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The EMAP Digital Atlas of Mouse Development

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  • Targeting MYCN in Neuroblastoma by BET Bromodomain Inhibition

    Targeting MYCN in Neuroblastoma by BET Bromodomain Inhibition

    Published OnlineFirst February 21, 2013; DOI: 10.1158/2159-8290.CD-12-0418 RESEARCH ARTICLE Targeting MYCN in Neuroblastoma by BET Bromodomain Inhibition Alexandre Puissant1,3, Stacey M. Frumm1,3, Gabriela Alexe1,3,5,6, Christopher F. Bassil1,3, Jun Qi2, Yvan H. Chanthery8, Erin A. Nekritz8, Rhamy Zeid2, William Clay Gustafson8, Patricia Greninger7, Matthew J. Garnett10, Ultan McDermott10, Cyril H. Benes7, Andrew L. Kung1,3, William A. Weiss8,9, James E. Bradner2,4, and Kimberly Stegmaier1,3,6 Downloaded from cancerdiscovery.aacrjournals.org on October 2, 2021. © 2013 American Association for Cancer Research. 15-CD-12-0418_p308-323.indd 1 22/02/13 12:15 AM Published OnlineFirst February 21, 2013; DOI: 10.1158/2159-8290.CD-12-0418 A BSTRACT Bromodomain inhibition comprises a promising therapeutic strategy in cancer, particularly for hematologic malignancies. To date, however, genomic biomarkers to direct clinical translation have been lacking. We conducted a cell-based screen of genetically defined cancer cell lines using a prototypical inhibitor of BET bromodomains. Integration of genetic features with chemosensitivity data revealed a robust correlation between MYCN amplification and sensitivity to bromodomain inhibition. We characterized the mechanistic and translational significance of this finding in neuroblastoma, a childhood cancer with frequent amplification of MYCN. Genome-wide expression analysis showed downregulation of the MYCN transcriptional program accompanied by suppression of MYCN transcription. Functionally, bromodomain-mediated inhibition of MYCN impaired growth and induced apoptosis in neuroblastoma. BRD4 knockdown phenocopied these effects, establishing BET bromodomains as transcriptional regulators of MYCN. BET inhibition conferred a significant survival advantage in 3 in vivo neuroblastoma models, providing a compelling rationale for developing BET bro- modomain inhibitors in patients with neuroblastoma.
  • Bioinformatics Integrated Analysis to Investigate Candidate Biomarkers and Associated Metabolites in Osteosarcoma

    Bioinformatics Integrated Analysis to Investigate Candidate Biomarkers and Associated Metabolites in Osteosarcoma

    Wang et al. Journal of Orthopaedic Surgery and Research (2021) 16:432 https://doi.org/10.1186/s13018-021-02578-0 RESEARCH ARTICLE Open Access Bioinformatics integrated analysis to investigate candidate biomarkers and associated metabolites in osteosarcoma Jun Wang, Mingzhi Gong, Zhenggang Xiong, Yangyang Zhao and Deguo Xing* Abstract Background: This study hoped to explore the potential biomarkers and associated metabolites during osteosarcoma (OS) progression based on bioinformatics integrated analysis. Methods: Gene expression profiles of GSE28424, including 19 human OS cell lines (OS group) and 4 human normal long bone tissue samples (control group), were downloaded. The differentially expressed genes (DEGs) in OS vs. control were investigated. The enrichment investigation was performed based on DEGs, followed by protein–protein interaction network analysis. Then, the feature genes associated with OS were explored, followed by survival analysis to reveal prognostic genes. The qRT-PCR assay was performed to test the expression of these genes. Finally, the OS- associated metabolites and disease-metabolic network were further investigated. Results: Totally, 357 DEGs were revealed between the OS vs. control groups. These DEGs, such as CXCL12, were mainly involved in functions like leukocyte migration. Then, totally, 38 feature genes were explored, of which 8 genes showed significant associations with the survival of patients. High expression of CXCL12, CEBPA, SPARCL1, CAT, TUBA1A, and ALDH1A1 was associated with longer survival time, while high expression of CFLAR and STC2 was associated with poor survival. Finally, a disease-metabolic network was constructed with 25 nodes including two disease-associated metabolites cyclophosphamide and bisphenol A (BPA). BPA showed interactions with multiple prognosis-related genes, such as CXCL12 and STC2.
  • Os9) and the Hypoxia Response Gene, Hypoxia Inducible Factor 1 (Hif1) Alpha, in Kidney Tubular Cells

    Os9) and the Hypoxia Response Gene, Hypoxia Inducible Factor 1 (Hif1) Alpha, in Kidney Tubular Cells

    North Carolina Agricultural and Technical State University Aggie Digital Collections and Scholarship Theses Electronic Theses and Dissertations 2013 Meprin Interaction With Osteosarcoma 9 (Os9) And The Hypoxia Response Gene, Hypoxia Inducible Factor 1 (Hif1) Alpha, In Kidney Tubular Cells Barry L. Martin North Carolina Agricultural and Technical State University Follow this and additional works at: https://digital.library.ncat.edu/theses Recommended Citation Martin, Barry L., "Meprin Interaction With Osteosarcoma 9 (Os9) And The Hypoxia Response Gene, Hypoxia Inducible Factor 1 (Hif1) Alpha, In Kidney Tubular Cells" (2013). Theses. 287. https://digital.library.ncat.edu/theses/287 This Thesis is brought to you for free and open access by the Electronic Theses and Dissertations at Aggie Digital Collections and Scholarship. It has been accepted for inclusion in Theses by an authorized administrator of Aggie Digital Collections and Scholarship. For more information, please contact [email protected]. Meprin Interaction with Osteosarcoma 9 (OS9) and the Hypoxia Response Gene, Hypoxia- inducible Factor 1 (HIF1) Alpha, in Kidney Tubular Cells Barry L. Martin North Carolina A&T State University A thesis submitted to the graduate faculty in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE Department: Biology Major: Biology Major Professor: Dr. Elimelda Moige Ongeri Greensboro, North Carolina 2013 i School of Graduate Studies North Carolina Agricultural and Technical State University This is to certify that the Master’s Thesis of Barry L. Martin has met the thesis requirements of North Carolina Agricultural and Technical State University Greensboro, North Carolina 2013 Approved by: Elimelda Moige Ongeri, PhD Jian Han, PhD Major Professor Committee Member Catherine White, PhD Scott Harrison, PhD Committee Member Committee Member Mary Smith, PhD Sanjiv Sarin, PhD Department Chair Dean, The Graduate School ii © Copyright by Barry L.
  • A Genome-Wide Association Study

    A Genome-Wide Association Study

    ISSN (Online) 2287-3406 Journal of Life Science 2021 Vol. 31. No. 6. 568~573 DOI : https://doi.org/10.5352/JLS.2021.31.6.568 - Note - The Association of Long Noncoding RNA LOC105372577 with Endoplasmic Reticulum Protein 29 Expression: A Genome-wide Association Study Soyeon Lee1, Kiang Kwon2, Younghwa Ko3 and O-Yu Kwon3* 1School of Systems Biomedical Science, College of Natural Sciences, Soongsil University, Seoul 06978, Korea 2Department of Clinical Laboratory Science, Wonkwang Health Science University, Iksan 54538, Korea 3Department of Anatomy & Cell Biology, College of Medicine, Chungnam National University, Daejeon 35015, Korea Received April 27, 2021 /Revised April 29, 2021 /Accepted April 30, 2021 This study identified genomic factors associated with endoplasmic reticulum protein (ERp)29 gene ex- pression in a genome-wide association study (GWAS) of genetic variants, including single-nucleotide polymorphisms (SNPs). In total, 373 European genes from the 1000 Genomes Project were analyzed. SNPs with an allelic frequency of less than or more than 5% were removed, resulting in 5,913,563 SNPs including in the analysis. The following expression quantitative trait loci (eQTL) from the long noncoding RNA LOC105372577 were strongly associated with ERp29 expression: rs6138266 (p<4.172e10), rs62193420 (p<1.173e10), and rs6138267 (p<2.041e10). These were strongly expressed in the testis and in the brain. The three eQTL were identified through a transcriptome-wide association study (TWAS) and showed a significant association with ERp29 and osteosarcoma amplified 9 (OS9) expression. Upstream sequences of rs6138266 were recognized by ChIP-seq data, while HaploReg was used to demonstrate how its regulatory DNA binds upstream of transcription factor 1 (USF1).
  • Embryo Makes Contact with the Endometrial Lining of the Uterus

    Embryo Makes Contact with the Endometrial Lining of the Uterus

    Week 1 • Week 1 - Early zygote • Stage 1 starts at the beginning of • Week 1 Carnegie stage – 1,2,3,4, fertilization • Fertilization • Stage 2 begins with the division • of the zygote into two cells and Zygote ends with the appearance of the • Morula blastocystic cavity • Blastocyst • Stage 3 begins when the blastocystic cavity first appears in the morula and ends when the zona (capsula) pellucida is shed as the embryo makes contact with the endometrial lining of the uterus. • Stage 4 is reserved for the attaching blastocyst to the endometrial lining Week 2 • Week 2 Implantation • Stage 5 Two distinct layers • Week 2 Carnegie stage -5,6 are evident in the • Trophoblast - outer cell trophoblast; 1) a thicker layer outer layer without cell boundaries, called the • Embryoblast - inner cell syncytiotrophoblast and 2) mass a thinner inner layer with • Implantation cell boundaries called the • Bilaminar embryo cytotrophoblast. • Stage 6 the first appearance of chorionic villi. Week 3 • • Stage 7 the presomite • Week 3 - Embryonic disc period and well defined • Week 3 - Carnegie stage – embryonic disc appearance 7,8, &9 of the notochordal process and the gastrulation • Gastrulation (primitive) node. • Notochord formation • Trilaminar embryo • Mesoderm • Somitogenesis • Neurogenesis Week 4 • The heart begins • Week 4 - Carnegie stage -10,11,12 &13 • Heart • Placodes • Pharyngeal arches • Week 5 • Week 7 - Head and limb • Carnegie stages stage 14 development stage 15 • Carnegie stages stage 18 • stage 19 • Week 6 - Early face • Week 8 deevelopment • Last embryonic stage • Carnegie stages Carnegie stage – 20 21 22 • Week 6 - Carnegie stage 16 &23 & 17 • Last week of embryonic development.
  • Early Embryonic Development Till Gastrulation (Humans)

    Early Embryonic Development Till Gastrulation (Humans)

    Gargi College Subject: Comparative Anatomy and Developmental Biology Class: Life Sciences 2 SEM Teacher: Dr Swati Bajaj Date: 17/3/2020 Time: 2:00 pm to 3:00 pm EARLY EMBRYONIC DEVELOPMENT TILL GASTRULATION (HUMANS) CLEAVAGE: Cleavage in mammalian eggs are among the slowest in the animal kingdom, taking place some 12-24 hours apart. The first cleavage occurs along the journey of the embryo from oviduct toward the uterus. Several features distinguish mammalian cleavage: 1. Rotational cleavage: the first cleavage is normal meridional division; however, in the second cleavage, one of the two blastomeres divides meridionally and the other divides equatorially. 2. Mammalian blastomeres do not all divide at the same time. Thus the embryo frequently contains odd numbers of cells. 3. The mammalian genome is activated during early cleavage and zygotically transcribed proteins are necessary for cleavage and development. (In humans, the zygotic genes are activated around 8 cell stage) 4. Compaction: Until the eight-cell stage, they form a loosely arranged clump. Following the third cleavage, cell adhesion proteins such as E-cadherin become expressed, and the blastomeres huddle together and form a compact ball of cells. Blatocyst: The descendents of the large group of external cells of Morula become trophoblast (trophoblast produce no embryonic structure but rather form tissues of chorion, extraembryonic membrane and portion of placenta) whereas the small group internal cells give rise to Inner Cell mass (ICM), (which will give rise to embryo proper). During the process of cavitation, the trophoblast cells secrete fluid into the Morula to create blastocoel. As the blastocoel expands, the inner cell mass become positioned on one side of the ring of trophoblast cells, resulting in the distinctive mammalian blastocyst.
  • Cultured Human Pre-Gastrulation Embryos

    Cultured Human Pre-Gastrulation Embryos

    Protocol for a developmental landscape of 3D- cultured human pre-gastrulation embryos Lifeng Xiang Yunnan Key Laboratory of Primate Biomedical Research; Institute of Primate Translational Medicine, Kunming University of Science and Technology Yu Yin Yunnan Key Laboratory of Primate Biomedical Research; Institute of Primate Translational Medicine, Kunming University of Science and Technology Tianqing Li ( [email protected] ) Yunnan Key Laboratory of Primate Biomedical Research; Institute of Primate Translational Medicine, Kunming University of Science and Technology Method Article Keywords: Human pre-gastrulation embryo, three-dimensional (3D) culture, primitive streak anlage, immunouorescence imaging, single cell RNA-seq Posted Date: December 12th, 2019 DOI: https://doi.org/10.21203/rs.2.16169/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 1/9 Abstract Human embryogenesis is not well understood. Knowledge detailing human pre-gastrulation embryonic development including spatial self-organization and cell type ontogeny remains limited by available two- dimensional technological platforms. Here, we present a three-dimensional (3D) blastocyst-culture system, which enables human blastocyst development through primitive streak anlage (PSA). By the 3D- platform combined with immunouorescence imaging and single-cell RNA-Seq, we reveal a developmental landscape of human pre-gastrulation embryos. Our protocol allows recording and analysis of embryo developmental landmarks and mechanisms from human blastocysts to pre- gastrulation stage (day 14 post- fertilization). Introduction Early human embryogenesis, such as architecture formation and cell type specication, is obscure owing to technical challenge and unavailable materials. Recent in vitro implantation platforms using a two- dimensional (2D) culture approach have revealed some developmental landmarks of in vivo early human embryos1,2.
  • Fresh Blastocyst Embryo Transfer Is Superior to Morula Embryo Transfer in Young Patients Undergoing in Vitro Fertilization

    Fresh Blastocyst Embryo Transfer Is Superior to Morula Embryo Transfer in Young Patients Undergoing in Vitro Fertilization

    Open Access Austin Journal of Reproductive Medicine & Infertility Research Article Fresh Blastocyst Embryo Transfer is Superior to Morula Embryo Transfer in Young Patients Undergoing in Vitro Fertilization Malik S1, Balassiano E1, Hobeika E1, Knochenhauer ES1,2 and Traub ML1,2* Abstract 1 Department of Obstetrics and Gynecology, Staten Island Objective: To determine if blastocyst embryo transfer yields better University Hospital, USA, 475 Seaview Avenue, Staten pregnancy outcomes compared to morula embryo transfer for fresh and frozen Island, NY, USA cycles and in donor oocyte recipients. 2Island Reproductive Services, USA, 1110 South Avenue, Suite 305, Staten Island, NY, USA Study Design: Retrospective cohort of patients undergoing in vitro fertilization at a single center. Fresh, frozen, and donor egg recipient cycles *Corresponding author: Traub ML, Department of between January 1, 2008 and December 31, 2012 were studied. Patients were Obstetrics and Gynecology, Staten Island University excluded if they were considered poor prognosis and underwent day 3 embryo Hospital, Island Reproductive Services, USA transfers. Received: April 16, 2015; Accepted: June 29, 2015; Results: In patients under age 35 undergoing fresh IVF cycle, implantation Published: June 30, 2015 rates (52% v 29%, p<0.01), clinical pregnancy rates (63% v 38%, p=0.001), and live birth rates (54% v 33%, p<0.01) were all higher after blastocyst embryo transfer. No differences were seen in other SART age groups during fresh IVF. For patients undergoing FET and in donor oocyte recipients, no differences in any pregnancy outcome were between blastocyst and morula embryo transfer. Conclusions: Blastocyst embryo transfer was found to improve pregnancy outcomes in young patients undergoing fresh IVF.
  • Human Development Summary

    Human Development Summary

    Human Development Laboratory Activity Gametogenesis Male The sperm develop within the highly coiled seminiferous tubules of the testes. When the sperm are fully mature they are extremely small, being little more than a bag of genetic material with a tail. The head of the sperm oell contains the nucleus and little else. The tail consists of a flagellum which allows the sperm to swim through the female reproductive tract to the egg. Female The egg is one of the largest cells in the body. As the egg ripens in the ovary it accumulates yolk which will serve as food for the young embryo until the placenta and umbilical cord are fully functional. Egg development is acomplished with the help of special nurse cells called follicle cells. When the egg is fully formed it bursts from the ovary in a process called ovulation. Ovulation is governed by complex nervous and hormonaI controls. After the egg is released from the ovary it enters the oviduct. Embryonic Development Fertilization Fertilization takes place in the fallopian tubes or oviducts. Although thousands of sperm cells may complete the trip to the egg only one will penetrate the cells outermost membrane and fertilize it. From this point on the egg is referred to as a zygote. Cleavage Divisions Almost as soon as the egg is fertilized it begins to divide. First into two cells, then 4, then 8 and so on. These divisions produce a solid clump of 32-64 cells called the morula. Blastocyst The morula continues its trip down the oviduct to the uterus.
  • A New Model for Human Blastocyst Development

    A New Model for Human Blastocyst Development

    Signal Transduction and Targeted Therapy www.nature.com/sigtrans RESEARCH HIGHLIGHT OPEN Blastoids: a new model for human blastocyst development Heiner Niemann1 and Bob Seamark2 Signal Transduction and Targeted Therapy (2021) 6:239; https://doi.org/10.1038/s41392-021-00663-8 Recently, two research groups report in Nature1,2 the ex-vivo and neither has yet been sufficiently disclosed for full assesment of production of blastocyst-like structures, called blastoids, that the blastoids. Given the specific embyo culture procedures required, exhibit many of the landmarks in human early development found the epigenetic status of the blastoids is of particular interest. in viable blastocysts (Fig. 1). Numerous studies have shown that in vitro culture of early embryos The formation of a blastocyst is a critical step in early embryo can profoundly affect normal patterns of DNA methylation, resulting development denoting a key change from the early cleavage stages in deviations from the physiological gene expression patterns.4 to gastrulation. Typically, the blastocyst, differentiated from the early Following fertilisation, the parental genomes undergo a wave of de- cleavage stages, is a fluid filled vesicular structure comprised of cells and re-methylation, during early embryogenesis, creating the of now, three distinct cell lineages, namely those of the trophoblast, methylation patterns, needed for normal development, through the outer enclosing cell layer, and those of the inner cell mass (ICM) the activation and silencing of specific genes. Typically, global with the hypoblast and epiblast, found in the central fluid filled methylation of the mammalian genome declines to a nadir at the cavity (the blastocoel).