Journal of Developmental Biology最新文献

{"title":"Signaling Pathways in Human Blastocyst Development: From Molecular Mechanisms to In Vitro Optimization.","authors":"Yan Jiao, Jiapeng Liu, Congge Li, Yuexin Hu, Sanjun Zhao","doi":"10.3390/jdb13030033","DOIUrl":"10.3390/jdb13030033","url":null,"abstract":"<p><p>In recent years, assisted reproductive technology (ART) has developed rapidly with the delay in reproductive age and the rise in infertility rates. During ART, blastocyst quality is a key factor affecting the rate of implantation and clinical pregnancy, and blastocyst formation is dependent on the precise regulation of multiple signaling pathways in preimplantation embryo development. In this review, we systematically analyze the molecular mechanisms of the core pathways, including Hippo, Wnt/β-catenin, FGF, Nodal, and BMP, in blastocyst lineage differentiation and morphogenesis, and assess the feasibility of optimizing in vitro culture by targeting key signaling nodes, as well as provide theoretical support for constructing research models of preimplantation embryos.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"13 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12452331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zebrafish Unga Is Required for Genomic Maintenance upon Genotoxic Stress and Male Fertility.","authors":"Latifa Kazzazy, Flóra Huba, Bálint Lóránt Hausz, Dávid Mező, Viktória Perey-Simon, Bálint Jezsó, Abdulrahman Seddik, Zoran Marinović, Judit Tóth, Angéla Békési, Beáta G Vértessy, Máté Varga","doi":"10.3390/jdb13030032","DOIUrl":"10.3390/jdb13030032","url":null,"abstract":"<p><p>DNA repair is a multifaceted biological process that involves multiple pathways to counter the types of damage the genome encounters throughout life. In the past decade zebrafish became a popular model organism to study various aspects of vertebrate DNA repair, and the characterization of several mutant lines deficient in key players of the repair pathways has significantly contributed to our understanding of the roles the corresponding proteins play in the maintenance of genomic integrity. Interestingly, the base-excision repair (BER) pathway remained one of the less characterized DNA repair processes in fish. Here we provide a detailed characterization of zebrafish deficient in one of the key components of BER, the uracil-DNA glycosylase Unga. We show that while these fish are viable, they display an altered response to genotoxic stress and <i>unga</i> mutant males show an interesting form of subfertility.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"13 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12452583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Profilin and Non-Canonical Wnt Signaling: Coordinating Cytoskeletal Dynamics from Development to Disease.","authors":"Samira Alam, Danielle Duncan, Sharmin Hasan","doi":"10.3390/jdb13030031","DOIUrl":"10.3390/jdb13030031","url":null,"abstract":"<p><p>Vertebrate embryonic development relies on tightly regulated signaling pathways that guide morphogenesis, cell fate specification, and tissue organization. Among these, the Wnt signaling pathway plays a central role, orchestrating key developmental events. The non-canonical Wnt pathways, including the Planar Cell Polarity and Wnt/Ca²⁺ branches, are especially critical for regulating cytoskeletal dynamics during gastrulation. Recent studies highlight that these pathways interface with cytoskeletal effectors to control actin remodeling in response to extracellular cues. One such effector is Profilin, a small, evolutionarily conserved actin-binding protein that modulates actin polymerization and cellular architecture. Profilins, particularly Profilin1 and 2, are known to interact with Daam1, a formin protein downstream of PCP signaling, thereby linking Wnt signals to actin cytoskeletal regulation. Emerging evidence suggests that Profilins are active signaling intermediates that contribute to morphogenetic processes. Their context-dependent interactions and differential expression across species also suggest that they play specialized roles in development and disease. This review synthesizes the current understanding of Profilin's role in non-canonical Wnt signaling, examining its molecular interactions and contributions to cytoskeletal control during development. By integrating data across model systems, we aim to clarify how Profilins function at the intersection of signaling and cytoskeletal dynamics, with implications for both developmental biology and disease pathogenesis.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"13 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12452346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Drosophila</i> COMPASS Complex Subunits Set1 and Ash2 Are Required for Oocyte Determination and Maintenance of the Synaptonemal Complex.","authors":"Brigite Cabrita, Mary Enyioko, Rui Gonçalo Martinho","doi":"10.3390/jdb13030030","DOIUrl":"10.3390/jdb13030030","url":null,"abstract":"<p><p>Female gametogenesis is orchestrated by dynamic epigenetic modifications. In mammals, SETDB1, a histone H3K9 methyltransferase, is required for proper meiotic progression and early embryonic development. In <i>Drosophila</i>, the ortholog of SETDB1 plays a critical role in germ cell differentiation, transposon silencing, and the transcriptional repression of specific germline genes during oocyte fate determination. Moreover, Polycomb group (PcG) proteins in both mammals and <i>Drosophila</i> are essential for primary oocyte viability and meiosis, functioning through the silencing of early prophase I genes during later stages of prophase. While the repressive roles of epigenetic regulators in both <i>Drosophila</i> and mammalian oogenesis are well characterized, the functions of epigenetic activators remain less defined. Gene expression is controlled by the opposing activities of PcG and Trithorax group (TrxG) proteins, with the latter constituting a diverse family of chromatin remodelling factors that include H3K4 methyltransferases. In <i>Drosophila</i>, SET domain containing 1 (Set1)-the ortholog of mammalian SETD1A/B-acts as the primary regulator of global H3K4me2/3 levels. Set1 is critical for germline stem cell (GSC) self-renewal, functioning through both cell-autonomous and non-cell-autonomous mechanisms, with its depletion in the germline resulting in a progressive loss of GSC. More recently, Set1 has been implicated in germline cyst differentiation, although the mechanisms underlying this role remain poorly understood due to the complexity of the observed phenotypes. To investigate this, we analyzed ovaries from recently eclosed females in which Set1 and its highly conserved COMPASS partner, absent, small, or homeotic discs 2 (Ash2), were depleted-thus minimizing the confounding effects from GSC loss. We observed striking defects in both oocyte determination and Synaptonemal Complex (SC) integrity in one- to two-day-old females, within otherwise normal egg chambers. Interestingly, while defects in oocyte fate and oocyte-chromatin architecture were partially recovered in older egg chambers, SC integrity remained compromised. These findings suggest a critical window for SC assembly during germline cyst differentiation, after which this assembly cannot occur.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"13 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12372144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144956407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GLP-1-Mediated Pregnancy and Neonatal Complications in Mice.","authors":"Rajalakshmi Ramamoorthy, Arianna K Carden, Hussain Hussain, Brian Z Druyan, Ping Ping Chen, Rima Hajjar, Carmen Fernandez, Nila Elumalai, Amirah B Rashed, Karen Young, Anna Rosa Speciale, Emily M West, Staci Marbin, Bradley Safro, Ian J Bishop, Arumugam R Jayakumar, Luis Sanchez-Ramos, Michael J Paidas","doi":"10.3390/jdb13030029","DOIUrl":"10.3390/jdb13030029","url":null,"abstract":"<p><p>Glucagon-like peptide 1 (GLP-1), a hormone derived from the proglucagon gene, regulates various physiological processes; however, its impact on pregnancy outcomes remains poorly understood. Assessing the effects of GLP-1 on neonates is vital as GLP-1 is increasingly administered during pregnancy. This study evaluates the effect of GLP-1 exposure on maternal complications and neonatal defects in mice. Pregnant female A/J mice received subcutaneous injections of recombinant GLP-1 (rGLP-1; 1000 nmol/kg) on embryonic day 1 (EP, early pregnancy) or day 15 (E15, late pregnancy). Maternal and neonatal body weights, morphology, and mortality were recorded, and mRNA sequencing was conducted to analyze gene expression in neonatal tissues. Maternal body weight decreased following rGLP-1 exposure, and pups born to both the early and late exposure groups experienced significant weight loss. Pups in the late exposure group exhibited uniform skin detachment and a dramatically higher mortality rate than those born to the early exposure group. Further, RT-PCR analysis confirms the significantly increased expression of selected genes in the skin and associated pathogenesis. RNA sequencing of pups' skin, brain, lung, and liver tissues from the late exposure group showed altered gene expression. Since maternal weight loss, increased neonatal mortality, and altered gene expression have been observed, GLP-1 receptor agonists (GLP-1RAs) should be avoided during pregnancy.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"13 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12372104/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144956391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Congenital Malformation of the Interatrial Septum-A Review of Its Development and Embryology with Clinical Implications.","authors":"Rui Caetano Oliveira, Paula Martins, Maria de Fátima Martins","doi":"10.3390/jdb13030028","DOIUrl":"10.3390/jdb13030028","url":null,"abstract":"<p><p>The development process of the heart and cardiovascular system is fundamental in human development and highly regulated by genetic factors. This process needs to be highly regulated to prevent malformations. Nevertheless, some heart defects may be identified, especially with modern imaging methodology. Atrial septal defects (ASDs) are particularly common. Understanding the mechanisms involved in ASD formation is fundamental for developing new treatment strategies. In this article, we explore cardiac development and embryology, with a focus on atrial septal defects and their clinical implications.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"13 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12372156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144956442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolution of the Jawed Vertebrate (Gnathostomata) Stomach Through Gene Repertoire Loss: Findings from Agastric Species.","authors":"Jackson Dann, Frank Grützner","doi":"10.3390/jdb13030027","DOIUrl":"10.3390/jdb13030027","url":null,"abstract":"<p><p>The stomach has been a highly conserved organ throughout vertebrate evolution; however, there are now over 20 lineages composed of monotremes, lungfish and teleost fish displaying a secondary loss of stomach function and morphology. This \"agastric phenotype\" has evolved convergently and is typified by a loss of gastric glands and gastric acid secretion and a near-to-complete loss of storage capacity of the stomach. All agastric species have lost the genes for gastric enzymes (<i>Pga</i> and <i>Pgc</i>) and proton pump subunits (<i>Atp4a</i> and <i>Atp4b</i>), and gastrin (<i>Gast</i>) has been lost in monotremes. As a key gastric hormone, the conservation of gastrin has not yet been investigated in the lungfish or agastric teleosts, and it is unclear how the loss of gastrin affects the evolution and selection of the native receptor (<i>Cckbr</i>), gastrin-releasing peptide (<i>Grp</i>) and gastrin-releasing peptide receptor (<i>Grpr</i>) in vertebrates. Furthermore, there are still many genes implicated in gastric development and function which have yet to be associated with the agastric phenotype. We analysed the evolution, selection and conservation of the gastrin pathway and a novel gastric gene repertoire (<i>Gkn1</i>, <i>Gkn2</i>, <i>Tff1</i>, <i>Tff2</i>, <i>Vsig1</i> and <i>Anxa10</i>) to determine the correlation with the agastric phenotype. We found that the loss of gastrin or its associated genes does not correlate with the agastric phenotype, and their conservation is due to multiple pleiotropic roles throughout vertebrate evolution. We found a loss of the gastric gene repertoire in the agastric phenotype, except in the echidna, which retained several genes (<i>Gkn1</i>, <i>Tff2</i> and <i>Vsig1</i>). Our findings suggest that the gastrin physiological pathway evolved differently in pleiotropic roles throughout vertebrate evolution and support the convergent evolution of the agastric phenotype through shared independent gene-loss events.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"13 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12372087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144956410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and Characterization of Static Craniofacial Defects in Pre-Metamorphic <i>Xenopus laevis</i> Tadpoles.","authors":"Emilie Jones, Jay Miguel Fonticella, Kelly A McLaughlin","doi":"10.3390/jdb13030026","DOIUrl":"10.3390/jdb13030026","url":null,"abstract":"<p><p>Craniofacial development is a complex, highly conserved process involving multiple tissue types and molecular pathways, with perturbations resulting in congenital defects that often require invasive surgical interventions to correct. Remarkably, some species, such as <i>Xenopus laevis</i>, can correct some craniofacial abnormalities during pre-metamorphic stages through thyroid hormone-independent mechanisms. However, the full scope of factors mediating remodeling initiation and coordination remain unclear. This study explores the differential remodeling responses of craniofacial defects by comparing the effects of two pharmacological agents, thioridazine-hydrochloride (thio) and ivermectin (IVM), on craniofacial morphology in <i>X. laevis</i>. Thio-exposure reliably induces a craniofacial defect that can remodel in pre-metamorphic animals, while IVM induces a permanent, non-correcting phenotype. We examined developmental changes from feeding stages to hindlimb bud stages and mapped the effects of each agent on the patterning of craniofacial tissue types including: cartilage, muscle, and nerves. Our findings reveal that thio-induced craniofacial defects exhibit significant consistent remodeling, particularly in muscle, with gene expression analysis revealing upregulation of key remodeling genes, <i>matrix metalloproteinases 1</i> and <i>13</i>, as well as their regulator, <i>prolactin.2</i>. In contrast, IVM-induced defects show no significant remodeling, highlighting the importance of specific molecular and cellular factors in pre-metamorphic craniofacial correction. Additionally, unique neuronal profiles suggest a previously underappreciated role for the nervous system in tissue remodeling. This study provides novel insights into the molecular and cellular mechanisms underlying craniofacial defect remodeling and lays the groundwork for future investigations into tissue repair in vertebrates.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"13 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12371963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144956474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deletion of <i>Ptpmt1</i> by <i>αMHC-Cre</i> in Mice Results in Left Ventricular Non-Compaction.","authors":"Lei Huang, Maowu Cao, Xiangbin Zhu, Na Li, Can Huang, Kunfu Ouyang, Ze'e Chen","doi":"10.3390/jdb13030025","DOIUrl":"10.3390/jdb13030025","url":null,"abstract":"<p><p><i>Background:</i> Left ventricular non-compaction cardiomyopathy (LVNC) is a congenital heart disease characterized by abnormal prenatal development of the left ventricle that has an aberrantly thick trabecular layer and a thinner compacted myocardial layer. However, the underlying molecular mechanisms of LVNC regulated by mitochondrial phosphatase genes remain largely unresolved. <i>Methods:</i> We generated a mouse model with cardiac-specific deletion (CKO) of <i>Ptpmt1</i>, a type of mitochondrial phosphatase gene, using the <i>αMHC-Cre</i>, and investigated the effects of cardiac-specific <i>Ptpmt1</i> deficiency on cardiac development. Morphological, histological, and immunofluorescent analyses were conducted in <i>Ptpmt1</i> CKO and littermate controls. A transcriptional atlas was identified by RNA sequencing (RNA-seq) analysis. <i>Results:</i> We found that CKO mice were born at the Mendelian ratio with normal body weights. However, most of the CKO mice died within 24 h after birth, developing spontaneous ventricular tachycardia. Morphological and histological analysis further revealed that newborn CKO mice developed an LVNC phenotype, evidenced by a thicker trabecular layer and a thinner myocardium layer, when compared with the littermate control. We then examined the embryonic hearts and found that such an LVNC phenotype could also be observed in CKO hearts at E15.5 but not at E13.5. We also performed the EdU incorporation assay and demonstrated that cardiac cell proliferation in both myocardium and trabecular layers was significantly reduced in CKO hearts at E15.5, which is also consistent with the dysregulation of genes associated with heart development and cardiomyocyte proliferation in CKO hearts at the same stage, as revealed by both the transcriptome analysis and the quantitative real-time PCR. Deletion of <i>Ptpmt1</i> in mouse cardiomyocytes also induced an increase in phosphorylated eIF2α and ATF4 levels, indicating a mitochondrial stress response in CKO hearts. <i>Conclusions:</i> Our results demonstrated that <i>Ptpmt1</i> may play an essential role in regulating left ventricular compaction during mouse heart development.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"13 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12286240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is <i>Hydra</i> Axis Definition a Fluctuation-Based Process Picking Up External Cues?","authors":"Mikhail A Zhukovsky, Si-Eun Sung, Albrecht Ott","doi":"10.3390/jdb13030024","DOIUrl":"10.3390/jdb13030024","url":null,"abstract":"<p><p>Axis definition plays a key role in the establishment of animal body plans, both in normal development and regeneration. The cnidarian <i>Hydra</i> can re-establish its simple body plan when regenerating from a random cell aggregate or a sufficiently small tissue fragment. At the beginning of regeneration, a hollow cellular spheroid forms, which then undergoes symmetry breaking and <i>de novo</i> body axis definition. In the past, we have published related work in a physics journal, which is difficult to read for scientists from other disciplines. Here, we review our work for readers not so familiar with this type of approach at a level that requires very little knowledge in mathematics. At the same time, we present a few aspects of <i>Hydra</i> biology that we believe to be linked to our work. These biological aspects may be of interest to physicists or members of related disciplines to better understand our approach. The proposed theoretical model is based on fluctuations of gene expression that are triggered by mechanical signaling, leading to increasingly large groups of cells acting in sync. With a single free parameter, the model quantitatively reproduces the experimentally observed expression pattern of the gene <i>ks1</i>, a marker for 'head forming potential'. We observed that <i>Hydra</i> positions its axis as a function of a weak temperature gradient, but in a non-intuitive way. Supposing that a large fluctuation including <i>ks1</i> expression is locked to define the head position, the model reproduces this behavior as well-without further changes. We explain why we believe that the proposed fluctuation-based symmetry breaking process agrees well with recent experimental findings where actin filament organization or anisotropic mechanical stimulation act as axis-positioning events. The model suggests that the <i>Hydra</i> spheroid exhibits huge sensitivity to external perturbations that will eventually position the axis.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":"13 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12286253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}