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  • 1
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    Overexpression of human kynurenine-3-monooxygenase protects against 3-hydroxykynurenine-mediated apoptosis through bidirectional nonlinear feedback (2016)
    Springer Nature
    Details
    Publication Date: 2016-04-15
    Description: Overexpression of human kynurenine-3-monooxygenase protects against 3-hydroxykynurenine-mediated apoptosis through bidirectional nonlinear feedback Cell Death and Disease 7, e2197 (April 2016). doi:10.1038/cddis.2016.87 Authors: K Wilson, M Auer, M Binnie, X Zheng, N T Pham, J P Iredale, S P Webster & D J Mole
    Electronic ISSN: 2041-4889
    Topics: Biology , Medicine
    Published by Springer Nature
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  • 2
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    Genomic and Phenotypic Characterization of a Wild Medaka Population: Towards the Establishment of an Isogenic Population Genetic Resource in Fish (2014)
    Genetics Society of America (GSA)
    Details
    Publication Date: 2014-03-22
    Description: Oryzias latipes (medaka) has been established as a vertebrate genetic model for more than a century and recently has been rediscovered outside its native Japan. The power of new sequencing methods now makes it possible to reinvigorate medaka genetics, in particular by establishing a near-isogenic panel derived from a single wild population. Here we characterize the genomes of wild medaka catches obtained from a single Southern Japanese population in Kiyosu as a precursor for the establishment of a near-isogenic panel of wild lines. The population is free of significant detrimental population structure and has advantageous linkage disequilibrium properties suitable for the establishment of the proposed panel. Analysis of morphometric traits in five representative inbred strains suggests phenotypic mapping will be feasible in the panel. In addition, high-throughput genome sequencing of these medaka strains confirms their evolutionary relationships on lines of geographic separation and provides further evidence that there has been little significant interbreeding between the Southern and Northern medaka population since the Southern/Northern population split. The sequence data suggest that the Southern Japanese medaka existed as a larger older population that went through a relatively recent bottleneck approximately 10,000 years ago. In addition, we detect patterns of recent positive selection in the Southern population. These data indicate that the genetic structure of the Kiyosu medaka samples is suitable for the establishment of a vertebrate near-isogenic panel and therefore inbreeding of 200 lines based on this population has commenced. Progress of this project can be tracked at http://www.ebi.ac.uk/birney-srv/medaka-ref-panel .
    Electronic ISSN: 2160-1836
    Topics: Biology
    Published by Genetics Society of America (GSA)
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  • 3
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    Association of exome sequences with plasma C-reactive protein levels in 〉9000 participants (2014)
    Oxford University Press
    Details
    Publication Date: 2014-12-24
    Description: C-reactive protein (CRP) concentration is a heritable systemic marker of inflammation that is associated with cardiovascular disease risk. Genome-wide association studies have identified CRP-associated common variants associated in ~25 genes. Our aims were to apply exome sequencing to (1) assess whether the candidate loci contain rare coding variants associated with CRP levels and (2) perform an exome-wide search for rare variants in novel genes associated with CRP levels. We exome-sequenced 6050 European-Americans (EAs) and 3109 African-Americans (AAs) from the NHLBI-ESP and the CHARGE consortia, and performed association tests of sequence data with measured CRP levels. In single-variant tests across candidate loci, a novel rare (minor allele frequency = 0.16%) CRP- coding variant (rs77832441-A; p.Thr59Met) was associated with 53% lower mean CRP levels ( P = 2.9 x 10 –6 ). We replicated the association of rs77832441 in an exome array analysis of 11 414 EAs ( P = 3.0 x 10 –15 ). Despite a strong effect on CRP levels, rs77832441 was not associated with inflammation-related phenotypes including coronary heart disease. We also found evidence for an AA-specific association of APOE- 2 rs7214 with higher CRP levels. At the exome-wide significance level ( P 〈 5.0 x 10 –8 ), we confirmed associations for reported common variants of HNF1A , CRP , IL6R and TOMM40 - APOE . In gene-based tests, a burden of rare/lower frequency variation in CRP in EAs ( P ≤ 6.8 x 10 –4 ) and in retinoic acid receptor-related orphan receptor α ( RORA ) in AAs ( P = 1.7 x 10 –3 ) were associated with CRP levels at the candidate gene level ( P 〈 2.0 x 10 –3 ). This inquiry did not elucidate novel genes, but instead demonstrated that variants distributed across the allele frequency spectrum within candidate genes contribute to CRP levels.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 4
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    Whole-exome imputation of sequence variants identified two novel alleles associated with adult body height in African Americans (2014)
    Oxford University Press
    Details
    Publication Date: 2014-11-21
    Description: Adult body height is a quantitative trait for which genome-wide association studies (GWAS) have identified numerous loci, primarily in European populations. These loci, comprising common variants, explain 〈10% of the phenotypic variance in height. We searched for novel associations between height and common (minor allele frequency, MAF ≥5%) or infrequent (0.5% 〈 MAF 〈 5%) variants across the exome in African Americans. Using a reference panel of 1692 African Americans and 471 Europeans from the National Heart, Lung, and Blood Institute's (NHLBI) Exome Sequencing Project (ESP), we imputed whole-exome sequence data into 13 719 African Americans with existing array-based GWAS data (discovery). Variants achieving a height-association threshold of P 〈 5E–06 in the imputed dataset were followed up in an independent sample of 1989 African Americans with whole-exome sequence data (replication). We used P 〈 2.5E–07 (=0.05/196 779 variants) to define statistically significant associations in meta-analyses combining the discovery and replication sets ( N = 15 708). We discovered and replicated three independent loci for association: 5p13.3/ C5orf22 /rs17410035 (MAF = 0.10, β = 0.64 cm, P = 8.3E–08), 13q14.2/ SPRYD7 /rs114089985 (MAF = 0.03, β = 1.46 cm, P = 4.8E–10) and 17q23.3/ GH2 /rs2006123 (MAF = 0.30; β = 0.47 cm; P = 4.7E–09). Conditional analyses suggested 5p13.3 (C5orf22/rs17410035) and 13q14.2 (SPRYD7/rs114089985) may harbor novel height alleles independent of previous GWAS-identified variants ( r 2 with GWAS loci 〈0.01); whereas 17q23.3/ GH2 /rs2006123 was correlated with GWAS-identified variants in European and African populations. Notably, 13q14.2/rs114089985 is infrequent in African Americans (MAF = 3%), extremely rare in European Americans (MAF = 0.03%), and monomorphic in Asian populations, suggesting it may be an African-American-specific height allele. Our findings demonstrate that whole-exome imputation of sequence variants can identify low-frequency variants and discover novel variants in non-European populations.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 5
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    Deep-sea oil plume enriches indigenous oil-degrading bacteria (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-08-26
    Description: The biological effects and expected fate of the vast amount of oil in the Gulf of Mexico from the Deepwater Horizon blowout are unknown owing to the depth and magnitude of this event. Here, we report that the dispersed hydrocarbon plume stimulated deep-sea indigenous gamma-Proteobacteria that are closely related to known petroleum degraders. Hydrocarbon-degrading genes coincided with the concentration of various oil contaminants. Changes in hydrocarbon composition with distance from the source and incubation experiments with environmental isolates demonstrated faster-than-expected hydrocarbon biodegradation rates at 5 degrees C. Based on these results, the potential exists for intrinsic bioremediation of the oil plume in the deep-water column without substantial oxygen drawdown.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hazen, Terry C -- Dubinsky, Eric A -- DeSantis, Todd Z -- Andersen, Gary L -- Piceno, Yvette M -- Singh, Navjeet -- Jansson, Janet K -- Probst, Alexander -- Borglin, Sharon E -- Fortney, Julian L -- Stringfellow, William T -- Bill, Markus -- Conrad, Mark E -- Tom, Lauren M -- Chavarria, Krystle L -- Alusi, Thana R -- Lamendella, Regina -- Joyner, Dominique C -- Spier, Chelsea -- Baelum, Jacob -- Auer, Manfred -- Zemla, Marcin L -- Chakraborty, Romy -- Sonnenthal, Eric L -- D'haeseleer, Patrik -- Holman, Hoi-Ying N -- Osman, Shariff -- Lu, Zhenmei -- Van Nostrand, Joy D -- Deng, Ye -- Zhou, Jizhong -- Mason, Olivia U -- New York, N.Y. -- Science. 2010 Oct 8;330(6001):204-8. doi: 10.1126/science.1195979. Epub 2010 Aug 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MS 70A-3317, One Cyclotron Road, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. tchazen@lbl.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20736401" target="_blank"〉PubMed〈/a〉
    Keywords: *Biodegradation, Environmental ; Biomass ; Colony Count, Microbial ; *Environmental Pollution ; Fatty Acids/analysis ; Gammaproteobacteria/classification/growth & development/isolation & ; purification/*metabolism ; Genes, Bacterial ; Genes, rRNA ; Hydrocarbons/*metabolism ; Molecular Sequence Data ; Oceanospirillaceae/classification/genetics/isolation & purification/*metabolism ; Petroleum/*metabolism ; Phospholipids/analysis ; Phylogeny ; Seawater/*microbiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 6
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    Structure and mechanism of the glycerol-3-phosphate transporter from Escherichia coli (2003)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2003-08-02
    Description: The major facilitator superfamily represents the largest group of secondary membrane transporters in the cell. Here we report the 3.3 angstrom resolution structure of a member of this superfamily, GlpT, which transports glycerol-3-phosphate into the cytoplasm and inorganic phosphate into the periplasm. The amino- and carboxyl-terminal halves of the protein exhibit a pseudo two-fold symmetry. Closed off to the periplasm, a centrally located substrate-translocation pore contains two arginines at its closed end, which comprise the substrate-binding site. Upon substrate binding, the protein adopts a more compact conformation. We propose that GlpT operates by a single-binding site, alternating-access mechanism through a rocker-switch type of movement.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Huang, Yafei -- Lemieux, M Joanne -- Song, Jinmei -- Auer, Manfred -- Wang, Da-Neng -- New York, N.Y. -- Science. 2003 Aug 1;301(5633):616-20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Skirball Institute of Biomolecular Medicine and Department of Cell Biology, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12893936" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Biological Transport ; Cell Membrane/chemistry ; Crystallization ; Crystallography, X-Ray ; Escherichia coli/*chemistry/enzymology ; Escherichia coli Proteins/chemistry/metabolism ; Glycerophosphates/*metabolism ; Helix-Turn-Helix Motifs ; Mass Spectrometry ; Membrane Transport Proteins/*chemistry/*metabolism ; Models, Molecular ; Molecular Sequence Data ; Periplasm/metabolism ; Phosphates/metabolism ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Protein Structure, Tertiary
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 7
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    PTEN action in leukaemia dictated by the tissue microenvironment (2014)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2014-05-09
    Description: PTEN encodes a lipid phosphatase that is underexpressed in many cancers owing to deletions, mutations or gene silencing. PTEN dephosphorylates phosphatidylinositol (3,4,5)-triphosphate, thereby opposing the activity of class I phosphatidylinositol 3-kinases that mediate growth- and survival-factor signalling through phosphatidylinositol 3-kinase effectors such as AKT and mTOR. To determine whether continued PTEN inactivation is required to maintain malignancy, here we generate an RNA interference-based transgenic mouse model that allows tetracycline-dependent regulation of PTEN in a time- and tissue-specific manner. Postnatal Pten knockdown in the haematopoietic compartment produced highly disseminated T-cell acute lymphoblastic leukaemia. Notably, reactivation of PTEN mainly reduced T-cell leukaemia dissemination but had little effect on tumour load in haematopoietic organs. Leukaemia infiltration into the intestine was dependent on CCR9 G-protein-coupled receptor signalling, which was amplified by PTEN loss. Our results suggest that in the absence of PTEN, G-protein-coupled receptors may have an unanticipated role in driving tumour growth and invasion in an unsupportive environment. They further reveal that the role of PTEN loss in tumour maintenance is not invariant and can be influenced by the tissue microenvironment, thereby producing a form of intratumoral heterogeneity that is independent of cancer genotype.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4165899/" 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/PMC4165899/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miething, Cornelius -- Scuoppo, Claudio -- Bosbach, Benedikt -- Appelmann, Iris -- Nakitandwe, Joy -- Ma, Jing -- Wu, Gang -- Lintault, Laura -- Auer, Martina -- Premsrirut, Prem K -- Teruya-Feldstein, Julie -- Hicks, James -- Benveniste, Helene -- Speicher, Michael R -- Downing, James R -- Lowe, Scott W -- P01 CA013106/CA/NCI NIH HHS/ -- P01 CA087497/CA/NCI NIH HHS/ -- P30 CA008748/CA/NCI NIH HHS/ -- P30 CA021765/CA/NCI NIH HHS/ -- P30 CA045508/CA/NCI NIH HHS/ -- S10 OD016282/OD/NIH HHS/ -- U01 CA105388/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Jun 19;510(7505):402-6. doi: 10.1038/nature13239. Epub 2014 May 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA [2] Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA [3] Department of Medicine I, Medical Center - University of Freiburg, 79106 Freiburg, Germany. ; Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA. ; Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA. ; 1] Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA [2] Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA. ; Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. ; 1] Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA [2] Howard Hughes Medical Institute, New York, New York 10065, USA. ; Institute of Human Genetics, Medical University of Graz, A-8010 Graz, Austria. ; Departments of Anesthesiology and Radiology, Stony Brook University, Stony Brook, New York 11794, USA. ; 1] Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA [2] Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA [3] Howard Hughes Medical Institute, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24805236" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chemokines/metabolism ; Gene Knockdown Techniques ; Leukemia/*enzymology/genetics/*physiopathology ; Mice, Transgenic ; PTEN Phosphohydrolase/*genetics/*metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; RNA Interference ; Receptors, G-Protein-Coupled/metabolism ; Signal Transduction ; Tumor Microenvironment/*physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 8
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    CIN-induced tumorigenesis [Genetics] (2012)
    National Academy of Sciences
    Details
    Publication Date: 2012-12-12
    Description: Genomic instability has been observed in essentially all sporadic carcinomas. Here we use Drosophila epithelial cells to address the role of chromosomal instability in cancer development as they have proved useful for elucidating the molecular mechanisms underlying tumorigenic growth. We first show that chromosomal instability leads to an apoptotic response....
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 9
    Electronic Resource
    Electronic Resource
    Reversible phase transitions in the Pt(111)-sulfur system
    Amsterdam : Elsevier
    Applications of Surface Science 17 (1983), S. 70-78 
    Details
    ISSN: 0378-5963
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/0378-5963(83)90112-5
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  • 10
    Electronic Resource
    Electronic Resource
    Wavy rolls in the Taylor–Bénard problem (1998)
    [S.l.] : American Institute of Physics (AIP)
    Physics of Fluids 10 (1998), S. 318-320 
    Details
    ISSN: 1089-7666
    Source: AIP Digital Archive
    Topics: Physics
    Notes: The Taylor–Bénard problem is realized in the narrow gap limit of fluid flow between differentially rotating coaxial cylinders which are kept at different temperatures. When the outer cylinder is heated and the centrifugal force by far exceeds gravity, buoyancy gives rise to the same axisymmetric vortices that are also realized in the isothermal Taylor–Couette system. The mathematical identity of the axisymmetric motions provides the basis for the analysis of nonaxisymmetric motions in the form of wavy vortices. It is shown that wavy convection rolls in a Rayleigh–Bénard layer and wavy Taylor vortices are special cases of the wavy rolls found as secondary bifurcation in the Taylor–Bénard problem. © 1998 American Institute of Physics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.869541
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