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  • 1
    Publication Date: 2012-10-26
    Description: Schizophrenia is a debilitating psychiatric disease with a strong genetic contribution, potentially linked to altered glutamatergic function in brain regions such as the prefrontal cortex (PFC). Here, we report converging evidence to support a functional candidate gene for schizophrenia. In post-mortem PFC from patients with schizophrenia, we detected decreased expression of MKK7 / MAP2K7 —a kinase activated by glutamatergic activity. While mice lacking one copy of the Map2k7 gene were overtly normal in a variety of behavioural tests, these mice showed a schizophrenia-like cognitive phenotype of impaired working memory. Additional support for MAP2K7 as a candidate gene came from a genetic association study. A substantial effect size (odds ratios: ~1.9) was observed for a common variant in a cohort of case and control samples collected in the Glasgow area and also in a replication cohort of samples of Northern European descent (most significant P -value: 3 x 10 –4 ). While some caution is warranted until these association data are further replicated, these results are the first to implicate the candidate gene MAP2K7 in genetic risk for schizophrenia. Complete sequencing of all MAP2K7 exons did not reveal any non-synonymous mutations. However, the MAP2K7 haplotype appeared to have functional effects, in that it influenced the level of expression of MAP2K7 mRNA in human PFC. Taken together, the results imply that reduced function of the MAP2K7-c-Jun N-terminal kinase (JNK) signalling cascade may underlie some of the neurochemical changes and core symptoms in schizophrenia.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
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  • 2
    Publication Date: 2011-04-23
    Description: The fission yeast clade--comprising Schizosaccharomyces pombe, S. octosporus, S. cryophilus, and S. japonicus--occupies the basal branch of Ascomycete fungi and is an important model of eukaryote biology. A comparative annotation of these genomes identified a near extinction of transposons and the associated innovation of transposon-free centromeres. Expression analysis established that meiotic genes are subject to antisense transcription during vegetative growth, which suggests a mechanism for their tight regulation. In addition, trans-acting regulators control new genes within the context of expanded functional modules for meiosis and stress response. Differences in gene content and regulation also explain why, unlike the budding yeast of Saccharomycotina, fission yeasts cannot use ethanol as a primary carbon source. These analyses elucidate the genome structure and gene regulation of fission yeast and provide tools for investigation across the Schizosaccharomyces clade.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3131103/" 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/PMC3131103/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rhind, Nicholas -- Chen, Zehua -- Yassour, Moran -- Thompson, Dawn A -- Haas, Brian J -- Habib, Naomi -- Wapinski, Ilan -- Roy, Sushmita -- Lin, Michael F -- Heiman, David I -- Young, Sarah K -- Furuya, Kanji -- Guo, Yabin -- Pidoux, Alison -- Chen, Huei Mei -- Robbertse, Barbara -- Goldberg, Jonathan M -- Aoki, Keita -- Bayne, Elizabeth H -- Berlin, Aaron M -- Desjardins, Christopher A -- Dobbs, Edward -- Dukaj, Livio -- Fan, Lin -- FitzGerald, Michael G -- French, Courtney -- Gujja, Sharvari -- Hansen, Klavs -- Keifenheim, Dan -- Levin, Joshua Z -- Mosher, Rebecca A -- Muller, Carolin A -- Pfiffner, Jenna -- Priest, Margaret -- Russ, Carsten -- Smialowska, Agata -- Swoboda, Peter -- Sykes, Sean M -- Vaughn, Matthew -- Vengrova, Sonya -- Yoder, Ryan -- Zeng, Qiandong -- Allshire, Robin -- Baulcombe, David -- Birren, Bruce W -- Brown, William -- Ekwall, Karl -- Kellis, Manolis -- Leatherwood, Janet -- Levin, Henry -- Margalit, Hanah -- Martienssen, Rob -- Nieduszynski, Conrad A -- Spatafora, Joseph W -- Friedman, Nir -- Dalgaard, Jacob Z -- Baumann, Peter -- Niki, Hironori -- Regev, Aviv -- Nusbaum, Chad -- BB/E023754/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- DP1 OD003958/OD/NIH HHS/ -- R01 GM069957/GM/NIGMS NIH HHS/ -- R01 GM076396/GM/NIGMS NIH HHS/ -- R01 HG004037/HG/NHGRI NIH HHS/ -- U54 HG003067/HG/NHGRI NIH HHS/ -- U54 HG003067-06/HG/NHGRI NIH HHS/ -- Biotechnology and Biological Sciences Research Council/United Kingdom -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 May 20;332(6032):930-6. doi: 10.1126/science.1203357. Epub 2011 Apr 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA. nick.rhind@umassmed.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21511999" target="_blank"〉PubMed〈/a〉
    Keywords: Centromere/genetics/physiology/ultrastructure ; DNA Transposable Elements ; Evolution, Molecular ; Gene Expression Profiling ; Gene Expression Regulation, Fungal ; Genes, Mating Type, Fungal ; *Genome, Fungal ; Genomics ; Glucose/metabolism ; Meiosis ; Molecular Sequence Annotation ; Molecular Sequence Data ; Phylogeny ; RNA, Antisense/genetics ; RNA, Fungal/genetics ; RNA, Small Interfering/genetics ; RNA, Untranslated/genetics ; Regulatory Elements, Transcriptional ; Schizosaccharomyces/*genetics/growth & development/metabolism ; Schizosaccharomyces pombe Proteins/genetics/metabolism ; Sequence Analysis, DNA ; Species Specificity ; Transcription Factors/genetics/metabolism ; Transcription, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 1998-02-07
    Description: Circulating lymphocytes are recruited from the blood to the tissue by rolling along the endothelium until being stopped by a signaling event linked to the Gialpha subunit of a heterotrimeric GTP-binding protein; that event then triggers rapid integrin-dependent adhesion. Four chemokines are now shown to induce such adhesion to intercellular adhesion molecule-1 and to induce arrest of rolling cells within 1 second under flow conditions similar to those of blood. SDF-1 (also called PBSF), 6-C-kine (also called Exodus-2), and MIP-3beta (also called ELC or Exodus-3) induced adhesion of most circulating lymphocytes, including most CD4+ T cells; and MIP-3alpha (also called LARC or Exodus-1) triggered adhesion of memory, but not naive, CD4+ T cells. Thus, chemokines can regulate the arrest of lymphocyte subsets under flowing conditions, which may allow them to control lymphocyte-endothelial cell recognition and lymphocyte recruitment in vivo.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Campbell, J J -- Hedrick, J -- Zlotnik, A -- Siani, M A -- Thompson, D A -- Butcher, E C -- 5T32CA090302/CA/NCI NIH HHS/ -- DK38707/DK/NIDDK NIH HHS/ -- GM37734/GM/NIGMS NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1998 Jan 16;279(5349):381-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Immunology and Vascular Biology, Department of Pathology, and Digestive Disease Center, Department of Medicine, Stanford University Medical School, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9430588" target="_blank"〉PubMed〈/a〉
    Keywords: Antigens, Surface/metabolism ; CD4-Positive T-Lymphocytes/*physiology ; *Cell Adhesion ; Chemokine CCL19 ; Chemokine CCL20 ; Chemokine CCL21 ; Chemokine CXCL12 ; Chemokines, CC/*pharmacology/physiology ; *Chemokines, CXC ; Humans ; Immunologic Memory ; Intercellular Adhesion Molecule-1/metabolism ; Lymphocytes/*physiology ; *Macrophage Inflammatory Proteins ; Membrane Proteins ; Receptors, CCR6 ; *Receptors, Chemokine ; Rheology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2007-10-20
    Description: Genetic analysis of mammalian color variation has provided fundamental insight into human biology and disease. In most vertebrates, two key genes, Agouti and Melanocortin 1 receptor (Mc1r), encode a ligand-receptor system that controls pigment type-switching, but in domestic dogs, a third gene is implicated, the K locus, whose genetic characteristics predict a previously unrecognized component of the melanocortin pathway. We identify the K locus as beta-defensin 103 (CBD103) and show that its protein product binds with high affinity to the Mc1r and has a simple and strong effect on pigment type-switching in domestic dogs and transgenic mice. These results expand the functional role of beta-defensins, a protein family previously implicated in innate immunity, and identify an additional class of ligands for signaling through melanocortin receptors.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2906624/" 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/PMC2906624/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Candille, Sophie I -- Kaelin, Christopher B -- Cattanach, Bruce M -- Yu, Bin -- Thompson, Darren A -- Nix, Matthew A -- Kerns, Julie A -- Schmutz, Sheila M -- Millhauser, Glenn L -- Barsh, Gregory S -- R01 DK064265/DK/NIDDK NIH HHS/ -- R01 DK064265-08/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2007 Nov 30;318(5855):1418-23. Epub 2007 Oct 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Genetics and Pediatrics, Stanford University, Stanford, CA, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17947548" target="_blank"〉PubMed〈/a〉
    Keywords: Agouti Signaling Protein/genetics/metabolism ; Amino Acid Sequence ; Animals ; Cell Line ; Chromosome Mapping ; Dogs/*genetics/metabolism ; Female ; Hair Color/*genetics ; Haplotypes ; Humans ; Keratinocytes/metabolism ; Male ; Mice ; Mice, Transgenic ; Molecular Sequence Data ; Mutation ; Polymorphism, Genetic ; Receptor, Melanocortin, Type 1/*metabolism ; Sequence Analysis, DNA ; Sequence Deletion ; Signal Transduction ; Skin/metabolism ; beta-Defensins/chemistry/*genetics/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2016-02-26
    Description: The fungal kingdom is the source of almost all industrial enzymes in use for lignocellulose bioprocessing. We developed a systems-level approach that integrates transcriptomic sequencing, proteomics, phenotype, and biochemical studies of relatively unexplored basal fungi. Anaerobic gut fungi isolated from herbivores produce a large array of biomass-degrading enzymes that synergistically degrade crude, untreated plant biomass and are competitive with optimized commercial preparations from Aspergillus and Trichoderma. Compared to these model platforms, gut fungal enzymes are unbiased in substrate preference due to a wealth of xylan-degrading enzymes. These enzymes are universally catabolite-repressed and are further regulated by a rich landscape of noncoding regulatory RNAs. Additionally, we identified several promising sequence-divergent enzyme candidates for lignocellulosic bioprocessing.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Solomon, Kevin V -- Haitjema, Charles H -- Henske, John K -- Gilmore, Sean P -- Borges-Rivera, Diego -- Lipzen, Anna -- Brewer, Heather M -- Purvine, Samuel O -- Wright, Aaron T -- Theodorou, Michael K -- Grigoriev, Igor V -- Regev, Aviv -- Thompson, Dawn A -- O'Malley, Michelle A -- New York, N.Y. -- Science. 2016 Mar 11;351(6278):1192-5. doi: 10.1126/science.aad1431. Epub 2016 Feb 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemical Engineering, University of California, Santa Barbara (UCSB), Santa Barbara, CA 93106, USA. ; Broad Institute of MIT and Harvard, Cambridge, MA 02143, USA. ; U.S. Department of Energy (DOE) Joint Genome Institute, 2800 Mitchell Drive, Walnut Creek, CA 94598, USA. ; Earth and Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA. Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, WA 99352, USA. ; Earth and Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA. ; Animal Production, Welfare and Veterinary Sciences, Harper Adams University, Newport, Shropshire TF10 8NB, UK. ; Department of Chemical Engineering, University of California, Santa Barbara (UCSB), Santa Barbara, CA 93106, USA. momalley@engineering.ucsb.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26912365" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Aspergillus/*enzymology/genetics/isolation & purification ; Biotechnology/*methods ; Cellulases/genetics/isolation & purification/*metabolism ; Cellulose/metabolism ; Gastrointestinal Tract/*microbiology ; Herbivory ; RNA, Untranslated/genetics ; Substrate Specificity ; Trichoderma/*enzymology/genetics/isolation & purification ; Xylans/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2017-07-07
    Description: The Precambrian core of North America was assembled in the Proterozoic by a series of collisions between Archean cratons. Among the orogenic belts, two stand out due to their significant spatial extent. The Paleoproterozoic Trans-Hudson Orogen (THO) and Mesoproterozoic Grenville Orogen extend for thousands of kilometers along-strike and hundreds of kilometers across-strike. Both have been compared to the present-day Himalayan-Karakoram-Tibetan Orogen (HKTO). Over the last 20–30 years, active and passive-source seismic studies have contributed a wealth of information about the present-day crustal structure and composition of the two orogens in Canada. The Proterozoic orogenic crust is generally thicker than that of neighboring Archean terranes, with a more variable Moho character, ranging from relatively sharp to highly diffuse. Both orogens have a prominent high-velocity lower-crustal layer, consistent with long-term preservation of a partially-eclogitized root at the base of the crust and similar to that inferred beneath the western HKTO. Crustal structure in the northern THO strongly resembles the lower-crustal structure of the HKTO, suggesting that Moho depths may have reached 60–70 km when the orogen was active. A prominent mid-crustal discontinuity beneath the central Grenville Province and changes in the patterns of seismic anisotropy in the THO crust beneath Hudson Bay provide geophysical evidence that lower-crustal flow likely played a role in the evolution of both orogens, similar to that inferred beneath the present-day HKTO. The seismic evidence from Canada supports the notion of tectonic uniformitarianism, at least as far back as the Paleoproterozoic.
    Print ISSN: 0278-7407
    Electronic ISSN: 1944-9194
    Topics: Geosciences
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 7
    Publication Date: 1983-01-01
    Print ISSN: 0149-1423
    Electronic ISSN: 1943-2674
    Topics: Geosciences
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  • 8
    ISSN: 1520-510X
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1520-510X
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    Inorganic chemistry 15 (1976), S. 2948-2950 
    ISSN: 1520-510X
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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