Developmental Dynamics最新文献

{"title":"Protein turnover downstream of the Nipbl/CRL4 axis contributes to abnormal development in zebrafish embryos","authors":"Annie C. Sanchez,&nbsp;Niusha Banoukh,&nbsp;Fiona Mensching,&nbsp;Robert V. Skibbens,&nbsp;M. Kathryn Iovine","doi":"10.1002/dvdy.70037","DOIUrl":"10.1002/dvdy.70037","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Mutations in cohesins cause cohesinopathies such as Cornelia de Lange Syndrome (CdLS) and Roberts Syndrome (RBS). Prior findings demonstrate that Esco2 (a cohesin activator) and Smc3 (a core cohesin subunit) regulate the CRL4 E3 ubiquitin ligase. <i>SMC3</i> mutations, however, account for a small percentage of CdLS. Here, we test whether <i>NIPBL</i>, which when mutated is responsible for 65% of CdLS cases, also regulates CRL4.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We report that Nipbl knockdown in zebrafish embryos produces developmental abnormalities and reduces the transcription of <i>ddb1</i>, which encodes a key component of CRL4 E3 ligase. The severity of phenotypes in Nipbl knockdown embryos is partially rescued by exogenous <i>ddb1</i> mRNA, demonstrating that CRL4 ligase function is downstream of Nipbl. These findings suggest that aberrant accumulation of CRL4 ligase substrates contributes to developmental abnormalities. To test this model, we identified candidate CRL4 substrates in zebrafish embryos by LC–MS. The results reveal that elevated expression of one of these candidates, <i>pparαa</i>, is sufficient to produce developmental defects in zebrafish embryos.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Nipbl impacts CRL4 ligase activity via regulation of <i>ddb1</i> expression. We provide evidence that the aberrant accumulation of substrates is sufficient to produce developmental abnormalities consistent with those observed in RBS and CdLS models.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":"255 4","pages":"403-416"},"PeriodicalIF":1.5,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://anatomypubs.onlinelibrary.wiley.com/doi/epdf/10.1002/dvdy.70037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110222","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":"Editorial highlights","authors":"Paul A. Trainor","doi":"10.1002/dvdy.70134","DOIUrl":"10.1002/dvdy.70134","url":null,"abstract":"&lt;p&gt;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 &lt;i&gt;Developmental Dynamics&lt;/i&gt; that illustrate the complex dynamics of developmental biology.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Meet the Editorial Team&lt;/b&gt; “An interview with Associate Editor David M. Ornitz, Washington University School of Medicine in St. Louis, St. Louis, MO, USA” by David Ornitz and Paul Trevorrow.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; For over three decades, Dr. Ornitz's research has focused on the function of fibroblast growth factors (FGFs) in development, physiology, response to injury, and cancer. His graduate training at the forefront of transgenic mouse technology laid the foundations for modeling the genetic pathogenesis of cancer and the discovery of heparan sulfate proteoglycans as essential cofactors for FGF signaling. With a focus on Fgf3, Fgf9, Fgf18, and Fgfr3, Dr. Ornitz has made significant contributions to our understanding of cardiovascular, inner ear, pulmonary, and skeletal biology.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Macrophages, Inflammation, and Cancer&lt;/b&gt; “Rodent monocyte-derived macrophages do not express CD163: Comparative analysis using macrophages from living boreoeutherians” by Yoichi Saito, Yukio Fujiwara, Yasuka Yamaguchi, Satomi Tanaka, Kyoko Miura, Yoshiyuki Hizukuri, Kyoko Yamashiro, Yasuhiro Hayashi, Yuta Nakashima and Yoshihiro Komohara.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Macrophages are important for the regulation of inflammation and can be broadly classified into two classes: M1-like macrophages, which induce inflammation; and M2-like macrophages, which function in anti-inflammatory responses, tissue regeneration and repair. Anti-inflammatory, M2-like macrophages express CD163, a scavenger receptor, on their cell surfaces, and a high density of CD163-positive tumor-associated macrophages (TAMs) is thought to correlate with poor prognosis in human patient tumors. However, CD163-positive macrophages only infiltrate the margins of a tumor, not the center, and the authors found that the macrophages that infiltrate tumors, wounds, and inflammatory sites are actually CD-163 negative. Furthermore, the absence of CD-163 expression in monocyte-derived macrophages is shared across the rodent clade. The authors discuss CD163-positive resident macrophages as an important driver of tumor growth irrespective of the animal species or cell type of origin and then suggest that in mice, CD163-positive macrophages originate from a subset of resident macrophages, specifically, fetal liver monocytes/macrophages. CD163 is a conserved protein, and it will be important to elucidate both the molecular and cellular functions of CD163 across a wide variety of diseases and a broad range of animals, including humans, livestock, pets, and other mammals.&lt;/","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":"255 4","pages":"367-368"},"PeriodicalIF":1.5,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://anatomypubs.onlinelibrary.wiley.com/doi/epdf/10.1002/dvdy.70134","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147708204","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":"255 4","pages":"363-366"},"PeriodicalIF":1.5,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148082029","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":"Rodent monocyte-derived macrophages do not express CD163: Comparative analysis using macrophages from living boreoeutherians","authors":"Yoichi Saito,&nbsp;Yukio Fujiwara,&nbsp;Yasuka L. Yamaguchi,&nbsp;Satomi S. Tanaka,&nbsp;Kyoko Miura,&nbsp;Yoshiyuki Hizukuri,&nbsp;Kyoko Yamashiro,&nbsp;Yasuhiro Hayashi,&nbsp;Yuta Nakashima,&nbsp;Yoshihiro Komohara","doi":"10.1002/dvdy.70036","DOIUrl":"10.1002/dvdy.70036","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>CD163 is a scavenger receptor predominantly expressed on the surfaces of macrophages in various mammalian species and is a marker of anti-inflammatory (M2-like) macrophages. High density of CD163-positive tumor-associated macrophages (TAMs) is associated with worse prognosis in various patient tumors. Interestingly, studies on mice have shown that CD163-positive TAMs only infiltrate the margins of tumor tissues, not the center. Based on these observations, we hypothesized that circulating monocyte-derived macrophages (MDMs), which are the origin of most TAMs, do not express CD163 in mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We examined CD163 expression in MDMs, differentiated from healthy animals in vitro, and in normal, pathogenic, and tumorigenic macrophages infiltrating various tumors and organs across multiple species including primates, rodents, cetartiodactylans, and carnivores. We found that MDMs, including TAMs, do not express CD163 in mice. Our findings also suggest that murine CD163-positive macrophages likely originate from a specific subset of resident macrophages, namely fetal liver monocytes/macrophages, as indicated by fetal analysis. Furthermore, we revealed that the CD163-negative expression pattern in MDMs is a trait shared by the rodent clade.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Rodent MDMs do not express CD163, a phenotype not shared with MDMs of other mammals. Our findings caution against the extrapolation of rodent experimental results to other animal models.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":"255 4","pages":"372-402"},"PeriodicalIF":1.5,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://anatomypubs.onlinelibrary.wiley.com/doi/epdf/10.1002/dvdy.70036","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985069","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":"Endoderm differentiates into a transient epidermis in the mouse perineum","authors":"Christine E. Larkins,&nbsp;Daniel M. Grunberg,&nbsp;Gabriel M. Daniels,&nbsp;Erik J. Feldtmann,&nbsp;Martin J. Cohn","doi":"10.1002/dvdy.70050","DOIUrl":"10.1002/dvdy.70050","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>In eutherian mammals, the embryonic cloaca is partitioned into genitourinary and anorectal canals by the urorectal septum. In the mouse embryo, the urorectal septum contributes to the perineum, which separates the anus from the external genitalia. During the growth of the urorectal septum, endodermal epithelium of the cloaca is displaced to the surface of the perineum, where endodermal cells are integrated into the developing skin. However, it is unknown whether the endodermal lineage of the perineum acquires true epidermal identity, an enigmatic fate for endodermal cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We find that endodermal cells that reach the surface of the perineum express markers of basal, spinous, and granular epidermis. During postnatal development, the endodermal lineage of the perineum epidermis undergoes terminal differentiation and desquamation and is replaced by adjacent ectoderm. Live imaging and single-cell tracking show that ectodermal cells move at a faster velocity in a lateral-to-medial direction, indicating convergence toward the narrow band of endoderm that lies between the anus and external genitalia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Cloacal endoderm differentiates into a non-renewing, transient epidermis at the midline of the perineum. Differences in directionality and velocity of cell movement patterns between endodermal and ectodermal cells suggest that the perineum epidermis develops by convergent extension.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":"255 4","pages":"430-440"},"PeriodicalIF":1.5,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144483555","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":"Meet the editorial team. An interview with Associate Editor David M. Ornitz, Washington University School of Medicine in St. Louis, St. Louis, MO, USA","authors":"David M. Ornitz,&nbsp;Paul Trevorrow","doi":"10.1002/dvdy.70120","DOIUrl":"10.1002/dvdy.70120","url":null,"abstract":"","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":"255 4","pages":"369-371"},"PeriodicalIF":1.5,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146149403","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":"Dynamics of postnatal bone development and epiphyseal synostosis in the caprine autopod","authors":"Christopher J. Panebianco,&nbsp;Maha Essaidi,&nbsp;Elijah Barnes,&nbsp;Ashley Williams,&nbsp;Karin Vancíková,&nbsp;Margot C. Labberté,&nbsp;Pieter Brama,&nbsp;Niamh C. Nowlan,&nbsp;Joel D. Boerckel","doi":"10.1002/dvdy.70038","DOIUrl":"10.1002/dvdy.70038","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Bones develop to structurally balance strength and mobility. Bone developmental dynamics are influenced by whether an animal is ambulatory at birth. Precocial species, which are ambulatory at birth, develop advanced skeletal maturity in utero and experience postnatal development under mechanical loading. Here, we characterized postnatal bone development in the lower forelimbs of precocial goats using microcomputed tomography and histology. Our analysis focused on the two phalanges 1 (P1) bones and the partially fused metacarpal bone of the goat autopod from birth through adulthood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>P1 cortical bone densified rapidly after birth, but cortical thickness increased continually through adulthood. Upon normalization by body mass, the P1 normalized polar moment of inertia was constant over time, suggestive of changes correlating with ambulatory loading. P1 trabecular bone increased in trabecular number and thickness until sexual maturity (12 months), while metacarpal trabeculae grew primarily through trabecular thickening. Unlike prenatal synostosis (i.e., bone fusion) of the metacarpal diaphysis, synostosis of the epiphyses occurred postnatally, prior to growth plate closure, through a unique fibrocartilaginous endochondral ossification.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings implicate ambulatory loading in postnatal bone development of precocial goats and identify a novel postnatal synostosis event in the caprine metacarpal epiphysis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":"255 4","pages":"417-429"},"PeriodicalIF":1.5,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12353835/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987352","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":"Early ultraviolet exposure disrupts late dorsal fin skeletal development in zebrafish.","authors":"Margaret K Keating, Julio Jaime, Abigail Mumme-Monheit, Lindsey A Neukirch, Grace E Gustafson, Raisa Bailon-Zambrano, Marlen C Rice, James A Gagnon, James T Nichols","doi":"10.1002/dvdy.70133","DOIUrl":"10.1002/dvdy.70133","url":null,"abstract":"<p><strong>Background: </strong>Most organisms on earth experience ultraviolet radiation. High levels of ultraviolet B radiation can cause DNA and protein damage. Zebrafish have become a popular model to investigate the impact of ultraviolet B radiation. Previous studies have identified that early ultraviolet B radiation damages the transient, larval fin fold by inducing apoptosis. However, until now it remained unknown how this early exposure affects late-forming skeletal structures.</p><p><strong>Results: </strong>We determined that ultraviolet B radiation at early stages results in skeletal phenotypes appearing weeks later. Specifically, the dorsal fin skeleton fails to form following early larval exposure. Additionally, this early treatment results in disorganization of the late-forming anal fin and vertebral skeletal structures. We found that inbreeding sensitizes fish to this environmental perturbation, resulting in greater penetrance and expressivity of ultraviolet B radiation-induced phenotypes. These skeletal phenotypes were preceded by larval fin fold damage, precluding mesenchymal skeletal progenitor invasion, resulting in disruption of dorsal fin skeletal development.</p><p><strong>Conclusions: </strong>Ultraviolet B exposure early in zebrafish development variably damages the larval fin fold, resulting in variable loss of the adult dorsal fin skeleton, a structure that develops much later in life.</p>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13426077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147662314","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":"Role of SoxE transcription factors in development and disease.","authors":"Merin Lawrence, Gerhard Schlosser","doi":"10.1002/dvdy.70130","DOIUrl":"https://doi.org/10.1002/dvdy.70130","url":null,"abstract":"<p><p>Sox8, Sox9, and Sox10 arose by multiple rounds of genome duplications from a single SoxE gene in ancestral vertebrates. In this review, we will briefly discuss the molecular structure and function of SoxE transcription factors and their evolutionary origin. We will then discuss their expression, function, and developmental disorders. SoxE proteins play critical roles during the development of multiple tissues in vertebrate embryos, including the neural crest, inner ear, cartilages, and glia cells of diverse origins, heart, gonads, and gastrointestinal tract. Because they recognize the same DNA sequence, possess conserved functional domains, and have overlapping expression profiles, SoxE proteins act partly redundantly in many contexts. However, Sox8, Sox9, and Sox10 also have many unique and tissue-specific functions. In particular, Sox9 plays an essential role in chondrogenesis, whereas Sox10 is a central regulator of pigment and glia cells. The highly context-specific regulation of different sets of target genes by SoxE factors is due to their ability to interact and cooperate with many other proteins including other transcription factors, cofactors, and enzymes, which modulate their regulatory activity. The activity of SoxE proteins is also frequently altered in a context-dependent fashion by post-translational modifications such as phosphorylation, acetylation, and SUMOylation.</p>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147510416","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":"Role of non-homologous end joining DNA repair during limb regeneration in Ambystoma mexicanum.","authors":"Esteban Torres-Dimas, García-Lepe Ulises Omar, Espinal-Centeno Annie, Cruz-Ramírez Alfredo, Bermúdez-Cruz Rosa María","doi":"10.1002/dvdy.70131","DOIUrl":"https://doi.org/10.1002/dvdy.70131","url":null,"abstract":"<p><strong>Background: </strong>Ambystoma mexicanum is renowned for its extraordinary regenerative capacity. Regardless of whether progenitor cells arise via dedifferentiation or stem cell activation, these cells must replicate DNA to proliferate before they ultimately differentiate. This rapid cell division increases the likelihood of DNA damage, requiring efficient repair mechanisms.</p><p><strong>Results: </strong>We focused on the non-homologous end joining pathway, responsible for repairing double-strand DNA breaks, and investigated the effects of 2 key components-KU70/80 and LIGIV- using chemical inhibitors STL127705 and SCR130, respectively. We assessed the impact of these inhibitors on axolotl limb regeneration, finding that treatment with the LIGIV inhibitor (SCR130) led to a positive growth trend in the regenerated area. Histological analysis of re-amputated limbs revealed no major morphological differences between treated and control animals. However, we observed a significant increase in the number of senescent cells in the regenerated tissue after KU70/80 inhibition (STL127705) at 32 days post-amputation, suggesting that DNA repair inhibition may promote senescence. Furthermore, we detected a dose-dependent increase in DNA damage, indicated by the γH2AX(Ser139) signal, specifically in cells' nuclei within the regenerated tissues.</p><p><strong>Conclusions: </strong>These findings suggest that DNA repair inhibition impacts regeneration, potentially through mechanisms linked to cellular senescence and DNA damage accumulation.</p>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147479638","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}