Network Analysis of Chip-Seq Data Reveals Key Genes in Prostate Cancer Yu Zhang1,2*, Zhen Huang2, Zhiqiang Zhu2, Jianwei Liu2, Xin Zheng2 and Yuhai Zhang1*
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Epstein-Barr Virus Viral Protein Lmp1 Increases Rap1
EPSTEIN-BARR VIRUS VIRAL PROTEIN LMP1 INCREASES RAP1 SUMOYLATION, ENHANCING TELOMERE MAINTENANCE DURING TUMORIGENESIS By WYATT TYLER CRAMBLET B.S., Biology, Gordon State College, 2016 A Thesis Submitted to the Faculty of Mercer University School of Medicine in Partial Fulfillment of the Requirements for the Degree MASTER OF SCIENCE IN BIOMEDICAL SCIENCE Macon, GA 2018 EPSTEIN-BARR VIRUS VIRAL PROTEIN LMP1 INCREASES RAP1 SUMOYLATION, ENHANCING TELOMERE MAINTENANCE DURING TUMORIGENESIS By WYATT TYLER CRAMBLET Approved: ___________________________________________ Date _________ Gretchen L. Bentz, Ph.D. Faculty Advisor for Thesis ___________________________________________ Date _________ Richard O. McCann, Ph.D. Thesis Committee Member ___________________________________________ Date _________ Laura Silo-Suh, Ph.D. Thesis Committee Member ___________________________________________ Date _________ Jon Shuman, Ph.D. Thesis Committee Member ___________________________________________ Date _________ Jean Sumner, MD Dean, Mercer University School of Medicine ACKNOWLEDGEMENTS I would like to thank the National Institutes of Health for providing the funding for this project and Mercer University School of Medicine for the opportunity for discovery and knowledge this experience has provided me. My utmost respect and gratitude goes to Dr. Gretchen Bentz. Along the course of my research Dr. Bentz has always provided what I required to be successful: materials, focus, experience, and understanding. Her guidance at both the lab and the writing desk is what has allowed me to accomplish the greatest achievement of my academic career. I thank Dr. Richard McCann and Dr. Christy Bridges who have been the Directors of the Master of Science Biomedical Sciences Program. Their leadership has been invaluable to my peers and me for becoming the professionals we set out to be. -
Specialissue
IMPACT FACTOR 4.096 an Open Access Journal by MDPI Genetic Regulation in Iron Homeostasis Guest Editor: Message from the Guest Editor Prof. Dr. Paweł Lipiński Iron is an essential cofactor for biological processes, since Department of Molecular Biology, it participates in multiple enzymatic reactions as a part of Institute of Genetics and Animal Biotechnology, Polish Academy iron–sulfur clusters, heme prosthetic groups, and other of Sciences, Jastrzębiec, 05-552 iron-containing centers. However, the propensity of iron to Magdalenka, Poland generate reactive free radicals through the Fenton reaction [email protected] makes this biometal a doubled-edged sword in a biological oxygen environment. Since there is no natural pathway for excreting excess iron from the organism, systemic iron homeostasis must be very tightly controlled. Deadline for manuscript submissions: Over the past twenty years, our understanding of iron closed (20 June 2021) metabolism has increased exponentially. Genetic studies of patients with inherited iron homeostasis disorders and the analysis of genetically modified laboratory animals have contributed to the identification of several new genes important in cellular and systemic iron homeostasis, and their roles have been intensively investigated. Nevertheless, despite such progress in the field of iron biology, our view of cellular and systemic iron metabolism is far from exhausted. I strongly encourage researchers from the “iron community” to submit original articles and reviews to this Special Issue of Genes. mdpi.com/si/68169 SpeciaIslsue IMPACT FACTOR 4.096 an Open Access Journal by MDPI Editor-in-Chief Message from the Editor-in-Chief Prof. Dr. J. Peter W. Young Genes are central to our understanding of biology, and Department of Biology, University modern advances such as genomics and genome editing of York, Heslington, York YO10 have maintained genetics as a vibrant, diverse and 5DD, UK fastmoving field. -
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IMPACT FACTOR 4.096 an Open Access Journal by MDPI Genotype-Phenotype Study in Disease Guest Editors: Message from the Guest Editors Prof. Dr. Michele Cioffi The study of inter-individual variability is essential for Department of Precision precision medicine. The study of polymorphic variants has Medicine, University of Campania "Luigi Vanvitelli", Via L. De become decisive in the understanding of mechanisms that Crecchio, 7, 80138 Naples, Italy underpin various multifactorial diseases (i.e., diabetes, [email protected] obesity, cancer, and cardiovascular disease). Prof. Dr. Maria Teresa Vietri All diseases have different degrees of genetic Department of Precision heterogeneity, for which the severity of the disease varies Medicine, University of Campania from individual to individual. The same pathological "Luigi Vanvitelli", Via L. De phenotype could be determined by different mutations in Crecchio, 7, 80138 Naples, Italy different genes. In multifactorial diseases, however, genetic mariateresa.vietri@ heterogeneity is much more widespread and frequent, so unicampania.it genes contribute to a different extent to the expression of phenotype. Deadline for manuscript Some genes do not cause disease but rather affect or submissions: cause particular aspects of the disease by behaving as closed (5 August 2021) modifying genes. More recently it has been proposed that genetic variation may also explain some of the other features of clinical phenotype, such as disease duration. Although the genotype–phenotype link is not always clear, it allows improved therapy, evaluation of individual drug response, and understanding of the adaptive response of organisms to environmental stimuli. mdpi.com/si/71270 SpeciaIslsue IMPACT FACTOR 4.096 an Open Access Journal by MDPI Editor-in-Chief Message from the Editor-in-Chief Prof. -
Site-Specific Identification and Quantitation of Endogenous SUMO Modifications Under Native Conditions
ARTICLE DOI: 10.1038/s41467-017-01271-3 OPEN Site-specific identification and quantitation of endogenous SUMO modifications under native conditions Ryan J. Lumpkin1, Hongbo Gu2, Yiying Zhu2, Marilyn Leonard3, Alla S. Ahmad 1, Karl R. Clauser4, Jesse G. Meyer 1, Eric J. Bennett 3 & Elizabeth A. Komives1 fi fi 1234567890 Small ubiquitin-like modi er (SUMO) modi cation regulates numerous cellular processes. Unlike ubiquitin, detection of endogenous SUMOylated proteins is limited by the lack of naturally occurring protease sites in the C-terminal tail of SUMO proteins. Proteome-wide detection of SUMOylation sites on target proteins typically requires ectopic expression of mutant SUMOs with introduced tryptic sites. Here, we report a method for proteome-wide, site-level detection of endogenous SUMOylation that uses α-lytic protease, WaLP. WaLP digestion of SUMOylated proteins generates peptides containing SUMO-remnant diglycyl- lysine (KGG) at the site of SUMO modification. Using previously developed immuno-affinity isolation of KGG-containing peptides followed by mass spectrometry, we identified 1209 unique endogenous SUMO modification sites. We also demonstrate the impact of protea- some inhibition on ubiquitin and SUMO-modified proteomes using parallel quantitation of ubiquitylated and SUMOylated peptides. This methodological advancement enables deter- mination of endogenous SUMOylated proteins under completely native conditions. 1 Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093-0378, USA. 2 Proteomic Service Group Cell Signaling Technology, 3 Trask Lane, Danvers, MA 01923, USA. 3 Cell and Developmental Biology, University of California, San Diego, La Jolla, CA 92093-0380, USA. 4 Broad Institute of MIT and Harvard, 415 Main St, Cambridge, MA 02142, USA. -
Emerging Applications of Metabolomic and Genomic Profiling in Diabetic Clinical Medicine
Reviews/Commentaries/ADA Statements REVIEW Emerging Applications of Metabolomic and Genomic Profiling in Diabetic Clinical Medicine AINE M. MCKILLOP, PHD however, powerful methodologies are now PETER R. FLATT, PHD available for exploitation of novel quantita- tive and qualitative disease-related biomark- ers. Novel biomarkers are needed that are Clinical and epidemiological metabolomics provides a unique opportunity to look at genotype- independent of known clinical risk factors. phenotype relationships as well as the body’s responses to environmental and lifestyle factors. fl Fundamentally, metabolomics aims to Fundamentally, it provides information on the universal outcome of in uencing factors on monitor changes in products of metabo- disease states and has great potential in the early diagnosis, therapy monitoring, and understand- lism and provide valuable information on ing of the pathogenesis of disease. Diseases, such as diabetes, with a complex set of interactions fl between genetic and environmental factors, produce changes in the body’s biochemical profile, arangeofin uencing factors and gene- thereby providing potential markers for diagnosis and initiation of therapies. There is clearly related outcomes. Exploitation of genomic a need to discover new ways to aid diagnosis and assessment of glycemic status to help reduce technology in recent times has resulted in diabetes complications and improve the quality of life. Many factors, including peptides, proteins, many technical advances, and genomic metabolites, nucleic acids, and polymorphisms, have been proposed as putative biomarkers for analysis has now emerged as a valuable diabetes. Metabolomics is an approach used to identify and assess metabolic characteristics, changes, tool in predicting the body’s response to and phenotypes in response to influencing factors, such as environment, diet, lifestyle, and path- fi stimuli caused by disease or injury. -
Role of Ubiquitin and SUMO in Intracellular Trafficking
Curr. Issues Mol. Biol. (2020) 35: 99-108. Role of Ubiquitin and SUMO in Intracellular Trafcking Maria Sundvall1,2,3* 1Institute of Biomedicine, University of Turku, Turku, Finland. 2Western Cancer Centre FICAN West, Turku University Hospital, Turku, Finland. 3Department of Oncology and Radiotherapy, University of Turku, Turku, Finland. *Correspondence: [email protected] htps://doi.org/10.21775/cimb.035.099 Abstract behaviour. In addition to e.g. chemical groups, Precise location of proteins at a given time within such as phosphate groups, proteins can be modi- a cell is essential to convey specifc signals and fed by small polypeptides, such as ubiquitin and result in a relevant functional outcome. Small SUMO. Ubiquitin and SUMO share a similar ubiquitin-like modifcations, such as ubiquitin three-dimensional structure and are principally and SUMO, represent a delicate and diverse way covalently linked at lysine (K) residues of sub- to transiently regulate intracellular trafcking strate proteins by a similar conjugation pathway events of existing proteins in cells. Trafcking (Hershko et al., 1998; Hay, 2013). Unlike ubiq- of multiple proteins is controlled reversibly by uitin, SUMO is preferentially atached at SUMO ubiquitin and/or SUMO directly or indirectly via consensus sites ΨKxE in substrates Ψ = hydropho- regulation of transport machinery components. bic residue with high preference for I or V, x = any Regulation is dynamic and multilayered, involv- amino acid) under steady state conditions, but ing active crosstalk and interdependence between under stress conditions in particular more non- post-translational modifcations. However, in consensus sites are SUMOylated (Hendriks et al., most cases regulation appears very complex, and 2016). -
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IMPACT Indexed in: FACTOR PubMed 4.096 genes an Open Access Journal by MDPI Academic Open Access Publishing since 1996 IMPACT Indexed in: FACTOR PubMed genes 4.096 an Open Access Journal by MDPI Editor-in-Chief Message from the Editor-in-Chief Prof. Dr. J. Peter W. Young Genes are central to our understanding of biology, and modern advances such as genomics and genome editing have maintained genetics as a vibrant, diverse and fast- moving field. There is a need for good quality, open access journals in this area, and the Genes team aims to provide expert manuscript handling, serious peer review, and rapid publication across the whole discipline of genetics. Starting in 2010, the journal is now well established and recognised. Why not consider Genes for your next genetics paper? Author Benefits Open Access Unlimited and free access for readers No Copyright Constraints Retain copyright of your work and free use of your article Impact Factor 4.096 (2020 Journal Citation Reports®) High Visibility SCIE-Science Citation Index Expanded (Clarivate Analytics), MEDLINE (NLM), PubMed (NLM), Scopus (Elsevier) Rapid Publication Manuscripts are peer-reviewed and a first decision provided to authors approximately 17.4 days after submission; acceptance to publication is undertaken in 2.8 days (median values for papers published in this journal in the first half of 2021) Discounts on Article Processing Charges (APC) If you belong to an institute that participates with the MDPI Institutional Open Access Program No Space Constraints, No Extra Space or Color Charges No restriction on the length of the papers, number of figures or colors Aims and Scope Genes (ISSN 2073-4425) is an international, peer-reviewed, open access journal which provides an advanced forum for studies on all aspects of genetics and genomics from the molecular to the population level. -
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medRxiv preprint doi: https://doi.org/10.1101/2020.12.29.20248986; this version posted January 4, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . Insights into the molecular mechanism of anticancer drug ruxolitinib repurposable in COVID-19 therapy Manisha Mandal Department of Physiology, MGM Medical College, Kishanganj-855107, India Email: [email protected], ORCID: https://orcid.org/0000-0002-9562-5534 Shyamapada Mandal* Department of Zoology, University of Gour Banga, Malda-732103, India Email: [email protected], ORCID: https://orcid.org/0000-0002-9488-3523 *Corresponding author: Email: [email protected]; [email protected] Abstract Due to non-availability of specific therapeutics against COVID-19, repurposing of approved drugs is a reasonable option. Cytokines imbalance in COVID-19 resembles cancer; exploration of anti-inflammatory agents, might reduce COVID-19 mortality. The current study investigates the effect of ruxolitinib treatment in SARS-CoV-2 infected alveolar cells compared to the uninfected one from the GSE5147507 dataset. The protein-protein interaction network, biological process and functional enrichment of differentially expressed genes were studied using STRING App of the Cytoscape software and R programming tools. The present study indicated that ruxolitinib treatment elicited similar response equivalent to that of SARS-CoV-2 uninfected situation by inducing defense response in host against virus infection by RLR and NOD like receptor pathways. Further, the effect of ruxolitinib in SARS- CoV-2 infection was mainly caused by significant suppression of IFIH1, IRF7 and MX1 genes as well as inhibition of DDX58/IFIH1-mediated induction of interferon- I and -II signalling. -
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IMPACT FACTOR 4.096 an Open Access Journal by MDPI Shared Mechanisms and Multimorbidity for Immune-Mediated Diseases Guest Editor: Message from the Guest Editor Dr. Calliope Dendrou Immune-mediated diseases (IMDs) currently affect Wellcome Centre for Human approximately 10% of the global population and are Genetics, University of Oxford increasing in incidence. These diseases are typically [email protected] chronic, multifactorial conditions with no cure, and they therefore pose a substantial burden for affected individuals, their families, and the healthcare system. Deadline for manuscript However, understanding the biological pathways that are submissions: common to different IMDs and their co-morbid clinical closed (16 October 2020) phenotypes can aid the development of strategies for the improvement treatment and management of multiple conditions. This Special Issue will highlight recent advances in genetics and functional genomics that are facilitating the determination of pathophysiological mechanisms that are shared across multiple IMDs and that drive co-morbidity between IMDs and with other disorders. These advances include the development of new approaches for investigating cross-trait associations; the utilization of big data sets; and the implementation of high-throughput, high-resolution methods for patient immunoprofiling, including single-cell genomics. We welcome the submission of reviews, perspectives, short communications, and research articles. mdpi.com/si/25791 SpeciaIslsue IMPACT FACTOR 4.096 an Open Access Journal by MDPI Editor-in-Chief Message from the Editor-in-Chief Prof. Dr. J. Peter W. Young Genes are central to our understanding of biology, and Department of Biology, University modern advances such as genomics and genome editing of York, Heslington, York YO10 have maintained genetics as a vibrant, diverse and 5DD, UK fastmoving field. -
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IMPACT FACTOR 4.096 an Open Access Journal by MDPI Prospects in Transgenic Technology 2020 Guest Editors: Message from the Guest Editors Dr. Wojtek Auerbach Dear colleagues, 1. Embryonic Stem Cells Technologies, Regeneron With the advent of gene editing technologies, the ability to Pharmaceuticals, Tarrytown, NY manipulate genomes has become amenable to nearly all 10591, USA 2. President International Society species. Gene modification protocols that lead to new for Transgenic Technologies ways of generating genetically engineered model systems president@ transtechsociety.org are being developed at an exponential pace, with new techniques reported almost daily. With this technology, we Dr. Jan Parker-Thornburg may be able to easily generate models of diseases affecting Department of Genetics, both humans and other animals, increase food production University of Texas MD Anderson Cancer Center, Houston, TX worldwide, and perform gene therapy to alleviate disease, 77030, USA among the many possibilities. However, success should be [email protected] based on an understanding of when to use newer vs. established technologies. Scientists should be aware of both expected and unexpected consequences of the particular method chosen for gene modification. Analyses Deadline for manuscript and assessments that take into account such submissions: closed (29 February 2020) consequences are critical for acceptance by society, as is an ethical approach to determining what uses such technology can have. This Special Issue of Genes welcomes original research manuscripts and review papers that address the science and ethics of gene modification. Guest Editors Dr. Wojtek Auerbach Dr. Jan Parker-Thornburg mdpi.com/si/27883 SpeciaIslsue IMPACT FACTOR 4.096 an Open Access Journal by MDPI Editor-in-Chief Message from the Editor-in-Chief Prof. -
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IMPACT FACTOR 4.096 an Open Access Journal by MDPI Genetics and Genomics of Probiotic Organisms Guest Editor: Message from the Guest Editor Dr. Paola Mattarelli Probiotics are microorganisms typically associated with Department of Agricultural and human and animal gastrointestinal tract strictly related to Food Sciences, University of the wellbeing of the host. Bifidobacteria and lactobacilli Bologna, Viale Fanin 44, 40127 Bologna, Italy are considered the main probiotics, but some strains of [email protected] other genera such as Leuconostoc, Pediococcus and Lactococcus other than some yeasts are also considered and commercially utilized as probiotics. A rational design to screen the most relevant properties is fundamental for Deadline for manuscript the selection of the most appropriate probiotic for specific submissions: closed (30 November 2020) targets such as immunostimulatory, anti-inflammatory, and antipathogenic activity. More recently, comparative genomics of multiple genomes within and between related species and genera have been considered of great value to explore metabolic activities of probiotic microorganisms. This Special Issue welcomes submissions related to genetic and genomic characterization of strains belonging to bacteria and yeasts to screen and identify interesting metabolic activities and or biomolecules for probe applications in animal and human hosts. Rational design of wet-lab experiments linked to genetic and genomic study to screen for the most relevant probiotic properties is also welcome. mdpi.com/si/39099 SpeciaIslsue IMPACT FACTOR 4.096 an Open Access Journal by MDPI Editor-in-Chief Message from the Editor-in-Chief Prof. Dr. J. Peter W. Young Genes are central to our understanding of biology, and Department of Biology, University modern advances such as genomics and genome editing of York, Heslington, York YO10 have maintained genetics as a vibrant, diverse and 5DD, UK fastmoving field. -
Bioinformatic Gene Analysis for Potential Biomarkers And
Zou et al. J Transl Med (2019) 17:45 https://doi.org/10.1186/s12967-019-1790-x Journal of Translational Medicine RESEARCH Open Access Bioinformatic gene analysis for potential biomarkers and therapeutic targets of atrial fbrillation-related stroke Rongjun Zou1†, Dingwen Zhang1†, Lei Lv1†, Wanting Shi2, Zijiao Song3, Bin Yi1, Bingjia Lai4, Qian Chen5, Songran Yang6,7* and Ping Hua1* Abstract Background: Atrial fbrillation (AF) is one of the most prevalent sustained arrhythmias, however, epidemiological data may understate its actual prevalence. Meanwhile, AF is considered to be a major cause of ischemic strokes due to irregular heart-rhythm, coexisting chronic vascular infammation, and renal insufciency, and blood stasis. We studied co-expressed genes to understand relationships between atrial fbrillation (AF) and stroke and reveal potential biomarkers and therapeutic targets of AF-related stroke. Methods: AF-and stroke-related diferentially expressed genes (DEGs) were identifed via bioinformatic analysis Gene Expression Omnibus (GEO) datasets GSE79768 and GSE58294, respectively. Subsequently, extensive target prediction and network analyses methods were used to assess protein–protein interaction (PPI) networks, Gene Ontology (GO) terms and pathway enrichment for DEGs, and co-expressed DEGs coupled with corresponding predicted miRNAs involved in AF and stroke were assessed as well. Results: We identifed 489, 265, 518, and 592 DEGs in left atrial specimens and cardioembolic stroke blood samples at < 3, 5, and 24 h, respectively. LRRK2, CALM1, CXCR4, TLR4, CTNNB1, and CXCR2 may be implicated in AF and the hub- genes of CD19, FGF9, SOX9, GNGT1, and NOG may be associated with stroke. Finally, co-expressed DEGs of ZNF566, PDZK1IP1, ZFHX3, and PITX2 coupled with corresponding predicted miRNAs, especially miR-27a-3p, miR-27b-3p, and miR-494-3p may be signifcantly associated with AF-related stroke.