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  • Mice  (31)
  • American Association for the Advancement of Science (AAAS)  (31)
  • Institute of Physics (IOP)
  • Springer Nature
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  • 1
    Publication Date: 2002-06-01
    Description: The high degree of similarity between the mouse and human genomes is demonstrated through analysis of the sequence of mouse chromosome 16 (Mmu 16), which was obtained as part of a whole-genome shotgun assembly of the mouse genome. The mouse genome is about 10% smaller than the human genome, owing to a lower repetitive DNA content. Comparison of the structure and protein-coding potential of Mmu 16 with that of the homologous segments of the human genome identifies regions of conserved synteny with human chromosomes (Hsa) 3, 8, 12, 16, 21, and 22. Gene content and order are highly conserved between Mmu 16 and the syntenic blocks of the human genome. Of the 731 predicted genes on Mmu 16, 509 align with orthologs on the corresponding portions of the human genome, 44 are likely paralogous to these genes, and 164 genes have homologs elsewhere in the human genome; there are 14 genes for which we could find no human counterpart.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mural, Richard J -- Adams, Mark D -- Myers, Eugene W -- Smith, Hamilton O -- Miklos, George L Gabor -- Wides, Ron -- Halpern, Aaron -- Li, Peter W -- Sutton, Granger G -- Nadeau, Joe -- Salzberg, Steven L -- Holt, Robert A -- Kodira, Chinnappa D -- Lu, Fu -- Chen, Lin -- Deng, Zuoming -- Evangelista, Carlos C -- Gan, Weiniu -- Heiman, Thomas J -- Li, Jiayin -- Li, Zhenya -- Merkulov, Gennady V -- Milshina, Natalia V -- Naik, Ashwinikumar K -- Qi, Rong -- Shue, Bixiong Chris -- Wang, Aihui -- Wang, Jian -- Wang, Xin -- Yan, Xianghe -- Ye, Jane -- Yooseph, Shibu -- Zhao, Qi -- Zheng, Liansheng -- Zhu, Shiaoping C -- Biddick, Kendra -- Bolanos, Randall -- Delcher, Arthur L -- Dew, Ian M -- Fasulo, Daniel -- Flanigan, Michael J -- Huson, Daniel H -- Kravitz, Saul A -- Miller, Jason R -- Mobarry, Clark M -- Reinert, Knut -- Remington, Karin A -- Zhang, Qing -- Zheng, Xiangqun H -- Nusskern, Deborah R -- Lai, Zhongwu -- Lei, Yiding -- Zhong, Wenyan -- Yao, Alison -- Guan, Ping -- Ji, Rui-Ru -- Gu, Zhiping -- Wang, Zhen-Yuan -- Zhong, Fei -- Xiao, Chunlin -- Chiang, Chia-Chien -- Yandell, Mark -- Wortman, Jennifer R -- Amanatides, Peter G -- Hladun, Suzanne L -- Pratts, Eric C -- Johnson, Jeffery E -- Dodson, Kristina L -- Woodford, Kerry J -- Evans, Cheryl A -- Gropman, Barry -- Rusch, Douglas B -- Venter, Eli -- Wang, Mei -- Smith, Thomas J -- Houck, Jarrett T -- Tompkins, Donald E -- Haynes, Charles -- Jacob, Debbie -- Chin, Soo H -- Allen, David R -- Dahlke, Carl E -- Sanders, Robert -- Li, Kelvin -- Liu, Xiangjun -- Levitsky, Alexander A -- Majoros, William H -- Chen, Quan -- Xia, Ashley C -- Lopez, John R -- Donnelly, Michael T -- Newman, Matthew H -- Glodek, Anna -- Kraft, Cheryl L -- Nodell, Marc -- Ali, Feroze -- An, Hui-Jin -- Baldwin-Pitts, Danita -- Beeson, Karen Y -- Cai, Shuang -- Carnes, Mark -- Carver, Amy -- Caulk, Parris M -- Center, Angela -- Chen, Yen-Hui -- Cheng, Ming-Lai -- Coyne, My D -- Crowder, Michelle -- Danaher, Steven -- Davenport, Lionel B -- Desilets, Raymond -- Dietz, Susanne M -- Doup, Lisa -- Dullaghan, Patrick -- Ferriera, Steven -- Fosler, Carl R -- Gire, Harold C -- Gluecksmann, Andres -- Gocayne, Jeannine D -- Gray, Jonathan -- Hart, Brit -- Haynes, Jason -- Hoover, Jeffery -- Howland, Tim -- Ibegwam, Chinyere -- Jalali, Mena -- Johns, David -- Kline, Leslie -- Ma, Daniel S -- MacCawley, Steven -- Magoon, Anand -- Mann, Felecia -- May, David -- McIntosh, Tina C -- Mehta, Somil -- Moy, Linda -- Moy, Mee C -- Murphy, Brian J -- Murphy, Sean D -- Nelson, Keith A -- Nuri, Zubeda -- Parker, Kimberly A -- Prudhomme, Alexandre C -- Puri, Vinita N -- Qureshi, Hina -- Raley, John C -- Reardon, Matthew S -- Regier, Megan A -- Rogers, Yu-Hui C -- Romblad, Deanna L -- Schutz, Jakob -- Scott, John L -- Scott, Richard -- Sitter, Cynthia D -- Smallwood, Michella -- Sprague, Arlan C -- Stewart, Erin -- Strong, Renee V -- Suh, Ellen -- Sylvester, Karena -- Thomas, Reginald -- Tint, Ni Ni -- Tsonis, Christopher -- Wang, Gary -- Wang, George -- Williams, Monica S -- Williams, Sherita M -- Windsor, Sandra M -- Wolfe, Keriellen -- Wu, Mitchell M -- Zaveri, Jayshree -- Chaturvedi, Kabir -- Gabrielian, Andrei E -- Ke, Zhaoxi -- Sun, Jingtao -- Subramanian, Gangadharan -- Venter, J Craig -- Pfannkoch, Cynthia M -- Barnstead, Mary -- Stephenson, Lisa D -- New York, N.Y. -- Science. 2002 May 31;296(5573):1661-71.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Celera Genomics, 45 West Gude Drive, Rockville, MD 20850, USA. richard.mural@celera.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12040188" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Composition ; Chromosomes/*genetics ; Chromosomes, Human/genetics ; Computational Biology ; Conserved Sequence ; Databases, Nucleic Acid ; Evolution, Molecular ; Genes ; Genetic Markers ; *Genome ; *Genome, Human ; Genomics ; Humans ; Mice ; Mice, Inbred A/genetics ; Mice, Inbred DBA/genetics ; Mice, Inbred Strains/*genetics ; Molecular Sequence Data ; Physical Chromosome Mapping ; Proteins/chemistry/genetics ; Sequence Alignment ; *Sequence Analysis, DNA ; Species Specificity ; *Synteny
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    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2002-07-06
    Description: Nonsense codons that prematurely terminate translation generate potentially deleterious truncated proteins. Here, we show that the T cell receptor-beta (TCRbeta) gene, which acquires in-frame nonsense codons at high frequency during normal lymphocyte development, gives rise to an alternatively spliced transcript [alternative messenger RNA (alt-mRNA)] that skips the offending mutations that generate such nonsense codons. This alt-mRNA is up-regulated by a transfer RNA-dependent scanning mechanism that responds specifically to mutations that disrupt the reading frame. The finding that translation signals regulate the levels of alternatively spliced mRNAs generated in the nucleus may alter the current view of how gene expression is controlled in eukaryotic cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Jun -- Hamilton, John I -- Carter, Mark S -- Li, Shulin -- Wilkinson, Miles F -- New York, N.Y. -- Science. 2002 Jul 5;297(5578):108-10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, The University of Texas M. D. Anderson Cancer Center, Box 180, 1515 Holcombe Boulevard, Houston, TX 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12098701" target="_blank"〉PubMed〈/a〉
    Keywords: *Alternative Splicing ; Animals ; Cell Nucleus/genetics/metabolism ; *Codon, Nonsense ; Enhancer Elements, Genetic ; Exons ; Frameshift Mutation ; HeLa Cells ; Humans ; Introns ; Mice ; Mutation, Missense ; Protein Biosynthesis ; RNA, Messenger/genetics/metabolism ; *Reading Frames ; Receptors, Antigen, T-Cell, alpha-beta/*genetics ; Up-Regulation
    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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  • 3
    Publication Date: 1999-12-03
    Description: The crystal structure of a complex involving the D10 T cell receptor (TCR), 16-residue foreign peptide antigen, and the I-Ak self major histocompatibility complex (MHC) class II molecule is reported at 3.2 angstrom resolution. The D10 TCR is oriented in an orthogonal mode relative to its peptide-MHC (pMHC) ligand, necessitated by the amino-terminal extension of peptide residues projecting from the MHC class II antigen-binding groove as part of a mini beta sheet. Consequently, the disposition of D10 complementarity-determining region loops is altered relative to that of most pMHCI-specific TCRs; the latter TCRs assume a diagonal orientation, although with substantial variability. Peptide recognition, which involves P-1 to P8 residues, is dominated by the Valpha domain, which also binds to the class II MHC beta1 helix. That docking is limited to one segment of MHC-bound peptide offers an explanation for epitope recognition and altered peptide ligand effects, suggests a structural basis for alloreactivity, and illustrates how bacterial superantigens can span the TCR-pMHCII surface.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reinherz, E L -- Tan, K -- Tang, L -- Kern, P -- Liu, J -- Xiong, Y -- Hussey, R E -- Smolyar, A -- Hare, B -- Zhang, R -- Joachimiak, A -- Chang, H C -- Wagner, G -- Wang, J -- AI/CA37581/AI/NIAID NIH HHS/ -- AI19807/AI/NIAID NIH HHS/ -- GM56008/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1999 Dec 3;286(5446):1913-21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Immunobiology, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10583947" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens/*chemistry/immunology/metabolism ; Binding Sites ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/immunology ; Conalbumin/chemistry/immunology ; Crystallization ; Crystallography, X-Ray ; Histocompatibility Antigens Class I/immunology ; Histocompatibility Antigens Class II/*chemistry/immunology/metabolism ; Hydrogen Bonding ; Ligands ; Mice ; Mice, Inbred AKR ; Models, Molecular ; Oligopeptides/chemistry/immunology/metabolism ; Protein Conformation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Receptors, Antigen, T-Cell, alpha-beta/*chemistry/immunology/metabolism ; Superantigens/immunology/metabolism ; Thymus Gland/cytology/immunology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-04-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Volkow, N D -- Gatley, S J -- Fowler, J S -- Wang, G J -- Swanson, J -- New York, N.Y. -- Science. 2000 Apr 7;288(5463):11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Department, Brookhaven National Laboratory, Upton, NY 11973-5000, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10766624" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Attention Deficit Disorder with Hyperactivity/*drug therapy ; Brain/metabolism ; Carrier Proteins/genetics/metabolism/physiology ; Central Nervous System Stimulants/*pharmacology/therapeutic use ; Dopamine/physiology ; Dopamine Plasma Membrane Transport Proteins ; Humans ; Membrane Glycoproteins/metabolism ; *Membrane Transport Proteins ; Methylphenidate/*pharmacology/therapeutic use ; Mice ; Mice, Knockout ; Motor Activity/*drug effects ; *Nerve Tissue Proteins ; Serotonin/*metabolism ; Serotonin Plasma Membrane Transport Proteins
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1997-03-28
    Description: Neuroendocrine hormones of the hypothalamus-pituitary-thyroid axis can exert positive or negative immunoregulatory effects on intestinal lymphocytes. Small intestine epithelial cells were found to express receptors for thyrotropin-releasing hormone (TRH) and to be a primary source of intestine-derived thyroid-stimulating hormone (TSH). The gene for the TSH receptor (TSH-R) was expressed in intestinal T cells but not in epithelial cells, which suggested a hormone-mediated link between lymphoid and nonhematopoietic components of the intestine. Because mice with congenitally mutant TSH-R (hyt/hyt mice) have a selectively impaired intestinal T cell repertoire, TSH may be a key immunoregulatory mediator in the intestine.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, J -- Whetsell, M -- Klein, J R -- DK35566/DK/NIDDK NIH HHS/ -- R01 DK035566/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1997 Mar 28;275(5308):1937-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Science and Mervin Bovaird Center for Studies in Molecular Biology and Biotechnology, University of Tulsa, Tulsa, OK 74104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9072972" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Homeostasis ; *Immunity, Mucosal ; Intestinal Mucosa/cytology/*immunology/metabolism ; Intestine, Small/cytology/immunology/metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Nude ; Point Mutation ; Receptors, Thyrotropin/genetics/metabolism ; Receptors, Thyrotropin-Releasing Hormone/genetics/metabolism ; T-Lymphocyte Subsets/immunology/metabolism ; T-Lymphocytes/*immunology/metabolism ; Thyrotropin/genetics/*metabolism ; Thyrotropin-Releasing Hormone/*metabolism/pharmacology
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  • 6
    Publication Date: 2006-02-25
    Description: Apoptosis in the immune system is critical for maintaining self-tolerance and preventing autoimmunity. Nevertheless, inhibiting apoptosis in lymphocytes is not alone sufficient to break self-tolerance, suggesting the involvement of other cell types. We investigated whether apoptosis in dendritic cells (DCs) helps regulate self-tolerance by generating transgenic mice expressing the baculoviral caspase inhibitor, p35, in DCs (DC-p35). DC-p35 mice displayed defective DC apoptosis, resulting in their accumulation and, in turn, chronic lymphocyte activation and systemic autoimmune manifestations. The observation that a defect in DC apoptosis can independently lead to autoimmunity is consistent with a central role for these cells in maintaining immune self-tolerance.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Min -- Wang, Yui-Hsi -- Wang, Yihong -- Huang, Li -- Sandoval, Hector -- Liu, Yong-Jun -- Wang, Jin -- New York, N.Y. -- Science. 2006 Feb 24;311(5764):1160-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, Baylor College of Medicine, Houston, TX 77030, USA. minc@bcm.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16497935" target="_blank"〉PubMed〈/a〉
    Keywords: Adoptive Transfer ; Aging ; Animals ; Antibodies, Antinuclear/analysis ; *Apoptosis ; *Autoimmunity ; B-Lymphocytes/immunology ; Caspase Inhibitors ; Cell Survival ; Dendritic Cells/*immunology/*physiology ; Kidney/immunology ; Lung/immunology ; Lymphocyte Activation ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Transgenic ; *Self Tolerance ; Spleen/immunology ; T-Lymphocytes/immunology ; Viral Proteins/genetics/metabolism
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  • 7
    Publication Date: 2008-05-24
    Description: beta-Arrestins have important roles in the regulation of seven-transmembrane receptors (7TMRs). Smoothened (Smo) is a 7TMR that mediates effects of Hedgehog on developmental processes and whose dysregulation may cause tumorigenesis. beta-Arrestins are required for endocytosis of Smo and signaling to Gli transcription factors. In mammalian cells, Smo-dependent signaling requires translocation to primary cilia. We demonstrated that beta-arrestins mediate the activity-dependent interaction of Smo and the kinesin motor protein Kif3A. This multimeric complex localized to primary cilia and was disrupted in cells transfected with beta-arrestin small interfering RNA. beta-Arrestin 1 or beta-arrestin 2 depletion prevented the localization of Smo to primary cilia and the Smo-dependent activation of Gli. These results suggest roles for beta-arrestins in mediating the intracellular transport of a 7TMR to its obligate subcellular location for signaling.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2587210/" 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/PMC2587210/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kovacs, Jeffrey J -- Whalen, Erin J -- Liu, Renshui -- Xiao, Kunhong -- Kim, Jihee -- Chen, Minyong -- Wang, Jiangbo -- Chen, Wei -- Lefkowitz, Robert J -- 5R01 CA113656-02/CA/NCI NIH HHS/ -- 5T32 AI007217-25/AI/NIAID NIH HHS/ -- HL16037/HL/NHLBI NIH HHS/ -- HL70631/HL/NHLBI NIH HHS/ -- R01 CA113656/CA/NCI NIH HHS/ -- R01 CA113656-02/CA/NCI NIH HHS/ -- R01 CA113656-03/CA/NCI NIH HHS/ -- R01 HL016037/HL/NHLBI NIH HHS/ -- R01 HL016037-35/HL/NHLBI NIH HHS/ -- R01 HL070631/HL/NHLBI NIH HHS/ -- R01 HL070631-04/HL/NHLBI NIH HHS/ -- T32 AI007217/AI/NIAID NIH HHS/ -- T32 AI007217-25/AI/NIAID NIH HHS/ -- T32 AI007217-26/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2008 Jun 27;320(5884):1777-81. doi: 10.1126/science.1157983. Epub 2008 May 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18497258" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arrestins/genetics/*metabolism ; Cilia/*metabolism ; Hedgehog Proteins/metabolism ; Kinesin/*metabolism ; Mice ; Microscopy, Confocal ; Molecular Motor Proteins/*metabolism ; NIH 3T3 Cells ; Protein Transport ; RNA Interference ; Receptors, G-Protein-Coupled/*metabolism ; Recombinant Fusion Proteins/metabolism ; Signal Transduction ; Transcription Factors/metabolism ; Transfection
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  • 8
    Publication Date: 2011-04-23
    Description: Genetic regulation of mammalian heart size is poorly understood. Hippo signaling represents an organ-size control pathway in Drosophila, where it also inhibits cell proliferation and promotes apoptosis in imaginal discs. To determine whether Hippo signaling controls mammalian heart size, we inactivated Hippo pathway components in the developing mouse heart. Hippo-deficient embryos had overgrown hearts with elevated cardiomyocyte proliferation. Gene expression profiling and chromatin immunoprecipitation revealed that Hippo signaling negatively regulates a subset of Wnt target genes. Genetic interaction studies indicated that beta-catenin heterozygosity suppressed the Hippo cardiomyocyte overgrowth phenotype. Furthermore, the Hippo effector Yap interacts with beta-catenin on Sox2 and Snai2 genes. These data uncover a nuclear interaction between Hippo and Wnt signaling that restricts cardiomyocyte proliferation and controls heart size.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3133743/" 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/PMC3133743/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Heallen, Todd -- Zhang, Min -- Wang, Jun -- Bonilla-Claudio, Margarita -- Klysik, Ela -- Johnson, Randy L -- Martin, James F -- R01 DE012324/DE/NIDCR NIH HHS/ -- R01 DE012324-12/DE/NIDCR NIH HHS/ -- R01 HD052785/HD/NICHD NIH HHS/ -- R01 HD052785-05/HD/NICHD NIH HHS/ -- R01 HD060579/HD/NICHD NIH HHS/ -- R01 HD060579-02/HD/NICHD NIH HHS/ -- R01 HL093484/HL/NHLBI NIH HHS/ -- R01 HL093484-01A1/HL/NHLBI NIH HHS/ -- R01HD052785/HD/NICHD NIH HHS/ -- R01HD060579/HD/NICHD NIH HHS/ -- T32 DE15355-04/DE/NIDCR NIH HHS/ -- New York, N.Y. -- Science. 2011 Apr 22;332(6028):458-61. doi: 10.1126/science.1199010.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Biosciences and Technology, Texas A&M System Health Science Center, 2121 West Holcombe Boulevard, Houston, TX 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21512031" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/metabolism ; Animals ; Cardiomegaly/metabolism ; Cell Cycle Proteins/genetics/metabolism ; Cell Nucleus/metabolism ; Cell Proliferation ; Chromatin Immunoprecipitation ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Heart/*anatomy & histology/embryology ; Mice ; Mice, Transgenic ; Myocardium/cytology ; Myocytes, Cardiac/*cytology/*metabolism ; Organ Size ; Phosphoproteins/metabolism ; Phosphorylation ; Protein-Serine-Threonine Kinases/genetics/*metabolism ; SOXB1 Transcription Factors/genetics/metabolism ; *Signal Transduction ; Transcription Factors/genetics/metabolism ; Wnt Proteins/*metabolism ; beta Catenin/genetics/metabolism
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  • 9
    Publication Date: 2012-04-12
    Description: Osteoarthritis (OA) is a degenerative joint disease that involves the destruction of articular cartilage and eventually leads to disability. Molecules that promote the selective differentiation of multipotent mesenchymal stem cells (MSCs) into chondrocytes may stimulate the repair of damaged cartilage. Using an image-based high-throughput screen, we identified the small molecule kartogenin, which promotes chondrocyte differentiation (median effective concentration = 100 nM), shows chondroprotective effects in vitro, and is efficacious in two OA animal models. Kartogenin binds filamin A, disrupts its interaction with the transcription factor core-binding factor beta subunit (CBFbeta), and induces chondrogenesis by regulating the CBFbeta-RUNX1 transcriptional program. This work provides new insights into the control of chondrogenesis that may ultimately lead to a stem cell-based therapy for osteoarthritis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Johnson, Kristen -- Zhu, Shoutian -- Tremblay, Matthew S -- Payette, Joshua N -- Wang, Jianing -- Bouchez, Laure C -- Meeusen, Shelly -- Althage, Alana -- Cho, Charles Y -- Wu, Xu -- Schultz, Peter G -- New York, N.Y. -- Science. 2012 May 11;336(6082):717-21. doi: 10.1126/science.1215157. Epub 2012 Apr 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA. kjohnson@gnf.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22491093" target="_blank"〉PubMed〈/a〉
    Keywords: Anilides/administration & dosage/chemistry/*pharmacology/therapeutic use ; Animals ; Cartilage, Articular/*cytology ; Cattle ; Cell Nucleus/metabolism ; Chondrocytes/cytology/*drug effects/metabolism/physiology ; *Chondrogenesis ; Contractile Proteins/metabolism ; Core Binding Factor Alpha 2 Subunit/metabolism ; Core Binding Factor beta Subunit/metabolism ; Disease Models, Animal ; Filamins ; High-Throughput Screening Assays ; Humans ; Mesenchymal Stromal Cells/cytology/*drug effects/physiology ; Mice ; Microfilament Proteins/metabolism ; Osteoarthritis/*drug therapy/pathology/physiopathology ; Phthalic Acids/administration & dosage/chemistry/*pharmacology/therapeutic use ; Regeneration ; Small Molecule Libraries ; Structure-Activity Relationship
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  • 10
    Publication Date: 2012-03-17
    Description: Neurotransmitters are released through nascent fusion pores, which ordinarily dilate after bilayer fusion, preventing consistent biochemical studies. We used lipid bilayer nanodiscs as fusion partners; their rigid protein framework prevents dilation and reveals properties of the fusion pore induced by SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor). We found that although only one SNARE per nanodisc is required for maximum rates of bilayer fusion, efficient release of content on the physiologically relevant time scale of synaptic transmission apparently requires three or more SNARE complexes (SNAREpins) and the native transmembrane domain of vesicle-associated membrane protein 2 (VAMP2). We suggest that several SNAREpins simultaneously zippering their SNARE transmembrane helices within the freshly fused bilayers provide a radial force that prevents the nascent pore from resealing during synchronous neurotransmitter release.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3736847/" 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/PMC3736847/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shi, Lei -- Shen, Qing-Tao -- Kiel, Alexander -- Wang, Jing -- Wang, Hong-Wei -- Melia, Thomas J -- Rothman, James E -- Pincet, Frederic -- R01 DK027044/DK/NIDDK NIH HHS/ -- R37 DK027044/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2012 Mar 16;335(6074):1355-9. doi: 10.1126/science.1214984.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, School of Medicine, Yale University, New Haven, CT 06520, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22422984" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/metabolism ; Diffusion ; *Lipid Bilayers ; Liposomes ; *Membrane Fusion ; Membrane Proteins/chemistry/metabolism ; Mice ; Neurotransmitter Agents/metabolism ; Protein Structure, Tertiary ; Proteolipids/chemistry ; Rats ; Recombinant Fusion Proteins/chemistry/metabolism ; SNARE Proteins/*chemistry/*metabolism ; Synaptic Transmission ; Synaptic Vesicles/*chemistry/metabolism ; Synaptosomal-Associated Protein 25/chemistry/metabolism ; Syntaxin 1/chemistry/metabolism ; Vesicle-Associated Membrane Protein 2/*chemistry/*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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