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  • 1
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    Molecular mechanism of ERCC6 autoregulation [Biochemistry] (2014)
    National Academy of Sciences
    Details
    Publication Date: 2014-12-31
    Description: CSB/ERCC6 (Cockayne syndrome B protein/excision repair cross-complementation group 6), a member of a subfamily of SWI2/SNF2 (SWItch/sucrose nonfermentable)-related chromatin remodelers, plays crucial roles in gene expression and the maintenance of genome integrity. Here, we report the mechanism of the autoregulation of Rhp26, which is the homolog of CSB/ERCC6 in Schizosaccharomyces...
    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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  • 2
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    Functionally diverse type V CRISPR-Cas systems (2019)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2019
    Description: 〈p〉Type V CRISPR-Cas systems are distinguished by a single RNA-guided RuvC domain-containing effector, Cas12. Although effectors of subtypes V-A (Cas12a) and V-B (Cas12b) have been studied in detail, the distinct domain architectures and diverged RuvC sequences of uncharacterized Cas12 proteins suggest unexplored functional diversity. Here, we identify and characterize Cas12c, -g, -h, and -i. Cas12c, -h, and -i demonstrate RNA-guided double-stranded DNA (dsDNA) interference activity. Cas12i exhibits markedly different efficiencies of CRISPR RNA spacer complementary and noncomplementary strand cleavage resulting in predominant dsDNA nicking. Cas12g is an RNA-guided ribonuclease (RNase) with collateral RNase and single-strand DNase activities. Our study reveals the functional diversity emerging along different routes of type V CRISPR-Cas evolution and expands the CRISPR toolbox.〈/p〉
    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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  • 3
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    Boutique neutrons advance 40Ar/39Ar geochronology (2019)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2019
    Description: 〈p〉We designed and tested a compact deuteron-deuteron fusion neutron generator for application to 〈sup〉40〈/sup〉Ar/〈sup〉39〈/sup〉Ar geochronology. The nearly monoenergetic neutrons produced for sample irradiation are anticipated to provide several advantages compared with conventional fission spectrum neutrons: Reduction of collateral nuclear reactions increases age accuracy and precision. Irradiation parameters within the neutron generator are more controllable compared with fission reactors. Confidence in the prediction of recoil energies is improved, and their likely reduction potentially broadens applicability of the dating method to fine-grained materials without vacuum encapsulation. Resolution of variation in the 〈sup〉39〈/sup〉K(n,p)〈sup〉39〈/sup〉Ar neutron capture cross section at 1.3 to 3.2 MeV and discovery of a strong resonance at ~2.4 MeV illuminate future pathways to improve the technique for 〈sup〉40〈/sup〉Ar/〈sup〉39〈/sup〉Ar dating.〈/p〉
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 4
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    flowDensity: reproducing manual gating of flow cytometry data by automated density-based cell population identification (2015)
    Oxford University Press
    Details
    Publication Date: 2015-02-13
    Description: : flowDensity facilitates reproducible, high-throughput analysis of flow cytometry data by automating a predefined manual gating approach. The algorithm is based on a sequential bivariate gating approach that generates a set of predefined cell populations. It chooses the best cut-off for individual markers using characteristics of the density distribution. The Supplementary Material is linked to the online version of the manuscript. Availability and implementation: R source code freely available through BioConductor ( http://master.bioconductor.org/packages/devel/bioc/html/flowDensity.html .). Data available from FlowRepository.org (dataset FR-FCM-ZZBW). Contact: rbrinkman@bccrc.ca Supplementary information: Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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  • 5
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    Mutations in FKBP10, which result in Bruck syndrome and recessive forms of osteogenesis imperfecta, inhibit the hydroxylation of telopeptide lysines in bone collagen (2012)
    Oxford University Press
    Details
    Publication Date: 2012-12-15
    Description: Although biallelic mutations in non-collagen genes account for 〈10% of individuals with osteogenesis imperfecta, the characterization of these genes has identified new pathways and potential interventions that could benefit even those with mutations in type I collagen genes. We identified mutations in FKBP10 , which encodes the 65 kDa prolyl cis–trans isomerase, FKBP65, in 38 members of 21 families with OI. These include 10 families from the Samoan Islands who share a founder mutation. Of the mutations, three are missense; the remainder either introduce premature termination codons or create frameshifts both of which result in mRNA instability. In four families missense mutations result in loss of most of the protein. The clinical effects of these mutations are short stature, a high incidence of joint contractures at birth and progressive scoliosis and fractures, but there is remarkable variability in phenotype even within families. The loss of the activity of FKBP65 has several effects: type I procollagen secretion is slightly delayed, the stabilization of the intact trimer is incomplete and there is diminished hydroxylation of the telopeptide lysyl residues involved in intermolecular cross-link formation in bone. The phenotype overlaps with that seen with mutations in PLOD2 (Bruck syndrome II), which encodes LH2, the enzyme that hydroxylates the telopeptide lysyl residues. These findings define a set of genes, FKBP10 , PLOD2 and SERPINH1 , that act during procollagen maturation to contribute to molecular stability and post-translational modification of type I procollagen, without which bone mass and quality are abnormal and fractures and contractures result.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 6
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    Assembly of membrane proteins on oil drops [Applied Physical Sciences] (2016)
    National Academy of Sciences
    Details
    Publication Date: 2016-01-21
    Description: Single-span membrane proteins (ssMPs) represent approximately one-half of all membrane proteins and play important roles in cellular communications. However, like all membrane proteins, ssMPs are prone to misfolding and aggregation because of the hydrophobicity of transmembrane helices, making them difficult to study using common aqueous solution-based approaches. Detergents and membrane...
    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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  • 7
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    Programmable protein circuits in living cells (2018)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2018-09-21
    Description: Synthetic protein-level circuits could enable engineering of powerful new cellular behaviors. Rational protein circuit design would be facilitated by a composable protein-protein regulation system in which individual protein components can regulate one another to create a variety of different circuit architectures. In this study, we show that engineered viral proteases can function as composable protein components, which can together implement a broad variety of circuit-level functions in mammalian cells. In this system, termed CHOMP (circuits of hacked orthogonal modular proteases), input proteases dock with and cleave target proteases to inhibit their function. These components can be connected to generate regulatory cascades, binary logic gates, and dynamic analog signal-processing functions. To demonstrate the utility of this system, we rationally designed a circuit that induces cell death in response to upstream activators of the Ras oncogene. Because CHOMP circuits can perform complex functions yet be encoded as single transcripts and delivered without genomic integration, they offer a scalable platform to facilitate protein circuit engineering for biotechnological applications.
    Keywords: Molecular Biology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 8
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    Requirement for Atm in ionizing radiation-induced cell death in the developing central nervous system (1998)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1998-06-06
    Description: Ataxia telangiectasia (AT) is characterized by progressive neurodegeneration that results from mutation of the ATM gene. However, neither the normal function of ATM in the nervous system nor the biological basis of the degeneration in AT is known. Resistance to apoptosis in the developing central nervous system (CNS) of Atm-/- mice was observed after ionizing radiation. This lack of death occurred in diverse regions of the CNS, including the cerebellum, which is markedly affected in AT. In wild-type, but not Atm-/- mice, up-regulation of p53 coincided with cell death, suggesting that Atm-dependent apoptosis in the CNS is mediated by p53. Further, p53 null mice showed a similar lack of radiation-induced cell death in the developing nervous system. Atm may function at a developmental survival checkpoint that serves to eliminate neurons with excessive DNA damage.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Herzog, K H -- Chong, M J -- Kapsetaki, M -- Morgan, J I -- McKinnon, P J -- CA-21765/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1998 May 15;280(5366):1089-91.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Developmental Neurobiology, St. Jude Children's Research Hospital, 332 North Lauderdale, Memphis, TN 38101, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9582124" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Apoptosis ; Ataxia Telangiectasia Mutated Proteins ; Brain/*cytology/*radiation effects ; Cell Cycle Proteins ; Cerebellum/cytology/radiation effects ; DNA-Binding Proteins ; Genes, p53 ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Neurons/*cytology/radiation effects ; Phenotype ; *Protein-Serine-Threonine Kinases ; Proteins/genetics/*physiology ; Radiation, Ionizing ; Retina/cytology ; Thymus Gland/cytology/radiation effects ; Tumor Suppressor Protein p53/physiology ; Tumor Suppressor Proteins ; Up-Regulation
    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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  • 9
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    Functionally diverse type V CRISPR-Cas systems (2018)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2018
    Description: 〈p〉Type V CRISPR-Cas systems are distinguished by a single RNA-guided RuvC domain-containing effector, Cas12. Although effectors of subtypes V-A (Cas12a) and V-B (Cas12b) have been studied in detail, the distinct domain architectures and diverged RuvC sequences of uncharacterized Cas12 proteins suggest unexplored functional diversity. Here, we identify and characterize Cas12c, g, h, and i. Cas12c, h, and i demonstrate RNA-guided double-stranded (ds) DNA interference activity. Cas12i exhibits markedly different efficiencies of crRNA spacer complementary and non-complementary strand cleavage resulting in predominant dsDNA nicking. Cas12g is an RNA-guided RNase with collateral RNase and single-stranded DNase activities. Our study reveals the functional diversity emerging along different routes of type V CRISPR-Cas evolution and expands the CRISPR toolbox.〈/p〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 10
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    An anatomically comprehensive atlas of the adult human brain transcriptome (2012)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2012-09-22
    Description: Neuroanatomically precise, genome-wide maps of transcript distributions are critical resources to complement genomic sequence data and to correlate functional and genetic brain architecture. Here we describe the generation and analysis of a transcriptional atlas of the adult human brain, comprising extensive histological analysis and comprehensive microarray profiling of approximately 900 neuroanatomically precise subdivisions in two individuals. Transcriptional regulation varies enormously by anatomical location, with different regions and their constituent cell types displaying robust molecular signatures that are highly conserved between individuals. Analysis of differential gene expression and gene co-expression relationships demonstrates that brain-wide variation strongly reflects the distributions of major cell classes such as neurons, oligodendrocytes, astrocytes and microglia. Local neighbourhood relationships between fine anatomical subdivisions are associated with discrete neuronal subtypes and genes involved with synaptic transmission. The neocortex displays a relatively homogeneous transcriptional pattern, but with distinct features associated selectively with primary sensorimotor cortices and with enriched frontal lobe expression. Notably, the spatial topography of the neocortex is strongly reflected in its molecular topography-the closer two cortical regions, the more similar their transcriptomes. This freely accessible online data resource forms a high-resolution transcriptional baseline for neurogenetic studies of normal and abnormal human brain function.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4243026/" 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/PMC4243026/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hawrylycz, Michael J -- Lein, Ed S -- Guillozet-Bongaarts, Angela L -- Shen, Elaine H -- Ng, Lydia -- Miller, Jeremy A -- van de Lagemaat, Louie N -- Smith, Kimberly A -- Ebbert, Amanda -- Riley, Zackery L -- Abajian, Chris -- Beckmann, Christian F -- Bernard, Amy -- Bertagnolli, Darren -- Boe, Andrew F -- Cartagena, Preston M -- Chakravarty, M Mallar -- Chapin, Mike -- Chong, Jimmy -- Dalley, Rachel A -- Daly, Barry David -- Dang, Chinh -- Datta, Suvro -- Dee, Nick -- Dolbeare, Tim A -- Faber, Vance -- Feng, David -- Fowler, David R -- Goldy, Jeff -- Gregor, Benjamin W -- Haradon, Zeb -- Haynor, David R -- Hohmann, John G -- Horvath, Steve -- Howard, Robert E -- Jeromin, Andreas -- Jochim, Jayson M -- Kinnunen, Marty -- Lau, Christopher -- Lazarz, Evan T -- Lee, Changkyu -- Lemon, Tracy A -- Li, Ling -- Li, Yang -- Morris, John A -- Overly, Caroline C -- Parker, Patrick D -- Parry, Sheana E -- Reding, Melissa -- Royall, Joshua J -- Schulkin, Jay -- Sequeira, Pedro Adolfo -- Slaughterbeck, Clifford R -- Smith, Simon C -- Sodt, Andy J -- Sunkin, Susan M -- Swanson, Beryl E -- Vawter, Marquis P -- Williams, Derric -- Wohnoutka, Paul -- Zielke, H Ronald -- Geschwind, Daniel H -- Hof, Patrick R -- Smith, Stephen M -- Koch, Christof -- Grant, Seth G N -- Jones, Allan R -- 066717/Wellcome Trust/United Kingdom -- 077155/Wellcome Trust/United Kingdom -- 1C76HF15069-01-00/PHS HHS/ -- 1C76HF19619-01-00/PHS HHS/ -- G0700399/Medical Research Council/United Kingdom -- G0802238/Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2012 Sep 20;489(7416):391-9. doi: 10.1038/nature11405.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Allen Institute for Brain Science, Seattle, Washington 98103, USA. mikeh@alleninstitute.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22996553" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; *Anatomy, Artistic ; Animals ; *Atlases as Topic ; Brain/*anatomy & histology/cytology/*metabolism ; Calbindins ; Databases, Genetic ; Dopamine/metabolism ; *Gene Expression Profiling ; Health ; Hippocampus/cytology/metabolism ; Humans ; In Situ Hybridization ; Internet ; Macaca mulatta/anatomy & histology/genetics ; Male ; Mice ; Neocortex/anatomy & histology/cytology/metabolism ; Oligonucleotide Array Sequence Analysis ; Post-Synaptic Density/genetics ; RNA, Messenger/analysis/genetics ; S100 Calcium Binding Protein G/genetics ; Species Specificity ; Transcriptome/*genetics
    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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