Han Yang, Yong Zhu, Xin Li, Zuiming Jiang, Wenting Dai
{"title":"RNF216 affects the stability of STAU2 in the hypothalamus","authors":"Han Yang, Yong Zhu, Xin Li, Zuiming Jiang, Wenting Dai","doi":"10.1111/dgd.12877","DOIUrl":"10.1111/dgd.12877","url":null,"abstract":"<p>Idiopathic hypogonadotropic hypogonadism (IHH) is a rare disease characterized by gonadal failure due to deficiency in gonadotropin-releasing hormone (GnRH) synthesis, secretion, or action. <i>RNF216</i> variants have been recently identified in patients with IHH. Ring finger protein 216 (RNF216), as a ubiquitin E3 ligase, catalyzes the ubiquitination of target proteins with high specificity, which consequently modulates the stability, localization, and interaction of the target protein. In this study, we found that RNF216 interacted with Staufen2 (STAU2) and affected the stability of STAU2 through the ubiquitin–proteasome pathway. STAU2, as a double-stranded RNA-binding protein enriched in the nervous system, plays a role in RNA transport, RNA stability, translation, anchoring, and synaptic plasticity. Further, we revealed that STAU2 levels in the hypothalamus of <i>RNF216</i><sup>−/−</sup> mice were increased compared with wild-type (WT) mice. The change in STAU2 protein homeostasis may affect a series of RNA cargoes. Therefore, we analyzed the changes in RNA levels in the hypothalamus of <i>RNF216</i><sup>−/−</sup> mice and WT mice by RNA sequencing. We found that deletion of <i>RNF216</i> led to decreased activities of the prolactin signaling pathway, neuroactive ligand–receptor interaction, GnRH signaling pathway, and ovarian steroidogenesis. The weakening of these signal pathways is likely to affect the secretion of GnRH, thereby affecting the development of gonads. Therefore, our study suggests that STAU2 may be a potential therapeutic target for IHH. Further experiments are needed to demonstrate the association between the weakening of these signaling pathways and the RNA-binding protein STAU2.</p>","PeriodicalId":50589,"journal":{"name":"Development Growth & Differentiation","volume":"65 7","pages":"408-417"},"PeriodicalIF":2.5,"publicationDate":"2023-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9941352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Heloysa Araujo-Silva, Augusto Monteiro de Souza, João Paulo Medeiros Mamede, Silvia Regina Batistuzzo de Medeiros, Ana Carolina Luchiari
{"title":"Individual differences in response to alcohol and nicotine in zebrafish: Gene expression and behavior","authors":"Heloysa Araujo-Silva, Augusto Monteiro de Souza, João Paulo Medeiros Mamede, Silvia Regina Batistuzzo de Medeiros, Ana Carolina Luchiari","doi":"10.1111/dgd.12876","DOIUrl":"10.1111/dgd.12876","url":null,"abstract":"<p>Alcohol and nicotine are psychoactive substances responsible for serious health consequences. Although the biological mechanisms of alcohol and nicotine have been studied extensively, individual differences in the response to these drugs have received little attention. Here we evaluated gene expression and behavior of bold and shy individuals after acute exposure to alcohol and nicotine. For this, zebrafish were classified as bold and shy individuals based on emergence tests, and then fish were exposed to 0.00, 0.10, and 0.50% alcohol or 0.00, 1.00, and 5.00 mg/L nicotine and their anxiety-like and locomotor behavior was observed. After behavioral assessment, brain mRNA expression (<i>ache</i>, <i>bdnf, gaba1</i>, <i>gad1b</i>, <i>th1</i>, and <i>tph</i>1) was evaluated. Locomotion patterns differed between profiles depending on alcohol and nicotine concentration. Anxiety increased in shy fish and decreased in bold fish after exposure to both drugs. Alcohol exposure induced an increase in <i>tph1</i> mRNA expression in bold fish, while <i>bdnf</i> mRNA expression was increased in shy fish. Nicotine increased <i>ache</i>, <i>bdnf</i>, and <i>tph1</i> mRNA levels in both profiles, but at higher levels in bold fish. Based on our research, we found that alcohol induces anxiogenic effects in both bold and shy zebrafish. Additionally, shy individuals exposed to a low concentration of nicotine exhibited stronger anxiety-like responses than their bold counterparts. These findings further support the validity of using zebrafish as a dependable tool for studying the effects of drugs and uncovering the underlying mechanisms associated with individual variations.</p>","PeriodicalId":50589,"journal":{"name":"Development Growth & Differentiation","volume":"65 8","pages":"434-445"},"PeriodicalIF":2.5,"publicationDate":"2023-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/dgd.12876","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9883388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The crucial role of CTCF in mitotic progression during early development of sea urchin","authors":"Kaichi Watanabe, Megumi Fujita, Kazuko Okamoto, Hajime Yoshioka, Miki Moriwaki, Hideki Tagashira, Akinori Awazu, Takashi Yamamoto, Naoaki Sakamoto","doi":"10.1111/dgd.12875","DOIUrl":"10.1111/dgd.12875","url":null,"abstract":"<p>CCCTC-binding factor (CTCF), an insulator protein with 11 zinc fingers, is enriched at the boundaries of topologically associated domains (TADs) in eukaryotic genomes. In this study, we isolated and analyzed the cDNAs encoding HpCTCF, the CTCF homolog in the sea urchin <i>Hemicentrotus pulcherrimus</i>, to investigate its expression patterns and functions during the early development of sea urchin. HpCTCF contains nine zinc fingers corresponding to fingers 2–10 of the vertebrate CTCF. Expression pattern analysis revealed that <i>HpCTCF</i> mRNA was detected at all developmental stages and in the entire embryo. Upon expressing the HpCTCF-GFP fusion protein in early embryos, we observed its uniform distribution within interphase nuclei. However, during mitosis, it disappeared from the chromosomes and subsequently reassembled on the chromosome during telophase. Moreover, the morpholino-mediated knockdown of <i>HpCTCF</i> resulted in mitotic arrest during the morula to blastula stage. Most of the arrested chromosomes were not phospholylated at serine 10 of histone H3, indicating that mitosis was arrested at the telophase by HpCTCF depletion. Furthermore, impaired sister chromatid segregation was observed using time-lapse imaging of <i>HpCTCF</i>-knockdown embryos. Thus, HpCTCF is essential for mitotic progression during the early development of sea urchins, especially during the telophase-to-interphase transition. However, the normal development of pluteus larvae in CRISPR-mediated <i>HpCTCF</i>-knockout embryos suggests that disruption of zygotic HpCTCF expression has little effect on embryonic and larval development.</p>","PeriodicalId":50589,"journal":{"name":"Development Growth & Differentiation","volume":"65 7","pages":"395-407"},"PeriodicalIF":2.5,"publicationDate":"2023-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9847509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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 maternal spiralian-specific homeobox gene SPILE-E in the specification of blastomeres along the animal–vegetal axis during the early cleavage stages of mollusks","authors":"Yoshiaki Morino, Hiroki Yoshikawa","doi":"10.1111/dgd.12874","DOIUrl":"10.1111/dgd.12874","url":null,"abstract":"<p>Spiralians, one of the major clades of bilaterians, share a unique development known as spiralian development, characterized by the formation of tiers of cells called quartets, which exhibit different developmental potentials along the animal–vegetal axis. Recently, spiralian-specific TALE-type homeobox genes (SPILE) have been identified, some of which show zygotic and staggered expression patterns along the animal–vegetal axis and function in quartet specification in mollusks. However, it is unclear which maternal molecular components control the zygotic expression of these transcription factors. In this study, we focused on SPILE-E, a maternal transcription factor, and investigated its expression and function in mollusks. We found that the maternal and ubiquitous expression of SPILE-E in the cleavage stages is conserved in molluskan species, including limpets, mussels, and chitons. We knocked down SPILE-E in limpets and revealed that the expression of transcription factors specifically expressed in the first quartet (1q<sup>2</sup>; <i>foxj1b</i>) and second quartet (2q; <i>SPILE-B</i>) was abolished, whereas the macromere-quartet marker (<i>SPILE-C</i>) was ectopically expressed in 1q<sup>2</sup> in SPILE-E morphants. Moreover, we showed that the expression of <i>SPILE-A</i>, which upregulates <i>SPILE-B</i> but represses <i>SPILE-C</i> expression, decreased in SPILE-E morphants. Consistent with changes in the expression pattern of the above transcription factors, SPILE-E-morphant larvae exhibited patchy or complete loss of expression of marker genes of ciliated cells and shell fields, possibly reflecting incomplete specification of 1q<sup>2</sup> and 2q. Our results provide a molecular framework for quartet specification and highlight the importance of maternal lineage-specific transcription factors in the development and evolution of spiralians.</p>","PeriodicalId":50589,"journal":{"name":"Development Growth & Differentiation","volume":"65 7","pages":"384-394"},"PeriodicalIF":2.5,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9767012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Plastic brain structure changes associated with the division of labor and aging in termites","authors":"Tomoki Ishibashi, A.S.M. Waliullah, Shuhei Aramaki, Masaki Kamiya, Tomoaki Kahyo, Katsumasa Nakamura, Eisuke Tasaki, Mamoru Takata, Mitsutoshi Setou, Kenji Matsuura","doi":"10.1111/dgd.12873","DOIUrl":"10.1111/dgd.12873","url":null,"abstract":"<p>Division of labor is a prominent feature of social insect societies, where different castes engage in different specialized tasks. As brain differences are associated with behavioral differences, brain anatomy may be linked to caste polymorphism. Here, we show that termite brain morphology changes markedly with caste differentiation and age in the termite, <i>Reticulitermes speratus</i>. Brain morphology was shown to be associated with reproductive division of labor, with reproductive individuals (alates and neotenic reproductives) having larger brains than nonreproductives (workers and soldiers). Micro-computed tomography (CT) imaging and dissection observations showed that the king's brain morphology changed markedly with shrinkage of the optic lobes during their long life in the dark. Behavioral experiments showed that mature primary kings lose visual function as a result of optic lobe shrinkage. These results suggested that termites restructure their nervous systems to perform necessary tasks as they undergo caste differentiation, and that they also show flexible changes in brain morphology even after the final molt. This study showed that brain morphology in social insects is linked to caste and aging, and that the evolution of the division of labor is underpinned by the development of diverse neural systems for specialized tasks.</p>","PeriodicalId":50589,"journal":{"name":"Development Growth & Differentiation","volume":"65 7","pages":"374-383"},"PeriodicalIF":2.5,"publicationDate":"2023-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/dgd.12873","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10157950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Optogenetic control of medaka behavior with channelrhodopsin","authors":"Takahide Seki, Hideaki Takeuchi, Satoshi Ansai","doi":"10.1111/dgd.12872","DOIUrl":"10.1111/dgd.12872","url":null,"abstract":"<p>Optogenetics enables the manipulation of neural activity with high spatiotemporal resolution in genetically defined neurons. The method is widely used in various model animals in the neuroscience and physiology fields. Channelrhodopsins are robust tools for optogenetic manipulation, but they have not yet been used for studies in medaka. In the present study, we used the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated knock-in approach to establish a transgenic medaka strain expressing the <i>Chloromonas oogama</i> channelrhodopsin (CoChR) in the <i>ISL LIM homeobox 1</i> (<i>isl1</i>) locus. We demonstrated that light stimuli elicited specific behavioral responses, such as bending or turning locomotion in the embryos and pectoral fin movements in the larvae and adults. The response probabilities and intensities of these movements could be controlled by adjusting the intensity, duration, or wavelength of each light stimulus. Furthermore, we demonstrated that the pectoral fin movements in the adult stage could be elicited using a laser pointer to irradiate region including the caudal hind brain and the rostral spinal cord. Our results indicate that CoChR allows for manipulation of medaka behaviors by activating targeted neurons, which will further our understanding of the detailed neural mechanisms of motor control or social behaviors in medaka.</p>","PeriodicalId":50589,"journal":{"name":"Development Growth & Differentiation","volume":"65 6","pages":"288-299"},"PeriodicalIF":2.5,"publicationDate":"2023-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10052644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Automated contour extraction for light-sheet microscopy images of zebrafish embryos based on object edge detection algorithm","authors":"Akiko Kondow, Kiyoshi Ohnuma, Atsushi Taniguchi, Joe Sakamoto, Makoto Asashima, Kagayaki Kato, Yasuhiro Kamei, Shigenori Nonaka","doi":"10.1111/dgd.12871","DOIUrl":"10.1111/dgd.12871","url":null,"abstract":"<p>Embryo contour extraction is the initial step in the quantitative analysis of embryo morphology, and it is essential for understanding the developmental process. Recent developments in light-sheet microscopy have enabled the in toto time-lapse imaging of embryos, including zebrafish. However, embryo contour extraction from images generated via light-sheet microscopy is challenging owing to the large amount of data and the variable sizes, shapes, and textures of objects. In this report, we provide a workflow for extracting the contours of zebrafish blastula and gastrula without contour labeling of an embryo. This workflow is based on the edge detection method using a change point detection approach. We assessed the performance of the edge detection method and compared it with widely used edge detection and segmentation methods. The results showed that the edge detection accuracy of the proposed method was superior to those of the Sobel, Laplacian of Gaussian, adaptive threshold, Multi Otsu, and k-means clustering-based methods, and the noise robustness of the proposed method was superior to those of the Multi Otsu and k-means clustering-based methods. The proposed workflow was shown to be useful for automating small-scale contour extractions of zebrafish embryos that cannot be specifically labeled owing to constraints, such as the availability of microscopic channels. This workflow may offer an option for contour extraction when deep learning-based approaches or existing non-deep learning-based methods cannot be applied.</p>","PeriodicalId":50589,"journal":{"name":"Development Growth & Differentiation","volume":"65 6","pages":"311-320"},"PeriodicalIF":2.5,"publicationDate":"2023-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10411491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Involvement of the scalloped gene in morphogenesis of the wing margin via regulating cell growth in a hemimetabolous insect Gryllus bimaculatus","authors":"Takahisa Yamashita, Takahiro Ohde, Taro Nakamura, Yoshiyasu Ishimaru, Takahito Watanabe, Sayuri Tomonari, Yuki Nakamura, Sumihare Noji, Taro Mito","doi":"10.1111/dgd.12869","DOIUrl":"10.1111/dgd.12869","url":null,"abstract":"<p>The acquisition of wings was a key event in insect evolution. As hemimetabolous insects were the first group to acquire functional wings, establishing the mechanisms of wing formation in this group could provide useful insights into their evolution. In this study, we aimed to elucidate the expression and function of the gene scalloped (<i>sd</i>), which is involved in wing formation in <i>Drosophila melanogaster</i>, and in <i>Gryllus bimaculatus</i> mainly during postembryonic development. Expression analysis showed that <i>sd</i> is expressed in the tergal edge, legs, antennae, labrum, and cerci during embryogenesis and in the distal margin of the wing pads from at least the sixth instar in the mid to late stages. Because <i>sd</i> knockout caused early lethality, nymphal RNA interference experiments were performed. Malformations were observed in the wings, ovipositor, and antennae. By analyzing the effects on wing morphology, it was revealed that <i>sd</i> is mainly involved in the formation of the margin, possibly through the regulation of cell proliferation. In conclusion, <i>sd</i> might regulate the local growth of wing pads and influence wing margin morphology in <i>Gryllus.</i></p>","PeriodicalId":50589,"journal":{"name":"Development Growth & Differentiation","volume":"65 6","pages":"348-359"},"PeriodicalIF":2.5,"publicationDate":"2023-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10090927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Daughter cells inherit YAP localization from mother cells in early preimplantation embryos","authors":"Tomoaki Otsuka, Hiromi Shimojo, Hiroshi Sasaki","doi":"10.1111/dgd.12870","DOIUrl":"10.1111/dgd.12870","url":null,"abstract":"<p>The first stage of cell differentiation during mouse development is the differentiation into the trophectoderm and inner cell mass, which occurs during the 8–32-cell stages of preimplantation embryos. This differentiation is regulated by the Hippo signaling pathway. At the 32-cell stage, embryos establish a position-dependent distribution of the Hippo pathway coactivator, Yes-associated protein 1 (YAP, encoded by <i>Yap1</i>). The outer and inner cells showed nuclear and cytoplasmic localization of YAP, respectively. However, the process by which embryos establish position-dependent YAP localization remains elusive. Here, we established a YAP-reporter mouse line, <i>Yap1</i><sup><i>mScarlet</i></sup>, and examined YAP–mScarlet protein dynamics during the 8–32-cell stages using live imaging. During mitosis, YAP–mScarlet diffused throughout the cells. YAP–mScarlet dynamics in daughter cells varied depending on the cell division patterns. YAP–mScarlet localization in daughter cells at the completion of cell division coincided with that in mother cells. Experimental manipulation of YAP–mScarlet localization in mother cells also altered its localization in daughter cells upon completion of cell division. In daughter cells, YAP–mScarlet localization gradually changed to the final pattern. In some divisions during the 8–16-cell stages, the cytoplasmic YAP–mScarlet localization preceded cell internalization. These results suggest that cell position is not a primary determinant of YAP localization and that the Hippo signaling status of the mother cell is inherited by the daughter cells, which likely contributes to the stabilization of the cell fate specification process beyond cell division.</p>","PeriodicalId":50589,"journal":{"name":"Development Growth & Differentiation","volume":"65 6","pages":"360-369"},"PeriodicalIF":2.5,"publicationDate":"2023-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10097198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sakae Kikuyama, Kazutoshi Yamamoto, Fumiyo Toyoda, Tom Kouki, Reiko Okada
{"title":"Hormonal and pheromonal studies on amphibians with special reference to metamorphosis and reproductive behavior","authors":"Sakae Kikuyama, Kazutoshi Yamamoto, Fumiyo Toyoda, Tom Kouki, Reiko Okada","doi":"10.1111/dgd.12868","DOIUrl":"10.1111/dgd.12868","url":null,"abstract":"<p>In this article, we review studies which have been conducted to investigate the hormonal influence on metamorphosis in bullfrog (<i>Rana catesbeiana</i>) and Japanese toad (<i>Bufo japonicus</i>) larvae, in addition to studies conducted on the hormonal and pheromonal control of reproductive behavior in red-bellied newts (<i>Cynops pyrrhogaster</i>). Metamorphosis was studied with an emphasis on the roles of prolactin (PRL) and thyrotropin (TSH). The release of PRL was shown to be regulated by thyrotropin-releasing hormone (TRH) and that of TSH was evidenced to be regulated by corticotropin-releasing factor. The significance of the fact that the neuropeptide that controls the secretion of TSH is different from those encountered in mammals is discussed in consideration of the observation that the release of TRH, which stimulates the release of PRL, is enhanced when the animals are subjected to a cold temperature. Findings that were made by using melanin-rich cells of <i>Bufo</i> embryos and larvae, such as the determination of the origin of the adenohypophyseal primordium, identification of the pancreatic chitinase, and involvement of the rostral preoptic recess organ as the hypothalamic inhibitory center of α-melanocyte-stimulating hormone (α-MSH) secretion, are mentioned in this article. In addition, the involvement of hormones in eliciting courtship behavior in male red-bellied newts and the discovery of the peptide sex pheromones and hormonal control of their secretion are also discussed in the present article.</p>","PeriodicalId":50589,"journal":{"name":"Development Growth & Differentiation","volume":"65 6","pages":"321-336"},"PeriodicalIF":2.5,"publicationDate":"2023-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10052593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}