The FEM R Package: Identification of Functional Epigenetic Modules
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FK506-Binding Protein 12.6/1B, a Negative Regulator of [Ca2+], Rescues Memory and Restores Genomic Regulation in the Hippocampus of Aging Rats
This Accepted Manuscript has not been copyedited and formatted. The final version may differ from this version. A link to any extended data will be provided when the final version is posted online. Research Articles: Neurobiology of Disease FK506-Binding Protein 12.6/1b, a negative regulator of [Ca2+], rescues memory and restores genomic regulation in the hippocampus of aging rats John C. Gant1, Eric M. Blalock1, Kuey-Chu Chen1, Inga Kadish2, Olivier Thibault1, Nada M. Porter1 and Philip W. Landfield1 1Department of Pharmacology & Nutritional Sciences, University of Kentucky, Lexington, KY 40536 2Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL 35294 DOI: 10.1523/JNEUROSCI.2234-17.2017 Received: 7 August 2017 Revised: 10 October 2017 Accepted: 24 November 2017 Published: 18 December 2017 Author contributions: J.C.G. and P.W.L. designed research; J.C.G., E.M.B., K.-c.C., and I.K. performed research; J.C.G., E.M.B., K.-c.C., I.K., and P.W.L. analyzed data; J.C.G., E.M.B., O.T., N.M.P., and P.W.L. wrote the paper. Conflict of Interest: The authors declare no competing financial interests. NIH grants AG004542, AG033649, AG052050, AG037868 and McAlpine Foundation for Neuroscience Research Corresponding author: Philip W. Landfield, [email protected], Department of Pharmacology & Nutritional Sciences, University of Kentucky, 800 Rose Street, UKMC MS 307, Lexington, KY 40536 Cite as: J. Neurosci ; 10.1523/JNEUROSCI.2234-17.2017 Alerts: Sign up at www.jneurosci.org/cgi/alerts to receive customized email alerts when the fully formatted version of this article is published. -
Accurate Annotation of Human Protein-Coding Small Open Reading Frames
HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author Nat Chem Manuscript Author Biol. Author Manuscript Author manuscript; available in PMC 2020 June 09. Published in final edited form as: Nat Chem Biol. 2020 April ; 16(4): 458–468. doi:10.1038/s41589-019-0425-0. Accurate annotation of human protein-coding small open reading frames Thomas F. Martinez1,*, Qian Chu1, Cynthia Donaldson1, Dan Tan1, Maxim N. Shokhirev2, Alan Saghatelian1,* 1Clayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, La Jolla, California 92037, USA 2Razavi Newman Integrative Genomics Bioinformatics Core, Salk Institute for Biological Studies, La Jolla, California 92037, USA Abstract Functional protein-coding small open reading frames (smORFs) are emerging as an important class of genes. However, the number of translated smORFs in the human genome is unclear because proteogenomic methods are not sensitive enough, and, as we show, Ribo-Seq strategies require additional measures to ensure comprehensive and accurate smORF annotation. Here, we integrate de novo transcriptome assembly and Ribo-Seq into an improved workflow that overcomes obstacles with previous methods to more confidently annotate thousands of smORFs. Evolutionary conservation analyses suggest that hundreds of smORF-encoded microproteins are likely functional. Additionally, many smORFs are regulated during fundamental biological processes, such as cell stress. Peptides derived from smORFs are also detectable on human leukocyte antigen complexes, revealing smORFs as a source of antigens. Thus, by including additional validation into our smORF annotation workflow, we accurately identify thousands of unannotated translated smORFs that will provide a rich pool of unexplored, functional human genes. Annotation of open reading frames (ORFs) from genome sequencing was initially carried out by locating in-frame start (AUG) and stop codons1–3. -
Mutants in Three Novel Complementation Groups Inhibit
Mutants in Three Novel Complementation Groups Inhibit Membrane Protein Insertion into and Soluble Protein Translocation across the Endoplasmic Reticulum Membrane of Saccharomyces cerevisiae Neil Green,* Hong Fang, $ and Peter Walter* *Department ofBiochemistry and Biophysics, School ofMedicine, University of California, San Francisco, California 94143-0448; and tDepartment of Microbiology and Immunology, School ofMedicine, Vanderbilt University, Nashville, Tennessee 37232-2363 Abstract. We have isolated mutants that inhibit mem- tations in SEC61 and SEC63, which were previously brane protein insertion into the ER membrane of Sac- isolated as mutants inhibiting the translocation of solu- charomyces cerevisiae. The mutants were contained in ble proteins, also affect the insertion of membrane three complementation groups, which we have named proteins into the ER. Taken together our data indicate SEC70, SEC1, and SEC72. The mutants also inhib- that the process of protein translocation across the ER ited the translocation of soluble proteins into the lu- membrane involves a much larger number of gene men of the ER, indicating that they pleiotropically products than previously appreciated . Moreover, differ- affect protein transport across and insertion into the ent translocation substrates appear to have different re- ER membrane. Surprisingly, the mutants inhibited the quirements for components of the cellular targeting translocation and insertion of different proteins to dras- and translocation apparatus . tically different degrees. We have also shown that mu- SCENT genetic studies in Saccharomyces cerevisiae Interestingly, not all proteins passing through the secretory have shown that the SEC61, SEC62, and SEC63 pathway were equally affected by mutations in SEC61, SEC- genes are required for secretory protein translocation 62, and SEC63 ; the translocation of pre-invertase showed into the lumen of the ER (Deshaies and Schekman, 1987; little inhibition in mutant cells (Rothblatt et al., 1989) and Rothblatt et al., 1989). -
SEC62 Rabbit Polyclonal Antibody – TA319720 | Origene
OriGene Technologies, Inc. 9620 Medical Center Drive, Ste 200 Rockville, MD 20850, US Phone: +1-888-267-4436 [email protected] EU: [email protected] CN: [email protected] Product datasheet for TA319720 SEC62 Rabbit Polyclonal Antibody Product data: Product Type: Primary Antibodies Applications: IF, IHC, WB Recommended Dilution: WB: 0.5 - 1 ug/mL, ICC: 5 ug/mL, IF: 20 ug/mL Reactivity: Human, Mouse, Rat Host: Rabbit Isotype: IgG Clonality: Polyclonal Immunogen: SEC62 antibody was raised against an 18 amino acid synthetic peptide near the carboxy terminus of human SEC62. Formulation: SEC62 Antibody is supplied in PBS containing 0.02% sodium azide. Concentration: 1ug/ul Purification: SEC62 Antibody is affinity chromatography purified via peptide column. Conjugation: Unconjugated Storage: Store at -20°C as received. Stability: Stable for 12 months from date of receipt. Gene Name: SEC62 homolog, preprotein translocation factor Database Link: NP_003253 Entrez Gene 69276 MouseEntrez Gene 294912 RatEntrez Gene 7095 Human Q99442 Background: SEC62 Antibody: SEC62 is an integral membrane protein located in the rough endoplasmic reticulum (ER) and is part of the SEC61-SEC62-SEC63 complex that is the central component of the protein translocation apparatus of the ER membrane. It is speculated that SEC61- SEC62-SEC63 may perform post-translational protein translocation into the ER and might also perform the backward transport of ER proteins that are subject to the ubiquitin-proteasome- dependent degradation pathway. Silencing of this gene with RNAi dramatically reduced the migration and invasive potential of numerous tumor cell lines, suggesting that it may be an attractive target for therapy of various tumors. -
Gene Expression Imputation Across Multiple Brain Regions Provides Insights Into Schizophrenia Risk
VU Research Portal Gene expression imputation across multiple brain regions provides insights into schizophrenia risk iPSYCH-GEMS Schizophrenia Working Group; CommonMind Consortium; The Schizophrenia Working Group of the PsyUniversity of Copenhagenchiatric Genomics Consortium published in Nature Genetics 2019 DOI (link to publisher) 10.1038/s41588-019-0364-4 document version Publisher's PDF, also known as Version of record document license Article 25fa Dutch Copyright Act Link to publication in VU Research Portal citation for published version (APA) iPSYCH-GEMS Schizophrenia Working Group, CommonMind Consortium, & The Schizophrenia Working Group of the PsyUniversity of Copenhagenchiatric Genomics Consortium (2019). Gene expression imputation across multiple brain regions provides insights into schizophrenia risk. Nature Genetics, 51(4), 659–674. https://doi.org/10.1038/s41588-019-0364-4 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal ? Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. E-mail address: [email protected] Download date: 28. -
Sec62/Ki67 and P16/Ki67 Dual-Staining Immunocytochemistry
Archives of Gynecology and Obstetrics (2019) 299:825–833 https://doi.org/10.1007/s00404-018-5021-0 GYNECOLOGIC ONCOLOGY Sec62/Ki67 and p16/Ki67 dual‑staining immunocytochemistry in vulvar cytology for the identifcation of vulvar intraepithelial neoplasia and vulvar cancer: a pilot study Ferenc Zoltan Takacs1 · Julia Caroline Radosa1 · Florian Bochen2 · Ingolf Juhasz‑Böss1 · Erich‑Franz Solomayer1 · Rainer M. Bohle3 · Georg‑Peter Breitbach1 · Bernard Schick2 · Maximilian Linxweiler2 Received: 22 October 2018 / Accepted: 12 December 2018 / Published online: 4 January 2019 © Springer-Verlag GmbH Germany, part of Springer Nature 2019 Abstract Purpose The aim of this study was to analyze the diagnostic performance of a newly established immunocytochemical dual-staining protocol for the simultaneous expression of SEC62 and Ki67 in vulvar liquid-based cytology specimens for the identifcation of vulvar intraepithelial neoplasia (VIN) and vulvar cancer. In addition, we investigated the p16/Ki67 dual stain, which has already been established in cervical cytology. Materials and methods For this pilot study, residual material from liquid-based cytology was collected retrospectively from 45 women. The presence of one or more double-immunoreactive cells was considered as a positive test result for Sec62/Ki67 and p16/Ki67 dual staining. The test results were correlated with the course of histology. Results All cases of VIN and vulvar cancer were Sec62/Ki67 and p16/Ki67 dual-stain positive, and normal and low-grade squamous intraepithelial lesions were all negative. The sensitivity of cytology for VIN + cases was 100% (22/22), whereas punch biopsy classifed one case of vulvar carcinoma as infammation. All cases with high-intensity (grades 3 and 4) Sec62 staining in Sec62/Ki67-positive cases were carcinomas. -
Ma-And-Mayr-Cell-2018.Pdf
Article A Membraneless Organelle Associated with the Endoplasmic Reticulum Enables 30UTR-Mediated Protein-Protein Interactions Graphical Abstract Authors Weirui Ma, Christine Mayr Correspondence [email protected] In Brief ER-associated granules foster selective protein-protein interactions dictated by the nucleotide composition of the encoding mRNA. Highlights d TIS granules are membraneless organelles intertwined with the endoplasmic reticulum d TIS11B forms TIS granules that enrich or exclude specific mRNAs and proteins in vivo d TIS granules enable translation of mRNAs with AU-rich elements at an ER subdomain d Specific protein-protein interactions can only be formed in the TIS granule region Ma & Mayr, 2018, Cell 175, 1–15 November 29, 2018 ª 2018 Elsevier Inc. https://doi.org/10.1016/j.cell.2018.10.007 Please cite this article in press as: Ma and Mayr, A Membraneless Organelle Associated with the Endoplasmic Reticulum Enables 30UTR- Mediated Protein-Protein Interactions, Cell (2018), https://doi.org/10.1016/j.cell.2018.10.007 Article A Membraneless Organelle Associated with the Endoplasmic Reticulum Enables 30UTR-Mediated Protein-Protein Interactions Weirui Ma1 and Christine Mayr1,2,* 1Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA 2Lead Contact *Correspondence: [email protected] https://doi.org/10.1016/j.cell.2018.10.007 SUMMARY cesses, including signaling and the addition of post-translational modifications (Li et al., 2012; Su et al., 2016). Approximately half of human genes generate mRNAs One type of membraneless organelles are RNA granules that with alternative 30 untranslated regions (30UTRs). contain mRNA transcripts packaged into ribonucleoprotein as- Through 30UTR-mediated protein-protein interac- semblies (Han et al., 2012). -
Rab18 Promotes Lipid Droplet (LD) Growth by Tethering the ER to Lds Through SNARE and NRZ Interactions
Published Online: 24 January, 2018 | Supp Info: http://doi.org/10.1083/jcb.201704184 Article Downloaded from jcb.rupress.org on August 7, 2018 Rab18 promotes lipid droplet (LD) growth by tethering the ER to LDs through SNARE and NRZ interactions Dijin Xu,1* Yuqi Li,1* Lizhen Wu,1* Ying Li,1 Dongyu Zhao,1 Jinhai Yu,1 Tuozhi Huang,1 Charles Ferguson,2 Robert G. Parton,2,3 Hongyuan Yang,4 and Peng Li1 1State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing, China 2Institute for Molecular Bioscience and 3Centre for Microscopy and Microanalysis, University of Queensland, Brisbane, Australia 4School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia Lipid incorporation from endoplasmic reticulum (ER) to lipid droplet (LD) is important in controlling LD growth and intra- cellular lipid homeostasis. However, the molecular link mediating ER and LD cross talk remains elusive. Here, we identi- fied Rab18 as an important Rab guanosine triphosphatase in controlling LD growth and maturation.Rab18 deficiency resulted in a drastically reduced number of mature LDs and decreased lipid storage, and was accompanied by increased ER stress. Rab3GAP1/2, the GEF of Rab18, promoted LD growth by activating and targeting Rab18 to LDs. LD-associated Rab18 bound specifically to the ER-associated NAG-RINT1-ZW10 (NRZ) tethering complex and their associated SNAREs (Syntaxin18, Use1, BNIP1), resulting in the recruitment of ER to LD and the formation of direct ER–LD contact. Cells with defects in the NRZ/SNA RE complex function showed reduced LD growth and lipid storage. -
Identification of Differentially Expressed Genes in Human Bladder Cancer Through Genome-Wide Gene Expression Profiling
521-531 24/7/06 18:28 Page 521 ONCOLOGY REPORTS 16: 521-531, 2006 521 Identification of differentially expressed genes in human bladder cancer through genome-wide gene expression profiling KAZUMORI KAWAKAMI1,3, HIDEKI ENOKIDA1, TOKUSHI TACHIWADA1, TAKENARI GOTANDA1, KENGO TSUNEYOSHI1, HIROYUKI KUBO1, KENRYU NISHIYAMA1, MASAKI TAKIGUCHI2, MASAYUKI NAKAGAWA1 and NAOHIKO SEKI3 1Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520; Departments of 2Biochemistry and Genetics, and 3Functional Genomics, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan Received February 15, 2006; Accepted April 27, 2006 Abstract. Large-scale gene expression profiling is an effective CKS2 gene not only as a potential biomarker for diagnosing, strategy for understanding the progression of bladder cancer but also for staging human BC. This is the first report (BC). The aim of this study was to identify genes that are demonstrating that CKS2 expression is strongly correlated expressed differently in the course of BC progression and to with the progression of human BC. establish new biomarkers for BC. Specimens from 21 patients with pathologically confirmed superficial (n=10) or Introduction invasive (n=11) BC and 4 normal bladder samples were studied; samples from 14 of the 21 BC samples were subjected Bladder cancer (BC) is among the 5 most common to microarray analysis. The validity of the microarray results malignancies worldwide, and the 2nd most common tumor of was verified by real-time RT-PCR. Of the 136 up-regulated the genitourinary tract and the 2nd most common cause of genes we detected, 21 were present in all 14 BCs examined death in patients with cancer of the urinary tract (1-7). -
Identification of Rab18 As an Essential Host Factor for Bkpyv Infection Using a Whole Genome RNA 2 Interference Screen
bioRxiv preprint doi: https://doi.org/10.1101/157602; this version posted June 29, 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-NC-ND 4.0 International license. 1 Identification of Rab18 as an Essential Host Factor for BKPyV Infection Using a Whole Genome RNA 2 Interference Screen 3 4 Linbo Zhaoa, Michael J. Imperialea,b,* 5 6 aDepartment of Microbiology and Immunology, bComprehensive Cancer Center, University of Michigan, 7 Ann Arbor, MI, 48109, USA 8 9 10 11 12 13 14 15 16 17 18 * Corresponding author. Department of Microbiology and Immunology, 1150 West Medical Center 19 Drive, 5724 Medical Science II, Ann Arbor, MI 48109-5620, USA. Tel. +1 (734) 763 9162. Fax: +1 (734) 20 764 3562. 21 E-mail addresses: [email protected] (L. Zhao); [email protected] (M.J. Imperiale). 22 23 24 1 bioRxiv preprint doi: https://doi.org/10.1101/157602; this version posted June 29, 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-NC-ND 4.0 International license. 25 Abstract 26 27 BK polyomavirus (BKPyV) is a human pathogen first isolated in 1971. BKPyV infection is ubiquitous in the 28 human population, with over 80% of adults worldwide being seropositive for BKPyV. BKPyV infection is 29 usually asymptomatic; however, BKPyV reactivation in immunosuppressed transplant patients causes 30 two diseases, polyomavirus-associated nephropathy and hemorrhagic cystitis. -
Rare Mutations in RINT1 Predispose Carriers to Breast and Lynch Syndrome–Spectrum Cancers
Published OnlineFirst May 2, 2014; DOI: 10.1158/2159-8290.CD-14-0212 RESEARCH ARTICLE Rare Mutations in RINT1 Predispose Carriers to Breast and Lynch Syndrome–Spectrum Cancers Daniel J. Park 1 , K a y o k o Ta o 7 , Florence Le Calvez-Kelm 17 , Tu Nguyen-Dumont 1 , Nivonirina Robinot 17 , Fleur Hammet1 , Fabrice Odefrey 1 , Helen Tsimiklis 1 , Zhi L. Teo 1 , Louise B. Thingholm 1 , Erin L. Young 7 , Catherine Voegele 17 , Andrew Lonie 4 , Bernard J. Pope 2 , 4 , Terrell C. Roane 10 , Russell Bell 7 , Hao Hu 11 , Shankaracharya 11 , Chad D. Huff 11 , Jonathan Ellis 6 , Jun Li 6 , Igor V. Makunin 6 , Esther M. John 12 , 13 , Irene L. Andrulis 19 , Mary B. Terry 14 , Mary Daly 15 , Saundra S. Buys 9 , Carrie Snyder 16 , Henry T. Lynch 16 , Peter Devilee20 , Graham G. Giles 3 , 5 , John L. Hopper 3 , 21 , Bing-Jian Feng 8 , 9 , Fabienne Lesueur 17 , 18 , Sean V. Tavtigian 7 , Melissa C. Southey 1 , and David E. Goldgar 8 , 9 ABSTRACT Approximately half of the familial aggregation of breast cancer remains unex- plained. A multiple-case breast cancer family exome-sequencing study identifi ed three likely pathogenic mutations in RINT1 (NM_021930.4) not present in public sequencing data- bases: RINT1 c.343C>T (p.Q115X), c.1132_1134del (p.M378del), and c.1207G>T (p.D403Y). On the basis of this fi nding, a population-based case–control mutation-screening study was conducted that identifi ed 29 carriers of rare (minor allele frequency < 0.5%), likely pathogenic variants: 23 in 1,313 early-onset breast cancer cases and six in 1,123 frequency-matched controls [OR, 3.24; 95% confi - dence interval (CI), 1.29–8.17; P = 0.013]. -
Trypsin-Encoding PRSS1-PRSS2 Variations
ARTICLE Acute Lymphoblastic Leukemia Ferrata Storti Foundation Trypsin-encoding PRSS1-PRSS2 variations influence the risk of asparaginase-associated pancreatitis in children with acute lymphoblastic leukemia: a Ponte di Legno toxicity working group report Haematologica 2019 Benjamin O. Wolthers,1 Thomas L. Frandsen,1 Chirag J. Patel,2 Rachid Abaji,3 Volume 104(3):556-563 Andishe Attarbaschi,4 Shlomit Barzilai,5 Antonella Colombini,6 Gabriele Escherich,7 Marie Grosjean,8 Maja Krajinovic,3,9 Eric Larsen,10 Der-Cherng Liang,11 Anja Möricke,12 Kirsten K. Rasmussen,1 Sujith Samarasinghe,13 Lewis B. Silverman,14 Inge M. van der Sluis,15 Martin Stanulla,16 Morten Tulstrup,1 Rachita Yadav,8,17 Wenjian Yang,18 Ester Zapotocka,19 Ramneek Gupta8 and Kjeld Schmiegelow1,20 on behalf of the Ponte di Legno toxicity working group 1Department of Pediatrics and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen, Denmark; 2Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA; 3CHU Sainte-Justine Research Center and Department of Pharmacology, University of Montreal, QC, Canada; 4Department of Pediatric Hematology and Oncology, St Anna Children's Hospital and Department of Pediatric and Adolescent Medicine, Medical University of Vienna, Austria; 5Pediatric Hematology and Oncology, Schneider Children's Medical Center of Israel, Petah-Tikva, Israel and Sackler Faculty of Medicine, Tel Aviv University, Israel; 6Department of Pediatrics, Ospedale San Gerardo, University of Milano-Bicocca, Fondazione MBBM, Monza, Italy;