(APC) Is Required for Normal Development of Skin and Thymus
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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. -
Hormone Therapy Use and Breast Tissue DNA
http://www.diva-portal.org This is the published version of a paper published in Epigenetics. Citation for the original published paper (version of record): Harlid, S., Xu, Z., Kirk, E., Wilson, L E., Troester, M A. et al. (2019) Hormone therapy use and breast tissue DNA methylation: analysis of epigenome wide data from the normal breast study Epigenetics, 14(2): 146-157 https://doi.org/10.1080/15592294.2019.1580111 Access to the published version may require subscription. N.B. When citing this work, cite the original published paper. Permanent link to this version: http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-157445 EPIGENETICS 2019, VOL. 14, NO. 2, 146–157 https://doi.org/10.1080/15592294.2019.1580111 RESEARCH PAPER Hormone therapy use and breast tissue DNA methylation: analysis of epigenome wide data from the normal breast study Sophia Harlid a,b, Zongli Xuc, Erin Kirkd, Lauren E. Wilson c,e, Melissa A. Troesterd, and Jack A. Taylor a,c aEpigenetics & Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA; bDepartment of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden; cEpidemiology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA; dDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; eDepartment of Population Health Sciences, Duke University School of Medicine, Durham, NC, USA ABSTRACT ARTICLE HISTORY Hormone therapy (HT) is associated with increased risk of breast cancer, strongly dependent on Received 4 September 2018 type, duration, and recency of use. HT use could affect cancer risk by changing breast tissue Revised 21 December 2018 transcriptional programs. -
A Significant Soluble Keratin Fraction In
Journal of Cell Science 105, 433-444 (1993) 433 Printed in Great Britain © The Company of Biologists Limited 1993 A significant soluble keratin fraction in ‘simple’ epithelial cells Lack of an apparent phosphorylation and glycosylation role in keratin solubility Chih-Fong Chou*, Carrie L. Riopel, Lusijah S. Rott and M. Bishr Omary† Palo Alto Veterans Administration Medical Center and the Digestive Disease Center at Stanford University, School of Medicine, 3801 Miranda Avenue, GI 111, Palo Alto, CA 94304, USA *Author for reprint requests †Author for correspondence SUMMARY We studied the solubility of keratin polypeptides 8 and aments in vitro as determined by electron microscopy. 18 (K8/18), which are the predominant intermediate fil- Cross-linking of soluble K8/18 followed by immunopre- aments in the human colonic epithelial cell line HT29. cipitation resulted in dimeric and tetrameric forms, We find that asynchronously growing cells (G0/G1 stage based on migration in SDS-polyacrylamide gels. In of the cell cycle) have a substantial pool of soluble ker- addition, cross-linked and native soluble K8/18 showed atin that constitutes approx. 5% of total cellular ker- similar migration on nondenaturing gels and similar atin. This soluble keratin pool was observed after sedimentation after sucrose density gradient centrifu- immunoprecipitation of K8/18 from the cytosolic frac- gation. Our results indicate that simple epithelial ker- tion of cells disrupted using three detergent-free meth- atins are appreciably more soluble than previously rec- ods. Several other cell lines showed a similar significant ognized. The soluble keratin form is assembly competent soluble cytosolic K8/18 pool. -
Identifying the Optimal Gene and Gene Set in Hepatocellular Carcinoma Based on Differential Expression and Differential Co-Expression Algorithm
1066 ONCOLOGY REPORTS 37: 1066-1074, 2017 Identifying the optimal gene and gene set in hepatocellular carcinoma based on differential expression and differential co-expression algorithm LI-YANG DONG1*, WEI-ZHONG ZHOU1*, JUN-WEI NI1, WEI XIANG1, WEN-HAO HU1, CHANG YU1 and HAI-YAN LI2 Departments of 1Invasive Technology and 2Rehabilitation, The First Affiliated Hospital of Wenzhou Medical University, Ouhai, Wenzhou, Zhejiang 325000, P.R. China Received June 23, 2016; Accepted August 10, 2016 DOI: 10.3892/or.2016.5333 * Abstract. The objective of this study was to identify the with ΔG = 18.681 and 24 HDE-HDC partitions in total. In optimal gene and gene set for hepatocellular carcinoma conclusion, we successfully investigated the optimal gene, (HCC) utilizing differential expression and differential MAPRE1, and gene set, nucleoside metabolic process, which co-expression (DEDC) algorithm. The DEDC algorithm may be potential biomarkers for targeted therapy and provide consisted of four parts: calculating differential expression significant insight for revealing the pathological mechanism (DE) by absolute t-value in t-statistics; computing differential underlying HCC. co-expression (DC) based on Z-test; determining optimal thresholds on the basis of Chi-squared (χ2) maximization and Introduction the corresponding gene was the optimal gene; and evaluating functional relevance of genes categorized into different Hepatocellular carcinoma (HCC) is the fifth most common partitions to determine the optimal gene set with highest mean cancer worldwide and the third leading cause of cancer-related * minimum functional information (FI) gain (ΔG). The optimal mortality (1), making it urgent to identify early diagnostic thresholds divided genes into four partitions, high DE and markers and therapeutic targets (2). -
ARHGEF4 (NM 015320) Human Tagged ORF Clone Product Data
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 RC215591 ARHGEF4 (NM_015320) Human Tagged ORF Clone Product data: Product Type: Expression Plasmids Product Name: ARHGEF4 (NM_015320) Human Tagged ORF Clone Tag: Myc-DDK Symbol: ARHGEF4 Synonyms: ASEF; ASEF1; GEF4; SMIM39; STM6 Vector: pCMV6-Entry (PS100001) E. coli Selection: Kanamycin (25 ug/mL) Cell Selection: Neomycin This product is to be used for laboratory only. Not for diagnostic or therapeutic use. View online » ©2021 OriGene Technologies, Inc., 9620 Medical Center Drive, Ste 200, Rockville, MD 20850, US 1 / 5 ARHGEF4 (NM_015320) Human Tagged ORF Clone – RC215591 ORF Nucleotide >RC215591 representing NM_015320 Sequence: Red=Cloning site Blue=ORF Green=Tags(s) TTTTGTAATACGACTCACTATAGGGCGGCCGGGAATTCGTCGACTGGATCCGGTACCGAGGAGATCTGCC GCCGCGATCGCC ATGCCCTGGGAAGAACCAGCAGGTGAGAAGCCCAGTTGCTCTCACAGTCAGAAGGCATTCCACATGGAGC CTGCCCAGAAGCCCTGCTTCACCACTGACATGGTGACATGGGCCCTCCTCTGCATCTCTGCAGAGACTGT GCGTGGGGAGGCTCCTTCACAGCCTAGGGGCATCCCTCACCGCTCGCCCGTCAGTGTGGATGACCTGTGG CTGGAGAAGACACAGAGAAAGAAGTTGCAGAAGCAGGCCCACATCGAAAGGAGGCTGCACATAGGGGCAG TGCACAAAGATGGAGTCAAGTGCTGGAGAAAGACGATCATTACCTCTCCAGAGTCTTTGAATCTCCCTAG AAGAAGCCATCCACTCTCCCAGAGTGCTCCAACGGGACTGAACCACATGGGCTGGCCAGAGCACACACCA GGCACTGCCATGCCTGATGGAGCTCTGGACACAGCTGTCTGCGCTGACGAAGTGGGGAGCGAGGAGGACC TGTATGATGACCTGCACAGCTCCAGCCACCACTACAGCCACCCTGGAGGGGGTGGGGAGCAGCTGGCTAT CAATGAGCTCATCAGCGATGGCAGTGTGGTCTGCGCTGAAGCACTCTGGGACCATGTCACCATGGACGAC -
Genome-Wide Rnai Screening Identifies Human Proteins with A
RESOURCES Genome-wide RNAi screening identifies human proteins with a regulatory function in the early secretory pathway Jeremy C. Simpson1,7, Brigitte Joggerst2, Vibor Laketa2, Fatima Verissimo2, Cihan Cetin2, Holger Erfle2,6, Mariana G. Bexiga1, Vasanth R. Singan1, Jean-Karim Hériché3, Beate Neumann3, Alvaro Mateos2, Jonathon Blake4, Stephanie Bechtel5, Vladimir Benes4, Stefan Wiemann5, Jan Ellenberg2,3 and Rainer Pepperkok2,7 The secretory pathway in mammalian cells has evolved to facilitate the transfer of cargo molecules to internal and cell surface membranes. Use of automated microscopy-based genome-wide RNA interference screens in cultured human cells allowed us to identify 554 proteins influencing secretion. Cloning, fluorescent-tagging and subcellular localization analysis of 179 of these proteins revealed that more than two-thirds localize to either the cytoplasm or membranes of the secretory and endocytic pathways. The depletion of 143 of them resulted in perturbations in the organization of the COPII and/or COPI vesicular coat complexes of the early secretory pathway, or the morphology of the Golgi complex. Network analyses revealed a so far unappreciated link between early secretory pathway function, small GTP-binding protein regulation, actin cytoskeleton organization and EGF-receptor-mediated signalling. This work provides an important resource for an integrative understanding of global cellular organization and regulation of the secretory pathway in mammalian cells. Within higher eukaryotic cells membrane traffic pathways connect the Extensive efforts over many years have revealed a significant number various membrane-bounded organelles, thereby ensuring that they of regulators associated with the secretory pathway. Early biochemical retain the correct complement of proteins and lipids to maintain approaches to identify individual machinery components have started cellular homeostasis. -
(Arhgef4) Deficiency Enhances Spatial and Object Recognition Memory
https://doi.org/10.5607/en20049 Exp Neurobiol. 2020 Oct;29(5):334-343. pISSN 1226-2560 • eISSN 2093-8144 Short Communication Rho Guanine Nucleotide Exchange Factor 4 (Arhgef4) Deficiency Enhances Spatial and Object Recognition Memory Ki-Seo Yoo1, Kina Lee1, Yong-Seok Lee2, Won-Jong Oh3 and Hyong Kyu Kim1* 1Department of Medicine and Microbiology, Graduate Program in Neuroscience, College of Medicine, Chungbuk National University, Cheongju 28644, 2Department of Physiology, Department of Biomedical Science, Seoul National University College of Medicine, Seoul 03080, 3Neurovascular Unit Research Group, Korea Brain Research Institute, Daegu 41062, Korea Guanine nucleotide exchange factors (GEFs) play multiple functional roles in neurons. In a previous study, we reported that Arhgef4 (Rho guanine nucleotide exchange factor 4) functioned as a negative regulator of the excitatory synaptic function by sequestering postsynaptic density protein 95 (PSD-95). However, the role of Arhgef4 in behavior has not been examined. We performed comprehensive behavioral tests in knockout (KO) mice to investigate of the effects of Arhgef4 deficiency. We found that the expressed PSD-95 particle size was significantly increased in hippocampal neuronal cultures from Arhgef4 KO mice, which is consistent with the previous in vitro findings. Arhgef4 KO mice exhibited general motor activity and anxiety-like behavior comparable to those of the wild type littermates. However, spatial memory and object recognition memory were signifi- cantly enhanced in the Arhgef4 KO mice. Taken together, these data confirm the role of Arhgef4 as a negative synaptic regulator at the behavioral level. Key words: Arhgef4, PSD-95, Spatial memory, Recognition INTRODUCTION tin, a GEF of inhibitory synapses selectively activating the small GTPase Cdc42, results in a reduced capability of spatial learning Rho guanine nucleotide exchange factors (GEFs) are involved in and enhances anxiety-like behavior in collybistin-deficient mice the activation of Rho family GTPases by accelerating the exchange [4]. -
Relevance Network Between Chemosensitivity and Transcriptome in Human Hepatoma Cells1
Vol. 2, 199–205, February 2003 Molecular Cancer Therapeutics 199 Relevance Network between Chemosensitivity and Transcriptome in Human Hepatoma Cells1 Masaru Moriyama,2 Yujin Hoshida, topoisomerase II  expression, whereas it negatively Motoyuki Otsuka, ShinIchiro Nishimura, Naoya Kato, correlated with expression of carboxypeptidases A3 Tadashi Goto, Hiroyoshi Taniguchi, and Z. Response to nimustine was associated with Yasushi Shiratori, Naohiko Seki, and Masao Omata expression of superoxide dismutase 2. Department of Gastroenterology, Graduate School of Medicine, Relevance networks identified several negative University of Tokyo, Tokyo 113-8655 [M. M., Y. H., M. O., N. K., T. G., H. T., Y. S., M. O.]; Cellular Informatics Team, Computational Biology correlations between gene expression and resistance, Research Center, Tokyo 135-0064 [S. N.]; and Department of which were missed by hierarchical clustering. Our Functional Genomics, Graduate School of Medicine, Chiba University, results suggested the necessity of systematically Chiba 260-8670 [N. S.], Japan evaluating the transporting systems that may play a major role in resistance in hepatoma. This may provide Abstract useful information to modify anticancer drug action in Generally, hepatoma is not a chemosensitive tumor, hepatoma. and the mechanism of resistance to anticancer drugs is not fully elucidated. We aimed to comprehensively Introduction evaluate the relationship between chemosensitivity and Hepatoma is a major cause of death even in developed gene expression profile in human hepatoma cells, by countries, and its incidence is increasing (1). Despite the using microarray analysis, and analyze the data by progress of therapeutic technique (2), the efficacy of radical constructing relevance networks. therapy is hampered by frequent recurrence and advance of In eight hepatoma cell lines (HLE, HLF, Huh7, Hep3B, the tumor (3). -
Genome-Wide Enrichment Analysis Between Endometriosis and Obesity-Related Traits Reveals Novel Susceptibility Loci
Human Molecular Genetics, 2015, Vol. 24, No. 4 1185–1199 doi:10.1093/hmg/ddu516 Advance Access published on October 8, 2014 Genome-wide enrichment analysis between endometriosis and obesity-related traits reveals novel susceptibility loci Nilufer Rahmioglu1, Stuart Macgregor2, Alexander W. Drong1,A˚ sa K. Hedman1,5, Holly R. Harris6,7, Joshua C. Randall8, Inga Prokopenko1,9,10, The International Endogene Consortium (IEC), The GIANT Consortium, Dale R. Nyholt3, Andrew P. Morris1,11,{, Grant W. Montgomery4,{, Downloaded from https://academic.oup.com/hmg/article/24/4/1185/617584 by guest on 05 February 2021 Stacey A. Missmer6,{, Cecilia M. Lindgren1,12,{ and Krina T. Zondervan1,13,∗,{ 1Wellcome Trust Center for Human Genetics, University of Oxford, Oxford OX3 7BN, UK, 2Statistical Genetics, 3Neurogenetics, 4Molecular Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4029, Australia, 5Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden, 6Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women’s Hospital and Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA, 7Unit of Nutritional Epidemiology, Institute for Environmental Medicine, Karolinska Institutet, PO Box 210, SE-171 77 Stockholm, Sweden, 8Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK, 9Department of Genomics of Common Disease, Imperial College London, London W12 0NN, UK, 10Oxford Centre for Diabetes, Endocrinology and Metabolism, University -
Structures of the ß-Keratin Filaments and Keratin Intermediate Filaments in the Epidermal Appendages of Birds and Reptiles (Sauropsids)
G C A T T A C G G C A T genes Review Structures of the ß-Keratin Filaments and Keratin Intermediate Filaments in the Epidermal Appendages of Birds and Reptiles (Sauropsids) David A.D. Parry School of Fundamental Sciences, Massey University, Private Bag 11-222, Palmerston North 4442, New Zealand; [email protected]; Tel.: +64-6-9517620; Fax: +64-6-3557953 Abstract: The epidermal appendages of birds and reptiles (the sauropsids) include claws, scales, and feathers. Each has specialized physical properties that facilitate movement, thermal insulation, defence mechanisms, and/or the catching of prey. The mechanical attributes of each of these appendages originate from its fibril-matrix texture, where the two filamentous structures present, i.e., the corneous ß-proteins (CBP or ß-keratins) that form 3.4 nm diameter filaments and the α-fibrous molecules that form the 7–10 nm diameter keratin intermediate filaments (KIF), provide much of the required tensile properties. The matrix, which is composed of the terminal domains of the KIF molecules and the proteins of the epidermal differentiation complex (EDC) (and which include the terminal domains of the CBP), provides the appendages, with their ability to resist compression and torsion. Only by knowing the detailed structures of the individual components and the manner in which they interact with one another will a full understanding be gained of the physical properties of the tissues as a whole. Towards that end, newly-derived aspects of the detailed conformations of the two filamentous structures will be discussed and then placed in the context of former knowledge. -
The Abundance of Cis-Acting Loci Leading to Differential Allele
Yeo et al. BMC Genomics (2016) 17:620 DOI 10.1186/s12864-016-2922-9 RESEARCH ARTICLE Open Access The abundance of cis-acting loci leading to differential allele expression in F1 mice and their relationship to loci harboring genes affecting complex traits Seungeun Yeo1, Colin A. Hodgkinson1, Zhifeng Zhou1, Jeesun Jung2, Ming Leung1, Qiaoping Yuan1 and David Goldman1* Abstract Background: Genome-wide surveys have detected cis-acting quantitative trait loci altering levels of RNA transcripts (RNA-eQTLs) by associating SNV alleles to transcript levels. However, the sensitivity and specificity of detection of cis- expression quantitative trait loci (eQTLs) by genetic approaches, reliant as it is on measurements of transcript levels in recombinant inbred strains or offspring from arranged crosses, is unknown, as is their relationship to QTL’s for complex phenotypes. Results: We used transcriptome-wide differential allele expression (DAE) to detect cis-eQTLs in forebrain and kidney from reciprocal crosses between three mouse inbred strains, 129S1/SvlmJ, DBA/2J, and CAST/EiJ and C57BL/6 J. Two of these crosses were previously characterized for cis-eQTLs and QTLs for various complex phenotypes by genetic analysis of recombinant inbred (RI) strains. 5.4 %, 1.9 % and 1.5 % of genes assayed in forebrain of B6/ 129SF1, B6/DBAF1, and B6/CASTF1 mice, respectively, showed differential allelic expression, indicative of cis-acting alleles at these genes. Moreover, the majority of DAE QTLs were observed to be tissue-specific with only a small fraction showing cis-effects in both tissues. Comparing DAE QTLs in F1 mice to cis-eQTLs previously mapped in RI strains we observed that many of the cis-eQTLs were not confirmed by DAE. -
An Unconventional Interaction Between Dis1/TOG and Mal3/EB1 in Fission Yeast Promotes the Fidelity of Chromosome Segregation Yuzy Matsuo1,2, Sebastian P
© 2016. Published by The Company of Biologists Ltd | Journal of Cell Science (2016) 129, 4592-4606 doi:10.1242/jcs.197533 RESEARCH ARTICLE An unconventional interaction between Dis1/TOG and Mal3/EB1 in fission yeast promotes the fidelity of chromosome segregation Yuzy Matsuo1,2, Sebastian P. Maurer1,3,4, Masashi Yukawa5, Silva Zakian6, Martin R. Singleton6, Thomas Surrey1,* and Takashi Toda2,5,* ABSTRACT (Mitchison and Kirschner, 1984). Such dynamic properties of Dynamic microtubule plus-ends interact with various intracellular MTs play an essential role in many cellular processes including target regions such as the cell cortex and the kinetochore. Two intracellular transport, cell polarity and cell division (Desai and conserved families of microtubule plus-end-tracking proteins, the Mitchison, 1997). MT dynamics are regulated by a cohort of XMAP215, ch-TOG or CKAP5 family and the end-binding 1 (EB1, evolutionarily conserved MT-associated proteins (MAPs) also known as MAPRE1) family, play pivotal roles in regulating (Akhmanova and Steinmetz, 2008). A subclass of MAPs, MT microtubule dynamics. Here, we study the functional interplay plus-end-tracking proteins (+TIPs) have unique properties, as they between fission yeast Dis1, a member of the XMAP215/TOG can specifically interact with the dynamic ends of MTs, thereby family, and Mal3, an EB1 protein. Using an in vitro microscopy playing a decisive role in determining the characteristics of MT assay, we find that purified Dis1 autonomously tracks growing plus-ends in cells (Buey et al., 2012; Duellberg et al., 2013). In microtubule ends and is a bona fide microtubule polymerase. Mal3 particular, end-binding 1 (EB1, also known as MAPRE1) and Xenopus Homo recruits additional Dis1 to microtubule ends, explaining the ch-TOG [known as XMAP215 ( ) and CKAP5 ( sapiens synergistic enhancement of microtubule dynamicity by these ); hereafter denoted TOG] are important +TIPs because they proteins.