{"title":"Expression analysis of genes including Zfhx4 in mice and zebrafish reveals a temporospatial conserved molecular basis underlying craniofacial development.","authors":"Shujie Liu, Lin Xu, Makoto Kashima, Rika Narumi, Yoshifumi Takahata, Eriko Nakamura, Hirotoshi Shibuya, Masaru Tamura, Yuki Shida, Toshihiro Inubushi, Yuko Nukada, Masaaki Miyazawa, Kenji Hata, Riko Nishimura, Takashi Yamashiro, Junichi Tasaki, Hiroshi Kurosaka","doi":"10.1002/dvdy.740","DOIUrl":"https://doi.org/10.1002/dvdy.740","url":null,"abstract":"<p><strong>Background: </strong>Embryonic craniofacial development involves several cellular and molecular events that are evolutionarily conserved among vertebrates. Vertebrate models such as mice and zebrafish have been used to investigate the molecular and cellular etiologies underlying human craniofacial disorders, including orofacial clefts. However, the molecular mechanisms underlying embryonic development in these two species are unknown. Therefore, elucidating the shared mechanisms of craniofacial development between disease models is crucial to understanding the underlying mechanisms of phenotypes in individual species.</p><p><strong>Results: </strong>We selected mice and zebrafish as model organisms to compare various events during embryonic craniofacial development. We identified genes (Sox9, Zfhx3 and 4, Cjun, and Six1) exhibiting similar temporal expression patterns between these species through comprehensive and stage-matched gene expression analyses. Expression analysis revealed similar gene expression in hypothetically corresponding tissues, such as the mice palate and zebrafish ethmoid plate. Furthermore, loss-of-function analysis of Zfhx4/zfhx4, a causative gene of human craniofacial anomalies including orofacial cleft, in both species resulted in deformed skeletal elements such as the palatine and ethmoid plate in mice and zebrafish, respectively.</p><p><strong>Conclusions: </strong>These results demonstrate that these disease models share common molecular mechanisms, highlighting their usefulness in modeling craniofacial defects in humans.</p>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343561","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}
Vivien Bothe, Hendrik Müller, Neil Shubin, Nadia Fröbisch
{"title":"Effects of life history strategies and habitats on limb regeneration in plethodontid salamanders.","authors":"Vivien Bothe, Hendrik Müller, Neil Shubin, Nadia Fröbisch","doi":"10.1002/dvdy.742","DOIUrl":"https://doi.org/10.1002/dvdy.742","url":null,"abstract":"<p><strong>Background: </strong>Salamanders are the only tetrapods that exhibit the ability to fully regenerate limbs. The axolotl, a neotenic salamander, has become the model organism for regeneration research. Great advances have been made providing a detailed understanding of the morphological and molecular processes involved in limb regeneration. However, it remains largely unknown how limb regeneration varies across salamanders and how factors like variable life histories, ecologies, and limb functions have influenced and shaped regenerative capacities throughout evolution.</p><p><strong>Results: </strong>This study focuses on six species of plethodontid salamanders representing distinct life histories and habitats. Specimens were examined for regeneration ability after bite injuries as well as after controlled amputations. Morphological investigations revealed great regenerative abilities in all investigated species and frequent anatomical limb anomalies. Correlations were observed with respect to speed of regeneration and habitat.</p><p><strong>Conclusions: </strong>Investigating regeneration in non-model salamander taxa is essential for disentangling shared features of the regeneration process versus those that may be more taxon-specific. Gaining insights into variable aspects of regeneration under natural conditions and after conspecific biting rather than controlled amputations adds important new datapoints for understanding the evolutionary framework of regeneration and provides a broader context for interpreting findings made in the model organism axolotl.</p>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281898","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}
Amena Alsakran, Rashid Minhas, Atyaf S Hamied, Rod W Wilson, Mark Ramsdale, Tetsuhiro Kudoh
{"title":"Stage-by-stage exploration of normal embryonic development in the Arabian killifish, Aphanius dispar.","authors":"Amena Alsakran, Rashid Minhas, Atyaf S Hamied, Rod W Wilson, Mark Ramsdale, Tetsuhiro Kudoh","doi":"10.1002/dvdy.738","DOIUrl":"https://doi.org/10.1002/dvdy.738","url":null,"abstract":"<p><strong>Background: </strong>Arabian killifish, Aphanius dispar, lives in marine coastal areas of the Middle East, as well as in streams that experience a wide range of salinities and temperatures. It has been used as a mosquito control agent and for studying the toxicities of environmental pollutants. A. dispar's eggshell (chorion) and embryos are highly transparent and are suitable for high resolution microscopic observations, offering excellent visibility of live tissues.</p><p><strong>Results: </strong>In this study, the staging of normal embryonic development of A. dispar was described and investigated at different temperatures. Embryonic development was then examined under different thermal environments from 26 to 34°C. Our data suggest that temperature has a significant effect on embryonic development, with accelerated development at higher temperatures.</p><p><strong>Conclusion: </strong>A. dispar exhibits broad thermal tolerance and extended independent feeding capabilities, making it a promising model organism for toxicology and pathogenesis studies conducted over an extended period of time (12 days post-fertilization).</p>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281899","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}
Joshua A Moore, Rodrigo Moreno-Campos, Arielle S Noah, Eileen W Singleton, Rosa A Uribe
{"title":"BMP signaling pathway member expression is enriched in enteric neural progenitors and required for zebrafish enteric nervous system development.","authors":"Joshua A Moore, Rodrigo Moreno-Campos, Arielle S Noah, Eileen W Singleton, Rosa A Uribe","doi":"10.1002/dvdy.737","DOIUrl":"https://doi.org/10.1002/dvdy.737","url":null,"abstract":"<p><strong>Background: </strong>The vertebrate enteric nervous system (ENS) consists of a series of interconnected ganglia within the gastrointestinal (GI) tract, formed during development following migration of enteric neural crest cells (ENCCs) into the primitive gut tube. Much work has been done to unravel the complex nature of extrinsic and intrinsic factors that regulate processes that direct migration, proliferation, and differentiation of ENCCs. However, ENS development is a complex process, and we still have much to learn regarding the signaling factors that regulate ENCC development.</p><p><strong>Results: </strong>Here in zebrafish, through transcriptomic, in situ transcript expression, immunohistochemical analysis, and chemical attenuation, we identified a time-dependent role for bone morphogenetic protein (BMP) in the maintenance of Phox2bb<sup>+</sup> enteric progenitor numbers and/or time of differentiation of the progenitor pool. In support of our in silico transcriptomic analysis, we identified expression of a novel ENS ligand-encoding transcript, bmp5, within developmental regions of ENCCs. Through generation of a novel mutant bmp5<sup>wmr2</sup> and bmp5 crispants, we identified a functional role for BMP5 in proper GI tract colonization, whereby phox2bb<sup>+</sup> enteric progenitor numbers were reduced.</p><p><strong>Conclusion: </strong>Altogether, this work identified time-dependent roles for BMP signaling and a novel extrinsic factor, BMP5, that is necessary for vertebrate ENS formation.</p>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281897","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}
Lihong Kui, Peng Ma, Wenben Zhao, Bin Yan, Xiaojing Kuang, Bo Li, Ruishuang Geng, Tihua Zheng, Qingyin Zheng
{"title":"Developmental cochlear defects are involved in early‐onset hearing loss in A/J mice","authors":"Lihong Kui, Peng Ma, Wenben Zhao, Bin Yan, Xiaojing Kuang, Bo Li, Ruishuang Geng, Tihua Zheng, Qingyin Zheng","doi":"10.1002/dvdy.741","DOIUrl":"https://doi.org/10.1002/dvdy.741","url":null,"abstract":"BackgroundA/J mice exhibited a severe hearing loss (HL) at juvenile stage. Up‐to‐date, studies on HL in A/J mice have mostly focused on the damage or dysfunction of hair cells (HCs), spiral ganglion neurons (SGNs), and stereocilia. We examined A/J mice at the early postnatal stage and found that the damage and the loss of outer hair cells (OHCs) are not severe enough to explain the profound HL observed at this age, which suggests that other cochlear defects may be responsible for HL. To better understand the mechanisms of early‐onset HLin A/J mice, we characterized the pathology of the cochlea from postnatal day 3 to day 21.ResultsOur results showed defects in cochlear HC stereocilia and MET channel function as early as 3 days old. We also found abnormal localization and a significant reduction in the number of ribbon synapses in 2‐week‐old A/J mice. There are also abnormalities in the cochlear nerve innervation and terminal swellings in 3‐week‐old A/J mice.ConclusionAll of the abnormalities of cochlear existed in the A/J mice were identified in the juvenile stage and occurred before HCs or auditory nerve loss and was the initial pathological change. Our results suggest that developmental defects and subsequent cochlear degeneration are responsible for early‐onset hearing loss in A/J mice.","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":"65 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250811","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}
Mengjie Tu, Bingqian Ge, Jiali Li, Yanbing Pan, Binbin Zhao, Jiayang Han, Jialin Wu, Kaifeng Zhang, Guangchao Liu, Mengwen Hou, Man Yue, Xu Han, Tiantian Sun, Yang An
{"title":"Emerging biological functions of Twist1 in cell differentiation","authors":"Mengjie Tu, Bingqian Ge, Jiali Li, Yanbing Pan, Binbin Zhao, Jiayang Han, Jialin Wu, Kaifeng Zhang, Guangchao Liu, Mengwen Hou, Man Yue, Xu Han, Tiantian Sun, Yang An","doi":"10.1002/dvdy.736","DOIUrl":"https://doi.org/10.1002/dvdy.736","url":null,"abstract":"Twist1 is required for embryonic development and expresses after birth in mesenchymal stem cells derived from mesoderm, where it governs mesenchymal cell development. As a well‐known regulator of epithelial–mesenchymal transition or embryonic organogenesis, Twist1 is important in a variety of developmental systems, including mesoderm formation, neurogenesis, myogenesis, cranial neural crest cell migration, and differentiation. In this review, we first highlight the physiological significance of Twist1 in cell differentiation, including osteogenic, chondrogenic, and myogenic differentiation, and then detail its probable molecular processes and signaling pathways. On this premise, we summarize the significance of Twist1 in distinct developmental disorders and diseases to provide a reference for studies on cell differentiation/development‐related diseases.","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":"9 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142180922","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":"Editorial highlights","authors":"Paul A. Trainor","doi":"10.1002/dvdy.734","DOIUrl":"https://doi.org/10.1002/dvdy.734","url":null,"abstract":"<p>Every organism is a model organism for understanding development, evolution, disease, and regeneration, and we have only begun to scratch the surface of the interdisciplinary genetic, molecular, cellular, and developmental mechanisms that regulate these biological processes. These “Highlights” denote exciting advances recently reported in <i>Developmental Dynamics</i> that illustrate the complex dynamics of developmental biology.</p><p><b>Limb Development</b> “The limb dorsoventral axis: Lmx1b's role in development, pathology, evolution, and regeneration” by Alejandro Castilla-Ibeas, Sofía Zdral, Kerby Oberg, and Marian Ros. <i>Dev Dyn</i>. 253:9, pp. 798–814. https://doi.org/10.1002/dvdy.695. Limbs, which are crucial for locomotion, are thought to have evolved from fins in an aquatic ancestor as an adaptation to shallow water. Over time, limbs acquired complex characteristics built upon anterior-posterior, proximal-distal, and dorsal-ventral axes. Although limb development and patterning has been well studied, we still have much to learn about the dorsal-ventral axis. The dorsal domain of the limb houses the extensor muscles, ligaments, tendons, nerves, and vessels, whereas the ventral region contains flexor muscles among other tissues and structures. This review discusses our current understanding of dorsal-ventral patterning of the limb, bringing together the results of classic experiments with modern research, concepts, and interpretations. With an emphasis on Lmx1b, which specifies dorsal character and subsequently fate, the authors consider the role of dorsal-ventral patterning in the evolution of paired appendages and the association of variants in LMX1B in association with nail-patella syndrome. Finally, the role of dorsoventral patterning and polarity in digit tip regeneration in mammals is also considered further informing our understanding of limb function and evolutionary adaptations.</p><p><b>Neurodevelopment</b> “Disruption of Fuz in mouse embryos generates hypoplastic hindbrain development and reduced cranial nerve ganglia” by Carlo Donato Caiaffa, Yogeshwari Ambekar, Manmohan Singh, Ying Linda Lin, Bogdan Wlodarczyk, Salavat Aglyamov, Giuliano Scarcelli, Kirill Larin, and Richard Finnell. <i>Dev Dyn</i>. 253:9, pp. 846–858. https://doi.org/10.1002/dvdy.702. Neurulation is the process of neural tube formation from the neural plate, which subsequently forms the central nervous system, while also contributing to the peripheral nervous system. Perturbation of the early steps of neurulation can lead to neural tube defects, which are one of the most common birth defects, affecting about two in every 100 live births, or about 300,000 cases per year worldwide. Genetic mutations, environmental factors, and nutritional imbalances critically underpin the pathogenesis of most neural tube defects. The Fuz gene forms part of a macromolecular planar polarity effector required for ciliogenesis, and consequently, <i>Fuz</i> knockout mice exhibi","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":"253 9","pages":"796-797"},"PeriodicalIF":2.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dvdy.734","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142137664","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":"Developmental ecology in embryos of an estuarine pupfish endemic of the Yucatan peninsula: Survival out of water, metabolic depression, and asynchronous hatching.","authors":"Omar Domínguez-Castanedo, Sharon Valdez-Carbajal","doi":"10.1002/dvdy.732","DOIUrl":"https://doi.org/10.1002/dvdy.732","url":null,"abstract":"<p><strong>Background: </strong>Theory predicts that drought-resistant embryos with extended incubations are evolutionarily favored in environments with high mortality of larvae but safe for eggs. Here, we experimentally test, under common garden conditions, the effect of three incubation temperatures and media on embryonic developmental length, extended incubation out of the water, survival, metabolic rate, and hatching dynamics in the estuarine pupfish Garmanella pulchra. We also described the morphological changes of embryonic cortical structures related to air exposure.</p><p><strong>Results: </strong>We found that embryos incubated out of water in low and medium temperatures present an extended incubation period beyond their hatching capability with a deep metabolic depression. Also, these embryos exhibited a hatching asynchrony not related to water availability. Embryos incubated at high temperatures did not show extended incubation, with decreased probability of survival out of water. Our morphological observations of the embryonic cortical structures reveal that the perivitelline space and hair-like filaments buffer the deleterious drought effects.</p><p><strong>Conclusions: </strong>Our results reveal that G. pulchra possesses life-history traits typical of two separate phenomena: delay hatching and diapause; supporting a true continuum between them, rather than a dichotomy. The evolution of these traits may respond to aerial exposure during low tides in the estuaries of Yucatán they inhabit.</p>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016694","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}
Sarah Lusk, Sarah LaPotin, Jason S Presnell, Kristen M Kwan
{"title":"Increased Netrin downstream of overactive Hedgehog signaling disrupts optic fissure formation.","authors":"Sarah Lusk, Sarah LaPotin, Jason S Presnell, Kristen M Kwan","doi":"10.1002/dvdy.733","DOIUrl":"10.1002/dvdy.733","url":null,"abstract":"<p><strong>Background: </strong>Uveal coloboma, a developmental eye defect, is caused by failed development of the optic fissure, a ventral structure in the optic stalk and cup where axons exit the eye and vasculature enters. The Hedgehog (Hh) signaling pathway regulates optic fissure development: loss-of-function mutations in the Hh receptor ptch2 produce overactive Hh signaling and can result in coloboma. We previously proposed a model where overactive Hh signaling disrupts optic fissure formation by upregulating transcriptional targets acting both cell- and non-cell-autonomously. Here, we examine the Netrin family of secreted ligands as candidate Hh target genes.</p><p><strong>Results: </strong>We find multiple Netrin ligands upregulated in the zebrafish ptch2 mutant during optic fissure development. Using a gain-of-function approach to overexpress Netrin in a spatiotemporally specific manner, we find that netrin1a or netrin1b overexpression is sufficient to cause coloboma and disrupt wild-type optic fissure formation. We used loss-of-function alleles, CRISPR/Cas9 mutagenesis, and morpholino knockdown to test if loss of Netrin can rescue coloboma in the ptch2 mutant: loss of netrin genes does not rescue the ptch2 mutant phenotype.</p><p><strong>Conclusion: </strong>These results suggest that Netrin is sufficient but not required to disrupt optic fissure formation downstream of overactive Hh signaling in the ptch2 mutant.</p>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016695","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":"Hydrocortisone treatment as a tool to study conjunctival placode induction.","authors":"Paige M Drake, Tamara A Franz-Odendaal","doi":"10.1002/dvdy.729","DOIUrl":"https://doi.org/10.1002/dvdy.729","url":null,"abstract":"<p><strong>Background: </strong>Conjunctival placodes are a series of placodes that develop into the conjunctival (scleral) papillae and ultimately induce a series of scleral ossicles in the eyes of many vertebrates. This study establishes a hydrocortisone injection procedure (incl. dosage) that consistently inhibits all conjunctival papillae in the embryonic chicken eye. The effects of this hydrocortisone treatment on apoptosis, vasculature, and placode-related gene expression were assessed.</p><p><strong>Results: </strong>Hydrocortisone treatment does not increase apoptotic cell death or have a major effect on the ciliary artery or vascular plexus in the eye. β-catenin and Eda expression levels were not significantly altered following hydrocortisone treatment, despite the absence of conjunctival papillae. Notably, Fgf20 expression was significantly reduced following hydrocortisone treatment, and the distribution of β-catenin was altered.</p><p><strong>Conclusions: </strong>Our study showed that conjunctival papillae induction begins as early as HH27.5 (E5.5). Hydrocortisone treatment reduces Fgf20 expression independently of β-catenin and Eda and may instead affect other members of the Wnt/β-catenin or Eda/Edar pathways, or it may affect the ability of morphogens to diffuse through the extracellular matrix. This study contributes to a growing profile of gene expression data during placode development and enhances our understanding of how some vertebrate eyes develop these fascinating bones.</p>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888760","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}