Quantitative Description of Genomic Evolution of Olfactory Receptors
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Genetic Variation Across the Human Olfactory Receptor Repertoire Alters Odor Perception
bioRxiv preprint doi: https://doi.org/10.1101/212431; this version posted November 1, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Genetic variation across the human olfactory receptor repertoire alters odor perception Casey Trimmer1,*, Andreas Keller2, Nicolle R. Murphy1, Lindsey L. Snyder1, Jason R. Willer3, Maira Nagai4,5, Nicholas Katsanis3, Leslie B. Vosshall2,6,7, Hiroaki Matsunami4,8, and Joel D. Mainland1,9 1Monell Chemical Senses Center, Philadelphia, Pennsylvania, USA 2Laboratory of Neurogenetics and Behavior, The Rockefeller University, New York, New York, USA 3Center for Human Disease Modeling, Duke University Medical Center, Durham, North Carolina, USA 4Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA 5Department of Biochemistry, University of Sao Paulo, Sao Paulo, Brazil 6Howard Hughes Medical Institute, New York, New York, USA 7Kavli Neural Systems Institute, New York, New York, USA 8Department of Neurobiology and Duke Institute for Brain Sciences, Duke University Medical Center, Durham, North Carolina, USA 9Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA *[email protected] ABSTRACT The human olfactory receptor repertoire is characterized by an abundance of genetic variation that affects receptor response, but the perceptual effects of this variation are unclear. To address this issue, we sequenced the OR repertoire in 332 individuals and examined the relationship between genetic variation and 276 olfactory phenotypes, including the perceived intensity and pleasantness of 68 odorants at two concentrations, detection thresholds of three odorants, and general olfactory acuity. -
A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated. -
The Epigenetics of Diabetes, Obesity, Overweight and Cardiovascular Disease
AIMS Genetics, 6(3): 36–45. DOI: 10.3934/genet.2019.3.36 Received: 28 May 2019 Accepted: 25 July 2019 Published: 01 August 2019 http://www.aimspress.com/journal/Genetics Review The epigenetics of diabetes, obesity, overweight and cardiovascular disease Harem Othman Smail* Department of Biology, Faculty of science and health, Koya University Koya KOY45, Kurdistan Region-F.R. Iraq * Correspondence: Email: [email protected]; Tel: +09647705047235. Abstract: The objectives of this review were once to understand the roles of the epigenetics mechanism in different types of diabetes, obesity, overweight, and cardiovascular disease. Epigenetics represents a phenomenon of change heritable phenotypic expression of genetic records taking place except changes in DNA sequence. Epigenetic modifications can have an impact on a whole of metabolic disease with the aid of specific alteration of candidate genes based totally on the change of the target genes. In this review, I summarized the new findings in DNA methylation, histone modifications in each type of diabetes (type 1 and type 2), obesity, overweight, and cardiovascular disease. The involvement of histone alterations and DNA methylation in the development of metabolic diseases is now widely accepted recently many novel genes have been demonstrated that has roles in diabetes pathway and it can be used for detection prediabetic; however Over the modern-day years, mass spectrometry-based proteomics techniques positioned and mapped one-of a kind range of histone modifications linking obesity and metabolic diseases. The main point of these changes is rapidly growing; however, their points and roles in obesity are no longer properly understood in obesity. -
Identification of Candidate Biomarkers and Pathways Associated with Type 1 Diabetes Mellitus Using Bioinformatics Analysis
bioRxiv preprint doi: https://doi.org/10.1101/2021.06.08.447531; this version posted June 9, 2021. 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. Identification of candidate biomarkers and pathways associated with type 1 diabetes mellitus using bioinformatics analysis Basavaraj Vastrad1, Chanabasayya Vastrad*2 1. Department of Biochemistry, Basaveshwar College of Pharmacy, Gadag, Karnataka 582103, India. 2. Biostatistics and Bioinformatics, Chanabasava Nilaya, Bharthinagar, Dharwad 580001, Karnataka, India. * Chanabasayya Vastrad [email protected] Ph: +919480073398 Chanabasava Nilaya, Bharthinagar, Dharwad 580001 , Karanataka, India bioRxiv preprint doi: https://doi.org/10.1101/2021.06.08.447531; this version posted June 9, 2021. 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 Type 1 diabetes mellitus (T1DM) is a metabolic disorder for which the underlying molecular mechanisms remain largely unclear. This investigation aimed to elucidate essential candidate genes and pathways in T1DM by integrated bioinformatics analysis. In this study, differentially expressed genes (DEGs) were analyzed using DESeq2 of R package from GSE162689 of the Gene Expression Omnibus (GEO). Gene ontology (GO) enrichment analysis, REACTOME pathway enrichment analysis, and construction and analysis of protein-protein interaction (PPI) network, modules, miRNA-hub gene regulatory network and TF-hub gene regulatory network, and validation of hub genes were then performed. A total of 952 DEGs (477 up regulated and 475 down regulated genes) were identified in T1DM. GO and REACTOME enrichment result results showed that DEGs mainly enriched in multicellular organism development, detection of stimulus, diseases of signal transduction by growth factor receptors and second messengers, and olfactory signaling pathway. -
Olfactory Receptors in Non-Chemosensory Tissues
BMB Reports Invited Mini Review Olfactory receptors in non-chemosensory tissues NaNa Kang & JaeHyung Koo* Department of Brain Science, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 711-873, Korea Olfactory receptors (ORs) detect volatile chemicals that lead to freezing behavior (3-5). the initial perception of smell in the brain. The olfactory re- ORs are localized in the cilia of olfactory sensory neurons ceptor (OR) is the first protein that recognizes odorants in the (OSNs) in the olfactory epithelium (OE) and are activated by olfactory signal pathway and it is present in over 1,000 genes chemical cues, typically odorants at the molecular level, in mice. It is also the largest member of the G protein-coupled which lead to the perception of smell in the brain (6). receptors (GPCRs). Most ORs are extensively expressed in the Tremendous research was conducted since Buck and Axel iso- nasal olfactory epithelium where they perform the appropriate lated ORs as an OE-specific expression in 1991 (7). OR genes, physiological functions that fit their location. However, recent the largest family among the G protein-coupled receptors whole-genome sequencing shows that ORs have been found (GPCRs) (8), constitute more than 1,000 genes on the mouse outside of the olfactory system, suggesting that ORs may play chromosome (9, 10) and more than 450 genes in the human an important role in the ectopic expression of non-chemo- genome (11, 12). sensory tissues. The ectopic expressions of ORs and their phys- Odorant activation shows a distinct signal transduction iological functions have attracted more attention recently since pathway for odorant perception. -
Sean Raspet – Molecules
1. Commercial name: Fructaplex© IUPAC Name: 2-(3,3-dimethylcyclohexyl)-2,5,5-trimethyl-1,3-dioxane SMILES: CC1(C)CCCC(C1)C2(C)OCC(C)(C)CO2 Molecular weight: 240.39 g/mol Volume (cubic Angstroems): 258.88 Atoms number (non-hydrogen): 17 miLogP: 4.43 Structure: Biological Properties: Predicted Druglikenessi: GPCR ligand -0.23 Ion channel modulator -0.03 Kinase inhibitor -0.6 Nuclear receptor ligand 0.15 Protease inhibitor -0.28 Enzyme inhibitor 0.15 Commercial name: Fructaplex© IUPAC Name: 2-(3,3-dimethylcyclohexyl)-2,5,5-trimethyl-1,3-dioxane SMILES: CC1(C)CCCC(C1)C2(C)OCC(C)(C)CO2 Predicted Olfactory Receptor Activityii: OR2L13 83.715% OR1G1 82.761% OR10J5 80.569% OR2W1 78.180% OR7A2 77.696% 2. Commercial name: Sylvoxime© IUPAC Name: N-[4-(1-ethoxyethenyl)-3,3,5,5tetramethylcyclohexylidene]hydroxylamine SMILES: CCOC(=C)C1C(C)(C)CC(CC1(C)C)=NO Molecular weight: 239.36 Volume (cubic Angstroems): 252.83 Atoms number (non-hydrogen): 17 miLogP: 4.33 Structure: Biological Properties: Predicted Druglikeness: GPCR ligand -0.6 Ion channel modulator -0.41 Kinase inhibitor -0.93 Nuclear receptor ligand -0.17 Protease inhibitor -0.39 Enzyme inhibitor 0.01 Commercial name: Sylvoxime© IUPAC Name: N-[4-(1-ethoxyethenyl)-3,3,5,5tetramethylcyclohexylidene]hydroxylamine SMILES: CCOC(=C)C1C(C)(C)CC(CC1(C)C)=NO Predicted Olfactory Receptor Activity: OR52D1 71.900% OR1G1 70.394% 0R52I2 70.392% OR52I1 70.390% OR2Y1 70.378% 3. Commercial name: Hyperflor© IUPAC Name: 2-benzyl-1,3-dioxan-5-one SMILES: O=C1COC(CC2=CC=CC=C2)OC1 Molecular weight: 192.21 g/mol Volume -
Functional and Structural Characterization of Olfactory Receptors in Human Heart and Eye
DISSERTATION to obtain the degree Doctor Rerum Naturalium (Dr.rer.nat.) at the Faculty of Biology and Biotechnology International Graduate School Biosciences Ruhr-University Bochum Functional and structural characterization of olfactory receptors in human heart and eye Department of Cellphysiology submitted by Nikolina Jovancevic from Zadar, Croatia Bochum February 2016 First Referee: Prof. Dr. Dr. Dr. Hanns Hatt Second Referee: Prof. Dr. Stefan Wiese DISSERTATION zur Erlangung des Grades eines Doktors der Naturwissenschaften der Fakultät für Biologie und Biotechnologie an der Internationalen Graduiertenschule Biowissenschaften der Ruhr-Universität Bochum Funktionale und strukturelle Charakterisierung olfaktorischer Rezeptoren im humanen Herzen und Auge Lehrstuhl für Zellphysiologie vorgelegt von Nikolina Jovancevic aus Zadar, Kroatien Bochum Februar 2016 Referent: Prof. Dr. Dr. Dr. Hanns Hatt Korreferent: Prof. Dr. Stefan Wiese To my family TABLE OF CONTENTS TABEL OF CONTENT 1 INTRODUCTION 1 1.1 G protein-coupled receptors 1 1.1.1 General 1 1.1.2 Structure and classification 2 1.1.3 Olfactory Receptors 4 1.2 Function of olfactory receptors 9 1.2.1 The olfactory system 9 1.2.2 Ectopic expression of olfactory receptors 11 1.3 Excursus: Anatomy and physiology of the heart 13 1.3.1 Anatomy of the heart and blood circuit 14 1.3.2 The cardiac conduction system 15 1.3.3 Excitation-contraction coupling 16 1.3.4 Cardiac GPCRs: Modulation of cardiac contraction 17 1.4 Excursus: Anatomy and physiology of the eye 18 1.4.1 Anatomy of the retina 19 -
Designing Exons for Human Olfactory Receptor Gene Subfamilies Using a Mathematical Paradigm
Designing exons for human olfactory receptor gene subfamilies using a mathematical paradigm Sk. Sarif Hassana,c, Pabitra Pal Choudhurya, Amita Palb, R. L. Brahmacharyc and Arunava Goswamic,1 aApplied Statistics Unit, Indian Statistical Institute, 203 B. T. Road, Calcutta, 700108 India. [email protected] [P. P. C.]; [email protected] [S. S. H.]; b Bayesian Interdisciplinary Research Unit (BIRU), Indian Statistical Institute, 203 B. T. Road, Calcutta, 700108 India. [email protected] [A. P.] and cBiological Sciences Division, Indian Statistical Institute, 203 B. T. Road, Calcutta, 700108 India. [email protected] [A.G.]. Keywords Human olfactory receptor L-system ClustalW Star Model Olfaction Footnotes 1To whom correspondence should be addressed. E-mail: [email protected] / [email protected] Author contributions: A. G. and S. S. H. designed research; A. G. and S. S. H. performed research; P. P. C. and A. P. analyzed data; and A. G., S. S. H., P. P. C., A. P., and R. L. B. wrote the paper. Conflict of interest statement: The authors declare no conflict of interest. Abstract Ligands for only two human olfactory receptors are known. One of them, OR1D2, binds to Bourgeonal, a volatile chemical constituent of the fragrance of mythical flower, Lily of the valley or Our Lady's tears, Convallaria majalis (also the national flower of Finland) [Malnic B, Godfrey P-A, Buck L-B (2004) The human olfactory receptor gene family. Proc. Natl. Acad. Sci U. S. A. 101: 2584-2589 and Erratum in: Proc Natl Acad Sci U. S. A. (2004) 101: 7205]. OR1D2, OR1D4 and OR1D5 are three full length olfactory receptors present in an olfactory locus in human genome. -
Clinical, Molecular, and Immune Analysis of Dabrafenib-Trametinib
Supplementary Online Content Chen G, McQuade JL, Panka DJ, et al. Clinical, molecular and immune analysis of dabrafenib-trametinib combination treatment for metastatic melanoma that progressed during BRAF inhibitor monotherapy: a phase 2 clinical trial. JAMA Oncology. Published online April 28, 2016. doi:10.1001/jamaoncol.2016.0509. eMethods. eReferences. eTable 1. Clinical efficacy eTable 2. Adverse events eTable 3. Correlation of baseline patient characteristics with treatment outcomes eTable 4. Patient responses and baseline IHC results eFigure 1. Kaplan-Meier analysis of overall survival eFigure 2. Correlation between IHC and RNAseq results eFigure 3. pPRAS40 expression and PFS eFigure 4. Baseline and treatment-induced changes in immune infiltrates eFigure 5. PD-L1 expression eTable 5. Nonsynonymous mutations detected by WES in baseline tumors This supplementary material has been provided by the authors to give readers additional information about their work. © 2016 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/30/2021 eMethods Whole exome sequencing Whole exome capture libraries for both tumor and normal samples were constructed using 100ng genomic DNA input and following the protocol as described by Fisher et al.,3 with the following adapter modification: Illumina paired end adapters were replaced with palindromic forked adapters with unique 8 base index sequences embedded within the adapter. In-solution hybrid selection was performed using the Illumina Rapid Capture Exome enrichment kit with 38Mb target territory (29Mb baited). The targeted region includes 98.3% of the intervals in the Refseq exome database. Dual-indexed libraries were pooled into groups of up to 96 samples prior to hybridization. -
AKT-Mtor Signaling in Human Acute Myeloid Leukemia Cells and Its Association with Adverse Prognosis
Cancers 2018, 10, 332 S1 of S35 Supplementary Materials: Clonal Heterogeneity Reflected by PI3K- AKT-mTOR Signaling in Human Acute Myeloid Leukemia Cells and its Association with Adverse Prognosis Ina Nepstad, Kimberley Joanne Hatfield, Tor Henrik Anderson Tvedt, Håkon Reikvam and Øystein Bruserud Figure S1. Detection of clonal heterogeneity for 49 acute myeloid leukemia (AML) patients; the results from representative flow cytometric analyses of phosphatidylinositol-3-kinase-Akt-mechanistic target of rapamycin (PI3K-Akt-mTOR) activation. For each patient clonal heterogeneity was detected by analysis Cancers 2018, 10, 332 S2 of S35 of at least one mediator in the PI3K-Akt-mTOR pathway. Patient ID is shown in the upper right corner of each histogram. The figure documents the detection of dual populations for all patients, showing the results from one representative flow cytometric analysis for each of these 49 patients. The Y-axis represents the amount of cells, and the X-axis represents the fluorescence intensity. The stippled line shows the negative/unstained controls. Figure S2. Cell preparation and gating strategy. Flow cytometry was used for examination of the constitutive expression of the mediators in the PI3K-Akt-mTOR pathway/network in primary AML cells. Cryopreserved cells were thawed and washed before suspension cultures were prepared as described in Materials and methods. Briefly, cryopreserved and thawed primary leukemic cells were incubated for 20 minutes in RPMI-1640 (Sigma-Aldrich) before being directly fixed in 1.5% paraformaldehyde (PFA) and permeabilized with 100% ice-cold methanol. The cells were thereafter rehydrated by adding 2 mL phosphate buffered saline (PBS), gently re-suspended and then centrifuged. -
The Hypothalamus As a Hub for SARS-Cov-2 Brain Infection and Pathogenesis
bioRxiv preprint doi: https://doi.org/10.1101/2020.06.08.139329; this version posted June 19, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. The hypothalamus as a hub for SARS-CoV-2 brain infection and pathogenesis Sreekala Nampoothiri1,2#, Florent Sauve1,2#, Gaëtan Ternier1,2ƒ, Daniela Fernandois1,2 ƒ, Caio Coelho1,2, Monica ImBernon1,2, Eleonora Deligia1,2, Romain PerBet1, Vincent Florent1,2,3, Marc Baroncini1,2, Florence Pasquier1,4, François Trottein5, Claude-Alain Maurage1,2, Virginie Mattot1,2‡, Paolo GiacoBini1,2‡, S. Rasika1,2‡*, Vincent Prevot1,2‡* 1 Univ. Lille, Inserm, CHU Lille, Lille Neuroscience & Cognition, DistAlz, UMR-S 1172, Lille, France 2 LaBoratorY of Development and PlasticitY of the Neuroendocrine Brain, FHU 1000 daYs for health, EGID, School of Medicine, Lille, France 3 Nutrition, Arras General Hospital, Arras, France 4 Centre mémoire ressources et recherche, CHU Lille, LiCEND, Lille, France 5 Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Center for Infection and ImmunitY of Lille (CIIL), Lille, France. # and ƒ These authors contriButed equallY to this work. ‡ These authors directed this work *Correspondence to: [email protected] and [email protected] Short title: Covid-19: the hypothalamic hypothesis 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.06.08.139329; this version posted June 19, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. -
Associations Between Olfactory Pathway Gene Methylation Marks, Obesity Features and Dietary Intakes Omar Ramos-Lopez1,2†, Jose I
Ramos-Lopez et al. Genes & Nutrition (2019) 14:11 https://doi.org/10.1186/s12263-019-0635-9 RESEARCH Open Access Associations between olfactory pathway gene methylation marks, obesity features and dietary intakes Omar Ramos-Lopez1,2†, Jose I. Riezu-Boj1,3†, Fermin I. Milagro1,4, M. Angeles Zulet1,3,4, Jose L. Santos5, J. Alfredo Martinez1,3,4,6* and MENA project Abstract Background: Olfaction is an important sense influencing food preferences, appetite, and eating behaviors. This hypothesis-driven study aimed to assess associations between olfactory pathway gene methylation signatures, obesity features, and dietary intakes. Methods: A nutriepigenomic analysis was conducted in 474 adults from the Methyl Epigenome Network Association (MENA) project. Anthropometric measurements, clinical data, and serum metabolic profiles of the study population were obtained from structured databases of the MENA cohorts. Habitual dietary intake was assessed using a validated semiquantitative food frequency questionnaire. DNA methylation was measured in circulating white blood cells by microarray (Infinium Human Methylation 450 K BeadChips). FDR values (p < 0.0001) were used to select those CpGs that showed the best correlation with body mass index (BMI) and waist circumference (WC). Pathway analyses involving the characterization of genes involved in the olfactory transduction system were performed using KEGG and pathDIP reference databases. Results: Overall, 15 CpG sites at olfactory pathway genes were associated with BMI (p < 0.0001) and WC (p < 0.0001) after adjustments for potential confounding factors. Together, methylation levels at the15 CpG sites accounted for 22% and 20% of the variability in BMI and WC (r2 =0.219,p <0.001,andr2 =0.204,p < 0.001, respectively).