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  • 1
    Publication Date: 1999-12-03
    Description: Osteoporosis and other diseases of bone loss are a major public health problem. Here it is shown that the statins, drugs widely used for lowering serum cholesterol, also enhance new bone formation in vitro and in rodents. This effect was associated with increased expression of the bone morphogenetic protein-2 (BMP-2) gene in bone cells. Lovastatin and simvastatin increased bone formation when injected subcutaneously over the calvaria of mice and increased cancellous bone volume when orally administered to rats. Thus, in appropriate doses, statins may have therapeutic applications for the treatment of osteoporosis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mundy, G -- Garrett, R -- Harris, S -- Chan, J -- Chen, D -- Rossini, G -- Boyce, B -- Zhao, M -- Gutierrez, G -- New York, N.Y. -- Science. 1999 Dec 3;286(5446):1946-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉OsteoScreen, 2040 Babcock Road, San Antonio, TX 78229, USA. mundy@uthscsa.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10583956" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bone Density/*drug effects ; Bone Morphogenetic Protein 2 ; Bone Morphogenetic Proteins/biosynthesis/genetics/pharmacology ; Cell Line ; Female ; Fibroblast Growth Factor 1 ; Fibroblast Growth Factor 2/pharmacology ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology ; Lovastatin/*pharmacology ; Male ; Mice ; Mice, Inbred ICR ; Organ Culture Techniques ; Osteoblasts/*drug effects/metabolism ; Osteoclasts/drug effects ; Osteogenesis/*drug effects ; Osteoporosis/drug therapy ; Ovariectomy ; Promoter Regions, Genetic/drug effects ; Rats ; Recombinant Proteins/pharmacology ; Simvastatin/*pharmacology ; Skull ; Transfection ; *Transforming Growth Factor beta
    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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  • 2
    Publication Date: 2008-05-10
    Description: We present a draft genome sequence of the platypus, Ornithorhynchus anatinus. This monotreme exhibits a fascinating combination of reptilian and mammalian characters. For example, platypuses have a coat of fur adapted to an aquatic lifestyle; platypus females lactate, yet lay eggs; and males are equipped with venom similar to that of reptiles. Analysis of the first monotreme genome aligned these features with genetic innovations. We find that reptile and platypus venom proteins have been co-opted independently from the same gene families; milk protein genes are conserved despite platypuses laying eggs; and immune gene family expansions are directly related to platypus biology. Expansions of protein, non-protein-coding RNA and microRNA families, as well as repeat elements, are identified. Sequencing of this genome now provides a valuable resource for deep mammalian comparative analyses, as well as for monotreme biology and conservation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2803040/" 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/PMC2803040/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Warren, Wesley C -- Hillier, LaDeana W -- Marshall Graves, Jennifer A -- Birney, Ewan -- Ponting, Chris P -- Grutzner, Frank -- Belov, Katherine -- Miller, Webb -- Clarke, Laura -- Chinwalla, Asif T -- Yang, Shiaw-Pyng -- Heger, Andreas -- Locke, Devin P -- Miethke, Pat -- Waters, Paul D -- Veyrunes, Frederic -- Fulton, Lucinda -- Fulton, Bob -- Graves, Tina -- Wallis, John -- Puente, Xose S -- Lopez-Otin, Carlos -- Ordonez, Gonzalo R -- Eichler, Evan E -- Chen, Lin -- Cheng, Ze -- Deakin, Janine E -- Alsop, Amber -- Thompson, Katherine -- Kirby, Patrick -- Papenfuss, Anthony T -- Wakefield, Matthew J -- Olender, Tsviya -- Lancet, Doron -- Huttley, Gavin A -- Smit, Arian F A -- Pask, Andrew -- Temple-Smith, Peter -- Batzer, Mark A -- Walker, Jerilyn A -- Konkel, Miriam K -- Harris, Robert S -- Whittington, Camilla M -- Wong, Emily S W -- Gemmell, Neil J -- Buschiazzo, Emmanuel -- Vargas Jentzsch, Iris M -- Merkel, Angelika -- Schmitz, Juergen -- Zemann, Anja -- Churakov, Gennady -- Kriegs, Jan Ole -- Brosius, Juergen -- Murchison, Elizabeth P -- Sachidanandam, Ravi -- Smith, Carly -- Hannon, Gregory J -- Tsend-Ayush, Enkhjargal -- McMillan, Daniel -- Attenborough, Rosalind -- Rens, Willem -- Ferguson-Smith, Malcolm -- Lefevre, Christophe M -- Sharp, Julie A -- Nicholas, Kevin R -- Ray, David A -- Kube, Michael -- Reinhardt, Richard -- Pringle, Thomas H -- Taylor, James -- Jones, Russell C -- Nixon, Brett -- Dacheux, Jean-Louis -- Niwa, Hitoshi -- Sekita, Yoko -- Huang, Xiaoqiu -- Stark, Alexander -- Kheradpour, Pouya -- Kellis, Manolis -- Flicek, Paul -- Chen, Yuan -- Webber, Caleb -- Hardison, Ross -- Nelson, Joanne -- Hallsworth-Pepin, Kym -- Delehaunty, Kim -- Markovic, Chris -- Minx, Pat -- Feng, Yucheng -- Kremitzki, Colin -- Mitreva, Makedonka -- Glasscock, Jarret -- Wylie, Todd -- Wohldmann, Patricia -- Thiru, Prathapan -- Nhan, Michael N -- Pohl, Craig S -- Smith, Scott M -- Hou, Shunfeng -- Nefedov, Mikhail -- de Jong, Pieter J -- Renfree, Marilyn B -- Mardis, Elaine R -- Wilson, Richard K -- 062023/Wellcome Trust/United Kingdom -- HG002238/HG/NHGRI NIH HHS/ -- MC_U137761446/Medical Research Council/United Kingdom -- P01 CA013106/CA/NCI NIH HHS/ -- P01 CA013106-37/CA/NCI NIH HHS/ -- R01 GM59290/GM/NIGMS NIH HHS/ -- R01 HG002939/HG/NHGRI NIH HHS/ -- R01 HG004037/HG/NHGRI NIH HHS/ -- R01 HG004037-02/HG/NHGRI NIH HHS/ -- R01HG02385/HG/NHGRI NIH HHS/ -- Medical Research Council/United Kingdom -- England -- Nature. 2008 May 8;453(7192):175-83. doi: 10.1038/nature06936.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genome Sequencing Center, Washington University School of Medicine, Campus Box 8501, 4444 Forest Park Avenue, St Louis, Missouri 63108, USA. wwarren@wustl.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18464734" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Composition ; Dentition ; *Evolution, Molecular ; Female ; Genome/*genetics ; Genomic Imprinting/genetics ; Humans ; Immunity/genetics ; Male ; Mammals/genetics ; MicroRNAs/genetics ; Milk Proteins/genetics ; Phylogeny ; Platypus/*genetics/immunology/physiology ; Receptors, Odorant/genetics ; Repetitive Sequences, Nucleic Acid/genetics ; Reptiles/genetics ; Sequence Analysis, DNA ; Spermatozoa/metabolism ; Venoms/genetics ; Zona Pellucida/metabolism
    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: 2015-10-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Harris, Isaac S -- Brugge, Joan S -- England -- Nature. 2015 Nov 12;527(7577):170-1. doi: 10.1038/nature15644. Epub 2015 Oct 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology and the Ludwig Center at Harvard, Harvard Medical School, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26503052" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Female ; Humans ; Male ; Melanoma/*metabolism/*pathology ; Neoplasm Metastasis/*prevention & control ; *Oxidative Stress
    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: 2002-03-09
    Description: The classical recessive mouse mutant, Purkinje cell degeneration (pcd), exhibits adult-onset degeneration of cerebellar Purkinje neurons, retinal photoreceptors, olfactory bulb mitral neurons, and selected thalamic neurons, and has defective spermatogenesis. Here we identify Nna1 as the gene mutated in the original pcd and two additional pcd alleles (pcd2J and pcd3J). Nna1 encodes a putative nuclear protein containing a zinc carboxypeptidase domain initially identified by its induction in spinal motor neurons during axonal regeneration. The present study suggests an unexpected molecular link between neuronal degeneration and regeneration, and its results have potential implications for neurodegenerative diseases and male infertility.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fernandez-Gonzalez, Angeles -- La Spada, Albert R -- Treadaway, Jason -- Higdon, Jason C -- Harris, Belinda S -- Sidman, Richard L -- Morgan, James I -- Zuo, Jian -- CA 23944/CA/NCI NIH HHS/ -- CA21765/CA/NCI NIH HHS/ -- DC 04761/DC/NIDCD NIH HHS/ -- ES 10772/ES/NIEHS NIH HHS/ -- EY 12950/EY/NEI NIH HHS/ -- NS 40361/NS/NINDS NIH HHS/ -- RR 01183/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2002 Mar 8;295(5561):1904-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11884758" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; *Axotomy ; Blotting, Northern ; Brain/metabolism ; *Carboxypeptidases ; Chromosome Mapping ; Crosses, Genetic ; Female ; GTP-Binding Proteins/chemistry/*genetics/*physiology ; Gene Expression ; Genes ; In Situ Hybridization ; Male ; Mice ; Mice, Neurologic Mutants ; Molecular Sequence Data ; *Mutation ; Nerve Degeneration/*genetics ; Nerve Regeneration ; Neurons/metabolism ; Phenotype ; Purkinje Cells/cytology/*physiology ; RNA, Messenger/genetics/metabolism ; Retina/metabolism ; *Serine-Type D-Ala-D-Ala Carboxypeptidase ; Spermatogenesis ; Testis/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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  • 5
    Publication Date: 2011-01-29
    Description: 'Orang-utan' is derived from a Malay term meaning 'man of the forest' and aptly describes the southeast Asian great apes native to Sumatra and Borneo. The orang-utan species, Pongo abelii (Sumatran) and Pongo pygmaeus (Bornean), are the most phylogenetically distant great apes from humans, thereby providing an informative perspective on hominid evolution. Here we present a Sumatran orang-utan draft genome assembly and short read sequence data from five Sumatran and five Bornean orang-utan genomes. Our analyses reveal that, compared to other primates, the orang-utan genome has many unique features. Structural evolution of the orang-utan genome has proceeded much more slowly than other great apes, evidenced by fewer rearrangements, less segmental duplication, a lower rate of gene family turnover and surprisingly quiescent Alu repeats, which have played a major role in restructuring other primate genomes. We also describe a primate polymorphic neocentromere, found in both Pongo species, emphasizing the gradual evolution of orang-utan genome structure. Orang-utans have extremely low energy usage for a eutherian mammal, far lower than their hominid relatives. Adding their genome to the repertoire of sequenced primates illuminates new signals of positive selection in several pathways including glycolipid metabolism. From the population perspective, both Pongo species are deeply diverse; however, Sumatran individuals possess greater diversity than their Bornean counterparts, and more species-specific variation. Our estimate of Bornean/Sumatran speciation time, 400,000 years ago, is more recent than most previous studies and underscores the complexity of the orang-utan speciation process. Despite a smaller modern census population size, the Sumatran effective population size (N(e)) expanded exponentially relative to the ancestral N(e) after the split, while Bornean N(e) declined over the same period. Overall, the resources and analyses presented here offer new opportunities in evolutionary genomics, insights into hominid biology, and an extensive database of variation for conservation efforts.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3060778/" 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/PMC3060778/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Locke, Devin P -- Hillier, LaDeana W -- Warren, Wesley C -- Worley, Kim C -- Nazareth, Lynne V -- Muzny, Donna M -- Yang, Shiaw-Pyng -- Wang, Zhengyuan -- Chinwalla, Asif T -- Minx, Pat -- Mitreva, Makedonka -- Cook, Lisa -- Delehaunty, Kim D -- Fronick, Catrina -- Schmidt, Heather -- Fulton, Lucinda A -- Fulton, Robert S -- Nelson, Joanne O -- Magrini, Vincent -- Pohl, Craig -- Graves, Tina A -- Markovic, Chris -- Cree, Andy -- Dinh, Huyen H -- Hume, Jennifer -- Kovar, Christie L -- Fowler, Gerald R -- Lunter, Gerton -- Meader, Stephen -- Heger, Andreas -- Ponting, Chris P -- Marques-Bonet, Tomas -- Alkan, Can -- Chen, Lin -- Cheng, Ze -- Kidd, Jeffrey M -- Eichler, Evan E -- White, Simon -- Searle, Stephen -- Vilella, Albert J -- Chen, Yuan -- Flicek, Paul -- Ma, Jian -- Raney, Brian -- Suh, Bernard -- Burhans, Richard -- Herrero, Javier -- Haussler, David -- Faria, Rui -- Fernando, Olga -- Darre, Fleur -- Farre, Domenec -- Gazave, Elodie -- Oliva, Meritxell -- Navarro, Arcadi -- Roberto, Roberta -- Capozzi, Oronzo -- Archidiacono, Nicoletta -- Della Valle, Giuliano -- Purgato, Stefania -- Rocchi, Mariano -- Konkel, Miriam K -- Walker, Jerilyn A -- Ullmer, Brygg -- Batzer, Mark A -- Smit, Arian F A -- Hubley, Robert -- Casola, Claudio -- Schrider, Daniel R -- Hahn, Matthew W -- Quesada, Victor -- Puente, Xose S -- Ordonez, Gonzalo R -- Lopez-Otin, Carlos -- Vinar, Tomas -- Brejova, Brona -- Ratan, Aakrosh -- Harris, Robert S -- Miller, Webb -- Kosiol, Carolin -- Lawson, Heather A -- Taliwal, Vikas -- Martins, Andre L -- Siepel, Adam -- Roychoudhury, Arindam -- Ma, Xin -- Degenhardt, Jeremiah -- Bustamante, Carlos D -- Gutenkunst, Ryan N -- Mailund, Thomas -- Dutheil, Julien Y -- Hobolth, Asger -- Schierup, Mikkel H -- Ryder, Oliver A -- Yoshinaga, Yuko -- de Jong, Pieter J -- Weinstock, George M -- Rogers, Jeffrey -- Mardis, Elaine R -- Gibbs, Richard A -- Wilson, Richard K -- G0501331/Medical Research Council/United Kingdom -- HG002238/HG/NHGRI NIH HHS/ -- HG002385/HG/NHGRI NIH HHS/ -- MC_U137761446/Medical Research Council/United Kingdom -- P01 AG022064/AG/NIA NIH HHS/ -- R01 GM059290/GM/NIGMS NIH HHS/ -- R01 GM59290/GM/NIGMS NIH HHS/ -- R01 HG002939/HG/NHGRI NIH HHS/ -- U54 HG003079/HG/NHGRI NIH HHS/ -- U54 HG003079-08/HG/NHGRI NIH HHS/ -- U54 HG003273/HG/NHGRI NIH HHS/ -- Medical Research Council/United Kingdom -- England -- Nature. 2011 Jan 27;469(7331):529-33. doi: 10.1038/nature09687.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Genome Center at Washington University, Washington University School of Medicine, 4444 Forest Park Avenue, Saint Louis, Missouri 63108, USA. dlocke@wustl.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21270892" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Centromere/genetics ; Cerebrosides/metabolism ; Chromosomes ; Evolution, Molecular ; Female ; Gene Rearrangement/genetics ; Genetic Speciation ; *Genetic Variation ; Genetics, Population ; Genome/*genetics ; Humans ; Male ; Phylogeny ; Pongo abelii/*genetics ; Pongo pygmaeus/*genetics ; Population Density ; Population Dynamics ; Species Specificity
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2012-07-06
    Description: Mutations in the IDH1 and IDH2 genes encoding isocitrate dehydrogenases are frequently found in human glioblastomas and cytogenetically normal acute myeloid leukaemias (AML). These alterations are gain-of-function mutations in that they drive the synthesis of the 'oncometabolite' R-2-hydroxyglutarate (2HG). It remains unclear how IDH1 and IDH2 mutations modify myeloid cell development and promote leukaemogenesis. Here we report the characterization of conditional knock-in (KI) mice in which the most common IDH1 mutation, IDH1(R132H), is inserted into the endogenous murine Idh1 locus and is expressed in all haematopoietic cells (Vav-KI mice) or specifically in cells of the myeloid lineage (LysM-KI mice). These mutants show increased numbers of early haematopoietic progenitors and develop splenomegaly and anaemia with extramedullary haematopoiesis, suggesting a dysfunctional bone marrow niche. Furthermore, LysM-KI cells have hypermethylated histones and changes to DNA methylation similar to those observed in human IDH1- or IDH2-mutant AML. To our knowledge, our study is the first to describe the generation and characterization of conditional IDH1(R132H)-KI mice, and also the first report to demonstrate the induction of a leukaemic DNA methylation signature in a mouse model. Our report thus sheds light on the mechanistic links between IDH1 mutation and human AML.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4005896/" 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/PMC4005896/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sasaki, Masato -- Knobbe, Christiane B -- Munger, Joshua C -- Lind, Evan F -- Brenner, Dirk -- Brustle, Anne -- Harris, Isaac S -- Holmes, Roxanne -- Wakeham, Andrew -- Haight, Jillian -- You-Ten, Annick -- Li, Wanda Y -- Schalm, Stefanie -- Su, Shinsan M -- Virtanen, Carl -- Reifenberger, Guido -- Ohashi, Pamela S -- Barber, Dwayne L -- Figueroa, Maria E -- Melnick, Ari -- Zuniga-Pflucker, Juan-Carlos -- Mak, Tak W -- R01 AI081773/AI/NIAID NIH HHS/ -- Canadian Institutes of Health Research/Canada -- England -- Nature. 2012 Aug 30;488(7413):656-9. doi: 10.1038/nature11323.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network, Toronto, Ontario M5G 2C1, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22763442" target="_blank"〉PubMed〈/a〉
    Keywords: Aging ; Animals ; Bone Marrow/pathology ; Cell Lineage ; CpG Islands/genetics ; DNA Methylation ; Disease Models, Animal ; Epigenesis, Genetic/*genetics ; Female ; Gene Knock-In Techniques ; Glioma/pathology ; Hematopoiesis ; Hematopoietic Stem Cells/*cytology/metabolism ; Histones/metabolism ; Humans ; Isocitrate Dehydrogenase/*genetics/*metabolism ; Leukemia, Myeloid, Acute/genetics ; Male ; Mice ; Mutant Proteins/genetics/*metabolism ; Mutation/*genetics ; Myeloid Cells/cytology/metabolism ; Spleen/pathology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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