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  • 1
    Publication Date: 1999-07-27
    Description: Genetic selections were used to find peptides that inhibit biological pathways in budding yeast. The peptides were presented inside cells as peptamers, surface loops on a highly expressed and biologically inert carrier protein, a catalytically inactive derivative of staphylococcal nuclease. Peptamers that inhibited the pheromone signaling pathway, transcriptional silencing, and the spindle checkpoint were isolated. Putative targets for the inhibitors were identified by a combination of two-hybrid analysis and genetic dissection of the target pathways. This analysis identified Ydr517w as a component of the spindle checkpoint and reinforced earlier indications that Ste50 has both positive and negative roles in pheromone signaling. Analysis of transcript arrays showed that the peptamers were highly specific in their effects, which suggests that they may be useful reagents in organisms that lack sophisticated genetics as well as for identifying components of existing biological pathways that are potential targets for drug discovery.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Norman, T C -- Smith, D L -- Sorger, P K -- Drees, B L -- O'Rourke, S M -- Hughes, T R -- Roberts, C J -- Friend, S H -- Fields, S -- Murray, A W -- P41-RR11823/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 1999 Jul 23;285(5427):591-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, University of California, San Francisco, CA 94143-0444, USA. tnorman@microbia.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10417390" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Calcium-Calmodulin-Dependent Protein Kinases/metabolism ; Fungal Proteins/metabolism ; G1 Phase ; Galactose/metabolism ; Lipoproteins/metabolism ; Micrococcal Nuclease ; Mitosis ; Molecular Sequence Data ; Peptide Library ; Peptides/genetics/metabolism/*pharmacology ; Pheromones/*metabolism ; Protein Binding ; Protein-Serine-Threonine Kinases ; Protein-Tyrosine Kinases ; Saccharomyces cerevisiae/cytology/genetics/*metabolism ; *Saccharomyces cerevisiae Proteins ; *Selection, Genetic ; *Signal Transduction ; Spindle Apparatus/drug effects/*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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  • 2
    Publication Date: 2014-12-10
    Description: The widespread reorganization of cellular architecture in mitosis is achieved through extensive protein phosphorylation, driven by the coordinated activation of a mitotic kinase network and repression of counteracting phosphatases. Phosphatase activity must subsequently be restored to promote mitotic exit. Although Cdc14 phosphatase drives this reversal in budding yeast, protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A) activities have each been independently linked to mitotic exit control in other eukaryotes. Here we describe a mitotic phosphatase relay in which PP1 reactivation is required for the reactivation of both PP2A-B55 and PP2A-B56 to coordinate mitotic progression and exit in fission yeast. The staged recruitment of PP1 (the Dis2 isoform) to the regulatory subunits of the PP2A-B55 and PP2A-B56 (B55 also known as Pab1; B56 also known as Par1) holoenzymes sequentially activates each phosphatase. The pathway is blocked in early mitosis because the Cdk1-cyclin B kinase (Cdk1 also known as Cdc2) inhibits PP1 activity, but declining cyclin B levels later in mitosis permit PP1 to auto-reactivate. PP1 first reactivates PP2A-B55; this enables PP2A-B55 in turn to promote the reactivation of PP2A-B56 by dephosphorylating a PP1-docking site in PP2A-B56, thereby promoting the recruitment of PP1. PP1 recruitment to human, mitotic PP2A-B56 holoenzymes and the sequences of these conserved PP1-docking motifs suggest that PP1 regulates PP2A-B55 and PP2A-B56 activities in a variety of signalling contexts throughout eukaryotes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338534/" 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/PMC4338534/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grallert, Agnes -- Boke, Elvan -- Hagting, Anja -- Hodgson, Ben -- Connolly, Yvonne -- Griffiths, John R -- Smith, Duncan L -- Pines, Jonathon -- Hagan, Iain M -- 092096/Wellcome Trust/United Kingdom -- A13678/Cancer Research UK/United Kingdom -- A16406/Cancer Research UK/United Kingdom -- C147/A16406/Cancer Research UK/United Kingdom -- C29/A13678/Cancer Research UK/United Kingdom -- England -- Nature. 2015 Jan 1;517(7532):94-8. doi: 10.1038/nature14019. Epub 2014 Dec 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cell Division Group, CRUK Manchester Institute, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK. ; The Gurdon Institute, Tennis Court Road, University of Cambridge, Cambridge, CB2 1QN, UK. ; Biological Mass Spectrometry, CRUK Manchester Institute, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25487150" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Binding Sites ; CDC2 Protein Kinase/metabolism ; Chromosome Segregation ; Conserved Sequence ; Cyclin B/metabolism ; Enzyme Activation ; HeLa Cells ; Holoenzymes/metabolism ; Humans ; Isoenzymes/metabolism ; *Mitosis ; Molecular Sequence Data ; Phosphorylation ; Protein Phosphatase 1/*metabolism ; Protein Phosphatase 2/chemistry/*metabolism ; Protein Subunits/chemistry/metabolism ; Schizosaccharomyces/*cytology/*enzymology ; Schizosaccharomyces pombe Proteins/chemistry/metabolism ; Signal Transduction
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2012-10-16
    Description: Human movements contribute to the transmission of malaria on spatial scales that exceed the limits of mosquito dispersal. Identifying the sources and sinks of imported infections due to human travel and locating high-risk sites of parasite importation could greatly improve malaria control programs. Here, we use spatially explicit mobile phone data and malaria prevalence information from Kenya to identify the dynamics of human carriers that drive parasite importation between regions. Our analysis identifies importation routes that contribute to malaria epidemiology on regional spatial scales.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3675794/" 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/PMC3675794/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wesolowski, Amy -- Eagle, Nathan -- Tatem, Andrew J -- Smith, David L -- Noor, Abdisalan M -- Snow, Robert W -- Buckee, Caroline O -- 079080/Wellcome Trust/United Kingdom -- 092654/Wellcome Trust/United Kingdom -- 095127/Wellcome Trust/United Kingdom -- 1U54GM088558/GM/NIGMS NIH HHS/ -- U19 AI089674/AI/NIAID NIH HHS/ -- U19AI089674/AI/NIAID NIH HHS/ -- U54 GM088558/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2012 Oct 12;338(6104):267-70. doi: 10.1126/science.1223467.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Engineering and Public Policy, Carnegie Mellon University, Pittsburgh, PA 15221, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23066082" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Phones ; Communicable Disease Control ; Culicidae/*parasitology ; Humans ; Kenya/epidemiology ; Malaria, Falciparum/*embryology/prevention & control/*transmission ; *Plasmodium falciparum ; Prevalence ; Travel/*statistics & numerical data
    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: 2013-02-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chiyaka, C -- Tatem, A J -- Cohen, J M -- Gething, P W -- Johnston, G -- Gosling, R -- Laxminarayan, R -- Hay, S I -- Smith, D L -- 095066/Wellcome Trust/United Kingdom -- MR/K00669X/1/Medical Research Council/United Kingdom -- U19 AI089674/AI/NIAID NIH HHS/ -- U19AI089674/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2013 Feb 22;339(6122):909-10. doi: 10.1126/science.1229509.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Emerging Pathogens Institute, University of Florida, Gainesville, FL 32610, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23430640" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Basic Reproduction Number ; Culicidae ; *Disease Eradication ; Global Health ; *Health Policy ; Humans ; Insect Vectors ; Malaria/*prevention & control/transmission ; Mosquito Control
    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: 1998-03-07
    Description: The spindle checkpoint regulates the cell division cycle by keeping cells with defective spindles from leaving mitosis. In the two-hybrid system, three proteins that are components of the checkpoint, Mad1, Mad2, and Mad3, were shown to interact with Cdc20, a protein required for exit from mitosis. Mad2 and Mad3 coprecipitated with Cdc20 at all stages of the cell cycle. The binding of Mad2 depended on Mad1 and that of Mad3 on Mad1 and Mad2. Overexpression of Cdc20 allowed cells with a depolymerized spindle or damaged DNA to leave mitosis but did not overcome the arrest caused by unreplicated DNA. Mutants in Cdc20 that were resistant to the spindle checkpoint no longer bound Mad proteins, suggesting that Cdc20 is the target of the spindle checkpoint.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hwang, L H -- Lau, L F -- Smith, D L -- Mistrot, C A -- Hardwick, K G -- Hwang, E S -- Amon, A -- Murray, A W -- New York, N.Y. -- Science. 1998 Feb 13;279(5353):1041-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, University of California at San Francisco, San Francisco, CA 94143-0444, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9461437" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Anaphase ; Anaphase-Promoting Complex-Cyclosome ; Cadherins ; Calcium-Binding Proteins/metabolism ; *Carrier Proteins ; Cdc20 Proteins ; Cdh1 Proteins ; Cell Cycle Proteins/chemistry/genetics/*metabolism ; DNA Damage ; DNA Replication ; Fungal Proteins/chemistry/*metabolism ; Ligases/metabolism ; Mad2 Proteins ; *Mitosis ; Molecular Sequence Data ; Mutation ; Nuclear Proteins/metabolism ; Phosphoproteins/metabolism ; *Repressor Proteins ; Saccharomyces cerevisiae/*cytology/*metabolism ; *Saccharomyces cerevisiae Proteins ; Spindle Apparatus/*metabolism ; *Ubiquitin-Protein Ligase Complexes ; Ubiquitin-Protein Ligases
    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: 2010-05-21
    Description: The current and potential future impact of climate change on malaria is of major public health interest. The proposed effects of rising global temperatures on the future spread and intensification of the disease, and on existing malaria morbidity and mortality rates, substantively influence global health policy. The contemporary spatial limits of Plasmodium falciparum malaria and its endemicity within this range, when compared with comparable historical maps, offer unique insights into the changing global epidemiology of malaria over the last century. It has long been known that the range of malaria has contracted through a century of economic development and disease control. Here, for the first time, we quantify this contraction and the global decreases in malaria endemicity since approximately 1900. We compare the magnitude of these changes to the size of effects on malaria endemicity proposed under future climate scenarios and associated with widely used public health interventions. Our findings have two key and often ignored implications with respect to climate change and malaria. First, widespread claims that rising mean temperatures have already led to increases in worldwide malaria morbidity and mortality are largely at odds with observed decreasing global trends in both its endemicity and geographic extent. Second, the proposed future effects of rising temperatures on endemicity are at least one order of magnitude smaller than changes observed since about 1900 and up to two orders of magnitude smaller than those that can be achieved by the effective scale-up of key control measures. Predictions of an intensification of malaria in a warmer world, based on extrapolated empirical relationships or biological mechanisms, must be set against a context of a century of warming that has seen marked global declines in the disease and a substantial weakening of the global correlation between malaria endemicity and climate.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2885436/" 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/PMC2885436/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gething, Peter W -- Smith, David L -- Patil, Anand P -- Tatem, Andrew J -- Snow, Robert W -- Hay, Simon I -- 079080/Wellcome Trust/United Kingdom -- 079091/Wellcome Trust/United Kingdom -- England -- Nature. 2010 May 20;465(7296):342-5. doi: 10.1038/nature09098.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Spatial Ecology and Epidemiology Group, Tinbergen Building, Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK. peter.gething@zoo.ox.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20485434" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Global Health ; Global Warming/*statistics & numerical data ; Humans ; Malaria, Falciparum/*epidemiology/mortality/parasitology/*prevention & control ; Plasmodium falciparum/pathogenicity/physiology ; Public Health/statistics & numerical data
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2012-06-23
    Description: Avian A/H5N1 influenza viruses pose a pandemic threat. As few as five amino acid substitutions, or four with reassortment, might be sufficient for mammal-to-mammal transmission through respiratory droplets. From surveillance data, we found that two of these substitutions are common in A/H5N1 viruses, and thus, some viruses might require only three additional substitutions to become transmissible via respiratory droplets between mammals. We used a mathematical model of within-host virus evolution to study factors that could increase and decrease the probability of the remaining substitutions evolving after the virus has infected a mammalian host. These factors, combined with the presence of some of these substitutions in circulating strains, make a virus evolving in nature a potentially serious threat. These results highlight critical areas in which more data are needed for assessing, and potentially averting, this threat.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3426314/" 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/PMC3426314/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Russell, Colin A -- Fonville, Judith M -- Brown, Andre E X -- Burke, David F -- Smith, David L -- James, Sarah L -- Herfst, Sander -- van Boheemen, Sander -- Linster, Martin -- Schrauwen, Eefje J -- Katzelnick, Leah -- Mosterin, Ana -- Kuiken, Thijs -- Maher, Eileen -- Neumann, Gabriele -- Osterhaus, Albert D M E -- Kawaoka, Yoshihiro -- Fouchier, Ron A M -- Smith, Derek J -- DP1 OD000490/OD/NIH HHS/ -- DP1-OD000490-01/OD/NIH HHS/ -- HHSN266200700010C/AI/NIAID NIH HHS/ -- HHSN266200700010C/PHS HHS/ -- R01 AI 069274/AI/NIAID NIH HHS/ -- R56 AI069274/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2012 Jun 22;336(6088):1541-7. doi: 10.1126/science.1222526.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Zoology, University of Cambridge, Cambridge, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22723414" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological ; Air Microbiology ; Amino Acid Substitution ; Animals ; Birds ; *Evolution, Molecular ; Genetic Fitness ; Glycosylation ; Hemagglutinin Glycoproteins, Influenza Virus/*genetics/metabolism ; High-Throughput Nucleotide Sequencing ; Humans ; Influenza A Virus, H5N1 Subtype/*genetics/*pathogenicity ; Influenza in Birds/virology ; Influenza, Human/immunology/transmission/*virology ; Mammals ; Models, Biological ; Mutation ; Orthomyxoviridae Infections/transmission/*virology ; Probability ; RNA Replicase/*genetics ; Receptors, Virus/metabolism ; Respiratory System/*virology ; Selection, Genetic ; Sialic Acids/metabolism ; Viral Proteins/*genetics
    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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  • 8
    Publication Date: 2019-06-27
    Description: An iterative procedure applying matrix methods to accomplish an efficient algorithm for automatic computer reduction of wind-tunnel force-balance data has been developed. Balance equations are expressed in a matrix form that is convenient for storing balance sensitivities and interaction coefficient values for online or offline batch data reduction. The convergence of the iterative values to a unique solution of this system of equations is investigated, and it is shown that for balances which satisfy the criteria discussed, this type of solution does occur. Methods for making sensitivity adjustments and initial load effect considerations in wind-tunnel applications are also discussed, and the logic for determining the convergence accuracy limits for the iterative solution is given. This more efficient data reduction program is compared with the technique presently in use at the NASA Langley Research Center, and computational times on the order of one-third or less are demonstrated by use of this new program.
    Keywords: AERODYNAMICS
    Type: NASA-TN-D-6860 , L-8278
    Format: application/pdf
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  • 9
    Publication Date: 2019-07-13
    Description: Measurements of the response of a large frame-stringer panel excited by supersonic turbulent boundary layer are reported. The statistical description of the wall pressure fluctuations in terms of the mean flow parameters governing the turbulent boundary layer is given. These results can be used in the development of design criteria on the response of sidewall structure of a large airplane in supersonic flight, since both forcing field and structure are realistic. Results indicate the significant importance of the modal coupling and the acoustic damping. The acoustic damping plays a major role in the response of the structure.
    Keywords: AERODYNAMICS
    Type: AIAA PAPER 76-83 , Aerospace Sciences Meeting; Jan 26, 1976 - Jan 28, 1976; Washington, DC
    Format: text
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