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  • 1
    Publication Date: 2015-10-13
    Description: Inositol-1,4,5-trisphosphate receptors (InsP3Rs) are ubiquitous ion channels responsible for cytosolic Ca(2+) signalling and essential for a broad array of cellular processes ranging from contraction to secretion, and from proliferation to cell death. Despite decades of research on InsP3Rs, a mechanistic understanding of their structure-function relationship is lacking. Here we present the first, to our knowledge, near-atomic (4.7 A) resolution electron cryomicroscopy structure of the tetrameric mammalian type 1 InsP3R channel in its apo-state. At this resolution, we are able to trace unambiguously approximately 85% of the protein backbone, allowing us to identify the structural elements involved in gating and modulation of this 1.3-megadalton channel. Although the central Ca(2+)-conduction pathway is similar to other ion channels, including the closely related ryanodine receptor, the cytosolic carboxy termini are uniquely arranged in a left-handed alpha-helical bundle, directly interacting with the amino-terminal domains of adjacent subunits. This configuration suggests a molecular mechanism for allosteric regulation of channel gating by intracellular signals.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fan, Guizhen -- Baker, Matthew L -- Wang, Zhao -- Baker, Mariah R -- Sinyagovskiy, Pavel A -- Chiu, Wah -- Ludtke, Steven J -- Serysheva, Irina I -- P41 GM103832/GM/NIGMS NIH HHS/ -- P41GM103832/GM/NIGMS NIH HHS/ -- R01 GM072804/GM/NIGMS NIH HHS/ -- R01 GM079429/GM/NIGMS NIH HHS/ -- R01 GM080139/GM/NIGMS NIH HHS/ -- R01GM072804/GM/NIGMS NIH HHS/ -- R01GM079429/GM/NIGMS NIH HHS/ -- R01GM080139/GM/NIGMS NIH HHS/ -- R21 AR063255/AR/NIAMS NIH HHS/ -- R21 GM100229/GM/NIGMS NIH HHS/ -- R21AR063255/AR/NIAMS NIH HHS/ -- R21GM100229/GM/NIGMS NIH HHS/ -- S10 OD016279/OD/NIH HHS/ -- S10OD016279/OD/NIH HHS/ -- England -- Nature. 2015 Nov 19;527(7578):336-41. doi: 10.1038/nature15249. Epub 2015 Oct 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, Structural Biology Imaging Center, The University of Texas Medical School at Houston, 6431 Fannin Street, Houston, Texas 77030, USA. ; National Center for Macromolecular Imaging, Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26458101" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation ; Animals ; Apoproteins/chemistry/metabolism/ultrastructure ; Calcium/metabolism ; Calcium Signaling ; *Cryoelectron Microscopy ; Cytosol/chemistry/metabolism ; Inositol 1,4,5-Trisphosphate Receptors/chemistry/*metabolism/*ultrastructure ; Ion Channel Gating ; Models, Molecular ; Protein Folding ; Protein Structure, Quaternary ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Protein Subunits/chemistry/metabolism ; Rats ; Ryanodine Receptor Calcium Release Channel/chemistry/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2002-09-28
    Description: Molecular genetic studies of Drosophila melanogaster have led to profound advances in understanding the regulation of development. Here we report gene expression patterns for nearly one-third of all Drosophila genes during a complete time course of development. Mutations that eliminate eye or germline tissue were used to further analyze tissue-specific gene expression programs. These studies define major characteristics of the transcriptional programs that underlie the life cycle, compare development in males and females, and show that large-scale gene expression data collected from whole animals can be used to identify genes expressed in particular tissues and organs or genes involved in specific biological and biochemical processes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Arbeitman, Michelle N -- Furlong, Eileen E M -- Imam, Farhad -- Johnson, Eric -- Null, Brian H -- Baker, Bruce S -- Krasnow, Mark A -- Scott, Matthew P -- Davis, Ronald W -- White, Kevin P -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2002 Sep 27;297(5590):2270-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, Stanford University, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12351791" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Animals ; Cluster Analysis ; Drosophila Proteins/genetics/physiology ; Drosophila melanogaster/embryology/*genetics/*growth & development ; Embryo, Nonmammalian/physiology ; Female ; *Gene Expression ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; *Genes, Insect ; Germ Cells/physiology ; Larva/genetics ; Life Cycle Stages/*genetics ; Male ; Oligonucleotide Array Sequence Analysis ; Organ Specificity ; Pupa/genetics ; RNA, Messenger/genetics/metabolism ; Sex Characteristics ; 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: 2001-02-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baker, C S -- Lento, G M -- Cipriano, F -- Dalebout, M L -- Palumbi, S R -- New York, N.Y. -- Science. 2000 Dec 1;290(5497):1695-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11186388" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Commerce ; *Conservation of Natural Resources ; Ecosystem ; International Cooperation ; Japan ; *Whales
    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: 2001-02-07
    Description: Long sediment cores recovered from the deep portions of Lake Titicaca are used to reconstruct the precipitation history of tropical South America for the past 25,000 years. Lake Titicaca was a deep, fresh, and continuously overflowing lake during the last glacial stage, from before 25,000 to 15,000 calibrated years before the present (cal yr B.P.), signifying that during the last glacial maximum (LGM), the Altiplano of Bolivia and Peru and much of the Amazon basin were wetter than today. The LGM in this part of the Andes is dated at 21,000 cal yr B.P., approximately coincident with the global LGM. Maximum aridity and lowest lake level occurred in the early and middle Holocene (8000 to 5500 cal yr B.P.) during a time of low summer insolation. Today, rising levels of Lake Titicaca and wet conditions in Amazonia are correlated with anomalously cold sea-surface temperatures in the northern equatorial Atlantic. Likewise, during the deglacial and Holocene periods, there were several millennial-scale wet phases on the Altiplano and in Amazonia that coincided with anomalously cold periods in the equatorial and high-latitude North Atlantic, such as the Younger Dryas.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baker, P A -- Seltzer, G O -- Fritz, S C -- Dunbar, R B -- Grove, M J -- Tapia, P M -- Cross, S L -- Rowe, H D -- Broda, J P -- New York, N.Y. -- Science. 2001 Jan 26;291(5504):640-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Duke University, Division of Earth and Ocean Sciences, Durham, NC 27708, USA. pbaker@geo.duke.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11158674" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Atmosphere ; Bolivia ; Diatoms ; *Fresh Water ; *Geologic Sediments ; Peru ; Plankton ; *Rain ; Temperature ; Time ; *Tropical Climate
    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: 2001-04-21
    Description: Despite widespread interest in the evolution of social intelligence, little is known about how wild animals acquire and store information about social companions or whether individuals possessing enhanced social knowledge derive biological fitness benefits. Using playback experiments on African elephants (Loxodonta africana), we demonstrated that the possession of enhanced discriminatory abilities by the oldest individual in a group can influence the social knowledge of the group as a whole. These superior abilities for social discrimination may result in higher per capita reproductive success for female groups led by older individuals. Our findings imply that the removal of older, more experienced individuals, which are often targets for hunters because of their large size, could have serious consequences for endangered populations of advanced social mammals such as elephants and whales.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McComb, K -- Moss, C -- Durant, S M -- Baker, L -- Sayialel, S -- New York, N.Y. -- Science. 2001 Apr 20;292(5516):491-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Experimental Psychology, School of Biological Sciences, University of Sussex, Brighton BN1 9QG, UK. karenm@biols.susx.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11313492" target="_blank"〉PubMed〈/a〉
    Keywords: *Aging ; Animals ; *Behavior, Animal ; Biological Evolution ; Conservation of Natural Resources ; *Discrimination (Psychology) ; *Elephants/physiology ; Exploratory Behavior ; Female ; Kenya ; Reproduction ; Social Behavior ; *Vocalization, Animal
    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
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2001-10-06
    Description: Genome sequencing projects are producing linear amino acid sequences, but full understanding of the biological role of these proteins will require knowledge of their structure and function. Although experimental structure determination methods are providing high-resolution structure information about a subset of the proteins, computational structure prediction methods will provide valuable information for the large fraction of sequences whose structures will not be determined experimentally. The first class of protein structure prediction methods, including threading and comparative modeling, rely on detectable similarity spanning most of the modeled sequence and at least one known structure. The second class of methods, de novo or ab initio methods, predict the structure from sequence alone, without relying on similarity at the fold level between the modeled sequence and any of the known structures. In this Viewpoint, we begin by describing the essential features of the methods, the accuracy of the models, and their application to the prediction and understanding of protein function, both for single proteins and on the scale of whole genomes. We then discuss the important role that protein structure prediction methods play in the growing worldwide effort in structural genomics.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baker, D -- Sali, A -- GM 54762/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2001 Oct 5;294(5540):93-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA. dabaker@u.washington.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11588250" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; *Computational Biology ; Computer Simulation ; Databases, Factual ; *Genomics ; Humans ; Internet ; *Models, Molecular ; *Protein Conformation ; Protein Folding ; Protein Structure, Tertiary ; Proteins/*chemistry/genetics/physiology ; Sequence Alignment ; Software ; Templates, 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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  • 7
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1997-05-02
    Description: Analysis of viral and bacterial pathogenesis has revealed common themes in the ways in which plants and animals respond to pathogenic agents. Pathogenic bacteria use macromolecule delivery systems (types III and IV) to deliver microbial avirulence proteins and transfer DNA-protein complexes directly into plant cells. The molecular events that constitute critical steps of plant-pathogen interactions seem to involve ligand-receptor mechanisms for pathogen recognition and the induction of signal transduction pathways in the plant that lead to defense responses. Unraveling the molecular basis of disease resistance pathways has laid a foundation for the rational design of crop protection strategies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baker, B -- Zambryski, P -- Staskawicz, B -- Dinesh-Kumar, S P -- GM45244/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1997 May 2;276(5313):726-33.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Plant and Microbial Biology, University of California, Berkeley, CA 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9115193" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arabidopsis/genetics/microbiology/physiology/virology ; Bacteria/genetics ; *Bacterial Physiological Phenomena ; Biological Evolution ; Fungi/physiology ; Genes, Plant ; Immunity, Innate ; Plant Diseases/*microbiology ; Plant Physiological Phenomena ; Plant Proteins/*physiology ; Plants/genetics/*microbiology/virology ; *Signal Transduction
    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: 1989-04-14
    Description: Previous studies have demonstrated that allelic deletions of the short arm of chromosome 17 occur in over 75% of colorectal carcinomas. Twenty chromosome 17p markers were used to localize the common region of deletion in these tumors to a region contained within bands 17p12 to 17p13.3. This region contains the gene for the transformation-associated protein p53. Southern and Northern blot hybridization experiments provided no evidence for gross alterations of the p53 gene or surrounding sequences. As a more rigorous test of the possibility that p53 was a target of the deletions, the p53 coding regions from two tumors were analyzed; these two tumors, like most colorectal carcinomas, had allelic deletions of chromosome 17p and expressed considerable amounts of p53 messenger RNA from the remaining allele. The remaining p53 allele was mutated in both tumors, with an alanine substituted for valine at codon 143 of one tumor and a histidine substituted for arginine at codon 175 of the second tumor. Both mutations occurred in a highly conserved region of the p53 gene that was previously found to be mutated in murine p53 oncogenes. The data suggest that p53 gene mutations may be involved in colorectal neoplasia, perhaps through inactivation of a tumor suppressor function of the wild-type p53 gene.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baker, S J -- Fearon, E R -- Nigro, J M -- Hamilton, S R -- Preisinger, A C -- Jessup, J M -- vanTuinen, P -- Ledbetter, D H -- Barker, D F -- Nakamura, Y -- White, R -- Vogelstein, B -- GM07184/GM/NIGMS NIH HHS/ -- GM07309/GM/NIGMS NIH HHS/ -- HD20619/HD/NICHD NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1989 Apr 14;244(4901):217-21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Oncology Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2649981" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; *Chromosome Deletion ; *Chromosomes, Human, Pair 17/ultrastructure ; Colorectal Neoplasms/*genetics ; Humans ; Mice ; Mice, Nude ; *Mutation ; Neoplasm Proteins/*genetics ; Nucleic Acid Hybridization ; Oncogenes ; Phosphoproteins/*genetics ; Suppression, Genetic ; Tumor Suppressor Protein p53
    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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  • 9
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-12-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baker, R J -- Yates, T L -- New York, N.Y. -- Science. 1998 Nov 6;282(5391):1048-9; author reply 1049.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9841449" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; *Biology ; *Museums
    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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  • 10
    Publication Date: 2010-08-06
    Description: People exert large amounts of problem-solving effort playing computer games. Simple image- and text-recognition tasks have been successfully 'crowd-sourced' through games, but it is not clear if more complex scientific problems can be solved with human-directed computing. Protein structure prediction is one such problem: locating the biologically relevant native conformation of a protein is a formidable computational challenge given the very large size of the search space. Here we describe Foldit, a multiplayer online game that engages non-scientists in solving hard prediction problems. Foldit players interact with protein structures using direct manipulation tools and user-friendly versions of algorithms from the Rosetta structure prediction methodology, while they compete and collaborate to optimize the computed energy. We show that top-ranked Foldit players excel at solving challenging structure refinement problems in which substantial backbone rearrangements are necessary to achieve the burial of hydrophobic residues. Players working collaboratively develop a rich assortment of new strategies and algorithms; unlike computational approaches, they explore not only the conformational space but also the space of possible search strategies. The integration of human visual problem-solving and strategy development capabilities with traditional computational algorithms through interactive multiplayer games is a powerful new approach to solving computationally-limited scientific problems.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2956414/" 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/PMC2956414/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cooper, Seth -- Khatib, Firas -- Treuille, Adrien -- Barbero, Janos -- Lee, Jeehyung -- Beenen, Michael -- Leaver-Fay, Andrew -- Baker, David -- Popovic, Zoran -- Players, Foldit -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Aug 5;466(7307):756-60. doi: 10.1038/nature09304.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Computer Science and Engineering, University of Washington, Box 352350, Seattle, Washington 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20686574" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Computational Biology/*methods ; Computer Graphics ; Computer Simulation ; Cooperative Behavior ; Cues ; *Games, Experimental ; *Group Processes ; Humans ; Hydrogen Bonding ; Hydrophobic and Hydrophilic Interactions ; Imaging, Three-Dimensional ; *Internet ; Leisure Activities ; Models, Molecular ; Nuclear Magnetic Resonance, Biomolecular ; Photic Stimulation ; *Problem Solving ; Protein Conformation ; *Protein Folding ; Proteins/*chemistry/metabolism ; Stochastic Processes ; Thermodynamics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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