ALBERT

Description: Hundreds of pathways for degradation converge at ubiquitin recognition by a proteasome. Here, we found that the five known proteasomal ubiquitin receptors in yeast are collectively nonessential for ubiquitin recognition and identified a sixth receptor, Rpn1. A site ( T1: ) in the Rpn1 toroid recognized ubiquitin and ubiquitin-like ( UBL: ) domains of substrate shuttling factors. T1 structures with monoubiquitin or lysine 48 diubiquitin show three neighboring outer helices engaging two ubiquitins. T1 contributes a distinct substrate-binding pathway with preference for lysine 48-linked chains. Proximal to T1 within the Rpn1 toroid is a second UBL-binding site ( T2: ) that assists in ubiquitin chain disassembly, by binding the UBL of deubiquitinating enzyme Ubp6. Thus, a two-site recognition domain intrinsic to the proteasome uses distinct ubiquitin-fold ligands to assemble substrates, shuttling factors, and a deubiquitinating enzyme.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shi, Yuan -- Chen, Xiang -- Elsasser, Suzanne -- Stocks, Bradley B -- Tian, Geng -- Lee, Byung-Hoon -- Shi, Yanhong -- Zhang, Naixia -- de Poot, Stefanie A H -- Tuebing, Fabian -- Sun, Shuangwu -- Vannoy, Jacob -- Tarasov, Sergey G -- Engen, John R -- Finley, Daniel -- Walters, Kylie J -- New York, N.Y. -- Science. 2016 Feb 19;351(6275). pii: aad9421. doi: 10.1126/science.aad9421.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA. ; Protein Processing Section, Structural Biophysics Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. ; Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA. ; Protein Processing Section, Structural Biophysics Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. Department of Analytical Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, P. R. China. ; Department of Analytical Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, P. R. China. ; Protein Processing Section, Structural Biophysics Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. Linganore High School, Frederick, MD 21701, USA. ; Biophysics Resource, Structural Biophysics Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. ; Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA. j.engen@neu.edu kylie.walters@nih.gov daniel_finley@hms.harvard.edu. ; Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA. j.engen@neu.edu kylie.walters@nih.gov daniel_finley@hms.harvard.edu. ; Protein Processing Section, Structural Biophysics Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. j.engen@neu.edu kylie.walters@nih.gov daniel_finley@hms.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26912900" target="_blank"〉PubMed〈/a〉

Description: To explore the distinct genotypic and phenotypic states of melanoma tumors, we applied single-cell RNA sequencing (RNA-seq) to 4645 single cells isolated from 19 patients, profiling malignant, immune, stromal, and endothelial cells. Malignant cells within the same tumor displayed transcriptional heterogeneity associated with the cell cycle, spatial context, and a drug-resistance program. In particular, all tumors harbored malignant cells from two distinct transcriptional cell states, such that tumors characterized by high levels of the MITF transcription factor also contained cells with low MITF and elevated levels of the AXL kinase. Single-cell analyses suggested distinct tumor microenvironmental patterns, including cell-to-cell interactions. Analysis of tumor-infiltrating T cells revealed exhaustion programs, their connection to T cell activation and clonal expansion, and their variability across patients. Overall, we begin to unravel the cellular ecosystem of tumors and how single-cell genomics offers insights with implications for both targeted and immune therapies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tirosh, Itay -- Izar, Benjamin -- Prakadan, Sanjay M -- Wadsworth, Marc H 2nd -- Treacy, Daniel -- Trombetta, John J -- Rotem, Asaf -- Rodman, Christopher -- Lian, Christine -- Murphy, George -- Fallahi-Sichani, Mohammad -- Dutton-Regester, Ken -- Lin, Jia-Ren -- Cohen, Ofir -- Shah, Parin -- Lu, Diana -- Genshaft, Alex S -- Hughes, Travis K -- Ziegler, Carly G K -- Kazer, Samuel W -- Gaillard, Aleth -- Kolb, Kellie E -- Villani, Alexandra-Chloe -- Johannessen, Cory M -- Andreev, Aleksandr Y -- Van Allen, Eliezer M -- Bertagnolli, Monica -- Sorger, Peter K -- Sullivan, Ryan J -- Flaherty, Keith T -- Frederick, Dennie T -- Jane-Valbuena, Judit -- Yoon, Charles H -- Rozenblatt-Rosen, Orit -- Shalek, Alex K -- Regev, Aviv -- Garraway, Levi A -- 1U24CA180922/CA/NCI NIH HHS/ -- DP2 OD020839/OD/NIH HHS/ -- K99 CA194163/CA/NCI NIH HHS/ -- K99CA194163/CA/NCI NIH HHS/ -- P01CA163222/CA/NCI NIH HHS/ -- P30-CA14051/CA/NCI NIH HHS/ -- P50GM107618/GM/NIGMS NIH HHS/ -- R35CA197737/CA/NCI NIH HHS/ -- U54CA112962/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2016 Apr 8;352(6282):189-96. doi: 10.1126/science.aad0501.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA. Center for Cancer Precision Medicine, Dana-Farber Cancer Institute, Boston, MA 02215, USA. bizar@partners.org aregev@broadinstitute.org levi_garraway@dfci.harvard.edu. ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA. Department of Chemistry, MIT, Cambridge, MA 02142, USA. Ragon Institute of Massachusetts General Hospital, MIT and Harvard University, Cambridge, MA 02139, USA. ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA. Center for Cancer Precision Medicine, Dana-Farber Cancer Institute, Boston, MA 02215, USA. ; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. ; Program in Therapeutic Sciences, Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA. ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA. Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. ; HMS LINCS Center and Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA 02115, USA. ; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA. ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA. Ragon Institute of Massachusetts General Hospital, MIT and Harvard University, Cambridge, MA 02139, USA. Division of Health Sciences and Technology, Harvard Medical School, Boston, MA 02115, USA. ; Department of Surgical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA. Department of Surgical Oncology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. ; Program in Therapeutic Sciences, Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA. HMS LINCS Center and Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA 02115, USA. Ludwig Center at Harvard, Boston, MA 02215, USA. ; Division of Medical Oncology, Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA. ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA. Department of Chemistry, MIT, Cambridge, MA 02142, USA. Ragon Institute of Massachusetts General Hospital, MIT and Harvard University, Cambridge, MA 02139, USA. Division of Health Sciences and Technology, Harvard Medical School, Boston, MA 02115, USA. Department of Immunology, Massachusetts General Hospital, Boston, MA 02114, USA. ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Department of Biology and Koch Institute, MIT, Boston, MA 02142, USA. Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. bizar@partners.org aregev@broadinstitute.org levi_garraway@dfci.harvard.edu. ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. bizar@partners.org aregev@broadinstitute.org levi_garraway@dfci.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27124452" target="_blank"〉PubMed〈/a〉

Description: Computation can be performed in living cells by DNA-encoded circuits that process sensory information and control biological functions. Their construction is time-intensive, requiring manual part assembly and balancing of regulator expression. We describe a design environment, Cello, in which a user writes Verilog code that is automatically transformed into a DNA sequence. Algorithms build a circuit diagram, assign and connect gates, and simulate performance. Reliable circuit design requires the insulation of gates from genetic context, so that they function identically when used in different circuits. We used Cello to design 60 circuits forEscherichia coli(880,000 base pairs of DNA), for which each DNA sequence was built as predicted by the software with no additional tuning. Of these, 45 circuits performed correctly in every output state (up to 10 regulators and 55 parts), and across all circuits 92% of the output states functioned as predicted. Design automation simplifies the incorporation of genetic circuits into biotechnology projects that require decision-making, control, sensing, or spatial organization.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nielsen, Alec A K -- Der, Bryan S -- Shin, Jonghyeon -- Vaidyanathan, Prashant -- Paralanov, Vanya -- Strychalski, Elizabeth A -- Ross, David -- Densmore, Douglas -- Voigt, Christopher A -- P50 GM098792/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2016 Apr 1;352(6281):aac7341. doi: 10.1126/science.aac7341.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Synthetic Biology Center, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. ; Synthetic Biology Center, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Biological Design Center, Department of Biomedical Engineering, Department of Electrical and Computer Engineering, Boston University, Boston, MA 02215, USA. ; Biological Design Center, Department of Biomedical Engineering, Department of Electrical and Computer Engineering, Boston University, Boston, MA 02215, USA. ; Biosystems and Biomaterials Division, Material Measurement Laboratory, National Institute of Standards and Technology, Gaithersburg, MD 20817, USA. ; Synthetic Biology Center, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. cavoigt@gmail.com.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27034378" target="_blank"〉PubMed〈/a〉

Description: The U4/U6.U5 triple small nuclear ribonucleoprotein (tri-snRNP) is a major spliceosome building block. We obtained a three-dimensional structure of the 1.8-megadalton human tri-snRNP at a resolution of 7 angstroms using single-particle cryo-electron microscopy (cryo-EM). We fit all known high-resolution structures of tri-snRNP components into the EM density map and validated them by protein cross-linking. Our model reveals how the spatial organization of Brr2 RNA helicase prevents premature U4/U6 RNA unwinding in isolated human tri-snRNPs and how the ubiquitin C-terminal hydrolase-like protein Sad1 likely tethers the helicase Brr2 to its preactivation position. Comparison of our model with cryo-EM three-dimensional structures of the Saccharomyces cerevisiae tri-snRNP and Schizosaccharomyces pombe spliceosome indicates that Brr2 undergoes a marked conformational change during spliceosome activation, and that the scaffolding protein Prp8 is also rearranged to accommodate the spliceosome's catalytic RNA network.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Agafonov, Dmitry E -- Kastner, Berthold -- Dybkov, Olexandr -- Hofele, Romina V -- Liu, Wen-Ti -- Urlaub, Henning -- Luhrmann, Reinhard -- Stark, Holger -- New York, N.Y. -- Science. 2016 Mar 25;351(6280):1416-20. doi: 10.1126/science.aad2085. Epub 2016 Feb 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular Biochemistry, Max Planck Institute for Biophysical Chemistry, D-37077 Gottingen, Germany. ; Bioanalytical Mass Spectrometry, Max Planck Institute for Biophysical Chemistry, D-37077 Gottingen, Germany. Bioanalytics Group, Institute for Clinical Chemistry, University Medical Center Gottingen, D-37075 Gottingen, Germany. ; Department of 3D Electron Cryomicroscopy, Georg-August Universitat Gottingen, D-37077 Gottingen, Germany. Department of Structural Dynamics, Max Planck Institute for Biophysical Chemistry, D-37077 Gottingen, Germany. ; Bioanalytical Mass Spectrometry, Max Planck Institute for Biophysical Chemistry, D-37077 Gottingen, Germany. Bioanalytics Group, Institute for Clinical Chemistry, University Medical Center Gottingen, D-37075 Gottingen, Germany. reinhard.luehrmann@mpi-bpc.mpg.de hstark1@gwdg.de henning.urlaub@mpibpc.mpg.de. ; Department of Cellular Biochemistry, Max Planck Institute for Biophysical Chemistry, D-37077 Gottingen, Germany. reinhard.luehrmann@mpi-bpc.mpg.de hstark1@gwdg.de henning.urlaub@mpibpc.mpg.de. ; Department of 3D Electron Cryomicroscopy, Georg-August Universitat Gottingen, D-37077 Gottingen, Germany. Department of Structural Dynamics, Max Planck Institute for Biophysical Chemistry, D-37077 Gottingen, Germany. reinhard.luehrmann@mpi-bpc.mpg.de hstark1@gwdg.de henning.urlaub@mpibpc.mpg.de.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26912367" target="_blank"〉PubMed〈/a〉

Description: Bruns and Taylor argue that our finding of widespread distribution among Glomeromycota "virtual taxa" is undermined by the species definition applied. Although identifying appropriate species concepts and accessing taxonomically informative traits are challenges for microorganism biogeography, the virtual taxa represent a pragmatic classification that corresponds approximately to the species rank of classical Glomeromycota taxonomy, yet is applicable to environmental DNA.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Opik, Maarja -- Davison, John -- Moora, Mari -- Partel, Meelis -- Zobel, Martin -- New York, N.Y. -- Science. 2016 Feb 19;351(6275):826. doi: 10.1126/science.aad5495.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Botany, University of Tartu, 40 Lai Street, 51005 Tartu, Estonia. maarja.opik@ut.ee. ; Department of Botany, University of Tartu, 40 Lai Street, 51005 Tartu, Estonia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26912890" target="_blank"〉PubMed〈/a〉

Description: AMPA-type glutamate receptors (AMPARs), which are central mediators of rapid neurotransmission and synaptic plasticity, predominantly exist as heteromers of the subunits GluA1 to GluA4. Here we report the first AMPAR heteromer structures, which deviate substantially from existing GluA2 homomer structures. Crystal structures of the GluA2/3 and GluA2/4 N-terminal domains reveal a novel compact conformation with an alternating arrangement of the four subunits around a central axis. This organization is confirmed by cysteine cross-linking in full-length receptors, and it permitted us to determine the structure of an intact GluA2/3 receptor by cryogenic electron microscopy. Two models in the ligand-free state, at resolutions of 8.25 and 10.3 angstroms, exhibit substantial vertical compression and close associations between domain layers, reminiscent of N-methyl-D-aspartate receptors. Model 1 resembles a resting state and model 2 a desensitized state, thus providing snapshots of gating transitions in the nominal absence of ligand. Our data reveal organizational features of heteromeric AMPARs and provide a framework to decipher AMPAR architecture and signaling.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4852135/" 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/PMC4852135/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Herguedas, Beatriz -- Garcia-Nafria, Javier -- Cais, Ondrej -- Fernandez-Leiro, Rafael -- Krieger, James -- Ho, Hinze -- Greger, Ingo H -- MC_U105174197/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2016 Apr 29;352(6285):aad3873. doi: 10.1126/science.aad3873. Epub 2016 Mar 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Neurobiology Division, Medical Research Council (MRC) Laboratory of Molecular Biology, Cambridge, UK. ; Structural Studies Division, MRC Laboratory of Molecular Biology, Cambridge, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26966189" target="_blank"〉PubMed〈/a〉

Description: Sequencing of exomes and genomes has revealed abundant genetic variation affecting the coding sequences of human transcription factors (TFs), but the consequences of such variation remain largely unexplored. We developed a computational, structure-based approach to evaluate TF variants for their impact on DNA binding activity and used universal protein-binding microarrays to assay sequence-specific DNA binding activity across 41 reference and 117 variant alleles found in individuals of diverse ancestries and families with Mendelian diseases. We found 77 variants in 28 genes that affect DNA binding affinity or specificity and identified thousands of rare alleles likely to alter the DNA binding activity of human sequence-specific TFs. Our results suggest that most individuals have unique repertoires of TF DNA binding activities, which may contribute to phenotypic variation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4825693/" 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/PMC4825693/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barrera, Luis A -- Vedenko, Anastasia -- Kurland, Jesse V -- Rogers, Julia M -- Gisselbrecht, Stephen S -- Rossin, Elizabeth J -- Woodard, Jaie -- Mariani, Luca -- Kock, Kian Hong -- Inukai, Sachi -- Siggers, Trevor -- Shokri, Leila -- Gordan, Raluca -- Sahni, Nidhi -- Cotsapas, Chris -- Hao, Tong -- Yi, Song -- Kellis, Manolis -- Daly, Mark J -- Vidal, Marc -- Hill, David E -- Bulyk, Martha L -- P50 HG004233/HG/NHGRI NIH HHS/ -- R01 HG003985/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2016 Mar 25;351(6280):1450-4. doi: 10.1126/science.aad2257. Epub 2016 Mar 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, MA 02138, USA. Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, MA 02115, USA. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. ; Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. ; Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, MA 02138, USA. ; Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, MA 02115, USA. Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. Broad Institute of Harvard and MIT, Cambridge, MA 02139, USA. ; Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. Program in Biological and Biomedical Sciences, Harvard University, Cambridge, MA 02138, USA. ; Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA 02215, USA. Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA. Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. ; Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. Broad Institute of Harvard and MIT, Cambridge, MA 02139, USA. ; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Broad Institute of Harvard and MIT, Cambridge, MA 02139, USA. ; Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. Broad Institute of Harvard and MIT, Cambridge, MA 02139, USA. Center for Human Genetics Research and Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA 02114, USA. ; Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, MA 02138, USA. Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, MA 02115, USA. Broad Institute of Harvard and MIT, Cambridge, MA 02139, USA. Program in Biological and Biomedical Sciences, Harvard University, Cambridge, MA 02138, USA. Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA 02215, USA. Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27013732" target="_blank"〉PubMed〈/a〉

Description: p97 is a hexameric AAA+ adenosine triphosphatase (ATPase) that is an attractive target for cancer drug development. We report cryo-electron microscopy (cryo-EM) structures for adenosine diphosphate (ADP)-bound, full-length, hexameric wild-type p97 in the presence and absence of an allosteric inhibitor at resolutions of 2.3 and 2.4 angstroms, respectively. We also report cryo-EM structures (at resolutions of ~3.3, 3.2, and 3.3 angstroms, respectively) for three distinct, coexisting functional states of p97 with occupancies of zero, one, or two molecules of adenosine 5'-O-(3-thiotriphosphate) (ATPgammaS) per protomer. A large corkscrew-like change in molecular architecture, coupled with upward displacement of the N-terminal domain, is observed only when ATPgammaS is bound to both the D1 and D2 domains of the protomer. These cryo-EM structures establish the sequence of nucleotide-driven structural changes in p97 at atomic resolution. They also enable elucidation of the binding mode of an allosteric small-molecule inhibitor to p97 and illustrate how inhibitor binding at the interface between the D1 and D2 domains prevents propagation of the conformational changes necessary for p97 function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Banerjee, Soojay -- Bartesaghi, Alberto -- Merk, Alan -- Rao, Prashant -- Bulfer, Stacie L -- Yan, Yongzhao -- Green, Neal -- Mroczkowski, Barbara -- Neitz, R Jeffrey -- Wipf, Peter -- Falconieri, Veronica -- Deshaies, Raymond J -- Milne, Jacqueline L S -- Huryn, Donna -- Arkin, Michelle -- Subramaniam, Sriram -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2016 Feb 19;351(6275):871-5. doi: 10.1126/science.aad7974. Epub 2016 Jan 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Cell Biology, National Cancer Institute, Bethesda, MD 20892, USA. ; Small Molecule Discovery Center, Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco, CA 94143, USA. ; University of Pittsburgh Chemical Diversity Center, University of Pittsburgh, Pittsburgh, PA 15260, USA. ; Leidos Biomedical Research Inc., Frederick, MD 21702, USA. ; Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD 20892, USA. ; Division of Biology and Biological Engineering and Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91107, USA. ; Laboratory of Cell Biology, National Cancer Institute, Bethesda, MD 20892, USA. ss1@nih.gov.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26822609" target="_blank"〉PubMed〈/a〉

Description: Davison et al. (Reports, 28 August 2015, p. 970) claim that virtual taxa of Glomeromycota show little endemism and that endemism that exists is similar to the levels seen in plant families. We show that this is likely due to the conservative species definition rather than to any ecological pattern.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bruns, Thomas D -- Taylor, John W -- New York, N.Y. -- Science. 2016 Feb 19;351(6275):826. doi: 10.1126/science.aad4228.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Plant and Microbial Biology, 111 Koshland Hall, Berkeley, CA 94720-3102, USA. pogon@berkeley.edu. ; Department of Plant and Microbial Biology, 111 Koshland Hall, Berkeley, CA 94720-3102, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26912889" target="_blank"〉PubMed〈/a〉

Description: Recent studies have implicated long noncoding RNAs (lncRNAs) as regulators of many important biological processes. Here we report on the identification and characterization of a lncRNA, lnc13, that harbors a celiac disease-associated haplotype block and represses expression of certain inflammatory genes under homeostatic conditions. Lnc13 regulates gene expression by binding to hnRNPD, a member of a family of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). Upon stimulation, lnc13 levels are reduced, thereby allowing increased expression of the repressed genes. Lnc13 levels are significantly decreased in small intestinal biopsy samples from patients with celiac disease, which suggests that down-regulation of lnc13 may contribute to the inflammation seen in this disease. Furthermore, the lnc13 disease-associated variant binds hnRNPD less efficiently than its wild-type counterpart, thus helping to explain how these single-nucleotide polymorphisms contribute to celiac disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Castellanos-Rubio, Ainara -- Fernandez-Jimenez, Nora -- Kratchmarov, Radomir -- Luo, Xiaobing -- Bhagat, Govind -- Green, Peter H R -- Schneider, Robert -- Kiledjian, Megerditch -- Bilbao, Jose Ramon -- Ghosh, Sankar -- R01-AI093985/AI/NIAID NIH HHS/ -- R01-DK102180/DK/NIDDK NIH HHS/ -- R01-GM067005/GM/NIGMS NIH HHS/ -- R37-AI33443/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2016 Apr 1;352(6281):91-5. doi: 10.1126/science.aad0467.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA. ; Department of Genetics, Physical Anthropology, and Animal Physiology, University of the Basque Country (UPV-EHU), BioCruces Research Institute, Leioa 48940, Basque Country, Spain. ; Department of Pathology and Cell Biology, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA. ; Center for Celiac Disease, Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA. Alexandria Center for Life Sciences, New York University School of Medicine, New York, NY 10016, USA. ; Alexandria Center for Life Sciences, New York University School of Medicine, New York, NY 10016, USA. ; Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA. ; Department of Microbiology and Immunology, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA. sg2715@columbia.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27034373" target="_blank"〉PubMed〈/a〉

Description: Type IVa pili are filamentous cell surface structures observed in many bacteria. They pull cells forward by extending, adhering to surfaces, and then retracting. We used cryo-electron tomography of intact Myxococcus xanthus cells to visualize type IVa pili and the protein machine that assembles and retracts them (the type IVa pilus machine, or T4PM) in situ, in both the piliated and nonpiliated states, at a resolution of 3 to 4 nanometers. We found that T4PM comprises an outer membrane pore, four interconnected ring structures in the periplasm and cytoplasm, a cytoplasmic disc and dome, and a periplasmic stem. By systematically imaging mutants lacking defined T4PM proteins or with individual proteins fused to tags, we mapped the locations of all 10 T4PM core components and the minor pilins, thereby providing insights into pilus assembly, structure, and function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chang, Yi-Wei -- Rettberg, Lee A -- Treuner-Lange, Anke -- Iwasa, Janet -- Sogaard-Andersen, Lotte -- Jensen, Grant J -- R01 GM094800B/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2016 Mar 11;351(6278):aad2001. doi: 10.1126/science.aad2001. Epub 2016 Mar 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉California Institute of Technology, Pasadena, CA 91125, USA. Howard Hughes Medical Institute, Pasadena, CA 91125, USA. ; Howard Hughes Medical Institute, Pasadena, CA 91125, USA. ; Max Planck Institute for Terrestrial Microbiology, 35043 Marburg, Germany. ; University of Utah, Salt Lake City, UT 84112, USA. ; California Institute of Technology, Pasadena, CA 91125, USA. Howard Hughes Medical Institute, Pasadena, CA 91125, USA. jensen@caltech.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26965631" target="_blank"〉PubMed〈/a〉

Description: Nuclear pore complexes (NPCs) are 110-megadalton assemblies that mediate nucleocytoplasmic transport. NPCs are built from multiple copies of ~30 different nucleoporins, and understanding how these nucleoporins assemble into the NPC scaffold imposes a formidable challenge. Recently, it has been shown how the Y complex, a prominent NPC module, forms the outer rings of the nuclear pore. However, the organization of the inner ring has remained unknown until now. We used molecular modeling combined with cross-linking mass spectrometry and cryo-electron tomography to obtain a composite structure of the inner ring. This architectural map explains the vast majority of the electron density of the scaffold. We conclude that despite obvious differences in morphology and composition, the higher-order structure of the inner and outer rings is unexpectedly similar.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kosinski, Jan -- Mosalaganti, Shyamal -- von Appen, Alexander -- Teimer, Roman -- DiGuilio, Amanda L -- Wan, William -- Bui, Khanh Huy -- Hagen, Wim J H -- Briggs, John A G -- Glavy, Joseph S -- Hurt, Ed -- Beck, Martin -- 1R21AG047433-01/AG/NIA NIH HHS/ -- R21 AG047433/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2016 Apr 15;352(6283):363-5. doi: 10.1126/science.aaf0643.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany. ; Biochemistry Center of Heidelberg University, Im Neuenheimer Feld 328, D-69120 Heidelberg, Germany. ; Department of Chemistry, Chemical Biology and Biomedical Engineering, Stevens Institute of Technology, 507 River Street, Hoboken, NJ 07030, USA. ; Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada. ; Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany. Cell Biology and Biophysics Unit, EMBL, Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27081072" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dantzer, Ben -- New York, N.Y. -- Science. 2015 Feb 20;347(6224):822-3. doi: 10.1126/science.aaa6480.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Psychology and Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, MI 48109, USA. dantzer@umich.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25700499" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mervis, Jeffrey -- New York, N.Y. -- Science. 2015 Dec 18;350(6267):1454. doi: 10.1126/science.350.6267.1454.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26680170" target="_blank"〉PubMed〈/a〉

Description: The global biogeography of microorganisms remains largely unknown, in contrast to the well-studied diversity patterns of macroorganisms. We used arbuscular mycorrhizal (AM) fungus DNA from 1014 plant-root samples collected worldwide to determine the global distribution of these plant symbionts. We found that AM fungal communities reflected local environmental conditions and the spatial distance between sites. However, despite AM fungi apparently possessing limited dispersal ability, we found 93% of taxa on multiple continents and 34% on all six continents surveyed. This contrasts with the high spatial turnover of other fungal taxa and with the endemism displayed by plants at the global scale. We suggest that the biogeography of AM fungi is driven by unexpectedly efficient dispersal, probably via both abiotic and biotic vectors, including humans.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Davison, J -- Moora, M -- Opik, M -- Adholeya, A -- Ainsaar, L -- Ba, A -- Burla, S -- Diedhiou, A G -- Hiiesalu, I -- Jairus, T -- Johnson, N C -- Kane, A -- Koorem, K -- Kochar, M -- Ndiaye, C -- Partel, M -- Reier, U -- Saks, U -- Singh, R -- Vasar, M -- Zobel, M -- New York, N.Y. -- Science. 2015 Aug 28;349(6251):970-3. doi: 10.1126/science.aab1161.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Ecology and Earth Sciences, University of Tartu, Lai 40, Tartu 51005, Estonia. ; Centre for Mycorrhizal Research, The Energy and Resources Institute (TERI), India Habitat Centre, Lodhi Road, New Delhi 110 003, India. ; Laboratoire des Symbioses Tropicales et Mediterraneennes, Unite Mixte de Recherche 113, Laboratoire de Biologie et Physiologie Vegetales, Faculte des Sciences Exactes et Naturelles, Universite des Antilles, BP 592, 97159, Pointe-a-Pitre, Guadeloupe (French West Indies). ; Laboratoire Commun de Microbiologie de l'Institut de Recherche pour le Developpement-Institut Senegalais de Recherches Agricoles-Universite Cheikh Anta Diop (UCAD), Departement de Biologie Vegetale, UCAD, BP 5005 Dakar, Senegal. ; Institute of Ecology and Earth Sciences, University of Tartu, Lai 40, Tartu 51005, Estonia. Institute of Botany, Czech Academy of Sciences, Dukelska 135, 379 01 Trebon, Czech Republic. ; School of Earth Sciences and Environmental Sustainability, Northern Arizona University, Flagstaff, AZ 86011-5694, USA. ; Institute of Ecology and Earth Sciences, University of Tartu, Lai 40, Tartu 51005, Estonia. Netherlands Institute of Ecology, Droevendaalsesteeg 10, 6708 PB Wageningen, Netherlands. ; TERI-Deakin Nano Biotechnology Centre, Biotechnology and Management of Bioresources Division, TERI, India Habitat Centre, Lodhi Road, New Delhi 110 003, India.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26315436" target="_blank"〉PubMed〈/a〉

Description: Self-organized spatial vegetation patterning is widespread and has been described using models of scale-dependent feedback between plants and water on homogeneous substrates. As rainfall decreases, these models yield a characteristic sequence of patterns with increasingly sparse vegetation, followed by sudden collapse to desert. Thus, the final, spot-like pattern may provide early warning for such catastrophic shifts. In many arid ecosystems, however, termite nests impart substrate heterogeneity by altering soil properties, thereby enhancing plant growth. We show that termite-induced heterogeneity interacts with scale-dependent feedbacks to produce vegetation patterns at different spatial grains. Although the coarse-grained patterning resembles that created by scale-dependent feedback alone, it does not indicate imminent desertification. Rather, mound-field landscapes are more robust to aridity, suggesting that termites may help stabilize ecosystems under global change.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bonachela, Juan A -- Pringle, Robert M -- Sheffer, Efrat -- Coverdale, Tyler C -- Guyton, Jennifer A -- Caylor, Kelly K -- Levin, Simon A -- Tarnita, Corina E -- New York, N.Y. -- Science. 2015 Feb 6;347(6222):651-5. doi: 10.1126/science.1261487.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ 08544, USA. ; Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ 08544, USA. Mpala Research Centre, Post Office Box 555, Nanyuki, Kenya. ; Mpala Research Centre, Post Office Box 555, Nanyuki, Kenya. Department of Civil and Environmental Engineering, Princeton University, Princeton, NJ 08544, USA. ; Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ 08544, USA. Mpala Research Centre, Post Office Box 555, Nanyuki, Kenya. ctarnita@princeton.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25657247" target="_blank"〉PubMed〈/a〉

Description: Sedimentary basins in eastern Africa preserve a record of continental rifting and contain important fossil assemblages for interpreting hominin evolution. However, the record of hominin evolution between 3 and 2.5 million years ago (Ma) is poorly documented in surface outcrops, particularly in Afar, Ethiopia. Here we present the discovery of a 2.84- to 2.58-million-year-old fossil and hominin-bearing sediments in the Ledi-Geraru research area of Afar, Ethiopia, that have produced the earliest record of the genus Homo. Vertebrate fossils record a faunal turnover indicative of more open and probably arid habitats than those reconstructed earlier in this region, which is in broad agreement with hypotheses addressing the role of environmental forcing in hominin evolution at this time. Geological analyses constrain depositional and structural models of Afar and date the LD 350-1 Homo mandible to 2.80 to 2.75 Ma.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉DiMaggio, Erin N -- Campisano, Christopher J -- Rowan, John -- Dupont-Nivet, Guillaume -- Deino, Alan L -- Bibi, Faysal -- Lewis, Margaret E -- Souron, Antoine -- Garello, Dominique -- Werdelin, Lars -- Reed, Kaye E -- Arrowsmith, J Ramon -- New York, N.Y. -- Science. 2015 Mar 20;347(6228):1355-9. doi: 10.1126/science.aaa1415. Epub 2015 Mar 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Geosciences, Pennsylvania State University, University Park, PA 16802, USA. dimaggio@psu.edu kreed@asu.edu. ; Institute of Human Origins, School of Human Evolution and Social Change, Arizona State University, Tempe, AZ 85287, USA. ; CNRS Geosciences Rennes, Campus de Beaulieu, 35042 Rennes, France. ; Berkeley Geochronology Center, 2455 Ridge Road, Berkeley, CA 94709, USA. ; Museum fur Naturkunde, Leibniz Institute for Evolution and Biodiversity Science, Invalidenstrasse 43, 10115 Berlin, Germany. ; Biology Program, Stockton University, 101 Vera King Farris Drive, Galloway, NJ 08205, USA. ; Human Evolution Research Center, University of California, Berkeley, 3101 Valley Life Sciences Building, Berkeley, CA, 94720-3160, USA. ; School of Earth and Space Exploration, Arizona State University, Tempe, AZ 85287, USA. ; Swedish Museum of Natural History, Department of Palaeobiology, Box 50007, SE-10405 Stockholm, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25739409" target="_blank"〉PubMed〈/a〉

Description: TREK-2 (KCNK10/K2P10), a two-pore domain potassium (K2P) channel, is gated by multiple stimuli such as stretch, fatty acids, and pH and by several drugs. However, the mechanisms that control channel gating are unclear. Here we present crystal structures of the human TREK-2 channel (up to 3.4 angstrom resolution) in two conformations and in complex with norfluoxetine, the active metabolite of fluoxetine (Prozac) and a state-dependent blocker of TREK channels. Norfluoxetine binds within intramembrane fenestrations found in only one of these two conformations. Channel activation by arachidonic acid and mechanical stretch involves conversion between these states through movement of the pore-lining helices. These results provide an explanation for TREK channel mechanosensitivity, regulation by diverse stimuli, and possible off-target effects of the serotonin reuptake inhibitor Prozac.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dong, Yin Yao -- Pike, Ashley C W -- Mackenzie, Alexandra -- McClenaghan, Conor -- Aryal, Prafulla -- Dong, Liang -- Quigley, Andrew -- Grieben, Mariana -- Goubin, Solenne -- Mukhopadhyay, Shubhashish -- Ruda, Gian Filippo -- Clausen, Michael V -- Cao, Lishuang -- Brennan, Paul E -- Burgess-Brown, Nicola A -- Sansom, Mark S P -- Tucker, Stephen J -- Carpenter, Elisabeth P -- 084655/Wellcome Trust/United Kingdom -- 092809/Z/10/Z/Wellcome Trust/United Kingdom -- Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2015 Mar 13;347(6227):1256-9. doi: 10.1126/science.1261512.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, UK. ; Structural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, UK. Clarendon Laboratory, Department of Physics, University of Oxford, Oxford OX1 3PU, UK. ; Clarendon Laboratory, Department of Physics, University of Oxford, Oxford OX1 3PU, UK. OXION Initiative in Ion Channels and Disease, University of Oxford, Oxford OX1 3PN, UK. ; Clarendon Laboratory, Department of Physics, University of Oxford, Oxford OX1 3PU, UK. OXION Initiative in Ion Channels and Disease, University of Oxford, Oxford OX1 3PN, UK. Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK. ; Structural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, UK. Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK. ; Clarendon Laboratory, Department of Physics, University of Oxford, Oxford OX1 3PU, UK. ; Pfizer Neusentis, Granta Park, Cambridge CB21 6GS, UK. ; OXION Initiative in Ion Channels and Disease, University of Oxford, Oxford OX1 3PN, UK. Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK. ; Clarendon Laboratory, Department of Physics, University of Oxford, Oxford OX1 3PU, UK. OXION Initiative in Ion Channels and Disease, University of Oxford, Oxford OX1 3PN, UK. liz.carpenter@sgc.ox.ac.uk stephen.tucker@physics.ox.ac.uk. ; Structural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, UK. OXION Initiative in Ion Channels and Disease, University of Oxford, Oxford OX1 3PN, UK. liz.carpenter@sgc.ox.ac.uk stephen.tucker@physics.ox.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25766236" target="_blank"〉PubMed〈/a〉

Description: An important question in ecology is how mechanistic processes occurring among individuals drive large-scale patterns of community formation and change. Here we show that in two species of bluebirds, cycles of replacement of one by the other emerge as an indirect consequence of maternal influence on offspring behavior in response to local resource availability. Sampling across broad temporal and spatial scales, we found that western bluebirds, the more competitive species, bias the birth order of offspring by sex in a way that influences offspring aggression and dispersal, setting the stage for rapid increases in population density that ultimately result in the replacement of their sister species. Our results provide insight into how predictable community dynamics can occur despite the contingency of local behavioral interactions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Duckworth, Renee A -- Belloni, Virginia -- Anderson, Samantha R -- New York, N.Y. -- Science. 2015 Feb 20;347(6224):875-7. doi: 10.1126/science.1260154.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, AZ 85721, USA. rad3@email.arizona.edu. ; Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, AZ 85721, USA. Department of Tropical Medicine, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA 70112, USA. ; Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, AZ 85721, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25700519" target="_blank"〉PubMed〈/a〉

Description: Vegetation structure is a key determinant of ecosystems and ecosystem function, but paleoecological techniques to quantify it are lacking. We present a method for reconstructing leaf area index (LAI) based on light-dependent morphology of leaf epidermal cells and phytoliths derived from them. Using this proxy, we reconstruct LAI for the Cenozoic (49 million to 11 million years ago) of middle-latitude Patagonia. Our record shows that dense forests opened up by the late Eocene; open forests and shrubland habitats then fluctuated, with a brief middle-Miocene regreening period. Furthermore, endemic herbivorous mammals show accelerated tooth crown height evolution during open, yet relatively grass-free, shrubland habitat intervals. Our Patagonian LAI record provides a high-resolution, sensitive tool with which to dissect terrestrial ecosystem response to changing Southern Ocean conditions during the Cenozoic.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dunn, Regan E -- Stromberg, Caroline A E -- Madden, Richard H -- Kohn, Matthew J -- Carlini, Alfredo A -- New York, N.Y. -- Science. 2015 Jan 16;347(6219):258-61. doi: 10.1126/science.1260947.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology and Burke Museum of Natural History and Culture, University of Washington, Seattle, WA 98195, USA. dunnr@u.washington.edu. ; Department of Biology and Burke Museum of Natural History and Culture, University of Washington, Seattle, WA 98195, USA. ; Department of Organismal Biology and Anatomy, University of Chicago, Chicago, IL 60637, USA. ; Department of Geosciences, Boise State University, Boise, ID 83725, USA. ; Paleontologia de Vertebrados, Universidad Nacional de La Plata, Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), La Plata, Argentina.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25593182" target="_blank"〉PubMed〈/a〉

Description: Viruses influence ecosystems by modulating microbial population size, diversity, metabolic outputs, and gene flow. Here, we use quantitative double-stranded DNA (dsDNA) viral-fraction metagenomes (viromes) and whole viral community morphological data sets from 43 Tara Oceans expedition samples to assess viral community patterns and structure in the upper ocean. Protein cluster cataloging defined pelagic upper-ocean viral community pan and core gene sets and suggested that this sequence space is well-sampled. Analyses of viral protein clusters, populations, and morphology revealed biogeographic patterns whereby viral communities were passively transported on oceanic currents and locally structured by environmental conditions that affect host community structure. Together, these investigations establish a global ocean dsDNA viromic data set with analyses supporting the seed-bank hypothesis to explain how oceanic viral communities maintain high local diversity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brum, Jennifer R -- Ignacio-Espinoza, J Cesar -- Roux, Simon -- Doulcier, Guilhem -- Acinas, Silvia G -- Alberti, Adriana -- Chaffron, Samuel -- Cruaud, Corinne -- de Vargas, Colomban -- Gasol, Josep M -- Gorsky, Gabriel -- Gregory, Ann C -- Guidi, Lionel -- Hingamp, Pascal -- Iudicone, Daniele -- Not, Fabrice -- Ogata, Hiroyuki -- Pesant, Stephane -- Poulos, Bonnie T -- Schwenck, Sarah M -- Speich, Sabrina -- Dimier, Celine -- Kandels-Lewis, Stefanie -- Picheral, Marc -- Searson, Sarah -- Tara Oceans Coordinators -- Bork, Peer -- Bowler, Chris -- Sunagawa, Shinichi -- Wincker, Patrick -- Karsenti, Eric -- Sullivan, Matthew B -- New York, N.Y. -- Science. 2015 May 22;348(6237):1261498. doi: 10.1126/science.1261498.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, AZ 85721, USA. ; Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ 85721, USA. ; Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, AZ 85721, USA. Environmental and Evolutionary Genomics Section, Institut de Biologie de l'Ecole Normale Superieure (IBENS), CNRS, UMR8197, INSERM U1024, 75230 Paris, France. ; Department of Marine Biology and Oceanography, Institute of Marine Sciences (ICM)-CSIC, Pg. Maritim de la Barceloneta 37-49, Barcelona, E08003, Spain. ; Genoscope, Commissariat a l'Energie Atomique (CEA)-Institut de Genomique, 2 rue Gaston Cremieux, 91057 Evry, France. ; Department of Microbiology and Immunology, Rega Institute, KU Leuven, Herestraat 49, 3000 Leuven, Belgium. Center for the Biology of Disease, VIB KU Leuven, Herestraat 49, 3000 Leuven, Belgium. Department of Applied Biological Sciences, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium. ; CNRS, UMR 7144, Station Biologique de Roscoff, Place Georges Teissier, 29680 Roscoff, France. Sorbonne Universites, Universite Pierre et Marie Curie, Universite Paris 06, and UMR 7144, Station Biologique de Roscoff, Place Georges Teissier, 29680 Roscoff, France. ; CNRS, UMR 7093, Laboratoire d'oceanographie de Villefranche (LOV), Observatoire Oceanologique, 06230 Villefranche-sur-mer, France. Sorbonne Universites, Uiversite Pierre et Marie Curie, Universite Paris 06, UMR 7093, Laboratoire d'oceanographie de Villefranche (LOV), Observatoire Oceanologique, 06230 Villefranche-sur-mer, France. ; Soil, Water, and Environmental Science, University of Arizona, Tucson, AZ 85721, USA. ; Aix Marseille Universite, CNRS IGS UMR 7256, 13288 Marseille, France. ; Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Naples, Italy. ; Institute for Chemical Research, Kyoto University, Gokasho, Uji, Kyoto 611-0001, Japan. ; PANGAEA, Data Publisher for Earth and Environmental Science, University of Bremen, 28359 Bremen, Germany. MARUM, Center for Marine Environmental Sciences, University of Bremen, 28359 Bremen, Germany. ; Laboratoire de Physique des Oceans, Institut Universitaire Europeen de la Mer, Universite de Bretagne Occidentale (UBO-IUEM), Place Copernic, 29820 Plouzane, France. ; CNRS, UMR 7144, Station Biologique de Roscoff, Place Georges Teissier, 29680 Roscoff, France. Sorbonne Universites, Universite Pierre et Marie Curie, Universite Paris 06, and UMR 7144, Station Biologique de Roscoff, Place Georges Teissier, 29680 Roscoff, France. Institut de Biologie de l'Ecole Normale Superieure (IBENS), and INSERM U1024, and CNRS UMR 8197, Paris, 75005, France. ; Structural and Computational Biology, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany. Directors' Research, European Molecular Biology Laboratory Meyerhofstrasse 1, 69117 Heidelberg, Germany. ; Structural and Computational Biology, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany. Max-Delbruck-Centre for Molecular Medicine, 13092 Berlin, Germany. ; Institut de Biologie de l'Ecole Normale Superieure (IBENS), and INSERM U1024, and CNRS UMR 8197, Paris, 75005, France. ; Structural and Computational Biology, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany. ; Genoscope, Commissariat a l'Energie Atomique (CEA)-Institut de Genomique, 2 rue Gaston Cremieux, 91057 Evry, France. CNRS, UMR 8030, CP5706, 91057 Evry, France. Universite d'Evry, UMR 8030, CP5706, 91057 Evry, France. ; Institut de Biologie de l'Ecole Normale Superieure (IBENS), and INSERM U1024, and CNRS UMR 8197, Paris, 75005, France. Directors' Research, European Molecular Biology Laboratory Meyerhofstrasse 1, 69117 Heidelberg, Germany. mbsulli@gmail.com karsenti@embl.de. ; Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, AZ 85721, USA. Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ 85721, USA. Soil, Water, and Environmental Science, University of Arizona, Tucson, AZ 85721, USA. mbsulli@gmail.com karsenti@embl.de.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25999515" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Naeem, S -- Ingram, J C -- Varga, A -- Agardy, T -- Barten, P -- Bennett, G -- Bloomgarden, E -- Bremer, L L -- Burkill, P -- Cattau, M -- Ching, C -- Colby, M -- Cook, D C -- Costanza, R -- DeClerck, F -- Freund, C -- Gartner, T -- Goldman-Benner, R -- Gunderson, J -- Jarrett, D -- Kinzig, A P -- Kiss, A -- Koontz, A -- Kumar, P -- Lasky, J R -- Masozera, M -- Meyers, D -- Milano, F -- Naughton-Treves, L -- Nichols, E -- Olander, L -- Olmsted, P -- Perge, E -- Perrings, C -- Polasky, S -- Potent, J -- Prager, C -- Quetier, F -- Redford, K -- Saterson, K -- Thoumi, G -- Vargas, M T -- Vickerman, S -- Weisser, W -- Wilkie, D -- Wunder, S -- New York, N.Y. -- Science. 2015 Mar 13;347(6227):1206-7. doi: 10.1126/science.aaa1403. Epub 2015 Mar 12.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25766222" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hochberg, Yael V -- Fehder, Daniel C -- New York, N.Y. -- Science. 2015 Jun 12;348(6240):1202-3. doi: 10.1126/science.aab3351.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Rice University, Houston, TX 77251, USA. Massachusetts Institute of Technology, Cambridge, MA 02139, USA. National Bureau of Economic Research, Cambridge, MA 02138, USA. hochberg@rice.edu. ; Massachusetts Institute of Technology, Cambridge, MA 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26068829" target="_blank"〉PubMed〈/a〉

Description: The occurrence of Ebola virus (EBOV) in West Africa during 2013-2015 is unprecedented. Early reports suggested that in this outbreak EBOV is mutating twice as fast as previously observed, which indicates the potential for changes in transmissibility and virulence and could render current molecular diagnostics and countermeasures ineffective. We have determined additional full-length sequences from two clusters of imported EBOV infections into Mali, and we show that the nucleotide substitution rate (9.6 x 10(-4) substitutions per site per year) is consistent with rates observed in Central African outbreaks. In addition, overall variation among all genotypes observed remains low. Thus, our data indicate that EBOV is not undergoing rapid evolution in humans during the current outbreak. This finding has important implications for outbreak response and public health decisions and should alleviate several previously raised concerns.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hoenen, T -- Safronetz, D -- Groseth, A -- Wollenberg, K R -- Koita, O A -- Diarra, B -- Fall, I S -- Haidara, F C -- Diallo, F -- Sanogo, M -- Sarro, Y S -- Kone, A -- Togo, A C G -- Traore, A -- Kodio, M -- Dosseh, A -- Rosenke, K -- de Wit, E -- Feldmann, F -- Ebihara, H -- Munster, V J -- Zoon, K C -- Feldmann, H -- Sow, S -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2015 Apr 3;348(6230):117-9. doi: 10.1126/science.aaa5646. Epub 2015 Mar 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Hamilton, MT 59840, USA. ; Bioinformatics and Computational Biosciences Branch, NIAID, NIH, Bethesda, MD 20892, USA. ; Center of Research and Training for HIV and Tuberculosis, University of Science, Technique and Technologies of Bamako, Mali. ; World Health Organization Office, Bamako, Mali. ; Centre des Operations d'Urgence, Centre pour le Developpement des Vaccins (CVD-Mali), Centre National d'Appui a la lutte contre la Maladie, Ministere de la Sante et de l'Hygiene Publique, Bamako, Mali. ; World Health Organization Inter-Country Support Team, Ouagadougou, Burkina Faso. ; Rocky Mountain Veterinary Branch, Division of Intramural Research, NIAID, NIH, Hamilton, MT 59840, USA. ; Office of the Scientific Director, NIAID, NIH, Bethesda, MD 20895, USA. ; Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Hamilton, MT 59840, USA. feldmannh@niaid.nih.gov ssow@medicine.umaryland.edu. ; Centre des Operations d'Urgence, Centre pour le Developpement des Vaccins (CVD-Mali), Centre National d'Appui a la lutte contre la Maladie, Ministere de la Sante et de l'Hygiene Publique, Bamako, Mali. feldmannh@niaid.nih.gov ssow@medicine.umaryland.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25814067" target="_blank"〉PubMed〈/a〉

Description: DNA strand exchange plays a central role in genetic recombination across all kingdoms of life, but the physical basis for these reactions remains poorly defined. Using single-molecule imaging, we found that bacterial RecA and eukaryotic Rad51 and Dmc1 all stabilize strand exchange intermediates in precise three-nucleotide steps. Each step coincides with an energetic signature (0.3 kBT) that is conserved from bacteria to humans. Triplet recognition is strictly dependent on correct Watson-Crick pairing. Rad51, RecA, and Dmc1 can all step over mismatches, but only Dmc1 can stabilize mismatched triplets. This finding provides insight into why eukaryotes have evolved a meiosis-specific recombinase. We propose that canonical Watson-Crick base triplets serve as the fundamental unit of pairing interactions during DNA recombination.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4580133/" 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/PMC4580133/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Ja Yil -- Terakawa, Tsuyoshi -- Qi, Zhi -- Steinfeld, Justin B -- Redding, Sy -- Kwon, YoungHo -- Gaines, William A -- Zhao, Weixing -- Sung, Patrick -- Greene, Eric C -- CA146940/CA/NCI NIH HHS/ -- GM074739/GM/NIGMS NIH HHS/ -- R01 CA146940/CA/NCI NIH HHS/ -- R01 ES015252/ES/NIEHS NIH HHS/ -- R01 GM074739/GM/NIGMS NIH HHS/ -- R01ES015252/ES/NIEHS NIH HHS/ -- T32 GM007367/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Aug 28;349(6251):977-81. doi: 10.1126/science.aab2666.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA. ; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA. Department of Biophysics, Kyoto University, Sakyo, Kyoto, Japan. ; Department of Chemistry, Columbia University, New York, NY, USA. ; Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT, USA. ; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA. Howard Hughes Medical Institute, Columbia University, New York, NY, USA. ecg2108@cumc.columbia.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26315438" target="_blank"〉PubMed〈/a〉

Description: Variation in vectorial capacity for human malaria among Anopheles mosquito species is determined by many factors, including behavior, immunity, and life history. To investigate the genomic basis of vectorial capacity and explore new avenues for vector control, we sequenced the genomes of 16 anopheline mosquito species from diverse locations spanning ~100 million years of evolution. Comparative analyses show faster rates of gene gain and loss, elevated gene shuffling on the X chromosome, and more intron losses, relative to Drosophila. Some determinants of vectorial capacity, such as chemosensory genes, do not show elevated turnover but instead diversify through protein-sequence changes. This dynamism of anopheline genes and genomes may contribute to their flexible capacity to take advantage of new ecological niches, including adapting to humans as primary hosts.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4380271/" 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/PMC4380271/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Neafsey, Daniel E -- Waterhouse, Robert M -- Abai, Mohammad R -- Aganezov, Sergey S -- Alekseyev, Max A -- Allen, James E -- Amon, James -- Arca, Bruno -- Arensburger, Peter -- Artemov, Gleb -- Assour, Lauren A -- Basseri, Hamidreza -- Berlin, Aaron -- Birren, Bruce W -- Blandin, Stephanie A -- Brockman, Andrew I -- Burkot, Thomas R -- Burt, Austin -- Chan, Clara S -- Chauve, Cedric -- Chiu, Joanna C -- Christensen, Mikkel -- Costantini, Carlo -- Davidson, Victoria L M -- Deligianni, Elena -- Dottorini, Tania -- Dritsou, Vicky -- Gabriel, Stacey B -- Guelbeogo, Wamdaogo M -- Hall, Andrew B -- Han, Mira V -- Hlaing, Thaung -- Hughes, Daniel S T -- Jenkins, Adam M -- Jiang, Xiaofang -- Jungreis, Irwin -- Kakani, Evdoxia G -- Kamali, Maryam -- Kemppainen, Petri -- Kennedy, Ryan C -- Kirmitzoglou, Ioannis K -- Koekemoer, Lizette L -- Laban, Njoroge -- Langridge, Nicholas -- Lawniczak, Mara K N -- Lirakis, Manolis -- Lobo, Neil F -- Lowy, Ernesto -- MacCallum, Robert M -- Mao, Chunhong -- Maslen, Gareth -- Mbogo, Charles -- McCarthy, Jenny -- Michel, Kristin -- Mitchell, Sara N -- Moore, Wendy -- Murphy, Katherine A -- Naumenko, Anastasia N -- Nolan, Tony -- Novoa, Eva M -- O'Loughlin, Samantha -- Oringanje, Chioma -- Oshaghi, Mohammad A -- Pakpour, Nazzy -- Papathanos, Philippos A -- Peery, Ashley N -- Povelones, Michael -- Prakash, Anil -- Price, David P -- Rajaraman, Ashok -- Reimer, Lisa J -- Rinker, David C -- Rokas, Antonis -- Russell, Tanya L -- Sagnon, N'Fale -- Sharakhova, Maria V -- Shea, Terrance -- Simao, Felipe A -- Simard, Frederic -- Slotman, Michel A -- Somboon, Pradya -- Stegniy, Vladimir -- Struchiner, Claudio J -- Thomas, Gregg W C -- Tojo, Marta -- Topalis, Pantelis -- Tubio, Jose M C -- Unger, Maria F -- Vontas, John -- Walton, Catherine -- Wilding, Craig S -- Willis, Judith H -- Wu, Yi-Chieh -- Yan, Guiyun -- Zdobnov, Evgeny M -- Zhou, Xiaofan -- Catteruccia, Flaminia -- Christophides, George K -- Collins, Frank H -- Cornman, Robert S -- Crisanti, Andrea -- Donnelly, Martin J -- Emrich, Scott J -- Fontaine, Michael C -- Gelbart, William -- Hahn, Matthew W -- Hansen, Immo A -- Howell, Paul I -- Kafatos, Fotis C -- Kellis, Manolis -- Lawson, Daniel -- Louis, Christos -- Luckhart, Shirley -- Muskavitch, Marc A T -- Ribeiro, Jose M -- Riehle, Michael A -- Sharakhov, Igor V -- Tu, Zhijian -- Zwiebel, Laurence J -- Besansky, Nora J -- 092654/Wellcome Trust/United Kingdom -- R01 AI050243/AI/NIAID NIH HHS/ -- R01 AI063508/AI/NIAID NIH HHS/ -- R01 AI073745/AI/NIAID NIH HHS/ -- R01 AI076584/AI/NIAID NIH HHS/ -- R01 AI080799/AI/NIAID NIH HHS/ -- R01 AI104956/AI/NIAID NIH HHS/ -- R21 AI101459/AI/NIAID NIH HHS/ -- R56 AI107263/AI/NIAID NIH HHS/ -- SC1 AI109055/AI/NIAID NIH HHS/ -- U19 AI089686/AI/NIAID NIH HHS/ -- U19 AI110818/AI/NIAID NIH HHS/ -- U41 HG007234/HG/NHGRI NIH HHS/ -- U54 HG003067/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2015 Jan 2;347(6217):1258522. doi: 10.1126/science.1258522. Epub 2014 Nov 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genome Sequencing and Analysis Program, Broad Institute, 415 Main Street, Cambridge, MA 02142, USA. neafsey@broadinstitute.org nbesansk@nd.edu. ; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, 32 Vassar Street, Cambridge, MA 02139, USA. The Broad Institute of Massachusetts Institute of Technology and Harvard, 415 Main Street, Cambridge, MA 02142, USA. Department of Genetic Medicine and Development, University of Geneva Medical School, Rue Michel-Servet 1, 1211 Geneva, Switzerland. Swiss Institute of Bioinformatics, Rue Michel-Servet 1, 1211 Geneva, Switzerland. ; Department of Medical Entomology and Vector Control, School of Public Health and Institute of Health Researches, Tehran University of Medical Sciences, Tehran, Iran. ; George Washington University, Department of Mathematics and Computational Biology Institute, 45085 University Drive, Ashburn, VA 20147, USA. ; European Molecular Biology Laboratory, European Bioinformatics Institute, EMBL-EBI, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK. ; National Vector Borne Disease Control Programme, Ministry of Health, Tafea Province, Vanuatu. ; Department of Public Health and Infectious Diseases, Division of Parasitology, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy. ; Department of Biological Sciences, California State Polytechnic-Pomona, 3801 West Temple Avenue, Pomona, CA 91768, USA. ; Tomsk State University, 36 Lenina Avenue, Tomsk, Russia. ; Department of Computer Science and Engineering, Eck Institute for Global Health, 211B Cushing Hall, University of Notre Dame, Notre Dame, IN 46556, USA. ; Genome Sequencing and Analysis Program, Broad Institute, 415 Main Street, Cambridge, MA 02142, USA. ; Inserm, U963, F-67084 Strasbourg, France. CNRS, UPR9022, IBMC, F-67084 Strasbourg, France. ; Department of Life Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, UK. ; Faculty of Medicine, Health and Molecular Science, Australian Institute of Tropical Health Medicine, James Cook University, Cairns 4870, Australia. ; Department of Life Sciences, Imperial College London, Silwood Park Campus, Ascot SL5 7PY, UK. ; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, 32 Vassar Street, Cambridge, MA 02139, USA. The Broad Institute of Massachusetts Institute of Technology and Harvard, 415 Main Street, Cambridge, MA 02142, USA. ; Department of Mathematics, Simon Fraser University, 8888 University Drive, Burnaby, BC V5A 1S6, Canada. ; Department of Entomology and Nematology, One Shields Avenue, University of California-Davis, Davis, CA 95616, USA. ; Institut de Recherche pour le Developpement, Unites Mixtes de Recherche Maladies Infectieuses et Vecteurs Ecologie, Genetique, Evolution et Controle, 911, Avenue Agropolis, BP 64501 Montpellier, France. ; Division of Biology, Kansas State University, 271 Chalmers Hall, Manhattan, KS 66506, USA. ; Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology, Hellas, Nikolaou Plastira 100 GR-70013, Heraklion, Crete, Greece. ; Centre of Functional Genomics, University of Perugia, Perugia, Italy. ; Genomics Platform, Broad Institute, 415 Main Street, Cambridge, MA 02142, USA. ; Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou 01 BP 2208, Burkina Faso. ; Program of Genetics, Bioinformatics, and Computational Biology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. ; School of Life Sciences, University of Nevada, Las Vegas, NV 89154, USA. ; Department of Medical Research, No. 5 Ziwaka Road, Dagon Township, Yangon 11191, Myanmar. ; European Molecular Biology Laboratory, European Bioinformatics Institute, EMBL-EBI, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK. Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA. ; Boston College, 140 Commonwealth Avenue, Chestnut Hill, MA 02467, USA. ; Department of Biochemistry, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. Program of Genetics, Bioinformatics, and Computational Biology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. ; Harvard School of Public Health, Department of Immunology and Infectious Diseases, Boston, MA 02115, USA. Dipartimento di Medicina Sperimentale e Scienze Biochimiche, Universita degli Studi di Perugia, Perugia, Italy. ; Department of Entomology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. ; Computational Evolutionary Biology Group, Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK. ; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94143, USA. ; Department of Life Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, UK. Bioinformatics Research Laboratory, Department of Biological Sciences, New Campus, University of Cyprus, CY 1678 Nicosia, Cyprus. ; Wits Research Institute for Malaria, Faculty of Health Sciences, and Vector Control Reference Unit, National Institute for Communicable Diseases of the National Health Laboratory Service, Sandringham 2131, Johannesburg, South Africa. ; National Museums of Kenya, P.O. Box 40658-00100, Nairobi, Kenya. ; Department of Biology, University of Crete, 700 13 Heraklion, Greece. ; Eck Institute for Global Health and Department of Biological Sciences, University of Notre Dame, 317 Galvin Life Sciences Building, Notre Dame, IN 46556, USA. ; Virginia Bioinformatics Institute, 1015 Life Science Circle, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. ; Kenya Medical Research Institute-Wellcome Trust Research Programme, Centre for Geographic Medicine Research - Coast, P.O. Box 230-80108, Kilifi, Kenya. ; Harvard School of Public Health, Department of Immunology and Infectious Diseases, Boston, MA 02115, USA. ; Department of Entomology, 1140 East South Campus Drive, Forbes 410, University of Arizona, Tucson, AZ 85721, USA. ; Department of Medical Microbiology and Immunology, School of Medicine, University of California Davis, One Shields Avenue, Davis, CA 95616, USA. ; Department of Life Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, UK. Centre of Functional Genomics, University of Perugia, Perugia, Italy. ; Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, 3800 Spruce Street, Philadelphia, PA 19104, USA. ; Regional Medical Research Centre NE, Indian Council of Medical Research, P.O. Box 105, Dibrugarh-786 001, Assam, India. ; Department of Biology, New Mexico State University, Las Cruces, NM 88003, USA. Molecular Biology Program, New Mexico State University, Las Cruces, NM 88003, USA. ; Department of Vector Biology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK. ; Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN 37235, USA. ; Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN 37235, USA. Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235, USA. ; Department of Genetic Medicine and Development, University of Geneva Medical School, Rue Michel-Servet 1, 1211 Geneva, Switzerland. Swiss Institute of Bioinformatics, Rue Michel-Servet 1, 1211 Geneva, Switzerland. ; Department of Entomology, Texas A&M University, College Station, TX 77807, USA. ; Department of Parasitology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand. ; Fundacao Oswaldo Cruz, Avenida Brasil 4365, RJ Brazil. Instituto de Medicina Social, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil. ; School of Informatics and Computing, Indiana University, Bloomington, IN 47405, USA. ; Department of Physiology, School of Medicine, Center for Research in Molecular Medicine and Chronic Diseases, Instituto de Investigaciones Sanitarias, University of Santiago de Compostela, Santiago de Compostela, A Coruna, Spain. ; Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, CB10 1SA, UK. ; School of Natural Sciences and Psychology, Liverpool John Moores University, Liverpool L3 3AF, UK. ; Department of Cellular Biology, University of Georgia, Athens, GA 30602, USA. ; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, 32 Vassar Street, Cambridge, MA 02139, USA. The Broad Institute of Massachusetts Institute of Technology and Harvard, 415 Main Street, Cambridge, MA 02142, USA. Department of Computer Science, Harvey Mudd College, Claremont, CA 91711, USA. ; Program in Public Health, College of Health Sciences, University of California, Irvine, Hewitt Hall, Irvine, CA 92697, USA. ; Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235, USA. ; Department of Vector Biology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK. Malaria Programme, Wellcome Trust Sanger Institute, Cambridge CB10 1SJ, UK. ; Eck Institute for Global Health and Department of Biological Sciences, University of Notre Dame, 317 Galvin Life Sciences Building, Notre Dame, IN 46556, USA. Centre of Evolutionary and Ecological Studies (Marine Evolution and Conservation group), University of Groningen, Nijenborgh 7, NL-9747 AG Groningen, Netherlands. ; Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA. ; Department of Biology, Indiana University, Bloomington, IN 47405, USA. School of Informatics and Computing, Indiana University, Bloomington, IN 47405, USA. ; Centers for Disease Control and Prevention, 1600 Clifton Road NE MSG49, Atlanta, GA 30329, USA. ; Department of Biology, University of Crete, 700 13 Heraklion, Greece. Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology, Hellas, Nikolaou Plastira 100 GR-70013, Heraklion, Crete, Greece. Centre of Functional Genomics, University of Perugia, Perugia, Italy. ; Boston College, 140 Commonwealth Avenue, Chestnut Hill, MA 02467, USA. Biogen Idec, 14 Cambridge Center, Cambridge, MA 02142, USA. ; Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, 12735 Twinbrook Parkway, Rockville, MD 20852, USA. ; Department of Entomology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. Program of Genetics, Bioinformatics, and Computational Biology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. ; Program of Genetics, Bioinformatics, and Computational Biology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. Department of Biochemistry, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. ; Departments of Biological Sciences and Pharmacology, Institutes for Chemical Biology, Genetics and Global Health, Vanderbilt University and Medical Center, Nashville, TN 37235, USA. ; Eck Institute for Global Health and Department of Biological Sciences, University of Notre Dame, 317 Galvin Life Sciences Building, Notre Dame, IN 46556, USA. neafsey@broadinstitute.org nbesansk@nd.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25554792" target="_blank"〉PubMed〈/a〉

Description: Transcriptional enhancers direct precise on-off patterns of gene expression during development. To explore the basis for this precision, we conducted a high-throughput analysis of the Otx-a enhancer, which mediates expression in the neural plate of Ciona embryos in response to fibroblast growth factor (FGF) signaling and a localized GATA determinant. We provide evidence that enhancer specificity depends on submaximal recognition motifs having reduced binding affinities ("suboptimization"). Native GATA and ETS (FGF) binding sites contain imperfect matches to consensus motifs. Perfect matches mediate robust but ectopic patterns of gene expression. The native sites are not arranged at optimal intervals, and subtle changes in their spacing alter enhancer activity. Multiple tiers of enhancer suboptimization produce specific, but weak, patterns of expression, and we suggest that clusters of weak enhancers, including certain "superenhancers," circumvent this trade-off in specificity and activity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Farley, Emma K -- Olson, Katrina M -- Zhang, Wei -- Brandt, Alexander J -- Rokhsar, Daniel S -- Levine, Michael S -- GM46638/GM/NIGMS NIH HHS/ -- NS076542/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2015 Oct 16;350(6258):325-8. doi: 10.1126/science.aac6948.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology, Division of Genetics, Genomics and Development, Center for Integrative Genomics, University of California, Berkeley, CA 94720-3200, USA. Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA. msl2@princeton.edu ekfarley@princeton.edu. ; Department of Molecular and Cell Biology, Division of Genetics, Genomics and Development, Center for Integrative Genomics, University of California, Berkeley, CA 94720-3200, USA. Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA. ; Department of Medicine, University of California, San Diego, CA 92093-0688, USA. ; Department of Chemistry, University of California, Berkeley, CA 94720-3200, USA. ; Department of Molecular and Cell Biology, Division of Genetics, Genomics and Development, Center for Integrative Genomics, University of California, Berkeley, CA 94720-3200, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26472909" target="_blank"〉PubMed〈/a〉

Description: The carnivoran giant panda has a specialized bamboo diet, to which its alimentary tract is poorly adapted. Measurements of daily energy expenditure across five captive and three wild pandas averaged 5.2 megajoules (MJ)/day, only 37.7% of the predicted value (13.8 MJ/day). For the wild pandas, the mean was 6.2 MJ/day, or 45% of the mammalian expectation. Pandas achieve this exceptionally low expenditure in part by reduced sizes of several vital organs and low physical activity. In addition, circulating levels of thyroid hormones thyroxine (T4) and triiodothyronine (T3) averaged 46.9 and 64%, respectively, of the levels expected for a eutherian mammal of comparable size. A giant panda-unique mutation in the DUOX2 gene, critical for thyroid hormone synthesis, might explain these low thyroid hormone levels. A combination of morphological, behavioral, physiological, and genetic adaptations, leading to low energy expenditure, likely enables giant pandas to survive on a bamboo diet.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nie, Yonggang -- Speakman, John R -- Wu, Qi -- Zhang, Chenglin -- Hu, Yibo -- Xia, Maohua -- Yan, Li -- Hambly, Catherine -- Wang, Lu -- Wei, Wei -- Zhang, Jinguo -- Wei, Fuwen -- New York, N.Y. -- Science. 2015 Jul 10;349(6244):171-4. doi: 10.1126/science.aab2413.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. ; State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China. Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen, Scotland, UK. ; Beijing Key Laboratory of Captive Wildlife Technologies, Beijing Zoo, Beijing, China. ; Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen, Scotland, UK. ; State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China. ; Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. weifw@ioz.ac.cn.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26160943" target="_blank"〉PubMed〈/a〉

Description: The 18-kilodalton translocator protein (TSPO), proposed to be a key player in cholesterol transport into mitochondria, is highly expressed in steroidogenic tissues, metastatic cancer, and inflammatory and neurological diseases such as Alzheimer's and Parkinson's. TSPO ligands, including benzodiazepine drugs, are implicated in regulating apoptosis and are extensively used in diagnostic imaging. We report crystal structures (at 1.8, 2.4, and 2.5 angstrom resolution) of TSPO from Rhodobacter sphaeroides and a mutant that mimics the human Ala(147)--〉Thr(147) polymorphism associated with psychiatric disorders and reduced pregnenolone production. Crystals obtained in the lipidic cubic phase reveal the binding site of an endogenous porphyrin ligand and conformational effects of the mutation. The three crystal structures show the same tightly interacting dimer and provide insights into the controversial physiological role of TSPO and how the mutation affects cholesterol binding.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Fei -- Liu, Jian -- Zheng, Yi -- Garavito, R Michael -- Ferguson-Miller, Shelagh -- ACB-12002/PHS HHS/ -- AGM-12006/PHS HHS/ -- GM094625/GM/NIGMS NIH HHS/ -- GM26916/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Jan 30;347(6221):555-8. doi: 10.1126/science.1260590.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA. ; Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA. fergus20@msu.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25635101" target="_blank"〉PubMed〈/a〉

Description: Cytoplasmic aggregation of TDP-43, accompanied by its nuclear clearance, is a key common pathological hallmark of amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD). However, a limited understanding of this RNA-binding protein (RBP) impedes the clarification of pathogenic mechanisms underlying TDP-43 proteinopathy. In contrast to RBPs that regulate splicing of conserved exons, we found that TDP-43 repressed the splicing of nonconserved cryptic exons, maintaining intron integrity. When TDP-43 was depleted from mouse embryonic stem cells, these cryptic exons were spliced into messenger RNAs, often disrupting their translation and promoting nonsense-mediated decay. Moreover, enforced repression of cryptic exons prevented cell death in TDP-43-deficient cells. Furthermore, repression of cryptic exons was impaired in ALS-FTD cases, suggesting that this splicing defect could potentially underlie TDP-43 proteinopathy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ling, Jonathan P -- Pletnikova, Olga -- Troncoso, Juan C -- Wong, Philip C -- P50AG05146/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2015 Aug 7;349(6248):650-5. doi: 10.1126/science.aab0983.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA. ; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA. ; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA. Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA. wong@jhmi.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26250685" target="_blank"〉PubMed〈/a〉

Description: Coordinated replication and expression of the mitochondrial genome is critical for metabolically active cells during various stages of development. However, it is not known whether replication and transcription can occur simultaneously without interfering with each other and whether mitochondrial DNA copy number can be regulated by the transcription machinery. We found that interaction of human transcription elongation factor TEFM with mitochondrial RNA polymerase and nascent transcript prevents the generation of replication primers and increases transcription processivity and thereby serves as a molecular switch between replication and transcription, which appear to be mutually exclusive processes in mitochondria. TEFM may allow mitochondria to increase transcription rates and, as a consequence, respiration and adenosine triphosphate production without the need to replicate mitochondrial DNA, as has been observed during spermatogenesis and the early stages of embryogenesis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4677687/" 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/PMC4677687/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Agaronyan, Karen -- Morozov, Yaroslav I -- Anikin, Michael -- Temiakov, Dmitry -- R01 GM104231/GM/NIGMS NIH HHS/ -- R01GM104231/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Jan 30;347(6221):548-51. doi: 10.1126/science.aaa0986.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, School of Osteopathic Medicine, Rowan University, 2 Medical Center Drive, Stratford, NJ 08084, USA. ; Department of Cell Biology, School of Osteopathic Medicine, Rowan University, 2 Medical Center Drive, Stratford, NJ 08084, USA. temiakdm@rowan.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25635099" target="_blank"〉PubMed〈/a〉

Description: Voltage-gated sodium (Nav) channels propagate action potentials in excitable cells. Accordingly, Nav channels are therapeutic targets for many cardiovascular and neurological disorders. Selective inhibitors have been challenging to design because the nine mammalian Nav channel isoforms share high sequence identity and remain recalcitrant to high-resolution structural studies. Targeting the human Nav1.7 channel involved in pain perception, we present a protein-engineering strategy that has allowed us to determine crystal structures of a novel receptor site in complex with isoform-selective antagonists. GX-936 and related inhibitors bind to the activated state of voltage-sensor domain IV (VSD4), where their anionic aryl sulfonamide warhead engages the fourth arginine gating charge on the S4 helix. By opposing VSD4 deactivation, these compounds inhibit Nav1.7 through a voltage-sensor trapping mechanism, likely by stabilizing inactivated states of the channel. Residues from the S2 and S3 helices are key determinants of isoform selectivity, and bound phospholipids implicate the membrane as a modulator of channel function and pharmacology. Our results help to elucidate the molecular basis of voltage sensing and establish structural blueprints to design selective Nav channel antagonists.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ahuja, Shivani -- Mukund, Susmith -- Deng, Lunbin -- Khakh, Kuldip -- Chang, Elaine -- Ho, Hoangdung -- Shriver, Stephanie -- Young, Clint -- Lin, Sophia -- Johnson, J P Jr -- Wu, Ping -- Li, Jun -- Coons, Mary -- Tam, Christine -- Brillantes, Bobby -- Sampang, Honorio -- Mortara, Kyle -- Bowman, Krista K -- Clark, Kevin R -- Estevez, Alberto -- Xie, Zhiwei -- Verschoof, Henry -- Grimwood, Michael -- Dehnhardt, Christoph -- Andrez, Jean-Christophe -- Focken, Thilo -- Sutherlin, Daniel P -- Safina, Brian S -- Starovasnik, Melissa A -- Ortwine, Daniel F -- Franke, Yvonne -- Cohen, Charles J -- Hackos, David H -- Koth, Christopher M -- Payandeh, Jian -- New York, N.Y. -- Science. 2015 Dec 18;350(6267):aac5464. doi: 10.1126/science.aac5464.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Structural Biology, Genentech Inc., South San Francisco, CA 94080, USA. ; Department of Neuroscience, Genentech Inc., South San Francisco, CA 94080, USA. ; Department of Biology, Xenon Pharmaceuticals Inc., Burnaby, British Columbia, V5G 4W8, Canada. ; Department of Discovery Chemistry, Genentech Inc., South San Francisco, CA 94080, USA. ; Department of Biochemical and Cellular Pharmacology, Genentech Inc., South San Francisco, CA 94080, USA. ; Department of Chemistry, Xenon Pharmaceuticals Inc., Burnaby, British Columbia, V5G 4W8, Canada. ; Department of Neuroscience, Genentech Inc., South San Francisco, CA 94080, USA. hackos.david@gene.com koth.christopher@gene.com payandeh.jian@gene.com. ; Department of Structural Biology, Genentech Inc., South San Francisco, CA 94080, USA. hackos.david@gene.com koth.christopher@gene.com payandeh.jian@gene.com.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26680203" target="_blank"〉PubMed〈/a〉

Description: The ocean moderates anthropogenic climate change at the cost of profound alterations of its physics, chemistry, ecology, and services. Here, we evaluate and compare the risks of impacts on marine and coastal ecosystems-and the goods and services they provide-for growing cumulative carbon emissions under two contrasting emissions scenarios. The current emissions trajectory would rapidly and significantly alter many ecosystems and the associated services on which humans heavily depend. A reduced emissions scenario-consistent with the Copenhagen Accord's goal of a global temperature increase of less than 2 degrees C-is much more favorable to the ocean but still substantially alters important marine ecosystems and associated goods and services. The management options to address ocean impacts narrow as the ocean warms and acidifies. Consequently, any new climate regime that fails to minimize ocean impacts would be incomplete and inadequate.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gattuso, J-P -- Magnan, A -- Bille, R -- Cheung, W W L -- Howes, E L -- Joos, F -- Allemand, D -- Bopp, L -- Cooley, S R -- Eakin, C M -- Hoegh-Guldberg, O -- Kelly, R P -- Portner, H-O -- Rogers, A D -- Baxter, J M -- Laffoley, D -- Osborn, D -- Rankovic, A -- Rochette, J -- Sumaila, U R -- Treyer, S -- Turley, C -- New York, N.Y. -- Science. 2015 Jul 3;349(6243):aac4722. doi: 10.1126/science.aac4722.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratoire d'Oceanographie de Villefranche, CNRS-Institut National des Sciences de l'Univers, F-06230 Villefranche-sur-mer, France. Sorbonne Universites, Universite Pierre et Marie Curie, Univ Paris 06, Observatoire Oceanologique, F-06230 Villefranche-sur-mer, France. Institute for Sustainable Development and International Relations, Sciences Po, 27 rue Saint Guillaume, F-75007 Paris, France. gattuso@obs-vlfr.fr. ; Institute for Sustainable Development and International Relations, Sciences Po, 27 rue Saint Guillaume, F-75007 Paris, France. ; Secretariat of the Pacific Community, B.P. D5, 98848 Noumea Cedex, New Caledonia. ; Nippon Foundation-UBC Nereus Program, University of British Columbia (UBC), Vancouver, BC V6T 1Z4, Canada. ; Alfred Wegener Institute, Helmholtz Centre for Polar and Marine Research, Am Handelshafen 12, D-27570, Bremenrhaven, Germany. ; Climate and Environmental Physics, Physics Institute and Oeschger Centre for Climate Change Research, University of Bern, Sidlerstrasse 5, CH-3012 Bern, Switzerland. ; Centre Scientifique de Monaco, 8 Quai Antoine Ier, MC-98000 Monaco, Principality of Monaco. Institut Pierre Simon Laplace/Laboratoire des Science du Climat et de l'Environnement, UMR8212, CNRS-Commissariat a l'Energie Atomique et aux Energies Alternatives-Universite de Versailles Saint-Quentin-en-Yvelines, Gif sur Yvette, France. ; Ocean Conservancy, 1300 19th Street NW, 8th Floor, Washington, DC 20036, USA. ; Coral Reef Watch, National Oceanic and Atmospheric Administration, College Park, MD 20740, USA. ; Global Change Institute and Australian Research Council Centre for Excellence in Coral Reef Studies, University of Queensland, Building 20, St Lucia, 4072 Queensland, Australia. ; School of Marine and Environmental Affairs, University of Washington, 3707 Brooklyn Avenue NE, Seattle, WA 98105, USA. ; Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK. ; Scottish Natural Heritage, 231 Corstorphine Road, Edinburgh EH12 7AT, Scotland. ; IUCN, Rue Mauverney 28, CH-1196 Gland, Switzerland. ; Environment Laboratories, International Atomic Energy Agency, 4a Quai Antoine 1er, MC-98000 Monaco, Principality of Monaco. ; Program on Science, Technology, and Society, John F. Kennedy School of Government, Harvard University, 79 John F. Kennedy Street, Cambridge, MA 02138, USA. ; Institute for Sustainable Development and International Relations, Sciences Po, 27 rue Saint Guillaume, F-75007 Paris, France. Fisheries Economics Research Unit, University of British Columbia, Vancouver, BC V6T 1Z4, Canada. ; Plymouth Marine Laboratory, Prospect Place, The Hoe, Plymouth PL1 3DH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26138982" target="_blank"〉PubMed〈/a〉

Description: Bacterial adaptive immunity uses CRISPR (clustered regularly interspaced short palindromic repeats)-associated (Cas) proteins together with CRISPR transcripts for foreign DNA degradation. In type II CRISPR-Cas systems, activation of Cas9 endonuclease for DNA recognition upon guide RNA binding occurs by an unknown mechanism. Crystal structures of Cas9 bound to single-guide RNA reveal a conformation distinct from both the apo and DNA-bound states, in which the 10-nucleotide RNA "seed" sequence required for initial DNA interrogation is preordered in an A-form conformation. This segment of the guide RNA is essential for Cas9 to form a DNA recognition-competent structure that is poised to engage double-stranded DNA target sequences. We construe this as convergent evolution of a "seed" mechanism reminiscent of that used by Argonaute proteins during RNA interference in eukaryotes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jiang, Fuguo -- Zhou, Kaihong -- Ma, Linlin -- Gressel, Saskia -- Doudna, Jennifer A -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Jun 26;348(6242):1477-81. doi: 10.1126/science.aab1452.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA. ; Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA. ; Max Planck Institute for Biophysical Chemistry, 37077 Gottingen, Germany. ; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA. Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA. California Institute for Quantitative Biosciences, University of California, Berkeley, CA 94720, USA. Department of Chemistry, University of California, Berkeley, CA 94720, USA. Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. Innovative Genomics Initiative, University of California, Berkeley, CA 94720, USA. doudna@berkeley.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26113724" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Allred, Brady W -- Smith, W Kolby -- Twidwell, Dirac -- Haggerty, Julia H -- Running, Steven W -- Naugle, David E -- Fuhlendorf, Samuel D -- New York, N.Y. -- Science. 2015 Apr 24;348(6233):401-2. doi: 10.1126/science.aaa4785. Epub 2015 Apr 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉College of Forestry and Conservation, University of Montana, Missoula, MT 59812, USA. brady.allred@umontana.edu. ; College of Forestry and Conservation, University of Montana, Missoula, MT 59812, USA. Institute on the Environment, University of Minnesota, St. Paul, MN 55108, USA. ; Department of Agronomy and Horticulture, University of Nebraska-Lincoln, Lincoln, NE 68583, USA. ; Department of Earth Sciences, Montana State University, Bozeman, MT 59717, USA. ; College of Forestry and Conservation, University of Montana, Missoula, MT 59812, USA. ; Department of Natural Resource Ecology and Management, Oklahoma State University, Stillwater, OK 74078, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25908812" target="_blank"〉PubMed〈/a〉

Description: Transcription factors (TFs) bind specific sequences in promoter-proximal and -distal DNA elements to regulate gene transcription. RNA is transcribed from both of these DNA elements, and some DNA binding TFs bind RNA. Hence, RNA transcribed from regulatory elements may contribute to stable TF occupancy at these sites. We show that the ubiquitously expressed TF Yin-Yang 1 (YY1) binds to both gene regulatory elements and their associated RNA species across the entire genome. Reduced transcription of regulatory elements diminishes YY1 occupancy, whereas artificial tethering of RNA enhances YY1 occupancy at these elements. We propose that RNA makes a modest but important contribution to the maintenance of certain TFs at gene regulatory elements and suggest that transcription of regulatory elements produces a positive-feedback loop that contributes to the stability of gene expression programs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4720525/" 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/PMC4720525/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sigova, Alla A -- Abraham, Brian J -- Ji, Xiong -- Molinie, Benoit -- Hannett, Nancy M -- Guo, Yang Eric -- Jangi, Mohini -- Giallourakis, Cosmas C -- Sharp, Phillip A -- Young, Richard A -- HG002668/HG/NHGRI NIH HHS/ -- R01 HG002668/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2015 Nov 20;350(6263):978-81. doi: 10.1126/science.aad3346. Epub 2015 Oct 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA. ; Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. ; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA. David H. Koch Institute for Integrative Cancer Research, Cambridge, MA 02140, USA. ; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA. young@wi.mit.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26516199" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pennisi, Elizabeth -- New York, N.Y. -- Science. 2015 Dec 18;350(6267):1452. doi: 10.1126/science.350.6267.1452.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26680168" target="_blank"〉PubMed〈/a〉

Description: Morphinan alkaloids from the opium poppy are used for pain relief. The direction of metabolites to morphinan biosynthesis requires isomerization of (S)- to (R)-reticuline. Characterization of high-reticuline poppy mutants revealed a genetic locus, designated STORR [(S)- to (R)-reticuline] that encodes both cytochrome P450 and oxidoreductase modules, the latter belonging to the aldo-keto reductase family. Metabolite analysis of mutant alleles and heterologous expression demonstrate that the P450 module is responsible for the conversion of (S)-reticuline to 1,2-dehydroreticuline, whereas the oxidoreductase module converts 1,2-dehydroreticuline to (R)-reticuline rather than functioning as a P450 redox partner. Proteomic analysis confirmed that these two modules are contained on a single polypeptide in vivo. This modular assembly implies a selection pressure favoring substrate channeling. The fusion protein STORR may enable microbial-based morphinan production.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Winzer, Thilo -- Kern, Marcelo -- King, Andrew J -- Larson, Tony R -- Teodor, Roxana I -- Donninger, Samantha L -- Li, Yi -- Dowle, Adam A -- Cartwright, Jared -- Bates, Rachel -- Ashford, David -- Thomas, Jerry -- Walker, Carol -- Bowser, Tim A -- Graham, Ian A -- BB/K018809/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2015 Jul 17;349(6245):309-12. doi: 10.1126/science.aab1852. Epub 2015 Jun 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Novel Agricultural Products, Department of Biology, University of York, York YO10 5DD, UK. ; Bioscience Technology Facility, Department of Biology, University of York, York YO10 5DD, UK. ; GlaxoSmithKline, 1061 Mountain Highway, Post Office Box 168, Boronia, Victoria 3155, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26113639" target="_blank"〉PubMed〈/a〉

Description: The 5' leader of the HIV-1 genome contains conserved elements that direct selective packaging of the unspliced, dimeric viral RNA into assembling particles. By using a (2)H-edited nuclear magnetic resonance (NMR) approach, we determined the structure of a 155-nucleotide region of the leader that is independently capable of directing packaging (core encapsidation signal; Psi(CES)). The RNA adopts an unexpected tandem three-way junction structure, in which residues of the major splice donor and translation initiation sites are sequestered by long-range base pairing and guanosines essential for both packaging and high-affinity binding to the cognate Gag protein are exposed in helical junctions. The structure reveals how translation is attenuated, Gag binding promoted, and unspliced dimeric genomes selected, by the RNA conformer that directs packaging.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4492308/" 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/PMC4492308/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Keane, Sarah C -- Heng, Xiao -- Lu, Kun -- Kharytonchyk, Siarhei -- Ramakrishnan, Venkateswaran -- Carter, Gregory -- Barton, Shawn -- Hosic, Azra -- Florwick, Alyssa -- Santos, Justin -- Bolden, Nicholas C -- McCowin, Sayo -- Case, David A -- Johnson, Bruce A -- Salemi, Marco -- Telesnitsky, Alice -- Summers, Michael F -- 2T34 GM008663/GM/NIGMS NIH HHS/ -- P50 GM 103297/GM/NIGMS NIH HHS/ -- P50 GM103297/GM/NIGMS NIH HHS/ -- R01 GM042561/GM/NIGMS NIH HHS/ -- R01 GM42561/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 May 22;348(6237):917-21. doi: 10.1126/science.aaa9266.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute (HHMI) and Department of Chemistry and Biochemistry, University of Maryland Baltimore County (UMBC), 1000 Hilltop Circle, Baltimore, MD 21250, USA. ; Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109-5620, USA. ; Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ 08854, USA. ; One Moon Scientific, Incorporated, 839 Grant Avenue, Westfield, NJ 07090, USA, and City University of New York (CUNY) Advanced Science Research Center, 85 St. Nicholas Terrace, New York, NY 10031, USA. ; Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, and Emerging Pathogens Institute, University of Florida, Gainesville, FL 32610, USA. ; Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109-5620, USA. summers@hhmi.umbc.edu ateles@umich.edu. ; Howard Hughes Medical Institute (HHMI) and Department of Chemistry and Biochemistry, University of Maryland Baltimore County (UMBC), 1000 Hilltop Circle, Baltimore, MD 21250, USA. summers@hhmi.umbc.edu ateles@umich.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25999508" target="_blank"〉PubMed〈/a〉

Description: Splicing of precursor messenger RNA (pre-mRNA) in yeast is executed by the spliceosome, which consists of five small nuclear ribonucleoproteins (snRNPs), NTC (nineteen complex), NTC-related proteins (NTR), and a number of associated enzymes and cofactors. Here, we report the three-dimensional structure of a Schizosaccharomyces pombe spliceosome at 3.6-angstrom resolution, revealed by means of single-particle cryogenic electron microscopy. This spliceosome contains U2 and U5 snRNPs, NTC, NTR, U6 small nuclear RNA, and an RNA intron lariat. The atomic model includes 10,574 amino acids from 37 proteins and four RNA molecules, with a combined molecular mass of approximately 1.3 megadaltons. Spp42 (Prp8 in Saccharomyces cerevisiae), the key protein component of the U5 snRNP, forms a central scaffold and anchors the catalytic center. Both the morphology and the placement of protein components appear to have evolved to facilitate the dynamic process of pre-mRNA splicing. Our near-atomic-resolution structure of a central spliceosome provides a molecular framework for mechanistic understanding of pre-mRNA splicing.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yan, Chuangye -- Hang, Jing -- Wan, Ruixue -- Huang, Min -- Wong, Catherine C L -- Shi, Yigong -- New York, N.Y. -- Science. 2015 Sep 11;349(6253):1182-91. doi: 10.1126/science.aac7629. Epub 2015 Aug 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ministry of Education Key Laboratory of Protein Science, Tsinghua-Peking Joint Center for Life Sciences, Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China. ; National Center for Protein Science Shanghai, Institute of Biochemistry and Cell Biology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26292707" target="_blank"〉PubMed〈/a〉

Description: The shortage of organs for transplantation is a major barrier to the treatment of organ failure. Although porcine organs are considered promising, their use has been checked by concerns about the transmission of porcine endogenous retroviruses (PERVs) to humans. Here we describe the eradication of all PERVs in a porcine kidney epithelial cell line (PK15). We first determined the PK15 PERV copy number to be 62. Using CRISPR-Cas9, we disrupted all copies of the PERV pol gene and demonstrated a 〉1000-fold reduction in PERV transmission to human cells, using our engineered cells. Our study shows that CRISPR-Cas9 multiplexability can be as high as 62 and demonstrates the possibility that PERVs can be inactivated for clinical application of porcine-to-human xenotransplantation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yang, Luhan -- Guell, Marc -- Niu, Dong -- George, Haydy -- Lesha, Emal -- Grishin, Dennis -- Aach, John -- Shrock, Ellen -- Xu, Weihong -- Poci, Jurgen -- Cortazio, Rebeca -- Wilkinson, Robert A -- Fishman, Jay A -- Church, George -- P50 HG005550/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2015 Nov 27;350(6264):1101-4. doi: 10.1126/science.aad1191. Epub 2015 Oct 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Harvard Medical School, Boston, MA, USA. Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA, USA. eGenesis Biosciences, Boston, MA 02115, USA. gchurch@genetics.med.harvard.edu luhan.yang@egenesisbio.com. ; Department of Genetics, Harvard Medical School, Boston, MA, USA. Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA, USA. eGenesis Biosciences, Boston, MA 02115, USA. ; Department of Genetics, Harvard Medical School, Boston, MA, USA. College of Animal Sciences, Zhejiang University, Hangzhou 310058, China. ; Department of Genetics, Harvard Medical School, Boston, MA, USA. ; Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. ; Transplant Infectious Disease and Compromised Host Program, Massachusetts General Hospital, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26456528" target="_blank"〉PubMed〈/a〉

Description: Most spontaneous DNA double-strand breaks (DSBs) result from replication-fork breakage. Break-induced replication (BIR), a genome rearrangement-prone repair mechanism that requires the Pol32/POLD3 subunit of eukaryotic DNA Poldelta, was proposed to repair broken forks, but how genome destabilization is avoided was unknown. We show that broken fork repair initially uses error-prone Pol32-dependent synthesis, but that mutagenic synthesis is limited to within a few kilobases from the break by Mus81 endonuclease and a converging fork. Mus81 suppresses template switches between both homologous sequences and diverged human Alu repetitive elements, highlighting its importance for stability of highly repetitive genomes. We propose that lack of a timely converging fork or Mus81 may propel genome instability observed in cancer.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mayle, Ryan -- Campbell, Ian M -- Beck, Christine R -- Yu, Yang -- Wilson, Marenda -- Shaw, Chad A -- Bjergbaek, Lotte -- Lupski, James R -- Ira, Grzegorz -- F31 NS083159/NS/NINDS NIH HHS/ -- GM080600/GM/NIGMS NIH HHS/ -- HG006542/HG/NHGRI NIH HHS/ -- NS058529/NS/NINDS NIH HHS/ -- NS083159/NS/NINDS NIH HHS/ -- R01 GM080600/GM/NIGMS NIH HHS/ -- R01 NS058529/NS/NINDS NIH HHS/ -- U54 HG006542/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2015 Aug 14;349(6249):742-7. doi: 10.1126/science.aaa8391.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. ; Department of Molecular Biology and Genetics, University of Aarhus, Aarhus 8000, Denmark. ; Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. Department of Pediatrics, and Human Genome Sequencing Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. Texas Children's Hospital, Houston, TX 77030, USA. ; Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. gira@bcm.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26273056" target="_blank"〉PubMed〈/a〉

Description: Marine defaunation, or human-caused animal loss in the oceans, emerged forcefully only hundreds of years ago, whereas terrestrial defaunation has been occurring far longer. Though humans have caused few global marine extinctions, we have profoundly affected marine wildlife, altering the functioning and provisioning of services in every ocean. Current ocean trends, coupled with terrestrial defaunation lessons, suggest that marine defaunation rates will rapidly intensify as human use of the oceans industrializes. Though protected areas are a powerful tool to harness ocean productivity, especially when designed with future climate in mind, additional management strategies will be required. Overall, habitat degradation is likely to intensify as a major driver of marine wildlife loss. Proactive intervention can avert a marine defaunation disaster of the magnitude observed on land.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McCauley, Douglas J -- Pinsky, Malin L -- Palumbi, Stephen R -- Estes, James A -- Joyce, Francis H -- Warner, Robert R -- New York, N.Y. -- Science. 2015 Jan 16;347(6219):1255641. doi: 10.1126/science.1255641.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ecology, Evolution, and Marine Biology, University of California, Santa Barbara, CA 93106, USA. douglas.mccauley@lifesci.ucsb.edu. ; Department of Ecology, Evolution, and Natural Resources, Institute of Marine and Coastal Sciences, Rutgers University, New Brunswick, NJ 08901, USA. ; Department of Biology, Stanford University, Hopkins Marine Station, Pacific Grove, CA 93950, USA. ; Department of Ecology and Evolutionary Biology, University of California, Santa Cruz, CA 95060, USA. ; Department of Ecology, Evolution, and Marine Biology, University of California, Santa Barbara, CA 93106, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25593191" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stone, Richard -- New York, N.Y. -- Science. 2015 Sep 4;349(6252):1046-7. doi: 10.1126/science.349.6252.1046.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26339010" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Groner, Maya -- Breyta, Rachel -- Dobson, Andy -- Friedman, Carolyn S -- Froelich, Brett -- Garren, Melissa -- Gulland, Frances -- Maynard, Jeffrey -- Weil, Ernesto -- Wyllie-Echeverria, Sandy -- Harvell, Drew -- New York, N.Y. -- Science. 2015 Mar 13;347(6227):1210. doi: 10.1126/science.347.6227.1210-a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Veterinary and Epidemiological Research, Department of Health Management, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE, C1A 4P3, Canada. mgroner@upei.ca. ; School of Aquatic and Fishery Sciences, University of Washington, Seattle, WA 98195, USA. ; Department of Ecology and Evolutionary Biology, Princeton, NJ 08544, USA. ; Department of Marine Science, University of North Carolina, Chapel Hill, NC 27599, USA. ; Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. ; The Marine Mammal Center, Sausalito, CA 94965, USA. ; Department of Ecology and Evolutionary Biology, Cornell University, Ithaca, NY 14853, USA. ; Department of Marine Sciences, University of Puerto Rico, Mayaguez, Mayaguez, PR 00680, USA. ; Friday Harbor Laboratories, University of Washington, Friday Harbor, WA 98250, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25766223" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kintisch, Eli -- New York, N.Y. -- Science. 2015 Aug 7;349(6248):578-81. doi: 10.1126/science.349.6248.578.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26250666" target="_blank"〉PubMed〈/a〉

Description: The Protoaurignacian culture is pivotal to the debate about the timing of the arrival of modern humans in western Europe and the demise of Neandertals. However, which group is responsible for this culture remains uncertain. We investigated dental remains associated with the Protoaurignacian. The lower deciduous incisor from Riparo Bombrini is modern human, based on its morphology. The upper deciduous incisor from Grotta di Fumane contains ancient mitochondrial DNA of a modern human type. These teeth are the oldest human remains in an Aurignacian-related archaeological context, confirming that by 41,000 calendar years before the present, modern humans bearing Protoaurignacian culture spread into southern Europe. Because the last Neandertals date to 41,030 to 39,260 calendar years before the present, we suggest that the Protoaurignacian triggered the demise of Neandertals in this area.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Benazzi, S -- Slon, V -- Talamo, S -- Negrino, F -- Peresani, M -- Bailey, S E -- Sawyer, S -- Panetta, D -- Vicino, G -- Starnini, E -- Mannino, M A -- Salvadori, P A -- Meyer, M -- Paabo, S -- Hublin, J-J -- New York, N.Y. -- Science. 2015 May 15;348(6236):793-6. doi: 10.1126/science.aaa2773. Epub 2015 Apr 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cultural Heritage, University of Bologna, Via degli Ariani 1, 48121 Ravenna, Italy. Department of Human Evolution, Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, 04103 Leipzig, Germany. stefano.benazzi@unibo.it. ; Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, 04103 Leipzig, Germany. ; Department of Human Evolution, Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, 04103 Leipzig, Germany. ; Dipartimento di Antichita, Filosofia, Storia e Geografia, Universita di Genova, Via Balbi 2, 16126 Genova, Italy. ; Sezione di Scienze Preistoriche e Antropologiche, Dipartimento di Studi Umanistici, Corso Ercole I d'Este 32, Universita di Ferrara, 44100 Ferrara, Italy. ; Department of Human Evolution, Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, 04103 Leipzig, Germany. Center for the Study of Human Origins, Department of Anthropology, New York University, 25 Waverly Place, New York, NY 10003, USA. ; CNR Institute of Clinical Physiology, National Research Council, Via G. Moruzzi 1, 56124 Pisa, Italy. ; Museo Archeologico del Finale, Chiostri di Santa Caterina, 17024 Finale Ligure Borgo, Italy. ; Scuola di Scienze Umanistiche, Dipartimento di Studi Storici, Universita di Torino, via S. Ottavio 20, 10124 Torino, Italy. Museo Preistorico Nazionale dei Balzi Rossi, Via Balzi Rossi 9, 18039 Ventimiglia, Italy.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25908660" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rau, Greg H -- Greene, Charles H -- New York, N.Y. -- Science. 2015 Sep 25;349(6255):1459. doi: 10.1126/science.349.6255.1459-b.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Marine Sciences, University of California, Santa Cruz, CA 95064, USA. ghrau@sbcglobal.net. ; Ocean Resources and Ecosystems Program, Cornell University, Ithaca, NY 14853, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26404817" target="_blank"〉PubMed〈/a〉

Description: The field of optogenetics uses channelrhodopsins (ChRs) for light-induced neuronal activation. However, optimized tools for cellular inhibition at moderate light levels are lacking. We found that replacement of E90 in the central gate of ChR with positively charged residues produces chloride-conducting ChRs (ChloCs) with only negligible cation conductance. Molecular dynamics modeling unveiled that a high-affinity Cl(-)-binding site had been generated near the gate. Stabilizing the open state dramatically increased the operational light sensitivity of expressing cells (slow ChloC). In CA1 pyramidal cells, ChloCs completely inhibited action potentials triggered by depolarizing current injections or synaptic stimulation. Thus, by inverting the charge of the selectivity filter, we have created a class of directly light-gated anion channels that can be used to block neuronal output in a fully reversible fashion.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wietek, Jonas -- Wiegert, J Simon -- Adeishvili, Nona -- Schneider, Franziska -- Watanabe, Hiroshi -- Tsunoda, Satoshi P -- Vogt, Arend -- Elstner, Marcus -- Oertner, Thomas G -- Hegemann, Peter -- New York, N.Y. -- Science. 2014 Apr 25;344(6182):409-12. doi: 10.1126/science.1249375. Epub 2014 Mar 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Biology, Experimental Biophysics, Humboldt Universitat zu Berlin, D-10115 Berlin, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24674867" target="_blank"〉PubMed〈/a〉

Description: Evolutionary changes in traits involved in both ecological divergence and mate choice may produce reproductive isolation and speciation. However, there are few examples of such dual traits, and the genetic and molecular bases of their evolution have not been identified. We show that methyl-branched cuticular hydrocarbons (mbCHCs) are a dual trait that affects both desiccation resistance and mate choice in Drosophila serrata. We identify a fatty acid synthase mFAS (CG3524) responsible for mbCHC production in Drosophila and find that expression of mFAS is undetectable in oenocytes (cells that produce CHCs) of a closely related, desiccation-sensitive species, D. birchii, due in part to multiple changes in cis-regulatory sequences of mFAS. We suggest that ecologically influenced changes in the production of mbCHCs have contributed to reproductive isolation between the two species.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chung, Henry -- Loehlin, David W -- Dufour, Heloise D -- Vaccarro, Kathy -- Millar, Jocelyn G -- Carroll, Sean B -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Mar 7;343(6175):1148-51. doi: 10.1126/science.1249998. Epub 2014 Feb 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Laboratory of Molecular Biology, University of Wisconsin, Madison, WI 53706, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24526311" target="_blank"〉PubMed〈/a〉

Description: In its largest outbreak, Ebola virus disease is spreading through Guinea, Liberia, Sierra Leone, and Nigeria. We sequenced 99 Ebola virus genomes from 78 patients in Sierra Leone to ~2000x coverage. We observed a rapid accumulation of interhost and intrahost genetic variation, allowing us to characterize patterns of viral transmission over the initial weeks of the epidemic. This West African variant likely diverged from central African lineages around 2004, crossed from Guinea to Sierra Leone in May 2014, and has exhibited sustained human-to-human transmission subsequently, with no evidence of additional zoonotic sources. Because many of the mutations alter protein sequences and other biologically meaningful targets, they should be monitored for impact on diagnostics, vaccines, and therapies critical to outbreak response.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4431643/" 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/PMC4431643/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gire, Stephen K -- Goba, Augustine -- Andersen, Kristian G -- Sealfon, Rachel S G -- Park, Daniel J -- Kanneh, Lansana -- Jalloh, Simbirie -- Momoh, Mambu -- Fullah, Mohamed -- Dudas, Gytis -- Wohl, Shirlee -- Moses, Lina M -- Yozwiak, Nathan L -- Winnicki, Sarah -- Matranga, Christian B -- Malboeuf, Christine M -- Qu, James -- Gladden, Adrianne D -- Schaffner, Stephen F -- Yang, Xiao -- Jiang, Pan-Pan -- Nekoui, Mahan -- Colubri, Andres -- Coomber, Moinya Ruth -- Fonnie, Mbalu -- Moigboi, Alex -- Gbakie, Michael -- Kamara, Fatima K -- Tucker, Veronica -- Konuwa, Edwin -- Saffa, Sidiki -- Sellu, Josephine -- Jalloh, Abdul Azziz -- Kovoma, Alice -- Koninga, James -- Mustapha, Ibrahim -- Kargbo, Kandeh -- Foday, Momoh -- Yillah, Mohamed -- Kanneh, Franklyn -- Robert, Willie -- Massally, James L B -- Chapman, Sinead B -- Bochicchio, James -- Murphy, Cheryl -- Nusbaum, Chad -- Young, Sarah -- Birren, Bruce W -- Grant, Donald S -- Scheiffelin, John S -- Lander, Eric S -- Happi, Christian -- Gevao, Sahr M -- Gnirke, Andreas -- Rambaut, Andrew -- Garry, Robert F -- Khan, S Humarr -- Sabeti, Pardis C -- 095831/Wellcome Trust/United Kingdom -- 1DP2OD006514-01/OD/NIH HHS/ -- 1U01HG007480-01/HG/NHGRI NIH HHS/ -- 260864/European Research Council/International -- DP2 OD006514/OD/NIH HHS/ -- GM080177/GM/NIGMS NIH HHS/ -- HHSN272200900049C/AI/NIAID NIH HHS/ -- HHSN272200900049C/PHS HHS/ -- T32 GM080177/GM/NIGMS NIH HHS/ -- U01 HG007480/HG/NHGRI NIH HHS/ -- U19 AI110818/AI/NIAID NIH HHS/ -- U19 AI115589/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2014 Sep 12;345(6202):1369-72. doi: 10.1126/science.1259657. Epub 2014 Aug 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. ; Kenema Government Hospital, Kenema, Sierra Leone. andersen@broadinstitute.org augstgoba@yahoo.com psabeti@oeb.harvard.edu. ; Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. andersen@broadinstitute.org augstgoba@yahoo.com psabeti@oeb.harvard.edu. ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. ; Kenema Government Hospital, Kenema, Sierra Leone. ; Kenema Government Hospital, Kenema, Sierra Leone. Eastern Polytechnic College, Kenema, Sierra Leone. ; Institute of Evolutionary Biology, University of Edinburgh, Edinburgh EH9 3JT, UK. ; Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Systems Biology, Harvard Medical School, Boston, MA 02115, USA. ; Tulane University Medical Center, New Orleans, LA 70112, USA. ; Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA. ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Systems Biology, Harvard Medical School, Boston, MA 02115, USA. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. ; Redeemer's University, Ogun State, Nigeria. ; University of Sierra Leone, Freetown, Sierra Leone. ; Institute of Evolutionary Biology, University of Edinburgh, Edinburgh EH9 3JT, UK. Fogarty International Center, National Institutes of Health, Bethesda, MD 20892, USA. Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh EH9 3JT, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25214632" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Woodroffe, Rosie -- Hedges, Simon -- Durant, Sarah -- New York, N.Y. -- Science. 2014 Jul 25;345(6195):389-90. doi: 10.1126/science.345.6195.389-b. Epub 2014 Jul 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Zoology, Zoological Society of London, London, NW1 4RY, UK. rosie.woodroffe@ioz.ac.uk. ; Wildlife Conservation Society, Bronx, NY 10460, USA. ; Institute of Zoology, Zoological Society of London, London, NW1 4RY, UK. Wildlife Conservation Society, Bronx, NY 10460, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25061195" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pennisi, Elizabeth -- New York, N.Y. -- Science. 2014 Jun 27;344(6191):1470-1. doi: 10.1126/science.344.6191.1470.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24970076" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Woodroffe, Rosie -- Hedges, Simon -- Durant, Sarah M -- New York, N.Y. -- Science. 2014 Apr 4;344(6179):46-8. doi: 10.1126/science.1246251.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Zoology, Regent's Park, London NW1 4RY, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24700847" target="_blank"〉PubMed〈/a〉

Description: The excitatory neurotransmitter glutamate induces modulatory actions via the metabotropic glutamate receptors (mGlus), which are class C G protein-coupled receptors (GPCRs). We determined the structure of the human mGlu1 receptor seven-transmembrane (7TM) domain bound to a negative allosteric modulator, FITM, at a resolution of 2.8 angstroms. The modulator binding site partially overlaps with the orthosteric binding sites of class A GPCRs but is more restricted than most other GPCRs. We observed a parallel 7TM dimer mediated by cholesterols, which suggests that signaling initiated by glutamate's interaction with the extracellular domain might be mediated via 7TM interactions within the full-length receptor dimer. A combination of crystallography, structure-activity relationships, mutagenesis, and full-length dimer modeling provides insights about the allosteric modulation and activation mechanism of class C GPCRs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3991565/" 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/PMC3991565/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wu, Huixian -- Wang, Chong -- Gregory, Karen J -- Han, Gye Won -- Cho, Hyekyung P -- Xia, Yan -- Niswender, Colleen M -- Katritch, Vsevolod -- Meiler, Jens -- Cherezov, Vadim -- Conn, P Jeffrey -- Stevens, Raymond C -- P50 GM073197/GM/NIGMS NIH HHS/ -- R01 DK097376/DK/NIDDK NIH HHS/ -- R01 GM080403/GM/NIGMS NIH HHS/ -- R01 GM099842/GM/NIGMS NIH HHS/ -- R01 MH062646/MH/NIMH NIH HHS/ -- R01 MH090192/MH/NIMH NIH HHS/ -- R01 NS031373/NS/NINDS NIH HHS/ -- R21 NS078262/NS/NINDS NIH HHS/ -- R37 NS031373/NS/NINDS NIH HHS/ -- U54 GM094618/GM/NIGMS NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Apr 4;344(6179):58-64. doi: 10.1126/science.1249489. Epub 2014 Mar 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24603153" target="_blank"〉PubMed〈/a〉

Description: The human neocortex has numerous specialized functional areas whose formation is poorly understood. Here, we describe a 15-base pair deletion mutation in a regulatory element of GPR56 that selectively disrupts human cortex surrounding the Sylvian fissure bilaterally including "Broca's area," the primary language area, by disrupting regional GPR56 expression and blocking RFX transcription factor binding. GPR56 encodes a heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptor required for normal cortical development and is expressed in cortical progenitor cells. GPR56 expression levels regulate progenitor proliferation. GPR56 splice forms are highly variable between mice and humans, and the regulatory element of gyrencephalic mammals directs restricted lateral cortical expression. Our data reveal a mechanism by which control of GPR56 expression pattern by multiple alternative promoters can influence stem cell proliferation, gyral patterning, and, potentially, neocortex evolution.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4480613/" 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/PMC4480613/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bae, Byoung-Il -- Tietjen, Ian -- Atabay, Kutay D -- Evrony, Gilad D -- Johnson, Matthew B -- Asare, Ebenezer -- Wang, Peter P -- Murayama, Ayako Y -- Im, Kiho -- Lisgo, Steven N -- Overman, Lynne -- Sestan, Nenad -- Chang, Bernard S -- Barkovich, A James -- Grant, P Ellen -- Topcu, Meral -- Politsky, Jeffrey -- Okano, Hideyuki -- Piao, Xianhua -- Walsh, Christopher A -- 2R01NS035129/NS/NINDS NIH HHS/ -- G0700089/Medical Research Council/United Kingdom -- GR082557/Wellcome Trust/United Kingdom -- HHSN275200900011C/PHS HHS/ -- N01-HD-9-0011/HD/NICHD NIH HHS/ -- R01 NS035129/NS/NINDS NIH HHS/ -- U01 MH081896/MH/NIMH NIH HHS/ -- U01MH081896/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Feb 14;343(6172):764-8. doi: 10.1126/science.1244392.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Genetics and Genomics, Manton Center for Orphan Disease, and Howard Hughes Medical Institute, Boston Children's Hospital, Broad Institute of MIT and Harvard, and Departments of Pediatrics and Neurology, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24531968" target="_blank"〉PubMed〈/a〉

Description: The hierarchical packaging of eukaryotic chromatin plays a central role in transcriptional regulation and other DNA-related biological processes. Here, we report the 11-angstrom-resolution cryogenic electron microscopy (cryo-EM) structures of 30-nanometer chromatin fibers reconstituted in the presence of linker histone H1 and with different nucleosome repeat lengths. The structures show a histone H1-dependent left-handed twist of the repeating tetranucleosomal structural units, within which the four nucleosomes zigzag back and forth with a straight linker DNA. The asymmetric binding and the location of histone H1 in chromatin play a role in the formation of the 30-nanometer fiber. Our results provide mechanistic insights into how nucleosomes compact into higher-order chromatin fibers.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Song, Feng -- Chen, Ping -- Sun, Dapeng -- Wang, Mingzhu -- Dong, Liping -- Liang, Dan -- Xu, Rui-Ming -- Zhu, Ping -- Li, Guohong -- New York, N.Y. -- Science. 2014 Apr 25;344(6182):376-80. doi: 10.1126/science.1251413.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24763583" target="_blank"〉PubMed〈/a〉

Description: Reef-building in metazoans represents an important ecological innovation whereby individuals collectively enhance feeding efficiency and gain protection from competitors and predation. The appearance of metazoan reefs in the fossil record therefore indicates an adaptive response to complex ecological pressures. In the Nama Group, Namibia, we found evidence of reef-building by the earliest known skeletal metazoan, the globally distributed Cloudina, ~548 million years ago. These Cloudina reefs formed open frameworks without a microbial component but with mutual attachment and cementation between individuals. Orientated growth implies a passive suspension-feeding habit into nutrient-rich currents. The characteristics of Cloudina support the view that metazoan reef-building was promoted by the rise of substrate competitors and predators.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Penny, A M -- Wood, R -- Curtis, A -- Bowyer, F -- Tostevin, R -- Hoffman, K-H -- New York, N.Y. -- Science. 2014 Jun 27;344(6191):1504-6. doi: 10.1126/science.1253393.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of GeoSciences, University of Edinburgh, West Mains Road, Edinburgh EH9 3JW, UK. a.m.penny@ed.ac.uk. ; School of GeoSciences, University of Edinburgh, West Mains Road, Edinburgh EH9 3JW, UK. ; Department of Earth Sciences, University College London, Gower Street, London WC1E 6BT, UK. ; Geological Survey of Namibia, Private Bag 13297, Windhoek, Namibia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24970084" target="_blank"〉PubMed〈/a〉

Description: Reported trends in the mean and variability of coastal upwelling in eastern boundary currents have raised concerns about the future of these highly productive and biodiverse marine ecosystems. However, the instrumental records on which these estimates are based are insufficiently long to determine whether such trends exceed preindustrial limits. In the California Current, a 576-year reconstruction of climate variables associated with winter upwelling indicates that variability increased over the latter 20th century to levels equaled only twice during the past 600 years. This modern trend in variance may be unique, because it appears to be driven by an unprecedented succession of extreme, downwelling-favorable, winter climate conditions that profoundly reduce productivity for marine predators of commercial and conservation interest.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Black, Bryan A -- Sydeman, William J -- Frank, David C -- Griffin, Daniel -- Stahle, David W -- Garcia-Reyes, Marisol -- Rykaczewski, Ryan R -- Bograd, Steven J -- Peterson, William T -- New York, N.Y. -- Science. 2014 Sep 19;345(6203):1498-502. doi: 10.1126/science.1253209.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Texas Marine Science Institute, 750 Channel View Drive, Port Aransas, TX 78373, USA. bryan.black@utexas.edu. ; Farallon Institute for Advanced Ecosystem Research, 101 H Street, Suite Q, Petaluma, CA 94952, USA. ; Swiss Federal Research Institute WSL, Zurcherstrasse 111, CH-8903 Birmensdorf, Switzerland and Oeschger Centre for Climate Change Research, University of Bern, Zahringerstrasse 25, CH-3012 Bern, Switzerland. ; Department of Geology and Geophysics, Woods Hole Oceanographic Institution, 266 Woods Hole Road, Woods Hole, MA 02543, USA. ; Department of Geosciences, University of Arkansas, 216 Ozark Hall, Fayetteville, AR 72701, USA. ; Department of Biological Sciences and Marine Science Program, University of South Carolina, 701 Sumter Street, Columbia, SC 29208, USA. ; Environmental Research Division, Southwest Fisheries Science Center, National Oceanic and Atmospheric Administration (NOAA), 1352 Lighthouse Avenue, Pacific Grove, CA 93950, USA. ; Northwest Fisheries Science Center, Hatfield Marine Science Center, NOAA, 2030 Southeast Marine Science Drive, Newport, OR 97365, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25237100" target="_blank"〉PubMed〈/a〉

Description: Fucosylation of intestinal epithelial cells, catalyzed by fucosyltransferase 2 (Fut2), is a major glycosylation mechanism of host-microbiota symbiosis. Commensal bacteria induce epithelial fucosylation, and epithelial fucose is used as a dietary carbohydrate by many of these bacteria. However, the molecular and cellular mechanisms that regulate the induction of epithelial fucosylation are unknown. Here, we show that type 3 innate lymphoid cells (ILC3) induced intestinal epithelial Fut2 expression and fucosylation in mice. This induction required the cytokines interleukin-22 and lymphotoxin in a commensal bacteria-dependent and -independent manner, respectively. Disruption of intestinal fucosylation led to increased susceptibility to infection by Salmonella typhimurium. Our data reveal a role for ILC3 in shaping the gut microenvironment through the regulation of epithelial glycosylation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4774895/" 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/PMC4774895/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goto, Yoshiyuki -- Obata, Takashi -- Kunisawa, Jun -- Sato, Shintaro -- Ivanov, Ivaylo I -- Lamichhane, Aayam -- Takeyama, Natsumi -- Kamioka, Mariko -- Sakamoto, Mitsuo -- Matsuki, Takahiro -- Setoyama, Hiromi -- Imaoka, Akemi -- Uematsu, Satoshi -- Akira, Shizuo -- Domino, Steven E -- Kulig, Paulina -- Becher, Burkhard -- Renauld, Jean-Christophe -- Sasakawa, Chihiro -- Umesaki, Yoshinori -- Benno, Yoshimi -- Kiyono, Hiroshi -- 1R01DK098378/DK/NIDDK NIH HHS/ -- R01 DK098378/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2014 Sep 12;345(6202):1254009. doi: 10.1126/science.1254009. Epub 2014 Aug 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan. Microbe Division/Japan Collection of Microorganisms, RIKEN BioResource Center, Tsukuba 305-0074, Japan. ; Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. Microbe Division/Japan Collection of Microorganisms, RIKEN BioResource Center, Tsukuba 305-0074, Japan. ; Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. Laboratory of Vaccine Materials, National Institute of Biomedical Innovation, Osaka 567-0085, Japan. Division of Mucosal Immunology, International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. ; Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan. ; Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA. ; Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. ; Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. Nippon Institute for Biological Science, Tokyo 198-0024, Japan. ; Microbe Division/Japan Collection of Microorganisms, RIKEN BioResource Center, Tsukuba 305-0074, Japan. ; Yakult Central Institute, Tokyo 186-8650, Japan. ; Division of Innate Immune Regulation, International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. Department of Mucosal Immunology, School of Medicine, Chiba University, 1-8-1 Inohana, Chuou-ku, Chiba, 260-8670, Japan. ; Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan. ; Department of Obstetrics and Gynecology, Cellular and Molecular Biology Program, University of Michigan Medical Center, Ann Arbor, MI 48109-5617, USA. ; Institute of Experimental Immunology, University of Zurich, Winterthurerstrasse 190, Zurich CH-8057, Switzerland. ; Ludwig Institute for Cancer Research and Universite Catholique de Louvain, Brussels B-1200, Belgium. ; Nippon Institute for Biological Science, Tokyo 198-0024, Japan. Division of Bacterial Infection, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. Medical Mycology Research Center, Chiba University, Chiba 260-8673, Japan. ; Benno Laboratory, Innovation Center, RIKEN, Wako, Saitama 351-0198, Japan. ; Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan. Division of Mucosal Immunology, International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25214634" target="_blank"〉PubMed〈/a〉

Description: Some HIV-infected individuals develop broadly neutralizing antibodies (bNAbs), whereas most develop antibodies that neutralize only a narrow range of viruses (nNAbs). bNAbs, but not nNAbs, protect animals from experimental infection and are likely a key component of an effective vaccine. nNAbs and bNAbs target the same regions of the viral envelope glycoprotein (Env), but for reasons that remain unclear only nNAbs are elicited by Env immunization. We show that in contrast to germline-reverted (gl) bNAbs, glnNAbs recognized diverse recombinant Envs. Moreover, owing to binding affinity differences, nNAb B cell progenitors had an advantage in becoming activated and internalizing Env compared with bNAb B cell progenitors. We then identified an Env modification strategy that minimized the activation of nNAb B cells targeting epitopes that overlap those of bNAbs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4290850/" 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/PMC4290850/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McGuire, Andrew T -- Dreyer, Anita M -- Carbonetti, Sara -- Lippy, Adriana -- Glenn, Jolene -- Scheid, Johannes F -- Mouquet, Hugo -- Stamatatos, Leonidas -- P01 AI094419/AI/NIAID NIH HHS/ -- P01 AI094419-01/AI/NIAID NIH HHS/ -- U19 19AI109632-01/AI/NIAID NIH HHS/ -- U19 AI109632/AI/NIAID NIH HHS/ -- Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2014 Dec 12;346(6215):1380-3. doi: 10.1126/science.1259206.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Seattle Biomedical Research Institute, Seattle, WA 98109, USA. ; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA. ; Laboratory of Humoral Response to Pathogens, Department of Immunology, Institut Pasteur and CNRS-URA 1961, 75015 Paris, France. ; Seattle Biomedical Research Institute, Seattle, WA 98109, USA. Department of Global Health, University of Washington, Seattle, WA 98109, USA. lstamata@fhcrc.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25504724" target="_blank"〉PubMed〈/a〉

Description: Ecological specialization should minimize niche overlap, yet herbivorous neotropical flies (Blepharoneura) and their lethal parasitic wasps (parasitoids) exhibit both extreme specialization and apparent niche overlap in host plants. From just two plant species at one site in Peru, we collected 3636 flowers yielding 1478 fly pupae representing 14 Blepharoneura fly species, 18 parasitoid species (14 Bellopius species), and parasitoid-host associations, all discovered through analysis of molecular data. Multiple sympatric species specialize on the same sex flowers of the same fly host-plant species-which suggests extreme niche overlap; however, niche partitioning was exposed by interactions between wasps and flies. Most Bellopius species emerged as adults from only one fly species, yet evidence from pupae (preadult emergence samples) show that most Bellopius also attacked additional fly species but never emerged as adults from those flies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Condon, Marty A -- Scheffer, Sonja J -- Lewis, Matthew L -- Wharton, Robert -- Adams, Dean C -- Forbes, Andrew A -- New York, N.Y. -- Science. 2014 Mar 14;343(6176):1240-4. doi: 10.1126/science.1245007.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Cornell College, Mount Vernon, IA 52314, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24626926" target="_blank"〉PubMed〈/a〉

Description: In 1990, Andrew Bakun proposed that increasing greenhouse gas concentrations would force intensification of upwelling-favorable winds in eastern boundary current systems that contribute substantial services to society. Because there is considerable disagreement about whether contemporary wind trends support Bakun's hypothesis, we performed a meta-analysis of the literature on upwelling-favorable wind intensification. The preponderance of published analyses suggests that winds have intensified in the California, Benguela, and Humboldt upwelling systems and weakened in the Iberian system over time scales ranging up to 60 years; wind change is equivocal in the Canary system. Stronger intensification signals are observed at higher latitudes, consistent with the warming pattern associated with climate change. Overall, reported changes in coastal winds, although subtle and spatially variable, support Bakun's hypothesis of upwelling intensification in eastern boundary current systems.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sydeman, W J -- Garcia-Reyes, M -- Schoeman, D S -- Rykaczewski, R R -- Thompson, S A -- Black, B A -- Bograd, S J -- New York, N.Y. -- Science. 2014 Jul 4;345(6192):77-80. doi: 10.1126/science.1251635.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Farallon Institute for Advanced Ecosystem Research, Suite Q, 101 H Street, Petaluma, CA 94952, USA. wsydeman@comcast.net. ; Farallon Institute for Advanced Ecosystem Research, Suite Q, 101 H Street, Petaluma, CA 94952, USA. ; Faculty of Science, Health, Education and Engineering, University of the Sunshine Coast, Locked Bag 4, Maroochydore DC, Queensland 4558, Australia. ; Department of Biological Sciences and Marine Science Program, University of South Carolina, 701 Sumter Street, Columbia, SC 29208, USA. ; Farallon Institute for Advanced Ecosystem Research, Suite Q, 101 H Street, Petaluma, CA 94952, USA. Climate Impacts Group, University of Washington, Box 355674, Seattle, WA 98195, USA. ; Marine Science Institute, University of Texas, 750 Channel View Drive, Port Aransas, TX 78373, USA. ; Environmental Research Division, National Oceanic and Atmospheric Administration (NOAA) Southwest Fisheries Science Center, 1352 Lighthouse Avenue, Pacific Grove, CA 93950-2097, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24994651" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gramling, Carolyn -- New York, N.Y. -- Science. 2014 May 2;344(6183):463. doi: 10.1126/science.344.6183.463.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24786058" target="_blank"〉PubMed〈/a〉

Description: The New World Arctic, the last region of the Americas to be populated by humans, has a relatively well-researched archaeology, but an understanding of its genetic history is lacking. We present genome-wide sequence data from ancient and present-day humans from Greenland, Arctic Canada, Alaska, Aleutian Islands, and Siberia. We show that Paleo-Eskimos (~3000 BCE to 1300 CE) represent a migration pulse into the Americas independent of both Native American and Inuit expansions. Furthermore, the genetic continuity characterizing the Paleo-Eskimo period was interrupted by the arrival of a new population, representing the ancestors of present-day Inuit, with evidence of past gene flow between these lineages. Despite periodic abandonment of major Arctic regions, a single Paleo-Eskimo metapopulation likely survived in near-isolation for more than 4000 years, only to vanish around 700 years ago.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Raghavan, Maanasa -- DeGiorgio, Michael -- Albrechtsen, Anders -- Moltke, Ida -- Skoglund, Pontus -- Korneliussen, Thorfinn S -- Gronnow, Bjarne -- Appelt, Martin -- Gullov, Hans Christian -- Friesen, T Max -- Fitzhugh, William -- Malmstrom, Helena -- Rasmussen, Simon -- Olsen, Jesper -- Melchior, Linea -- Fuller, Benjamin T -- Fahrni, Simon M -- Stafford, Thomas Jr -- Grimes, Vaughan -- Renouf, M A Priscilla -- Cybulski, Jerome -- Lynnerup, Niels -- Lahr, Marta Mirazon -- Britton, Kate -- Knecht, Rick -- Arneborg, Jette -- Metspalu, Mait -- Cornejo, Omar E -- Malaspinas, Anna-Sapfo -- Wang, Yong -- Rasmussen, Morten -- Raghavan, Vibha -- Hansen, Thomas V O -- Khusnutdinova, Elza -- Pierre, Tracey -- Dneprovsky, Kirill -- Andreasen, Claus -- Lange, Hans -- Hayes, M Geoffrey -- Coltrain, Joan -- Spitsyn, Victor A -- Gotherstrom, Anders -- Orlando, Ludovic -- Kivisild, Toomas -- Villems, Richard -- Crawford, Michael H -- Nielsen, Finn C -- Dissing, Jorgen -- Heinemeier, Jan -- Meldgaard, Morten -- Bustamante, Carlos -- O'Rourke, Dennis H -- Jakobsson, Mattias -- Gilbert, M Thomas P -- Nielsen, Rasmus -- Willerslev, Eske -- New York, N.Y. -- Science. 2014 Aug 29;345(6200):1255832. doi: 10.1126/science.1255832.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Oster Voldgade 5-7, 1350 Copenhagen, Denmark. ; Department of Biology, Pennsylvania State University, 502 Wartik Laboratory, University Park, PA 16802, USA. ; Bioinformatics Centre, Department of Biology, University of Copenhagen, Ole Maaloes Vej 5, 2200 Copenhagen, Denmark. ; Bioinformatics Centre, Department of Biology, University of Copenhagen, Ole Maaloes Vej 5, 2200 Copenhagen, Denmark. Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA. ; Department of Evolutionary Biology, Uppsala University, Norbyvagen 18D, 75236 Uppsala, Sweden. Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. ; Arctic Centre at the Ethnographic Collections (SILA), National Museum of Denmark, Frederiksholms Kanal 12, 1220 Copenhagen, Denmark. ; Department of Anthropology, University of Toronto, Toronto, Ontario M5S 2S2, Canada. ; Arctic Studies Center, Post Office Box 37012, Department of Anthropology, MRC 112, National Museum of Natural History, Smithsonian Institution, Washington, DC 20013-7012, USA. ; Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Oster Voldgade 5-7, 1350 Copenhagen, Denmark. Department of Evolutionary Biology, Uppsala University, Norbyvagen 18D, 75236 Uppsala, Sweden. ; Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Kemitorvet, 2800 Kongens Lyngby, Denmark. ; AMS 14C Dating Centre, Department of Physics and Astronomy, Aarhus University, Ny Munkegade 120, 8000 Aarhus C, Denmark. ; Anthropological Laboratory, Institute of Forensic Medicine, Faculty of Health Sciences, University of Copenhagen, Frederik V's Vej 11, 2100 Copenhagen, Denmark. ; Department of Earth System Science, University of California, Irvine, CA 92697, USA. ; Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Oster Voldgade 5-7, 1350 Copenhagen, Denmark. AMS 14C Dating Centre, Department of Physics and Astronomy, Aarhus University, Ny Munkegade 120, 8000 Aarhus C, Denmark. ; Department of Archaeology, Memorial University, Queen's College, 210 Prince Philip Drive, St. John's, Newfoundland, A1C 5S7, Canada. Department of Human Evolution, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany. ; Department of Archaeology, Memorial University, Queen's College, 210 Prince Philip Drive, St. John's, Newfoundland, A1C 5S7, Canada. ; Canadian Museum of History, 100 Rue Laurier, Gatineau, Quebec K1A 0M8, Canada. Department of Anthropology, University of Western Ontario, 1151 Richmond Street North, London N6A 5C2, Canada. ; Leverhulme Centre for Human Evolutionary Studies, Department of Archaeology and Anthropology, University of Cambridge, Cambridge CB2 1QH, UK. ; Department of Human Evolution, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany. Department of Archaeology, University of Aberdeen, St. Mary's Building, Elphinstone Road, Aberdeen AB24 3UF, Scotland, UK. ; Department of Archaeology, University of Aberdeen, St. Mary's Building, Elphinstone Road, Aberdeen AB24 3UF, Scotland, UK. ; National Museum of Denmark, Frederiksholms kanal 12, 1220 Copenhagen, Denmark. School of Geosciences, University of Edinburgh, Edinburgh EH8 9XP, UK. ; Estonian Biocentre, Evolutionary Biology Group, Tartu 51010, Estonia. Department of Evolutionary Biology, University of Tartu, Tartu 51010, Estonia. ; Department of Genetics, School of Medicine, Stanford University, Stanford, CA 94305, USA. School of Biological Sciences, Washington State University, Post Office Box 644236, Pullman, WA 99164, USA. ; Department of Integrative Biology, University of California, Berkeley, CA 94720, USA. Ancestry.com DNA LLC, San Francisco, CA 94107, USA. ; Informatics and Bio-computing, Ontario Institute for Cancer Research, 661 University Avenue, Suite 510, Toronto, Ontario, M5G 0A3, Canada. ; Center for Genomic Medicine, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark. ; Institute of Biochemistry and Genetics, Ufa Scientific Center of Russian Academy of Sciences, Ufa, Russia. Department of Genetics and Fundamental Medicine, Bashkir State University, Ufa, Bashkortostan 450074, Russia. ; State Museum for Oriental Art, 12a, Nikitsky Boulevard, Moscow 119019, Russia. ; Greenland National Museum and Archives, Post Office Box 145, 3900 Nuuk, Greenland. ; Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. Department of Anthropology, Weinberg College of Arts and Sciences, Northwestern University, Evanston, IL 60208, USA. Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. ; Department of Anthropology, University of Utah, Salt Lake City, UT 84112, USA. ; Research Centre for Medical Genetics of Russian Academy of Medical Sciences, 1 Moskvorechie, Moscow 115478, Russia. ; Department of Archaeology and Classical Studies, Stockholm University, Stockholm, Sweden. ; Estonian Biocentre, Evolutionary Biology Group, Tartu 51010, Estonia. Department of Archaeology and Anthropology, University of Cambridge, Cambridge CB2 1QH, UK. ; Laboratory of Biological Anthropology, University of Kansas, Lawrence, KS 66045, USA. ; Department of Genetics, School of Medicine, Stanford University, Stanford, CA 94305, USA. ; Department of Evolutionary Biology, Uppsala University, Norbyvagen 18D, 75236 Uppsala, Sweden. ; Department of Integrative Biology, University of California, Berkeley, CA 94720, USA. ; Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Oster Voldgade 5-7, 1350 Copenhagen, Denmark. ewillerslev@snm.ku.dk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25170159" target="_blank"〉PubMed〈/a〉

Description: The ethanolamine utilization (eut) locus of Enterococcus faecalis, containing at least 19 genes distributed over four polycistronic messenger RNAs, appears to be regulated by a single adenosyl cobalamine (AdoCbl)-responsive riboswitch. We report that the AdoCbl-binding riboswitch is part of a small, trans-acting RNA, EutX, which additionally contains a dual-hairpin substrate for the RNA binding-response regulator, EutV. In the absence of AdoCbl, EutX uses this structure to sequester EutV. EutV is known to regulate the eut messenger RNAs by binding dual-hairpin structures that overlap terminators and thus prevent transcription termination. In the presence of AdoCbl, EutV cannot bind to EutX and, instead, causes transcriptional read through of multiple eut genes. This work introduces riboswitch-mediated control of protein sequestration as a posttranscriptional mechanism to coordinately regulate gene expression.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356242/" 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/PMC4356242/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉DebRoy, Sruti -- Gebbie, Margo -- Ramesh, Arati -- Goodson, Jonathan R -- Cruz, Melissa R -- van Hoof, Ambro -- Winkler, Wade C -- Garsin, Danielle A -- P30 DK056338/DK/NIDDK NIH HHS/ -- R01 AI076406/AI/NIAID NIH HHS/ -- R01 AI110432/AI/NIAID NIH HHS/ -- R01 GM099790/GM/NIGMS NIH HHS/ -- R01AI076406/AI/NIAID NIH HHS/ -- R01GM099790/GM/NIGMS NIH HHS/ -- R56 AI110432/AI/NIAID NIH HHS/ -- R56AI110432/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2014 Aug 22;345(6199):937-40. doi: 10.1126/science.1255091.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Molecular Genetics, The University of Texas Health Science Center at Houston, TX 77030, USA. ; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA. ; Department of Biochemistry, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. ; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA. danielle.a.garsin@uth.tmc.edu wwinkler@umd.edu. ; Department of Microbiology and Molecular Genetics, The University of Texas Health Science Center at Houston, TX 77030, USA. danielle.a.garsin@uth.tmc.edu wwinkler@umd.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25146291" target="_blank"〉PubMed〈/a〉

Description: The genetic changes underlying the initial steps of animal domestication are still poorly understood. We generated a high-quality reference genome for the rabbit and compared it to resequencing data from populations of wild and domestic rabbits. We identified more than 100 selective sweeps specific to domestic rabbits but only a relatively small number of fixed (or nearly fixed) single-nucleotide polymorphisms (SNPs) for derived alleles. SNPs with marked allele frequency differences between wild and domestic rabbits were enriched for conserved noncoding sites. Enrichment analyses suggest that genes affecting brain and neuronal development have often been targeted during domestication. We propose that because of a truly complex genetic background, tame behavior in rabbits and other domestic animals evolved by shifts in allele frequencies at many loci, rather than by critical changes at only a few domestication loci.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Carneiro, Miguel -- Rubin, Carl-Johan -- Di Palma, Federica -- Albert, Frank W -- Alfoldi, Jessica -- Barrio, Alvaro Martinez -- Pielberg, Gerli -- Rafati, Nima -- Sayyab, Shumaila -- Turner-Maier, Jason -- Younis, Shady -- Afonso, Sandra -- Aken, Bronwen -- Alves, Joel M -- Barrell, Daniel -- Bolet, Gerard -- Boucher, Samuel -- Burbano, Hernan A -- Campos, Rita -- Chang, Jean L -- Duranthon, Veronique -- Fontanesi, Luca -- Garreau, Herve -- Heiman, David -- Johnson, Jeremy -- Mage, Rose G -- Peng, Ze -- Queney, Guillaume -- Rogel-Gaillard, Claire -- Ruffier, Magali -- Searle, Steve -- Villafuerte, Rafael -- Xiong, Anqi -- Young, Sarah -- Forsberg-Nilsson, Karin -- Good, Jeffrey M -- Lander, Eric S -- Ferrand, Nuno -- Lindblad-Toh, Kerstin -- Andersson, Leif -- 095908/Wellcome Trust/United Kingdom -- U54 HG003067/HG/NHGRI NIH HHS/ -- WT095908/Wellcome Trust/United Kingdom -- WT098051/Wellcome Trust/United Kingdom -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2014 Aug 29;345(6200):1074-9. doi: 10.1126/science.1253714.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉CIBIO/InBIO, Centro de Investigacao em Biodiversidade e Recursos Geneticos, Campus Agrario de Vairao, Universidade do Porto, 4485-661, Vairao, Portugal. ; Science for Life Laboratory Uppsala, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden. ; Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, MA 02142, USA. Vertebrate and Health Genomics, The Genome Analysis Centre, Norwich, UK. ; Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany. ; Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, MA 02142, USA. ; Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden. ; Science for Life Laboratory Uppsala, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden. Department of Animal Production, Ain Shams University, Shoubra El-Kheima, Cairo, Egypt. ; Wellcome Trust Sanger Institute, Hinxton, UK. European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK. ; CIBIO/InBIO, Centro de Investigacao em Biodiversidade e Recursos Geneticos, Campus Agrario de Vairao, Universidade do Porto, 4485-661, Vairao, Portugal. Department of Genetics, University of Cambridge, Cambridge CB2 3EH, UK. ; Institut National de la Recherche Agronomique (INRA), UMR1388 Genetique, Physiologie et Systemes d'Elevage, F-31326 Castanet-Tolosan, France. ; Labovet Conseil, BP539, 85505 Les Herbiers Cedex, France. ; INRA, UMR1198 Biologie du Developpement et Reproduction, F-78350 Jouy-en-Josas, France. ; Department of Agricultural and Food Sciences, Division of Animal Sciences, University of Bologna, 40127 Bologna, Italy. ; Laboratory of Immunology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, MD 20892, USA. ; U.S. Department of Energy Joint Genome Institute, Lawrence Berkeley National Laboratory, 2800 Mitchell Drive, Walnut Creek, CA 94598, USA. ; ANTAGENE, Animal Genomics Laboratory, Lyon, France. ; INRA, UMR1313 Genetique Animale et Biologie Integrative, F- 78350, Jouy-en-Josas, France. ; Wellcome Trust Sanger Institute, Hinxton, UK. ; Instituto de Estudios Sociales Avanzados, (IESA-CSIC) Campo Santo de los Martires 7, Cordoba, Spain. ; Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. ; Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany. Division of Biological Sciences, The University of Montana, Missoula, MT 59812, USA. ; CIBIO/InBIO, Centro de Investigacao em Biodiversidade e Recursos Geneticos, Campus Agrario de Vairao, Universidade do Porto, 4485-661, Vairao, Portugal. Departamento de Biologia, Faculdade de Ciencias, Universidade do Porto, Rua do Campo Alegre sn. 4169-007 Porto, Portugal. ; Science for Life Laboratory Uppsala, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden. Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, MA 02142, USA. kersli@broadinstitute.org leif.andersson@imbim.uu.se. ; Science for Life Laboratory Uppsala, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden. Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden. Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843-4458, USA. kersli@broadinstitute.org leif.andersson@imbim.uu.se.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25170157" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ferreira, J -- Aragao, L E O C -- Barlow, J -- Barreto, P -- Berenguer, E -- Bustamante, M -- Gardner, T A -- Lees, A C -- Lima, A -- Louzada, J -- Pardini, R -- Parry, L -- Peres, C A -- Pompeu, P S -- Tabarelli, M -- Zuanon, J -- New York, N.Y. -- Science. 2014 Nov 7;346(6210):706-7. doi: 10.1126/science.1260194.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉See the supplementary materials for author af liations. joice.ferreira@embrapa.br. ; See the supplementary materials for author af liations.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25378611" target="_blank"〉PubMed〈/a〉

Description: The prevention of fertilization through self-pollination (or pollination by a close relative) in the Brassicaceae plant family is determined by the genotype of the plant at the self-incompatibility locus (S locus). The many alleles at this locus exhibit a dominance hierarchy that determines which of the two allelic specificities of a heterozygous genotype is expressed at the phenotypic level. Here, we uncover the evolution of how at least 17 small RNA (sRNA)-producing loci and their multiple target sites collectively control the dominance hierarchy among alleles within the gene controlling the pollen S-locus phenotype in a self-incompatible Arabidopsis species. Selection has created a dynamic repertoire of sRNA-target interactions by jointly acting on sRNA genes and their target sites, which has resulted in a complex system of regulation among alleles.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Durand, Eleonore -- Meheust, Raphael -- Soucaze, Marion -- Goubet, Pauline M -- Gallina, Sophie -- Poux, Celine -- Fobis-Loisy, Isabelle -- Guillon, Eline -- Gaude, Thierry -- Sarazin, Alexis -- Figeac, Martin -- Prat, Elisa -- Marande, William -- Berges, Helene -- Vekemans, Xavier -- Billiard, Sylvain -- Castric, Vincent -- New York, N.Y. -- Science. 2014 Dec 5;346(6214):1200-5. doi: 10.1126/science.1259442.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratoire Genetique et Evolution des Populations Vegetales, CNRS UMR 8198, Universite Lille 1, F-59655 Villeneuve d'Ascq cedex, France. ; Reproduction et Developpement des Plantes, Institut Federatif de Recherche 128, Centre National de la Recherche Scientifique, Institut National de la Recherche Agronomique, Universite Claude Bernard Lyon I, Ecole Normale Superieure de Lyon, F-69364 Lyon, Cedex 07, France. ; Department of Biology, Swiss Federal Institute of Technology Zurich, CH-8093 Zurich, Switzerland. ; UDSL Universite Lille 2 Droit et Sante, and Plate-forme de genomique fonctionnelle et structurale IFR-114, F-59000 Lille, France. ; Centre National des Ressources Genomiques Vegetales, INRA UPR 1258, Castanet-Tolosan, France. ; Laboratoire Genetique et Evolution des Populations Vegetales, CNRS UMR 8198, Universite Lille 1, F-59655 Villeneuve d'Ascq cedex, France. vincent.castric@univ-lille1.fr.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25477454" target="_blank"〉PubMed〈/a〉

Description: In theoretical ecology, traditional studies based on dynamical stability and numerical simulations have not found a unified answer to the effect of network architecture on community persistence. Here, we introduce a mathematical framework based on the concept of structural stability to explain such a disparity of results. We investigated the range of conditions necessary for the stable coexistence of all species in mutualistic systems. We show that the apparently contradictory conclusions reached by previous studies arise as a consequence of overseeing either the necessary conditions for persistence or its dependence on model parameterization. We show that observed network architectures maximize the range of conditions for species coexistence. We discuss the applicability of structural stability to study other types of interspecific interactions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rohr, Rudolf P -- Saavedra, Serguei -- Bascompte, Jordi -- New York, N.Y. -- Science. 2014 Jul 25;345(6195):1253497. doi: 10.1126/science.1253497.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Integrative Ecology Group, Estacion Biologica de Donana-Consejo Superior de Investigaciones Cientificas (EBD-CSIC), Calle Americo Vespucio s/n, E-41092 Sevilla, Spain. Unit of Ecology and Evolution, Department of Biology, University of Fribourg, Chemin du Musee 10, CH-1700 Fribourg, Switzerland. ; Integrative Ecology Group, Estacion Biologica de Donana-Consejo Superior de Investigaciones Cientificas (EBD-CSIC), Calle Americo Vespucio s/n, E-41092 Sevilla, Spain. ; Integrative Ecology Group, Estacion Biologica de Donana-Consejo Superior de Investigaciones Cientificas (EBD-CSIC), Calle Americo Vespucio s/n, E-41092 Sevilla, Spain. bascompte@ebd.csic.es.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25061214" target="_blank"〉PubMed〈/a〉

Description: Cellular memory is crucial to many natural biological processes and sophisticated synthetic biology applications. Existing cellular memories rely on epigenetic switches or recombinases, which are limited in scalability and recording capacity. In this work, we use the DNA of living cell populations as genomic "tape recorders" for the analog and distributed recording of long-term event histories. We describe a platform for generating single-stranded DNA (ssDNA) in vivo in response to arbitrary transcriptional signals. When coexpressed with a recombinase, these intracellularly expressed ssDNAs target specific genomic DNA addresses, resulting in precise mutations that accumulate in cell populations as a function of the magnitude and duration of the inputs. This platform could enable long-term cellular recorders for environmental and biomedical applications, biological state machines, and enhanced genome engineering strategies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4266475/" 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/PMC4266475/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Farzadfard, Fahim -- Lu, Timothy K -- 1DP2OD008435/OD/NIH HHS/ -- 1P50GM098792/GM/NIGMS NIH HHS/ -- DP2 OD008435/OD/NIH HHS/ -- P50 GM098792/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Nov 14;346(6211):1256272. doi: 10.1126/science.1256272.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Synthetic Biology Group, Research Laboratory of Electronics, Department of Electrical Engineering and Computer Science and Department of Biological Engineering, Massachusetts Institute of Technology (MIT), 77 Massachusetts Avenue, Cambridge, MA 02139, USA. MIT Synthetic Biology Center, 500 Technology Square, Cambridge, MA 02139, USA. MIT Microbiology Program, 77 Massachusetts Avenue, Cambridge, MA 02139, USA. ; Synthetic Biology Group, Research Laboratory of Electronics, Department of Electrical Engineering and Computer Science and Department of Biological Engineering, Massachusetts Institute of Technology (MIT), 77 Massachusetts Avenue, Cambridge, MA 02139, USA. MIT Synthetic Biology Center, 500 Technology Square, Cambridge, MA 02139, USA. MIT Microbiology Program, 77 Massachusetts Avenue, Cambridge, MA 02139, USA. timlu@mit.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25395541" target="_blank"〉PubMed〈/a〉

Description: Understanding the spatial organization of gene expression with single-nucleotide resolution requires localizing the sequences of expressed RNA transcripts within a cell in situ. Here, we describe fluorescent in situ RNA sequencing (FISSEQ), in which stably cross-linked complementary DNA (cDNA) amplicons are sequenced within a biological sample. Using 30-base reads from 8102 genes in situ, we examined RNA expression and localization in human primary fibroblasts with a simulated wound-healing assay. FISSEQ is compatible with tissue sections and whole-mount embryos and reduces the limitations of optical resolution and noisy signals on single-molecule detection. Our platform enables massively parallel detection of genetic elements, including gene transcripts and molecular barcodes, and can be used to investigate cellular phenotype, gene regulation, and environment in situ.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4140943/" 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/PMC4140943/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Je Hyuk -- Daugharthy, Evan R -- Scheiman, Jonathan -- Kalhor, Reza -- Yang, Joyce L -- Ferrante, Thomas C -- Terry, Richard -- Jeanty, Sauveur S F -- Li, Chao -- Amamoto, Ryoji -- Peters, Derek T -- Turczyk, Brian M -- Marblestone, Adam H -- Inverso, Samuel A -- Bernard, Amy -- Mali, Prashant -- Rios, Xavier -- Aach, John -- Church, George M -- GM080177/GM/NIGMS NIH HHS/ -- MH098977/MH/NIMH NIH HHS/ -- P50 HG005550/HG/NHGRI NIH HHS/ -- RC2 HL102815/HL/NHLBI NIH HHS/ -- RC2HL102815/HL/NHLBI NIH HHS/ -- T32 GM007753/GM/NIGMS NIH HHS/ -- T32 GM080177/GM/NIGMS NIH HHS/ -- U01 MH098977/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2014 Mar 21;343(6177):1360-3. doi: 10.1126/science.1250212. Epub 2014 Feb 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wyss Institute, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24578530" target="_blank"〉PubMed〈/a〉

Description: Mutations in the mitochondrial genome are associated with multiple diseases and biological processes; however, little is known about the extent of sequence variation in the mitochondrial transcriptome. By ultra-deeply sequencing mitochondrial RNA (〉6000x) from the whole blood of ~1000 individuals from the CARTaGENE project, we identified remarkable levels of sequence variation within and across individuals, as well as sites that show consistent patterns of posttranscriptional modification. Using a genome-wide association study, we find that posttranscriptional modification of functionally important sites in mitochondrial transfer RNAs (tRNAs) is under strong genetic control, largely driven by a missense mutation in MRPP3 that explains ~22% of the variance. These results reveal a major nuclear genetic determinant of posttranscriptional modification in mitochondria and suggest that tRNA posttranscriptional modification may affect cellular energy production.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hodgkinson, Alan -- Idaghdour, Youssef -- Gbeha, Elias -- Grenier, Jean-Christophe -- Hip-Ki, Elodie -- Bruat, Vanessa -- Goulet, Jean-Philippe -- de Malliard, Thibault -- Awadalla, Philip -- New York, N.Y. -- Science. 2014 Apr 25;344(6182):413-5. doi: 10.1126/science.1251110.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉CHU Sainte-Justine Research Centre, Department of Pediatrics, Faculty of Medicine, Universite de Montreal, 3175 Chemin de la Cote-Sainte-Catherine, Montreal, Quebec H3T 1C5, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24763589" target="_blank"〉PubMed〈/a〉

Description: In prokaryotes, RNA derived from type I and type III CRISPR loci direct large ribonucleoprotein complexes to destroy invading bacteriophage and plasmids. In Escherichia coli, this 405-kilodalton complex is called Cascade. We report the crystal structure of Cascade bound to a single-stranded DNA (ssDNA) target at a resolution of 3.03 angstroms. The structure reveals that the CRISPR RNA and target strands do not form a double helix but instead adopt an underwound ribbon-like structure. This noncanonical structure is facilitated by rotation of every sixth nucleotide out of the RNA-DNA hybrid and is stabilized by the highly interlocked organization of protein subunits. These studies provide insight into both the assembly and the activity of this complex and suggest a mechanism to enforce fidelity of target binding.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4427192/" 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/PMC4427192/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mulepati, Sabin -- Heroux, Annie -- Bailey, Scott -- GM097330/GM/NIGMS NIH HHS/ -- P41GM103393/GM/NIGMS NIH HHS/ -- P41GM103473/GM/NIGMS NIH HHS/ -- P41RR012408/RR/NCRR NIH HHS/ -- R01 GM097330/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Sep 19;345(6203):1479-84. doi: 10.1126/science.1256996. Epub 2014 Aug 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA. ; Photon Sciences Directorate, Brookhaven National Laboratory, Upton, NY 11973, USA. ; Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA. scott.bailey@jhu.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25123481" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cardinale, Bradley -- New York, N.Y. -- Science. 2014 Jun 6;344(6188):1098. doi: 10.1126/science.344.6188.1098-a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Natural Resources and Environment, University of Michigan, Ann Arbor, MI 48103, USA. bradcard@umich.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24904146" target="_blank"〉PubMed〈/a〉

Description: Ecologists have long sought to understand the factors controlling the structure of savanna vegetation. Using data from 2154 sites in savannas across Africa, Australia, and South America, we found that increasing moisture availability drives increases in fire and tree basal area, whereas fire reduces tree basal area. However, among continents, the magnitude of these effects varied substantially, so that a single model cannot adequately represent savanna woody biomass across these regions. Historical and environmental differences drive the regional variation in the functional relationships between woody vegetation, fire, and climate. These same differences will determine the regional responses of vegetation to future climates, with implications for global carbon stocks.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lehmann, Caroline E R -- Anderson, T Michael -- Sankaran, Mahesh -- Higgins, Steven I -- Archibald, Sally -- Hoffmann, William A -- Hanan, Niall P -- Williams, Richard J -- Fensham, Roderick J -- Felfili, Jeanine -- Hutley, Lindsay B -- Ratnam, Jayashree -- San Jose, Jose -- Montes, Ruben -- Franklin, Don -- Russell-Smith, Jeremy -- Ryan, Casey M -- Durigan, Giselda -- Hiernaux, Pierre -- Haidar, Ricardo -- Bowman, David M J S -- Bond, William J -- New York, N.Y. -- Science. 2014 Jan 31;343(6170):548-52. doi: 10.1126/science.1247355.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, Macquarie University, New South Wales 2109, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24482480" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pawar, Samraat -- New York, N.Y. -- Science. 2014 Jul 25;345(6195):383. doi: 10.1126/science.1256466.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Life Sciences, Imperial College London, Silwood Park, Ascot, Berkshire SL5 7PY, U K. s.pawar@imperial.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25061191" target="_blank"〉PubMed〈/a〉

Description: Rapid advances in DNA synthesis techniques have made it possible to engineer viruses, biochemical pathways and assemble bacterial genomes. Here, we report the synthesis of a functional 272,871-base pair designer eukaryotic chromosome, synIII, which is based on the 316,617-base pair native Saccharomyces cerevisiae chromosome III. Changes to synIII include TAG/TAA stop-codon replacements, deletion of subtelomeric regions, introns, transfer RNAs, transposons, and silent mating loci as well as insertion of loxPsym sites to enable genome scrambling. SynIII is functional in S. cerevisiae. Scrambling of the chromosome in a heterozygous diploid reveals a large increase in a-mater derivatives resulting from loss of the MATalpha allele on synIII. The complete design and synthesis of synIII establishes S. cerevisiae as the basis for designer eukaryotic genome biology.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4033833/" 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/PMC4033833/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Annaluru, Narayana -- Muller, Heloise -- Mitchell, Leslie A -- Ramalingam, Sivaprakash -- Stracquadanio, Giovanni -- Richardson, Sarah M -- Dymond, Jessica S -- Kuang, Zheng -- Scheifele, Lisa Z -- Cooper, Eric M -- Cai, Yizhi -- Zeller, Karen -- Agmon, Neta -- Han, Jeffrey S -- Hadjithomas, Michalis -- Tullman, Jennifer -- Caravelli, Katrina -- Cirelli, Kimberly -- Guo, Zheyuan -- London, Viktoriya -- Yeluru, Apurva -- Murugan, Sindurathy -- Kandavelou, Karthikeyan -- Agier, Nicolas -- Fischer, Gilles -- Yang, Kun -- Martin, J Andrew -- Bilgel, Murat -- Bohutski, Pavlo -- Boulier, Kristin M -- Capaldo, Brian J -- Chang, Joy -- Charoen, Kristie -- Choi, Woo Jin -- Deng, Peter -- DiCarlo, James E -- Doong, Judy -- Dunn, Jessilyn -- Feinberg, Jason I -- Fernandez, Christopher -- Floria, Charlotte E -- Gladowski, David -- Hadidi, Pasha -- Ishizuka, Isabel -- Jabbari, Javaneh -- Lau, Calvin Y L -- Lee, Pablo A -- Li, Sean -- Lin, Denise -- Linder, Matthias E -- Ling, Jonathan -- Liu, Jaime -- Liu, Jonathan -- London, Mariya -- Ma, Henry -- Mao, Jessica -- McDade, Jessica E -- McMillan, Alexandra -- Moore, Aaron M -- Oh, Won Chan -- Ouyang, Yu -- Patel, Ruchi -- Paul, Marina -- Paulsen, Laura C -- Qiu, Judy -- Rhee, Alex -- Rubashkin, Matthew G -- Soh, Ina Y -- Sotuyo, Nathaniel E -- Srinivas, Venkatesh -- Suarez, Allison -- Wong, Andy -- Wong, Remus -- Xie, Wei Rose -- Xu, Yijie -- Yu, Allen T -- Koszul, Romain -- Bader, Joel S -- Boeke, Jef D -- Chandrasegaran, Srinivasan -- 092076/Wellcome Trust/United Kingdom -- GM077291/GM/NIGMS NIH HHS/ -- R01 GM077291/GM/NIGMS NIH HHS/ -- R01 GM090192/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Apr 4;344(6179):55-8. doi: 10.1126/science.1249252. Epub 2014 Mar 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Environmental Health Sciences, Johns Hopkins University (JHU) School of Public Health, Baltimore, MD 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24674868" target="_blank"〉PubMed〈/a〉

Description: Robustness, the maintenance of a character in the presence of genetic change, can help preserve adaptive traits but also may hinder evolvability, the ability to bring forth novel adaptations. We used genotype networks to analyze the binding site repertoires of 193 transcription factors from mice and yeast, providing empirical evidence that robustness and evolvability need not be conflicting properties. Network vertices represent binding sites where two sites are connected if they differ in a single nucleotide. We show that the binding sites of larger genotype networks are not only more robust, but the sequences adjacent to such networks can also bind more transcription factors, thus demonstrating that robustness can facilitate evolvability.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Payne, Joshua L -- Wagner, Andreas -- New York, N.Y. -- Science. 2014 Feb 21;343(6173):875-7. doi: 10.1126/science.1249046.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Zurich, Institute of Evolutionary Biology and Environmental Studies, Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24558158" target="_blank"〉PubMed〈/a〉

Description: Small molecules are useful tools for probing the biological function and therapeutic potential of individual proteins, but achieving selectivity is challenging when the target protein shares structural domains with other proteins. The Bromo and Extra-Terminal (BET) proteins have attracted interest because of their roles in transcriptional regulation, epigenetics, and cancer. The BET bromodomains (protein interaction modules that bind acetyl-lysine) have been targeted by potent small-molecule inhibitors, but these inhibitors lack selectivity for individual family members. We developed an ethyl derivative of an existing small-molecule inhibitor, I-BET/JQ1, and showed that it binds leucine/alanine mutant bromodomains with nanomolar affinity and achieves up to 540-fold selectivity relative to wild-type bromodomains. Cell culture studies showed that blockade of the first bromodomain alone is sufficient to displace a specific BET protein, Brd4, from chromatin. Expansion of this approach could help identify the individual roles of single BET proteins in human physiology and disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4458378/" 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/PMC4458378/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baud, Matthias G J -- Lin-Shiao, Enrique -- Cardote, Teresa -- Tallant, Cynthia -- Pschibul, Annica -- Chan, Kwok-Ho -- Zengerle, Michael -- Garcia, Jordi R -- Kwan, Terence T-L -- Ferguson, Fleur M -- Ciulli, Alessio -- 097945/Z/11/Z/Wellcome Trust/United Kingdom -- 100476/Z/12/Z/Wellcome Trust/United Kingdom -- BB/G023123/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/J001201/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2014 Oct 31;346(6209):638-41. doi: 10.1126/science.1249830. Epub 2014 Oct 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, James Black Centre, Dow Street, Dundee, DD1 5EH, UK. Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK. ; Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, James Black Centre, Dow Street, Dundee, DD1 5EH, UK. ; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK. ; Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, James Black Centre, Dow Street, Dundee, DD1 5EH, UK. Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK. a.ciulli@dundee.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25323695" target="_blank"〉PubMed〈/a〉

Description: Animal migrations span the globe, involving immense numbers of individuals from a wide range of taxa. Migrants transport nutrients, energy, and other organisms as they forage and are preyed upon throughout their journeys. These highly predictable, pulsed movements across large spatial scales render migration a potentially powerful yet underappreciated dimension of biodiversity that is intimately embedded within resident communities. We review examples from across the animal kingdom to distill fundamental processes by which migratory animals influence communities and ecosystems, demonstrating that they can uniquely alter energy flow, food-web topology and stability, trophic cascades, and the structure of metacommunities. Given the potential for migration to alter ecological networks worldwide, we suggest an integrative framework through which community dynamics and ecosystem functioning may explicitly consider animal migrations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bauer, S -- Hoye, B J -- New York, N.Y. -- Science. 2014 Apr 4;344(6179):1242552. doi: 10.1126/science.1242552.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bird Migration, Swiss Ornithological Institute, 6204 Sempach, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24700862" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stokstad, Erik -- New York, N.Y. -- Science. 2014 Mar 21;343(6177):1301. doi: 10.1126/science.343.6177.1301.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24653015" target="_blank"〉PubMed〈/a〉

Description: In certain human cancers, the expression of critical oncogenes is driven from large regulatory elements, called super-enhancers, that recruit much of the cell's transcriptional apparatus and are defined by extensive acetylation of histone H3 lysine 27 (H3K27ac). In a subset of T-cell acute lymphoblastic leukemia (T-ALL) cases, we found that heterozygous somatic mutations are acquired that introduce binding motifs for the MYB transcription factor in a precise noncoding site, which creates a super-enhancer upstream of the TAL1 oncogene. MYB binds to this new site and recruits its H3K27 acetylase-binding partner CBP, as well as core components of a major leukemogenic transcriptional complex that contains RUNX1, GATA-3, and TAL1 itself. Additionally, most endogenous super-enhancers found in T-ALL cells are occupied by MYB and CBP, which suggests a general role for MYB in super-enhancer initiation. Thus, this study identifies a genetic mechanism responsible for the generation of oncogenic super-enhancers in malignant cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4720521/" 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/PMC4720521/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mansour, Marc R -- Abraham, Brian J -- Anders, Lars -- Berezovskaya, Alla -- Gutierrez, Alejandro -- Durbin, Adam D -- Etchin, Julia -- Lawton, Lee -- Sallan, Stephen E -- Silverman, Lewis B -- Loh, Mignon L -- Hunger, Stephen P -- Sanda, Takaomi -- Young, Richard A -- Look, A Thomas -- 1R01CA176746-01/CA/NCI NIH HHS/ -- 5P01CA109901-08/CA/NCI NIH HHS/ -- 5P01CA68484/CA/NCI NIH HHS/ -- CA114766/CA/NCI NIH HHS/ -- CA120215/CA/NCI NIH HHS/ -- CA167124/CA/NCI NIH HHS/ -- CA29139/CA/NCI NIH HHS/ -- CA30969/CA/NCI NIH HHS/ -- CA98413/CA/NCI NIH HHS/ -- CA98543/CA/NCI NIH HHS/ -- P01 CA109901/CA/NCI NIH HHS/ -- P30 CA014051/CA/NCI NIH HHS/ -- R01 HG002668/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2014 Dec 12;346(6215):1373-7. doi: 10.1126/science.1259037. Epub 2014 Nov 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA. Department of Haematology, UCL Cancer Institute, University College London, London WC1E 6BT, UK. ; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA. ; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA. ; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA. Division of Pediatric Hematology-Oncology, Boston Children's Hospital, MA 02115, USA. ; Department of Pediatrics, Benioff Children's Hospital, University of California San Francisco, CA 94143, USA. ; Pediatric Hematology/Oncology/BMT, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO 80045, USA. ; Cancer Science Institute of Singapore, National University of Singapore, and Department of Medicine, Yong Loo Lin School of Medicine, 117599, Singapore. ; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA. thomas_look@dfci.harvard.edu young@wi.mit.edu. ; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA. Division of Pediatric Hematology-Oncology, Boston Children's Hospital, MA 02115, USA. thomas_look@dfci.harvard.edu young@wi.mit.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25394790" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McNutt, Marcia -- New York, N.Y. -- Science. 2014 Mar 21;343(6177):1289. doi: 10.1126/science.1253412.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Marcia McNutt is Editor-in-Chief of Science.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24653006" target="_blank"〉PubMed〈/a〉

Description: The signal recognition particle (SRP) is central to membrane protein targeting; SRP RNA is essential for SRP assembly, elongation arrest, and activation of SRP guanosine triphosphatases. In eukaryotes, SRP function relies on the SRP68-SRP72 heterodimer. We present the crystal structures of the RNA-binding domain of SRP68 (SRP68-RBD) alone and in complex with SRP RNA and SRP19. SRP68-RBD is a tetratricopeptide-like module that binds to a RNA three-way junction, bends the RNA, and inserts an alpha-helical arginine-rich motif (ARM) into the major groove. The ARM opens the conserved 5f RNA loop, which in ribosome-bound SRP establishes a contact to ribosomal RNA. Our data provide the structural basis for eukaryote-specific, SRP68-driven RNA remodeling required for protein translocation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grotwinkel, Jan Timo -- Wild, Klemens -- Segnitz, Bernd -- Sinning, Irmgard -- New York, N.Y. -- Science. 2014 Apr 4;344(6179):101-4. doi: 10.1126/science.1249094.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Heidelberg University Biochemistry Center (BZH), INF 328, D-69120 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24700861" target="_blank"〉PubMed〈/a〉

Description: Cytoplasmic plant immune receptors recognize specific pathogen effector proteins and initiate effector-triggered immunity. In Arabidopsis, the immune receptors RPS4 and RRS1 are both required to activate defense to three different pathogens. We show that RPS4 and RRS1 physically associate. Crystal structures of the N-terminal Toll-interleukin-1 receptor/resistance (TIR) domains of RPS4 and RRS1, individually and as a heterodimeric complex (respectively at 2.05, 1.75, and 2.65 angstrom resolution), reveal a conserved TIR/TIR interaction interface. We show that TIR domain heterodimerization is required to form a functional RRS1/RPS4 effector recognition complex. The RPS4 TIR domain activates effector-independent defense, which is inhibited by the RRS1 TIR domain through the heterodimerization interface. Thus, RPS4 and RRS1 function as a receptor complex in which the two components play distinct roles in recognition and signaling.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Williams, Simon J -- Sohn, Kee Hoon -- Wan, Li -- Bernoux, Maud -- Sarris, Panagiotis F -- Segonzac, Cecile -- Ve, Thomas -- Ma, Yan -- Saucet, Simon B -- Ericsson, Daniel J -- Casey, Lachlan W -- Lonhienne, Thierry -- Winzor, Donald J -- Zhang, Xiaoxiao -- Coerdt, Anne -- Parker, Jane E -- Dodds, Peter N -- Kobe, Bostjan -- Jones, Jonathan D G -- New York, N.Y. -- Science. 2014 Apr 18;344(6181):299-303. doi: 10.1126/science.1247357.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Chemistry and Molecular Biosciences and Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD 4072, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24744375" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kelly, Ryan P -- Port, Jesse A -- Yamahara, Kevan M -- Martone, Rebecca G -- Lowell, Natalie -- Thomsen, Philip Francis -- Mach, Megan E -- Bennett, Meredith -- Prahler, Erin -- Caldwell, Margaret R -- Crowder, Larry B -- New York, N.Y. -- Science. 2014 Jun 27;344(6191):1455-6. doi: 10.1126/science.1251156. Epub 2014 Jun 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Marine and Environmental Affairs, University of Washington, Seattle, WA 98103, USA. Center for Ocean Solutions, Stanford University, Stanford, CA 94305, USA. rpkelly@uw.edu. ; Center for Ocean Solutions, Stanford University, Stanford, CA 94305, USA. ; School of Marine and Environmental Affairs, University of Washington, Seattle, WA 98103, USA. ; Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Copenhagen, Denmark.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24970068" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pennisi, Elizabeth -- New York, N.Y. -- Science. 2014 Jan 31;343(6170):472-3. doi: 10.1126/science.343.6170.472.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24482456" target="_blank"〉PubMed〈/a〉

Description: Plant floral stem cells divide a limited number of times before they stop and terminally differentiate, but the mechanisms that control this timing remain unclear. The precise temporal induction of the Arabidopsis zinc finger repressor KNUCKLES (KNU) is essential for the coordinated growth and differentiation of floral stem cells. We identify an epigenetic mechanism in which the floral homeotic protein AGAMOUS (AG) induces KNU at ~2 days of delay. AG binding sites colocalize with a Polycomb response element in the KNU upstream region. AG binding to the KNU promoter causes the eviction of the Polycomb group proteins from the locus, leading to cell division-dependent induction. These analyses demonstrate that floral stem cells measure developmental timing by a division-dependent epigenetic timer triggered by Polycomb eviction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sun, Bo -- Looi, Liang-Sheng -- Guo, Siyi -- He, Zemiao -- Gan, Eng-Seng -- Huang, Jiangbo -- Xu, Yifeng -- Wee, Wan-Yi -- Ito, Toshiro -- New York, N.Y. -- Science. 2014 Jan 31;343(6170):1248559. doi: 10.1126/science.1248559.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Temasek Life Sciences Laboratory, 1 Research Link, National University of Singapore, Singapore 117604, Republic of Singapore.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24482483" target="_blank"〉PubMed〈/a〉