></div>","PeriodicalId":50579,"journal":{"name":"Differentiation","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140054043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}