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  • 1
    Publication Date: 2009-05-05
    Description: Culture is typically viewed as consisting of traits inherited epigenetically, through social learning. However, cultural diversity has species-typical constraints, presumably of genetic origin. A celebrated, if contentious, example is whether a universal grammar constrains syntactic diversity in human languages. Oscine songbirds exhibit song learning and provide biologically tractable models of culture: members of a species show individual variation in song and geographically separated groups have local song dialects. Different species exhibit distinct song cultures, suggestive of genetic constraints. Without such constraints, innovations and copying errors should cause unbounded variation over multiple generations or geographical distance, contrary to observations. Here we report an experiment designed to determine whether wild-type song culture might emerge over multiple generations in an isolated colony founded by isolates, and, if so, how this might happen and what type of social environment is required. Zebra finch isolates, unexposed to singing males during development, produce song with characteristics that differ from the wild-type song found in laboratory or natural colonies. In tutoring lineages starting from isolate founders, we quantified alterations in song across tutoring generations in two social environments: tutor-pupil pairs in sound-isolated chambers and an isolated semi-natural colony. In both settings, juveniles imitated the isolate tutors but changed certain characteristics of the songs. These alterations accumulated over learning generations. Consequently, songs evolved towards the wild-type in three to four generations. Thus, species-typical song culture can appear de novo. Our study has parallels with language change and evolution. In analogy to models in quantitative genetics, we model song culture as a multigenerational phenotype partly encoded genetically in an isolate founding population, influenced by environmental variables and taking multiple generations to emerge.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2693086/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2693086/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Feher, Olga -- Wang, Haibin -- Saar, Sigal -- Mitra, Partha P -- Tchernichovski, Ofer -- R01 DC004722/DC/NIDCD NIH HHS/ -- R01 DC004722-09/DC/NIDCD NIH HHS/ -- England -- Nature. 2009 May 28;459(7246):564-8. doi: 10.1038/nature07994. Epub 2009 May 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, City College, City University of New York, New York 10031, USA. olcifeher@gmail.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19412161" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Evolution ; *Culture ; Female ; Finches/*physiology ; Instinct ; Learning/physiology ; Male ; *Models, Biological ; Social Isolation ; Vocalization, Animal/*physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2009-07-10
    Description: Variable, diversity and joining gene segment (V(D)J) recombination assembles immunoglobulin heavy or light chain (IgH or IgL) variable region exons in developing bone marrow B cells, whereas class switch recombination (CSR) exchanges IgH constant region exons in peripheral B cells. Both processes use directed DNA double-strand breaks (DSBs) repaired by non-homologous end-joining (NHEJ). Errors in either V(D)J recombination or CSR can initiate chromosomal translocations, including oncogenic IgH locus (Igh) to c-myc (also known as Myc) translocations of peripheral B cell lymphomas. Collaboration between these processes has also been proposed to initiate translocations. However, the occurrence of V(D)J recombination in peripheral B cells is controversial. Here we show that activated NHEJ-deficient splenic B cells accumulate V(D)J-recombination-associated breaks at the lambda IgL locus (Igl), as well as CSR-associated Igh breaks, often in the same cell. Moreover, Igl and Igh breaks are frequently joined to form translocations, a phenomenon associated with specific Igh-Igl co-localization. Igh and c-myc also co-localize in these cells; correspondingly, the introduction of frequent c-myc DSBs robustly promotes Igh-c-myc translocations. Our studies show peripheral B cells that attempt secondary V(D)J recombination, and determine a role for mechanistic factors in promoting recurrent translocations in tumours.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2907259/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2907259/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Jing H -- Gostissa, Monica -- Yan, Catherine T -- Goff, Peter -- Hickernell, Thomas -- Hansen, Erica -- Difilippantonio, Simone -- Wesemann, Duane R -- Zarrin, Ali A -- Rajewsky, Klaus -- Nussenzweig, Andre -- Alt, Frederick W -- 5P01CA92625/CA/NCI NIH HHS/ -- P01 CA092625/CA/NCI NIH HHS/ -- P01 CA092625-010001/CA/NCI NIH HHS/ -- P01 CA092625-020001/CA/NCI NIH HHS/ -- P01 CA092625-060006/CA/NCI NIH HHS/ -- P01 CA092625-070006/CA/NCI NIH HHS/ -- P01 CA092625-080006/CA/NCI NIH HHS/ -- P01 CA092625-090006/CA/NCI NIH HHS/ -- R01 AI077595/AI/NIAID NIH HHS/ -- R01 AI077595-02/AI/NIAID NIH HHS/ -- T32 CA009382/CA/NCI NIH HHS/ -- T32 CA009382-27/CA/NCI NIH HHS/ -- T32 CA009382-28/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- Intramural NIH HHS/ -- England -- Nature. 2009 Jul 9;460(7252):231-6. doi: 10.1038/nature08159.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19587764" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; B-Lymphocytes/*metabolism ; Cytidine Deaminase/deficiency/genetics/metabolism ; DNA Breaks, Double-Stranded ; DNA-Binding Proteins/deficiency/metabolism ; Female ; Gene Rearrangement, B-Lymphocyte/*genetics ; Genes, Immunoglobulin/*genetics ; Genes, myc/genetics ; Homeodomain Proteins/metabolism ; Immunoglobulin Class Switching/*genetics ; Immunoglobulin Heavy Chains/genetics ; Immunoglobulin kappa-Chains/genetics ; Immunoglobulin lambda-Chains/genetics ; Integrases/genetics/metabolism ; Interphase ; Lymphocyte Activation ; Male ; Mice ; Receptors, Complement 3d/genetics ; Recombination, Genetic/genetics ; Spleen/cytology/immunology ; Translocation, Genetic/*genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2015-10-20
    Description: The development of life-threatening cancer metastases at distant organs requires disseminated tumour cells' adaptation to, and co-evolution with, the drastically different microenvironments of metastatic sites. Cancer cells of common origin manifest distinct gene expression patterns after metastasizing to different organs. Clearly, the dynamic interaction between metastatic tumour cells and extrinsic signals at individual metastatic organ sites critically effects the subsequent metastatic outgrowth. Yet, it is unclear when and how disseminated tumour cells acquire the essential traits from the microenvironment of metastatic organs that prime their subsequent outgrowth. Here we show that both human and mouse tumour cells with normal expression of PTEN, an important tumour suppressor, lose PTEN expression after dissemination to the brain, but not to other organs. The PTEN level in PTEN-loss brain metastatic tumour cells is restored after leaving the brain microenvironment. This brain microenvironment-dependent, reversible PTEN messenger RNA and protein downregulation is epigenetically regulated by microRNAs from brain astrocytes. Mechanistically, astrocyte-derived exosomes mediate an intercellular transfer of PTEN-targeting microRNAs to metastatic tumour cells, while astrocyte-specific depletion of PTEN-targeting microRNAs or blockade of astrocyte exosome secretion rescues the PTEN loss and suppresses brain metastasis in vivo. Furthermore, this adaptive PTEN loss in brain metastatic tumour cells leads to an increased secretion of the chemokine CCL2, which recruits IBA1-expressing myeloid cells that reciprocally enhance the outgrowth of brain metastatic tumour cells via enhanced proliferation and reduced apoptosis. Our findings demonstrate a remarkable plasticity of PTEN expression in metastatic tumour cells in response to different organ microenvironments, underpinning an essential role of co-evolution between the metastatic cells and their microenvironment during the adaptive metastatic outgrowth. Our findings signify the dynamic and reciprocal cross-talk between tumour cells and the metastatic niche; importantly, they provide new opportunities for effective anti-metastasis therapies, especially of consequence for brain metastasis patients.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Lin -- Zhang, Siyuan -- Yao, Jun -- Lowery, Frank J -- Zhang, Qingling -- Huang, Wen-Chien -- Li, Ping -- Li, Min -- Wang, Xiao -- Zhang, Chenyu -- Wang, Hai -- Ellis, Kenneth -- Cheerathodi, Mujeeburahiman -- McCarty, Joseph H -- Palmieri, Diane -- Saunus, Jodi -- Lakhani, Sunil -- Huang, Suyun -- Sahin, Aysegul A -- Aldape, Kenneth D -- Steeg, Patricia S -- Yu, Dihua -- 5R00CA158066-05/CA/NCI NIH HHS/ -- P01-CA099031/CA/NCI NIH HHS/ -- P30 CA016672/CA/NCI NIH HHS/ -- R00 CA158066/CA/NCI NIH HHS/ -- R01 CA194697/CA/NCI NIH HHS/ -- R01-CA112567-06/CA/NCI NIH HHS/ -- R01CA184836/CA/NCI NIH HHS/ -- England -- Nature. 2015 Nov 5;527(7576):100-4. doi: 10.1038/nature15376. Epub 2015 Oct 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. ; Cancer Biology Program, Graduate School of Biomedical Sciences, Houston, Texas 77030, USA. ; Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana 46556, USA. ; Department of Neurosurgery, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. ; Woman's Malignancies Branch, National Cancer Institute, Bethesda, Maryland 20892, USA. ; The University of Queensland Centre for Clinical Research, Brisbane, Queensland 4029, Australia. ; The School of Medicine and Pathology Queensland, Brisbane, Queensland 4029, Australia. ; The Royal Brisbane and Women's Hospital, Brisbane, Queensland 4029, Australia. ; Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. ; Center for Molecular Medicine, China Medical University, Taichung 40402, Taiwan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26479035" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological/genetics ; Animals ; Astrocytes/cytology/metabolism ; Brain/metabolism/pathology ; Brain Neoplasms/metabolism/*pathology/*secondary ; Cell Proliferation/genetics ; Chemokine CCL2/secretion ; DNA-Binding Proteins/metabolism ; Down-Regulation/genetics ; Evolution, Molecular ; Exosomes/*genetics/metabolism/secretion ; Female ; *Gene Expression Regulation, Neoplastic ; *Gene Silencing ; Genes, Tumor Suppressor ; Humans ; Male ; Mice ; MicroRNAs/*genetics ; PTEN Phosphohydrolase/*deficiency/genetics ; RNA, Messenger/analysis/genetics ; *Tumor Microenvironment/genetics ; Tumor Suppressor Proteins/deficiency/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2007-04-14
    Description: The rhesus macaque (Macaca mulatta) is an abundant primate species that diverged from the ancestors of Homo sapiens about 25 million years ago. Because they are genetically and physiologically similar to humans, rhesus monkeys are the most widely used nonhuman primate in basic and applied biomedical research. We determined the genome sequence of an Indian-origin Macaca mulatta female and compared the data with chimpanzees and humans to reveal the structure of ancestral primate genomes and to identify evidence for positive selection and lineage-specific expansions and contractions of gene families. A comparison of sequences from individual animals was used to investigate their underlying genetic diversity. The complete description of the macaque genome blueprint enhances the utility of this animal model for biomedical research and improves our understanding of the basic biology of the species.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rhesus Macaque Genome Sequencing and Analysis Consortium -- Gibbs, Richard A -- Rogers, Jeffrey -- Katze, Michael G -- Bumgarner, Roger -- Weinstock, George M -- Mardis, Elaine R -- Remington, Karin A -- Strausberg, Robert L -- Venter, J Craig -- Wilson, Richard K -- Batzer, Mark A -- Bustamante, Carlos D -- Eichler, Evan E -- Hahn, Matthew W -- Hardison, Ross C -- Makova, Kateryna D -- Miller, Webb -- Milosavljevic, Aleksandar -- Palermo, Robert E -- Siepel, Adam -- Sikela, James M -- Attaway, Tony -- Bell, Stephanie -- Bernard, Kelly E -- Buhay, Christian J -- Chandrabose, Mimi N -- Dao, Marvin -- Davis, Clay -- Delehaunty, Kimberly D -- Ding, Yan -- Dinh, Huyen H -- Dugan-Rocha, Shannon -- Fulton, Lucinda A -- Gabisi, Ramatu Ayiesha -- Garner, Toni T -- Godfrey, Jennifer -- Hawes, Alicia C -- Hernandez, Judith -- Hines, Sandra -- Holder, Michael -- Hume, Jennifer -- Jhangiani, Shalini N -- Joshi, Vandita -- Khan, Ziad Mohid -- Kirkness, Ewen F -- Cree, Andrew -- Fowler, R Gerald -- Lee, Sandra -- Lewis, Lora R -- Li, Zhangwan -- Liu, Yih-Shin -- Moore, Stephanie M -- Muzny, Donna -- Nazareth, Lynne V -- Ngo, Dinh Ngoc -- Okwuonu, Geoffrey O -- Pai, Grace -- Parker, David -- Paul, Heidie A -- Pfannkoch, Cynthia -- Pohl, Craig S -- Rogers, Yu-Hui -- Ruiz, San Juana -- Sabo, Aniko -- Santibanez, Jireh -- Schneider, Brian W -- Smith, Scott M -- Sodergren, Erica -- Svatek, Amanda F -- Utterback, Teresa R -- Vattathil, Selina -- Warren, Wesley -- White, Courtney Sherell -- Chinwalla, Asif T -- Feng, Yucheng -- Halpern, Aaron L -- Hillier, Ladeana W -- Huang, Xiaoqiu -- Minx, Pat -- Nelson, Joanne O -- Pepin, Kymberlie H -- Qin, Xiang -- Sutton, Granger G -- Venter, Eli -- Walenz, Brian P -- Wallis, John W -- Worley, Kim C -- Yang, Shiaw-Pyng -- Jones, Steven M -- Marra, Marco A -- Rocchi, Mariano -- Schein, Jacqueline E -- Baertsch, Robert -- Clarke, Laura -- Csuros, Miklos -- Glasscock, Jarret -- Harris, R Alan -- Havlak, Paul -- Jackson, Andrew R -- Jiang, Huaiyang -- Liu, Yue -- Messina, David N -- Shen, Yufeng -- Song, Henry Xing-Zhi -- Wylie, Todd -- Zhang, Lan -- Birney, Ewan -- Han, Kyudong -- Konkel, Miriam K -- Lee, Jungnam -- Smit, Arian F A -- Ullmer, Brygg -- Wang, Hui -- Xing, Jinchuan -- Burhans, Richard -- Cheng, Ze -- Karro, John E -- Ma, Jian -- Raney, Brian -- She, Xinwei -- Cox, Michael J -- Demuth, Jeffery P -- Dumas, Laura J -- Han, Sang-Gook -- Hopkins, Janet -- Karimpour-Fard, Anis -- Kim, Young H -- Pollack, Jonathan R -- Vinar, Tomas -- Addo-Quaye, Charles -- Degenhardt, Jeremiah -- Denby, Alexandra -- Hubisz, Melissa J -- Indap, Amit -- Kosiol, Carolin -- Lahn, Bruce T -- Lawson, Heather A -- Marklein, Alison -- Nielsen, Rasmus -- Vallender, Eric J -- Clark, Andrew G -- Ferguson, Betsy -- Hernandez, Ryan D -- Hirani, Kashif -- Kehrer-Sawatzki, Hildegard -- Kolb, Jessica -- Patil, Shobha -- Pu, Ling-Ling -- Ren, Yanru -- Smith, David Glenn -- Wheeler, David A -- Schenck, Ian -- Ball, Edward V -- Chen, Rui -- Cooper, David N -- Giardine, Belinda -- Hsu, Fan -- Kent, W James -- Lesk, Arthur -- Nelson, David L -- O'brien, William E -- Prufer, Kay -- Stenson, Peter D -- Wallace, James C -- Ke, Hui -- Liu, Xiao-Ming -- Wang, Peng -- Xiang, Andy Peng -- Yang, Fan -- Barber, Galt P -- Haussler, David -- Karolchik, Donna -- Kern, Andy D -- Kuhn, Robert M -- Smith, Kayla E -- Zwieg, Ann S -- 062023/Wellcome Trust/United Kingdom -- R01 HG002939/HG/NHGRI NIH HHS/ -- U54 HG003068/HG/NHGRI NIH HHS/ -- U54 HG003079/HG/NHGRI NIH HHS/ -- U54 HG003273/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2007 Apr 13;316(5822):222-34.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA. agibbs@bcm.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17431167" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biomedical Research ; *Evolution, Molecular ; Female ; Gene Duplication ; Gene Rearrangement ; Genetic Diseases, Inborn ; Genetic Variation ; *Genome ; Humans ; Macaca mulatta/*genetics ; Male ; Multigene Family ; Mutation ; Pan troglodytes/genetics ; Sequence Analysis, DNA ; Species Specificity
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2007-03-03
    Description: Coronary artery disease (CAD) is the leading cause of death worldwide and is commonly caused by a constellation of risk factors called the metabolic syndrome. We characterized a family with autosomal dominant early CAD, features of the metabolic syndrome (hyperlipidemia, hypertension, and diabetes), and osteoporosis. These traits showed genetic linkage to a short segment of chromosome 12p, in which we identified a missense mutation in LRP6, which encodes a co-receptor in the Wnt signaling pathway. The mutation, which substitutes cysteine for arginine at a highly conserved residue of an epidermal growth factor-like domain, impairs Wnt signaling in vitro. These results link a single gene defect in Wnt signaling to CAD and multiple cardiovascular risk factors.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2945222/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2945222/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mani, Arya -- Radhakrishnan, Jayaram -- Wang, He -- Mani, Alaleh -- Mani, Mohammad-Ali -- Nelson-Williams, Carol -- Carew, Khary S -- Mane, Shrikant -- Najmabadi, Hossein -- Wu, Dan -- Lifton, Richard P -- K08 HD041481/HD/NICHD NIH HHS/ -- K08 HD041481-01/HD/NICHD NIH HHS/ -- P01DK68229/DK/NIDDK NIH HHS/ -- P50 HL55007/HL/NHLBI NIH HHS/ -- R01 AR051476/AR/NIAMS NIH HHS/ -- R01 AR051476-01A1/AR/NIAMS NIH HHS/ -- R01 AR051476-02/AR/NIAMS NIH HHS/ -- R01 AR051476-03/AR/NIAMS NIH HHS/ -- R01 AR051476-04/AR/NIAMS NIH HHS/ -- New York, N.Y. -- Science. 2007 Mar 2;315(5816):1278-82.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Internal Medicine, Howard Hughes Medical Institute and Yale University School of Medicine, New Haven, CT 06510, USA. arya.mani@yale.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17332414" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Aged ; Aged, 80 and over ; Amino Acid Substitution ; Animals ; Chromosomes, Human, Pair 12/genetics ; Coronary Disease/*genetics/metabolism ; Family Health ; Female ; Genetic Linkage ; *Genetic Predisposition to Disease ; Humans ; LDL-Receptor Related Proteins/*genetics/physiology ; Lipids/blood ; Low Density Lipoprotein Receptor-Related Protein-6 ; Male ; Metabolic Syndrome X/*genetics/metabolism ; Mice ; Middle Aged ; *Mutation, Missense ; NIH 3T3 Cells ; Osteoporosis/genetics ; Pedigree ; Risk Factors ; Signal Transduction ; Wnt Proteins/metabolism
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  • 6
    Publication Date: 2011-04-09
    Description: Small nuclear RNAs (snRNAs) are essential factors in messenger RNA splicing. By means of homozygosity mapping and deep sequencing, we show that a gene encoding U4atac snRNA, a component of the minor U12-dependent spliceosome, is mutated in individuals with microcephalic osteodysplastic primordial dwarfism type I (MOPD I), a severe developmental disorder characterized by extreme intrauterine growth retardation and multiple organ abnormalities. Functional assays showed that mutations (30G〉A, 51G〉A, 55G〉A, and 111G〉A) associated with MOPD I cause defective U12-dependent splicing. Endogenous U12-dependent but not U2-dependent introns were found to be poorly spliced in MOPD I patient fibroblast cells. The introduction of wild-type U4atac snRNA into MOPD I cells enhanced U12-dependent splicing. These results illustrate the critical role of minor intron splicing in human development.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3380448/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3380448/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉He, Huiling -- Liyanarachchi, Sandya -- Akagi, Keiko -- Nagy, Rebecca -- Li, Jingfeng -- Dietrich, Rosemary C -- Li, Wei -- Sebastian, Nikhil -- Wen, Bernard -- Xin, Baozhong -- Singh, Jarnail -- Yan, Pearlly -- Alder, Hansjuerg -- Haan, Eric -- Wieczorek, Dagmar -- Albrecht, Beate -- Puffenberger, Erik -- Wang, Heng -- Westman, Judith A -- Padgett, Richard A -- Symer, David E -- de la Chapelle, Albert -- GM079527/GM/NIGMS NIH HHS/ -- GM093074/GM/NIGMS NIH HHS/ -- P30 CA16058/CA/NCI NIH HHS/ -- R01 GM079527/GM/NIGMS NIH HHS/ -- R01 GM079527-04/GM/NIGMS NIH HHS/ -- R01 GM093074/GM/NIGMS NIH HHS/ -- R01 GM093074-01A1/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2011 Apr 8;332(6026):238-40. doi: 10.1126/science.1200587.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Human Cancer Genetics Program, Ohio State University, Columbus, OH 43210, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21474760" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line ; Chromosomes, Human, Pair 2/genetics ; Dwarfism/genetics/metabolism ; Female ; Fetal Growth Retardation/genetics/metabolism ; Humans ; Introns ; Inverted Repeat Sequences ; Male ; Microcephaly/genetics/metabolism ; *Mutation ; Nucleic Acid Conformation ; Osteochondrodysplasias/genetics/metabolism ; Pedigree ; *RNA Splicing ; RNA, Small Nuclear/chemistry/*genetics/metabolism ; Spliceosomes/*genetics/metabolism
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2012-12-01
    Description: Notch signaling affects many developmental and cellular processes and has been implicated in congenital disorders, stroke, and numerous cancers. The Notch receptor binds its ligands Delta and Serrate and is able to discriminate between them in different contexts. However, the specific domains in Notch responsible for this selectivity are poorly defined. Through genetic screens in Drosophila, we isolated a mutation, Notch(jigsaw), that affects Serrate- but not Delta-dependent signaling. Notch(jigsaw) carries a missense mutation in epidermal growth factor repeat-8 (EGFr-8) and is defective in Serrate binding. A homologous point mutation in mammalian Notch2 also exhibits defects in signaling of a mammalian Serrate homolog, Jagged1. Hence, an evolutionarily conserved valine in EGFr-8 is essential for ligand selectivity and provides a molecular handle to study numerous Notch-dependent signaling events.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3663443/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3663443/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yamamoto, Shinya -- Charng, Wu-Lin -- Rana, Nadia A -- Kakuda, Shinako -- Jaiswal, Manish -- Bayat, Vafa -- Xiong, Bo -- Zhang, Ke -- Sandoval, Hector -- David, Gabriela -- Wang, Hao -- Haltiwanger, Robert S -- Bellen, Hugo J -- 1RC4GM096355-01/GM/NIGMS NIH HHS/ -- 5K12GM084897/GM/NIGMS NIH HHS/ -- 5P30HD024064/HD/NICHD NIH HHS/ -- 5R01GM061126-12/GM/NIGMS NIH HHS/ -- 5R01GM067858/GM/NIGMS NIH HHS/ -- 5T32-HD055200/HD/NICHD NIH HHS/ -- K12 GM084897/GM/NIGMS NIH HHS/ -- P30 HD024064/HD/NICHD NIH HHS/ -- R01 GM061126/GM/NIGMS NIH HHS/ -- R01 GM067858/GM/NIGMS NIH HHS/ -- RC4 GM096355/GM/NIGMS NIH HHS/ -- T32 HD055200/HD/NICHD NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2012 Nov 30;338(6111):1229-32. doi: 10.1126/science.1228745.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23197537" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Substitution ; Animals ; Calcium-Binding Proteins/*metabolism ; Cells, Cultured ; DNA Mutational Analysis ; Drosophila Proteins/*genetics/*metabolism ; Drosophila melanogaster/genetics/*metabolism ; Epidermal Growth Factor/genetics ; Evolution, Molecular ; Humans ; Intercellular Signaling Peptides and Proteins/*metabolism ; Intracellular Signaling Peptides and Proteins/*metabolism ; Ligands ; Male ; Membrane Proteins/*metabolism ; Methionine/genetics ; Molecular Sequence Data ; Mutation ; Receptor, Notch2/genetics/metabolism ; Receptors, Notch/*genetics/*metabolism ; Tandem Repeat Sequences/genetics ; Valine/genetics ; X Chromosome/genetics
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2003-03-22
    Description: The Polycomb group (PcG) protein Eed is implicated in regulation of imprinted X-chromosome inactivation in extraembryonic cells but not of random X inactivation in embryonic cells. The Drosophila homolog of the Eed-Ezh2 PcG protein complex achieves gene silencing through methylation of histone H3 on lysine 27 (H3-K27), which suggests a role for H3-K27 methylation in imprinted X inactivation. Here we demonstrate that transient recruitment of the Eed-Ezh2 complex to the inactive X chromosome (Xi) occurs during initiation of X inactivation in both extraembryonic and embryonic cells and is accompanied by H3-K27 methylation. Recruitment of the complex and methylation on the Xi depend on Xist RNA but are independent of its silencing function. Together, our results suggest a role for Eed-Ezh2-mediated H3-K27 methylation during initiation of both imprinted and random X inactivation and demonstrate that H3-K27 methylation is not sufficient for silencing of the Xi.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Plath, Kathrin -- Fang, Jia -- Mlynarczyk-Evans, Susanna K -- Cao, Ru -- Worringer, Kathleen A -- Wang, Hengbin -- de la Cruz, Cecile C -- Otte, Arie P -- Panning, Barbara -- Zhang, Yi -- New York, N.Y. -- Science. 2003 Apr 4;300(5616):131-5. Epub 2003 Mar 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA 94143, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12649488" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blastocyst/metabolism/*physiology ; Cell Differentiation ; Cell Nucleus/metabolism ; Cells, Cultured ; *Dosage Compensation, Genetic ; Female ; Fluorescent Antibody Technique ; Genomic Imprinting ; HeLa Cells ; Histones/*metabolism ; Humans ; In Situ Hybridization, Fluorescence ; Lysine/metabolism ; Male ; Methylation ; Mice ; Mutation ; Polycomb Repressive Complex 2 ; RNA, Long Noncoding ; RNA, Untranslated/genetics/metabolism ; Repressor Proteins/metabolism ; Stem Cells/metabolism/*physiology ; Transgenes ; Trophoblasts/*physiology ; X Chromosome/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2012-07-18
    Description: The inflammasome regulates the release of caspase activation-dependent cytokines, including interleukin (IL)-1beta, IL-18 and high-mobility group box 1 (HMGB1). By studying HMGB1 release mechanisms, here we identify a role for double-stranded RNA-dependent protein kinase (PKR, also known as EIF2AK2) in inflammasome activation. Exposure of macrophages to inflammasome agonists induced PKR autophosphorylation. PKR inactivation by genetic deletion or pharmacological inhibition severely impaired inflammasome activation in response to double-stranded RNA, ATP, monosodium urate, adjuvant aluminium, rotenone, live Escherichia coli, anthrax lethal toxin, DNA transfection and Salmonella typhimurium infection. PKR deficiency significantly inhibited the secretion of IL-1beta, IL-18 and HMGB1 in E. coli-induced peritonitis. PKR physically interacts with several inflammasome components, including NOD-like receptor (NLR) family pyrin domain-containing 3 (NLRP3), NLRP1, NLR family CARD domain-containing protein 4 (NLRC4), absent in melanoma 2 (AIM2), and broadly regulates inflammasome activation. PKR autophosphorylation in a cell-free system with recombinant NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC, also known as PYCARD) and pro-caspase-1 reconstitutes inflammasome activity. These results show a crucial role for PKR in inflammasome activation, and indicate that it should be possible to pharmacologically target this molecule to treat inflammation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4163918/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4163918/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lu, Ben -- Nakamura, Takahisa -- Inouye, Karen -- Li, Jianhua -- Tang, Yiting -- Lundback, Peter -- Valdes-Ferrer, Sergio I -- Olofsson, Peder S -- Kalb, Thomas -- Roth, Jesse -- Zou, Yongrui -- Erlandsson-Harris, Helena -- Yang, Huan -- Ting, Jenny P-Y -- Wang, Haichao -- Andersson, Ulf -- Antoine, Daniel J -- Chavan, Sangeeta S -- Hotamisligil, Gokhan S -- Tracey, Kevin J -- DK052539/DK/NIDDK NIH HHS/ -- G0700654/Medical Research Council/United Kingdom -- R01 DK052539/DK/NIDDK NIH HHS/ -- R01 GM057226/GM/NIGMS NIH HHS/ -- R01 GM062508/GM/NIGMS NIH HHS/ -- R01 GM62508/GM/NIGMS NIH HHS/ -- England -- Nature. 2012 Aug 30;488(7413):670-4. doi: 10.1038/nature11290.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, New York 11030, USA. blu@nshs.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22801494" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/metabolism ; Adenosine Triphosphate/pharmacology ; Animals ; Antigens, Bacterial/pharmacology ; Apoptosis Regulatory Proteins/metabolism ; Bacterial Toxins/pharmacology ; CARD Signaling Adaptor Proteins/metabolism ; Calcium-Binding Proteins/metabolism ; Carrier Proteins/metabolism ; Cell Line ; Cells, Cultured ; Crystallins/metabolism ; Escherichia coli/immunology/physiology ; Escherichia coli Infections/immunology/metabolism ; Female ; HMGB1 Protein/blood/*secretion ; Humans ; Inflammasomes/agonists/*metabolism ; Interleukin-18/blood ; Interleukin-1beta/blood ; Interleukin-6/analysis/blood ; Macrophages, Peritoneal/drug effects/metabolism ; Male ; Membrane Proteins/metabolism ; Mice ; Mice, Inbred C57BL ; Peritonitis/metabolism ; Phosphorylation ; RNA, Double-Stranded/immunology/pharmacology ; Rotenone/pharmacology ; Salmonella Infections/immunology/metabolism ; Salmonella typhimurium/immunology/physiology ; Transfection ; Uric Acid/pharmacology ; eIF-2 Kinase/antagonists & inhibitors/deficiency/genetics/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2012-11-16
    Description: The daily solar cycle allows organisms to synchronize their circadian rhythms and sleep-wake cycles to the correct temporal niche. Changes in day-length, shift-work, and transmeridian travel lead to mood alterations and cognitive function deficits. Sleep deprivation and circadian disruption underlie mood and cognitive disorders associated with irregular light schedules. Whether irregular light schedules directly affect mood and cognitive functions in the context of normal sleep and circadian rhythms remains unclear. Here we show, using an aberrant light cycle that neither changes the amount and architecture of sleep nor causes changes in the circadian timing system, that light directly regulates mood-related behaviours and cognitive functions in mice. Animals exposed to the aberrant light cycle maintain daily corticosterone rhythms, but the overall levels of corticosterone are increased. Despite normal circadian and sleep structures, these animals show increased depression-like behaviours and impaired hippocampal long-term potentiation and learning. Administration of the antidepressant drugs fluoxetine or desipramine restores learning in mice exposed to the aberrant light cycle, suggesting that the mood deficit precedes the learning impairments. To determine the retinal circuits underlying this impairment of mood and learning, we examined the behavioural consequences of this light cycle in animals that lack intrinsically photosensitive retinal ganglion cells. In these animals, the aberrant light cycle does not impair mood and learning, despite the presence of the conventional retinal ganglion cells and the ability of these animals to detect light for image formation. These findings demonstrate the ability of light to influence cognitive and mood functions directly through intrinsically photosensitive retinal ganglion cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3549331/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3549331/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉LeGates, Tara A -- Altimus, Cara M -- Wang, Hui -- Lee, Hey-Kyoung -- Yang, Sunggu -- Zhao, Haiqing -- Kirkwood, Alfredo -- Weber, E Todd -- Hattar, Samer -- R01 AG034606/AG/NIA NIH HHS/ -- R01 GM076430/GM/NIGMS NIH HHS/ -- England -- Nature. 2012 Nov 22;491(7425):594-8. doi: 10.1038/nature11673. Epub 2012 Nov 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Johns Hopkins University, Baltimore, Maryland 21218, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23151476" target="_blank"〉PubMed〈/a〉
    Keywords: Affect/drug effects/physiology/*radiation effects ; Animals ; Antidepressive Agents/pharmacology ; Body Temperature Regulation/physiology/radiation effects ; Circadian Rhythm/physiology ; Cognition/drug effects/physiology/radiation effects ; Corticosterone/metabolism ; Depression/etiology/physiopathology ; Desipramine/pharmacology ; Fluoxetine/pharmacology ; Learning/drug effects/physiology/*radiation effects ; *Light ; Long-Term Potentiation/drug effects ; Male ; Memory/physiology/radiation effects ; Mice ; Photoperiod ; Retinal Ganglion Cells/drug effects/*metabolism/*radiation effects ; *Rod Opsins/analysis ; Sleep/physiology ; Wakefulness/physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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