ALBERT

All Library Books, journals and Electronic Records Telegrafenberg

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • Articles  (1,068)
  • Molecular Sequence Data  (585)
  • Cell Line  (543)
  • Cell & Developmental Biology
  • Chemical Engineering
  • LUNAR AND PLANETARY EXPLORATION
  • Limnology
  • 2005-2009  (1,068)
Collection
Keywords
Years
Year
  • 1
    Publication Date: 2009-12-23
    Description: Reprogramming of somatic cell nuclei to yield induced pluripotent stem (iPS) cells makes possible derivation of patient-specific stem cells for regenerative medicine. However, iPS cell generation is asynchronous and slow (2-3 weeks), the frequency is low (〈0.1%), and DNA demethylation constitutes a bottleneck. To determine regulatory mechanisms involved in reprogramming, we generated interspecies heterokaryons (fused mouse embryonic stem (ES) cells and human fibroblasts) that induce reprogramming synchronously, frequently and fast. Here we show that reprogramming towards pluripotency in single heterokaryons is initiated without cell division or DNA replication, rapidly (1 day) and efficiently (70%). Short interfering RNA (siRNA)-mediated knockdown showed that activation-induced cytidine deaminase (AID, also known as AICDA) is required for promoter demethylation and induction of OCT4 (also known as POU5F1) and NANOG gene expression. AID protein bound silent methylated OCT4 and NANOG promoters in fibroblasts, but not active demethylated promoters in ES cells. These data provide new evidence that mammalian AID is required for active DNA demethylation and initiation of nuclear reprogramming towards pluripotency in human somatic cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2906123/" 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/PMC2906123/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bhutani, Nidhi -- Brady, Jennifer J -- Damian, Mara -- Sacco, Alessandra -- Corbel, Stephane Y -- Blau, Helen M -- AG009521/AG/NIA NIH HHS/ -- AG024987/AG/NIA NIH HHS/ -- AI007328/AI/NIAID NIH HHS/ -- R01 AG009521/AG/NIA NIH HHS/ -- R01 AG009521-25/AG/NIA NIH HHS/ -- R01 AG024987/AG/NIA NIH HHS/ -- R01 AG024987-05/AG/NIA NIH HHS/ -- T32 AI007328/AI/NIAID NIH HHS/ -- U01 HL100397/HL/NHLBI NIH HHS/ -- England -- Nature. 2010 Feb 25;463(7284):1042-7. doi: 10.1038/nature08752.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Baxter Laboratory for Stem Cell Biology, Institute for Stem Cell Biology and Regenerative Medicine, Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94305-5175, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20027182" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Division ; Cell Fusion ; Cell Line ; Cells, Cultured ; Cellular Reprogramming/genetics/*physiology ; Chromatin Immunoprecipitation ; Cytidine Deaminase/deficiency/genetics/*metabolism ; DNA/chemistry/genetics/metabolism ; *DNA Methylation ; DNA Replication ; Embryonic Stem Cells/cytology/metabolism ; Fibroblasts/cytology/metabolism ; Gene Expression Regulation ; Gene Knockdown Techniques ; Homeodomain Proteins/genetics ; Humans ; Induced Pluripotent Stem Cells/*cytology/enzymology/*metabolism ; Lung/cytology/embryology ; Mice ; Models, Biological ; Octamer Transcription Factor-3/genetics ; Promoter Regions, Genetic/genetics ; Time Factors
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 2
    Publication Date: 2009-06-02
    Description: The generation of induced pluripotent stem (iPS) cells has enabled the derivation of patient-specific pluripotent cells and provided valuable experimental platforms to model human disease. Patient-specific iPS cells are also thought to hold great therapeutic potential, although direct evidence for this is still lacking. Here we show that, on correction of the genetic defect, somatic cells from Fanconi anaemia patients can be reprogrammed to pluripotency to generate patient-specific iPS cells. These cell lines appear indistinguishable from human embryonic stem cells and iPS cells from healthy individuals. Most importantly, we show that corrected Fanconi-anaemia-specific iPS cells can give rise to haematopoietic progenitors of the myeloid and erythroid lineages that are phenotypically normal, that is, disease-free. These data offer proof-of-concept that iPS cell technology can be used for the generation of disease-corrected, patient-specific cells with potential value for cell therapy applications.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2720823/" 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/PMC2720823/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Raya, Angel -- Rodriguez-Piza, Ignasi -- Guenechea, Guillermo -- Vassena, Rita -- Navarro, Susana -- Barrero, Maria Jose -- Consiglio, Antonella -- Castella, Maria -- Rio, Paula -- Sleep, Eduard -- Gonzalez, Federico -- Tiscornia, Gustavo -- Garreta, Elena -- Aasen, Trond -- Veiga, Anna -- Verma, Inder M -- Surralles, Jordi -- Bueren, Juan -- Izpisua Belmonte, Juan Carlos -- R01 HL053670/HL/NHLBI NIH HHS/ -- R01 HL053670-14/HL/NHLBI NIH HHS/ -- England -- Nature. 2009 Jul 2;460(7251):53-9. doi: 10.1038/nature08129. Epub 2009 May 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Regenerative Medicine in Barcelona, Dr. Aiguader 88, 08003 Barcelona, Spain.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19483674" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line ; Cellular Reprogramming ; Fanconi Anemia/*pathology/*therapy ; Health ; Hematopoietic Stem Cells/*cytology/metabolism ; Humans ; Pluripotent Stem Cells/*cytology/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 3
    Publication Date: 2009-05-05
    Description: A20 is a negative regulator of the NF-kappaB pathway and was initially identified as being rapidly induced after tumour-necrosis factor-alpha stimulation. It has a pivotal role in regulation of the immune response and prevents excessive activation of NF-kappaB in response to a variety of external stimuli; recent genetic studies have disclosed putative associations of polymorphic A20 (also called TNFAIP3) alleles with autoimmune disease risk. However, the involvement of A20 in the development of human cancers is unknown. Here we show, using a genome-wide analysis of genetic lesions in 238 B-cell lymphomas, that A20 is a common genetic target in B-lineage lymphomas. A20 is frequently inactivated by somatic mutations and/or deletions in mucosa-associated tissue lymphoma (18 out of 87; 21.8%) and Hodgkin's lymphoma of nodular sclerosis histology (5 out of 15; 33.3%), and, to a lesser extent, in other B-lineage lymphomas. When re-expressed in a lymphoma-derived cell line with no functional A20 alleles, wild-type A20, but not mutant A20, resulted in suppression of cell growth and induction of apoptosis, accompanied by downregulation of NF-kappaB activation. The A20-deficient cells stably generated tumours in immunodeficient mice, whereas the tumorigenicity was effectively suppressed by re-expression of A20. In A20-deficient cells, suppression of both cell growth and NF-kappaB activity due to re-expression of A20 depended, at least partly, on cell-surface-receptor signalling, including the tumour-necrosis factor receptor. Considering the physiological function of A20 in the negative modulation of NF-kappaB activation induced by multiple upstream stimuli, our findings indicate that uncontrolled signalling of NF-kappaB caused by loss of A20 function is involved in the pathogenesis of subsets of B-lineage lymphomas.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kato, Motohiro -- Sanada, Masashi -- Kato, Itaru -- Sato, Yasuharu -- Takita, Junko -- Takeuchi, Kengo -- Niwa, Akira -- Chen, Yuyan -- Nakazaki, Kumi -- Nomoto, Junko -- Asakura, Yoshitaka -- Muto, Satsuki -- Tamura, Azusa -- Iio, Mitsuru -- Akatsuka, Yoshiki -- Hayashi, Yasuhide -- Mori, Hiraku -- Igarashi, Takashi -- Kurokawa, Mineo -- Chiba, Shigeru -- Mori, Shigeo -- Ishikawa, Yuichi -- Okamoto, Koji -- Tobinai, Kensei -- Nakagama, Hitoshi -- Nakahata, Tatsutoshi -- Yoshino, Tadashi -- Kobayashi, Yukio -- Ogawa, Seishi -- England -- Nature. 2009 Jun 4;459(7247):712-6. doi: 10.1038/nature07969. Epub 2009 May 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Genomics Project, Department of Pediatrics, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19412163" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis/physiology ; Cell Line ; Cysteine Endopeptidases/*genetics/*metabolism ; DNA-Binding Proteins ; Gene Expression ; *Gene Silencing ; Genome/genetics ; Humans ; Intracellular Signaling Peptides and Proteins/*genetics/*metabolism ; Lymphoma, B-Cell/*genetics/*physiopathology ; Mice ; NF-kappa B/genetics/metabolism ; Nuclear Proteins/*genetics/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 4
    Publication Date: 2009-07-31
    Description: Acid-sensing ion channels are proton-activated, sodium-selective channels composed of three subunits, and are members of the superfamily of epithelial sodium channels, mechanosensitive and FMRF-amide peptide-gated ion channels. These ubiquitous eukaryotic ion channels have essential roles in biological activities as diverse as sodium homeostasis, taste and pain. Despite their crucial roles in biology and their unusual trimeric subunit stoichiometry, there is little knowledge of the structural and chemical principles underlying their ion channel architecture and ion-binding sites. Here we present the structure of a functional acid-sensing ion channel in a desensitized state at 3 A resolution, the location and composition of the approximately 8 A 'thick' desensitization gate, and the trigonal antiprism coordination of caesium ions bound in the extracellular vestibule. Comparison of the acid-sensing ion channel structure with the ATP-gated P2X(4) receptor reveals similarity in pore architecture and aqueous vestibules, suggesting that there are unanticipated yet common structural and mechanistic principles.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2845979/" 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/PMC2845979/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gonzales, Eric B -- Kawate, Toshimitsu -- Gouaux, Eric -- F32 GM083615/GM/NIGMS NIH HHS/ -- F32 GM083615-01/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Jul 30;460(7255):599-604. doi: 10.1038/nature08218.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vollum Institute, Oregon Health and Science University, 3181 Southwest Sam Jackson Park Road, Portland, Oregon 97239, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19641589" target="_blank"〉PubMed〈/a〉
    Keywords: Acid Sensing Ion Channels ; Animals ; Binding Sites ; CHO Cells ; Cell Line ; Cesium/metabolism ; Chickens/*physiology ; Cricetinae ; Cricetulus ; Crystallization ; Humans ; Ions/metabolism ; *Models, Molecular ; Nerve Tissue Proteins/*chemistry ; Protein Structure, Tertiary ; Receptors, Purinergic P2/*chemistry ; Receptors, Purinergic P2X ; Sodium Channels/*chemistry ; Zebrafish/*physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 5
    Publication Date: 2009-03-27
    Description: Toll-like receptors (TLRs) recognize microbial components, and evoke inflammation and immune responses. TLR stimulation activates complex gene expression networks that regulate the magnitude and duration of the immune reaction. Here we identify the TLR-inducible gene Zc3h12a as an immune response modifier that has an essential role in preventing immune disorders. Zc3h12a-deficient mice suffered from severe anaemia, and most died within 12 weeks. Zc3h12a(-/-) mice also showed augmented serum immunoglobulin levels and autoantibody production, together with a greatly increased number of plasma cells, as well as infiltration of plasma cells to the lung. Most Zc3h12a(-/-) splenic T cells showed effector/memory characteristics and produced interferon-gamma in response to T-cell receptor stimulation. Macrophages from Zc3h12a(-/-) mice showed highly increased production of interleukin (IL)-6 and IL-12p40 (also known as IL12b), but not TNF, in response to TLR ligands. Although the activation of TLR signalling pathways was normal, Il6 messenger RNA decay was severely impaired in Zc3h12a(-/-) macrophages. Overexpression of Zc3h12a accelerated Il6 mRNA degradation via its 3'-untranslated region (UTR), and destabilized RNAs with 3'-UTRs for genes including Il6, Il12p40 and the calcitonin receptor gene Calcr. Zc3h12a contains a putative amino-terminal nuclease domain, and the expressed protein had RNase activity, consistent with a role in the decay of Il6 mRNA. Together, these results indicate that Zc3h12a is an essential RNase that prevents immune disorders by directly controlling the stability of a set of inflammatory genes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Matsushita, Kazufumi -- Takeuchi, Osamu -- Standley, Daron M -- Kumagai, Yutaro -- Kawagoe, Tatsukata -- Miyake, Tohru -- Satoh, Takashi -- Kato, Hiroki -- Tsujimura, Tohru -- Nakamura, Haruki -- Akira, Shizuo -- P01 AI070167/AI/NIAID NIH HHS/ -- England -- Nature. 2009 Apr 30;458(7242):1185-90. doi: 10.1038/nature07924. Epub 2009 Mar 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19322177" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions/genetics/metabolism ; Anemia/complications/genetics ; Animals ; Autoantibodies/blood/immunology ; Autoimmune Diseases/complications/immunology ; Cell Line ; Cytokines/biosynthesis/genetics ; Fetal Diseases/immunology ; Humans ; Immunity/*genetics/*immunology ; Inflammation Mediators/metabolism ; Interleukin-6/genetics ; Macrophages, Peritoneal/immunology/metabolism ; Mice ; Plasma Cells/cytology ; *RNA Stability ; Ribonucleases/deficiency/genetics/*metabolism ; T-Lymphocytes/immunology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 6
    Publication Date: 2009-11-06
    Description: The activation of innate immune responses by nucleic acids is crucial to protective and pathological immunities and is mediated by the transmembrane Toll-like receptors (TLRs) and cytosolic receptors. However, it remains unknown whether a mechanism exists that integrates these nucleic-acid-sensing systems. Here we show that high-mobility group box (HMGB) proteins 1, 2 and 3 function as universal sentinels for nucleic acids. HMGBs bind to all immunogenic nucleic acids examined with a correlation between affinity and immunogenic potential. Hmgb1(-/-) and Hmgb2(-/-) mouse cells are defective in type-I interferon and inflammatory cytokine induction by DNA or RNA targeted to activate the cytosolic nucleic-acid-sensing receptors; cells in which the expression of all three HMGBs is suppressed show a more profound defect, accompanied by impaired activation of the transcription factors interferon regulatory factor 3 (IRF3) and nuclear factor (NF)-kappaB. The absence of HMGBs also severely impairs the activation of TLR3, TLR7 and TLR9 by their cognate nucleic acids. Our results therefore indicate a hierarchy in the nucleic-acid-mediated activation of immune responses, wherein the selective activation of nucleic-acid-sensing receptors is contingent on the more promiscuous sensing of nucleic acids by HMGBs. These findings may have implications for understanding the evolution of the innate immune system and for the treatment of immunological disorders.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yanai, Hideyuki -- Ban, Tatsuma -- Wang, ZhiChao -- Choi, Myoung Kwon -- Kawamura, Takeshi -- Negishi, Hideo -- Nakasato, Makoto -- Lu, Yan -- Hangai, Sho -- Koshiba, Ryuji -- Savitsky, David -- Ronfani, Lorenza -- Akira, Shizuo -- Bianchi, Marco E -- Honda, Kenya -- Tamura, Tomohiko -- Kodama, Tatsuhiko -- Taniguchi, Tadatsugu -- England -- Nature. 2009 Nov 5;462(7269):99-103. doi: 10.1038/nature08512.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19890330" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Cytosol/immunology ; DNA/immunology ; HMGB Proteins/deficiency/genetics/*immunology/*metabolism ; HMGB1 Protein/deficiency/genetics/immunology/metabolism ; HMGB2 Protein/deficiency/genetics/immunology/metabolism ; Immunity, Innate/*immunology ; Interferon Regulatory Factor-3/metabolism ; Mice ; Mice, Inbred C57BL ; Models, Immunological ; NF-kappa B/metabolism ; Nucleic Acids/*immunology ; Nucleotides/chemistry/immunology/metabolism ; RNA/immunology ; Signal Transduction ; Toll-Like Receptors/immunology ; Virus Diseases/immunology/virology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 7
    Publication Date: 2009-11-26
    Description: Mutations in the enzyme cytosolic isocitrate dehydrogenase 1 (IDH1) are a common feature of a major subset of primary human brain cancers. These mutations occur at a single amino acid residue of the IDH1 active site, resulting in loss of the enzyme's ability to catalyse conversion of isocitrate to alpha-ketoglutarate. However, only a single copy of the gene is mutated in tumours, raising the possibility that the mutations do not result in a simple loss of function. Here we show that cancer-associated IDH1 mutations result in a new ability of the enzyme to catalyse the NADPH-dependent reduction of alpha-ketoglutarate to R(-)-2-hydroxyglutarate (2HG). Structural studies demonstrate that when arginine 132 is mutated to histidine, residues in the active site are shifted to produce structural changes consistent with reduced oxidative decarboxylation of isocitrate and acquisition of the ability to convert alpha-ketoglutarate to 2HG. Excess accumulation of 2HG has been shown to lead to an elevated risk of malignant brain tumours in patients with inborn errors of 2HG metabolism. Similarly, in human malignant gliomas harbouring IDH1 mutations, we find markedly elevated levels of 2HG. These data demonstrate that the IDH1 mutations result in production of the onco-metabolite 2HG, and indicate that the excess 2HG which accumulates in vivo contributes to the formation and malignant progression of gliomas.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2818760/" 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/PMC2818760/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dang, Lenny -- White, David W -- Gross, Stefan -- Bennett, Bryson D -- Bittinger, Mark A -- Driggers, Edward M -- Fantin, Valeria R -- Jang, Hyun Gyung -- Jin, Shengfang -- Keenan, Marie C -- Marks, Kevin M -- Prins, Robert M -- Ward, Patrick S -- Yen, Katharine E -- Liau, Linda M -- Rabinowitz, Joshua D -- Cantley, Lewis C -- Thompson, Craig B -- Vander Heiden, Matthew G -- Su, Shinsan M -- P01 CA104838/CA/NCI NIH HHS/ -- P01 CA104838-05/CA/NCI NIH HHS/ -- P30 EB009998/EB/NIBIB NIH HHS/ -- R01 CA105463/CA/NCI NIH HHS/ -- R01 CA105463-06/CA/NCI NIH HHS/ -- R21 CA128620/CA/NCI NIH HHS/ -- England -- Nature. 2009 Dec 10;462(7274):739-44. doi: 10.1038/nature08617. Epub .〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Agios Pharmaceuticals, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19935646" target="_blank"〉PubMed〈/a〉
    Keywords: Arginine/genetics ; Brain Neoplasms/*genetics/*metabolism/pathology ; Catalytic Domain ; Cell Line ; Crystallography, X-Ray ; Disease Progression ; Enzyme Assays ; Glioma/genetics/metabolism/pathology ; Glutarates/*metabolism ; Histidine/genetics/metabolism ; Humans ; Isocitrate Dehydrogenase/*genetics/*metabolism ; Ketoglutaric Acids/metabolism ; Models, Molecular ; Mutant Proteins/*genetics/*metabolism ; Mutation/genetics ; Protein Conformation
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 8
    Publication Date: 2009-07-25
    Description: MicroRNAs (miRNAs) have emerged as key post-transcriptional regulators of gene expression, involved in diverse physiological and pathological processes. Although miRNAs can function as both tumour suppressors and oncogenes in tumour development, a widespread downregulation of miRNAs is commonly observed in human cancers and promotes cellular transformation and tumorigenesis. This indicates an inherent significance of small RNAs in tumour suppression. However, the connection between tumour suppressor networks and miRNA biogenesis machineries has not been investigated in depth. Here we show that a central tumour suppressor, p53, enhances the post-transcriptional maturation of several miRNAs with growth-suppressive function, including miR-16-1, miR-143 and miR-145, in response to DNA damage. In HCT116 cells and human diploid fibroblasts, p53 interacts with the Drosha processing complex through the association with DEAD-box RNA helicase p68 (also known as DDX5) and facilitates the processing of primary miRNAs to precursor miRNAs. We also found that transcriptionally inactive p53 mutants interfere with a functional assembly between Drosha complex and p68, leading to attenuation of miRNA processing activity. These findings suggest that transcription-independent modulation of miRNA biogenesis is intrinsically embedded in a tumour suppressive program governed by p53. Our study reveals a previously unrecognized function of p53 in miRNA processing, which may underlie key aspects of cancer biology.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Suzuki, Hiroshi I -- Yamagata, Kaoru -- Sugimoto, Koichi -- Iwamoto, Takashi -- Kato, Shigeaki -- Miyazono, Kohei -- England -- Nature. 2009 Jul 23;460(7254):529-33. doi: 10.1038/nature08199.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19626115" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line ; DNA Damage/physiology ; Gene Expression Regulation ; HCT116 Cells ; Humans ; MicroRNAs/*metabolism ; Mutation ; *RNA Processing, Post-Transcriptional ; Ribonuclease III/metabolism ; Tumor Suppressor Protein p53/genetics/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 9
    Publication Date: 2009-10-30
    Description: The leading cause of infertility in men and women is quantitative and qualitative defects in human germ-cell (oocyte and sperm) development. Yet, it has not been possible to examine the unique developmental genetics of human germ-cell formation and differentiation owing to inaccessibility of germ cells during fetal development. Although several studies have shown that germ cells can be differentiated from mouse and human embryonic stem cells, human germ cells differentiated in these studies generally did not develop beyond the earliest stages. Here we used a germ-cell reporter to quantify and isolate primordial germ cells derived from both male and female human embryonic stem cells. By silencing and overexpressing genes that encode germ-cell-specific cytoplasmic RNA-binding proteins (not transcription factors), we modulated human germ-cell formation and developmental progression. We observed that human DAZL (deleted in azoospermia-like) functions in primordial germ-cell formation, whereas closely related genes DAZ and BOULE (also called BOLL) promote later stages of meiosis and development of haploid gametes. These results are significant to the generation of gametes for future basic science and potential clinical applications.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3133736/" 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/PMC3133736/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kee, Kehkooi -- Angeles, Vanessa T -- Flores, Martha -- Nguyen, Ha Nam -- Reijo Pera, Renee A -- R01 HD047721/HD/NICHD NIH HHS/ -- R01 HD047721-06/HD/NICHD NIH HHS/ -- R01HD047721/HD/NICHD NIH HHS/ -- U54 HD055764/HD/NICHD NIH HHS/ -- U54 HD055764-015755/HD/NICHD NIH HHS/ -- U54HD055764/HD/NICHD NIH HHS/ -- England -- Nature. 2009 Nov 12;462(7270):222-5. doi: 10.1038/nature08562. Epub 2009 Oct 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Human Embryonic Stem Cell Research and Education, Institute for Stem Cell Biology & Regenerative Medicine, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford University, Palo Alto, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19865085" target="_blank"〉PubMed〈/a〉
    Keywords: Bone Morphogenetic Proteins/metabolism ; Cell Count ; *Cell Differentiation ; Cell Line ; Cellular Reprogramming ; Embryonic Stem Cells/cytology/metabolism ; Female ; Gene Expression ; Gene Silencing ; Genes, Reporter ; Germ Cells/*cytology/*metabolism ; *Haploidy ; Humans ; Male ; Meiosis ; Organ Specificity ; RNA-Binding Proteins/genetics/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 10
    Publication Date: 2009-07-31
    Description: P2X receptors are cation-selective ion channels gated by extracellular ATP, and are implicated in diverse physiological processes, from synaptic transmission to inflammation to the sensing of taste and pain. Because P2X receptors are not related to other ion channel proteins of known structure, there is at present no molecular foundation for mechanisms of ligand-gating, allosteric modulation and ion permeation. Here we present crystal structures of the zebrafish P2X(4) receptor in its closed, resting state. The chalice-shaped, trimeric receptor is knit together by subunit-subunit contacts implicated in ion channel gating and receptor assembly. Extracellular domains, rich in beta-strands, have large acidic patches that may attract cations, through fenestrations, to vestibules near the ion channel. In the transmembrane pore, the 'gate' is defined by an approximately 8 A slab of protein. We define the location of three non-canonical, intersubunit ATP-binding sites, and suggest that ATP binding promotes subunit rearrangement and ion channel opening.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2720809/" 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/PMC2720809/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kawate, Toshimitsu -- Michel, Jennifer Carlisle -- Birdsong, William T -- Gouaux, Eric -- U54 GM075026/GM/NIGMS NIH HHS/ -- U54 GM075026-04/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Jul 30;460(7255):592-8. doi: 10.1038/nature08198.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vollum Institute, Oregon Health and Science University, 3181 Southwest Sam Jackson Park Road, Oregon 97239, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19641588" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Animals ; Binding Sites ; Cell Line ; Crystallography, X-Ray ; Gadolinium/metabolism ; Humans ; Ion Channels/antagonists & inhibitors/*chemistry ; Membrane Proteins/chemistry ; *Models, Molecular ; Protein Binding ; Protein Folding ; Protein Structure, Tertiary ; Purinergic P2 Receptor Antagonists ; Receptors, Purinergic P2/*chemistry ; Receptors, Purinergic P2X4 ; Zebrafish/*physiology ; Zebrafish Proteins/antagonists & inhibitors/*chemistry
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 11
    Publication Date: 2009-07-25
    Description: African primates are naturally infected with over 40 different simian immunodeficiency viruses (SIVs), two of which have crossed the species barrier and generated human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2). Unlike the human viruses, however, SIVs do not generally cause acquired immunodeficiency syndrome (AIDS) in their natural hosts. Here we show that SIVcpz, the immediate precursor of HIV-1, is pathogenic in free-ranging chimpanzees. By following 94 members of two habituated chimpanzee communities in Gombe National Park, Tanzania, for over 9 years, we found a 10- to 16-fold higher age-corrected death hazard for SIVcpz-infected (n = 17) compared to uninfected (n = 77) chimpanzees. We also found that SIVcpz-infected females were less likely to give birth and had a higher infant mortality rate than uninfected females. Immunohistochemistry and in situ hybridization of post-mortem spleen and lymph node samples from three infected and two uninfected chimpanzees revealed significant CD4(+) T-cell depletion in all infected individuals, with evidence of high viral replication and extensive follicular dendritic cell virus trapping in one of them. One female, who died within 3 years of acquiring SIVcpz, had histopathological findings consistent with end-stage AIDS. These results indicate that SIVcpz, like HIV-1, is associated with progressive CD4(+) T-cell loss, lymphatic tissue destruction and premature death. These findings challenge the prevailing view that all natural SIV infections are non-pathogenic and suggest that SIVcpz has a substantial negative impact on the health, reproduction and lifespan of chimpanzees in the wild.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2872475/" 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/PMC2872475/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Keele, Brandon F -- Jones, James Holland -- Terio, Karen A -- Estes, Jacob D -- Rudicell, Rebecca S -- Wilson, Michael L -- Li, Yingying -- Learn, Gerald H -- Beasley, T Mark -- Schumacher-Stankey, Joann -- Wroblewski, Emily -- Mosser, Anna -- Raphael, Jane -- Kamenya, Shadrack -- Lonsdorf, Elizabeth V -- Travis, Dominic A -- Mlengeya, Titus -- Kinsel, Michael J -- Else, James G -- Silvestri, Guido -- Goodall, Jane -- Sharp, Paul M -- Shaw, George M -- Pusey, Anne E -- Hahn, Beatrice H -- HHSN266200400088C/PHS HHS/ -- P30 AI 27767/AI/NIAID NIH HHS/ -- P30 AI027767/AI/NIAID NIH HHS/ -- P30 AI027767-21A17134/AI/NIAID NIH HHS/ -- R01 AI058715/AI/NIAID NIH HHS/ -- R01 AI058715-06A1/AI/NIAID NIH HHS/ -- R01 AI50529/AI/NIAID NIH HHS/ -- R01 AI58715/AI/NIAID NIH HHS/ -- R37 AI050529/AI/NIAID NIH HHS/ -- R37 AI050529-06A1/AI/NIAID NIH HHS/ -- RR-00165/RR/NCRR NIH HHS/ -- T32 GM008111/GM/NIGMS NIH HHS/ -- U19 AI067854/AI/NIAID NIH HHS/ -- U19 AI067854-059010/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Jul 23;460(7254):515-9. doi: 10.1038/nature08200.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19626114" target="_blank"〉PubMed〈/a〉
    Keywords: Acquired Immunodeficiency Syndrome/pathology ; Africa ; Animals ; Animals, Wild ; CD4-Positive T-Lymphocytes/immunology ; Female ; Humans ; Male ; Molecular Sequence Data ; Pan troglodytes/*virology ; Prevalence ; Simian Acquired Immunodeficiency ; Syndrome/epidemiology/immunology/*mortality/*pathology ; Simian Immunodeficiency Virus/*physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 12
    Publication Date: 2009-03-10
    Description: Acetylation within the globular core domain of histone H3 on lysine 56 (H3K56) has recently been shown to have a critical role in packaging DNA into chromatin following DNA replication and repair in budding yeast. However, the function or occurrence of this specific histone mark has not been studied in multicellular eukaryotes, mainly because the Rtt109 enzyme that is known to mediate acetylation of H3K56 (H3K56ac) is fungal-specific. Here we demonstrate that the histone acetyl transferase CBP (also known as Nejire) in flies and CBP and p300 (Ep300) in humans acetylate H3K56, whereas Drosophila Sir2 and human SIRT1 and SIRT2 deacetylate H3K56ac. The histone chaperones ASF1A in humans and Asf1 in Drosophila are required for acetylation of H3K56 in vivo, whereas the histone chaperone CAF-1 (chromatin assembly factor 1) in humans and Caf1 in Drosophila are required for the incorporation of histones bearing this mark into chromatin. We show that, in response to DNA damage, histones bearing acetylated K56 are assembled into chromatin in Drosophila and human cells, forming foci that colocalize with sites of DNA repair. Furthermore, acetylation of H3K56 is increased in multiple types of cancer, correlating with increased levels of ASF1A in these tumours. Our identification of multiple proteins regulating the levels of H3K56 acetylation in metazoans will allow future studies of this critical and unique histone modification that couples chromatin assembly to DNA synthesis, cell proliferation and cancer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2756583/" 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/PMC2756583/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Das, Chandrima -- Lucia, M Scott -- Hansen, Kirk C -- Tyler, Jessica K -- CA95641/CA/NCI NIH HHS/ -- GM64475/GM/NIGMS NIH HHS/ -- R01 CA095641/CA/NCI NIH HHS/ -- R01 CA095641-07/CA/NCI NIH HHS/ -- R01 GM064475/GM/NIGMS NIH HHS/ -- R01 GM064475-07/GM/NIGMS NIH HHS/ -- England -- Nature. 2009 May 7;459(7243):113-7. doi: 10.1038/nature07861. Epub 2009 Mar 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, PO Box 6511, Aurora Colorado 80045, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19270680" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Animals ; Cell Cycle Proteins/metabolism ; Cell Line ; Chromosomal Proteins, Non-Histone/metabolism ; DNA Damage/physiology ; Drosophila Proteins/metabolism ; Drosophila melanogaster/*enzymology ; HeLa Cells ; Histone Deacetylases/metabolism ; Histones/*metabolism ; Humans ; Lysine/*metabolism ; Molecular Chaperones/metabolism ; Retinoblastoma-Binding Protein 4 ; Sirtuin 1 ; Sirtuin 2 ; Sirtuins/metabolism ; p300-CBP Transcription Factors/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 13
    Publication Date: 2009-07-31
    Description: Reactive oxygen species (ROS) produced by NADPH oxidase function as defence and signalling molecules related to innate immunity and various cellular responses. The activation of NADPH oxidase in response to plasma membrane receptor activation depends on the phosphorylation of cytoplasmic oxidase subunits, their translocation to membranes and the assembly of all NADPH oxidase components. Tumour necrosis factor (TNF) is a prominent stimulus of ROS production, but the molecular mechanisms by which TNF activates NADPH oxidase are poorly understood. Here we identify riboflavin kinase (RFK, formerly known as flavokinase) as a previously unrecognized TNF-receptor-1 (TNFR1)-binding protein that physically and functionally couples TNFR1 to NADPH oxidase. In mouse and human cells, RFK binds to both the TNFR1-death domain and to p22(phox), the common subunit of NADPH oxidase isoforms. RFK-mediated bridging of TNFR1 and p22(phox) is a prerequisite for TNF-induced but not for Toll-like-receptor-induced ROS production. Exogenous flavin mononucleotide or FAD was able to substitute fully for TNF stimulation of NADPH oxidase in RFK-deficient cells. RFK is rate-limiting in the synthesis of FAD, an essential prosthetic group of NADPH oxidase. The results suggest that TNF, through the activation of RFK, enhances the incorporation of FAD in NADPH oxidase enzymes, a critical step for the assembly and activation of NADPH oxidase.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yazdanpanah, Benjamin -- Wiegmann, Katja -- Tchikov, Vladimir -- Krut, Oleg -- Pongratz, Carola -- Schramm, Michael -- Kleinridders, Andre -- Wunderlich, Thomas -- Kashkar, Hamid -- Utermohlen, Olaf -- Bruning, Jens C -- Schutze, Stefan -- Kronke, Martin -- England -- Nature. 2009 Aug 27;460(7259):1159-63. doi: 10.1038/nature08206. Epub 2009 Jul 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19641494" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Cytochrome b Group/metabolism ; Enzyme Activation ; Fibroblasts ; Flavin Mononucleotide/metabolism ; Flavin-Adenine Dinucleotide/biosynthesis/metabolism ; HeLa Cells ; Humans ; Isoenzymes/chemistry/metabolism ; Membrane Glycoproteins/metabolism ; Mice ; NADH, NADPH Oxidoreductases/metabolism ; NADPH Oxidase/chemistry/*metabolism ; Phosphotransferases (Alcohol Group Acceptor)/deficiency/genetics/*metabolism ; Protein Binding ; Protein Structure, Tertiary ; Reactive Oxygen Species/metabolism ; Receptors, Tumor Necrosis Factor, Type I/chemistry/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 14
    Publication Date: 2009-06-30
    Description: One of the most distinctive steps in the development of the vertebrate nervous system occurs at mitotic exit when cells lose multipotency and begin to develop stable connections that will persist for a lifetime. This transition is accompanied by a switch in ATP-dependent chromatin-remodelling mechanisms that appears to coincide with the final mitotic division of neurons. This switch involves the exchange of the BAF53a (also known as ACTL6a) and BAF45a (PHF10) subunits within Swi/Snf-like neural-progenitor-specific BAF (npBAF) complexes for the homologous BAF53b (ACTL6b) and BAF45b (DPF1) subunits within neuron-specific BAF (nBAF) complexes in post-mitotic neurons. The subunits of the npBAF complex are essential for neural-progenitor proliferation, and mice with reduced dosage for the genes encoding its subunits have defects in neural-tube closure similar to those in human spina bifida, one of the most serious congenital birth defects. In contrast, BAF53b and the nBAF complex are essential for an evolutionarily conserved program of post-mitotic neural development and dendritic morphogenesis. Here we show that this essential transition is mediated by repression of BAF53a by miR-9* and miR-124. We find that BAF53a repression is mediated by sequences in the 3' untranslated region corresponding to the recognition sites for miR-9* and miR-124, which are selectively expressed in post-mitotic neurons. Mutation of these sites led to persistent expression of BAF53a and defective activity-dependent dendritic outgrowth in neurons. In addition, overexpression of miR-9* and miR-124 in neural progenitors caused reduced proliferation. Previous studies have indicated that miR-9* and miR-124 are repressed by the repressor-element-1-silencing transcription factor (REST, also known as NRSF). Indeed, expression of REST in post-mitotic neurons led to derepression of BAF53a, indicating that REST-mediated repression of microRNAs directs the essential switch of chromatin regulatory complexes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2921580/" 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/PMC2921580/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yoo, Andrew S -- Staahl, Brett T -- Chen, Lei -- Crabtree, Gerald R -- 2 T32 HD007249/HD/NICHD NIH HHS/ -- AI060037/AI/NIAID NIH HHS/ -- HD55391/HD/NICHD NIH HHS/ -- NS046789/NS/NINDS NIH HHS/ -- R01 HD055391/HD/NICHD NIH HHS/ -- R01 NS046789/NS/NINDS NIH HHS/ -- R01 NS046789-08/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Jul 30;460(7255):642-6. doi: 10.1038/nature08139. Epub 2009 Jun 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, and Department of Developmental Biology, Stanford University, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19561591" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions/metabolism ; Actins/genetics/metabolism ; Animals ; CHO Cells ; Cell Line ; Chromatin Assembly and Disassembly/genetics/*physiology ; Chromosomal Proteins, Non-Histone/genetics/metabolism ; Cricetinae ; Cricetulus ; DNA-Binding Proteins/genetics/metabolism ; Dendrites/physiology ; *Gene Expression Regulation, Developmental ; Mice ; Mice, Transgenic ; MicroRNAs/*metabolism ; Mitosis ; Nervous System/cytology/*embryology ; Neurons/cytology ; Repressor Proteins/metabolism ; Stem Cells/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 15
    Publication Date: 2009-07-03
    Description: The generation and expansion of diverse cardiovascular cell lineages is a critical step during human cardiogenesis, with major implications for congenital heart disease. Unravelling the mechanisms for the diversification of human heart cell lineages has been hampered by the lack of genetic tools to purify early cardiac progenitors and define their developmental potential. Recent studies in the mouse embryo have identified a multipotent cardiac progenitor that contributes to all of the major cell types in the murine heart. In contrast to murine development, human cardiogenesis has a much longer onset of heart cell lineage diversification and expansion, suggesting divergent pathways. Here we identify a diverse set of human fetal ISL1(+) cardiovascular progenitors that give rise to the cardiomyocyte, smooth muscle and endothelial cell lineages. Using two independent transgenic and gene-targeting approaches in human embryonic stem cell lines, we show that purified ISL1(+) primordial progenitors are capable of self-renewal and expansion before differentiation into the three major cell types in the heart. These results lay the foundation for the generation of human model systems for cardiovascular disease and novel approaches for human regenerative cardiovascular medicine.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bu, Lei -- Jiang, Xin -- Martin-Puig, Silvia -- Caron, Leslie -- Zhu, Shenjun -- Shao, Ying -- Roberts, Drucilla J -- Huang, Paul L -- Domian, Ibrahim J -- Chien, Kenneth R -- England -- Nature. 2009 Jul 2;460(7251):113-7. doi: 10.1038/nature08191.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cardiovascular Research Center, Massachusetts General Hospital, Charles River Plaza/CPZN 3208, 185 Cambridge Street, Boston, Massachusetts 02114, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19571884" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Differentiation ; Cell Division ; Cell Line ; *Cell Lineage ; Coculture Techniques ; Embryonic Stem Cells/cytology/metabolism ; Endothelial Cells/cytology ; Fetus/cytology/embryology ; Heart/embryology ; Homeodomain Proteins/*metabolism ; Humans ; LIM-Homeodomain Proteins ; Multipotent Stem Cells/*cytology/*metabolism ; Muscle, Smooth/cytology ; Myocardium/*cytology ; Myocytes, Cardiac/cytology ; Transcription Factors ; Wnt Proteins/metabolism ; Wnt3 Protein
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 16
    Publication Date: 2009-09-29
    Description: Activation of Janus kinase 2 (JAK2) by chromosomal translocations or point mutations is a frequent event in haematological malignancies. JAK2 is a non-receptor tyrosine kinase that regulates several cellular processes by inducing cytoplasmic signalling cascades. Here we show that human JAK2 is present in the nucleus of haematopoietic cells and directly phosphorylates Tyr 41 (Y41) on histone H3. Heterochromatin protein 1alpha (HP1alpha), but not HP1beta, specifically binds to this region of H3 through its chromo-shadow domain. Phosphorylation of H3Y41 by JAK2 prevents this binding. Inhibition of JAK2 activity in human leukaemic cells decreases both the expression of the haematopoietic oncogene lmo2 and the phosphorylation of H3Y41 at its promoter, while simultaneously increasing the binding of HP1alpha at the same site. Tauhese results identify a previously unrecognized nuclear role for JAK2 in the phosphorylation of H3Y41 and reveal a direct mechanistic link between two genes, jak2 and lmo2, involved in normal haematopoiesis and leukaemia.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3785147/" 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/PMC3785147/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dawson, Mark A -- Bannister, Andrew J -- Gottgens, Berthold -- Foster, Samuel D -- Bartke, Till -- Green, Anthony R -- Kouzarides, Tony -- 089957/Wellcome Trust/United Kingdom -- 12765/Cancer Research UK/United Kingdom -- G0800784/Medical Research Council/United Kingdom -- MC_UP_1102/2/Medical Research Council/United Kingdom -- Cancer Research UK/United Kingdom -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2009 Oct 8;461(7265):819-22. doi: 10.1038/nature08448. Epub 2009 Sep 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cambridge Institute for Medical Research and Department of Haematology, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19783980" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing ; Animals ; Binding Sites ; Cell Line ; Cell Nucleus/enzymology ; Chromatin/chemistry/*metabolism ; Chromosomal Proteins, Non-Histone/*metabolism ; DNA-Binding Proteins/genetics ; Gene Expression Regulation, Neoplastic ; Hematopoiesis/genetics ; Hematopoietic Stem Cells/cytology/enzymology ; Histones/chemistry/genetics/*metabolism ; Humans ; Janus Kinase 2/antagonists & inhibitors/*metabolism ; LIM Domain Proteins ; Leukemia/enzymology/genetics/metabolism/pathology ; Metalloproteins/genetics ; Mice ; Oncogenes/genetics ; Phosphorylation ; Promoter Regions, Genetic/genetics ; Protein Binding ; Proto-Oncogene Proteins ; Signal Transduction ; Tyrosine/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 17
    Publication Date: 2009-04-24
    Description: Mammals rely heavily on olfaction to interact adequately with each other and with their environment. They make use of seven-transmembrane G-protein-coupled receptors to identify odorants and pheromones. These receptors are present on dendrites of olfactory sensory neurons located in the main olfactory or vomeronasal sensory epithelia, and pertain to the odorant, trace amine-associated receptor and vomeronasal type 1 (ref. 4) or 2 (refs 5-7) receptor superfamilies. Whether these four sensor classes represent the complete olfactory molecular repertoire used by mammals to make sense of the outside world is unknown. Here we report the expression of formyl peptide receptor-related genes by vomeronasal sensory neurons, in multiple mammalian species. Similar to the four known olfactory receptor gene classes, these genes encode seven-transmembrane proteins, and are characterized by monogenic transcription and a punctate expression pattern in the sensory neuroepithelium. In vitro expression of mouse formyl peptide receptor-like 1, 3, 4, 6 and 7 provides sensitivity to disease/inflammation-related ligands. Establishing an in situ approach that combines whole-mount vomeronasal preparations with dendritic calcium imaging in the intact neuroepithelium, we show neuronal responses to the same molecules, which therefore represent a new class of vomeronasal agonists. Taken together, these results suggest that formyl peptide receptor-like proteins have an olfactory function associated with the identification of pathogens, or of pathogenic states.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Riviere, Stephane -- Challet, Ludivine -- Fluegge, Daniela -- Spehr, Marc -- Rodriguez, Ivan -- England -- Nature. 2009 May 28;459(7246):574-7. doi: 10.1038/nature08029.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Zoology and Animal Biology, and National Center of Competence Frontiers in Genetics, University of Geneva, 1205 Geneva, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19387439" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium Signaling ; Cell Line ; Dendrites/drug effects/metabolism ; *Disease ; Gene Expression Profiling ; Humans ; Inflammation/pathology ; Ligands ; Mice ; Olfactory Perception/drug effects/*physiology ; Olfactory Receptor Neurons/cytology/drug effects/*metabolism ; Organ Specificity ; Receptors, Formyl Peptide/genetics/*metabolism ; Smell/drug effects/*physiology ; Vomeronasal Organ/*cytology/drug effects/physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 18
    Publication Date: 2009-09-01
    Description: Induced pluripotent stem (iPS) cells have been generated from mouse and human somatic cells by ectopic expression of four transcription factors (OCT4 (also called POU5F1), SOX2, c-Myc and KLF4). We previously reported that Oct4 alone is sufficient to reprogram directly adult mouse neural stem cells to iPS cells. Here we report the generation of one-factor human iPS cells from human fetal neural stem cells (one-factor (1F) human NiPS cells) by ectopic expression of OCT4 alone. One-factor human NiPS cells resemble human embryonic stem cells in global gene expression profiles, epigenetic status, as well as pluripotency in vitro and in vivo. These findings demonstrate that the transcription factor OCT4 is sufficient to reprogram human neural stem cells to pluripotency. One-factor iPS cell generation will advance the field further towards understanding reprogramming and generating patient-specific pluripotent stem cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Jeong Beom -- Greber, Boris -- Arauzo-Bravo, Marcos J -- Meyer, Johann -- Park, Kook In -- Zaehres, Holm -- Scholer, Hans R -- England -- Nature. 2009 Oct 1;461(7264):649-3. doi: 10.1038/nature08436.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max Planck Institute for Molecular Biomedicine, Department of Cell and Developmental Biology, Rontgenstrasse 20, 48149 Munster, NRW, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19718018" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biomarkers/analysis ; *Cell Dedifferentiation ; Cell Differentiation ; Cell Line ; *Cellular Reprogramming ; DNA Methylation ; Embryonic Stem Cells/cytology/metabolism ; Epigenesis, Genetic ; Fetus/*cytology ; Gene Expression Profiling ; Germ Layers/cytology/metabolism ; Humans ; Mice ; Neurons/*cytology/metabolism ; Octamer Transcription Factor-3/genetics/*metabolism ; Pluripotent Stem Cells/*cytology/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 19
    Publication Date: 2009-10-23
    Description: NF-kappaB transcription factors function as crucial regulators of inflammatory and immune responses as well as of cell survival. They have also been implicated in cellular transformation and tumorigenesis. However, despite extensive biochemical characterization of NF-kappaB signalling during the past twenty years, the requirement for NF-kappaB in tumour development in vivo, particularly in solid tumours, is not completely understood. Here we show that the NF-kappaB pathway is required for the development of tumours in a mouse model of lung adenocarcinoma. Concomitant loss of p53 (also known as Trp53) and expression of oncogenic Kras(G12D) resulted in NF-kappaB activation in primary mouse embryonic fibroblasts. Conversely, in lung tumour cell lines expressing Kras(G12D) and lacking p53, p53 restoration led to NF-kappaB inhibition. Furthermore, the inhibition of NF-kappaB signalling induced apoptosis in p53-null lung cancer cell lines. Inhibition of the pathway in lung tumours in vivo, from the time of tumour initiation or after tumour progression, resulted in significantly reduced tumour development. Together, these results indicate a critical function for NF-kappaB signalling in lung tumour development and, further, that this requirement depends on p53 status. These findings also provide support for the development of NF-kappaB inhibitory drugs as targeted therapies for the treatment of patients with defined mutations in Kras and p53.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2780341/" 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/PMC2780341/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Meylan, Etienne -- Dooley, Alison L -- Feldser, David M -- Shen, Lynn -- Turk, Erin -- Ouyang, Chensi -- Jacks, Tyler -- P30 CA014051/CA/NCI NIH HHS/ -- P30 CA014051-37/CA/NCI NIH HHS/ -- P30 CA014051-38/CA/NCI NIH HHS/ -- P30-CA14051/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Nov 5;462(7269):104-7. doi: 10.1038/nature08462. Epub 2009 Oct 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Koch Institute for Integrative Cancer Research, and Department of Biology, and Howard Hughes Medical Institute, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19847165" target="_blank"〉PubMed〈/a〉
    Keywords: Adenocarcinoma/*metabolism/*pathology ; Animals ; Apoptosis ; Carcinoma, Non-Small-Cell Lung/metabolism/pathology ; Cell Line ; Cell Line, Tumor ; Cell Survival ; Cells, Cultured ; DNA/metabolism ; *Disease Models, Animal ; Fibroblasts ; Genes, p53/genetics ; Humans ; Lung Neoplasms/*metabolism/*pathology ; Mice ; NF-kappa B/antagonists & inhibitors/*metabolism ; Oncogene Protein p21(ras)/genetics/metabolism ; *Signal Transduction ; Transcription Factor RelA/metabolism ; Tumor Suppressor Protein p53/deficiency/genetics/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 20
    Publication Date: 2009-04-07
    Description: The versatility of Ca2+ signals derives from their spatio-temporal organization. For Ca2+ signals initiated by inositol-1,4,5-trisphosphate (InsP3), this requires local interactions between InsP3 receptors (InsP3Rs) mediated by their rapid stimulation and slower inhibition by cytosolic Ca2+. This allows hierarchical recruitment of Ca2+ release events as the InsP3 concentration increases. Single InsP3Rs respond first, then clustered InsP3Rs open together giving a local 'Ca2+ puff', and as puffs become more frequent they ignite regenerative Ca2+ waves. Using nuclear patch-clamp recording, here we demonstrate that InsP3Rs are initially randomly distributed with an estimated separation of 1 m. Low concentrations of InsP3 cause InsP3Rs to aggregate rapidly and reversibly into small clusters of about four closely associated InsP3Rs. At resting cytosolic [Ca2+], clustered InsP3Rs open independently, but with lower open probability, shorter open time, and less InsP3 sensitivity than lone InsP3Rs. Increasing cytosolic [Ca2+] reverses the inhibition caused by clustering, InsP3R gating becomes coupled, and the duration of multiple openings is prolonged. Clustering both exposes InsP3Rs to local Ca2+ rises and increases the effects of Ca2+. Dynamic regulation of clustering by InsP3 retunes InsP3R sensitivity to InsP3 and Ca2+, facilitating hierarchical recruitment of the elementary events that underlie all InsP3-evoked Ca2+ signals.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2702691/" 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/PMC2702691/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Taufiq-Ur-Rahman -- Skupin, Alexander -- Falcke, Martin -- Taylor, Colin W -- 085295/Wellcome Trust/United Kingdom -- BBE0046601/Biotechnology and Biological Sciences Research Council/United Kingdom -- Biotechnology and Biological Sciences Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2009 Apr 2;458(7238):655-9. doi: 10.1038/nature07763.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, Tennis Court Road, Cambridge CB2 1PD, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19348050" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/*metabolism ; *Calcium Signaling ; Cell Line ; Cytosol/metabolism ; Inositol 1,4,5-Trisphosphate/*metabolism ; Inositol 1,4,5-Trisphosphate Receptors/*metabolism ; Ion Channel Gating ; Patch-Clamp Techniques ; Protein Transport ; Rats
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 21
    Publication Date: 2009-04-10
    Description: The repair of DNA double-strand breaks (DSBs) is tightly regulated during the cell cycle. In G1 phase, the absence of a sister chromatid means that repair of DSBs occurs through non-homologous end-joining or microhomology-mediated end-joining (MMEJ). These pathways often involve loss of DNA sequences at the break site and are therefore error-prone. In late S and G2 phases, even though DNA end-joining pathways remain functional, there is an increase in repair of DSBs by homologous recombination, which is mostly error-free. Consequently, the relative contribution of these different pathways to DSB repair in the cell cycle has a large influence on the maintenance of genetic integrity. It has remained unknown how DSBs are directed for repair by different, potentially competing, repair pathways. Here we identify a role for CtIP (also known as RBBP8) in this process in the avian B-cell line DT40. We establish that CtIP is required not only for repair of DSBs by homologous recombination in S/G2 phase but also for MMEJ in G1. The function of CtIP in homologous recombination, but not MMEJ, is dependent on the phosphorylation of serine residue 327 and recruitment of BRCA1. Cells expressing CtIP protein that cannot be phosphorylated at serine 327 are specifically defective in homologous recombination and have a decreased level of single-stranded DNA after DNA damage, whereas MMEJ remains unaffected. Our data support a model in which phosphorylation of serine 327 of CtIP as cells enter S phase and the recruitment of BRCA1 functions as a molecular switch to shift the balance of DSB repair from error-prone DNA end-joining to error-free homologous recombination.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2857324/" 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/PMC2857324/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yun, Maximina H -- Hiom, Kevin -- MC_U105184300/Medical Research Council/United Kingdom -- U.1051.03.005(78826)/Medical Research Council/United Kingdom -- England -- Nature. 2009 May 21;459(7245):460-3. doi: 10.1038/nature07955. Epub 2009 Apr 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Protein and Nucleic Acid Chemistry, MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19357644" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Avian Proteins/*metabolism ; B-Lymphocytes/cytology/metabolism ; BRCA1 Protein/*metabolism ; Carrier Proteins/genetics/*metabolism ; *Cell Cycle ; Cell Line ; Chickens ; Cisplatin/pharmacology ; *DNA Breaks, Double-Stranded/radiation effects ; DNA Repair/genetics/*physiology ; G1 Phase ; G2 Phase ; Humans ; Nuclear Proteins/genetics/*metabolism ; Phosphorylation ; Phosphoserine/metabolism ; Recombination, Genetic/genetics ; S Phase ; X-Rays
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 22
    Publication Date: 2009-11-13
    Description: Cohesin not only links sister chromatids but also inhibits the transcriptional machinery's interaction with and movement along chromatin. In contrast, replication forks must traverse such cohesin-associated obstructions to duplicate the entire genome in S phase. How this occurs is unknown. Through single-molecule analysis, we demonstrate that the replication factor C (RFC)-CTF18 clamp loader (RFC(CTF18)) controls the velocity, spacing and restart activity of replication forks in human cells and is required for robust acetylation of cohesin's SMC3 subunit and sister chromatid cohesion. Unexpectedly, we discovered that cohesin acetylation itself is a central determinant of fork processivity, as slow-moving replication forks were found in cells lacking the Eco1-related acetyltransferases ESCO1 or ESCO2 (refs 8-10) (including those derived from Roberts' syndrome patients, in whom ESCO2 is biallelically mutated) and in cells expressing a form of SMC3 that cannot be acetylated. This defect was a consequence of cohesin's hyperstable interaction with two regulatory cofactors, WAPL and PDS5A (refs 12, 13); removal of either cofactor allowed forks to progress rapidly without ESCO1, ESCO2, or RFC(CTF18). Our results show a novel mechanism for clamp-loader-dependent fork progression, mediated by the post-translational modification and structural remodelling of the cohesin ring. Loss of this regulatory mechanism leads to the spontaneous accrual of DNA damage and may contribute to the abnormalities of the Roberts' syndrome cohesinopathy.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2777716/" 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/PMC2777716/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Terret, Marie-Emilie -- Sherwood, Rebecca -- Rahman, Sadia -- Qin, Jun -- Jallepalli, Prasad V -- R01 CA107342/CA/NCI NIH HHS/ -- R01 CA107342-05/CA/NCI NIH HHS/ -- R01 GM094972/GM/NIGMS NIH HHS/ -- England -- Nature. 2009 Nov 12;462(7270):231-4. doi: 10.1038/nature08550.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19907496" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Acetyltransferases/deficiency/genetics ; Carrier Proteins/genetics/metabolism ; Cell Aging ; Cell Cycle Proteins/chemistry/*metabolism ; Cell Line ; Chromatids/metabolism ; Chromosomal Proteins, Non-Histone/chemistry/deficiency/genetics/*metabolism ; DNA Damage ; DNA Replication/drug effects/*physiology ; Humans ; Mutagens/toxicity ; Nuclear Proteins/genetics/metabolism ; Protein Subunits/metabolism ; Proto-Oncogene Proteins/metabolism ; Replication Protein C/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 23
    Publication Date: 2009-10-16
    Description: Epigenetic modifications at the histone level affect gene regulation in response to extracellular signals. However, regulated epigenetic modifications at the DNA level, especially active DNA demethylation, in gene activation are not well understood. Here we report that DNA methylation/demethylation is hormonally switched to control transcription of the cytochrome p450 27B1 (CYP27B1) gene. Reflecting vitamin-D-mediated transrepression of the CYP27B1 gene by the negative vitamin D response element (nVDRE), methylation of CpG sites ((5m)CpG) is induced by vitamin D in this gene promoter. Conversely, treatment with parathyroid hormone, a hormone known to activate the CYP27B1 gene, induces active demethylation of the (5m)CpG sites in this promoter. Biochemical purification of a complex associated with the nVDRE-binding protein (VDIR, also known as TCF3) identified two DNA methyltransferases, DNMT1 and DNMT3B, for methylation of CpG sites, as well as a DNA glycosylase, MBD4 (ref. 10). Protein-kinase-C-phosphorylated MBD4 by parathyroid hormone stimulation promotes incision of methylated DNA through glycosylase activity, and a base-excision repair process seems to complete DNA demethylation in the MBD4-bound promoter. Such parathyroid-hormone-induced DNA demethylation and subsequent transcriptional derepression are impaired in Mbd4(-/-) mice. Thus, the present findings suggest that methylation switching at the DNA level contributes to the hormonal control of transcription.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Mi-Sun -- Kondo, Takeshi -- Takada, Ichiro -- Youn, Min-Young -- Yamamoto, Yoko -- Takahashi, Sayuri -- Matsumoto, Takahiro -- Fujiyama, Sally -- Shirode, Yuko -- Yamaoka, Ikuko -- Kitagawa, Hirochika -- Takeyama, Ken-ichi -- Shibuya, Hiroshi -- Ohtake, Fumiaki -- Kato, Shigeaki -- England -- Nature. 2009 Oct 15;461(7266):1007-12. doi: 10.1038/nature08456.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉ERATO, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchisi, Saitama 332-0012, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19829383" target="_blank"〉PubMed〈/a〉
    Keywords: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase/genetics ; Animals ; Cell Line ; CpG Islands/genetics ; DNA (Cytosine-5-)-Methyltransferase/metabolism ; DNA Glycosylases/metabolism ; DNA Methylation/*drug effects ; Down-Regulation/drug effects ; Endodeoxyribonucleases/deficiency/genetics ; Mice ; Parathyroid Hormone/*pharmacology ; Phosphorylation ; Protein Kinase C/metabolism ; Response Elements/genetics ; Transcription, Genetic/*drug effects ; Vitamin D/pharmacology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 24
    Publication Date: 2009-07-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thomas Scott, Christopher -- Owen-Smith, Jason -- McCormick, Jennifer -- England -- Nature. 2009 Jul 2;460(7251):33. doi: 10.1038/460033b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19571864" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line ; *Federal Government ; *Guidelines as Topic ; Humans ; *National Institutes of Health (U.S.) ; *Stem Cells ; United States
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 25
    Publication Date: 2009-07-28
    Description: Progressive telomere attrition or uncapping of the shelterin complex elicits a DNA damage response as a result of a cell's inability to distinguish dysfunctional telomeric ends from DNA double-strand breaks. Telomere deprotection activates both ataxia telangiectasia mutated (ATM) and telangiectasia and Rad3-related (ATR) kinase-dependent DNA damage response pathways, and promotes efficient non-homologous end-joining (NHEJ) of dysfunctional telomeres. The mammalian MRE11-RAD50-NBS1 (MRN; NBS1 is also known as NBN) complex interacts with ATM to sense chromosomal double-strand breaks and coordinate global DNA damage responses. Although the MRN complex accumulates at dysfunctional telomeres, it is not known whether mammalian MRN promotes repair at these sites. Here we address this question by using mouse alleles that either inactivate the entire MRN complex or eliminate only the nuclease activities of MRE11 (ref. 8). We show that cells lacking MRN do not activate ATM when telomeric repeat binding factor 2 (TRF2) is removed from telomeres, and ligase 4 (LIG4)-dependent chromosome end-to-end fusions are markedly reduced. Residual chromatid fusions involve only telomeres generated by leading strand synthesis. Notably, although cells deficient for MRE11 nuclease activity efficiently activate ATM and recruit 53BP1 (also known as TP53BP1) to deprotected telomeres, the 3' telomeric overhang persists to prevent NHEJ-mediated chromosomal fusions. Removal of shelterin proteins that protect the 3' overhang in the setting of MRE11 nuclease deficiency restores LIG4-dependent chromosome fusions. Our data indicate a critical role for the MRN complex in sensing dysfunctional telomeres, and show that in the absence of TRF2, MRE11 nuclease activity removes the 3' telomeric overhang to promote chromosome fusions. MRE11 can also protect newly replicated leading strand telomeres from NHEJ by promoting 5' strand resection to generate POT1a-TPP1-bound 3' overhangs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2760383/" 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/PMC2760383/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Deng, Yibin -- Guo, Xiaolan -- Ferguson, David O -- Chang, Sandy -- K01CA124461/CA/NCI NIH HHS/ -- P30 CA046592/CA/NCI NIH HHS/ -- R01 AG028888/AG/NIA NIH HHS/ -- R01 AG028888-02/AG/NIA NIH HHS/ -- R01 CA129037/CA/NCI NIH HHS/ -- R01 CA129037-02/CA/NCI NIH HHS/ -- R01 HL079118/HL/NHLBI NIH HHS/ -- England -- Nature. 2009 Aug 13;460(7257):914-8. doi: 10.1038/nature08196. Epub 2009 Jul 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Box 1010, The M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19633651" target="_blank"〉PubMed〈/a〉
    Keywords: ATP-Binding Cassette Transporters/genetics/metabolism ; Alleles ; Animals ; Ataxia Telangiectasia Mutated Proteins ; Cell Cycle Proteins/genetics/metabolism ; Cell Line ; Chromosomal Proteins, Non-Histone ; Chromosome Aberrations ; DNA Damage ; DNA Ligases/metabolism ; DNA Repair Enzymes/deficiency/genetics/*metabolism ; DNA-Binding Proteins/deficiency/genetics/*metabolism ; Fibroblasts ; Intracellular Signaling Peptides and Proteins/metabolism ; Mice ; Nuclear Proteins/deficiency/genetics/metabolism ; Protein-Serine-Threonine Kinases/metabolism ; Telomere/genetics/*metabolism ; Telomeric Repeat Binding Protein 2/deficiency/metabolism ; Tumor Suppressor Proteins/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 26
    Publication Date: 2009-01-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Knoepfler, Paul -- England -- Nature. 2009 Jan 22;457(7228):361. doi: 10.1038/457361e.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of California, Davis, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19158746" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line ; Comparative Genomic Hybridization ; Embryonic Stem Cells/*cytology/*pathology ; Humans ; Neoplasms/*pathology ; Neoplastic Stem Cells/pathology ; Pluripotent Stem Cells/*cytology/*pathology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 27
    Publication Date: 2009-08-13
    Description: Since the initial description of induced pluripotent stem (iPS) cells created by forced expression of four transcription factors in mouse fibroblasts, the technique has been used to generate embryonic stem (ES)-cell-like pluripotent cells from a variety of cell types in other species, including primates and rat. It has become a popular means to reprogram somatic genomes into an embryonic-like pluripotent state, and a preferred alternative to somatic-cell nuclear transfer and somatic-cell fusion with ES cells. However, iPS cell reprogramming remains slow and inefficient. Notably, no live animals have been produced by the most stringent tetraploid complementation assay, indicative of a failure to create fully pluripotent cells. Here we report the generation of several iPS cell lines that are capable of generating viable, fertile live-born progeny by tetraploid complementation. These iPS cells maintain a pluripotent potential that is very close to ES cells generated from in vivo or nuclear transfer embryos. We demonstrate the practicality of using iPS cells as useful tools for the characterization of cellular reprogramming and developmental potency, and confirm that iPS cells can attain true pluripotency that is similar to that of ES cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhao, Xiao-yang -- Li, Wei -- Lv, Zhuo -- Liu, Lei -- Tong, Man -- Hai, Tang -- Hao, Jie -- Guo, Chang-long -- Ma, Qing-wen -- Wang, Liu -- Zeng, Fanyi -- Zhou, Qi -- England -- Nature. 2009 Sep 3;461(7260):86-90. doi: 10.1038/nature08267.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19672241" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blastocyst/cytology/physiology ; Cell Dedifferentiation/physiology ; Cell Line ; Cell Lineage ; Cellular Reprogramming ; Embryo, Mammalian/cytology/embryology/metabolism ; Embryonic Stem Cells/cytology/physiology ; Female ; Fibroblasts/cytology ; Gene Expression Profiling ; Genetic Complementation Test ; Male ; Mice ; Mice, SCID ; Pluripotent Stem Cells/cytology/*physiology ; *Polyploidy ; Pregnancy ; *Reproductive Techniques ; Survival Rate ; Teratoma
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 28
    Publication Date: 2009-09-04
    Description: We live in a macroscopic three-dimensional (3D) world, but our best description of the structure of matter is at the atomic and molecular scale. Understanding the relationship between the two scales requires a bridge from the molecular world to the macroscopic world. Connecting these two domains with atomic precision is a central goal of the natural sciences, but it requires high spatial control of the 3D structure of matter. The simplest practical route to producing precisely designed 3D macroscopic objects is to form a crystalline arrangement by self-assembly, because such a periodic array has only conceptually simple requirements: a motif that has a robust 3D structure, dominant affinity interactions between parts of the motif when it self-associates, and predictable structures for these affinity interactions. Fulfilling these three criteria to produce a 3D periodic system is not easy, but should readily be achieved with well-structured branched DNA motifs tailed by sticky ends. Complementary sticky ends associate with each other preferentially and assume the well-known B-DNA structure when they do so; the helically repeating nature of DNA facilitates the construction of a periodic array. It is essential that the directions of propagation associated with the sticky ends do not share the same plane, but extend to form a 3D arrangement of matter. Here we report the crystal structure at 4 A resolution of a designed, self-assembled, 3D crystal based on the DNA tensegrity triangle. The data demonstrate clearly that it is possible to design and self-assemble a well-ordered macromolecular 3D crystalline lattice with precise control.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2764300/" 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/PMC2764300/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zheng, Jianping -- Birktoft, Jens J -- Chen, Yi -- Wang, Tong -- Sha, Ruojie -- Constantinou, Pamela E -- Ginell, Stephan L -- Mao, Chengde -- Seeman, Nadrian C -- 1R21EB007472/EB/NIBIB NIH HHS/ -- R21 EB007472/EB/NIBIB NIH HHS/ -- R21 EB007472-03/EB/NIBIB NIH HHS/ -- England -- Nature. 2009 Sep 3;461(7260):74-7. doi: 10.1038/nature08274.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, New York University, New York 10003, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19727196" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Crystallization ; Crystallography, X-Ray ; DNA/*chemistry/genetics ; *Drug Design ; Molecular Sequence Data ; *Nucleic Acid Conformation
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 29
    Publication Date: 2009-02-06
    Description: The influenza virus polymerase, a heterotrimer composed of three subunits, PA, PB1 and PB2, is responsible for replication and transcription of the eight separate segments of the viral RNA genome in the nuclei of infected cells. The polymerase synthesizes viral messenger RNAs using short capped primers derived from cellular transcripts by a unique 'cap-snatching' mechanism. The PB2 subunit binds the 5' cap of host pre-mRNAs, which are subsequently cleaved after 10-13 nucleotides by the viral endonuclease, hitherto thought to reside in the PB2 (ref. 5) or PB1 (ref. 2) subunits. Here we describe biochemical and structural studies showing that the amino-terminal 209 residues of the PA subunit contain the endonuclease active site. We show that this domain has intrinsic RNA and DNA endonuclease activity that is strongly activated by manganese ions, matching observations reported for the endonuclease activity of the intact trimeric polymerase. Furthermore, this activity is inhibited by 2,4-dioxo-4-phenylbutanoic acid, a known inhibitor of the influenza endonuclease. The crystal structure of the domain reveals a structural core closely resembling resolvases and type II restriction endonucleases. The active site comprises a histidine and a cluster of three acidic residues, conserved in all influenza viruses, which bind two manganese ions in a configuration similar to other two-metal-dependent endonucleases. Two active site residues have previously been shown to specifically eliminate the polymerase endonuclease activity when mutated. These results will facilitate the optimisation of endonuclease inhibitors as potential new anti-influenza drugs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dias, Alexandre -- Bouvier, Denis -- Crepin, Thibaut -- McCarthy, Andrew A -- Hart, Darren J -- Baudin, Florence -- Cusack, Stephen -- Ruigrok, Rob W H -- England -- Nature. 2009 Apr 16;458(7240):914-8. doi: 10.1038/nature07745. Epub 2009 Feb 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Unit of Virus Host-Cell Interactions, UJF-EMBL-CNRS, UMR 5233, 6 rue Jules Horowitz, BP181, 38042 Grenoble Cedex 9, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19194459" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Catalytic Domain ; Endonucleases/chemistry/*metabolism ; Enzyme Stability ; Histidine/metabolism ; Humans ; Influenza A Virus, H3N2 Subtype/*enzymology ; Influenza A Virus, H5N1 Subtype/enzymology ; Influenzavirus C/enzymology ; Manganese/metabolism/pharmacology ; Models, Molecular ; Molecular Sequence Data ; Protein Subunits/*chemistry/*metabolism ; RNA Caps/*metabolism ; RNA Replicase/*chemistry/*metabolism ; Viral Proteins/*chemistry/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 30
    Publication Date: 2009-09-11
    Description: Phytophthora infestans is the most destructive pathogen of potato and a model organism for the oomycetes, a distinct lineage of fungus-like eukaryotes that are related to organisms such as brown algae and diatoms. As the agent of the Irish potato famine in the mid-nineteenth century, P. infestans has had a tremendous effect on human history, resulting in famine and population displacement. To this day, it affects world agriculture by causing the most destructive disease of potato, the fourth largest food crop and a critical alternative to the major cereal crops for feeding the world's population. Current annual worldwide potato crop losses due to late blight are conservatively estimated at $6.7 billion. Management of this devastating pathogen is challenged by its remarkable speed of adaptation to control strategies such as genetically resistant cultivars. Here we report the sequence of the P. infestans genome, which at approximately 240 megabases (Mb) is by far the largest and most complex genome sequenced so far in the chromalveolates. Its expansion results from a proliferation of repetitive DNA accounting for approximately 74% of the genome. Comparison with two other Phytophthora genomes showed rapid turnover and extensive expansion of specific families of secreted disease effector proteins, including many genes that are induced during infection or are predicted to have activities that alter host physiology. These fast-evolving effector genes are localized to highly dynamic and expanded regions of the P. infestans genome. This probably plays a crucial part in the rapid adaptability of the pathogen to host plants and underpins its evolutionary potential.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Haas, Brian J -- Kamoun, Sophien -- Zody, Michael C -- Jiang, Rays H Y -- Handsaker, Robert E -- Cano, Liliana M -- Grabherr, Manfred -- Kodira, Chinnappa D -- Raffaele, Sylvain -- Torto-Alalibo, Trudy -- Bozkurt, Tolga O -- Ah-Fong, Audrey M V -- Alvarado, Lucia -- Anderson, Vicky L -- Armstrong, Miles R -- Avrova, Anna -- Baxter, Laura -- Beynon, Jim -- Boevink, Petra C -- Bollmann, Stephanie R -- Bos, Jorunn I B -- Bulone, Vincent -- Cai, Guohong -- Cakir, Cahid -- Carrington, James C -- Chawner, Megan -- Conti, Lucio -- Costanzo, Stefano -- Ewan, Richard -- Fahlgren, Noah -- Fischbach, Michael A -- Fugelstad, Johanna -- Gilroy, Eleanor M -- Gnerre, Sante -- Green, Pamela J -- Grenville-Briggs, Laura J -- Griffith, John -- Grunwald, Niklaus J -- Horn, Karolyn -- Horner, Neil R -- Hu, Chia-Hui -- Huitema, Edgar -- Jeong, Dong-Hoon -- Jones, Alexandra M E -- Jones, Jonathan D G -- Jones, Richard W -- Karlsson, Elinor K -- Kunjeti, Sridhara G -- Lamour, Kurt -- Liu, Zhenyu -- Ma, Lijun -- Maclean, Daniel -- Chibucos, Marcus C -- McDonald, Hayes -- McWalters, Jessica -- Meijer, Harold J G -- Morgan, William -- Morris, Paul F -- Munro, Carol A -- O'Neill, Keith -- Ospina-Giraldo, Manuel -- Pinzon, Andres -- Pritchard, Leighton -- Ramsahoye, Bernard -- Ren, Qinghu -- Restrepo, Silvia -- Roy, Sourav -- Sadanandom, Ari -- Savidor, Alon -- Schornack, Sebastian -- Schwartz, David C -- Schumann, Ulrike D -- Schwessinger, Ben -- Seyer, Lauren -- Sharpe, Ted -- Silvar, Cristina -- Song, Jing -- Studholme, David J -- Sykes, Sean -- Thines, Marco -- van de Vondervoort, Peter J I -- Phuntumart, Vipaporn -- Wawra, Stephan -- Weide, Rob -- Win, Joe -- Young, Carolyn -- Zhou, Shiguo -- Fry, William -- Meyers, Blake C -- van West, Pieter -- Ristaino, Jean -- Govers, Francine -- Birch, Paul R J -- Whisson, Stephen C -- Judelson, Howard S -- Nusbaum, Chad -- BB/E007120/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/G015244/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- G0400284/Medical Research Council/United Kingdom -- England -- Nature. 2009 Sep 17;461(7262):393-8. doi: 10.1038/nature08358. Epub 2009 Sep 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02141, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19741609" target="_blank"〉PubMed〈/a〉
    Keywords: Algal Proteins/genetics ; DNA Transposable Elements/genetics ; DNA, Intergenic/genetics ; Evolution, Molecular ; Genome/*genetics ; Host-Pathogen Interactions/genetics ; Humans ; Ireland ; Molecular Sequence Data ; Necrosis ; Phenotype ; Phytophthora infestans/*genetics/pathogenicity ; Plant Diseases/immunology/*microbiology ; Solanum tuberosum/immunology/*microbiology ; Starvation
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 31
    Publication Date: 2009-05-22
    Description: Cohesin-mediated sister chromatid cohesion is essential for chromosome segregation and post-replicative DNA repair. In addition, evidence from model organisms and from human genetics suggests that cohesin is involved in the control of gene expression. This non-canonical role has recently been rationalized by the findings that mammalian cohesin complexes are recruited to a subset of DNase I hypersensitive sites and to conserved noncoding sequences by the DNA-binding protein CTCF. CTCF functions at insulators (which control interactions between enhancers and promoters) and at boundary elements (which demarcate regions of distinct chromatin structure), and cohesin contributes to its enhancer-blocking activity. The underlying mechanisms remain unknown, and the full spectrum of cohesin functions remains to be determined. Here we show that cohesin forms the topological and mechanistic basis for cell-type-specific long-range chromosomal interactions in cis at the developmentally regulated cytokine locus IFNG. Hence, the ability of cohesin to constrain chromosome topology is used not only for the purpose of sister chromatid cohesion, but also to dynamically define the spatial conformation of specific loci. This new aspect of cohesin function is probably important for normal development and disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2869028/" 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/PMC2869028/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hadjur, Suzana -- Williams, Luke M -- Ryan, Natalie K -- Cobb, Bradley S -- Sexton, Tom -- Fraser, Peter -- Fisher, Amanda G -- Merkenschlager, Matthias -- G0900491/Medical Research Council/United Kingdom -- G117/530/Medical Research Council/United Kingdom -- MC_U120027516/Medical Research Council/United Kingdom -- U.1200(U.1200)/Medical Research Council/United Kingdom -- Medical Research Council/United Kingdom -- England -- Nature. 2009 Jul 16;460(7253):410-3. doi: 10.1038/nature08079. Epub 2009 May 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Lymphocyte Development Group, MRC Clinical Sciences Centre, Imperial College London, Du Cane Road, London W12 0NN, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19458616" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; CD4-Positive T-Lymphocytes/metabolism ; Cell Cycle Proteins/*metabolism ; Cell Line ; Chromosomal Proteins, Non-Histone/*metabolism ; Chromosomes/*genetics/*metabolism ; *Gene Expression Regulation, Developmental ; Histones/metabolism ; Humans ; Interferon-gamma/*genetics ; Mice ; Nuclear Proteins/genetics/metabolism ; Organ Specificity ; Phosphoproteins/genetics/metabolism ; Repressor Proteins/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 32
    Publication Date: 2009-11-13
    Description: The signalling pathways controlling both the evolution and development of language in the human brain remain unknown. So far, the transcription factor FOXP2 (forkhead box P2) is the only gene implicated in Mendelian forms of human speech and language dysfunction. It has been proposed that the amino acid composition in the human variant of FOXP2 has undergone accelerated evolution, and this two-amino-acid change occurred around the time of language emergence in humans. However, this remains controversial, and whether the acquisition of these amino acids in human FOXP2 has any functional consequence in human neurons remains untested. Here we demonstrate that these two human-specific amino acids alter FOXP2 function by conferring differential transcriptional regulation in vitro. We extend these observations in vivo to human and chimpanzee brain, and use network analysis to identify novel relationships among the differentially expressed genes. These data provide experimental support for the functional relevance of changes in FOXP2 that occur on the human lineage, highlighting specific pathways with direct consequences for human brain development and disease in the central nervous system (CNS). Because FOXP2 has an important role in speech and language in humans, the identified targets may have a critical function in the development and evolution of language circuitry in humans.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2778075/" 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/PMC2778075/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Konopka, Genevieve -- Bomar, Jamee M -- Winden, Kellen -- Coppola, Giovanni -- Jonsson, Zophonias O -- Gao, Fuying -- Peng, Sophia -- Preuss, Todd M -- Wohlschlegel, James A -- Geschwind, Daniel H -- N01-HD-4-3368/HD/NICHD NIH HHS/ -- N01-HD-4-3383/HD/NICHD NIH HHS/ -- R21 MH075028/MH/NIMH NIH HHS/ -- R21 MH075028-02/MH/NIMH NIH HHS/ -- R21MH075028/MH/NIMH NIH HHS/ -- R37 MH060233/MH/NIMH NIH HHS/ -- R37 MH060233-06A1/MH/NIMH NIH HHS/ -- R37MH60233-06A1/MH/NIMH NIH HHS/ -- RR00165/RR/NCRR NIH HHS/ -- T32HD007032/HD/NICHD NIH HHS/ -- T32MH073526/MH/NIMH NIH HHS/ -- England -- Nature. 2009 Nov 12;462(7270):213-7. doi: 10.1038/nature08549.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Neurogenetics, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA. gena@alum.mit.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19907493" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/cytology/*embryology/*metabolism ; Cell Line ; Evolution, Molecular ; Forkhead Transcription Factors/chemistry/genetics/*metabolism ; *Gene Expression Regulation, Developmental ; Humans ; Language ; Pan troglodytes/embryology/genetics/metabolism ; Promoter Regions, Genetic/genetics ; Species Specificity ; Speech/physiology ; *Transcription, Genetic ; Transcriptional Activation
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 33
    Publication Date: 2009-10-09
    Description: PIWI-interacting RNAs (piRNAs) silence retrotransposons in Drosophila germ lines by associating with the PIWI proteins Argonaute 3 (AGO3), Aubergine (Aub) and Piwi. piRNAs in Drosophila are produced from intergenic repetitive genes and piRNA clusters by two systems: the primary processing pathway and the amplification loop. The amplification loop occurs in a Dicer-independent, PIWI-Slicer-dependent manner. However, primary piRNA processing remains elusive. Here we analysed piRNA processing in a Drosophila ovarian somatic cell line where Piwi, but not Aub or AGO3, is expressed; thus, only the primary piRNAs exist. In addition to flamenco, a Piwi-specific piRNA cluster, traffic jam (tj), a large Maf gene, was determined as a new piRNA cluster. piRNAs arising from tj correspond to the untranslated regions of tj messenger RNA and are sense-oriented. piRNA loading on to Piwi may occur in the cytoplasm. zucchini, a gene encoding a putative cytoplasmic nuclease, is required for tj-derived piRNA production. In tj and piwi mutant ovaries, somatic cells fail to intermingle with germ cells and Fasciclin III is overexpressed. Loss of tj abolishes Piwi expression in gonadal somatic cells. Thus, in gonadal somatic cells, tj gives rise simultaneously to two different molecules: the TJ protein, which activates Piwi expression, and piRNAs, which define the Piwi targets for silencing.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Saito, Kuniaki -- Inagaki, Sachi -- Mituyama, Toutai -- Kawamura, Yoshinori -- Ono, Yukiteru -- Sakota, Eri -- Kotani, Hazuki -- Asai, Kiyoshi -- Siomi, Haruhiko -- Siomi, Mikiko C -- England -- Nature. 2009 Oct 29;461(7268):1296-9. doi: 10.1038/nature08501. Epub 2009 Oct 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Keio University School of Medicine, Tokyo 160-8582, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19812547" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Argonaute Proteins ; Cell Adhesion Molecules, Neuronal/metabolism ; Cell Line ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster/genetics/*metabolism ; Endoribonucleases/metabolism ; Female ; Genes, Insect/genetics ; Genetic Loci/genetics ; Maf Transcription Factors, Large/genetics/*metabolism ; Male ; Ovary/cytology/metabolism ; Phenotype ; Proto-Oncogene Proteins/genetics/*metabolism ; RNA/biosynthesis/genetics/*metabolism ; RNA Interference ; RNA Processing, Post-Transcriptional ; RNA-Induced Silencing Complex/genetics/*metabolism ; Testis/cytology/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 34
    Publication Date: 2009-11-27
    Description: Homocitrate is a component of the iron-molybdenum cofactor in nitrogenase, where nitrogen fixation occurs. NifV, which encodes homocitrate synthase (HCS), has been identified from various diazotrophs but is not present in most rhizobial species that perform efficient nitrogen fixation only in symbiotic association with legumes. Here we show that the FEN1 gene of a model legume, Lotus japonicus, overcomes the lack of NifV in rhizobia for symbiotic nitrogen fixation. A Fix(-) (non-fixing) plant mutant, fen1, forms morphologically normal but ineffective nodules. The causal gene, FEN1, was shown to encode HCS by its ability to complement a HCS-defective mutant of Saccharomyces cerevisiae. Homocitrate was present abundantly in wild-type nodules but was absent from ineffective fen1 nodules. Inoculation with Mesorhizobium loti carrying FEN1 or Azotobacter vinelandii NifV rescued the defect in nitrogen-fixing activity of the fen1 nodules. Exogenous supply of homocitrate also recovered the nitrogen-fixing activity of the fen1 nodules through de novo nitrogenase synthesis in the rhizobial bacteroids. These results indicate that homocitrate derived from the host plant cells is essential for the efficient and continuing synthesis of the nitrogenase system in endosymbionts, and thus provide a molecular basis for the complementary and indispensable partnership between legumes and rhizobia in symbiotic nitrogen fixation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hakoyama, Tsuneo -- Niimi, Kaori -- Watanabe, Hirokazu -- Tabata, Ryohei -- Matsubara, Junichi -- Sato, Shusei -- Nakamura, Yasukazu -- Tabata, Satoshi -- Jichun, Li -- Matsumoto, Tsuyoshi -- Tatsumi, Kazuyuki -- Nomura, Mika -- Tajima, Shigeyuki -- Ishizaka, Masumi -- Yano, Koji -- Imaizumi-Anraku, Haruko -- Kawaguchi, Masayoshi -- Kouchi, Hiroshi -- Suganuma, Norio -- England -- Nature. 2009 Nov 26;462(7272):514-7. doi: 10.1038/nature08594.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Institute of Agrobiological Sciences, Tsukuba, Ibaraki 305-8602, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19940927" target="_blank"〉PubMed〈/a〉
    Keywords: Azotobacter vinelandii ; Gene Expression Regulation, Plant ; *Genes, Bacterial ; Genes, Plant/genetics ; Genetic Complementation Test ; Genome, Plant/*genetics ; Ketoglutaric Acids/metabolism ; Lotus/enzymology/*genetics/*metabolism ; Molecular Sequence Data ; Mutation/genetics ; Nitrogen Fixation/*genetics ; Oxo-Acid-Lyases/deficiency/genetics/metabolism ; Plant Proteins/genetics/metabolism ; Rhizobium/genetics/*metabolism ; Saccharomyces cerevisiae/enzymology/genetics ; Symbiosis/*genetics ; Tricarboxylic Acids/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 35
    Publication Date: 2009-12-18
    Description: Mutations in BRCA1 are associated with a high risk of breast and ovarian cancer. BRCA1 participates in the DNA damage response and acts as a ubiquitin ligase. However, its regulation remains poorly understood. Here we report that BRCA1 is modified by small ubiquitin-like modifier (SUMO) in response to genotoxic stress, and co-localizes at sites of DNA damage with SUMO1, SUMO2/3 and the SUMO-conjugating enzyme Ubc9. PIAS SUMO E3 ligases co-localize with and modulate SUMO modification of BRCA1, and are required for BRCA1 ubiquitin ligase activity in cells. In vitro SUMO modification of the BRCA1/BARD1 heterodimer greatly increases its ligase activity, identifying it as a SUMO-regulated ubiquitin ligase (SRUbL). Further, PIAS SUMO ligases are required for complete accumulation of double-stranded DNA (dsDNA) damage-repair proteins subsequent to RNF8 accrual, and for proficient double-strand break repair. These data demonstrate that the SUMOylation pathway plays a significant role in mammalian DNA damage response.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Morris, Joanna R -- Boutell, Chris -- Keppler, Melanie -- Densham, Ruth -- Weekes, Daniel -- Alamshah, Amin -- Butler, Laura -- Galanty, Yaron -- Pangon, Laurent -- Kiuchi, Tai -- Ng, Tony -- Solomon, Ellen -- 10331/Cancer Research UK/United Kingdom -- 6900577/Medical Research Council/United Kingdom -- C8820/A9494/Cancer Research UK/United Kingdom -- G0100152 #56891/Medical Research Council/United Kingdom -- G9600577/Medical Research Council/United Kingdom -- MC_UP_A550_1030/Medical Research Council/United Kingdom -- England -- Nature. 2009 Dec 17;462(7275):886-90. doi: 10.1038/nature08593.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medical and Molecular Genetics, King's College London, Guy's Medical School Campus, London SE1 9RT, UK. jo.morris@genetics.kcl.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20016594" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; BRCA1 Protein/*metabolism ; COS Cells ; Cell Line ; Cercopithecus aethiops ; DNA Breaks, Double-Stranded ; *DNA Damage ; DNA Repair ; HeLa Cells ; Histones/metabolism ; Humans ; Protein Inhibitors of Activated STAT/metabolism ; Small Ubiquitin-Related Modifier Proteins/*metabolism ; Ubiquitin-Conjugating Enzymes/metabolism ; Ubiquitin-Protein Ligases/metabolism ; Ubiquitination
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 36
    Publication Date: 2009-02-11
    Description: Multicellular organisms evolved sophisticated defence systems to confer protection against pathogens. An important characteristic of these immune systems is their ability to act both locally at the site of infection and at distal uninfected locations. In insects, such as Drosophila melanogaster, RNA interference (RNAi) mediates antiviral immunity. However, the antiviral RNAi defence in flies seems to be a local, cell-autonomous process, as flies are thought to be unable to generate a systemic RNAi response. Here we show that a recently defined double-stranded RNA (dsRNA) uptake pathway is essential for effective antiviral RNAi immunity in adult flies. Mutant flies defective in this dsRNA uptake pathway were hypersensitive to infection with Drosophila C virus and Sindbis virus. Mortality in dsRNA-uptake-defective flies was accompanied by 100-to 10(5)-fold increases in viral titres and higher levels of viral RNA. Furthermore, inoculating naked dsRNA into flies elicited a sequence-specific antiviral immune response that required an intact dsRNA uptake pathway. These findings suggest that spread of dsRNA to uninfected sites is essential for effective antiviral immunity. Notably, infection with green fluorescent protein (GFP)-tagged Sindbis virus suppressed expression of host-encoded GFP at a distal site. Thus, similar to protein-based immunity in vertebrates, the antiviral RNAi response in flies also relies on the systemic spread of a virus-specific immunity signal.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3978076/" 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/PMC3978076/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Saleh, Maria-Carla -- Tassetto, Michel -- van Rij, Ronald P -- Goic, Bertsy -- Gausson, Valerie -- Berry, Bassam -- Jacquier, Caroline -- Antoniewski, Christophe -- Andino, Raul -- AI064738/AI/NIAID NIH HHS/ -- AI40085/AI/NIAID NIH HHS/ -- R01 AI040085/AI/NIAID NIH HHS/ -- R01 AI064738/AI/NIAID NIH HHS/ -- England -- Nature. 2009 Mar 19;458(7236):346-50. doi: 10.1038/nature07712. Epub 2009 Feb 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, University of California, San Francisco 94122-2280, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19204732" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Drosophila melanogaster/genetics/*immunology/microbiology/*virology ; Micrococcus luteus/immunology ; Pectobacterium carotovorum/immunology ; RNA Interference/*immunology ; RNA Viruses/*immunology/physiology ; RNA, Double-Stranded/genetics/immunology/metabolism ; Sindbis Virus/genetics/growth & development/immunology ; Substrate Specificity
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 37
    Publication Date: 2009-07-22
    Description: Acquired uniparental disomy (aUPD) is a common feature of cancer genomes, leading to loss of heterozygosity. aUPD is associated not only with loss-of-function mutations of tumour suppressor genes, but also with gain-of-function mutations of proto-oncogenes. Here we show unique gain-of-function mutations of the C-CBL (also known as CBL) tumour suppressor that are tightly associated with aUPD of the 11q arm in myeloid neoplasms showing myeloproliferative features. The C-CBL proto-oncogene, a cellular homologue of v-Cbl, encodes an E3 ubiquitin ligase and negatively regulates signal transduction of tyrosine kinases. Homozygous C-CBL mutations were found in most 11q-aUPD-positive myeloid malignancies. Although the C-CBL mutations were oncogenic in NIH3T3 cells, c-Cbl was shown to functionally and genetically act as a tumour suppressor. C-CBL mutants did not have E3 ubiquitin ligase activity, but inhibited that of wild-type C-CBL and CBL-B (also known as CBLB), leading to prolonged activation of tyrosine kinases after cytokine stimulation. c-Cbl(-/-) haematopoietic stem/progenitor cells (HSPCs) showed enhanced sensitivity to a variety of cytokines compared to c-Cbl(+/+) HSPCs, and transduction of C-CBL mutants into c-Cbl(-/-) HSPCs further augmented their sensitivities to a broader spectrum of cytokines, including stem-cell factor (SCF, also known as KITLG), thrombopoietin (TPO, also known as THPO), IL3 and FLT3 ligand (FLT3LG), indicating the presence of a gain-of-function that could not be attributed to a simple loss-of-function. The gain-of-function effects of C-CBL mutants on cytokine sensitivity of HSPCs largely disappeared in a c-Cbl(+/+) background or by co-transduction of wild-type C-CBL, which suggests the pathogenic importance of loss of wild-type C-CBL alleles found in most cases of C-CBL-mutated myeloid neoplasms. Our findings provide a new insight into a role of gain-of-function mutations of a tumour suppressor associated with aUPD in the pathogenesis of some myeloid cancer subsets.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sanada, Masashi -- Suzuki, Takahiro -- Shih, Lee-Yung -- Otsu, Makoto -- Kato, Motohiro -- Yamazaki, Satoshi -- Tamura, Azusa -- Honda, Hiroaki -- Sakata-Yanagimoto, Mamiko -- Kumano, Keiki -- Oda, Hideaki -- Yamagata, Tetsuya -- Takita, Junko -- Gotoh, Noriko -- Nakazaki, Kumi -- Kawamata, Norihiko -- Onodera, Masafumi -- Nobuyoshi, Masaharu -- Hayashi, Yasuhide -- Harada, Hiroshi -- Kurokawa, Mineo -- Chiba, Shigeru -- Mori, Hiraku -- Ozawa, Keiya -- Omine, Mitsuhiro -- Hirai, Hisamaru -- Nakauchi, Hiromitsu -- Koeffler, H Phillip -- Ogawa, Seishi -- 2R01CA026038-30/CA/NCI NIH HHS/ -- England -- Nature. 2009 Aug 13;460(7257):904-8. doi: 10.1038/nature08240. Epub 2009 Jul 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Genomics Project, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19620960" target="_blank"〉PubMed〈/a〉
    Keywords: Allelic Imbalance ; Amino Acid Sequence ; Animals ; Base Sequence ; Chromosomes, Human, Pair 11/genetics ; Female ; *Genes, Tumor Suppressor ; Humans ; Leukemia, Myeloid/*genetics/metabolism/pathology ; Male ; Mice ; Mice, Knockout ; Mice, Nude ; Models, Molecular ; Molecular Sequence Data ; Mutant Proteins/chemistry/genetics/*metabolism ; Mutation ; NIH 3T3 Cells ; Neoplasm Transplantation ; Oncogenes/genetics ; Phosphorylation ; Protein Conformation ; Proto-Oncogene Proteins c-cbl/antagonists & ; inhibitors/chemistry/deficiency/*genetics/*metabolism ; Ubiquitination ; Uniparental Disomy/genetics ; ras Proteins/genetics/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 38
    Publication Date: 2009-10-13
    Description: To initiate gene transcription, RNA polymerase II (Pol II) requires the transcription factor IIB (B). Here we present the crystal structure of the complete Pol II-B complex at 4.3 A resolution, and complementary functional data. The results indicate the mechanism of transcription initiation, including the transition to RNA elongation. Promoter DNA is positioned over the Pol II active centre cleft with the 'B-core' domain that binds the wall at the end of the cleft. DNA is then opened with the help of the 'B-linker' that binds the Pol II rudder and clamp coiled-coil at the edge of the cleft. The DNA template strand slips into the cleft and is scanned for the transcription start site with the help of the 'B-reader' that approaches the active site. Synthesis of the RNA chain and rewinding of upstream DNA displace the B-reader and B-linker, respectively, to trigger B release and elongation complex formation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kostrewa, Dirk -- Zeller, Mirijam E -- Armache, Karim-Jean -- Seizl, Martin -- Leike, Kristin -- Thomm, Michael -- Cramer, Patrick -- England -- Nature. 2009 Nov 19;462(7271):323-30. doi: 10.1038/nature08548.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Gene Center Munich and Center for Integrated Protein Science Munich (CIPSM), Department of Chemistry and Biochemistry, Ludwig-Maximilians-Universitat Munchen, Feodor-Lynen-Strasse 25, 81377 Munich, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19820686" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacterial Proteins/chemistry ; DNA Polymerase II/*chemistry/*metabolism ; Humans ; *Models, Molecular ; Molecular Sequence Data ; Protein Structure, Quaternary ; Saccharomyces cerevisiae/*genetics/*metabolism ; Sequence Alignment ; TATA-Box Binding Protein/chemistry/metabolism ; Transcription Factor TFIIB/*chemistry/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 39
    Publication Date: 2009-06-19
    Description: Pluripotency of embryonic stem (ES) cells is controlled by defined transcription factors. During differentiation, mouse ES cells undergo global epigenetic reprogramming, as exemplified by X-chromosome inactivation (XCI) in which one female X chromosome is silenced to achieve gene dosage parity between the sexes. Somatic XCI is regulated by homologous X-chromosome pairing and counting, and by the random choice of future active and inactive X chromosomes. XCI and cell differentiation are tightly coupled, as blocking one process compromises the other and dedifferentiation of somatic cells to induced pluripotent stem cells is accompanied by X chromosome reactivation. Recent evidence suggests coupling of Xist expression to pluripotency factors occurs, but how the two are interconnected remains unknown. Here we show that Oct4 (also known as Pou5f1) lies at the top of the XCI hierarchy, and regulates XCI by triggering X-chromosome pairing and counting. Oct4 directly binds Tsix and Xite, two regulatory noncoding RNA genes of the X-inactivation centre, and also complexes with XCI trans-factors, Ctcf and Yy1 (ref. 17), through protein-protein interactions. Depletion of Oct4 blocks homologous X-chromosome pairing and results in the inactivation of both X chromosomes in female cells. Thus, we have identified the first trans-factor that regulates counting, and ascribed new functions to Oct4 during X-chromosome reprogramming.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3057664/" 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/PMC3057664/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Donohoe, Mary E -- Silva, Susana S -- Pinter, Stefan F -- Xu, Na -- Lee, Jeannie T -- GM58839/GM/NIGMS NIH HHS/ -- R01 GM058839/GM/NIGMS NIH HHS/ -- R01 GM058839-10/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Jul 2;460(7251):128-32. doi: 10.1038/nature08098. Epub 2009 Jun 17.〈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/19536159" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; *Chromosome Pairing ; Female ; Humans ; Male ; Mice ; Octamer Transcription Factor-3/deficiency/genetics/*metabolism ; Protein Binding ; RNA, Long Noncoding ; RNA, Untranslated/genetics ; Repressor Proteins/*metabolism ; SOXB1 Transcription Factors ; Transcriptional Activation ; X Chromosome/*genetics/*metabolism ; X Chromosome Inactivation/*genetics ; YY1 Transcription Factor/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 40
    Publication Date: 2009-04-03
    Description: In the course of synaptic transmission in the brain and periphery, acetylcholine receptors (AChRs) rapidly transduce a chemical signal into an electrical impulse. The speed of transduction is facilitated by rapid ACh association and dissociation, suggesting a binding site relatively non-selective for small cations. Selective transduction has been thought to originate from the ability of ACh, over that of other organic cations, to trigger the subsequent channel-opening step. However, transitions to and from the open state were shown to be similar for agonists with widely different efficacies. By studying mutant AChRs, we show here that the ultimate closed-to-open transition is agonist-independent and preceded by two primed closed states; the first primed state elicits brief openings, whereas the second elicits long-lived openings. Long-lived openings and the associated primed state are detected in the absence and presence of an agonist, and exhibit the same kinetic signatures under both conditions. By covalently locking the agonist-binding sites in the bound conformation, we find that each site initiates a priming step. Thus, a change in binding-site conformation primes the AChR for channel opening in a process that enables selective activation by ACh while maximizing the speed and efficiency of the biological response.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2712348/" 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/PMC2712348/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mukhtasimova, Nuriya -- Lee, Won Yong -- Wang, Hai-Long -- Sine, Steven M -- NS031744/NS/NINDS NIH HHS/ -- R01 NS031744/NS/NINDS NIH HHS/ -- R01 NS031744-18/NS/NINDS NIH HHS/ -- England -- Nature. 2009 May 21;459(7245):451-4. doi: 10.1038/nature07923. Epub 2009 Apr 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Receptor Biology Laboratory, Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19339970" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Disulfides/metabolism ; Electric Conductivity ; Humans ; Kinetics ; Models, Molecular ; *Movement ; Nicotinic Agonists/pharmacology ; Patch-Clamp Techniques ; Protein Structure, Tertiary ; Receptors, Nicotinic/*chemistry/genetics/*metabolism ; Synaptic Transmission/physiology ; Torpedo
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 41
    Publication Date: 2009-04-24
    Description: Ca(2+) mobilization from intracellular stores represents an important cell signalling process that is regulated, in mammalian cells, by inositol-1,4,5-trisphosphate (InsP(3)), cyclic ADP ribose and nicotinic acid adenine dinucleotide phosphate (NAADP). InsP(3) and cyclic ADP ribose cause the release of Ca(2+) from sarcoplasmic/endoplasmic reticulum stores by the activation of InsP(3) and ryanodine receptors (InsP(3)Rs and RyRs). In contrast, the nature of the intracellular stores targeted by NAADP and the molecular identity of the NAADP receptors remain controversial, although evidence indicates that NAADP mobilizes Ca(2+) from lysosome-related acidic compartments. Here we show that two-pore channels (TPCs) comprise a family of NAADP receptors, with human TPC1 (also known as TPCN1) and chicken TPC3 (TPCN3) being expressed on endosomal membranes, and human TPC2 (TPCN2) on lysosomal membranes when expressed in HEK293 cells. Membranes enriched with TPC2 show high affinity NAADP binding, and TPC2 underpins NAADP-induced Ca(2+) release from lysosome-related stores that is subsequently amplified by Ca(2+)-induced Ca(2+) release by InsP(3)Rs. Responses to NAADP were abolished by disrupting the lysosomal proton gradient and by ablating TPC2 expression, but were only attenuated by depleting endoplasmic reticulum Ca(2+) stores or by blocking InsP(3)Rs. Thus, TPCs form NAADP receptors that release Ca(2+) from acidic organelles, which can trigger further Ca(2+) signals via sarcoplasmic/endoplasmic reticulum. TPCs therefore provide new insights into the regulation and organization of Ca(2+) signals in animal cells, and will advance our understanding of the physiological role of NAADP.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2761823/" 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/PMC2761823/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Calcraft, Peter J -- Ruas, Margarida -- Pan, Zui -- Cheng, Xiaotong -- Arredouani, Abdelilah -- Hao, Xuemei -- Tang, Jisen -- Rietdorf, Katja -- Teboul, Lydia -- Chuang, Kai-Ting -- Lin, Peihui -- Xiao, Rui -- Wang, Chunbo -- Zhu, Yingmin -- Lin, Yakang -- Wyatt, Christopher N -- Parrington, John -- Ma, Jianjie -- Evans, A Mark -- Galione, Antony -- Zhu, Michael X -- 070772/Wellcome Trust/United Kingdom -- FS/05/050/British Heart Foundation/United Kingdom -- P30 NS045758/NS/NINDS NIH HHS/ -- P30 NS045758-05/NS/NINDS NIH HHS/ -- P30 NS045758-059003/NS/NINDS NIH HHS/ -- P30-NS045758/NS/NINDS NIH HHS/ -- R01 DK081654/DK/NIDDK NIH HHS/ -- R01 DK081654-01A1/DK/NIDDK NIH HHS/ -- R01 NS042183/NS/NINDS NIH HHS/ -- R01 NS042183-04/NS/NINDS NIH HHS/ -- R21 NS056942/NS/NINDS NIH HHS/ -- R21 NS056942-01/NS/NINDS NIH HHS/ -- England -- Nature. 2009 May 28;459(7246):596-600. doi: 10.1038/nature08030. Epub 2009 Apr 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Integrative Physiology, College of Medicine and Veterinary Medicine, University of Edinburgh, Hugh Robson Building, Edinburgh EH8 9XD, Scotland, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19387438" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/*metabolism ; Calcium Channels/genetics/*metabolism ; *Calcium Signaling/drug effects ; Cell Line ; Chickens ; Humans ; Hydrogen-Ion Concentration ; Insulin-Secreting Cells/drug effects/metabolism ; Mice ; Mice, Knockout ; Molecular Sequence Data ; NADP/*analogs & derivatives/metabolism/pharmacology ; Organelles/drug effects/*metabolism ; Protein Binding
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 42
    Publication Date: 2009-11-27
    Description: Most animals display internal and/or external left-right asymmetry. Several mechanisms for left-right asymmetry determination have been proposed for vertebrates and invertebrates but they are still not well characterized, particularly at the early developmental stage. The gastropods Lymnaea stagnalis and the closely related Lymnaea peregra have both the sinistral (recessive) and the dextral (dominant) snails within a species and the chirality is hereditary, determined by a single locus that functions maternally. Intriguingly, the handedness-determining gene(s) and the mechanisms are not yet identified. Here we show that in L. stagnalis, the chiral blastomere arrangement at the eight-cell stage (but not the two- or four-cell stage) determines the left-right asymmetry throughout the developmental programme, and acts upstream of the Nodal signalling pathway. Thus, we could demonstrate that mechanical micromanipulation of the third cleavage chirality (from the four- to the eight-cell stage) leads to reversal of embryonic handedness. These manipulated embryos grew to 'dextralized' sinistral and 'sinistralized' dextral snails-that is, normal healthy fertile organisms with all the usual left-right asymmetries reversed to that encoded by the mothers' genetic information. Moreover, manipulation reversed the embryonic nodal expression patterns. Using backcrossed F(7) congenic animals, we could demonstrate a strong genetic linkage between the handedness-determining gene(s) and the chiral cytoskeletal dynamics at the third cleavage that promotes the dominant-type blastomere arrangement. These results establish the crucial importance of the maternally determined blastomere arrangement at the eight-cell stage in dictating zygotic signalling pathways in the organismal chiromorphogenesis. Similar chiral blastomere configuration mechanisms may also operate upstream of the Nodal pathway in left-right patterning of deuterostomes/vertebrates.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kuroda, Reiko -- Endo, Bunshiro -- Abe, Masanori -- Shimizu, Miho -- England -- Nature. 2009 Dec 10;462(7274):790-4. doi: 10.1038/nature08597. Epub .〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Komaba, Meguro-ku, Tokyo 153-8902, Japan. ckuroda@mail.ecc.u-tokyo.ac.jp〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19940849" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Congenic ; Blastomeres/*cytology/physiology ; Body Patterning/genetics/*physiology ; Embryo, Nonmammalian/cytology/*embryology/metabolism ; Lymnaea/anatomy & histology/cytology/*embryology/genetics ; Molecular Sequence Data ; Nodal Protein/genetics/metabolism ; Situs Inversus/embryology/pathology ; Transcription Factors/genetics/metabolism ; Zygote/*cytology/*growth & development/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 43
    Publication Date: 2009-03-06
    Description: AMP-activated protein kinase (AMPK) is a metabolic fuel gauge conserved along the evolutionary scale in eukaryotes that senses changes in the intracellular AMP/ATP ratio. Recent evidence indicated an important role for AMPK in the therapeutic benefits of metformin, thiazolidinediones and exercise, which form the cornerstones of the clinical management of type 2 diabetes and associated metabolic disorders. In general, activation of AMPK acts to maintain cellular energy stores, switching on catabolic pathways that produce ATP, mostly by enhancing oxidative metabolism and mitochondrial biogenesis, while switching off anabolic pathways that consume ATP. This regulation can take place acutely, through the regulation of fast post-translational events, but also by transcriptionally reprogramming the cell to meet energetic needs. Here we demonstrate that AMPK controls the expression of genes involved in energy metabolism in mouse skeletal muscle by acting in coordination with another metabolic sensor, the NAD+-dependent type III deacetylase SIRT1. AMPK enhances SIRT1 activity by increasing cellular NAD+ levels, resulting in the deacetylation and modulation of the activity of downstream SIRT1 targets that include the peroxisome proliferator-activated receptor-gamma coactivator 1alpha and the forkhead box O1 (FOXO1) and O3 (FOXO3a) transcription factors. The AMPK-induced SIRT1-mediated deacetylation of these targets explains many of the convergent biological effects of AMPK and SIRT1 on energy metabolism.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3616311/" 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/PMC3616311/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Canto, Carles -- Gerhart-Hines, Zachary -- Feige, Jerome N -- Lagouge, Marie -- Noriega, Lilia -- Milne, Jill C -- Elliott, Peter J -- Puigserver, Pere -- Auwerx, Johan -- 231138/European Research Council/International -- DK069966/DK/NIDDK NIH HHS/ -- DK59820/DK/NIDDK NIH HHS/ -- England -- Nature. 2009 Apr 23;458(7241):1056-60. doi: 10.1038/nature07813.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS/INSERM/ULP, 67404 Illkirch, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19262508" target="_blank"〉PubMed〈/a〉
    Keywords: AMP-Activated Protein Kinases/*metabolism ; Acetylation ; Aminoimidazole Carboxamide/analogs & derivatives ; Animals ; Cell Line ; *Energy Metabolism/genetics ; Enzyme Activation ; Forkhead Transcription Factors/genetics ; Gene Expression Regulation ; Genes, Mitochondrial/genetics ; Male ; Mice ; Muscle, Skeletal/cytology/enzymology/metabolism ; Mutation ; NAD/*metabolism ; Oxygen Consumption ; Phosphorylation ; Ribonucleotides ; Sirtuin 1 ; Sirtuins/*metabolism ; Trans-Activators/genetics/metabolism ; Transcription Factors ; Transcription, Genetic
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 44
    Publication Date: 2009-10-23
    Description: Maturation of precursor transfer RNA (pre-tRNA) includes excision of the 5' leader and 3' trailer sequences, removal of introns and addition of the CCA terminus. Nucleotide modifications are incorporated at different stages of tRNA processing, after the RNA molecule adopts the proper conformation. In bacteria, tRNA(Ile2) lysidine synthetase (TilS) modifies cytidine into lysidine (L; 2-lysyl-cytidine) at the first anticodon of tRNA(Ile2) (refs 4-9). This modification switches tRNA(Ile2) from a methionine-specific to an isoleucine-specific tRNA. However, the aminoacylation of tRNA(Ile2) by methionyl-tRNA synthetase (MetRS), before the modification by TilS, might lead to the misincorporation of methionine in response to isoleucine codons. The mechanism used by bacteria to avoid this pitfall is unknown. Here we show that the TilS enzyme specifically recognizes and modifies tRNA(Ile2) in its precursor form, thereby avoiding translation errors. We identified the lysidine modification in pre-tRNA(Ile2) isolated from RNase-E-deficient Escherichia coli and did not detect mature tRNA(Ile2) lacking this modification. Our kinetic analyses revealed that TilS can modify both types of RNA molecule with comparable efficiencies. X-ray crystallography and mutational analyses revealed that TilS specifically recognizes the entire L-shape structure in pre-tRNA(Ile2) through extensive interactions coupled with sequential domain movements. Our results demonstrate how TilS prevents the recognition of tRNA(Ile2) by MetRS and achieves high specificity for its substrate. These two key points form the basis for maintaining the fidelity of isoleucine codon translation in bacteria. Our findings also provide a rationale for the necessity of incorporating specific modifications at the precursor level during tRNA biogenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nakanishi, Kotaro -- Bonnefond, Luc -- Kimura, Satoshi -- Suzuki, Tsutomu -- Ishitani, Ryuichiro -- Nureki, Osamu -- England -- Nature. 2009 Oct 22;461(7267):1144-8. doi: 10.1038/nature08474.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Information, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Kanagawa 225-8501, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19847269" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acyl-tRNA Synthetases/*chemistry/genetics/*metabolism ; Apoproteins/genetics/metabolism ; Bacillus subtilis ; Bacterial Proteins/*chemistry/genetics/*metabolism ; Base Sequence ; Catalytic Domain ; Crystallography, X-Ray ; Escherichia coli ; Geobacillus ; Kinetics ; Lysine/analogs & derivatives/metabolism ; Mass Spectrometry ; Models, Molecular ; Molecular Sequence Data ; *Protein Biosynthesis ; Pyrimidine Nucleosides/metabolism ; RNA, Transfer, Ile/genetics/metabolism ; Substrate Specificity
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 45
    Publication Date: 2009-05-01
    Description: An efficient method for making directed DNA sequence modifications to plant genes (gene targeting) is at present lacking, thereby frustrating efforts to dissect plant gene function and engineer crop plants that better meet the world's burgeoning need for food, fibre and fuel. Zinc-finger nucleases (ZFNs)-enzymes engineered to create DNA double-strand breaks at specific loci-are potent stimulators of gene targeting; for example, they can be used to precisely modify engineered reporter genes in plants. Here we demonstrate high-frequency ZFN-stimulated gene targeting at endogenous plant genes, namely the tobacco acetolactate synthase genes (ALS SuRA and SuRB), for which specific mutations are known to confer resistance to imidazolinone and sulphonylurea herbicides. Herbicide-resistance mutations were introduced into SuR loci by ZFN-mediated gene targeting at frequencies exceeding 2% of transformed cells for mutations as far as 1.3 kilobases from the ZFN cleavage site. More than 40% of recombinant plants had modifications in multiple SuR alleles. The observed high frequency of gene targeting indicates that it is now possible to efficiently make targeted sequence changes in endogenous plant genes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2743854/" 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/PMC2743854/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Townsend, Jeffrey A -- Wright, David A -- Winfrey, Ronnie J -- Fu, Fengli -- Maeder, Morgan L -- Joung, J Keith -- Voytas, Daniel F -- DP1 OD006862/OD/NIH HHS/ -- R01 GM069906/GM/NIGMS NIH HHS/ -- R01 GM069906-01A1/GM/NIGMS NIH HHS/ -- R01 GM069906-02/GM/NIGMS NIH HHS/ -- R01 GM069906-02S1/GM/NIGMS NIH HHS/ -- R01 GM069906-03/GM/NIGMS NIH HHS/ -- R01 GM069906-04/GM/NIGMS NIH HHS/ -- R01 GM069906-05/GM/NIGMS NIH HHS/ -- England -- Nature. 2009 May 21;459(7245):442-5. doi: 10.1038/nature07845. Epub 2009 Apr 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Development & Cell Biology, Iowa State University, Ames, Iowa 50011, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19404258" target="_blank"〉PubMed〈/a〉
    Keywords: Acetolactate Synthase/genetics ; Alleles ; Amino Acid Sequence ; Base Sequence ; Deoxyribonucleases/chemistry/genetics/*metabolism ; Food, Genetically Modified ; Gene Targeting/*methods ; Genes, Plant/*genetics ; Herbicide Resistance/genetics ; Herbicides/pharmacology ; Molecular Sequence Data ; Plants, Genetically Modified ; *Protein Engineering ; Recombination, Genetic/genetics ; Tobacco/drug effects/enzymology/*genetics ; Transformation, Genetic ; *Zinc Fingers
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 46
    Publication Date: 2009-05-22
    Description: Consistent with the role of microRNAs (miRNAs) in down-regulating gene expression by reducing the translation and/or stability of target messenger RNAs, the levels of specific miRNAs are important for correct embryonic development and have been linked to several forms of cancer. However, the regulatory mechanisms by which primary miRNAs (pri-miRNAs) are processed first to precursor miRNAs (pre-miRNAs) and then to mature miRNAs by the multiprotein Drosha and Dicer complexes, respectively, remain largely unknown. The KH-type splicing regulatory protein (KSRP, also known as KHSRP) interacts with single-strand AU-rich-element-containing mRNAs and is a key mediator of mRNA decay. Here we show in mammalian cells that KSRP also serves as a component of both Drosha and Dicer complexes and regulates the biogenesis of a subset of miRNAs. KSRP binds with high affinity to the terminal loop of the target miRNA precursors and promotes their maturation. This mechanism is required for specific changes in target mRNA expression that affect specific biological programs, including proliferation, apoptosis and differentiation. These findings reveal an unexpected mechanism that links KSRP to the machinery regulating maturation of a cohort of miRNAs that, in addition to its role in promoting mRNA decay, independently serves to integrate specific regulatory programs of protein expression.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2768332/" 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/PMC2768332/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Trabucchi, Michele -- Briata, Paola -- Garcia-Mayoral, Mariaflor -- Haase, Astrid D -- Filipowicz, Witold -- Ramos, Andres -- Gherzi, Roberto -- Rosenfeld, Michael G -- 082088/Wellcome Trust/United Kingdom -- DK018477/DK/NIDDK NIH HHS/ -- DK39949/DK/NIDDK NIH HHS/ -- GFP04003/Telethon/Italy -- HL065445/HL/NHLBI NIH HHS/ -- MC_U117533887/Medical Research Council/United Kingdom -- MC_U117574558/Medical Research Council/United Kingdom -- R37 DK039949/DK/NIDDK NIH HHS/ -- R37 DK039949-26/DK/NIDDK NIH HHS/ -- R37 DK039949-27/DK/NIDDK NIH HHS/ -- WT022088MA/Wellcome Trust/United Kingdom -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Jun 18;459(7249):1010-4. doi: 10.1038/nature08025. Epub 2009 May 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department and School of Medicine, University of California, San Diego, 9500 Gilman Drive, Room 345, La Jolla, California 92093-0648, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19458619" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Mice ; MicroRNAs/*biosynthesis/genetics/metabolism ; RNA Processing, Post-Transcriptional ; RNA-Binding Proteins/*metabolism ; Ribonuclease III/chemistry/metabolism ; Trans-Activators/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 47
    Publication Date: 2009-06-12
    Description: Osteoblasts and endothelium constitute functional niches that support haematopoietic stem cells in mammalian bone marrow. Adult bone marrow also contains adipocytes, the number of which correlates inversely with the haematopoietic activity of the marrow. Fatty infiltration of haematopoietic red marrow follows irradiation or chemotherapy and is a diagnostic feature in biopsies from patients with marrow aplasia. To explore whether adipocytes influence haematopoiesis or simply fill marrow space, we compared the haematopoietic activity of distinct regions of the mouse skeleton that differ in adiposity. Here we show, by flow cytometry, colony-forming activity and competitive repopulation assay, that haematopoietic stem cells and short-term progenitors are reduced in frequency in the adipocyte-rich vertebrae of the mouse tail relative to the adipocyte-free vertebrae of the thorax. In lipoatrophic A-ZIP/F1 'fatless' mice, which are genetically incapable of forming adipocytes, and in mice treated with the peroxisome proliferator-activated receptor-gamma inhibitor bisphenol A diglycidyl ether, which inhibits adipogenesis, marrow engraftment after irradiation is accelerated relative to wild-type or untreated mice. These data implicate adipocytes as predominantly negative regulators of the bone-marrow microenvironment, and indicate that antagonizing marrow adipogenesis may enhance haematopoietic recovery in clinical bone-marrow transplantation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2831539/" 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/PMC2831539/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Naveiras, Olaia -- Nardi, Valentina -- Wenzel, Pamela L -- Hauschka, Peter V -- Fahey, Frederic -- Daley, George Q -- DP1 OD000256/OD/NIH HHS/ -- DP1 OD000256-01/OD/NIH HHS/ -- R01 DK059279/DK/NIDDK NIH HHS/ -- R01 DK059279-06/DK/NIDDK NIH HHS/ -- R01 DK070055/DK/NIDDK NIH HHS/ -- R01 DK070055-01/DK/NIDDK NIH HHS/ -- T32- HL -7623/HL/NHLBI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Jul 9;460(7252):259-63. doi: 10.1038/nature08099. Epub 2009 Jun 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Pediatric Hematology/Oncology, Children's Hospital Boston and Dana Farber Cancer Institute, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19516257" target="_blank"〉PubMed〈/a〉
    Keywords: Adipocytes/cytology/drug effects/*physiology ; Adipogenesis/drug effects ; Adiposity/physiology ; Animals ; Benzhydryl Compounds ; Bone Marrow Cells/*cytology/*metabolism ; Bone Marrow Transplantation ; Cell Line ; Epoxy Compounds/pharmacology ; Femur ; *Hematopoiesis/drug effects ; Hematopoietic Stem Cells/cytology/metabolism ; Homeostasis ; Mice ; Mice, Inbred C57BL ; Osteogenesis ; Spine/cytology/metabolism ; Stromal Cells ; Tail ; Thorax ; Tibia
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 48
    Publication Date: 2009-02-13
    Description: Despite decades of research, the identity of the cells generating the first haematopoietic cells in mammalian embryos is unknown. Indeed, whether blood cells arise from mesodermal cells, mesenchymal progenitors, bipotent endothelial-haematopoietic precursors or haemogenic endothelial cells remains controversial. Proximity of endothelial and blood cells at sites of embryonic haematopoiesis, as well as their similar gene expression, led to the hypothesis of the endothelium generating blood. However, owing to lacking technology it has been impossible to observe blood cell emergence continuously at the single-cell level, and the postulated existence of haemogenic endothelial cells remains disputed. Here, using new imaging and cell-tracking methods, we show that embryonic endothelial cells can be haemogenic. By continuous long-term single-cell observation of mouse mesodermal cells generating endothelial cell and blood colonies, it was possible to detect haemogenic endothelial cells giving rise to blood cells. Living endothelial and haematopoietic cells were identified by simultaneous detection of morphology and multiple molecular and functional markers. Detachment of nascent blood cells from endothelium is not directly linked to asymmetric cell division, and haemogenic endothelial cells are specified from cells already expressing endothelial markers. These results improve our understanding of the developmental origin of mammalian blood and the potential generation of haematopoietic stem cells from embryonic stem cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Eilken, Hanna M -- Nishikawa, Shin-Ichi -- Schroeder, Timm -- England -- Nature. 2009 Feb 12;457(7231):896-900. doi: 10.1038/nature07760.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Stem Cell Research, Helmholtz Center Munich-German Research Center for Environmental Health (GmbH), 85764 Neuherberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19212410" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blood Cells/*cytology ; *Cell Differentiation ; Cell Line ; Embryo, Mammalian/cytology/embryology ; Embryonic Stem Cells/cytology ; Hemangioblasts/*cytology ; *Image Processing, Computer-Assisted ; Mesoderm/cytology ; Mice ; Microscopy, Fluorescence ; *Video Recording
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 49
    Publication Date: 2009-11-10
    Description: Direct reprogramming of somatic cells into induced pluripotent stem (iPS) cells can be achieved by overexpression of Oct4, Sox2, Klf4 and c-Myc transcription factors, but only a minority of donor somatic cells can be reprogrammed to pluripotency. Here we demonstrate that reprogramming by these transcription factors is a continuous stochastic process where almost all mouse donor cells eventually give rise to iPS cells on continued growth and transcription factor expression. Additional inhibition of the p53/p21 pathway or overexpression of Lin28 increased the cell division rate and resulted in an accelerated kinetics of iPS cell formation that was directly proportional to the increase in cell proliferation. In contrast, Nanog overexpression accelerated reprogramming in a predominantly cell-division-rate-independent manner. Quantitative analyses define distinct cell-division-rate-dependent and -independent modes for accelerating the stochastic course of reprogramming, and suggest that the number of cell divisions is a key parameter driving epigenetic reprogramming to pluripotency.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2789972/" 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/PMC2789972/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hanna, Jacob -- Saha, Krishanu -- Pando, Bernardo -- van Zon, Jeroen -- Lengner, Christopher J -- Creyghton, Menno P -- van Oudenaarden, Alexander -- Jaenisch, Rudolf -- R01 CA087869/CA/NCI NIH HHS/ -- R01 CA087869-09/CA/NCI NIH HHS/ -- R01 HD045022/HD/NICHD NIH HHS/ -- R01 HD045022-06/HD/NICHD NIH HHS/ -- R01-CA087869/CA/NCI NIH HHS/ -- R01-HDO45022/PHS HHS/ -- R37 CA084198/CA/NCI NIH HHS/ -- R37 CA084198-09/CA/NCI NIH HHS/ -- R37-CA084198/CA/NCI NIH HHS/ -- U54CA143874/CA/NCI NIH HHS/ -- England -- Nature. 2009 Dec 3;462(7273):595-601. doi: 10.1038/nature08592. Epub 2009 Nov 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA. Hanna@wi.mit.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19898493" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Differentiation ; Cell Division ; Cell Line ; *Cellular Reprogramming ; Gene Expression Regulation, Developmental ; Mice ; Mice, SCID ; Models, Biological ; Pluripotent Stem Cells/*cytology/*metabolism ; Time Factors ; Transcription Factors/genetics/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 50
    Publication Date: 2009-05-15
    Description: Biomechanical forces are emerging as critical regulators of embryogenesis, particularly in the developing cardiovascular system. After initiation of the heartbeat in vertebrates, cells lining the ventral aspect of the dorsal aorta, the placental vessels, and the umbilical and vitelline arteries initiate expression of the transcription factor Runx1 (refs 3-5), a master regulator of haematopoiesis, and give rise to haematopoietic cells. It remains unknown whether the biomechanical forces imposed on the vascular wall at this developmental stage act as a determinant of haematopoietic potential. Here, using mouse embryonic stem cells differentiated in vitro, we show that fluid shear stress increases the expression of Runx1 in CD41(+)c-Kit(+) haematopoietic progenitor cells, concomitantly augmenting their haematopoietic colony-forming potential. Moreover, we find that shear stress increases haematopoietic colony-forming potential and expression of haematopoietic markers in the para-aortic splanchnopleura/aorta-gonads-mesonephros of mouse embryos and that abrogation of nitric oxide, a mediator of shear-stress-induced signalling, compromises haematopoietic potential in vitro and in vivo. Collectively, these data reveal a critical role for biomechanical forces in haematopoietic development.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2782763/" 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/PMC2782763/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Adamo, Luigi -- Naveiras, Olaia -- Wenzel, Pamela L -- McKinney-Freeman, Shannon -- Mack, Peter J -- Gracia-Sancho, Jorge -- Suchy-Dicey, Astrid -- Yoshimoto, Momoko -- Lensch, M William -- Yoder, Mervin C -- Garcia-Cardena, Guillermo -- Daley, George Q -- R01 AI080759/AI/NIAID NIH HHS/ -- R01 AI080759-01/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Jun 25;459(7250):1131-5. doi: 10.1038/nature08073. Epub 2009 May 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19440194" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Aorta/cytology/embryology ; *Cell Differentiation ; Cell Line ; Cells, Cultured ; Core Binding Factor Alpha 2 Subunit/genetics ; Embryonic Stem Cells ; Endothelium-Dependent Relaxing Factors/pharmacology ; Female ; Gene Expression Regulation, Developmental ; Hematopoiesis/*physiology ; Hematopoietic Stem Cells/*cytology/drug effects ; Mice ; Nitric Oxide/pharmacology ; Pregnancy ; *Stress, Mechanical
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 51
    Publication Date: 2009-02-03
    Description: It has been proposed that during embryonic development haematopoietic cells arise from a mesodermal progenitor with both endothelial and haematopoietic potential called the haemangioblast. A conflicting theory instead associates the first haematopoietic cells with a phenotypically differentiated endothelial cell that has haematopoietic potential (that is, a haemogenic endothelium). Support for the haemangioblast concept was initially provided by the identification during mouse embryonic stem cell differentiation of a clonal precursor, the blast colony-forming cell (BL-CFC), which gives rise to blast colonies with both endothelial and haematopoietic components. Although recent studies have now provided evidence for the presence of this bipotential precursor in vivo, the precise mechanism for generation of haematopoietic cells from the haemangioblast still remains completely unknown. Here we demonstrate that the haemangioblast generates haematopoietic cells through the formation of a haemogenic endothelium intermediate, providing the first direct link between these two precursor populations. The cell population containing the haemogenic endothelium is transiently generated during BL-CFC development. This cell population is also present in gastrulating mouse embryos and generates haematopoietic cells on further culture. At the molecular level, we demonstrate that the transcription factor Tal1 (also known as Scl; ref. 10) is indispensable for the establishment of this haemogenic endothelium population whereas the core binding factor Runx1 (also known as AML1; ref. 11) is critical for generation of definitive haematopoietic cells from haemogenic endothelium. Together our results merge the two a priori conflicting theories on the origin of haematopoietic development into a single linear developmental process.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2661201/" 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/PMC2661201/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lancrin, Christophe -- Sroczynska, Patrycja -- Stephenson, Catherine -- Allen, Terry -- Kouskoff, Valerie -- Lacaud, Georges -- A5297/Cancer Research UK/United Kingdom -- Cancer Research UK/United Kingdom -- England -- Nature. 2009 Feb 12;457(7231):892-5. doi: 10.1038/nature07679. Epub 2009 Jan 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Research UK Stem Cell Biology Group.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19182774" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Core Binding Factor Alpha 2 Subunit/metabolism ; Embryo, Mammalian/cytology/embryology ; Gene Expression Regulation, Developmental ; Hemangioblasts/*cytology ; Hematopoietic Stem Cells/*cytology ; Mice ; Mice, Inbred ICR ; Oncogene Proteins, Fusion/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 52
    Publication Date: 2009-08-21
    Description: Normal epithelial cells require matrix attachment for survival, and the ability of tumour cells to survive outside their natural extracellular matrix (ECM) niches is dependent on acquisition of anchorage independence. Although apoptosis is the most rapid mechanism for eliminating cells lacking appropriate ECM attachment, recent reports suggest that non-apoptotic death processes prevent survival when apoptosis is inhibited in matrix-deprived cells. Here we demonstrate that detachment of mammary epithelial cells from ECM causes an ATP deficiency owing to the loss of glucose transport. Overexpression of ERBB2 rescues the ATP deficiency by restoring glucose uptake through stabilization of EGFR and phosphatidylinositol-3-OH kinase (PI(3)K) activation, and this rescue is dependent on glucose-stimulated flux through the antioxidant-generating pentose phosphate pathway. Notably, we found that the ATP deficiency could be rescued by antioxidant treatment without rescue of glucose uptake. This rescue was found to be dependent on stimulation of fatty acid oxidation, which is inhibited by detachment-induced reactive oxygen species (ROS). The significance of these findings was supported by evidence of an increase in ROS in matrix-deprived cells in the luminal space of mammary acini, and the discovery that antioxidants facilitate the survival of these cells and enhance anchorage-independent colony formation. These results show both the importance of matrix attachment in regulating metabolic activity and an unanticipated mechanism for cell survival in altered matrix environments by antioxidant restoration of ATP generation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2931797/" 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/PMC2931797/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schafer, Zachary T -- Grassian, Alexandra R -- Song, Loling -- Jiang, Zhenyang -- Gerhart-Hines, Zachary -- Irie, Hanna Y -- Gao, Sizhen -- Puigserver, Pere -- Brugge, Joan S -- K25 CA100290-03/CA/NCI NIH HHS/ -- K25 CA100290-04/CA/NCI NIH HHS/ -- R01 CA105134/CA/NCI NIH HHS/ -- R01 CA105134-09/CA/NCI NIH HHS/ -- England -- Nature. 2009 Sep 3;461(7260):109-13. doi: 10.1038/nature08268. Epub 2009 Aug 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19693011" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Anoikis/physiology ; Antioxidants/*metabolism ; Breast/cytology/metabolism/pathology ; Breast Neoplasms/metabolism/pathology ; Cell Adhesion ; Cell Line ; Cell Survival ; Enzyme Activation ; Epithelial Cells/cytology/*metabolism/pathology ; Extracellular Matrix/*metabolism ; Fatty Acids/metabolism ; Glucose/metabolism ; Humans ; Oncogenes/genetics/*physiology ; Pentose Phosphate Pathway/physiology ; Phosphatidylinositol 3-Kinases/metabolism ; Reactive Oxygen Species/metabolism ; Receptor, Epidermal Growth Factor/metabolism ; Receptor, ErbB-2/genetics/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 53
    Publication Date: 2009-09-11
    Description: Phagocytic removal of apoptotic cells occurs efficiently in vivo such that even in tissues with significant apoptosis, very few apoptotic cells are detectable. This is thought to be due to the release of 'find-me' signals by apoptotic cells that recruit motile phagocytes such as monocytes, macrophages and dendritic cells, leading to the prompt clearance of the dying cells. However, the identity and in vivo relevance of such find-me signals are not well understood. Here, through several lines of evidence, we identify extracellular nucleotides as a critical apoptotic cell find-me signal. We demonstrate the caspase-dependent release of ATP and UTP (in equimolar quantities) during the early stages of apoptosis by primary thymocytes and cell lines. Purified nucleotides at these concentrations were sufficient to induce monocyte recruitment comparable to that of apoptotic cell supernatants. Enzymatic removal of ATP and UTP (by apyrase or the expression of ectopic CD39) abrogated the ability of apoptotic cell supernatants to recruit monocytes in vitro and in vivo. We then identified the ATP/UTP receptor P2Y(2) as a critical sensor of nucleotides released by apoptotic cells using RNA interference-mediated depletion studies in monocytes, and macrophages from P2Y(2)-null mice. The relevance of nucleotides in apoptotic cell clearance in vivo was revealed by two approaches. First, in a murine air-pouch model, apoptotic cell supernatants induced a threefold greater recruitment of monocytes and macrophages than supernatants from healthy cells did; this recruitment was abolished by depletion of nucleotides and was significantly decreased in P2Y(2)(-/-) (also known as P2ry2(-/-)) mice. Second, clearance of apoptotic thymocytes was significantly impaired by either depletion of nucleotides or interference with P2Y receptor function (by pharmacological inhibition or in P2Y(2)(-/-) mice). These results identify nucleotides as a critical find-me cue released by apoptotic cells to promote P2Y(2)-dependent recruitment of phagocytes, and provide evidence for a clear relationship between a find-me signal and efficient corpse clearance in vivo.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2851546/" 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/PMC2851546/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Elliott, Michael R -- Chekeni, Faraaz B -- Trampont, Paul C -- Lazarowski, Eduardo R -- Kadl, Alexandra -- Walk, Scott F -- Park, Daeho -- Woodson, Robin I -- Ostankovich, Marina -- Sharma, Poonam -- Lysiak, Jeffrey J -- Harden, T Kendall -- Leitinger, Norbert -- Ravichandran, Kodi S -- R01 GM064709/GM/NIGMS NIH HHS/ -- R01 GM064709-07/GM/NIGMS NIH HHS/ -- R01 GM069998/GM/NIGMS NIH HHS/ -- R01 GM069998-04/GM/NIGMS NIH HHS/ -- England -- Nature. 2009 Sep 10;461(7261):282-6. doi: 10.1038/nature08296.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, Virginia 22908, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19741708" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/*metabolism/pharmacology/secretion ; Animals ; Apoptosis/*physiology ; Cell Line ; Cells, Cultured ; Chemotactic Factors/metabolism/pharmacology/secretion ; Chemotaxis/drug effects ; Culture Media, Conditioned/chemistry/metabolism/pharmacology ; Humans ; Jurkat Cells ; Macrophage Activation/drug effects ; Macrophages/cytology/drug effects/metabolism ; Mice ; Mice, Inbred C57BL ; Monocytes/cytology/drug effects/metabolism ; Phagocytes/*cytology/drug effects/metabolism ; Phagocytosis/drug effects/*physiology ; Purinergic P2 Receptor Antagonists ; Receptors, Purinergic P2/deficiency/genetics/metabolism ; Receptors, Purinergic P2Y2 ; *Signal Transduction/drug effects ; Thymus Gland/*cytology ; Uridine Triphosphate/*metabolism/pharmacology/secretion
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 54
    Publication Date: 2009-06-26
    Description: The ecology, behaviour and genetics of our closest living relatives, the nonhuman primates, should help us to understand the evolution of our own lineage. Although a large amount of data has been amassed on primate ecology and behaviour, much less is known about the functional and evolutionary genetic aspects of primate biology, especially in wild primates. As a result, even in well-studied populations in which nongenetic factors that influence adaptively important characteristics have been identified, we have almost no understanding of the underlying genetic basis for such traits. Here, we report on the functional consequences of genetic variation at the malaria-related FY (DARC) gene in a well-studied population of yellow baboons (Papio cynocephalus) living in Amboseli National Park in Kenya. FY codes for a chemokine receptor normally expressed on the erythrocyte surface that is the known entry point for the malarial parasite Plasmodium vivax. We identified variation in the cis-regulatory region of the baboon FY gene that was associated with phenotypic variation in susceptibility to Hepatocystis, a malaria-like pathogen that is common in baboons. Genetic variation in this region also influenced gene expression in vivo in wild individuals, a result we confirmed using in vitro reporter gene assays. The patterns of genetic variation in and around this locus were also suggestive of non-neutral evolution, raising the possibility that the evolution of the FY cis-regulatory region in baboons has exhibited both mechanistic and selective parallels with the homologous region in humans. Together, our results represent the first reported association and functional characterization linking genetic variation and a complex trait in a natural population of nonhuman primates.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tung, Jenny -- Primus, Alexander -- Bouley, Andrew J -- Severson, Tonya F -- Alberts, Susan C -- Wray, Gregory A -- England -- Nature. 2009 Jul 16;460(7253):388-91. doi: 10.1038/nature08149. Epub 2009 Jun 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Duke University, North Carolina 27708, USA. jt5@duke.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19553936" target="_blank"〉PubMed〈/a〉
    Keywords: Allelic Imbalance ; Animals ; Animals, Wild/*genetics/parasitology ; Cell Line, Tumor ; Duffy Blood-Group System/genetics ; *Evolution, Molecular ; Gene Expression Regulation/genetics ; Genetic Predisposition to Disease/*genetics ; Genotype ; Haemosporida/*physiology ; Humans ; Kenya ; Malaria/genetics/parasitology/*veterinary ; Molecular Sequence Data ; Papio cynocephalus/*genetics/parasitology ; Plasmodium vivax/physiology ; Polymorphism, Single Nucleotide/genetics ; Receptors, Cell Surface/*genetics/metabolism ; Regulatory Sequences, Nucleic Acid/genetics ; Sequence Homology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 55
    Publication Date: 2009-06-12
    Description: With 8.9 million new cases and 1.7 million deaths per year, tuberculosis is a leading global killer that has not been effectively controlled. The causative agent, Mycobacterium tuberculosis, proliferates within host macrophages where it modifies both its intracellular and local tissue environment, resulting in caseous granulomas with incomplete bacterial sterilization. Although infection by various mycobacterial species produces a cyclic AMP burst within macrophages that influences cell signalling, the underlying mechanism for the cAMP burst remains unclear. Here we show that among the 17 adenylate cyclase genes present in M. tuberculosis, at least one (Rv0386) is required for virulence. Furthermore, we demonstrate that the Rv0386 adenylate cyclase facilitates delivery of bacterial-derived cAMP into the macrophage cytoplasm. Loss of Rv0386 and the intramacrophage cAMP it delivers results in reductions in TNF-alpha production via the protein kinase A and cAMP response-element-binding protein pathway, decreased immunopathology in animal tissues, and diminished bacterial survival. Direct intoxication of host cells by bacterial-derived cAMP may enable M. tuberculosis to modify both its intracellular and tissue environments to facilitate its long-term survival.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Agarwal, Nisheeth -- Lamichhane, Gyanu -- Gupta, Radhika -- Nolan, Scott -- Bishai, William R -- AI30036/AI/NIAID NIH HHS/ -- AI36973/AI/NIAID NIH HHS/ -- AI37856/AI/NIAID NIH HHS/ -- England -- Nature. 2009 Jul 2;460(7251):98-102. doi: 10.1038/nature08123. Epub 2009 Jun 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Johns Hopkins School of Medicine, CRB2, Room 1.08, 1550 Orleans Street, Baltimore, Maryland 21231-1044, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19516256" target="_blank"〉PubMed〈/a〉
    Keywords: Adenylyl Cyclases/genetics/*metabolism ; Animals ; Cell Line ; Cyclic AMP/*metabolism ; Cyclic AMP Response Element-Binding Protein/metabolism ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Cytosol/metabolism/microbiology ; Macrophages/immunology/*metabolism/microbiology/*pathology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mycobacterium tuberculosis/*enzymology/genetics/growth & ; development/*pathogenicity ; Phosphoric Diester Hydrolases/genetics/metabolism ; Phosphorylation ; Tuberculosis/immunology/microbiology/*pathology ; Tumor Necrosis Factor-alpha/biosynthesis/secretion ; Virulence/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 56
    Publication Date: 2009-11-13
    Description: The mucosal immune system forms the largest part of the entire immune system, containing about three-quarters of all lymphocytes and producing grams of secretory IgA daily to protect the mucosal surface from pathogens. To evoke the mucosal immune response, antigens on the mucosal surface must be transported across the epithelial barrier into organized lymphoid structures such as Peyer's patches. This function, called antigen transcytosis, is mediated by specialized epithelial M cells. The molecular mechanisms promoting this antigen uptake, however, are largely unknown. Here we report that glycoprotein 2 (GP2), specifically expressed on the apical plasma membrane of M cells among enterocytes, serves as a transcytotic receptor for mucosal antigens. Recombinant GP2 protein selectively bound a subset of commensal and pathogenic enterobacteria, including Escherichia coli and Salmonella enterica serovar Typhimurium (S. Typhimurium), by recognizing FimH, a component of type I pili on the bacterial outer membrane. Consistently, these bacteria were colocalized with endogenous GP2 on the apical plasma membrane as well as in cytoplasmic vesicles in M cells. Moreover, deficiency of bacterial FimH or host GP2 led to defects in transcytosis of type-I-piliated bacteria through M cells, resulting in an attenuation of antigen-specific immune responses in Peyer's patches. GP2 is therefore a previously unrecognized transcytotic receptor on M cells for type-I-piliated bacteria and is a prerequisite for the mucosal immune response to these bacteria. Given that M cells are considered a promising target for oral vaccination against various infectious diseases, the GP2-dependent transcytotic pathway could provide a new target for the development of M-cell-targeted mucosal vaccines.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hase, Koji -- Kawano, Kazuya -- Nochi, Tomonori -- Pontes, Gemilson Soares -- Fukuda, Shinji -- Ebisawa, Masashi -- Kadokura, Kazunori -- Tobe, Toru -- Fujimura, Yumiko -- Kawano, Sayaka -- Yabashi, Atsuko -- Waguri, Satoshi -- Nakato, Gaku -- Kimura, Shunsuke -- Murakami, Takaya -- Iimura, Mitsutoshi -- Hamura, Kimiyo -- Fukuoka, Shin-Ichi -- Lowe, Anson W -- Itoh, Kikuji -- Kiyono, Hiroshi -- Ohno, Hiroshi -- DK43294/DK/NIDDK NIH HHS/ -- DK56339/DK/NIDDK NIH HHS/ -- England -- Nature. 2009 Nov 12;462(7270):226-30. doi: 10.1038/nature08529.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory for Epithelial Immunobiology, Research Center for Allergy and Immunology, RIKEN, Kanagawa 230-0045, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19907495" target="_blank"〉PubMed〈/a〉
    Keywords: Adhesins, Escherichia coli/genetics/immunology/*metabolism ; Animals ; Antigens, Bacterial/genetics/immunology/*metabolism ; Cell Line ; Epithelial Cells/*immunology/metabolism ; Escherichia coli/immunology/metabolism ; Fimbriae Proteins/genetics/immunology/*metabolism ; GPI-Linked Proteins ; Glycoproteins ; HeLa Cells ; Humans ; Immunity, Mucosal/*immunology ; Intestines/cytology ; Membrane Glycoproteins/*metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Peyer's Patches/*cytology/immunology ; Salmonella typhimurium/genetics/immunology/metabolism ; Substrate Specificity
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 57
    Publication Date: 2009-06-26
    Description: The integrity of polarized epithelia is critical for development and human health. Many questions remain concerning the full complement and the function of the proteins that regulate cell polarity. Here we report that the Drosophila FERM proteins Yurt (Yrt) and Coracle (Cora) and the membrane proteins Neurexin IV (Nrx-IV) and Na(+),K(+)-ATPase are a new group of functionally cooperating epithelial polarity proteins. This 'Yrt/Cora group' promotes basolateral membrane stability and shows negative regulatory interactions with the apical determinant Crumbs (Crb). Genetic analyses indicate that Nrx-IV and Na(+),K(+)-ATPase act together with Cora in one pathway, whereas Yrt acts in a second redundant pathway. Moreover, we show that the Yrt/Cora group is essential for epithelial polarity during organogenesis but not when epithelial polarity is first established or during terminal differentiation. This property of Yrt/Cora group proteins explains the recovery of polarity in embryos lacking the function of the Lethal giant larvae (Lgl) group of basolateral polarity proteins. We also find that the mammalian Yrt orthologue EPB41L5 (also known as YMO1 and Limulus) is required for lateral membrane formation, indicating a conserved function of Yrt proteins in epithelial polarity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Laprise, Patrick -- Lau, Kimberly M -- Harris, Kathryn P -- Silva-Gagliardi, Nancy F -- Paul, Sarah M -- Beronja, Slobodan -- Beitel, Greg J -- McGlade, C Jane -- Tepass, Ulrich -- England -- Nature. 2009 Jun 25;459(7250):1141-5. doi: 10.1038/nature08067.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario M5S 3G5, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19553998" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Adhesion Molecules, Neuronal/genetics/*metabolism ; Cell Line ; Cell Polarity ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster/*embryology/enzymology/genetics/metabolism ; Epithelium/embryology/*physiology ; Gene Knockdown Techniques ; Membrane Proteins/genetics/*metabolism ; Mutation ; Phenotype ; Sodium-Potassium-Exchanging ATPase/genetics/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 58
    Publication Date: 2009-08-12
    Description: The overexpression of defined transcription factors in somatic cells results in their reprogramming into induced pluripotent stem (iPS) cells. The extremely low efficiency and slow kinetics of in vitro reprogramming suggest that further rare events are required to generate iPS cells. The nature and identity of these events, however, remain elusive. We noticed that the reprogramming potential of primary murine fibroblasts into iPS cells decreases after serial passaging and the concomitant onset of senescence. Consistent with the notion that loss of replicative potential provides a barrier for reprogramming, here we show that cells with low endogenous p19(Arf) (encoded by the Ink4a/Arf locus, also known as Cdkn2a locus) protein levels and immortal fibroblasts deficient in components of the Arf-Trp53 pathway yield iPS cell colonies with up to threefold faster kinetics and at a significantly higher efficiency than wild-type cells, endowing almost every somatic cell with the potential to form iPS cells. Notably, the acute genetic ablation of Trp53 (also known as p53) in cellular subpopulations that normally fail to reprogram rescues their ability to produce iPS cells. Our results show that the acquisition of immortality is a crucial and rate-limiting step towards the establishment of a pluripotent state in somatic cells and underscore the similarities between induced pluripotency and tumorigenesis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3987892/" 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/PMC3987892/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Utikal, Jochen -- Polo, Jose M -- Stadtfeld, Matthias -- Maherali, Nimet -- Kulalert, Warakorn -- Walsh, Ryan M -- Khalil, Adam -- Rheinwald, James G -- Hochedlinger, Konrad -- DP2 OD003266/OD/NIH HHS/ -- England -- Nature. 2009 Aug 27;460(7259):1145-8. doi: 10.1038/nature08285. Epub 2009 Aug 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine, Harvard Stem Cell Institute, 185 Cambridge Street, Boston, Massachusetts 02114, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19668190" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Aging/*physiology ; Cell Differentiation ; Cell Division ; Cell Line ; Cells, Cultured ; Cellular Reprogramming/*physiology ; Cyclin-Dependent Kinase Inhibitor p16/deficiency/genetics/metabolism ; Down-Regulation ; Fibroblasts/cytology/metabolism ; Gene Expression ; Humans ; Keratinocytes ; Kinetics ; Mice ; Mice, SCID ; Pluripotent Stem Cells/*cytology/metabolism ; Tumor Suppressor Protein p53/deficiency/genetics/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 59
    Publication Date: 2009-03-20
    Description: In the study of complex mammalian behaviours, technological limitations have prevented spatiotemporally precise control over intracellular signalling processes. Here we report the development of a versatile family of genetically encoded optical tools ('optoXRs') that leverage common structure-function relationships among G-protein-coupled receptors (GPCRs) to recruit and control, with high spatiotemporal precision, receptor-initiated biochemical signalling pathways. In particular, we have developed and characterized two optoXRs that selectively recruit distinct, targeted signalling pathways in response to light. The two optoXRs exerted opposing effects on spike firing in nucleus accumbens in vivo, and precisely timed optoXR photostimulation in nucleus accumbens by itself sufficed to drive conditioned place preference in freely moving mice. The optoXR approach allows testing of hypotheses regarding the causal impact of biochemical signalling in behaving mammals, in a targetable and temporally precise manner.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Airan, Raag D -- Thompson, Kimberly R -- Fenno, Lief E -- Bernstein, Hannah -- Deisseroth, Karl -- England -- Nature. 2009 Apr 23;458(7241):1025-9. doi: 10.1038/nature07926. Epub 2009 Mar 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bioengineering, Stanford University, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19295515" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cattle ; Cell Line ; Cricetinae ; Cyclic AMP Response Element-Binding Protein/metabolism ; *Genetic Engineering ; Humans ; Intracellular Space/*metabolism/radiation effects ; Mice ; Nucleus Accumbens/cytology/physiology/radiation effects ; Receptors, Adrenergic, alpha-1/genetics/metabolism ; Receptors, Adrenergic, beta-2/genetics/metabolism ; Receptors, G-Protein-Coupled/genetics/*metabolism ; Recombinant Fusion Proteins/genetics/*metabolism ; Reward ; Rhodopsin/genetics/metabolism ; *Signal Transduction/radiation effects ; Structure-Activity Relationship ; Time Factors
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 60
    Publication Date: 2009-09-01
    Description: The orphan receptor tyrosine kinase ErbB2 (also known as HER2 or Neu) transforms cells when overexpressed, and it is an important therapeutic target in human cancer. Structural studies have suggested that the oncogenic (and ligand-independent) signalling properties of ErbB2 result from the absence of a key intramolecular 'tether' in the extracellular region that autoinhibits other human ErbB receptors, including the epidermal growth factor (EGF) receptor. Although ErbB2 is unique among the four human ErbB receptors, here we show that it is the closest structural relative of the single EGF receptor family member in Drosophila melanogaster (dEGFR). Genetic and biochemical data show that dEGFR is tightly regulated by growth factor ligands, yet a crystal structure shows that it, too, lacks the intramolecular tether seen in human EGFR, ErbB3 and ErbB4. Instead, a distinct set of autoinhibitory interdomain interactions hold unliganded dEGFR in an inactive state. All of these interactions are maintained (and even extended) in ErbB2, arguing against the suggestion that ErbB2 lacks autoinhibition. We therefore suggest that normal and pathogenic ErbB2 signalling may be regulated by ligands in the same way as dEGFR. Our findings have important implications for ErbB2 regulation in human cancer, and for developing therapeutic approaches that target novel aspects of this orphan receptor.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2762480/" 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/PMC2762480/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Alvarado, Diego -- Klein, Daryl E -- Lemmon, Mark A -- R01 CA079992/CA/NCI NIH HHS/ -- R01 CA079992-09/CA/NCI NIH HHS/ -- R01 CA079992-10/CA/NCI NIH HHS/ -- R01 CA125432/CA/NCI NIH HHS/ -- R01 CA125432-01A1/CA/NCI NIH HHS/ -- R01 CA125432-02/CA/NCI NIH HHS/ -- R01 CA125432-03/CA/NCI NIH HHS/ -- England -- Nature. 2009 Sep 10;461(7261):287-91. doi: 10.1038/nature08297. Epub 2009 Aug 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, 809C Stellar-Chance Laboratories, 422 Curie Boulevard, Philadelphia, Pennsylvania 19104-6059, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19718021" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Crystallography, X-Ray ; Drosophila Proteins/*antagonists & inhibitors/chemistry/genetics/*metabolism ; Drosophila melanogaster/chemistry/*metabolism ; Enzyme Activation ; Humans ; Ligands ; Models, Molecular ; Protein Structure, Tertiary ; Receptor, Epidermal Growth Factor/*antagonists & ; inhibitors/chemistry/genetics/*metabolism ; Receptor, ErbB-2/antagonists & inhibitors/*chemistry/*metabolism ; Receptors, Invertebrate Peptide/*antagonists & ; inhibitors/chemistry/genetics/*metabolism ; Scattering, Small Angle ; Solubility ; X-Ray Diffraction
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 61
    Publication Date: 2009-07-07
    Description: To reach the mammalian gut, enteric bacteria must pass through the stomach. Many such organisms survive exposure to the harsh gastric environment (pH 1.5-4) by mounting extreme acid-resistance responses, one of which, the arginine-dependent system of Escherichia coli, has been studied at levels of cellular physiology, molecular genetics and protein biochemistry. This multiprotein system keeps the cytoplasm above pH 5 during acid challenge by continually pumping protons out of the cell using the free energy of arginine decarboxylation. At the heart of the process is a 'virtual proton pump' in the inner membrane, called AdiC, that imports L-arginine from the gastric juice and exports its decarboxylation product agmatine. AdiC belongs to the APC superfamily of membrane proteins, which transports amino acids, polyamines and organic cations in a multitude of biological roles, including delivery of arginine for nitric oxide synthesis, facilitation of insulin release from pancreatic beta-cells, and, when inappropriately overexpressed, provisioning of certain fast-growing neoplastic cells with amino acids. High-resolution structures and detailed transport mechanisms of APC transporters are currently unknown. Here we describe a crystal structure of AdiC at 3.2 A resolution. The protein is captured in an outward-open, substrate-free conformation with transmembrane architecture remarkably similar to that seen in four other families of apparently unrelated transport proteins.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2745212/" 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/PMC2745212/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fang, Yiling -- Jayaram, Hariharan -- Shane, Tania -- Kolmakova-Partensky, Ludmila -- Wu, Fang -- Williams, Carole -- Xiong, Yong -- Miller, Christopher -- P30 EB009998/EB/NIBIB NIH HHS/ -- R01 GM031768/GM/NIGMS NIH HHS/ -- R01 GM031768-26/GM/NIGMS NIH HHS/ -- R01 GM089688/GM/NIGMS NIH HHS/ -- T32 NS 07292/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Aug 20;460(7258):1040-3. doi: 10.1038/nature08201. Epub 2009 Jul 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Howard Hughes Medical Institute, Brandeis University, Waltham, Massachusetts 02454, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19578361" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Transport Systems/*chemistry/metabolism ; Antiporters/*chemistry/metabolism ; Bacterial Proteins/*chemistry ; Crystallography, X-Ray ; Escherichia coli/*chemistry ; Escherichia coli Proteins/*chemistry/metabolism ; Models, Molecular ; Molecular Sequence Data ; Multigene Family ; Protein Conformation ; Salmonella typhi/*chemistry ; Structural Homology, Protein
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 62
    Publication Date: 2009-07-03
    Description: The cytokine leukaemia inhibitory factor (LIF) integrates signals into mouse embryonic stem (ES) cells to maintain pluripotency. Although the Jak-Stat3 pathway is essential and sufficient to mediate LIF signals, it is still unclear how these signals are linked to the core circuitry of pluripotency-associated transcription factors, consisting of Oct3/4 (also called Pou5f1), Sox2 and Nanog. Here we show that two LIF signalling pathways are each connected to the core circuitry via different transcription factors. In mouse ES cells, Klf4 is mainly activated by the Jak-Stat3 pathway and preferentially activates Sox2, whereas Tbx3 is preferentially regulated by the phosphatidylinositol-3-OH kinase-Akt and mitogen-activated protein kinase pathways and predominantly stimulates Nanog. In the absence of LIF, artificial expression of Klf4 or Tbx3 is sufficient to maintain pluripotency while maintaining the expression of Oct3/4. Notably, overexpression of Nanog supports LIF-independent self-renewal of mouse ES cells in the absence of Klf4 and Tbx3 activity. Therefore, Klf4 and Tbx3 are involved in mediating LIF signalling to the core circuitry but are not directly associated with the maintenance of pluripotency, because ES cells keep pluripotency without their expression in the particular context.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Niwa, Hitoshi -- Ogawa, Kazuya -- Shimosato, Daisuke -- Adachi, Kenjiro -- England -- Nature. 2009 Jul 2;460(7251):118-22. doi: 10.1038/nature08113.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory for Pluripotent Cell Studies, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 6500047, Japan. niwa@cdb.riken.jp〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19571885" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Embryonic Stem Cells/*cytology/*metabolism ; Gene Expression Regulation ; Homeodomain Proteins/genetics/metabolism ; Janus Kinases/metabolism ; Kruppel-Like Transcription Factors/genetics/metabolism ; Leukemia Inhibitory Factor/*metabolism ; MAP Kinase Signaling System ; Mice ; Phosphatidylinositol 3-Kinases/metabolism ; Pluripotent Stem Cells/*cytology/*metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; STAT3 Transcription Factor/metabolism ; *Signal Transduction ; T-Box Domain Proteins/genetics/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 63
    Publication Date: 2009-08-04
    Description: Polymerization of actin filaments directed by the actin-related protein (Arp)2/3 complex supports many types of cellular movements. However, questions remain regarding the relative contributions of Arp2/3 complex versus other mechanisms of actin filament nucleation to processes such as path finding by neuronal growth cones; this is because of the lack of simple methods to inhibit Arp2/3 complex reversibly in living cells. Here we describe two classes of small molecules that bind to different sites on the Arp2/3 complex and inhibit its ability to nucleate actin filaments. CK-0944636 binds between Arp2 and Arp3, where it appears to block movement of Arp2 and Arp3 into their active conformation. CK-0993548 inserts into the hydrophobic core of Arp3 and alters its conformation. Both classes of compounds inhibit formation of actin filament comet tails by Listeria and podosomes by monocytes. Two inhibitors with different mechanisms of action provide a powerful approach for studying the Arp2/3 complex in living cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2780427/" 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/PMC2780427/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nolen, B J -- Tomasevic, N -- Russell, A -- Pierce, D W -- Jia, Z -- McCormick, C D -- Hartman, J -- Sakowicz, R -- Pollard, T D -- F32 GM074374-02/GM/NIGMS NIH HHS/ -- GM-066311/GM/NIGMS NIH HHS/ -- GM074374-02/GM/NIGMS NIH HHS/ -- P01 GM066311/GM/NIGMS NIH HHS/ -- P01 GM066311-01A1/GM/NIGMS NIH HHS/ -- P30 EB009998/EB/NIBIB NIH HHS/ -- England -- Nature. 2009 Aug 20;460(7258):1031-4. doi: 10.1038/nature08231. Epub 2009 Aug 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06520, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19648907" target="_blank"〉PubMed〈/a〉
    Keywords: Actin Cytoskeleton/drug effects/metabolism ; Actin-Related Protein 2/antagonists & inhibitors/chemistry/metabolism ; Actin-Related Protein 2-3 Complex/*antagonists & inhibitors/chemistry/metabolism ; Actin-Related Protein 3/antagonists & inhibitors/chemistry/metabolism ; Actins/chemistry/metabolism ; Animals ; Biopolymers/chemistry/metabolism ; Cattle ; Cell Line ; Crystallography, X-Ray ; Humans ; Hydrophobic and Hydrophilic Interactions ; Indoles/classification/metabolism/pharmacology ; Listeria/physiology ; Models, Molecular ; Monocytes/immunology ; Protein Conformation/drug effects ; Schizosaccharomyces ; Thiazoles/chemistry/classification/metabolism/pharmacology ; Thiophenes/classification/metabolism/pharmacology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 64
    Publication Date: 2009-05-29
    Description: The AMP-activated protein kinase (AMPK) is characterized by its ability to bind to AMP, which enables it to adjust enzymatic activity by sensing the cellular energy status and maintain the balance between ATP production and consumption in eukaryotic cells. It also has important roles in the regulation of cell growth and proliferation, and in the establishment and maintenance of cell polarity. These important functions have rendered AMPK an important drug target for obesity, type 2 diabetes and cancer treatments. However, the regulatory mechanism of AMPK activity by AMP binding remains unsolved. Here we report the crystal structures of an unphosphorylated fragment of the AMPK alpha-subunit (KD-AID) from Schizosaccharomyces pombe that contains both the catalytic kinase domain and an autoinhibitory domain (AID), and of a phosphorylated kinase domain from Saccharomyces cerevisiae (Snf1-pKD). The AID binds, from the 'backside', to the hinge region of its kinase domain, forming contacts with both amino-terminal and carboxy-terminal lobes. Structural analyses indicate that AID binding might constrain the mobility of helix alphaC, hence resulting in an autoinhibited KD-AID with much lower kinase activity than that of the kinase domain alone. AMP activates AMPK both allosterically and by inhibiting dephosphorylation. Further in vitro kinetic studies demonstrate that disruption of the KD-AID interface reverses the autoinhibition and these AMPK heterotrimeric mutants no longer respond to the change in AMP concentration. The structural and biochemical data have shown the primary mechanism of AMPK autoinhibition and suggest a conformational switch model for AMPK activation by AMP.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Lei -- Jiao, Zhi-Hao -- Zheng, Li-Sha -- Zhang, Yuan-Yuan -- Xie, Shu-Tao -- Wang, Zhi-Xin -- Wu, Jia-Wei -- England -- Nature. 2009 Jun 25;459(7250):1146-9. doi: 10.1038/nature08075. Epub 2009 May 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MOE Key Laboratory of Bioinformatics, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19474788" target="_blank"〉PubMed〈/a〉
    Keywords: AMP-Activated Protein Kinases/*chemistry/*metabolism ; Adenosine Monophosphate/metabolism ; Amino Acid Sequence ; Animals ; *Models, Molecular ; Molecular Sequence Data ; Mutation ; Phosphorylation ; Protein Structure, Tertiary ; Rats ; Saccharomyces cerevisiae/*enzymology ; Schizosaccharomyces/*enzymology ; Sequence Alignment
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 65
    Publication Date: 2009-05-16
    Description: RNA interference pathways use small RNAs to mediate gene silencing in eukaryotes. In addition to small interfering RNAs (siRNAs) and microRNAs, several types of endogenously produced small RNAs have important roles in gene regulation, germ cell maintenance and transposon silencing. The production of some of these RNAs requires the synthesis of aberrant RNAs (aRNAs) or pre-siRNAs, which are specifically recognized by RNA-dependent RNA polymerases to make double-stranded RNA. The mechanism for aRNA synthesis and recognition is largely unknown. Here we show that DNA damage induces the expression of the Argonaute protein QDE-2 and a new class of small RNAs in the filamentous fungus Neurospora crassa. This class of small RNAs, known as qiRNAs because of their interaction with QDE-2, are about 20-21 nucleotides long (several nucleotides shorter than Neurospora siRNAs), with a strong preference for uridine at the 5' end, and originate mostly from the ribosomal DNA locus. The production of qiRNAs requires the RNA-dependent RNA polymerase QDE-1, the Werner and Bloom RecQ DNA helicase homologue QDE-3 and dicers. qiRNA biogenesis also requires DNA-damage-induced aRNAs as precursors, a process that is dependent on both QDE-1 and QDE-3. Notably, our results suggest that QDE-1 is the DNA-dependent RNA polymerase that produces aRNAs. Furthermore, the Neurospora RNA interference mutants show increased sensitivity to DNA damage, suggesting a role for qiRNAs in the DNA-damage response by inhibiting protein translation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2859615/" 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/PMC2859615/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Heng-Chi -- Chang, Shwu-Shin -- Choudhary, Swati -- Aalto, Antti P -- Maiti, Mekhala -- Bamford, Dennis H -- Liu, Yi -- R01 GM068496/GM/NIGMS NIH HHS/ -- R01 GM068496-07/GM/NIGMS NIH HHS/ -- R01 GM084283/GM/NIGMS NIH HHS/ -- R01 GM084283-01A1/GM/NIGMS NIH HHS/ -- England -- Nature. 2009 May 14;459(7244):274-7. doi: 10.1038/nature08041.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19444217" target="_blank"〉PubMed〈/a〉
    Keywords: DNA Damage/*genetics ; DNA Helicases/genetics/metabolism ; DNA, Ribosomal/genetics ; DNA, Single-Stranded ; Fungal Proteins/biosynthesis/genetics/metabolism ; *Gene Expression Regulation, Fungal ; Molecular Sequence Data ; Neurospora crassa/enzymology/*genetics ; Protein Biosynthesis ; RNA Replicase/genetics/metabolism ; RNA, Fungal/*biosynthesis/*genetics/metabolism ; RNA, Small Interfering/*biosynthesis/*genetics/metabolism ; Templates, Genetic
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 66
    Publication Date: 2009-07-28
    Description: The discovery of intrinsically photosensitive retinal ganglion cells has overthrown the long-held belief that rods and cones are the exclusive retinal photoreceptors. Intrinsically photosensitive retinal ganglion cells use melanopsin as the photopigment, and mediate non-image-forming visual functions such as circadian photoentrainment. In fish, in situ hybridization studies indicated that melanopsin is present in retinal horizontal cells-lateral association neurons critical for creating the centre-surround receptive fields of visual neurons. This raises the question of whether fish horizontal cells are intrinsically photosensitive. This notion was examined previously in flat-mount roach retina, but all horizontal-cell light response disappeared after synaptic transmission was blocked, making any conclusion difficult to reach. To examine this question directly, we have now recorded from single, acutely dissociated horizontal cells from catfish and goldfish. We found that light induced a response in catfish cone horizontal cells, but not rod horizontal cells, consisting of a modulation of the nifedipine-sensitive, voltage-gated calcium current. The light response was extremely slow, lasting for many minutes. Similar light responses were observed in a high percentage of goldfish horizontal cells. We have cloned two melanopsin genes and one vertebrate ancient (VA) opsin gene from catfish. In situ hybridization indicated that melanopsin, but less likely VA opsin, was expressed in the horizontal-cell layer of catfish retina. This intrinsic light response may serve to modulate, over a long timescale, lateral inhibition mediated by these cells. Thus, at least in some vertebrates, there are retinal non-rod/non-cone photoreceptors involved primarily in image-forming vision.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2737592/" 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/PMC2737592/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cheng, Ning -- Tsunenari, Takashi -- Yau, King-Wai -- R01 DC006904/DC/NIDCD NIH HHS/ -- R01 DC006904-01/DC/NIDCD NIH HHS/ -- R01 DC006904-02/DC/NIDCD NIH HHS/ -- R01 DC006904-03/DC/NIDCD NIH HHS/ -- R01 DC006904-04/DC/NIDCD NIH HHS/ -- R01 DC006904-05/DC/NIDCD NIH HHS/ -- R01 EY006837/EY/NEI NIH HHS/ -- R01 EY006837-16A1/EY/NEI NIH HHS/ -- R01 EY006837-17/EY/NEI NIH HHS/ -- R01 EY006837-18/EY/NEI NIH HHS/ -- R01 EY006837-19/EY/NEI NIH HHS/ -- R01 EY006837-20A1/EY/NEI NIH HHS/ -- R01 EY006837-21/EY/NEI NIH HHS/ -- R01 EY006837-22/EY/NEI NIH HHS/ -- R01 EY014596/EY/NEI NIH HHS/ -- R01 EY014596-01/EY/NEI NIH HHS/ -- R01 EY014596-02/EY/NEI NIH HHS/ -- R01 EY014596-03/EY/NEI NIH HHS/ -- R01 EY014596-04/EY/NEI NIH HHS/ -- R01 EY014596-05/EY/NEI NIH HHS/ -- R01 EY014596-06/EY/NEI NIH HHS/ -- R01 EY014596-07/EY/NEI NIH HHS/ -- R01 EY014596-07S1/EY/NEI NIH HHS/ -- R37 EY006837/EY/NEI NIH HHS/ -- R37 EY006837-13/EY/NEI NIH HHS/ -- R37 EY006837-14/EY/NEI NIH HHS/ -- R37 EY006837-15/EY/NEI NIH HHS/ -- R37 EY006837-15S1/EY/NEI NIH HHS/ -- England -- Nature. 2009 Aug 13;460(7257):899-903. doi: 10.1038/nature08175. Epub 2009 Jul 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. chengn2@mail.nih.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19633653" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/metabolism ; *Catfishes ; Cloning, Molecular ; Electric Conductivity ; Fish Proteins/genetics/metabolism ; Gene Expression Profiling ; *Goldfish ; Ion Channel Gating/drug effects/radiation effects ; *Light ; Molecular Sequence Data ; Nifedipine/pharmacology ; Opsins/genetics ; RNA, Messenger/analysis/genetics ; Retinal Cone Photoreceptor Cells/cytology/drug effects/radiation effects ; Retinal Horizontal Cells/drug effects/*radiation effects ; Retinal Rod Photoreceptor Cells/cytology ; Rod Opsins/genetics/metabolism ; Time Factors
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 67
    Publication Date: 2009-03-20
    Description: The human body is composed of diverse cell types with distinct functions. Although it is known that lineage specification depends on cell-specific gene expression, which in turn is driven by promoters, enhancers, insulators and other cis-regulatory DNA sequences for each gene, the relative roles of these regulatory elements in this process are not clear. We have previously developed a chromatin-immunoprecipitation-based microarray method (ChIP-chip) to locate promoters, enhancers and insulators in the human genome. Here we use the same approach to identify these elements in multiple cell types and investigate their roles in cell-type-specific gene expression. We observed that the chromatin state at promoters and CTCF-binding at insulators is largely invariant across diverse cell types. In contrast, enhancers are marked with highly cell-type-specific histone modification patterns, strongly correlate to cell-type-specific gene expression programs on a global scale, and are functionally active in a cell-type-specific manner. Our results define over 55,000 potential transcriptional enhancers in the human genome, significantly expanding the current catalogue of human enhancers and highlighting the role of these elements in cell-type-specific gene expression.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2910248/" 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/PMC2910248/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Heintzman, Nathaniel D -- Hon, Gary C -- Hawkins, R David -- Kheradpour, Pouya -- Stark, Alexander -- Harp, Lindsey F -- Ye, Zhen -- Lee, Leonard K -- Stuart, Rhona K -- Ching, Christina W -- Ching, Keith A -- Antosiewicz-Bourget, Jessica E -- Liu, Hui -- Zhang, Xinmin -- Green, Roland D -- Lobanenkov, Victor V -- Stewart, Ron -- Thomson, James A -- Crawford, Gregory E -- Kellis, Manolis -- Ren, Bing -- R01 HG004037/HG/NHGRI NIH HHS/ -- R01 HG004037-02/HG/NHGRI NIH HHS/ -- U01 HG003151/HG/NHGRI NIH HHS/ -- U01 HG003151-01/HG/NHGRI NIH HHS/ -- U01 HG003151-01S1/HG/NHGRI NIH HHS/ -- U01 HG003151-02/HG/NHGRI NIH HHS/ -- U01 HG003151-03/HG/NHGRI NIH HHS/ -- U01 HG003151-03S1/HG/NHGRI NIH HHS/ -- U01 HG003151-03S2/HG/NHGRI NIH HHS/ -- Intramural NIH HHS/ -- England -- Nature. 2009 May 7;459(7243):108-12. doi: 10.1038/nature07829. Epub 2009 Mar 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ludwig Institute for Cancer Research, UCSD School of Medicine, 9500 Gilman Drive, La Jolla, California 92093-0653, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19295514" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Cell Line ; *Cell Physiological Phenomena ; Chromatin/genetics ; *Gene Expression Regulation ; Genome, Human/genetics ; HeLa Cells ; Histones/*metabolism ; Humans ; K562 Cells ; Promoter Regions, Genetic/genetics ; Transcription Factors/*genetics/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 68
    Publication Date: 2009-03-20
    Description: Calcium/calmodulin-dependent kinase II (CaMKII) plays a central part in long-term potentiation (LTP), which underlies some forms of learning and memory. Here we monitored the spatiotemporal dynamics of CaMKII activation in individual dendritic spines during LTP using two-photon fluorescence lifetime imaging microscopy, in combination with two-photon glutamate uncaging. Induction of LTP and associated spine enlargement in single spines triggered transient ( approximately 1 min) CaMKII activation restricted to the stimulated spines. CaMKII in spines was specifically activated by NMDA receptors and L-type voltage-sensitive calcium channels, presumably by nanodomain Ca(2+) near the channels, in response to glutamate uncaging and depolarization, respectively. The high degree of compartmentalization and channel specificity of CaMKII signalling allow stimuli-specific spatiotemporal patterns of CaMKII signalling and may be important for synapse-specificity of synaptic plasticity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2719773/" 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/PMC2719773/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Seok-Jin R -- Escobedo-Lozoya, Yasmin -- Szatmari, Erzsebet M -- Yasuda, Ryohei -- AS1398/Autism Speaks/ -- R01 MH080047/MH/NIMH NIH HHS/ -- R01 MH080047-01/MH/NIMH NIH HHS/ -- R01 MH080047-02/MH/NIMH NIH HHS/ -- R01MH08004/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Mar 19;458(7236):299-304. doi: 10.1038/nature07842.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19295602" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/antagonists & inhibitors/metabolism ; Calcium Channels, L-Type/metabolism ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics/*metabolism ; Cell Line ; Cells, Cultured ; Chelating Agents/pharmacology ; Dendritic Spines/*enzymology/*physiology ; Enzyme Activation/drug effects ; Fluorescence ; Fluorescence Resonance Energy Transfer ; Glutamic Acid/metabolism ; Hippocampus/cytology ; Humans ; Kinetics ; Long-Term Potentiation/*physiology ; Photons ; Rats ; Receptors, N-Methyl-D-Aspartate/metabolism ; Synapses/metabolism ; Synaptic Potentials/physiology ; Time Factors
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 69
    Publication Date: 2009-01-23
    Description: Host- and pathogen-associated cytoplasmic double-stranded DNA triggers the activation of a NALP3 (also known as cryopyrin and NLRP3)-independent inflammasome, which activates caspase-1 leading to maturation of pro-interleukin-1beta and inflammation. The nature of the cytoplasmic-DNA-sensing inflammasome is currently unknown. Here we show that AIM2 (absent in melanoma 2), an interferon-inducible HIN-200 family member that contains an amino-terminal pyrin domain and a carboxy-terminal oligonucleotide/oligosaccharide-binding domain, senses cytoplasmic DNA by means of its oligonucleotide/oligosaccharide-binding domain and interacts with ASC (apoptosis-associated speck-like protein containing a CARD) through its pyrin domain to activate caspase-1. The interaction of AIM2 with ASC also leads to the formation of the ASC pyroptosome, which induces pyroptotic cell death in cells containing caspase-1. Knockdown of AIM2 by short interfering RNA reduced inflammasome/pyroptosome activation by cytoplasmic DNA in human and mouse macrophages, whereas stable expression of AIM2 in the non-responsive human embryonic kidney 293T cell line conferred responsiveness to cytoplasmic DNA. Our results show that cytoplasmic DNA triggers formation of the AIM2 inflammasome by inducing AIM2 oligomerization. This study identifies AIM2 as an important inflammasome component that senses potentially dangerous cytoplasmic DNA, leading to activation of the ASC pyroptosome and caspase-1.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2862225/" 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/PMC2862225/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fernandes-Alnemri, Teresa -- Yu, Je-Wook -- Datta, Pinaki -- Wu, Jianghong -- Alnemri, Emad S -- AG14357/AG/NIA NIH HHS/ -- AR055398/AR/NIAMS NIH HHS/ -- R01 AG014357/AG/NIA NIH HHS/ -- R01 AG014357-11/AG/NIA NIH HHS/ -- R01 AR055398/AR/NIAMS NIH HHS/ -- R01 AR055398-11A2/AR/NIAMS NIH HHS/ -- England -- Nature. 2009 Mar 26;458(7237):509-13. doi: 10.1038/nature07710. Epub 2009 Jan 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, Center for Apoptosis Research, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19158676" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis Regulatory Proteins ; Caspase 1/metabolism ; Cell Death ; Cell Line ; Cytoplasm/*genetics ; Cytoskeletal Proteins/metabolism ; DNA/immunology/*metabolism ; DNA-Binding Proteins ; Enzyme Activation ; Humans ; Inflammation/*metabolism/*pathology ; Mice ; Nuclear Proteins/chemistry/deficiency/genetics/*metabolism ; Protein Binding
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 70
    Publication Date: 2009-09-11
    Description: Despite existing guidelines on access to data and bioresources, good practice is not widespread. A meeting of mouse researchers in Rome proposes ways to promote a culture of sharing.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schofield, Paul N -- Bubela, Tania -- Weaver, Thomas -- Portilla, Lili -- Brown, Stephen D -- Hancock, John M -- Einhorn, David -- Tocchini-Valentini, Glauco -- Hrabe de Angelis, Martin -- Rosenthal, Nadia -- CASIMIR Rome Meeting participants -- 062023/Wellcome Trust/United Kingdom -- 077198/Wellcome Trust/United Kingdom -- MC_U142684171/Medical Research Council/United Kingdom -- England -- Nature. 2009 Sep 10;461(7261):171-3. doi: 10.1038/461171a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, CB2 3EG, UK. PS@mole.bio.cam.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19741686" target="_blank"〉PubMed〈/a〉
    Keywords: *Access to Information ; Animals ; Cell Line ; *Cooperative Behavior ; Guidelines as Topic ; Information Storage and Retrieval ; Licensure ; Mice ; Models, Animal ; *Publishing/standards ; *Research/standards ; Research Design ; Rome ; Technology Transfer
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 71
    facet.materialart.
    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2009-01-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schrope, Mark -- England -- Nature. 2009 Jan 15;457(7227):252-3. doi: 10.1038/457252a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19148075" target="_blank"〉PubMed〈/a〉
    Keywords: Bioterrorism/prevention & control/trends ; Cell Line ; Conservation of Natural Resources/history/trends ; Embryonic Stem Cells/cytology ; Federal Government/*history ; History, 21st Century ; Humans ; Science/economics/*history/trends ; Space Flight/history/trends ; United States
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 72
    Publication Date: 2009-05-22
    Description: Rab GTPases and SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) are evolutionarily conserved essential components of the eukaryotic intracellular transport system. Although pairing of cognate SNAREs is sufficient to fuse membranes in vitro, a complete reconstitution of the Rab-SNARE machinery has never been achieved. Here we report the reconstitution of the early endosomal canine Rab5 GTPase, its key regulators and effectors together with SNAREs into proteoliposomes using a set of 17 recombinant human proteins. These vesicles behave like minimal 'synthetic' endosomes, fusing with purified early endosomes or with each other in vitro. Membrane fusion measured by content-mixing and morphological assays requires the cooperativity between Rab5 effectors and cognate SNAREs which, together, form a more efficient 'core machinery' than SNAREs alone. In reconstituting a fusion mechanism dependent on both a Rab GTPase and SNAREs, our work shows that the two machineries act coordinately to increase the specificity and efficiency of the membrane tethering and fusion process.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ohya, Takeshi -- Miaczynska, Marta -- Coskun, Unal -- Lommer, Barbara -- Runge, Anja -- Drechsel, David -- Kalaidzidis, Yannis -- Zerial, Marino -- England -- Nature. 2009 Jun 25;459(7250):1091-7. doi: 10.1038/nature08107. Epub 2009 May 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01309, Dresden, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19458617" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Cricetinae ; Cytosol/metabolism ; Dogs ; Endosomes/metabolism/*physiology ; Humans ; Membrane Fusion/*physiology ; Microscopy, Electron ; Proteolipids/metabolism/ultrastructure ; Recombinant Proteins/metabolism ; SNARE Proteins/*metabolism ; Vesicular Transport Proteins/metabolism ; rab GTP-Binding Proteins/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 73
    Publication Date: 2009-06-30
    Description: Innate immunity is stimulated not only by viral or bacterial components, but also by non-microbial danger signals (damage-associated molecular patterns). One of the damage-associated molecular patterns is chromosomal DNA that escapes degradation. In programmed cell death and erythropoiesis, DNA from dead cells or nuclei expelled from erythroblasts is digested by DNase II in the macrophages after they are engulfed. DNase II(-/-) (also known as Dnase2a(-/-)) mice suffer from severe anaemia or chronic arthritis due to interferon-beta (IFN-beta) and tumour necrosis factor-alpha (TNF-alpha) produced from the macrophages carrying undigested DNA in a Toll-like receptor (TLR)-independent mechanism. Here we show that Eyes absent 4 (EYA4), originally identified as a co-transcription factor, stimulates the expression of IFN-beta and CXCL10 in response to the undigested DNA of apoptotic cells. EYA4 enhanced the innate immune response against viruses (Newcastle disease virus and vesicular stomatitis virus), and could associate with signalling molecules (IPS-1 (also known as MAVS), STING (TMEM173) and NLRX1). Three groups have previously shown that EYA has phosphatase activity. We found that mouse EYA family members act as a phosphatase for both phosphotyrosine and phosphothreonine. The haloacid dehalogenase domain at the carboxy terminus contained the tyrosine-phosphatase, and the amino-terminal half carried the threonine-phosphatase. Mutations of the threonine-phosphatase, but not the tyrosine-phosphatase, abolished the ability of EYA4 to enhance the innate immune response, suggesting that EYA regulates the innate immune response by modulating the phosphorylation state of signal transducers for the intracellular pathogens.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Okabe, Yasutaka -- Sano, Teruyuki -- Nagata, Shigekazu -- England -- Nature. 2009 Jul 23;460(7254):520-4. doi: 10.1038/nature08138. Epub 2009 Jun 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida-Konoe, Kyoto 606-8501, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19561593" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis ; Cell Line ; Chemokine CXCL10/metabolism ; Gene Expression Regulation/*immunology ; Humans ; Immunity, Innate/*immunology ; Interferon-beta/metabolism ; Membrane Proteins/metabolism ; Mice ; Mitochondrial Proteins/metabolism ; Phosphoprotein Phosphatases/*metabolism ; Signal Transduction ; Trans-Activators/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 74
    Publication Date: 2009-03-20
    Description: For more than 140 years, pollen tube guidance in flowering plants has been thought to be mediated by chemoattractants derived from target ovules. However, there has been no convincing evidence of any particular molecule being the true attractant that actually controls the navigation of pollen tubes towards ovules. Emerging data indicate that two synergid cells on the side of the egg cell emit a diffusible, species-specific signal to attract the pollen tube at the last step of pollen tube guidance. Here we report that secreted, cysteine-rich polypeptides (CRPs) in a subgroup of defensin-like proteins are attractants derived from the synergid cells. We isolated synergid cells of Torenia fournieri, a unique plant with a protruding embryo sac, to identify transcripts encoding secreted proteins as candidate molecules for the chemoattractant(s). We found two CRPs, abundantly and predominantly expressed in the synergid cell, which are secreted to the surface of the egg apparatus. Moreover, they showed activity in vitro to attract competent pollen tubes of their own species and were named as LUREs. Injection of morpholino antisense oligomers against the LUREs impaired pollen tube attraction, supporting the finding that LUREs are the attractants derived from the synergid cells of T. fournieri.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Okuda, Satohiro -- Tsutsui, Hiroki -- Shiina, Keiko -- Sprunck, Stefanie -- Takeuchi, Hidenori -- Yui, Ryoko -- Kasahara, Ryushiro D -- Hamamura, Yuki -- Mizukami, Akane -- Susaki, Daichi -- Kawano, Nao -- Sakakibara, Takashi -- Namiki, Shoko -- Itoh, Kie -- Otsuka, Kurataka -- Matsuzaki, Motomichi -- Nozaki, Hisayoshi -- Kuroiwa, Tsuneyoshi -- Nakano, Akihiko -- Kanaoka, Masahiro M -- Dresselhaus, Thomas -- Sasaki, Narie -- Higashiyama, Tetsuya -- England -- Nature. 2009 Mar 19;458(7236):357-61. doi: 10.1038/nature07882.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8602, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19295610" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Angiosperms/*cytology/drug effects/genetics/*growth & development ; Chemotactic Factors/chemistry/*metabolism/pharmacology/*secretion ; Defensins/chemistry/*metabolism/pharmacology/*secretion ; Expressed Sequence Tags ; Molecular Sequence Data ; Oligonucleotides, Antisense/genetics ; Pollen Tube/drug effects/genetics/*growth & development ; RNA, Plant/antagonists & inhibitors/genetics/metabolism ; Transcription, Genetic
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 75
    Publication Date: 2009-03-06
    Description: An alphabeta T-cell response depends on the recognition of antigen plus major histocompatibility complex (MHC) proteins by its antigen receptor (TCR). The ability of peripheral alphabeta T cells to recognize MHC is at least partly determined by MHC-dependent thymic selection, by which an immature T cell survives only if its TCR can recognize self MHC. This process may allow MHC-reactive TCRs to be selected from a repertoire with completely random and unbiased specificities. However, analysis of thymocytes before positive selection indicated that TCR proteins might have a predetermined ability to bind MHC. Here we show that specific germline-encoded amino acids in the TCR promote 'generic' MHC recognition and control thymic selection. In mice expressing single, rearranged TCR beta-chains, individual mutation of amino acids in the complementarity-determining region (CDR) 2beta to Ala reduced development of the entire TCR repertoire. Altogether, these results show that thymic selection is controlled by germline-encoded MHC contact points in the alphabeta TCR and indicate that the diversity of the peripheral T-cell repertoire is enhanced by this 'built-in' specificity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2679808/" 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/PMC2679808/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Scott-Browne, James P -- White, Janice -- Kappler, John W -- Gapin, Laurent -- Marrack, Philippa -- AI057485/AI/NIAID NIH HHS/ -- AI18785/AI/NIAID NIH HHS/ -- AI22295/AI/NIAID NIH HHS/ -- P01 AI022295/AI/NIAID NIH HHS/ -- P01 AI022295-22/AI/NIAID NIH HHS/ -- P30 CA046934/CA/NCI NIH HHS/ -- P30 CA046934-19/CA/NCI NIH HHS/ -- P30 CA046934-20/CA/NCI NIH HHS/ -- P30 CA046934-21/CA/NCI NIH HHS/ -- R01 AI018785/AI/NIAID NIH HHS/ -- R01 AI018785-26/AI/NIAID NIH HHS/ -- R01 AI057485/AI/NIAID NIH HHS/ -- R01 AI057485-05/AI/NIAID NIH HHS/ -- R21 AI076463/AI/NIAID NIH HHS/ -- R21 AI076463-01A1/AI/NIAID NIH HHS/ -- R56 AI017134/AI/NIAID NIH HHS/ -- R56 AI017134-28/AI/NIAID NIH HHS/ -- T32 AI007405/AI/NIAID NIH HHS/ -- T32 AI007405-17/AI/NIAID NIH HHS/ -- T32 AI007405-18/AI/NIAID NIH HHS/ -- T32 AI07405/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Apr 23;458(7241):1043-6. doi: 10.1038/nature07812. Epub 2009 Mar 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Integrated Department of Immunology, National Jewish Health and University of Colorado Denver, Denver, Colorado 80206, USA. james.scott-browne@ucdenver.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19262510" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acids/*genetics/*metabolism ; Animals ; Bone Marrow/immunology/metabolism ; Cell Line ; Chimera/immunology/metabolism ; Complementarity Determining Regions/chemistry/genetics/immunology ; Germ Cells/*metabolism ; Hybridomas/immunology ; Major Histocompatibility Complex/immunology ; Mice ; Receptors, Antigen, T-Cell, alpha-beta/*chemistry/deficiency/genetics/*immunology ; Thymus Gland/*cytology/*immunology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 76
    facet.materialart.
    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2009-07-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wadman, Meredith -- England -- Nature. 2009 Jul 9;460(7252):156-7. doi: 10.1038/460156a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19587729" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line ; *Embryo Research ; *Guidelines as Topic ; Humans ; *National Institutes of Health (U.S.) ; Registries ; *Stem Cells/cytology ; United States
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 77
    Publication Date: 2009-10-16
    Description: DNA cytosine methylation is a central epigenetic modification that has essential roles in cellular processes including genome regulation, development and disease. Here we present the first genome-wide, single-base-resolution maps of methylated cytosines in a mammalian genome, from both human embryonic stem cells and fetal fibroblasts, along with comparative analysis of messenger RNA and small RNA components of the transcriptome, several histone modifications, and sites of DNA-protein interaction for several key regulatory factors. Widespread differences were identified in the composition and patterning of cytosine methylation between the two genomes. Nearly one-quarter of all methylation identified in embryonic stem cells was in a non-CG context, suggesting that embryonic stem cells may use different methylation mechanisms to affect gene regulation. Methylation in non-CG contexts showed enrichment in gene bodies and depletion in protein binding sites and enhancers. Non-CG methylation disappeared upon induced differentiation of the embryonic stem cells, and was restored in induced pluripotent stem cells. We identified hundreds of differentially methylated regions proximal to genes involved in pluripotency and differentiation, and widespread reduced methylation levels in fibroblasts associated with lower transcriptional activity. These reference epigenomes provide a foundation for future studies exploring this key epigenetic modification in human disease and development.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2857523/" 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/PMC2857523/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lister, Ryan -- Pelizzola, Mattia -- Dowen, Robert H -- Hawkins, R David -- Hon, Gary -- Tonti-Filippini, Julian -- Nery, Joseph R -- Lee, Leonard -- Ye, Zhen -- Ngo, Que-Minh -- Edsall, Lee -- Antosiewicz-Bourget, Jessica -- Stewart, Ron -- Ruotti, Victor -- Millar, A Harvey -- Thomson, James A -- Ren, Bing -- Ecker, Joseph R -- R01 HG003523/HG/NHGRI NIH HHS/ -- R01 HG003523-01/HG/NHGRI NIH HHS/ -- R01 HG003523-02/HG/NHGRI NIH HHS/ -- R01 HG003523-03/HG/NHGRI NIH HHS/ -- U01 1U01ES017166-01/ES/NIEHS NIH HHS/ -- U01 ES017166/ES/NIEHS NIH HHS/ -- England -- Nature. 2009 Nov 19;462(7271):315-22. doi: 10.1038/nature08514. Epub 2009 Oct 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19829295" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line ; Cluster Analysis ; DNA/metabolism ; *DNA Methylation ; DNA-Binding Proteins/metabolism ; Embryonic Stem Cells/metabolism ; *Epigenesis, Genetic ; Genome/*genetics ; Humans
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 78
    facet.materialart.
    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2009-04-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wadman, Meredith -- England -- Nature. 2009 Apr 23;458(7241):950-1. doi: 10.1038/458950a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19396105" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line ; Embryo Research/economics/*legislation & jurisprudence ; *Embryonic Stem Cells ; *Federal Government ; Female ; *Guidelines as Topic/standards ; Humans ; Male ; National Institutes of Health (U.S.)/*legislation & jurisprudence ; United States
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 79
    Publication Date: 2009-04-28
    Description: Dengue fever is the most frequent arthropod-borne viral disease of humans, with almost half of the world's population at risk of infection. The high prevalence, lack of an effective vaccine, and absence of specific treatment conspire to make dengue fever a global public health threat. Given their compact genomes, dengue viruses (DENV-1-4) and other flaviviruses probably require an extensive number of host factors; however, only a limited number of human, and an even smaller number of insect host factors, have been identified. Here we identify insect host factors required for DENV-2 propagation, by carrying out a genome-wide RNA interference screen in Drosophila melanogaster cells using a well-established 22,632 double-stranded RNA library. This screen identified 116 candidate dengue virus host factors (DVHFs). Although some were previously associated with flaviviruses (for example, V-ATPases and alpha-glucosidases), most of the DVHFs were newly implicated in dengue virus propagation. The dipteran DVHFs had 82 readily recognizable human homologues and, using a targeted short-interfering-RNA screen, we showed that 42 of these are human DVHFs. This indicates notable conservation of required factors between dipteran and human hosts. This work suggests new approaches to control infection in the insect vector and the mammalian host.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3462662/" 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/PMC3462662/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sessions, October M -- Barrows, Nicholas J -- Souza-Neto, Jayme A -- Robinson, Timothy J -- Hershey, Christine L -- Rodgers, Mary A -- Ramirez, Jose L -- Dimopoulos, George -- Yang, Priscilla L -- Pearson, James L -- Garcia-Blanco, Mariano A -- 1R01AI061576-01/AI/NIAID NIH HHS/ -- 1R01AI076442/AI/NIAID NIH HHS/ -- 1SA0RR024572-1/RR/NCRR NIH HHS/ -- 5P30-CA14236/CA/NCI NIH HHS/ -- 5U54-AI057157-05S/AI/NIAID NIH HHS/ -- R01 AI076442/AI/NIAID NIH HHS/ -- R01 AI078997/AI/NIAID NIH HHS/ -- R01 AI078997-01A1/AI/NIAID NIH HHS/ -- R01 AI078997-02/AI/NIAID NIH HHS/ -- R01 GM067761/GM/NIGMS NIH HHS/ -- R21 AI090188/AI/NIAID NIH HHS/ -- R21 AI090188-01/AI/NIAID NIH HHS/ -- R21 NS063845/NS/NINDS NIH HHS/ -- R21-AI64925/AI/NIAID NIH HHS/ -- T32 AI007417/AI/NIAID NIH HHS/ -- U54 AI057157/AI/NIAID NIH HHS/ -- U54 AI057159/AI/NIAID NIH HHS/ -- England -- Nature. 2009 Apr 23;458(7241):1047-50. doi: 10.1038/nature07967.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19396146" target="_blank"〉PubMed〈/a〉
    Keywords: Aedes/genetics/virology ; Animals ; Cell Line ; Conserved Sequence/*genetics/physiology ; Dengue Virus/*physiology ; Drosophila melanogaster/*genetics/physiology/*virology ; Gene Knockdown Techniques ; Genome, Insect/genetics ; Host-Pathogen Interactions/*genetics ; Humans ; Insect Vectors/*genetics/*physiology ; RNA Interference ; RNA, Double-Stranded/genetics/metabolism ; Virus Replication
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 80
    Publication Date: 2009-01-23
    Description: The innate immune system senses nucleic acids by germline-encoded pattern recognition receptors. RNA is sensed by Toll-like receptor members TLR3, TLR7 and TLR8, or by the RNA helicases RIG-I (also known as DDX58) and MDA-5 (IFIH1). Little is known about sensors for cytoplasmic DNA that trigger antiviral and/or inflammatory responses. The best characterized of these responses involves activation of the TANK-binding kinase (TBK1)-interferon regulatory factor 3 (IRF3) signalling axis to trigger transcriptional induction of type I interferon genes. A second, less well-defined pathway leads to the activation of an 'inflammasome' that, via caspase-1, controls the catalytic cleavage of the pro-forms of the cytokines IL1beta and IL18 (refs 6, 7). Using mouse and human cells, here we identify the PYHIN (pyrin and HIN domain-containing protein) family member absent in melanoma 2 (AIM2) as a receptor for cytosolic DNA, which regulates caspase-1. The HIN200 domain of AIM2 binds to DNA, whereas the pyrin domain (but not that of the other PYHIN family members) associates with the adaptor molecule ASC (apoptosis-associated speck-like protein containing a caspase activation and recruitment domain) to activate both NF-kappaB and caspase-1. Knockdown of Aim2 abrogates caspase-1 activation in response to cytoplasmic double-stranded DNA and the double-stranded DNA vaccinia virus. Collectively, these observations identify AIM2 as a new receptor for cytoplasmic DNA, which forms an inflammasome with the ligand and ASC to activate caspase-1.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2726264/" 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/PMC2726264/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hornung, Veit -- Ablasser, Andrea -- Charrel-Dennis, Marie -- Bauernfeind, Franz -- Horvath, Gabor -- Caffrey, Daniel R -- Latz, Eicke -- Fitzgerald, Katherine A -- AI-065483/AI/NIAID NIH HHS/ -- AI-067497/AI/NIAID NIH HHS/ -- R01 AI067497/AI/NIAID NIH HHS/ -- R01 AI067497-03/AI/NIAID NIH HHS/ -- R01 AI067497-04/AI/NIAID NIH HHS/ -- R01 AI067497-05/AI/NIAID NIH HHS/ -- England -- Nature. 2009 Mar 26;458(7237):514-8. doi: 10.1038/nature07725. Epub 2009 Jan 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA. veit.hornung@uni-bonn.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19158675" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis Regulatory Proteins ; Caspase 1/*metabolism ; Cell Death ; Cell Line ; Cytoskeletal Proteins/genetics/*metabolism ; Cytosol/*metabolism ; DNA/immunology/*metabolism ; DNA-Binding Proteins ; Enzyme Activation ; Humans ; Inflammation/enzymology/*metabolism/pathology ; Mice ; Nuclear Proteins/chemistry/genetics/*metabolism ; Poly dA-dT/immunology ; Protein Binding ; Vaccinia virus/immunology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 81
    Publication Date: 2009-07-03
    Description: Stem cells are controlled, in part, by genetic pathways frequently dysregulated during human tumorigenesis. Either stimulation of Wnt/beta-catenin signalling or overexpression of telomerase is sufficient to activate quiescent epidermal stem cells in vivo, although the mechanisms by which telomerase exerts these effects are not understood. Here we show that telomerase directly modulates Wnt/beta-catenin signalling by serving as a cofactor in a beta-catenin transcriptional complex. The telomerase protein component TERT (telomerase reverse transcriptase) interacts with BRG1 (also called SMARCA4), a SWI/SNF-related chromatin remodelling protein, and activates Wnt-dependent reporters in cultured cells and in vivo. TERT serves an essential role in formation of the anterior-posterior axis in Xenopus laevis embryos, and this defect in Wnt signalling manifests as homeotic transformations in the vertebrae of Tert(-/-) mice. Chromatin immunoprecipitation of the endogenous TERT protein from mouse gastrointestinal tract shows that TERT physically occupies gene promoters of Wnt-dependent genes. These data reveal an unanticipated role for telomerase as a transcriptional modulator of the Wnt/beta-catenin signalling pathway.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4349391/" 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/PMC4349391/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Park, Jae-Il -- Venteicher, Andrew S -- Hong, Ji Yeon -- Choi, Jinkuk -- Jun, Sohee -- Shkreli, Marina -- Chang, Woody -- Meng, Zhaojing -- Cheung, Peggie -- Ji, Hong -- McLaughlin, Margaret -- Veenstra, Timothy D -- Nusse, Roel -- McCrea, Pierre D -- Artandi, Steven E -- CA111691/CA/NCI NIH HHS/ -- CA125453/CA/NCI NIH HHS/ -- P30 CA124435/CA/NCI NIH HHS/ -- R01 CA111691/CA/NCI NIH HHS/ -- R01 CA125453/CA/NCI NIH HHS/ -- England -- Nature. 2009 Jul 2;460(7251):66-72. doi: 10.1038/nature08137.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19571879" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Choristoma/genetics/pathology ; Chromatin/*genetics ; DNA Helicases/metabolism ; Genes, Reporter/genetics ; HeLa Cells ; Humans ; Intestine, Small/metabolism ; Mice ; Nuclear Proteins/metabolism ; Oocytes/cytology/growth & development ; Plasmids/genetics ; Promoter Regions, Genetic/genetics ; *Signal Transduction ; Somites/abnormalities/embryology ; Telomerase/*metabolism ; Transcription Factors/metabolism ; Wnt Proteins/genetics/*metabolism ; Wnt3 Protein ; Xenopus laevis/embryology ; beta Catenin/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 82
    Publication Date: 2009-06-19
    Description: Macrophages are aptly positioned to function as the primary line of defence against invading pathogens in many organs, including the lung and peritoneum. Their ability to phagocytose and clear microorganisms has been well documented. Macrophages possess several substances with which they can kill bacteria, including reactive oxygen species, nitric oxide, and antimicrobial proteins. We proposed that macrophage-derived proteinases may contribute to the antimicrobial properties of macrophages. Macrophage elastase (also known as matrix metalloproteinase 12 or MMP12) is an enzyme predominantly expressed in mature tissue macrophages and is implicated in several disease processes, including emphysema. Physiological functions for MMP12 have not been described. Here we show that Mmp12(-/-) mice exhibit impaired bacterial clearance and increased mortality when challenged with both gram-negative and gram-positive bacteria at macrophage-rich portals of entry, such as the peritoneum and lung. Intracellular stores of MMP12 are mobilized to macrophage phagolysosomes after the ingestion of bacterial pathogens. Once inside phagolysosomes, MMP12 adheres to bacterial cell walls where it disrupts cellular membranes resulting in bacterial death. The antimicrobial properties of MMP12 do not reside within its catalytic domain, but rather within the carboxy-terminal domain. This domain contains a unique four amino acid sequence on an exposed beta loop of the protein that is required for the observed antimicrobial activity. The present study represents, to our knowledge, the first report of direct antimicrobial activity by a matrix metallopeptidase, and describes a new antimicrobial peptide that is sequentially and structurally unique in nature.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2885871/" 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/PMC2885871/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Houghton, A McGarry -- Hartzell, William O -- Robbins, Clinton S -- Gomis-Ruth, F Xavier -- Shapiro, Steven D -- R01 HL082541/HL/NHLBI NIH HHS/ -- R01 HL082541-01/HL/NHLBI NIH HHS/ -- England -- Nature. 2009 Jul 30;460(7255):637-41. doi: 10.1038/nature08181. Epub 2009 Jun 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA. houghtonm@dom.pitt.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19536155" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Anti-Bacterial Agents/pharmacology ; Bacterial Infections/*enzymology ; *Bacterial Physiological Phenomena ; Humans ; Kaplan-Meier Estimate ; Klebsiella pneumoniae/drug effects ; Macrophages/*enzymology/*microbiology ; Matrix Metalloproteinase 12/chemistry/genetics/*metabolism/pharmacology ; Mice ; Mice, Knockout ; Models, Molecular ; Molecular Sequence Data ; Protein Structure, Tertiary ; Staphylococcus aureus/drug effects
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 83
    facet.materialart.
    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2009-03-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wadman, Meredith -- England -- Nature. 2009 Feb 26;457(7233):1068. doi: 10.1038/4571068a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19256078" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line ; Embryo Research/*economics/*legislation & jurisprudence ; *Embryonic Stem Cells ; *Federal Government ; Humans ; United States
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 84
    Publication Date: 2009-08-25
    Description: The ability of cells to sense and respond to mechanical force underlies diverse processes such as touch and hearing in animals, gravitropism in plants, and bacterial osmoregulation. In bacteria, mechanosensation is mediated by the mechanosensitive channels of large (MscL), small (MscS), potassium-dependent (MscK) and mini (MscM) conductances. These channels act as 'emergency relief valves' protecting bacteria from lysis upon acute osmotic down-shock. Among them, MscL has been intensively studied since the original identification and characterization 15 years ago. MscL is reversibly and directly gated by changes in membrane tension. In the open state, MscL forms a non-selective 3 nS conductance channel which gates at tensions close to the lytic limit of the bacterial membrane. An earlier crystal structure at 3.5 A resolution of a pentameric MscL from Mycobacterium tuberculosis represents a closed-state or non-conducting conformation. MscL has a complex gating behaviour; it exhibits several intermediates between the closed and open states, including one putative non-conductive expanded state and at least three sub-conducting states. Although our understanding of the closed and open states of MscL has been increasing, little is known about the structures of the intermediate states despite their importance in elucidating the complete gating process of MscL. Here we present the crystal structure of a carboxy-terminal truncation mutant (Delta95-120) of MscL from Staphylococcus aureus (SaMscL(CDelta26)) at 3.8 A resolution. Notably, SaMscL(CDelta26) forms a tetrameric channel with both transmembrane helices tilted away from the membrane normal at angles close to that inferred for the open state, probably corresponding to a non-conductive but partially expanded intermediate state.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2737600/" 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/PMC2737600/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Zhenfeng -- Gandhi, Chris S -- Rees, Douglas C -- GM084211/GM/NIGMS NIH HHS/ -- R01 GM084211/GM/NIGMS NIH HHS/ -- R01 GM084211-01/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Sep 3;461(7260):120-4. doi: 10.1038/nature08277. Epub 2009 Aug 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19701184" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacterial Proteins/*chemistry/metabolism ; Crystallography, X-Ray ; Ion Channel Gating ; Ion Channels/*chemistry/metabolism ; Models, Biological ; Models, Molecular ; Molecular Sequence Data ; Mycobacterium tuberculosis/chemistry/metabolism ; Pressure ; Protein Structure, Quaternary ; Staphylococcus aureus/*chemistry ; Structural Homology, Protein
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 85
    Publication Date: 2009-10-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lo, Bernard -- Conklin, Bruce R -- England -- Nature. 2009 Oct 1;461(7264):593. doi: 10.1038/461593b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19794473" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Animals ; Cell Line ; Humans ; Informed Consent/*standards ; Male ; *Pluripotent Stem Cells/cytology/transplantation ; Testis/cytology ; *Tissue Donors
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 86
    Publication Date: 2009-11-06
    Description: Genomes are organized into high-level three-dimensional structures, and DNA elements separated by long genomic distances can in principle interact functionally. Many transcription factors bind to regulatory DNA elements distant from gene promoters. Although distal binding sites have been shown to regulate transcription by long-range chromatin interactions at a few loci, chromatin interactions and their impact on transcription regulation have not been investigated in a genome-wide manner. Here we describe the development of a new strategy, chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) for the de novo detection of global chromatin interactions, with which we have comprehensively mapped the chromatin interaction network bound by oestrogen receptor alpha (ER-alpha) in the human genome. We found that most high-confidence remote ER-alpha-binding sites are anchored at gene promoters through long-range chromatin interactions, suggesting that ER-alpha functions by extensive chromatin looping to bring genes together for coordinated transcriptional regulation. We propose that chromatin interactions constitute a primary mechanism for regulating transcription in mammalian genomes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2774924/" 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/PMC2774924/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fullwood, Melissa J -- Liu, Mei Hui -- Pan, You Fu -- Liu, Jun -- Xu, Han -- Mohamed, Yusoff Bin -- Orlov, Yuriy L -- Velkov, Stoyan -- Ho, Andrea -- Mei, Poh Huay -- Chew, Elaine G Y -- Huang, Phillips Yao Hui -- Welboren, Willem-Jan -- Han, Yuyuan -- Ooi, Hong Sain -- Ariyaratne, Pramila N -- Vega, Vinsensius B -- Luo, Yanquan -- Tan, Peck Yean -- Choy, Pei Ye -- Wansa, K D Senali Abayratna -- Zhao, Bing -- Lim, Kar Sian -- Leow, Shi Chi -- Yow, Jit Sin -- Joseph, Roy -- Li, Haixia -- Desai, Kartiki V -- Thomsen, Jane S -- Lee, Yew Kok -- Karuturi, R Krishna Murthy -- Herve, Thoreau -- Bourque, Guillaume -- Stunnenberg, Hendrik G -- Ruan, Xiaoan -- Cacheux-Rataboul, Valere -- Sung, Wing-Kin -- Liu, Edison T -- Wei, Chia-Lin -- Cheung, Edwin -- Ruan, Yijun -- 1U54HG004557-01/HG/NHGRI NIH HHS/ -- R01 HG004456/HG/NHGRI NIH HHS/ -- R01 HG004456-01/HG/NHGRI NIH HHS/ -- R01 HG004456-02/HG/NHGRI NIH HHS/ -- R01 HG004456-03/HG/NHGRI NIH HHS/ -- R01HG003521-01/HG/NHGRI NIH HHS/ -- R01HG004456-01/HG/NHGRI NIH HHS/ -- U54 HG004557/HG/NHGRI NIH HHS/ -- U54 HG004557-01/HG/NHGRI NIH HHS/ -- U54 HG004557-02/HG/NHGRI NIH HHS/ -- U54 HG004557-03/HG/NHGRI NIH HHS/ -- U54 HG004557-04/HG/NHGRI NIH HHS/ -- England -- Nature. 2009 Nov 5;462(7269):58-64. doi: 10.1038/nature08497.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore 138672.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19890323" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Cell Line ; Chromatin/*genetics/*metabolism ; Chromatin Immunoprecipitation ; Cross-Linking Reagents ; Estrogen Receptor alpha/*metabolism ; Formaldehyde ; Genome, Human/*genetics ; Humans ; Promoter Regions, Genetic/genetics ; Protein Binding ; Reproducibility of Results ; Sequence Analysis, DNA ; Transcription, Genetic ; Transcriptional Activation
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 87
    Publication Date: 2009-12-18
    Description: DNA double-strand breaks (DSBs) are highly cytotoxic lesions that are generated by ionizing radiation and various DNA-damaging chemicals. Following DSB formation, cells activate the DNA-damage response (DDR) protein kinases ATM, ATR and DNA-PK (also known as PRKDC). These then trigger histone H2AX (also known as H2AFX) phosphorylation and the accumulation of proteins such as MDC1, 53BP1 (also known as TP53BP1), BRCA1, CtIP (also known as RBBP8), RNF8 and RNF168/RIDDLIN into ionizing radiation-induced foci (IRIF) that amplify DSB signalling and promote DSB repair. Attachment of small ubiquitin-related modifier (SUMO) to target proteins controls diverse cellular functions. Here, we show that SUMO1, SUMO2 and SUMO3 accumulate at DSB sites in mammalian cells, with SUMO1 and SUMO2/3 accrual requiring the E3 ligase enzymes PIAS4 and PIAS1. We also establish that PIAS1 and PIAS4 are recruited to damage sites via mechanisms requiring their SAP domains, and are needed for the productive association of 53BP1, BRCA1 and RNF168 with such regions. Furthermore, we show that PIAS1 and PIAS4 promote DSB repair and confer ionizing radiation resistance. Finally, we establish that PIAS1 and PIAS4 are required for effective ubiquitin-adduct formation mediated by RNF8, RNF168 and BRCA1 at sites of DNA damage. These findings thus identify PIAS1 and PIAS4 as components of the DDR and reveal how protein recruitment to DSB sites is controlled by coordinated SUMOylation and ubiquitylation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2904806/" 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/PMC2904806/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Galanty, Yaron -- Belotserkovskaya, Rimma -- Coates, Julia -- Polo, Sophie -- Miller, Kyle M -- Jackson, Stephen P -- 086861/Wellcome Trust/United Kingdom -- 11224/Cancer Research UK/United Kingdom -- A5290/Cancer Research UK/United Kingdom -- Cancer Research UK/United Kingdom -- England -- Nature. 2009 Dec 17;462(7275):935-9. doi: 10.1038/nature08657.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Wellcome Trust and Cancer Research UK Gurdon Institute, and Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20016603" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; BRCA1 Protein/metabolism ; Cell Line ; Cell Line, Tumor ; *DNA Breaks, Double-Stranded ; *DNA Repair ; DNA-Binding Proteins/genetics/metabolism ; Fluorescence Recovery After Photobleaching ; Humans ; Intracellular Signaling Peptides and Proteins/genetics/metabolism ; Models, Biological ; Phosphorylation ; Protein Inhibitors of Activated STAT/chemistry/genetics/*metabolism ; Protein Structure, Tertiary ; Replication Protein A/metabolism ; Small Ubiquitin-Related Modifier Proteins/genetics/*metabolism ; Ubiquitin-Conjugating Enzymes/genetics/metabolism ; Ubiquitin-Protein Ligases/metabolism ; Ubiquitination
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 88
    Publication Date: 2009-08-28
    Description: Cyanobacteria of the Synechococcus and Prochlorococcus genera are important contributors to photosynthetic productivity in the open oceans. Recently, core photosystem II (PSII) genes were identified in cyanophages and proposed to function in photosynthesis and in increasing viral fitness by supplementing the host production of these proteins. Here we show evidence for the presence of photosystem I (PSI) genes in the genomes of viruses that infect these marine cyanobacteria, using pre-existing metagenomic data from the global ocean sampling expedition as well as from viral biomes. The seven cyanobacterial core PSI genes identified in this study, psaA, B, C, D, E, K and a unique J and F fusion, form a cluster in cyanophage genomes, suggestive of selection for a distinct function in the virus life cycle. The existence of this PSI cluster was confirmed with overlapping and long polymerase chain reaction on environmental DNA from the Northern Line Islands. Potentially, the seven proteins encoded by the viral genes are sufficient to form an intact monomeric PSI complex. Projection of viral predicted peptides on the cyanobacterial PSI crystal structure suggested that the viral-PSI components might provide a unique way of funnelling reducing power from respiratory and other electron transfer chains to the PSI.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4605144/" 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/PMC4605144/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sharon, Itai -- Alperovitch, Ariella -- Rohwer, Forest -- Haynes, Matthew -- Glaser, Fabian -- Atamna-Ismaeel, Nof -- Pinter, Ron Y -- Partensky, Frederic -- Koonin, Eugene V -- Wolf, Yuri I -- Nelson, Nathan -- Beja, Oded -- Z99 LM999999/Intramural NIH HHS/ -- England -- Nature. 2009 Sep 10;461(7261):258-62. doi: 10.1038/nature08284. Epub 2009 Aug 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Faculty of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19710652" target="_blank"〉PubMed〈/a〉
    Keywords: Adhesins, Bacterial/chemistry/genetics ; Amino Acid Sequence ; Bacteriophages/*genetics/metabolism ; Biodiversity ; Genes, Bacterial/genetics ; Genes, Viral/*genetics ; Genome, Bacterial/genetics ; Genome, Viral/*genetics ; Geography ; Lipoproteins/chemistry/genetics ; Models, Molecular ; Molecular Sequence Data ; Oceans and Seas ; Open Reading Frames/genetics ; Oxidation-Reduction ; Photosynthesis/genetics ; Photosystem I Protein Complex/chemistry/*genetics ; Phylogeny ; Polymerase Chain Reaction ; Prochlorococcus/*virology ; Protein Conformation ; Seawater/*microbiology ; Synechococcus/*virology ; Viral Proteins/chemistry/genetics/metabolism ; Water Microbiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 89
    Publication Date: 2009-09-18
    Description: The stability of the Wnt pathway transcription factor beta-catenin is tightly regulated by the multi-subunit destruction complex. Deregulated Wnt pathway activity has been implicated in many cancers, making this pathway an attractive target for anticancer therapies. However, the development of targeted Wnt pathway inhibitors has been hampered by the limited number of pathway components that are amenable to small molecule inhibition. Here, we used a chemical genetic screen to identify a small molecule, XAV939, which selectively inhibits beta-catenin-mediated transcription. XAV939 stimulates beta-catenin degradation by stabilizing axin, the concentration-limiting component of the destruction complex. Using a quantitative chemical proteomic approach, we discovered that XAV939 stabilizes axin by inhibiting the poly-ADP-ribosylating enzymes tankyrase 1 and tankyrase 2. Both tankyrase isoforms interact with a highly conserved domain of axin and stimulate its degradation through the ubiquitin-proteasome pathway. Thus, our study provides new mechanistic insights into the regulation of axin protein homeostasis and presents new avenues for targeted Wnt pathway therapies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Huang, Shih-Min A -- Mishina, Yuji M -- Liu, Shanming -- Cheung, Atwood -- Stegmeier, Frank -- Michaud, Gregory A -- Charlat, Olga -- Wiellette, Elizabeth -- Zhang, Yue -- Wiessner, Stephanie -- Hild, Marc -- Shi, Xiaoying -- Wilson, Christopher J -- Mickanin, Craig -- Myer, Vic -- Fazal, Aleem -- Tomlinson, Ronald -- Serluca, Fabrizio -- Shao, Wenlin -- Cheng, Hong -- Shultz, Michael -- Rau, Christina -- Schirle, Markus -- Schlegl, Judith -- Ghidelli, Sonja -- Fawell, Stephen -- Lu, Chris -- Curtis, Daniel -- Kirschner, Marc W -- Lengauer, Christoph -- Finan, Peter M -- Tallarico, John A -- Bouwmeester, Tewis -- Porter, Jeffery A -- Bauer, Andreas -- Cong, Feng -- England -- Nature. 2009 Oct 1;461(7264):614-20. doi: 10.1038/nature08356. Epub 2009 Sep 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Novartis Institutes for Biomedical Research, 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19759537" target="_blank"〉PubMed〈/a〉
    Keywords: Axin Protein ; Cell Division/drug effects ; Cell Line ; Cell Line, Tumor ; Colorectal Neoplasms/drug therapy/metabolism ; Heterocyclic Compounds, 3-Ring/pharmacology ; Humans ; Proteasome Endopeptidase Complex/metabolism ; Protein Binding ; Proteomics ; Repressor Proteins/chemistry/*metabolism ; Signal Transduction/*drug effects ; Tankyrases/*antagonists & inhibitors/metabolism ; Transcription, Genetic/drug effects ; Ubiquitin/metabolism ; Ubiquitination ; Wnt Proteins/*antagonists & inhibitors/metabolism ; beta Catenin/antagonists & inhibitors/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 90
    Publication Date: 2009-02-24
    Description: Life and death fate decisions allow cells to avoid massive apoptotic death in response to genotoxic stress. Although the regulatory mechanisms and signalling pathways controlling DNA repair and apoptosis are well characterized, the precise molecular strategies that determine the ultimate choice of DNA repair and survival or apoptotic cell death remain incompletely understood. Here we report that a protein tyrosine phosphatase, EYA, is involved in promoting efficient DNA repair rather than apoptosis in response to genotoxic stress in mammalian embryonic kidney cells by executing a damage-signal-dependent dephosphorylation of an H2AX carboxy-terminal tyrosine phosphate (Y142). This post-translational modification determines the relative recruitment of either DNA repair or pro-apoptotic factors to the tail of serine phosphorylated histone H2AX (gamma-H2AX) and allows it to function as an active determinant of repair/survival versus apoptotic responses to DNA damage, revealing an additional phosphorylation-dependent mechanism that modulates survival/apoptotic decisions during mammalian organogenesis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2692521/" 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/PMC2692521/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cook, Peter J -- Ju, Bong Gun -- Telese, Francesca -- Wang, Xiangting -- Glass, Christopher K -- Rosenfeld, Michael G -- R01 CA097134/CA/NCI NIH HHS/ -- R01 CA097134-06A1/CA/NCI NIH HHS/ -- R01 CA097134-07/CA/NCI NIH HHS/ -- R01 DK039949/DK/NIDDK NIH HHS/ -- R01 DK039949-17S1/DK/NIDDK NIH HHS/ -- R01 DK039949-18/DK/NIDDK NIH HHS/ -- R01 HL065445/HL/NHLBI NIH HHS/ -- R01 HL065445-08/HL/NHLBI NIH HHS/ -- R01 HL065445-09/HL/NHLBI NIH HHS/ -- R01 NS034934/NS/NINDS NIH HHS/ -- R01 NS034934-18/NS/NINDS NIH HHS/ -- R01 NS034934-19/NS/NINDS NIH HHS/ -- R01 NS034934-20A1/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Apr 2;458(7238):591-6. doi: 10.1038/nature07849. Epub 2009 Feb 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute School of Medicine, University of California, San Diego, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19234442" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Apoptosis ; Ataxia Telangiectasia Mutated Proteins ; Cell Cycle Proteins/metabolism ; Cell Line ; Cell Survival ; DNA Damage ; DNA Repair ; DNA-Binding Proteins/deficiency/genetics/metabolism ; Histones/deficiency/genetics/*metabolism ; Humans ; Intracellular Signaling Peptides and Proteins/deficiency/genetics/metabolism ; Mice ; Nuclear Proteins/deficiency/genetics/metabolism ; Phosphorylation ; Phosphotyrosine/metabolism ; Protein Binding ; Protein Tyrosine Phosphatases/deficiency/genetics/metabolism ; Protein-Serine-Threonine Kinases/metabolism ; Substrate Specificity ; Tumor Suppressor Proteins/metabolism ; Tyrosine/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 91
    Publication Date: 2009-09-01
    Description: A long-sought goal in structural biology has been the imaging of membrane proteins in their membrane environments. This goal has been achieved with electron crystallography in those special cases where a protein forms highly ordered arrays in lipid bilayers. It has also been achieved by NMR methods in proteins up to 50 kilodaltons (kDa) in size, although milligram quantities of protein and isotopic labelling are required. For structural analysis of large soluble proteins in microgram quantities, an increasingly powerful method that does not require crystallization is single-particle reconstruction from electron microscopy of cryogenically cooled samples (electron cryomicroscopy (cryo-EM)). Here we report the first single-particle cryo-EM study of a membrane protein, the human large-conductance calcium- and voltage-activated potassium channel (BK), in a lipid environment. The new method is called random spherically constrained (RSC) single-particle reconstruction. BK channels, members of the six-transmembrane-segment (6TM) ion channel family, were reconstituted at low density into lipid vesicles (liposomes), and their function was verified by a potassium flux assay. Vesicles were also frozen in vitreous ice and imaged in an electron microscope. From images of 8,400 individual protein particles, a three-dimensional (3D) reconstruction of the BK channel and its membrane environment was obtained at a resolution of 1.7-2.0 nm. Not requiring the formation of crystals, the RSC approach promises to be useful in the structural study of many other membrane proteins as well.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2797367/" 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/PMC2797367/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Liguo -- Sigworth, Fred J -- P01 GM062580/GM/NIGMS NIH HHS/ -- P01 GM062580-06A10007/GM/NIGMS NIH HHS/ -- P01 GM062580-070007/GM/NIGMS NIH HHS/ -- P01 GM062580-080007/GM/NIGMS NIH HHS/ -- R01 NS021501/NS/NINDS NIH HHS/ -- R01 NS021501-19/NS/NINDS NIH HHS/ -- R01 NS021501-19S1/NS/NINDS NIH HHS/ -- R01 NS021501-20/NS/NINDS NIH HHS/ -- R01 NS021501-21/NS/NINDS NIH HHS/ -- R01 NS021501-22/NS/NINDS NIH HHS/ -- R01 NS021501-23/NS/NINDS NIH HHS/ -- R01 NS021501-24/NS/NINDS NIH HHS/ -- S10 RR014739/RR/NCRR NIH HHS/ -- S10 RR014739-01/RR/NCRR NIH HHS/ -- S10 RR014739-018020/RR/NCRR NIH HHS/ -- England -- Nature. 2009 Sep 10;461(7261):292-5. doi: 10.1038/nature08291. Epub 2009 Aug 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Physiology, Yale University, 333 Cedar Street, New Haven, Connecticut 06520, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19718020" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line ; Cryoelectron Microscopy/*methods ; Humans ; Ion Channel Gating ; Large-Conductance Calcium-Activated Potassium Channel alpha ; Subunits/*chemistry/genetics/metabolism/*ultrastructure ; Liposomes/chemistry/*metabolism ; Membrane Lipids/*metabolism ; Membrane Potentials ; Models, Molecular ; Potassium/metabolism ; Protein Structure, Tertiary ; Proteolipids/chemistry/metabolism ; Substrate Specificity
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 92
    Publication Date: 2009-04-17
    Description: Annual plants complete their life cycle in one year and initiate flowering only once, whereas perennials live for many years and flower repeatedly. How perennials undergo repeated cycles of vegetative growth and flowering that are synchronized to the changing seasons has not been extensively studied. Flowering is best understood in annual Arabidopsis thaliana, but many closely related species, such as Arabis alpina, are perennials. We identified the A. alpina mutant perpetual flowering 1 (pep1), and showed that PEP1 contributes to three perennial traits. It limits the duration of flowering, facilitating a return to vegetative development, prevents some branches from undergoing the floral transition allowing polycarpic growth habit, and confers a flowering response to winter temperatures that restricts flowering to spring. Here we show that PEP1 is the orthologue of the A. thaliana gene FLOWERING LOCUS C (FLC). The FLC transcription factor inhibits flowering until A. thaliana is exposed to winter temperatures, which trigger chromatin modifications that stably repress FLC transcription. In contrast, PEP1 is only transiently repressed by low temperatures, causing repeated seasonal cycles of repression and activation of PEP1 transcription that allow it to carry out functions characteristic of the cyclical life history of perennials. The patterns of chromatin modifications at FLC and PEP1 differ correlating with their distinct expression patterns. Thus we describe a critical mechanism by which flowering regulation differs between related perennial and annual species, and propose that differences in chromatin regulation contribute to this variation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Renhou -- Farrona, Sara -- Vincent, Coral -- Joecker, Anika -- Schoof, Heiko -- Turck, Franziska -- Alonso-Blanco, Carlos -- Coupland, George -- Albani, Maria C -- England -- Nature. 2009 May 21;459(7245):423-7. doi: 10.1038/nature07988. Epub 2009 Apr 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max Planck Institute for Plant Breeding Research, Carl von Linne Weg 10, D-50829 Cologne, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19369938" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/genetics ; Arabidopsis Proteins/genetics ; Arabis/anatomy & histology/genetics/*growth & development ; Chromatin/genetics ; Flowers/genetics/*growth & development ; Gene Expression Regulation, Plant ; Genes, Plant/genetics ; Histones/metabolism ; MADS Domain Proteins/genetics ; Methylation ; Molecular Sequence Data ; Mutation ; *Periodicity ; Plant Proteins/genetics/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 93
    Publication Date: 2009-07-17
    Description: Schistosoma mansoni is responsible for the neglected tropical disease schistosomiasis that affects 210 million people in 76 countries. Here we present analysis of the 363 megabase nuclear genome of the blood fluke. It encodes at least 11,809 genes, with an unusual intron size distribution, and new families of micro-exon genes that undergo frequent alternative splicing. As the first sequenced flatworm, and a representative of the Lophotrochozoa, it offers insights into early events in the evolution of the animals, including the development of a body pattern with bilateral symmetry, and the development of tissues into organs. Our analysis has been informed by the need to find new drug targets. The deficits in lipid metabolism that make schistosomes dependent on the host are revealed, and the identification of membrane receptors, ion channels and more than 300 proteases provide new insights into the biology of the life cycle and new targets. Bioinformatics approaches have identified metabolic chokepoints, and a chemogenomic screen has pinpointed schistosome proteins for which existing drugs may be active. The information generated provides an invaluable resource for the research community to develop much needed new control tools for the treatment and eradication of this important and neglected disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2756445/" 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/PMC2756445/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Berriman, Matthew -- Haas, Brian J -- LoVerde, Philip T -- Wilson, R Alan -- Dillon, Gary P -- Cerqueira, Gustavo C -- Mashiyama, Susan T -- Al-Lazikani, Bissan -- Andrade, Luiza F -- Ashton, Peter D -- Aslett, Martin A -- Bartholomeu, Daniella C -- Blandin, Gaelle -- Caffrey, Conor R -- Coghlan, Avril -- Coulson, Richard -- Day, Tim A -- Delcher, Art -- DeMarco, Ricardo -- Djikeng, Appolinaire -- Eyre, Tina -- Gamble, John A -- Ghedin, Elodie -- Gu, Yong -- Hertz-Fowler, Christiane -- Hirai, Hirohisha -- Hirai, Yuriko -- Houston, Robin -- Ivens, Alasdair -- Johnston, David A -- Lacerda, Daniela -- Macedo, Camila D -- McVeigh, Paul -- Ning, Zemin -- Oliveira, Guilherme -- Overington, John P -- Parkhill, Julian -- Pertea, Mihaela -- Pierce, Raymond J -- Protasio, Anna V -- Quail, Michael A -- Rajandream, Marie-Adele -- Rogers, Jane -- Sajid, Mohammed -- Salzberg, Steven L -- Stanke, Mario -- Tivey, Adrian R -- White, Owen -- Williams, David L -- Wortman, Jennifer -- Wu, Wenjie -- Zamanian, Mostafa -- Zerlotini, Adhemar -- Fraser-Liggett, Claire M -- Barrell, Barclay G -- El-Sayed, Najib M -- 086151/Wellcome Trust/United Kingdom -- 5D43TW006580/TW/FIC NIH HHS/ -- 5D43TW007012-03/TW/FIC NIH HHS/ -- AI054711-01A2/AI/NIAID NIH HHS/ -- AI48828/AI/NIAID NIH HHS/ -- R01 GM083873/GM/NIGMS NIH HHS/ -- R01 GM083873-07/GM/NIGMS NIH HHS/ -- R01 GM083873-08/GM/NIGMS NIH HHS/ -- R01 LM006845/LM/NLM NIH HHS/ -- R01 LM006845-08/LM/NLM NIH HHS/ -- R01 LM006845-09/LM/NLM NIH HHS/ -- U01 AI048828/AI/NIAID NIH HHS/ -- U01 AI048828-01/AI/NIAID NIH HHS/ -- U01 AI048828-02/AI/NIAID NIH HHS/ -- WT085775/Z/08/Z/Wellcome Trust/United Kingdom -- England -- Nature. 2009 Jul 16;460(7253):352-8. doi: 10.1038/nature08160.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust Sanger Institute, Cambridge CB10 1SD, UK. mb4@sanger.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19606141" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Evolution ; Exons/genetics ; Genes, Helminth/genetics ; Genome, Helminth/*genetics ; Host-Parasite Interactions/genetics ; Introns/genetics ; Molecular Sequence Data ; Physical Chromosome Mapping ; Schistosoma mansoni/drug effects/embryology/*genetics/physiology ; Schistosomiasis mansoni/drug therapy/parasitology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 94
    Publication Date: 2009-01-06
    Description: Insulin resistance, a hallmark of type 2 diabetes, is a defect of insulin in stimulating insulin receptor signalling, which has become one of the most serious public health threats. Upon stimulation by insulin, insulin receptor recruits and phosphorylates insulin receptor substrate proteins, leading to activation of the phosphatidylinositol-3-OH kinase (PI(3)K)-Akt pathway. Activated Akt phosphorylates downstream kinases and transcription factors, thus mediating most of the metabolic actions of insulin. Beta-arrestins mediate biological functions of G-protein-coupled receptors by linking activated receptors with distinct sets of accessory and effecter proteins, thereby determining the specificity, efficiency and capacity of signals. Here we show that in diabetic mouse models, beta-arrestin-2 is severely downregulated. Knockdown of beta-arrestin-2 exacerbates insulin resistance, whereas administration of beta-arrestin-2 restores insulin sensitivity in mice. Further investigation reveals that insulin stimulates the formation of a new beta-arrestin-2 signal complex, in which beta-arrestin-2 scaffolds Akt and Src to insulin receptor. Loss or dysfunction of beta-arrestin-2 results in deficiency of this signal complex and disturbance of insulin signalling in vivo, thereby contributing to the development of insulin resistance and progression of type 2 diabetes. Our findings provide new insight into the molecular pathogenesis of insulin resistance, and implicate new preventive and therapeutic strategies against insulin resistance and type 2 diabetes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Luan, Bing -- Zhao, Jian -- Wu, Haiya -- Duan, Baoyu -- Shu, Guangwen -- Wang, Xiaoying -- Li, Dangsheng -- Jia, Weiping -- Kang, Jiuhong -- Pei, Gang -- England -- Nature. 2009 Feb 26;457(7233):1146-9. doi: 10.1038/nature07617.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, and Graduate School of the Chinese Academy of Sciences.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19122674" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arrestins/*deficiency/genetics/pharmacology ; Cell Line ; Cell Line, Tumor ; Diabetes Mellitus, Type 2/metabolism ; Disease Models, Animal ; Down-Regulation ; Gene Knockdown Techniques ; Humans ; Insulin/pharmacology ; Insulin Resistance/genetics/*physiology ; Mice ; Mice, Knockout ; Mutation/genetics ; Proto-Oncogene Proteins c-akt/metabolism ; Proto-Oncogene Proteins pp60(c-src)/metabolism ; Receptor, Insulin/metabolism ; Signal Transduction
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 95
    Publication Date: 2009-08-07
    Description: Long interspersed element 1 (LINE-1 or L1) retrotransposons have markedly affected the human genome. L1s must retrotranspose in the germ line or during early development to ensure their evolutionary success, yet the extent to which this process affects somatic cells is poorly understood. We previously demonstrated that engineered human L1s can retrotranspose in adult rat hippocampus progenitor cells in vitro and in the mouse brain in vivo. Here we demonstrate that neural progenitor cells isolated from human fetal brain and derived from human embryonic stem cells support the retrotransposition of engineered human L1s in vitro. Furthermore, we developed a quantitative multiplex polymerase chain reaction that detected an increase in the copy number of endogenous L1s in the hippocampus, and in several regions of adult human brains, when compared to the copy number of endogenous L1s in heart or liver genomic DNAs from the same donor. These data suggest that de novo L1 retrotransposition events may occur in the human brain and, in principle, have the potential to contribute to individual somatic mosaicism.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2909034/" 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/PMC2909034/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Coufal, Nicole G -- Garcia-Perez, Jose L -- Peng, Grace E -- Yeo, Gene W -- Mu, Yangling -- Lovci, Michael T -- Morell, Maria -- O'Shea, K Sue -- Moran, John V -- Gage, Fred H -- GM069985/GM/NIGMS NIH HHS/ -- GM082970/GM/NIGMS NIH HHS/ -- MH082070/MH/NIMH NIH HHS/ -- NS048187/NS/NINDS NIH HHS/ -- P20 GM069985/GM/NIGMS NIH HHS/ -- P20 GM069985-010001/GM/NIGMS NIH HHS/ -- R01 GM060518/GM/NIGMS NIH HHS/ -- R01 GM082970/GM/NIGMS NIH HHS/ -- R01 GM082970-03/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Aug 27;460(7259):1127-31. doi: 10.1038/nature08248. Epub 2009 Aug 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19657334" target="_blank"〉PubMed〈/a〉
    Keywords: 5' Untranslated Regions/genetics ; Brain/cytology ; Cell Line ; Chromatin Immunoprecipitation ; DNA Methylation ; Embryonic Stem Cells/*cytology/*metabolism ; Fetus/cytology ; Gene Dosage ; Humans ; Neurons/*cytology/*metabolism ; Polymerase Chain Reaction ; Retroelements/*genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 96
    facet.materialart.
    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2009-04-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pera, Martin F -- England -- Nature. 2009 Apr 9;458(7239):715-6. doi: 10.1038/458715a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19360075" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Differentiation/genetics/*physiology ; Cell Line ; Chimera ; Cytological Techniques ; Humans ; Pluripotent Stem Cells/*cytology/physiology ; Transduction, Genetic
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 97
    Publication Date: 2009-02-11
    Description: Osteoclasts are the only somatic cells with bone-resorbing capacity and, as such, they have a critical role not only in normal bone homeostasis (called 'bone remodelling') but also in the pathogenesis of bone destructive disorders such as rheumatoid arthritis and osteoporosis. A major focus of research in the field has been on gene regulation by osteoclastogenic cytokines such as receptor activator of NF-kappaB-ligand (RANKL, also known as TNFSF11) and TNF-alpha, both of which have been well documented to contribute to osteoclast terminal differentiation. A crucial process that has been less well studied is the trafficking of osteoclast precursors to and from the bone surface, where they undergo cell fusion to form the fully differentiated multinucleated cells that mediate bone resorption. Here we report that sphingosine-1-phosphate (S1P), a lipid mediator enriched in blood, induces chemotaxis and regulates the migration of osteoclast precursors not only in culture but also in vivo, contributing to the dynamic control of bone mineral homeostasis. Cells with the properties of osteoclast precursors express functional S1P(1) receptors and exhibit positive chemotaxis along an S1P gradient in vitro. Intravital two-photon imaging of bone tissues showed that a potent S1P(1) agonist, SEW2871, stimulated motility of osteoclast precursor-containing monocytoid populations in vivo. Osteoclast/monocyte (CD11b, also known as ITGAM) lineage-specific conditional S1P(1) knockout mice showed osteoporotic changes due to increased osteoclast attachment to the bone surface. Furthermore, treatment with the S1P(1) agonist FTY720 relieved ovariectomy-induced osteoporosis in mice by reducing the number of mature osteoclasts attached to the bone surface. Together, these data provide evidence that S1P controls the migratory behaviour of osteoclast precursors, dynamically regulating bone mineral homeostasis, and identifies a critical control point in osteoclastogenesis that may have potential as a therapeutic target.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2785034/" 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/PMC2785034/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ishii, Masaru -- Egen, Jackson G -- Klauschen, Frederick -- Meier-Schellersheim, Martin -- Saeki, Yukihiko -- Vacher, Jean -- Proia, Richard L -- Germain, Ronald N -- ZIA AI000545-21/Intramural NIH HHS/ -- England -- Nature. 2009 Mar 26;458(7237):524-8. doi: 10.1038/nature07713. Epub 2009 Feb 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Lymphocyte Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19204730" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bone Density/drug effects ; Bone Resorption ; Bone and Bones/anatomy & histology/*drug effects/metabolism ; Cell Line ; Cell Lineage ; Chemotaxis/*drug effects ; Female ; Fingolimod Hydrochloride ; Homeostasis/*drug effects ; Lysophospholipids/*pharmacology ; Mice ; Mice, Inbred C57BL ; Monocytes/*cytology/*drug effects/metabolism ; Osteoclasts/*cytology ; Osteoporosis/etiology/prevention & control ; Ovariectomy/adverse effects ; Propylene Glycols ; Receptors, Lysosphingolipid/genetics/metabolism ; Sphingosine/*analogs & derivatives/pharmacology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 98
    Publication Date: 2009-10-02
    Description: Efficient neurotransmission at chemical synapses relies on spatial congruence between the presynaptic active zone, where synaptic vesicles fuse, and the postsynaptic differentiation, where neurotransmitter receptors concentrate. Diverse molecular systems have evolved to localize receptors at synapses, but in most cases, they rely on scaffolding proteins localized below the plasma membrane. A few systems have been suggested to control the synaptic localization of neurotransmitter receptors through extracellular interactions, such as the pentraxins that bind AMPA receptors and trigger their aggregation. However, it is not yet clear whether these systems have a central role in the organization of postsynaptic domains in vivo or rather provide modulatory functions. Here we describe an extracellular scaffold that is necessary to cluster acetylcholine receptors at neuromuscular junctions in the nematode Caenorhabditis elegans. It involves the ectodomain of the previously identified transmembrane protein LEV-10 (ref. 6) and a novel extracellular protein, LEV-9. LEV-9 is secreted by the muscle cells and localizes at cholinergic neuromuscular junctions. Acetylcholine receptors, LEV-9 and LEV-10 are interdependent for proper synaptic localization and physically interact based on biochemical evidence. Notably, the function of LEV-9 relies on eight complement control protein (CCP) domains. These domains, also called 'sushi domains', are usually found in proteins regulating complement activity in the vertebrate immune system. Because the complement system does not exist in protostomes, our results suggest that some of the numerous uncharacterized CCP proteins expressed in the mammalian brain might be directly involved in the organization of the synapse, independently from immune functions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gendrel, Marie -- Rapti, Georgia -- Richmond, Janet E -- Bessereau, Jean-Louis -- R01 MH073156/MH/NIMH NIH HHS/ -- England -- Nature. 2009 Oct 15;461(7266):992-6. doi: 10.1038/nature08430. Epub 2009 Sep 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉ENS, Biology Department, Paris, F-75005 France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19794415" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caenorhabditis elegans/cytology/*metabolism ; Caenorhabditis elegans Proteins/*chemistry/genetics/*metabolism/secretion ; Membrane Proteins/genetics/metabolism ; Molecular Sequence Data ; Muscles/metabolism ; Neuromuscular Junction/metabolism ; Organ Specificity ; Protein Binding ; Protein Structure, Tertiary ; Protein Transport ; Receptors, Cholinergic/*metabolism ; Viral Proteins/*chemistry
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 99
    Publication Date: 2009-03-03
    Description: Clostridium difficile is the leading cause of infectious diarrhoea in hospitals worldwide, because of its virulence, spore-forming ability and persistence. C. difficile-associated diseases are induced by antibiotic treatment or disruption of the normal gastrointestinal flora. Recently, morbidity and mortality resulting from C. difficile-associated diseases have increased significantly due to changes in the virulence of the causative strains and antibiotic usage patterns. Since 2002, epidemic toxinotype III NAP1/027 strains, which produce high levels of the major virulence factors, toxin A and toxin B, have emerged. These toxins have 63% amino acid sequence similarity and are members of the large clostridial glucosylating toxin family, which are monoglucosyltransferases that are pro-inflammatory, cytotoxic and enterotoxic in the human colon. Inside host cells, both toxins catalyse the transfer of glucose onto the Rho family of GTPases, leading to cell death. However, the role of these toxins in the context of a C. difficile infection is unknown. Here we describe the construction of isogenic tcdA and tcdB (encoding toxin A and B, respectively) mutants of a virulent C. difficile strain and their use in the hamster disease model to show that toxin B is a key virulence determinant. Previous studies showed that purified toxin A alone can induce most of the pathology observed after infection of hamsters with C. difficile and that toxin B is not toxic in animals unless it is co-administered with toxin A, suggesting that the toxins act synergistically. Our work provides evidence that toxin B, not toxin A, is essential for virulence. Furthermore, it is clear that the importance of these toxins in the context of infection cannot be predicted exclusively from studies using purified toxins, reinforcing the importance of using the natural infection process to dissect the role of toxins in disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2679968/" 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/PMC2679968/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lyras, Dena -- O'Connor, Jennifer R -- Howarth, Pauline M -- Sambol, Susan P -- Carter, Glen P -- Phumoonna, Tongted -- Poon, Rachael -- Adams, Vicki -- Vedantam, Gayatri -- Johnson, Stuart -- Gerding, Dale N -- Rood, Julian I -- AI057637/AI/NIAID NIH HHS/ -- R01 AI057637/AI/NIAID NIH HHS/ -- R01 AI057637-01A1/AI/NIAID NIH HHS/ -- England -- Nature. 2009 Apr 30;458(7242):1176-9. doi: 10.1038/nature07822. Epub 2009 Mar 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Australian Bacterial Pathogenesis Program, Department of Microbiology, Monash University, Victoria 3800, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19252482" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacterial Adhesion ; Bacterial Proteins/biosynthesis/genetics/*metabolism/pharmacology ; Bacterial Toxins/biosynthesis/genetics/*metabolism/pharmacology ; Cell Line ; Clostridium difficile/genetics/*pathogenicity ; Cricetinae ; Disease Models, Animal ; Enterotoxins/genetics/metabolism ; Humans ; Mutation ; Virulence
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 100
    Publication Date: 2009-08-13
    Description: Influenza A viruses cause recurrent outbreaks at local or global scale with potentially severe consequences for human health and the global economy. Recently, a new strain of influenza A virus was detected that causes disease in and transmits among humans, probably owing to little or no pre-existing immunity to the new strain. On 11 June 2009 the World Health Organization declared that the infections caused by the new strain had reached pandemic proportion. Characterized as an influenza A virus of the H1N1 subtype, the genomic segments of the new strain were most closely related to swine viruses. Most human infections with swine-origin H1N1 influenza viruses (S-OIVs) seem to be mild; however, a substantial number of hospitalized individuals do not have underlying health issues, attesting to the pathogenic potential of S-OIVs. To achieve a better assessment of the risk posed by the new virus, we characterized one of the first US S-OIV isolates, A/California/04/09 (H1N1; hereafter referred to as CA04), as well as several other S-OIV isolates, in vitro and in vivo. In mice and ferrets, CA04 and other S-OIV isolates tested replicate more efficiently than a currently circulating human H1N1 virus. In addition, CA04 replicates efficiently in non-human primates, causes more severe pathological lesions in the lungs of infected mice, ferrets and non-human primates than a currently circulating human H1N1 virus, and transmits among ferrets. In specific-pathogen-free miniature pigs, CA04 replicates without clinical symptoms. The assessment of human sera from different age groups suggests that infection with human H1N1 viruses antigenically closely related to viruses circulating in 1918 confers neutralizing antibody activity to CA04. Finally, we show that CA04 is sensitive to approved and experimental antiviral drugs, suggesting that these compounds could function as a first line of defence against the recently declared S-OIV pandemic.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2748827/" 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/PMC2748827/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Itoh, Yasushi -- Shinya, Kyoko -- Kiso, Maki -- Watanabe, Tokiko -- Sakoda, Yoshihiro -- Hatta, Masato -- Muramoto, Yukiko -- Tamura, Daisuke -- Sakai-Tagawa, Yuko -- Noda, Takeshi -- Sakabe, Saori -- Imai, Masaki -- Hatta, Yasuko -- Watanabe, Shinji -- Li, Chengjun -- Yamada, Shinya -- Fujii, Ken -- Murakami, Shin -- Imai, Hirotaka -- Kakugawa, Satoshi -- Ito, Mutsumi -- Takano, Ryo -- Iwatsuki-Horimoto, Kiyoko -- Shimojima, Masayuki -- Horimoto, Taisuke -- Goto, Hideo -- Takahashi, Kei -- Makino, Akiko -- Ishigaki, Hirohito -- Nakayama, Misako -- Okamatsu, Masatoshi -- Takahashi, Kazuo -- Warshauer, David -- Shult, Peter A -- Saito, Reiko -- Suzuki, Hiroshi -- Furuta, Yousuke -- Yamashita, Makoto -- Mitamura, Keiko -- Nakano, Kunio -- Nakamura, Morio -- Brockman-Schneider, Rebecca -- Mitamura, Hiroshi -- Yamazaki, Masahiko -- Sugaya, Norio -- Suresh, M -- Ozawa, Makoto -- Neumann, Gabriele -- Gern, James -- Kida, Hiroshi -- Ogasawara, Kazumasa -- Kawaoka, Yoshihiro -- HHNSN266200700010C/NS/NINDS NIH HHS/ -- HHSN266200700010C/PHS HHS/ -- HHSN272200800060C/AI/NIAID NIH HHS/ -- R01 AI069274/AI/NIAID NIH HHS/ -- R01 AI069274-04/AI/NIAID NIH HHS/ -- U19 AI070503/AI/NIAID NIH HHS/ -- England -- Nature. 2009 Aug 20;460(7258):1021-5. doi: 10.1038/nature08260.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Shiga University of Medical Science, Ohtsu, Shiga 520-2192, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19672242" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Viral/immunology ; Antiviral Agents/pharmacology ; Cell Line ; Dogs ; Female ; Ferrets/virology ; HN Protein/metabolism ; Humans ; Influenza A Virus, H1N1 Subtype/drug effects/enzymology/pathogenicity/*physiology ; Lung/immunology/pathology/virology ; Macaca fascicularis/immunology/virology ; Male ; Mice ; Mice, Inbred BALB C ; Neutralization Tests ; Orthomyxoviridae Infections/immunology/transmission/virology ; Primate Diseases/pathology/virology ; Swine/*virology ; Swine Diseases/pathology/virology ; Swine, Miniature/virology ; Virus Replication
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...