Systems Genetic Discovery of Host-Microbiome Interactions
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Primate Specific Retrotransposons, Svas, in the Evolution of Networks That Alter Brain Function
Title: Primate specific retrotransposons, SVAs, in the evolution of networks that alter brain function. Olga Vasieva1*, Sultan Cetiner1, Abigail Savage2, Gerald G. Schumann3, Vivien J Bubb2, John P Quinn2*, 1 Institute of Integrative Biology, University of Liverpool, Liverpool, L69 7ZB, U.K 2 Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, The University of Liverpool, Liverpool L69 3BX, UK 3 Division of Medical Biotechnology, Paul-Ehrlich-Institut, Langen, D-63225 Germany *. Corresponding author Olga Vasieva: Institute of Integrative Biology, Department of Comparative genomics, University of Liverpool, Liverpool, L69 7ZB, [email protected] ; Tel: (+44) 151 795 4456; FAX:(+44) 151 795 4406 John Quinn: Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, The University of Liverpool, Liverpool L69 3BX, UK, [email protected]; Tel: (+44) 151 794 5498. Key words: SVA, trans-mobilisation, behaviour, brain, evolution, psychiatric disorders 1 Abstract The hominid-specific non-LTR retrotransposon termed SINE–VNTR–Alu (SVA) is the youngest of the transposable elements in the human genome. The propagation of the most ancient SVA type A took place about 13.5 Myrs ago, and the youngest SVA types appeared in the human genome after the chimpanzee divergence. Functional enrichment analysis of genes associated with SVA insertions demonstrated their strong link to multiple ontological categories attributed to brain function and the disorders. SVA types that expanded their presence in the human genome at different stages of hominoid life history were also associated with progressively evolving behavioural features that indicated a potential impact of SVA propagation on a cognitive ability of a modern human. -
S41467-020-18249-3.Pdf
ARTICLE https://doi.org/10.1038/s41467-020-18249-3 OPEN Pharmacologically reversible zonation-dependent endothelial cell transcriptomic changes with neurodegenerative disease associations in the aged brain Lei Zhao1,2,17, Zhongqi Li 1,2,17, Joaquim S. L. Vong2,3,17, Xinyi Chen1,2, Hei-Ming Lai1,2,4,5,6, Leo Y. C. Yan1,2, Junzhe Huang1,2, Samuel K. H. Sy1,2,7, Xiaoyu Tian 8, Yu Huang 8, Ho Yin Edwin Chan5,9, Hon-Cheong So6,8, ✉ ✉ Wai-Lung Ng 10, Yamei Tang11, Wei-Jye Lin12,13, Vincent C. T. Mok1,5,6,14,15 &HoKo 1,2,4,5,6,8,14,16 1234567890():,; The molecular signatures of cells in the brain have been revealed in unprecedented detail, yet the ageing-associated genome-wide expression changes that may contribute to neurovas- cular dysfunction in neurodegenerative diseases remain elusive. Here, we report zonation- dependent transcriptomic changes in aged mouse brain endothelial cells (ECs), which pro- minently implicate altered immune/cytokine signaling in ECs of all vascular segments, and functional changes impacting the blood–brain barrier (BBB) and glucose/energy metabolism especially in capillary ECs (capECs). An overrepresentation of Alzheimer disease (AD) GWAS genes is evident among the human orthologs of the differentially expressed genes of aged capECs, while comparative analysis revealed a subset of concordantly downregulated, functionally important genes in human AD brains. Treatment with exenatide, a glucagon-like peptide-1 receptor agonist, strongly reverses aged mouse brain EC transcriptomic changes and BBB leakage, with associated attenuation of microglial priming. We thus revealed tran- scriptomic alterations underlying brain EC ageing that are complex yet pharmacologically reversible. -
Wild-Type Bone Marrow Cells ) Mice with −/− in C1q-Deficient (C1qa
Reconstitution of the Complement Function in C1q-Deficient C1qa؊/؊) Mice with Wild-Type Bone Marrow Cells1) Franz Petry,2* Marina Botto,† Rafaela Holtappels,‡ Mark J. Walport,† and Michael Loos* Besides Ab-independent and Ab-dependent activation of the complement classical pathway in host defense, C1q plays a key role in the processing of immune complexes and in the clearance of apoptotic cells. In humans, C1q deficiency leads to systemic lupus erythematosus-like symptoms in over 90% of the cases, thus making this defect a strong disease susceptibility factor. Similarly, -C1q-deficient mice (C1qa؊/؊) develop systemic lupus erythematosus-like symptoms, such as autoantibodies and glomerulone phritis. We have previously provided evidence that C1q is produced by cells of the monocyte-macrophage lineage. In this study, .we have tested whether transplantation of bone marrow cells would be sufficient to reconstitute C1q levels in C1qa؊/؊ mice C1qa؊/؊ mice received a single graft of 107 bone marrow cells from wild-type (wt) donors after irradiation doses of 6, 7, 8, or 9 .Gy. Engraftment was monitored by a Y chromosome-specific PCR and a PCR that differentiated wt from C1qa؊/؊ genotype Serum levels of C1q Ag and C1 function increased rapidly in the recipient mice, and titers reached normal levels within 6 wk after bone marrow transplantation. In wt mice that received C1qa؊/؊ bone marrow, serum levels of C1q decreased constantly over time and became C1q deficient within 55 wk. These data clearly demonstrate that bone marrow-derived cells are the source of serum C1q and are competent to reconstitute normal C1q serum levels in C1q-deficient mice. -
Oas1b-Dependent Immune Transcriptional Profiles of West Nile
MULTIPARENTAL POPULATIONS Oas1b-dependent Immune Transcriptional Profiles of West Nile Virus Infection in the Collaborative Cross Richard Green,*,† Courtney Wilkins,*,† Sunil Thomas,*,† Aimee Sekine,*,† Duncan M. Hendrick,*,† Kathleen Voss,*,† Renee C. Ireton,*,† Michael Mooney,‡,§ Jennifer T. Go,*,† Gabrielle Choonoo,‡,§ Sophia Jeng,** Fernando Pardo-Manuel de Villena,††,‡‡ Martin T. Ferris,†† Shannon McWeeney,‡,§,** and Michael Gale Jr.*,†,1 *Department of Immunology and †Center for Innate Immunity and Immune Disease (CIIID), University of Washington, § Seattle, Washington 98109, ‡OHSU Knight Cancer Institute, Division of Bioinformatics and Computational Biology, Department of Medical Informatics and Clinical Epidemiology, and **Oregon Clinical and Translational Research Institute, Oregon Health & Science University, Portland, Oregon 97239, ††Department of Genetics and ‡‡Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27514 ABSTRACT The oligoadenylate-synthetase (Oas) gene locus provides innate immune resistance to virus KEYWORDS infection. In mouse models, variation in the Oas1b gene influences host susceptibility to flavivirus infection. Oas However, the impact of Oas variation on overall innate immune programming and global gene expression flavivirus among tissues and in different genetic backgrounds has not been defined. We examined how Oas1b acts viral infection in spleen and brain tissue to limit West Nile virus (WNV) susceptibility and disease across a range of innate immunity genetic backgrounds. The laboratory founder strains of the mouse Collaborative Cross (CC) (A/J, C57BL/6J, multiparental 129S1/SvImJ, NOD/ShiLtJ, and NZO/HlLtJ) all encode a truncated, defective Oas1b, whereas the three populations wild-derived inbred founder strains (CAST/EiJ, PWK/PhJ, and WSB/EiJ) encode a full-length OAS1B pro- Multi-parent tein. -
Evaluation of the Bacterial Diversity in the Human Tongue Coating Based on Genus-Specific Primers for 16S Rrna Sequencing
Hindawi BioMed Research International Volume 2017, Article ID 8184160, 12 pages https://doi.org/10.1155/2017/8184160 Research Article Evaluation of the Bacterial Diversity in the Human Tongue Coating Based on Genus-Specific Primers for 16S rRNA Sequencing Beili Sun,1 Dongrui Zhou,2 Jing Tu,1 and Zuhong Lu1,2 1 State Key Laboratory of Bioelectronics, Southeast University, Nanjing 210096, China 2Key Laboratory of Child Development and Learning Science, Ministry of Education of China, Southeast University, Nanjing 210096, China Correspondence should be addressed to Zuhong Lu; [email protected] Received 25 February 2017; Revised 20 June 2017; Accepted 20 July 2017; Published 20 August 2017 Academic Editor: Koichiro Wada Copyright © 2017 Beili Sun 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. The characteristics of tongue coating are very important symbols for disease diagnosis in traditional Chinese medicine (TCM) theory.Asahabitatoforalmicrobiota,bacteriaonthetonguedorsumhavebeenprovedtobethecauseofmanyoraldiseases.The high-throughput next-generation sequencing (NGS) platforms have been widely applied in the analysis of bacterial 16S rRNA gene. We developed a methodology based on genus-specific multiprimer amplification and ligation-based sequencing for microbiota analysis. In order to validate the efficiency of the approach, we thoroughly analyzed six tongue coating samples from lung cancer patients with different TCM types, and more than 600 genera of bacteria were detected by this platform. The results showed that ligation-based parallel sequencing combined with enzyme digestion and multiamplification could expand the effective length of sequencing reads and could be applied in the microbiota analysis. -
Whole Exome Sequencing in Families at High Risk for Hodgkin Lymphoma: Identification of a Predisposing Mutation in the KDR Gene
Hodgkin Lymphoma SUPPLEMENTARY APPENDIX Whole exome sequencing in families at high risk for Hodgkin lymphoma: identification of a predisposing mutation in the KDR gene Melissa Rotunno, 1 Mary L. McMaster, 1 Joseph Boland, 2 Sara Bass, 2 Xijun Zhang, 2 Laurie Burdett, 2 Belynda Hicks, 2 Sarangan Ravichandran, 3 Brian T. Luke, 3 Meredith Yeager, 2 Laura Fontaine, 4 Paula L. Hyland, 1 Alisa M. Goldstein, 1 NCI DCEG Cancer Sequencing Working Group, NCI DCEG Cancer Genomics Research Laboratory, Stephen J. Chanock, 5 Neil E. Caporaso, 1 Margaret A. Tucker, 6 and Lynn R. Goldin 1 1Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD; 2Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD; 3Ad - vanced Biomedical Computing Center, Leidos Biomedical Research Inc.; Frederick National Laboratory for Cancer Research, Frederick, MD; 4Westat, Inc., Rockville MD; 5Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD; and 6Human Genetics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA ©2016 Ferrata Storti Foundation. This is an open-access paper. doi:10.3324/haematol.2015.135475 Received: August 19, 2015. Accepted: January 7, 2016. Pre-published: June 13, 2016. Correspondence: [email protected] Supplemental Author Information: NCI DCEG Cancer Sequencing Working Group: Mark H. Greene, Allan Hildesheim, Nan Hu, Maria Theresa Landi, Jennifer Loud, Phuong Mai, Lisa Mirabello, Lindsay Morton, Dilys Parry, Anand Pathak, Douglas R. Stewart, Philip R. Taylor, Geoffrey S. Tobias, Xiaohong R. Yang, Guoqin Yu NCI DCEG Cancer Genomics Research Laboratory: Salma Chowdhury, Michael Cullen, Casey Dagnall, Herbert Higson, Amy A. -
Adiponectin and Related C1q/TNF-Related Proteins Bind Selectively to Anionic Phospholipids and Sphingolipids
Adiponectin and related C1q/TNF-related proteins bind selectively to anionic phospholipids and sphingolipids Jessica J. Yea,b, Xin Bianc,d, Jaechul Lima,b, and Ruslan Medzhitova,b,1 aHHMI, Yale University, New Haven, CT 06520; bDepartment of Immunobiology, Yale University School of Medicine, New Haven, CT 06520; cDepartment of Cell Biology, Yale University School of Medicine, New Haven, CT 06520; and dDepartment of Neuroscience, Yale University School of Medicine, New Haven, CT 06520 Contributed by Ruslan Medzhitov, April 14, 2020 (sent for review December 20, 2019; reviewed by Ido Amit and G. William Wong) Adiponectin (Acrp30) is an adipokine associated with protection 5-mers of trimers, respectively referred to as low molecular weight from cardiovascular disease, insulin resistance, and inflammation. (LMW), medium molecular weight (MMW), and high molecular Although its effects are conventionally attributed to binding weight (HMW) complexes. Adiponectin can also be cleaved by Adipor1/2 and T-cadherin, its abundance in circulation, role in serum elastases and thrombin between the globular C1q-like head ceramide metabolism, and homology to C1q suggest an overlooked domain and the collagenous tail domain, forming globular adi- role as a lipid-binding protein, possibly generalizable to other C1q/ ponectin (gAd). While gAd appears to bind AdipoR1/2 and ac- TNF-related proteins (CTRPs) and C1q family members. To investi- tivate AMPK more strongly than full-length protein (19, 20), levels gate this, adiponectin, representative family members, and variants of HMW multimers are more strongly associated with insulin were expressed in Expi293 cells and tested for binding to lipids in sensitivity (21, 22), have a longer half-life in circulation (18), and liposomes using density centrifugation. -
Supplementary Figures and Tables
SUPPLEMENTARY DATA Supplementary Figure 1. Isolation and culture of endothelial cells from surgical specimens of FVM. (A) Representative pre-surgical fundus photograph of a right eye exhibiting a FVM encroaching on the optic nerve (dashed line) causing tractional retinal detachment with blot hemorrhages throughout retina (arrow heads). (B) Magnetic beads (arrows) allow for separation and culturing of enriched cell populations from surgical specimens (scale bar = 100 μm). (C) Cultures of isolated cells stained positively for CD31 representing a successfully isolated enriched population (scale bar = 40 μm). ©2017 American Diabetes Association. Published online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db16-1035/-/DC1 SUPPLEMENTARY DATA Supplementary Figure 2. Efficient siRNA knockdown of RUNX1 expression and function demonstrated by qRT-PCR, Western Blot, and scratch assay. (A) RUNX1 siRNA induced a 60% reduction of RUNX1 expression measured by qRT-PCR 48 hrs post-transfection whereas expression of RUNX2 and RUNX3, the two other mammalian RUNX orthologues, showed no significant changes, indicating specificity of our siRNA. Functional inhibition of Runx1 signaling was demonstrated by a 330% increase in insulin-like growth factor binding protein-3 (IGFBP3) RNA expression level, a known target of RUNX1 inhibition. Western blot demonstrated similar reduction in protein levels. (B) siRNA- 2’s effect on RUNX1 was validated by qRT-PCR and western blot, demonstrating a similar reduction in both RNA and protein. Scratch assay demonstrates functional inhibition of RUNX1 by siRNA-2. ns: not significant, * p < 0.05, *** p < 0.001 ©2017 American Diabetes Association. Published online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db16-1035/-/DC1 SUPPLEMENTARY DATA Supplementary Table 1. -
Differential and Altered Spatial Distribution of Complement Expression in Age-Related Macular Degeneration
Physiology and Pharmacology Differential and Altered Spatial Distribution of Complement Expression in Age-Related Macular Degeneration John T. Demirs, Junzheng Yang, Maura A. Crowley, Michael Twarog, Omar Delgado, Yubin Qiu, Stephen Poor, Dennis S. Rice, Thaddeus P. Dryja,* Karen Anderson,** and Sha-Mei Liao Department of Ophthalmology, Novartis Institutes for Biomedical Research, Cambridge, Massachusetts, United States Correspondence: Sha-Mei Liao, 22 PURPOSE. Dysregulation of the alternative complement pathway is a major pathogenic Windsor Street, Cambridge, MA mechanism in age-related macular degeneration. We investigated whether locally synthe- 02139, USA; sized complement components contribute to AMD by profiling complement expression [email protected]. in postmortem eyes with and without AMD. Current affiliation: *Cogan Eye METHODS. AMD severity grade 1 to 4 was determined by analysis of postmortem acquired Pathology Laboratory, Massachusetts fundus images and hematoxylin and eosin stained histological sections. TaqMan (donor Eye and Ear, Boston, Massachusetts, eyes n = 39) and RNAscope/in situ hybridization (n = 10) were performed to detect United States. = ** Biogen, Cambridge, complement mRNA. Meso scale discovery assay and Western blot (n 31) were used to Massachusetts, United States. measure complement protein levels. Received: September 2, 2020 RESULTS. The levels of complement mRNA and protein expression were approximately Accepted: May 19, 2021 15- to 100-fold (P < 0.0001–0.001) higher in macular retinal pigment epithelium Published: June 23, 2021 (RPE)/choroid tissue than in neural retina, regardless of AMD grade status. Complement Citation: Demirs JT, Yang J, Crowley mRNA and protein levels were modestly elevated in vitreous and the macular neural MA, et al. -
Open Chen-Thesis Finalv5.Pdf
The Pennsylvania State University The Graduate School Department of Neural and Behavioral Sciences EPIGENETIC ANALYSIS OF IMMUNE ASSOCIATED SIGNALING MOLECULES DURING MOUSE RETINA DEVELOPMENT A Thesis in Anatomy by Chen Yang © 2013 Chen Yang Submitted in Partial Fulfillment of the Requirements for the Degree of Master of Science May 2013 The thesis of Chen Yang was reviewed and approved* by the following: Samuel Shao-Min Zhang Assistant Professor of Neural and Behavioral Sciences Thesis Advisor Colin J. Barnstable Department Head of Neural and Behavioral Sciences Professor of Neural and Behavioral Sciences Patricia J. McLaughlin Professor of Neural and Behavioral Sciences Director of Graduate Program in Anatomy *Signatures are on file in the Graduate School. ii ABSTRACT The retina is an immune-privileged organ. Many autoimmune diseases, such as AMD, glaucoma, and diabetic retinopathy, are caused by excessive inflammatory responses targeting self-tissue. The physiological functions of extracellular and intracellular signaling molecules of immune responses have been well characterized. The epigenetic aspects of these molecules in the retina, however, have not been well elucidated. In this study, we examined the expression of selected immune-related genes, and their transcriptional accessibility via epigenetic mapping, cluster analysis, and RT-PCR. Among these genes, interleukin receptor related genes and intracellular signaling molecules exhibit higher transcriptional accessibility. Epigenetic mapping of the toll-like receptor (TLR) family revealed that 3 out of 13 TLRs exhibit H3K4me2 accumulation during retina development, suggesting that TLR2, TLR3, and TLR9 are the only TLR members expressed in the retina. Most of the NF-κB signaling molecules exhibited transcriptional accessibility, implying their essential roles in inflammatory regulation during retina maturation. -
TRAFD1 (FLN29) Interacts with Plekhm1 and Regulates Osteoclast Acidification and Resorption
University of Massachusetts Medical School eScholarship@UMMS Open Access Articles Open Access Publications by UMMS Authors 2015-05-19 TRAFD1 (FLN29) Interacts with Plekhm1 and Regulates Osteoclast Acidification and Resorption Hanna Witwicka University of Massachusetts Medical School Et al. Let us know how access to this document benefits ou.y Follow this and additional works at: https://escholarship.umassmed.edu/oapubs Part of the Cell Biology Commons, and the Developmental Biology Commons Repository Citation Witwicka H, Jia H, Kutikov AB, Reyes-Gutierrez P, Li X, Odgren PR. (2015). TRAFD1 (FLN29) Interacts with Plekhm1 and Regulates Osteoclast Acidification and Resorption. Open Access Articles. https://doi.org/ 10.1371/journal.pone.0127537. Retrieved from https://escholarship.umassmed.edu/oapubs/2540 Creative Commons License This work is licensed under a Creative Commons Attribution 4.0 License. This material is brought to you by eScholarship@UMMS. It has been accepted for inclusion in Open Access Articles by an authorized administrator of eScholarship@UMMS. For more information, please contact [email protected]. RESEARCH ARTICLE TRAFD1 (FLN29) Interacts with Plekhm1 and Regulates Osteoclast Acidification and Resorption Hanna Witwicka, Hong Jia¤a, Artem Kutikov, Pablo Reyes-Gutierrez, Xiangdong Li¤b, Paul R. Odgren* Department of Cell and Developmental Biology, University of Massachusetts Medical School, Worcester, Massachusetts, 01655 United States of America ¤a Current address: Developmental Neurobiology Department, St. Jude Children's Research Hospital, Memphis, Tennessee, 38105 United States of America ¤b Current address: Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China * [email protected] Abstract Plekhm1 is a large, multi-modular, adapter protein implicated in osteoclast vesicle trafficking and bone resorption. -
Anti-TRAFD1 Antibody (ARG59831)
Product datasheet [email protected] ARG59831 Package: 100 μl anti-TRAFD1 antibody Store at: -20°C Summary Product Description Rabbit Polyclonal antibody recognizes TRAFD1 Tested Reactivity Hu Tested Application WB Host Rabbit Clonality Polyclonal Isotype IgG Target Name TRAFD1 Antigen Species Human Immunogen Recombinant fusion protein corresponding to aa. 1-260 of Human TRAFD1 (NP_006691.1). Conjugation Un-conjugated Alternate Names TRAF-type zinc finger domain-containing protein 1; FLN29; Protein FLN29 Application Instructions Application table Application Dilution WB 1:500 - 1:1000 Application Note * The dilutions indicate recommended starting dilutions and the optimal dilutions or concentrations should be determined by the scientist. Positive Control A-375 Calculated Mw 65 kDa Observed Size 78 kDa Properties Form Liquid Purification Affinity purified. Buffer PBS (pH 7.3), 0.02% Sodium azide and 50% Glycerol. Preservative 0.02% Sodium azide Stabilizer 50% Glycerol Storage instruction For continuous use, store undiluted antibody at 2-8°C for up to a week. For long-term storage, aliquot and store at -20°C. Storage in frost free freezers is not recommended. Avoid repeated freeze/thaw cycles. Suggest spin the vial prior to opening. The antibody solution should be gently mixed before use. Note For laboratory research only, not for drug, diagnostic or other use. www.arigobio.com 1/2 Bioinformation Gene Symbol TRAFD1 Gene Full Name TRAF-type zinc finger domain containing 1 Background The innate immune system confers host defense against viral and microbial infection, and TRAFD1 is a negative feedback regulator that controls excessive immune responses (Sanada et al., 2008 [PubMed 18849341]).[supplied by OMIM, Dec 2009] Function Negative feedback regulator that controls excessive innate immune responses.