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Multistage Analysis of Variants in the Inflammation Pathway and Lung Cancer Risk in Smokers
Published OnlineFirst May 9, 2012; DOI: 10.1158/1055-9965.EPI-12-0352-T Cancer Epidemiology, Research Article Biomarkers & Prevention Multistage Analysis of Variants in the Inflammation Pathway and Lung Cancer Risk in Smokers Margaret R. Spitz1, Ivan P. Gorlov2, Qiong Dong3, Xifeng Wu3, Wei Chen4, David W. Chang3, Carol J. Etzel3, Neil E. Caporaso5, Yang Zhao8, David C. Christiani8, Paul Brennan9, Demetrius Albanes7, Jianxin Shi6, Michael Thun10, Maria Teresa Landi5, and Christopher I. Amos4 Abstract Background: Tobacco-induced lung cancer is characterized by a deregulated inflammatory microenviron- ment. Variants in multiple genes in inflammation pathways may contribute to risk of lung cancer. Methods: We therefore conducted a three-stage comprehensive pathway analysis (discovery, replication, and meta-analysis) of inflammation gene variants in ever-smoking lung cancer cases and controls. A discovery set (1,096 cases and 727 controls) and an independent and nonoverlapping internal replication set (1,154 cases and 1,137 controls) were derived from an ongoing case–control study. For discovery, we used an iSelect BeadChip to interrogate a comprehensive panel of 11,737 inflammation pathway single-nucleotide poly- morphisms (SNP) and selected nominally significant (P < 0.05) SNPs for internal replication. Results: There were six SNPs that achieved statistical significance (P < 0.05) in the internal replication data set with concordant risk estimates for former smokers and five concordant and replicated SNPs in current smokers. Replicated hits were further tested in a subsequent meta-analysis using external data derived from two published genome-wide association studies (GWAS) and a case–control study. Two of these variants (a BCL2L14 SNP in former smokers and an SNP in IL2RB in current smokers) were further validated. -
Supplementary Materials: Evaluation of Cytotoxicity and Α-Glucosidase Inhibitory Activity of Amide and Polyamino-Derivatives of Lupane Triterpenoids
Supplementary Materials: Evaluation of cytotoxicity and α-glucosidase inhibitory activity of amide and polyamino-derivatives of lupane triterpenoids Oxana B. Kazakova1*, Gul'nara V. Giniyatullina1, Akhat G. Mustafin1, Denis A. Babkov2, Elena V. Sokolova2, Alexander A. Spasov2* 1Ufa Institute of Chemistry of the Ufa Federal Research Centre of the Russian Academy of Sciences, 71, pr. Oktyabrya, 450054 Ufa, Russian Federation 2Scientific Center for Innovative Drugs, Volgograd State Medical University, Novorossiyskaya st. 39, Volgograd 400087, Russian Federation Correspondence Prof. Dr. Oxana B. Kazakova Ufa Institute of Chemistry of the Ufa Federal Research Centre of the Russian Academy of Sciences 71 Prospeсt Oktyabrya Ufa, 450054 Russian Federation E-mail: [email protected] Prof. Dr. Alexander A. Spasov Scientific Center for Innovative Drugs of the Volgograd State Medical University 39 Novorossiyskaya st. Volgograd, 400087 Russian Federation E-mail: [email protected] Figure S1. 1H and 13C of compound 2. H NH N H O H O H 2 2 Figure S2. 1H and 13C of compound 4. NH2 O H O H CH3 O O H H3C O H 4 3 Figure S3. Anticancer screening data of compound 2 at single dose assay 4 Figure S4. Anticancer screening data of compound 7 at single dose assay 5 Figure S5. Anticancer screening data of compound 8 at single dose assay 6 Figure S6. Anticancer screening data of compound 9 at single dose assay 7 Figure S7. Anticancer screening data of compound 12 at single dose assay 8 Figure S8. Anticancer screening data of compound 13 at single dose assay 9 Figure S9. Anticancer screening data of compound 14 at single dose assay 10 Figure S10. -
Effects of Stressors on Differential Gene Expression And
EFFECTS OF STRESSORS ON DIFFERENTIAL GENE EXPRESSION AND SECONDARY METABOLITES BY AXINELLA CORRUGATA by Jennifer Grima A Thesis Submitted to the Faculty of Charles E. Schmidt College of Science in Partial Fulfillment of the Requirements for the Degree of Master of Science Florida Atlantic University Boca Raton, Florida May 2013 ACKNOWLEDGEMENTS This thesis was made possible by the help and support of my mentors and friends. Without their guidance and expertise, I would not have been able to accomplish all that I have. Their belief and encouragement in my efforts have motivated and inspired me along through this journey and into a new era in my life. First and foremost, I am grateful to Dr. Shirley Pomponi for taking on the role as my advisor and giving me the opportunity to experience life as a researcher. Not only has she guided me in my scientific studies, she has become a wonderful, lifelong friend. Dr. Pomponi and Dr. Amy Wright have also provided financial support that enabled me to conduct the research and complete this thesis. I would also like to acknowledge Dr. Amy Wright for her willingness to tender advice on all things chemistry related as well as providing me with the space, equipment, and supplies to conduct the chemical analyses. I am grateful to Dr. Esther Guzman who not only served as a committee member, but has also been readily available to help me in any endeavor, whether it be research or personal related. She is truly one of kind with her breadth of knowledge in research and her loyal and caring character. -
DNA·RNA Triple Helix Formation Can Function As a Cis-Acting Regulatory
DNA·RNA triple helix formation can function as a cis-acting regulatory mechanism at the human β-globin locus Zhuo Zhoua, Keith E. Gilesa,b,c, and Gary Felsenfelda,1 aLaboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892; bUniversity of Alabama at Birmingham Stem Cell Institute, University of Alabama at Birmingham, Birmingham, AL 35294; and cDepartment of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35294 Contributed by Gary Felsenfeld, February 4, 2019 (sent for review January 4, 2019; reviewed by James Douglas Engel and Sergei M. Mirkin) We have identified regulatory mechanisms in which an RNA tran- of the criteria necessary to establish the presence of a triplex script forms a DNA duplex·RNA triple helix with a gene or one of its structure, we first describe and characterize triplex formation at regulatory elements, suggesting potential auto-regulatory mecha- the FAU gene in human erythroid K562 cells. FAU encodes a nisms in vivo. We describe an interaction at the human β-globin protein that is a fusion containing fubi, a ubiquitin-like protein, locus, in which an RNA segment embedded in the second intron of and ribosomal protein S30. Although fubi function is unknown, the β-globin gene forms a DNA·RNA triplex with the HS2 sequence posttranslational processing produces S30, a component of the within the β-globin locus control region, a major regulator of glo- 40S ribosome. We used this system to refine methods necessary bin expression. We show in human K562 cells that the triplex is to detect triplex formation and to distinguish it from R-loop stable in vivo. -
Genes with 5' Terminal Oligopyrimidine Tracts Preferentially Escape Global Suppression of Translation by the SARS-Cov-2 NSP1 Protein
Downloaded from rnajournal.cshlp.org on September 28, 2021 - Published by Cold Spring Harbor Laboratory Press Genes with 5′ terminal oligopyrimidine tracts preferentially escape global suppression of translation by the SARS-CoV-2 Nsp1 protein Shilpa Raoa, Ian Hoskinsa, Tori Tonna, P. Daniela Garciaa, Hakan Ozadama, Elif Sarinay Cenika, Can Cenika,1 a Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA 1Corresponding author: [email protected] Key words: SARS-CoV-2, Nsp1, MeTAFlow, translation, ribosome profiling, RNA-Seq, 5′ TOP, Ribo-Seq, gene expression 1 Downloaded from rnajournal.cshlp.org on September 28, 2021 - Published by Cold Spring Harbor Laboratory Press Abstract Viruses rely on the host translation machinery to synthesize their own proteins. Consequently, they have evolved varied mechanisms to co-opt host translation for their survival. SARS-CoV-2 relies on a non-structural protein, Nsp1, for shutting down host translation. However, it is currently unknown how viral proteins and host factors critical for viral replication can escape a global shutdown of host translation. Here, using a novel FACS-based assay called MeTAFlow, we report a dose-dependent reduction in both nascent protein synthesis and mRNA abundance in cells expressing Nsp1. We perform RNA-Seq and matched ribosome profiling experiments to identify gene-specific changes both at the mRNA expression and translation level. We discover that a functionally-coherent subset of human genes are preferentially translated in the context of Nsp1 expression. These genes include the translation machinery components, RNA binding proteins, and others important for viral pathogenicity. Importantly, we uncovered a remarkable enrichment of 5′ terminal oligo-pyrimidine (TOP) tracts among preferentially translated genes. -
UNDERGRADUATE RESEARCH SYMPOSIUM 03.31.17 March 31St, 2017
Sev ent h Annu a l UNDERGRADUATE RESEARCH SYMPOSIUM 03.31.17 March 31st, 2017 Live Oak Pavilion and Grand Palm Room Boca Raton Campus WELCOME Welcome to the 7th Annual Undergraduate Research Sym- posium, which showcases undergraduate students at FAU who are engaged in research, scholarship and creative ac- tivities. Students present their findings through poster or visual and oral or performing arts presentations, and rep- resent all disciplines, all colleges, and all campuses of FAU. Few activities are as rewarding intellectually as research and inquiry. In addition to the acquisition of invaluable re- search skills, students learn how knowledge is created and how that knowledge can be overturned with new evidence or new perspectives. Such scholarly activities engage stu- dents in working independently, overcoming obstacles, and learning the importance of ethics and personal conduct in the research process. The Office of Undergraduate Research and Inquiry (OURI) serves as a centralized support office of both faculty and students who are engaged in undergraduate research and inquiry. We offer and support university wide programs such as undergraduate research grants, annual undergraduate research symposia, and undergraduate research journals, to name a few. We also support all departments and all col- leges across all campuses in their undergraduate research and inquiry initiatives. The Undergraduate Research Symposium is part of our University’s Quality Enhancement Plan (QEP) efforts aimed at expanding a culture of undergraduate research -
Lorena Novoa-Aponte
A Strain: fl/fl ∆hep Strain: fl/fl ∆hep AnalysisAAV: ofLuc the ironLuc chaperonePCBP1-WT PCBP1PCBP1-∆Fe interactome:PCBP1-∆RNA PCBP1 variant intersection of DNA repair and iron traffickingAAV: Luc Luc WT ∆Fe ∆RNA PCBP1 −40 Lorena Novoa-Aponte a*, Sarju J. Patel a, Olga Protchenko a, James Wohlschlegel b, Caroline C. Philpott a −40 PCBP1, IHC PCBP1, GAPDH - a Genetics and Metabolism Section,a NIDDK, NIH, Bethesda, MD, USA. b Department of Biological Chemistry, UCLA, Los Angeles, CA, USA C.C. Philpott, et al. *[email protected] 80 B P = 0.0262 60 40 1. Iron is essential but toxic 2. Increased DNA damage in cells lacking PCBP1 ns H&E ? + 20 C.C. Philpott, et al. Iron is used as an essential cofactor by several enzymes involved in DNA ⦿ Increased TUNEL in cells and tissue livers from mice lacking PCBP1. ? replication and repair. However, unchaperoned iron promotes redox ⦿ PCBP1 binds both, iron and single-stranded nucleicTG, nmol/mg protein 0 acids. stress that may affect DNA stability. Strain: Δhep Δhep Δhep ? ⦿ The iron binding activity of PCBP1 controls suppressionAAV: of DNA damage C WT ∆Fe ∆RNA PCBP1 variant ? Iron storage HEK293 cells Mouse Liver ? A 8 siNT+P1var 100 ? A 8 var siPCBP1 2 ? Mammals use the iron siNT+P1 ns var Fe-S cluster assembly 6 siPCBP1+P1siPCBP1 80 ADI1 TUNEL chaperone PCBP1 to var ? 6 siPCBP1+P1 metalate several iron- 60 = 0.0468 = 0.0354 = 0.0465 cell / mm population P P P population + dependent enzymes + 4 + 4 ? 40 Degradation of HIF1α Fig. 3. Iron chaperone-mediated handling of cytosolic labile iron pool. -
A 14.8 Mb 12P Deletion Disrupting ETV6 in a Patient with Myelodysplastic Syndrome
tics: Cu ne rr e en G t y R r e a t s i e d a e r r c e h Valetto et al., Hereditary Genet 2017, 6:1 H Hereditary Genetics DOI: 10.4172/2161-1041.1000174 ISSN: 2161-1041 Research Article Open Access A 14.8 Mb 12p Deletion Disrupting ETV6 in a Patient with Myelodysplastic Syndrome Angelo Valetto 1*, Veronica Bertini1, Elena Ciabatti2,3, Maria Immacolata Ferreri1, Alice Guazzelli1, Antonio Azzarà2, Susanna Grassi2, Alessia Azzarà1, Francesca Guerrini2, Iacopo Petrini2,4 and Sara Galimberti2 1Laboratory of Medical Genetics, A.O.U.P., S. Chiara Hospital, Pisa, Italy 2Department of Clinical and Experimental Medicine, Section of Hematology, University of Pisa, Pisa, Italy 3GenOMeC, University of Siena 4Department of translational Research and New Technologies in Medicine, University of Pisa, Pisa, Italy *Corresponding author: Valetto A, Laboratory of Medical Genetics, A.O.U.P., S. Chiara Hospital, Pisa, Italy, Tel: +39050992777; E-mail: [email protected] Received Date: Oct 27, 2016; Accepted Date: Mar 16, 2017; Published Date: Mar 21, 2017 Copyright: © 2017 Valetto A, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract We present on a new case of myelodysplastic syndrome characterized by array Comparative Genomic Hybridization. This technique confirmed the monosomy 7, detected by conventional cytogenetics, and revealed also a deletion on the short arm of chromosome 12. This deletion extends for about 14.8 Mb and breaks ETV6 gene. -
Transcriptomic and Epigenomic Characterization of the Developing Bat Wing
ARTICLES OPEN Transcriptomic and epigenomic characterization of the developing bat wing Walter L Eckalbar1,2,9, Stephen A Schlebusch3,9, Mandy K Mason3, Zoe Gill3, Ash V Parker3, Betty M Booker1,2, Sierra Nishizaki1,2, Christiane Muswamba-Nday3, Elizabeth Terhune4,5, Kimberly A Nevonen4, Nadja Makki1,2, Tara Friedrich2,6, Julia E VanderMeer1,2, Katherine S Pollard2,6,7, Lucia Carbone4,8, Jeff D Wall2,7, Nicola Illing3 & Nadav Ahituv1,2 Bats are the only mammals capable of powered flight, but little is known about the genetic determinants that shape their wings. Here we generated a genome for Miniopterus natalensis and performed RNA-seq and ChIP-seq (H3K27ac and H3K27me3) analyses on its developing forelimb and hindlimb autopods at sequential embryonic stages to decipher the molecular events that underlie bat wing development. Over 7,000 genes and several long noncoding RNAs, including Tbx5-as1 and Hottip, were differentially expressed between forelimb and hindlimb, and across different stages. ChIP-seq analysis identified thousands of regions that are differentially modified in forelimb and hindlimb. Comparative genomics found 2,796 bat-accelerated regions within H3K27ac peaks, several of which cluster near limb-associated genes. Pathway analyses highlighted multiple ribosomal proteins and known limb patterning signaling pathways as differentially regulated and implicated increased forelimb mesenchymal condensation in differential growth. In combination, our work outlines multiple genetic components that likely contribute to bat wing formation, providing insights into this morphological innovation. The order Chiroptera, commonly known as bats, is the only group of To characterize the genetic differences that underlie divergence in mammals to have evolved the capability of flight. -
Research Article Sex Difference of Ribosome in Stroke-Induced Peripheral Immunosuppression by Integrated Bioinformatics Analysis
Hindawi BioMed Research International Volume 2020, Article ID 3650935, 15 pages https://doi.org/10.1155/2020/3650935 Research Article Sex Difference of Ribosome in Stroke-Induced Peripheral Immunosuppression by Integrated Bioinformatics Analysis Jian-Qin Xie ,1,2,3 Ya-Peng Lu ,1,3 Hong-Li Sun ,1,3 Li-Na Gao ,2,3 Pei-Pei Song ,2,3 Zhi-Jun Feng ,3 and Chong-Ge You 2,3 1Department of Anesthesiology, Lanzhou University Second Hospital, Lanzhou, Gansu 730030, China 2Laboratory Medicine Center, Lanzhou University Second Hospital, Lanzhou, Gansu 730030, China 3The Second Clinical Medical College of Lanzhou University, Lanzhou, Gansu 730030, China Correspondence should be addressed to Chong-Ge You; [email protected] Received 13 April 2020; Revised 8 October 2020; Accepted 18 November 2020; Published 3 December 2020 Academic Editor: Rudolf K. Braun Copyright © 2020 Jian-Qin Xie et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Ischemic stroke (IS) greatly threatens human health resulting in high mortality and substantial loss of function. Recent studies have shown that the outcome of IS has sex specific, but its mechanism is still unclear. This study is aimed at identifying the sexually dimorphic to peripheral immune response in IS progression, predicting potential prognostic biomarkers that can lead to sex- specific outcome, and revealing potential treatment targets. Gene expression dataset GSE37587, including 68 peripheral whole blood samples which were collected within 24 hours from known onset of symptom and again at 24-48 hours after onset (20 women and 14 men), was downloaded from the Gene Expression Omnibus (GEO) datasets. -
A New Tool to Probe Protein Synthesis in Human Cells Through Capture and Identification of the Eif4e-Mrna Interactome
bioRxiv preprint doi: https://doi.org/10.1101/2020.04.18.047571; this version posted April 18, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. capCLIP: a new tool to probe protein synthesis in human cells through capture and identification of the eIF4E-mRNA interactome. Kirk B. Jensen,1,2,* B. Kate Dredge,3 John Toubia,3,4 Xin Jin,1,5 Valentina Iadevaia,6 Gregory J. Goodall3,7 and Christopher G. Proud1,2 1Lifelong Health, South Australian Health & Medical Research Institute, North Terrace, Adelaide 5000, Australia 2School of Biological Sciences, Faculty of Sciences, University of Adelaide, Adelaide 5005, Australia 3Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA 5000, Australia 4ACRF Cancer Genomics Facility, Centre for Cancer Biology, SA Pathology and University of South Australia, Frome Road, Adelaide SA 5000, Australia 5School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao, China; 6School of Biosciences and Medicine, University of Surrey, Guildford, Surrey GU2 7XH, United Kingdom. 7Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide 5005, Australia * Corresponding author: telephone +61 8 8128 4908; [email protected] 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.04.18.047571; this version posted April 18, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract Translation initiation of eukaryotic mRNAs commences with recognition of the m7G cap by the cap- binding protein eIF4E and the subsequent recruitment of additional translation initiation factors to the mRNA’s 5′ end. -
Global Analysis of LARP1 Translation Targets Reveals Tunable and Dynamic Features of 5′ TOP Motifs
Global analysis of LARP1 translation targets reveals tunable and dynamic features of 5′ TOP motifs Lucas Philippea,1, Antonia M. G. van den Elzena,1, Maegan J. Watsona, and Carson C. Thoreena,2 aDepartment of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, CT 06510 Edited by Alan G. Hinnebusch, National Institutes of Health, Bethesda, MD, and approved January 29, 2020 (received for review July 25, 2019) Terminal oligopyrimidine (TOP) motifs are sequences at the 5′ ends recent findings have hinted that the RNA-binding protein La- of mRNAs that link their translation to the mTOR Complex 1 related protein 1 (LARP1) may have a central role (8–10). (mTORC1) nutrient-sensing signaling pathway. They are com- LARP1 is a large protein (150 kDa) with several RNA-binding monly regarded as discrete elements that reside on ∼100 mRNAs domains. Its central region contains a La motif (LaM) domain that mostly encode translation factors. However, the full spectrum that defines the La-related protein (LARP) superfamily, along of TOP sequences and their prevalence throughout the transcrip- with an adjacent RNA recognition motif-like (RRM-L) domain. tome remain unclear, primarily because of uncertainty over the Its C terminus encodes a domain known as the DM15 region. This mechanism that detects them. Here, we globally analyzed trans- domain is unique to LARP1 and its closely related homolog lation targets of La-related protein 1 (LARP1), an RNA-binding pro- LARP1B, and is therefore also known as the LARP1 domain (11). tein and mTORC1 effector that has been shown to repress TOP Several observations suggest that LARP1 directly represses TOP mRNA translation in a few specific cases.