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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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〉

Description: Epistatic interactions between mutations can make evolutionary trajectories contingent on the chance occurrence of initial mutations. We used experimental evolution in Saccharomyces cerevisiae to quantify this contingency, finding differences in adaptability among 64 closely related genotypes. Despite these differences, sequencing of 104 evolved clones showed that initial genotype did not constrain future mutational trajectories. Instead, reconstructed combinations of mutations revealed a pattern of diminishing-returns epistasis: Beneficial mutations have consistently smaller effects in fitter backgrounds. Taken together, these results show that beneficial mutations affecting a variety of biological processes are globally coupled; they interact strongly, but only through their combined effect on fitness. As a consequence, fitness evolution follows a predictable trajectory even though sequence-level adaptation is stochastic.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4314286/" 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/PMC4314286/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kryazhimskiy, Sergey -- Rice, Daniel P -- Jerison, Elizabeth R -- Desai, Michael M -- GM104239/GM/NIGMS NIH HHS/ -- R01 GM104239/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Jun 27;344(6191):1519-22. doi: 10.1126/science.1250939.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA. FAS Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA. skryazhi@oeb.harvard.edu mdesai@oeb.harvard.edu. ; Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA. FAS Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA. ; Department of Physics, Harvard University, Cambridge, MA 02138, USA. FAS Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA. ; Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA. Department of Physics, Harvard University, Cambridge, MA 02138, USA. FAS Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA. skryazhi@oeb.harvard.edu mdesai@oeb.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24970088" target="_blank"〉PubMed〈/a〉

Description: Tight junctions are cell-cell adhesion structures in epithelial cell sheets that surround organ compartments in multicellular organisms and regulate the permeation of ions through the intercellular space. Claudins are the major constituents of tight junctions and form strands that mediate cell adhesion and function as paracellular barriers. We report the structure of mammalian claudin-15 at a resolution of 2.4 angstroms. The structure reveals a characteristic beta-sheet fold comprising two extracellular segments, which is anchored to a transmembrane four-helix bundle by a consensus motif. Our analyses suggest potential paracellular pathways with distinctive charges on the extracellular surface, providing insight into the molecular basis of ion homeostasis across tight junctions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Suzuki, Hiroshi -- Nishizawa, Tomohiro -- Tani, Kazutoshi -- Yamazaki, Yuji -- Tamura, Atsushi -- Ishitani, Ryuichiro -- Dohmae, Naoshi -- Tsukita, Sachiko -- Nureki, Osamu -- Fujiyoshi, Yoshinori -- New York, N.Y. -- Science. 2014 Apr 18;344(6181):304-7. doi: 10.1126/science.1248571.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cellular and Structural Physiology Institute, Nagoya University, Chikusa, Nagoya 464-8601, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24744376" target="_blank"〉PubMed〈/a〉

Description: Iron sequestration provides an innate defense, termed nutritional immunity, leading pathogens to scavenge iron from hosts. Although the molecular basis of this battle for iron is established, its potential as a force for evolution at host-pathogen interfaces is unknown. We show that the iron transport protein transferrin is engaged in ancient and ongoing evolutionary conflicts with TbpA, a transferrin surface receptor from bacteria. Single substitutions in transferrin at rapidly evolving sites reverse TbpA binding, providing a mechanism to counteract bacterial iron piracy among great apes. Furthermore, the C2 transferrin polymorphism in humans evades TbpA variants from Haemophilus influenzae, revealing a functional basis for standing genetic variation. These findings identify a central role for nutritional immunity in the persistent evolutionary conflicts between primates and bacterial pathogens.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4455941/" 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/PMC4455941/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barber, Matthew F -- Elde, Nels C -- 1F32GM108288/GM/NIGMS NIH HHS/ -- GM090042/GM/NIGMS NIH HHS/ -- R00 GM090042/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Dec 12;346(6215):1362-6. doi: 10.1126/science.1259329.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112, USA. ; Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112, USA. nelde@genetics.utah.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25504720" target="_blank"〉PubMed〈/a〉

Description: Cancer genome characterization has revealed driver mutations in genes that govern ubiquitylation; however, the mechanisms by which these alterations promote tumorigenesis remain incompletely characterized. Here, we analyzed changes in the ubiquitin landscape induced by prostate cancer-associated mutations of SPOP, an E3 ubiquitin ligase substrate-binding protein. SPOP mutants impaired ubiquitylation of a subset of proteins in a dominant-negative fashion. Of these, DEK and TRIM24 emerged as effector substrates consistently up-regulated by SPOP mutants. We highlight DEK as a SPOP substrate that exhibited decreases in ubiquitylation and proteasomal degradation resulting from heteromeric complexes of wild-type and mutant SPOP protein. DEK stabilization promoted prostate epithelial cell invasion, which implicated DEK as an oncogenic effector. More generally, these results provide a framework to decipher tumorigenic mechanisms linked to dysregulated ubiquitylation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4257137/" 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/PMC4257137/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Theurillat, Jean-Philippe P -- Udeshi, Namrata D -- Errington, Wesley J -- Svinkina, Tanya -- Baca, Sylvan C -- Pop, Marius -- Wild, Peter J -- Blattner, Mirjam -- Groner, Anna C -- Rubin, Mark A -- Moch, Holger -- Prive, Gilbert G -- Carr, Steven A -- Garraway, Levi A -- T32 GM007753/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Oct 3;346(6205):85-9. doi: 10.1126/science.1250255. Epub 2014 Oct 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Harvard Medical School, Boston, MA 02115, USA. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. ; The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. ; Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada. Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario M5G 2M9, Canada. ; Harvard Medical School, Boston, MA 02115, USA. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. ; Institute of Surgical Pathology, University Hospital Zurich, ZH 8091 Zurich, Switzerland. ; Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY 10065, USA. ; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. ; Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY 10065, USA. Institute for Precision Medicine of Weill Cornell and New York Presbyterian Hospital, New York, NY 10065, USA. ; The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Harvard Medical School, Boston, MA 02115, USA. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, MA 02115, USA. levi_garraway@dfci.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25278611" target="_blank"〉PubMed〈/a〉

Description: The evolution of the ratite birds has been widely attributed to vicariant speciation, driven by the Cretaceous breakup of the supercontinent Gondwana. The early isolation of Africa and Madagascar implies that the ostrich and extinct Madagascan elephant birds (Aepyornithidae) should be the oldest ratite lineages. We sequenced the mitochondrial genomes of two elephant birds and performed phylogenetic analyses, which revealed that these birds are the closest relatives of the New Zealand kiwi and are distant from the basal ratite lineage of ostriches. This unexpected result strongly contradicts continental vicariance and instead supports flighted dispersal in all major ratite lineages. We suggest that convergence toward gigantism and flightlessness was facilitated by early Tertiary expansion into the diurnal herbivory niche after the extinction of the dinosaurs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mitchell, Kieren J -- Llamas, Bastien -- Soubrier, Julien -- Rawlence, Nicolas J -- Worthy, Trevor H -- Wood, Jamie -- Lee, Michael S Y -- Cooper, Alan -- New York, N.Y. -- Science. 2014 May 23;344(6186):898-900. doi: 10.1126/science.1251981.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Australian Centre for Ancient DNA, School of Earth and Environmental Sciences, University of Adelaide, North Terrace Campus, South Australia 5005, Australia. ; School of Biological Sciences, Flinders University, South Australia 5001, Australia. ; Landcare Research, Post Office Box 40, Lincoln 7640, New Zealand. ; Australian Centre for Ancient DNA, School of Earth and Environmental Sciences, University of Adelaide, North Terrace Campus, South Australia 5005, Australia. South Australian Museum, North Terrace, South Australia 5000, Australia. ; Australian Centre for Ancient DNA, School of Earth and Environmental Sciences, University of Adelaide, North Terrace Campus, South Australia 5005, Australia. alan.cooper@adelaide.edu.au.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24855267" target="_blank"〉PubMed〈/a〉

Description: Transcription by RNA polymerase (RNAP) is interrupted by pauses that play diverse regulatory roles. Although individual pauses have been studied in vitro, the determinants of pauses in vivo and their distribution throughout the bacterial genome remain unknown. Using nascent transcript sequencing, we identified a 16-nucleotide consensus pause sequence in Escherichia coli that accounts for known regulatory pause sites as well as ~20,000 new in vivo pause sites. In vitro single-molecule and ensemble analyses demonstrate that these pauses result from RNAP-nucleic acid interactions that inhibit next-nucleotide addition. The consensus sequence also leads to pausing by RNAPs from diverse lineages and is enriched at translation start sites in both E. coli and Bacillus subtilis. Our results thus reveal a conserved mechanism unifying known and newly identified pause events.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4108260/" 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/PMC4108260/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Larson, Matthew H -- Mooney, Rachel A -- Peters, Jason M -- Windgassen, Tricia -- Nayak, Dhananjaya -- Gross, Carol A -- Block, Steven M -- Greenleaf, William J -- Landick, Robert -- Weissman, Jonathan S -- F32 GM100611/GM/NIGMS NIH HHS/ -- F32 GM108222/GM/NIGMS NIH HHS/ -- P50 GM102706/GM/NIGMS NIH HHS/ -- R01 GM038660/GM/NIGMS NIH HHS/ -- R01 GM102790/GM/NIGMS NIH HHS/ -- R37 GM057035/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 May 30;344(6187):1042-7. doi: 10.1126/science.1251871. Epub 2014 May 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Pharmacology, Howard Hughes Medical Institute, California Institute for Quantitative Biosciences, Center for RNA Systems Biology, University of California, San Francisco, San Francisco, CA 94158, USA. ; Department of Biochemistry, University of Wisconsin, Madison, WI 53706, USA. ; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA. ; Department of Biological Sciences, Stanford University, Stanford, CA 94025, USA. Department of Applied Physics; Stanford University, Stanford, CA 94025, USA. ; Department of Genetics, Stanford University, Stanford, CA 94025, USA. wjg@stanford.edu landick@biochem.wisc.edu weissman@cmp.ucsf.edu. ; Department of Biochemistry, University of Wisconsin, Madison, WI 53706, USA. Department of Bacteriology, University of Wisconsin, Madison, WI 53706, USA. wjg@stanford.edu landick@biochem.wisc.edu weissman@cmp.ucsf.edu. ; Department of Cellular and Molecular Pharmacology, Howard Hughes Medical Institute, California Institute for Quantitative Biosciences, Center for RNA Systems Biology, University of California, San Francisco, San Francisco, CA 94158, USA. wjg@stanford.edu landick@biochem.wisc.edu weissman@cmp.ucsf.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24789973" target="_blank"〉PubMed〈/a〉

Description: Signaling from JAK (Janus kinase) protein kinases to STAT (signal transducers and activators of transcription) transcription factors is key to many aspects of biology and medicine, yet the mechanism by which cytokine receptors initiate signaling is enigmatic. We present a complete mechanistic model for activation of receptor-bound JAK2, based on an archetypal cytokine receptor, the growth hormone receptor. For this, we used fluorescence resonance energy transfer to monitor positioning of the JAK2 binding motif in the receptor dimer, substitution of the receptor extracellular domains with Jun zippers to control the position of its transmembrane (TM) helices, atomistic modeling of TM helix movements, and docking of the crystal structures of the JAK2 kinase and its inhibitory pseudokinase domain with an opposing kinase-pseudokinase domain pair. Activation of the receptor dimer induced a separation of its JAK2 binding motifs, driven by a ligand-induced transition from a parallel TM helix pair to a left-handed crossover arrangement. This separation leads to removal of the pseudokinase domain from the kinase domain of the partner JAK2 and pairing of the two kinase domains, facilitating trans-activation. This model may well generalize to other class I cytokine receptors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brooks, Andrew J -- Dai, Wei -- O'Mara, Megan L -- Abankwa, Daniel -- Chhabra, Yash -- Pelekanos, Rebecca A -- Gardon, Olivier -- Tunny, Kathryn A -- Blucher, Kristopher M -- Morton, Craig J -- Parker, Michael W -- Sierecki, Emma -- Gambin, Yann -- Gomez, Guillermo A -- Alexandrov, Kirill -- Wilson, Ian A -- Doxastakis, Manolis -- Mark, Alan E -- Waters, Michael J -- New York, N.Y. -- Science. 2014 May 16;344(6185):1249783. doi: 10.1126/science.1249783.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The University of Queensland, Institute for Molecular Bioscience (IMB), St Lucia, Queensland 4072, Australia. m.waters@uq.edu.au a.brooks@uq.edu.au. ; Department of Chemical and Biomolecular Engineering, University of Houston, Houston, TX 77004, USA. ; The University of Queensland, School of Chemistry and Molecular Biosciences, St Lucia, Queensland 4072, Australia. ; The University of Queensland, Institute for Molecular Bioscience (IMB), St Lucia, Queensland 4072, Australia. ; Biota Structural Biology Laboratory and Australian Cancer Research Foundation (ACRF) Rational Drug Discovery Centre, St Vincent's Institute of Medical Research, Fitzroy, Victoria 3065, Australia. ; Biota Structural Biology Laboratory and Australian Cancer Research Foundation (ACRF) Rational Drug Discovery Centre, St Vincent's Institute of Medical Research, Fitzroy, Victoria 3065, Australia. Department of Biochemistry and Molecular Biology and Bio21 Institute, University of Melbourne, Parkville, Victoria 3052, Australia. ; Scripps Research Institute, La Jolla, CA 92037, USA. ; The University of Queensland, Institute for Molecular Bioscience (IMB), St Lucia, Queensland 4072, Australia. The University of Queensland, School of Chemistry and Molecular Biosciences, St Lucia, Queensland 4072, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24833397" target="_blank"〉PubMed〈/a〉

Description: MicroRNAs (miRNAs) control expression of thousands of genes in plants and animals. miRNAs function by guiding Argonaute proteins to complementary sites in messenger RNAs (mRNAs) targeted for repression. We determined crystal structures of human Argonaute-2 (Ago2) bound to a defined guide RNA with and without target RNAs representing miRNA recognition sites. These structures suggest a stepwise mechanism, in which Ago2 primarily exposes guide nucleotides (nt) 2 to 5 for initial target pairing. Pairing to nt 2 to 5 promotes conformational changes that expose nt 2 to 8 and 13 to 16 for further target recognition. Interactions with the guide-target minor groove allow Ago2 to interrogate target RNAs in a sequence-independent manner, whereas an adenosine binding-pocket opposite guide nt 1 further facilitates target recognition. Spurious slicing of miRNA targets is avoided through an inhibitory coordination of one catalytic magnesium ion. These results explain the conserved nucleotide-pairing patterns in animal miRNA target sites first observed over two decades ago.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4313529/" 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/PMC4313529/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schirle, Nicole T -- Sheu-Gruttadauria, Jessica -- MacRae, Ian J -- P41 GM103403/GM/NIGMS NIH HHS/ -- R01 GM104475/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Oct 31;346(6209):608-13. doi: 10.1126/science.1258040.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. ; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. macrae@scripps.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25359968" target="_blank"〉PubMed〈/a〉

Description: To study the evolutionary dynamics of regulatory DNA, we mapped 〉1.3 million deoxyribonuclease I-hypersensitive sites (DHSs) in 45 mouse cell and tissue types, and systematically compared these with human DHS maps from orthologous compartments. We found that the mouse and human genomes have undergone extensive cis-regulatory rewiring that combines branch-specific evolutionary innovation and loss with widespread repurposing of conserved DHSs to alternative cell fates, and that this process is mediated by turnover of transcription factor (TF) recognition elements. Despite pervasive evolutionary remodeling of the location and content of individual cis-regulatory regions, within orthologous mouse and human cell types the global fraction of regulatory DNA bases encoding recognition sites for each TF has been strictly conserved. Our findings provide new insights into the evolutionary forces shaping mammalian regulatory DNA landscapes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4337786/" 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/PMC4337786/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vierstra, Jeff -- Rynes, Eric -- Sandstrom, Richard -- Zhang, Miaohua -- Canfield, Theresa -- Hansen, R Scott -- Stehling-Sun, Sandra -- Sabo, Peter J -- Byron, Rachel -- Humbert, Richard -- Thurman, Robert E -- Johnson, Audra K -- Vong, Shinny -- Lee, Kristen -- Bates, Daniel -- Neri, Fidencio -- Diegel, Morgan -- Giste, Erika -- Haugen, Eric -- Dunn, Douglas -- Wilken, Matthew S -- Josefowicz, Steven -- Samstein, Robert -- Chang, Kai-Hsin -- Eichler, Evan E -- De Bruijn, Marella -- Reh, Thomas A -- Skoultchi, Arthur -- Rudensky, Alexander -- Orkin, Stuart H -- Papayannopoulou, Thalia -- Treuting, Piper M -- Selleri, Licia -- Kaul, Rajinder -- Groudine, Mark -- Bender, M A -- Stamatoyannopoulos, John A -- 1RC2HG005654/HG/NHGRI NIH HHS/ -- 2R01HD04399709/HD/NICHD NIH HHS/ -- P30 CA008748/CA/NCI NIH HHS/ -- R01 DK096266/DK/NIDDK NIH HHS/ -- R01 EY021482/EY/NEI NIH HHS/ -- R01 HD043997/HD/NICHD NIH HHS/ -- R37 DK044746/DK/NIDDK NIH HHS/ -- R37DK44746/DK/NIDDK NIH HHS/ -- RC2 HG005654/HG/NHGRI NIH HHS/ -- U54 HG007010/HG/NHGRI NIH HHS/ -- U54HG007010/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Nov 21;346(6212):1007-12. doi: 10.1126/science.1246426.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA. ; Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. ; Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA. ; Department of Biological Structure, University of Washington, Seattle, WA 98195, USA. ; Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. Howard Hughes Medical Institute. ; Division of Hematology, Department of Medicine, University of Washington, Seattle, WA 98195, USA. ; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA. Howard Hughes Medical Institute. ; Medical Research Council (MRC) Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DS, UK. ; Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. ; Howard Hughes Medical Institute. Division of Hematology/Oncology, Children's Hospital Boston and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA. ; Department of Comparative Medicine, University of Washington, Seattle, WA 98195, USA. ; Department of Cell and Developmental Biology, Weill Medical College of Cornell University, New York, NY 10065, USA. ; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA. Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA. ; Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. Department of Radiation Oncology, University of Washington, Seattle, WA 98109, USA. ; Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. Department of Pediatrics, University of Washington, Seattle, WA 98195, USA. ; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA. Division of Oncology, Department of Medicine, University of Washington, Seattle, WA 98195, USA. jstam@uw.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25411453" target="_blank"〉PubMed〈/a〉

Description: Calcium homeostasis balances passive calcium leak and active calcium uptake. Human Bax inhibitor-1 (hBI-1) is an antiapoptotic protein that mediates a calcium leak and is representative of a highly conserved and widely distributed family, the transmembrane Bax inhibitor motif (TMBIM) proteins. Here, we present crystal structures of a bacterial homolog and characterize its calcium leak activity. The structure has a seven-transmembrane-helix fold that features two triple-helix sandwiches wrapped around a central C-terminal helix. Structures obtained in closed and open conformations are reversibly interconvertible by change of pH. A hydrogen-bonded, pKa (where Ka is the acid dissociation constant)-perturbed pair of conserved aspartate residues explains the pH dependence of this transition, and biochemical studies show that pH regulates calcium influx in proteoliposomes. Homology models for hBI-1 provide insights into TMBIM-mediated calcium leak and cytoprotective activity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4119810/" 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/PMC4119810/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chang, Yanqi -- Bruni, Renato -- Kloss, Brian -- Assur, Zahra -- Kloppmann, Edda -- Rost, Burkhard -- Hendrickson, Wayne A -- Liu, Qun -- GM095315/GM/NIGMS NIH HHS/ -- GM107462/GM/NIGMS NIH HHS/ -- R01 GM107462/GM/NIGMS NIH HHS/ -- U54 GM095315/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Jun 6;344(6188):1131-5. doi: 10.1126/science.1252043.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉New York Consortium on Membrane Protein Structure, New York Structural Biology Center, New York, NY 10027, USA. ; Department of Physiology and Cellular Biophysics, Columbia University, New York, NY 10032, USA. ; New York Consortium on Membrane Protein Structure, New York Structural Biology Center, New York, NY 10027, USA. Department of Bioinformatics and Computational Biology, Fakultat fur Informatik, Technische Universitat Munchen, Garching, Germany. ; New York Consortium on Membrane Protein Structure, New York Structural Biology Center, New York, NY 10027, USA. Department of Physiology and Cellular Biophysics, Columbia University, New York, NY 10032, USA. New York Structural Biology Center, National Synchrotron Light Source (NSLS) X4, Brookhaven National Laboratory, Upton, NY 11973, USA. Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA. ; New York Consortium on Membrane Protein Structure, New York Structural Biology Center, New York, NY 10027, USA. New York Structural Biology Center, National Synchrotron Light Source (NSLS) X4, Brookhaven National Laboratory, Upton, NY 11973, USA. qunliu@bnl.gov.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24904158" target="_blank"〉PubMed〈/a〉

Description: Flaviviruses are emerging human pathogens and worldwide health threats. During infection, pathogenic subgenomic flaviviral RNAs (sfRNAs) are produced by resisting degradation by the 5'--〉3' host cell exonuclease Xrn1 through an unknown RNA structure-based mechanism. Here, we present the crystal structure of a complete Xrn1-resistant flaviviral RNA, which contains interwoven pseudoknots within a compact structure that depends on highly conserved nucleotides. The RNA's three-dimensional topology creates a ringlike conformation, with the 5' end of the resistant structure passing through the ring from one side of the fold to the other. Disruption of this structure prevents formation of sfRNA during flaviviral infection. Thus, sfRNA formation results from an RNA fold that interacts directly with Xrn1, presenting the enzyme with a structure that confounds its helicase activity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4163914/" 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/PMC4163914/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chapman, Erich G -- Costantino, David A -- Rabe, Jennifer L -- Moon, Stephanie L -- Wilusz, Jeffrey -- Nix, Jay C -- Kieft, Jeffrey S -- P30 CA046934/CA/NCI NIH HHS/ -- P30CA046934/CA/NCI NIH HHS/ -- U54 AI-065357/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Apr 18;344(6181):307-10. doi: 10.1126/science.1250897.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Denver, Aurora, CO 80045, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24744377" target="_blank"〉PubMed〈/a〉

Description: Because of differences in craniofacial morphology and dentition between the earliest American skeletons and modern Native Americans, separate origins have been postulated for them, despite genetic evidence to the contrary. We describe a near-complete human skeleton with an intact cranium and preserved DNA found with extinct fauna in a submerged cave on Mexico's Yucatan Peninsula. This skeleton dates to between 13,000 and 12,000 calendar years ago and has Paleoamerican craniofacial characteristics and a Beringian-derived mitochondrial DNA (mtDNA) haplogroup (D1). Thus, the differences between Paleoamericans and Native Americans probably resulted from in situ evolution rather than separate ancestry.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chatters, James C -- Kennett, Douglas J -- Asmerom, Yemane -- Kemp, Brian M -- Polyak, Victor -- Blank, Alberto Nava -- Beddows, Patricia A -- Reinhardt, Eduard -- Arroyo-Cabrales, Joaquin -- Bolnick, Deborah A -- Malhi, Ripan S -- Culleton, Brendan J -- Erreguerena, Pilar Luna -- Rissolo, Dominique -- Morell-Hart, Shanti -- Stafford, Thomas W Jr -- New York, N.Y. -- Science. 2014 May 16;344(6185):750-4. doi: 10.1126/science.1252619.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Applied Paleoscience and DirectAMS, 10322 NE 190th Street, Bothell, WA 98011, USA. paleosci@gmail.com. ; Department of Anthropology and Institutes of Energy and the Environment, Pennsylvania State University, University Park, PA 16802, USA. ; Department of Earth and Planetary Sciences, University of New Mexico, Albuquerque, NM 87131-0001, USA. ; Department of Anthropology and School of Biological Sciences, Washington State University, Pullman, WA 99164, USA. ; Bay Area Underwater Explorers, Berkeley, CA, USA. ; Department of Earth and Planetary Sciences, Northwestern University, Evanston, IL 60208, USA. ; School of Geography and Earth Sciences, McMaster University, Hamilton, Ontario L8S 4K1, Canada. ; Instituto Nacional Antropologia e Historia, Colonia Centro Historico, 06060, Mexico City, DF, Mexico. ; Department of Anthropology and Population Research Center, University of Texas at Austin, Austin, TX 78712, USA. ; Institute for Genomic Biology, University of Illinois, Urbana-Champaign, IL 61801, USA. ; Subdireccion de Arqueologia Subacuatica, Instituto Nacional de Antropologia e Historia, 06070 Mexico City, Mexico. ; Waitt Institute, La Jolla, CA 92038-1948, USA. ; Department of Anthropology, Stanford University, Stanford, CA 94305, USA. ; Centre for AMS C, Department of Physics and Astronomy, Aarhus University, Aarhus, Denmark, and Centre for GeoGenetics, Natural History Museum of Denmark, Geological Museum, Copenhagen, Denmark.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24833392" target="_blank"〉PubMed〈/a〉

Description: The 18-kilodalton translocator protein TSPO is found in mitochondrial membranes and mediates the import of cholesterol and porphyrins into mitochondria. In line with the role of TSPO in mitochondrial function, TSPO ligands are used for a variety of diagnostic and therapeutic applications in animals and humans. We present the three-dimensional high-resolution structure of mammalian TSPO reconstituted in detergent micelles in complex with its high-affinity ligand PK11195. The TSPO-PK11195 structure is described by a tight bundle of five transmembrane alpha helices that form a hydrophobic pocket accepting PK11195. Ligand-induced stabilization of the structure of TSPO suggests a molecular mechanism for the stimulation of cholesterol transport into mitochondria.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jaremko, Lukasz -- Jaremko, Mariusz -- Giller, Karin -- Becker, Stefan -- Zweckstetter, Markus -- New York, N.Y. -- Science. 2014 Mar 21;343(6177):1363-6. doi: 10.1126/science.1248725.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max-Planck-Institut fur Biophysikalische Chemie, 37077 Gottingen, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24653034" target="_blank"〉PubMed〈/a〉

Description: Antiretroviral treatment (ART) of HIV infection suppresses viral replication. Yet if ART is stopped, virus reemerges because of the persistence of infected cells. We evaluated the contribution of infected-cell proliferation and sites of proviral integration to HIV persistence. A total of 534 HIV integration sites (IS) and 63 adjacent HIV env sequences were derived from three study participants over 11.3 to 12.7 years of ART. Each participant had identical viral sequences integrated at the same position in multiple cells, demonstrating infected-cell proliferation. Integrations were overrepresented in genes associated with cancer and favored in 12 genes across multiple participants. Over time on ART, a greater proportion of persisting proviruses were in proliferating cells. HIV integration into specific genes may promote proliferation of HIV-infected cells, slowing viral decay during ART.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4230336/" 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/PMC4230336/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wagner, Thor A -- McLaughlin, Sherry -- Garg, Kavita -- Cheung, Charles Y K -- Larsen, Brendan B -- Styrchak, Sheila -- Huang, Hannah C -- Edlefsen, Paul T -- Mullins, James I -- Frenkel, Lisa M -- 201311CVI-322424-244686/Canadian Institutes of Health Research/Canada -- K23 AI077357/AI/NIAID NIH HHS/ -- K23AI077357/AI/NIAID NIH HHS/ -- P30 AI027757/AI/NIAID NIH HHS/ -- R01 AI091550/AI/NIAID NIH HHS/ -- R01 AI111806/AI/NIAID NIH HHS/ -- R01AI091550/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2014 Aug 1;345(6196):570-3. doi: 10.1126/science.1256304. Epub 2014 Jul 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Seattle Children's Research Institute, 1900 9th Avenue, Seattle, WA 98101, USA. University of Washington, Seattle, WA, USA. ; Fred Hutchinson Cancer Research Center, Seattle, WA, USA. ; University of Washington, Seattle, WA, USA. ; Seattle Children's Research Institute, 1900 9th Avenue, Seattle, WA 98101, USA. ; University of Washington, Seattle, WA, USA. Fred Hutchinson Cancer Research Center, Seattle, WA, USA. ; Seattle Children's Research Institute, 1900 9th Avenue, Seattle, WA 98101, USA. University of Washington, Seattle, WA, USA. lfrenkel@uw.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25011556" target="_blank"〉PubMed〈/a〉

Description: To better determine the history of modern birds, we performed a genome-scale phylogenetic analysis of 48 species representing all orders of Neoaves using phylogenomic methods created to handle genome-scale data. We recovered a highly resolved tree that confirms previously controversial sister or close relationships. We identified the first divergence in Neoaves, two groups we named Passerea and Columbea, representing independent lineages of diverse and convergently evolved land and water bird species. Among Passerea, we infer the common ancestor of core landbirds to have been an apex predator and confirm independent gains of vocal learning. Among Columbea, we identify pigeons and flamingoes as belonging to sister clades. Even with whole genomes, some of the earliest branches in Neoaves proved challenging to resolve, which was best explained by massive protein-coding sequence convergence and high levels of incomplete lineage sorting that occurred during a rapid radiation after the Cretaceous-Paleogene mass extinction event about 66 million years ago.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4405904/" 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/PMC4405904/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jarvis, Erich D -- Mirarab, Siavash -- Aberer, Andre J -- Li, Bo -- Houde, Peter -- Li, Cai -- Ho, Simon Y W -- Faircloth, Brant C -- Nabholz, Benoit -- Howard, Jason T -- Suh, Alexander -- Weber, Claudia C -- da Fonseca, Rute R -- Li, Jianwen -- Zhang, Fang -- Li, Hui -- Zhou, Long -- Narula, Nitish -- Liu, Liang -- Ganapathy, Ganesh -- Boussau, Bastien -- Bayzid, Md Shamsuzzoha -- Zavidovych, Volodymyr -- Subramanian, Sankar -- Gabaldon, Toni -- Capella-Gutierrez, Salvador -- Huerta-Cepas, Jaime -- Rekepalli, Bhanu -- Munch, Kasper -- Schierup, Mikkel -- Lindow, Bent -- Warren, Wesley C -- Ray, David -- Green, Richard E -- Bruford, Michael W -- Zhan, Xiangjiang -- Dixon, Andrew -- Li, Shengbin -- Li, Ning -- Huang, Yinhua -- Derryberry, Elizabeth P -- Bertelsen, Mads Frost -- Sheldon, Frederick H -- Brumfield, Robb T -- Mello, Claudio V -- Lovell, Peter V -- Wirthlin, Morgan -- Schneider, Maria Paula Cruz -- Prosdocimi, Francisco -- Samaniego, Jose Alfredo -- Vargas Velazquez, Amhed Missael -- Alfaro-Nunez, Alonzo -- Campos, Paula F -- Petersen, Bent -- Sicheritz-Ponten, Thomas -- Pas, An -- Bailey, Tom -- Scofield, Paul -- Bunce, Michael -- Lambert, David M -- Zhou, Qi -- Perelman, Polina -- Driskell, Amy C -- Shapiro, Beth -- Xiong, Zijun -- Zeng, Yongli -- Liu, Shiping -- Li, Zhenyu -- Liu, Binghang -- Wu, Kui -- Xiao, Jin -- Yinqi, Xiong -- Zheng, Qiuemei -- Zhang, Yong -- Yang, Huanming -- Wang, Jian -- Smeds, Linnea -- Rheindt, Frank E -- Braun, Michael -- Fjeldsa, Jon -- Orlando, Ludovic -- Barker, F Keith -- Jonsson, Knud Andreas -- Johnson, Warren -- Koepfli, Klaus-Peter -- O'Brien, Stephen -- Haussler, David -- Ryder, Oliver A -- Rahbek, Carsten -- Willerslev, Eske -- Graves, Gary R -- Glenn, Travis C -- McCormack, John -- Burt, Dave -- Ellegren, Hans -- Alstrom, Per -- Edwards, Scott V -- Stamatakis, Alexandros -- Mindell, David P -- Cracraft, Joel -- Braun, Edward L -- Warnow, Tandy -- Jun, Wang -- Gilbert, M Thomas P -- Zhang, Guojie -- DP1 OD000448/OD/NIH HHS/ -- DP1OD000448/OD/NIH HHS/ -- R24 GM092842/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Dec 12;346(6215):1320-31. doi: 10.1126/science.1253451.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurobiology, Howard Hughes Medical Institute (HHMI), and Duke University Medical Center, Durham, NC 27710, USA. jarvis@neuro.duke.edu tandywarnow@gmail.com mtpgilbert@gmail.com wangj@genomics.cn zhanggj@genomics.cn. ; Department of Computer Science, The University of Texas at Austin, Austin, TX 78712, USA. ; Scientific Computing Group, Heidelberg Institute for Theoretical Studies, Heidelberg, Germany. ; China National GeneBank, BGI-Shenzhen, Shenzhen 518083, China. College of Medicine and Forensics, Xi'an Jiaotong University Xi'an 710061, China. Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Oster Voldgade 5-7, 1350 Copenhagen, Denmark. ; Department of Biology, New Mexico State University, Las Cruces, NM 88003, USA. ; China National GeneBank, BGI-Shenzhen, Shenzhen 518083, China. Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Oster Voldgade 5-7, 1350 Copenhagen, Denmark. ; School of Biological Sciences, University of Sydney, Sydney, New South Wales 2006, Australia. ; Department of Ecology and Evolutionary Biology, University of California, Los Angeles, CA 90095, USA. Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA. ; CNRS UMR 5554, Institut des Sciences de l'Evolution de Montpellier, Universite Montpellier II Montpellier, France. ; Department of Neurobiology, Howard Hughes Medical Institute (HHMI), and Duke University Medical Center, Durham, NC 27710, USA. ; Department of Evolutionary Biology, Evolutionary Biology Centre, Uppsala University, SE-752 36 Uppsala Sweden. ; Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Oster Voldgade 5-7, 1350 Copenhagen, Denmark. ; China National GeneBank, BGI-Shenzhen, Shenzhen 518083, China. ; Department of Biology, New Mexico State University, Las Cruces, NM 88003, USA. Biodiversity and Biocomplexity Unit, Okinawa Institute of Science and Technology Onna-son, Okinawa 904-0495, Japan. ; Department of Statistics and Institute of Bioinformatics, University of Georgia, Athens, GA 30602, USA. ; Laboratoire de Biometrie et Biologie Evolutive, Centre National de la Recherche Scientifique, Universite de Lyon, F-69622 Villeurbanne, France. ; Environmental Futures Research Institute, Griffith University, Nathan, Queensland 4111, Australia. ; Bioinformatics and Genomics Programme, Centre for Genomic Regulation, Dr. Aiguader 88, 08003 Barcelona, Spain. Universitat Pompeu Fabra, Barcelona, Spain. Institucio Catalana de Recerca i Estudis Avancats, Barcelona, Spain. ; Bioinformatics and Genomics Programme, Centre for Genomic Regulation, Dr. Aiguader 88, 08003 Barcelona, Spain. Universitat Pompeu Fabra, Barcelona, Spain. ; Joint Institute for Computational Sciences, The University of Tennessee, Oak Ridge National Laboratory, Oak Ridge, TN 37831, USA. ; Bioinformatics Research Centre, Aarhus University, DK-8000 Aarhus C, Denmark. ; The Genome Institute, Washington University School of Medicine, St Louis, MI 63108, USA. ; Department of Biochemistry, Molecular Biology, Entomology and Plant Pathology, Mississippi State University, Mississippi State, MS 39762, USA. Institute for Genomics, Biocomputing and Biotechnology, Mississippi State University, Mississippi State, MS 39762, USA. Department of Biological Sciences, Texas Tech University, Lubbock, TX 79409, USA. ; Department of Ecology and Evolutionary Biology, University of California Santa Cruz (UCSC), Santa Cruz, CA 95064, USA. ; Organisms and Environment Division, Cardiff School of Biosciences, Cardiff University Cardiff CF10 3AX, Wales, UK. ; Organisms and Environment Division, Cardiff School of Biosciences, Cardiff University Cardiff CF10 3AX, Wales, UK. Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China. ; International Wildlife Consultants, Carmarthen SA33 5YL, Wales, UK. ; College of Medicine and Forensics, Xi'an Jiaotong University Xi'an, 710061, China. ; State Key Laboratory for Agrobiotechnology, China Agricultural University, Beijing 100094, China. ; Department of Ecology and Evolutionary Biology, Tulane University, New Orleans, LA 70118, USA. Museum of Natural Science and Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA. ; Center for Zoo and Wild Animal Health, Copenhagen Zoo Roskildevej 38, DK-2000 Frederiksberg, Denmark. ; Museum of Natural Science and Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA. ; Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR 97239, USA. Brazilian Avian Genome Consortium (CNPq/FAPESPA-SISBIO Aves), Federal University of Para, Belem, Para, Brazil. ; Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR 97239, USA. ; Brazilian Avian Genome Consortium (CNPq/FAPESPA-SISBIO Aves), Federal University of Para, Belem, Para, Brazil. Institute of Biological Sciences, Federal University of Para, Belem, Para, Brazil. ; Brazilian Avian Genome Consortium (CNPq/FAPESPA-SISBIO Aves), Federal University of Para, Belem, Para, Brazil. Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro RJ 21941-902, Brazil. ; Centre for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark Kemitorvet 208, 2800 Kgs Lyngby, Denmark. ; Breeding Centre for Endangered Arabian Wildlife, Sharjah, United Arab Emirates. ; Dubai Falcon Hospital, Dubai, United Arab Emirates. ; Canterbury Museum Rolleston Avenue, Christchurch 8050, New Zealand. ; Trace and Environmental DNA Laboratory Department of Environment and Agriculture, Curtin University, Perth, Western Australia 6102, Australia. ; Department of Integrative Biology, University of California, Berkeley, CA 94720, USA. ; Laboratory of Genomic Diversity, National Cancer Institute Frederick, MD 21702, USA. Institute of Molecular and Cellular Biology, SB RAS and Novosibirsk State University, Novosibirsk, Russia. ; Smithsonian Institution National Museum of Natural History, Washington, DC 20013, USA. ; BGI-Shenzhen, Shenzhen 518083, China. ; Department of Biological Sciences, National University of Singapore, Republic of Singapore. ; Department of Vertebrate Zoology, National Museum of Natural History, Smithsonian Suitland, MD 20746, USA. ; Center for Macroecology, Evolution and Climate, Natural History Museum of Denmark, University of Copenhagen, Universitetsparken 15, DK-2100 Copenhagen O, Denmark. ; Bell Museum of Natural History, University of Minnesota, Saint Paul, MN 55108, USA. ; Center for Macroecology, Evolution and Climate, Natural History Museum of Denmark, University of Copenhagen, Universitetsparken 15, DK-2100 Copenhagen O, Denmark. Department of Life Sciences, Natural History Museum, Cromwell Road, London SW7 5BD, UK. Department of Life Sciences, Imperial College London, Silwood Park Campus, Ascot SL5 7PY, UK. ; Smithsonian Conservation Biology Institute, National Zoological Park, Front Royal, VA 22630, USA. ; Smithsonian Conservation Biology Institute, National Zoological Park, Washington, DC 20008, USA. ; Theodosius Dobzhansky Center for Genome Bioinformatics, St. Petersburg State University, St. Petersburg, Russia 199004. Oceanographic Center, Nova Southeastern University, Ft Lauderdale, FL 33004, USA. ; Center for Biomolecular Science and Engineering, UCSC, Santa Cruz, CA 95064, USA. ; San Diego Zoo Institute for Conservation Research, Escondido, CA 92027, USA. ; Center for Macroecology, Evolution and Climate, Natural History Museum of Denmark, University of Copenhagen, Universitetsparken 15, DK-2100 Copenhagen O, Denmark. Department of Life Sciences, Imperial College London, Silwood Park Campus, Ascot SL5 7PY, UK. ; Center for Macroecology, Evolution and Climate, Natural History Museum of Denmark, University of Copenhagen, Universitetsparken 15, DK-2100 Copenhagen O, Denmark. Department of Vertebrate Zoology, MRC-116, National Museum of Natural History, Smithsonian Institution, Washington, DC 20013, USA. ; Department of Environmental Health Science, University of Georgia, Athens, GA 30602, USA. ; Moore Laboratory of Zoology and Department of Biology, Occidental College, Los Angeles, CA 90041, USA. ; Department of Genomics and Genetics, The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Campus, Midlothian EH25 9RG, UK. ; Swedish Species Information Centre, Swedish University of Agricultural Sciences Box 7007, SE-750 07 Uppsala, Sweden. Key Laboratory of Zoological Systematics and Evolution, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China. ; Department of Organismic and Evolutionary Biology and Museum of Comparative Zoology, Harvard University, Cambridge, MA 02138, USA. ; Scientific Computing Group, Heidelberg Institute for Theoretical Studies, Heidelberg, Germany. Institute of Theoretical Informatics, Department of Informatics, Karlsruhe Institute of Technology, D- 76131 Karlsruhe, Germany. ; Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158, USA. ; Department of Ornithology, American Museum of Natural History, New York, NY 10024, USA. ; Department of Biology and Genetics Institute, University of Florida, Gainesville, FL 32611, USA. ; Department of Computer Science, The University of Texas at Austin, Austin, TX 78712, USA. Departments of Bioengineering and Computer Science, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. jarvis@neuro.duke.edu tandywarnow@gmail.com mtpgilbert@gmail.com wangj@genomics.cn zhanggj@genomics.cn. ; BGI-Shenzhen, Shenzhen 518083, China. Department of Biology, University of Copenhagen, Ole Maaloes Vej 5, 2200 Copenhagen, Denmark. Princess Al Jawhara Center of Excellence in the Research of Hereditary Disorders, King Abdulaziz University, Jeddah 21589, Saudi Arabia. Macau University of Science and Technology, Avenida Wai long, Taipa, Macau 999078, China. Department of Medicine, University of Hong Kong, Hong Kong. jarvis@neuro.duke.edu tandywarnow@gmail.com mtpgilbert@gmail.com wangj@genomics.cn zhanggj@genomics.cn. ; Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Oster Voldgade 5-7, 1350 Copenhagen, Denmark. Trace and Environmental DNA Laboratory Department of Environment and Agriculture, Curtin University, Perth, Western Australia 6102, Australia. jarvis@neuro.duke.edu tandywarnow@gmail.com mtpgilbert@gmail.com wangj@genomics.cn zhanggj@genomics.cn. ; China National GeneBank, BGI-Shenzhen, Shenzhen 518083, China. Centre for Social Evolution, Department of Biology, Universitetsparken 15, University of Copenhagen, DK-2100 Copenhagen, Denmark. jarvis@neuro.duke.edu tandywarnow@gmail.com mtpgilbert@gmail.com wangj@genomics.cn zhanggj@genomics.cn.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25504713" target="_blank"〉PubMed〈/a〉

Description: In plants, multiple lineages have evolved sex chromosomes independently, providing a powerful comparative framework, but few specific determinants controlling the expression of a specific sex have been identified. We investigated sex determinants in the Caucasian persimmon, Diospyros lotus, a dioecious plant with heterogametic males (XY). Male-specific short nucleotide sequences were used to define a male-determining region. A combination of transcriptomics and evolutionary approaches detected a Y-specific sex-determinant candidate, OGI, that displays male-specific conservation among Diospyros species. OGI encodes a small RNA targeting the autosomal MeGI gene, a homeodomain transcription factor regulating anther fertility in a dosage-dependent fashion. This identification of a feminizing gene suppressed by a Y-chromosome-encoded small RNA contributes to our understanding of the evolution of sex chromosome systems in higher plants.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Akagi, Takashi -- Henry, Isabelle M -- Tao, Ryutaro -- Comai, Luca -- New York, N.Y. -- Science. 2014 Oct 31;346(6209):646-50. doi: 10.1126/science.1257225. Epub 2014 Oct 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Plant Biology and Genome Center, University of California Davis, Davis, CA, USA. Laboratory of Pomology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan. ; Department of Plant Biology and Genome Center, University of California Davis, Davis, CA, USA. ; Laboratory of Pomology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan. rtao@kais.kyoto-u.ac.jp lcomai@ucdavis.edu. ; Department of Plant Biology and Genome Center, University of California Davis, Davis, CA, USA. rtao@kais.kyoto-u.ac.jp lcomai@ucdavis.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25359977" target="_blank"〉PubMed〈/a〉

Description: Peptidoglycan (PG) is a polysaccharide matrix that protects bacteria from osmotic lysis. Inhibition of its biogenesis is a proven strategy for killing bacteria with antibiotics. The assembly of PG requires disaccharide-pentapeptide building blocks attached to a polyisoprene lipid carrier called lipid II. Although the stages of lipid II synthesis are known, the identity of the essential flippase that translocates it across the cytoplasmic membrane for PG polymerization is unclear. We developed an assay for lipid II flippase activity and used a chemical genetic strategy to rapidly and specifically block flippase function. We combined these approaches to demonstrate that MurJ is the lipid II flippase in Escherichia coli.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4163187/" 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/PMC4163187/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sham, Lok-To -- Butler, Emily K -- Lebar, Matthew D -- Kahne, Daniel -- Bernhardt, Thomas G -- Ruiz, Natividad -- F32 GM103056/GM/NIGMS NIH HHS/ -- F32GM103056/GM/NIGMS NIH HHS/ -- R01 AI099144/AI/NIAID NIH HHS/ -- R01 GM076710/GM/NIGMS NIH HHS/ -- R01 GM100951/GM/NIGMS NIH HHS/ -- R01AI099144/AI/NIAID NIH HHS/ -- R01GM100951/GM/NIGMS NIH HHS/ -- R01GM76710/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Jul 11;345(6193):220-2. doi: 10.1126/science.1254522.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA. ; Department of Microbiology, Ohio State University, Columbus, OH 43210, USA. ; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA. ; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA. ; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA. thomas_bernhardt@hms.harvard.edu ruiz.82@osu.edu. ; Department of Microbiology, Ohio State University, Columbus, OH 43210, USA. thomas_bernhardt@hms.harvard.edu ruiz.82@osu.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25013077" target="_blank"〉PubMed〈/a〉

Description: Cucurbitacins are triterpenoids that confer a bitter taste in cucurbits such as cucumber, melon, watermelon, squash, and pumpkin. These compounds discourage most pests on the plant and have also been shown to have antitumor properties. With genomics and biochemistry, we identified nine cucumber genes in the pathway for biosynthesis of cucurbitacin C and elucidated four catalytic steps. We discovered transcription factors Bl (Bitter leaf) and Bt (Bitter fruit) that regulate this pathway in leaves and fruits, respectively. Traces in genomic signatures indicated that selection imposed on Bt during domestication led to derivation of nonbitter cucurbits from their bitter ancestors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shang, Yi -- Ma, Yongshuo -- Zhou, Yuan -- Zhang, Huimin -- Duan, Lixin -- Chen, Huiming -- Zeng, Jianguo -- Zhou, Qian -- Wang, Shenhao -- Gu, Wenjia -- Liu, Min -- Ren, Jinwei -- Gu, Xingfang -- Zhang, Shengping -- Wang, Ye -- Yasukawa, Ken -- Bouwmeester, Harro J -- Qi, Xiaoquan -- Zhang, Zhonghua -- Lucas, William J -- Huang, Sanwen -- New York, N.Y. -- Science. 2014 Nov 28;346(6213):1084-8. doi: 10.1126/science.1259215.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Key Laboratory of Biology and Genetic Improvement of Horticultural Crops of the Ministry of Agriculture, Sino-Dutch Joint Laboratory of Horticultural Genomics, Beijing 100081, China. Agricultural Genomic Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518124, China. ; Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Key Laboratory of Biology and Genetic Improvement of Horticultural Crops of the Ministry of Agriculture, Sino-Dutch Joint Laboratory of Horticultural Genomics, Beijing 100081, China. College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, China. ; Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Key Laboratory of Biology and Genetic Improvement of Horticultural Crops of the Ministry of Agriculture, Sino-Dutch Joint Laboratory of Horticultural Genomics, Beijing 100081, China. Horticulture and Landscape College, Hunan Agricultural University, National Chinese Medicinal Herbs Technology Center, Changsha 410128, China. ; Institute of Botany, Chinese Academy of Sciences, Beijing 100093, China. ; Hunan Vegetable Research Institute, Hunan Academy of Agricultural Sciences, Changsha 410125, China. ; Horticulture and Landscape College, Hunan Agricultural University, National Chinese Medicinal Herbs Technology Center, Changsha 410128, China. ; Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Key Laboratory of Biology and Genetic Improvement of Horticultural Crops of the Ministry of Agriculture, Sino-Dutch Joint Laboratory of Horticultural Genomics, Beijing 100081, China. ; Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Key Laboratory of Biology and Genetic Improvement of Horticultural Crops of the Ministry of Agriculture, Sino-Dutch Joint Laboratory of Horticultural Genomics, Beijing 100081, China. College of Life Sciences, Wuhan University, Wuhan 430072, China. ; Institute of Microbiology, Chinese Academy of Sciences, Beijing 100190, China. ; School of Pharmacy, Nihon University, Tokyo 101-8308, Japan. ; Laboratory of Plant Physiology, Wageningen University, Wageningen 6700, Netherlands. ; Department of Plant Biology, College of Biological Sciences, University of California, Davis, CA 95616, USA. ; Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Key Laboratory of Biology and Genetic Improvement of Horticultural Crops of the Ministry of Agriculture, Sino-Dutch Joint Laboratory of Horticultural Genomics, Beijing 100081, China. Agricultural Genomic Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518124, China. huangsanwen@caas.cn.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25430763" target="_blank"〉PubMed〈/a〉

Description: The essential bacterial protein FtsZ is a guanosine triphosphatase that self-assembles into a structure at the division site termed the "Z ring". During cytokinesis, the Z ring exerts a constrictive force on the membrane by using the chemical energy of guanosine triphosphate hydrolysis. However, the structural basis of this constriction remains unresolved. Here, we present the crystal structure of a guanosine diphosphate-bound Mycobacterium tuberculosis FtsZ protofilament, which exhibits a curved conformational state. The structure reveals a longitudinal interface that is important for function. The protofilament curvature highlights a hydrolysis-dependent conformational switch at the T3 loop that leads to longitudinal bending between subunits, which could generate sufficient force to drive cytokinesis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3816583/" 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/PMC3816583/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Ying -- Hsin, Jen -- Zhao, Lingyun -- Cheng, Yiwen -- Shang, Weina -- Huang, Kerwyn Casey -- Wang, Hong-Wei -- Ye, Sheng -- 1F32GM100677-01A1/GM/NIGMS NIH HHS/ -- DP2 OD006466/OD/NIH HHS/ -- DP2OD006466/OD/NIH HHS/ -- F32 GM100677/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Jul 26;341(6144):392-5. doi: 10.1126/science.1239248.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Life Sciences Institute, Zhejiang University, Hangzhou, 310058 Zhejiang, P.R. China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23888039" target="_blank"〉PubMed〈/a〉

Description: An understanding of ctenophore biology is critical for reconstructing events that occurred early in animal evolution. Toward this goal, we have sequenced, assembled, and annotated the genome of the ctenophore Mnemiopsis leidyi. Our phylogenomic analyses of both amino acid positions and gene content suggest that ctenophores rather than sponges are the sister lineage to all other animals. Mnemiopsis lacks many of the genes found in bilaterian mesodermal cell types, suggesting that these cell types evolved independently. The set of neural genes in Mnemiopsis is similar to that of sponges, indicating that sponges may have lost a nervous system. These results present a newly supported view of early animal evolution that accounts for major losses and/or gains of sophisticated cell types, including nerve and muscle cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3920664/" 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/PMC3920664/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ryan, Joseph F -- Pang, Kevin -- Schnitzler, Christine E -- Nguyen, Anh-Dao -- Moreland, R Travis -- Simmons, David K -- Koch, Bernard J -- Francis, Warren R -- Havlak, Paul -- NISC Comparative Sequencing Program -- Smith, Stephen A -- Putnam, Nicholas H -- Haddock, Steven H D -- Dunn, Casey W -- Wolfsberg, Tyra G -- Mullikin, James C -- Martindale, Mark Q -- Baxevanis, Andreas D -- ZIA HG000140-13/Intramural NIH HHS/ -- ZIA HG000140-14/Intramural NIH HHS/ -- ZIA HG000140-15/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2013 Dec 13;342(6164):1242592. doi: 10.1126/science.1242592.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genome Technology Branch, Division of Intramural Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24337300" target="_blank"〉PubMed〈/a〉

Description: DNA methylation is implicated in mammalian brain development and plasticity underlying learning and memory. We report the genome-wide composition, patterning, cell specificity, and dynamics of DNA methylation at single-base resolution in human and mouse frontal cortex throughout their lifespan. Widespread methylome reconfiguration occurs during fetal to young adult development, coincident with synaptogenesis. During this period, highly conserved non-CG methylation (mCH) accumulates in neurons, but not glia, to become the dominant form of methylation in the human neuronal genome. Moreover, we found an mCH signature that identifies genes escaping X-chromosome inactivation. Last, whole-genome single-base resolution 5-hydroxymethylcytosine (hmC) maps revealed that hmC marks fetal brain cell genomes at putative regulatory regions that are CG-demethylated and activated in the adult brain and that CG demethylation at these hmC-poised loci depends on Tet2 activity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3785061/" 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/PMC3785061/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lister, Ryan -- Mukamel, Eran A -- Nery, Joseph R -- Urich, Mark -- Puddifoot, Clare A -- Johnson, Nicholas D -- Lucero, Jacinta -- Huang, Yun -- Dwork, Andrew J -- Schultz, Matthew D -- Yu, Miao -- Tonti-Filippini, Julian -- Heyn, Holger -- Hu, Shijun -- Wu, Joseph C -- Rao, Anjana -- Esteller, Manel -- He, Chuan -- Haghighi, Fatemeh G -- Sejnowski, Terrence J -- Behrens, M Margarita -- Ecker, Joseph R -- AI44432/AI/NIAID NIH HHS/ -- CA151535/CA/NCI NIH HHS/ -- HD065812/HD/NICHD NIH HHS/ -- HG006827/HG/NHGRI NIH HHS/ -- K99NS080911/NS/NINDS NIH HHS/ -- MH094670/MH/NIMH NIH HHS/ -- R01 AI044432/AI/NIAID NIH HHS/ -- R01 CA151535/CA/NCI NIH HHS/ -- R01 HD065812/HD/NICHD NIH HHS/ -- R01 HG006827/HG/NHGRI NIH HHS/ -- R01 MH094670/MH/NIMH NIH HHS/ -- R01 MH094774/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Aug 9;341(6146):1237905. doi: 10.1126/science.1237905. Epub 2013 Jul 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA. ryan.lister@uwa.edu.au〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23828890" target="_blank"〉PubMed〈/a〉

Description: Gene expression in organisms involves many factors and is tightly controlled. Although much is known about the initial phase of transcription by RNA polymerase III (Pol III), the enzyme that synthesizes the majority of RNA molecules in eukaryotic cells, termination is poorly understood. Here, we show that the extensive structure of Pol III-synthesized transcripts dictates the release of elongation complexes at the end of genes. The poly-T termination signal, which does not cause termination in itself, causes catalytic inactivation and backtracking of Pol III, thus committing the enzyme to termination and transporting it to the nearest RNA secondary structure, which facilitates Pol III release. Similarity between termination mechanisms of Pol III and bacterial RNA polymerase suggests that hairpin-dependent termination may date back to the common ancestor of multisubunit RNA polymerases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3760304/" 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/PMC3760304/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nielsen, Soren -- Yuzenkova, Yulia -- Zenkin, Nikolay -- 202994/European Research Council/International -- BB/F013558/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/J006378/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2013 Jun 28;340(6140):1577-80. doi: 10.1126/science.1237934.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University, Baddiley-Clark Building, Richardson Road, Newcastle upon Tyne, NE2 4AX, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23812715" target="_blank"〉PubMed〈/a〉

Description: RNA chaperones are ubiquitous, heterogeneous proteins essential for RNA structural biogenesis and function. We investigated the mechanism of chaperone-mediated RNA folding by following the time-resolved dimerization of the packaging domain of a retroviral RNA at nucleotide resolution. In the absence of the nucleocapsid (NC) chaperone, dimerization proceeded through multiple, slow-folding intermediates. In the presence of NC, dimerization occurred rapidly through a single structural intermediate. The RNA binding domain of heterogeneous nuclear ribonucleoprotein A1 protein, a structurally unrelated chaperone, also accelerated dimerization. Both chaperones interacted primarily with guanosine residues. Replacing guanosine with more weakly pairing inosine yielded an RNA that folded rapidly without a facilitating chaperone. These results show that RNA chaperones can simplify RNA folding landscapes by weakening intramolecular interactions involving guanosine and explain many RNA chaperone activities.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338410/" 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/PMC4338410/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grohman, Jacob K -- Gorelick, Robert J -- Lickwar, Colin R -- Lieb, Jason D -- Bower, Brian D -- Znosko, Brent M -- Weeks, Kevin M -- GM031819/GM/NIGMS NIH HHS/ -- GM064803/GM/NIGMS NIH HHS/ -- GM072518/GM/NIGMS NIH HHS/ -- HHSN261200800001E/PHS HHS/ -- R01 GM031819/GM/NIGMS NIH HHS/ -- R01 GM064803/GM/NIGMS NIH HHS/ -- T32 GM007092/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Apr 12;340(6129):190-5. doi: 10.1126/science.1230715. Epub 2013 Mar 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, University of North Carolina, Chapel Hill, NC 27599-3290, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23470731" target="_blank"〉PubMed〈/a〉

Description: Organofluorines represent a rapidly expanding proportion of molecules that are used in pharmaceuticals, diagnostics, agrochemicals, and materials. Despite the prevalence of fluorine in synthetic compounds, the known biological scope is limited to a single pathway that produces fluoroacetate. Here, we demonstrate that this pathway can be exploited as a source of fluorinated building blocks for introduction of fluorine into natural-product scaffolds. Specifically, we have constructed pathways involving two polyketide synthase systems, and we show that fluoroacetate can be used to incorporate fluorine into the polyketide backbone in vitro. We further show that fluorine can be inserted site-selectively and introduced into polyketide products in vivo. These results highlight the prospects for the production of complex fluorinated natural products using synthetic biology.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4057101/" 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/PMC4057101/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Walker, Mark C -- Thuronyi, Benjamin W -- Charkoudian, Louise K -- Lowry, Brian -- Khosla, Chaitan -- Chang, Michelle C Y -- 1 DP2 OD008696/OD/NIH HHS/ -- 1 T32 GMO66698/PHS HHS/ -- 1S10RR023679-01/RR/NCRR NIH HHS/ -- F32 CA137994/CA/NCI NIH HHS/ -- R01 GM087934/GM/NIGMS NIH HHS/ -- S10 RR16634-01/RR/NCRR NIH HHS/ -- T32 GM066698/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Sep 6;341(6150):1089-94. doi: 10.1126/science.1242345.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720-1460, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24009388" target="_blank"〉PubMed〈/a〉

Description: Serotonin or 5-hydroxytryptamine (5-HT) regulates a wide spectrum of human physiology through the 5-HT receptor family. We report the crystal structures of the human 5-HT1B G protein-coupled receptor bound to the agonist antimigraine medications ergotamine and dihydroergotamine. The structures reveal similar binding modes for these ligands, which occupy the orthosteric pocket and an extended binding pocket close to the extracellular loops. The orthosteric pocket is formed by residues conserved in the 5-HT receptor family, clarifying the family-wide agonist activity of 5-HT. Compared with the structure of the 5-HT2B receptor, the 5-HT1B receptor displays a 3 angstrom outward shift at the extracellular end of helix V, resulting in a more open extended pocket that explains subtype selectivity. Together with docking and mutagenesis studies, these structures provide a comprehensive structural basis for understanding receptor-ligand interactions and designing subtype-selective serotonergic drugs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3644373/" 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/PMC3644373/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Chong -- Jiang, Yi -- Ma, Jinming -- Wu, Huixian -- Wacker, Daniel -- Katritch, Vsevolod -- Han, Gye Won -- Liu, Wei -- Huang, Xi-Ping -- Vardy, Eyal -- McCorvy, John D -- Gao, Xiang -- Zhou, X Edward -- Melcher, Karsten -- Zhang, Chenghai -- Bai, Fang -- Yang, Huaiyu -- Yang, Linlin -- Jiang, Hualiang -- Roth, Bryan L -- Cherezov, Vadim -- Stevens, Raymond C -- Xu, H Eric -- P50 GM073197/GM/NIGMS NIH HHS/ -- R01 DA027170/DA/NIDA NIH HHS/ -- R01 DA27170/DA/NIDA NIH HHS/ -- R01 DK071662/DK/NIDDK NIH HHS/ -- R01 MH061887/MH/NIMH NIH HHS/ -- R01 MH61887/MH/NIMH NIH HHS/ -- U19 MH082441/MH/NIMH NIH HHS/ -- U19 MH82441/MH/NIMH 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. 2013 May 3;340(6132):610-4. doi: 10.1126/science.1232807. Epub 2013 Mar 21.〈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/23519210" target="_blank"〉PubMed〈/a〉

Description: Allostery is well documented for proteins but less recognized for DNA-protein interactions. Here, we report that specific binding of a protein on DNA is substantially stabilized or destabilized by another protein bound nearby. The ternary complex's free energy oscillates as a function of the separation between the two proteins with a periodicity of ~10 base pairs, the helical pitch of B-form DNA, and a decay length of ~15 base pairs. The binding affinity of a protein near a DNA hairpin is similarly dependent on their separation, which-together with molecular dynamics simulations-suggests that deformation of the double-helical structure is the origin of DNA allostery. The physiological relevance of this phenomenon is illustrated by its effect on gene expression in live bacteria and on a transcription factor's affinity near nucleosomes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3586787/" 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/PMC3586787/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Sangjin -- Brostromer, Erik -- Xing, Dong -- Jin, Jianshi -- Chong, Shasha -- Ge, Hao -- Wang, Siyuan -- Gu, Chan -- Yang, Lijiang -- Gao, Yi Qin -- Su, Xiao-dong -- Sun, Yujie -- Xie, X Sunney -- DP1 OD000277/OD/NIH HHS/ -- New York, N.Y. -- Science. 2013 Feb 15;339(6121):816-9. doi: 10.1126/science.1229223.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23413354" target="_blank"〉PubMed〈/a〉

Description: In antiviral RNA interference (RNAi), the DICER enzyme processes virus-derived double-stranded RNA (dsRNA) into small interfering RNAs (siRNAs) that guide ARGONAUTE proteins to silence complementary viral RNA. As a counterdefense, viruses deploy viral suppressors of RNAi (VSRs). Well-established in plants and invertebrates, the existence of antiviral RNAi remains unknown in mammals. Here, we show that undifferentiated mouse cells infected with encephalomyocarditis virus (EMCV) or Nodamura virus (NoV) accumulate ~22-nucleotide RNAs with all the signature features of siRNAs. These derive from viral dsRNA replication intermediates, incorporate into AGO2, are eliminated in Dicer knockout cells, and decrease in abundance upon cell differentiation. Furthermore, genetically ablating a NoV-encoded VSR that antagonizes DICER during authentic infections reduces NoV accumulation, which is rescued in RNAi-deficient mouse cells. We conclude that antiviral RNAi operates in mammalian cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3853215/" 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/PMC3853215/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maillard, P V -- Ciaudo, C -- Marchais, A -- Li, Y -- Jay, F -- Ding, S W -- Voinnet, Olivier -- R01 AI052447/AI/NIAID NIH HHS/ -- R01 GM094396/GM/NIGMS NIH HHS/ -- RC1 GM091896/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Oct 11;342(6155):235-8. doi: 10.1126/science.1241930.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Swiss Federal Institute of Technology Zurich (ETH-Z), Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24115438" target="_blank"〉PubMed〈/a〉

Description: Engineering wireframe architectures and scaffolds of increasing complexity is one of the important challenges in nanotechnology. We present a design strategy to create gridiron-like DNA structures. A series of four-arm junctions are used as vertices within a network of double-helical DNA fragments. Deliberate distortion of the junctions from their most relaxed conformations ensures that a scaffold strand can traverse through individual vertices in multiple directions. DNA gridirons were assembled, ranging from two-dimensional arrays with reconfigurability to multilayer and three-dimensional structures and curved objects.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Han, Dongran -- Pal, Suchetan -- Yang, Yang -- Jiang, Shuoxing -- Nangreave, Jeanette -- Liu, Yan -- Yan, Hao -- New York, N.Y. -- Science. 2013 Mar 22;339(6126):1412-5. doi: 10.1126/science.1232252.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA. dongran.han@asu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23520107" target="_blank"〉PubMed〈/a〉

Description: The 2013 outbreak of avian-origin H7N9 influenza in eastern China has raised concerns about its ability to transmit in the human population. The hemagglutinin glycoprotein of most human H7N9 viruses carries Leu(226), a residue linked to adaptation of H2N2 and H3N2 pandemic viruses to human receptors. However, glycan array analysis of the H7 hemagglutinin reveals negligible binding to humanlike alpha2-6-linked receptors and strong preference for a subset of avian-like alpha2-3-linked glycans recognized by all avian H7 viruses. Crystal structures of H7N9 hemagglutinin and six hemagglutinin-glycan complexes have elucidated the structural basis for preferential recognition of avian-like receptors. These findings suggest that the current human H7N9 viruses are poorly adapted for efficient human-to-human transmission.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3954636/" 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/PMC3954636/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xu, Rui -- de Vries, Robert P -- Zhu, Xueyong -- Nycholat, Corwin M -- McBride, Ryan -- Yu, Wenli -- Paulson, James C -- Wilson, Ian A -- GM62116/GM/NIGMS NIH HHS/ -- P41GM103393/GM/NIGMS NIH HHS/ -- P41RR001209/RR/NCRR NIH HHS/ -- R56 AI099275/AI/NIAID NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Dec 6;342(6163):1230-5. doi: 10.1126/science.1243761.〈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/24311689" target="_blank"〉PubMed〈/a〉

Description: Ten years ago, the discovery of Mimivirus, a virus infecting Acanthamoeba, initiated a reappraisal of the upper limits of the viral world, both in terms of particle size (〉0.7 micrometers) and genome complexity (〉1000 genes), dimensions typical of parasitic bacteria. The diversity of these giant viruses (the Megaviridae) was assessed by sampling a variety of aquatic environments and their associated sediments worldwide. We report the isolation of two giant viruses, one off the coast of central Chile, the other from a freshwater pond near Melbourne (Australia), without morphological or genomic resemblance to any previously defined virus families. Their micrometer-sized ovoid particles contain DNA genomes of at least 2.5 and 1.9 megabases, respectively. These viruses are the first members of the proposed "Pandoravirus" genus, a term reflecting their lack of similarity with previously described microorganisms and the surprises expected from their future study.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Philippe, Nadege -- Legendre, Matthieu -- Doutre, Gabriel -- Coute, Yohann -- Poirot, Olivier -- Lescot, Magali -- Arslan, Defne -- Seltzer, Virginie -- Bertaux, Lionel -- Bruley, Christophe -- Garin, Jerome -- Claverie, Jean-Michel -- Abergel, Chantal -- New York, N.Y. -- Science. 2013 Jul 19;341(6143):281-6. doi: 10.1126/science.1239181.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural and Genomic Information Laboratory, UMR 7256 CNRS Aix-Marseille Universite, 163 Avenue de Luminy, Case 934, 13288 Marseille cedex 9, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23869018" target="_blank"〉PubMed〈/a〉

Description: Toll-like receptor 7 (TLR7) and TLR8 recognize single-stranded RNA and initiate innate immune responses. Several synthetic agonists of TLR7-TLR8 display novel therapeutic potential; however, the molecular basis for ligand recognition and activation of signaling by TLR7 or TLR8 is largely unknown. In this study, the crystal structures of unliganded and ligand-induced activated human TLR8 dimers were elucidated. Ligand recognition was mediated by a dimerization interface formed by two protomers. Upon ligand stimulation, the TLR8 dimer was reorganized such that the two C termini were brought into proximity. The loop between leucine-rich repeat 14 (LRR14) and LRR15 was cleaved; however, the N- and C-terminal halves remained associated and contributed to ligand recognition and dimerization. Thus, ligand binding induces reorganization of the TLR8 dimer, which enables downstream signaling processes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tanji, Hiromi -- Ohto, Umeharu -- Shibata, Takuma -- Miyake, Kensuke -- Shimizu, Toshiyuki -- New York, N.Y. -- Science. 2013 Mar 22;339(6126):1426-9. doi: 10.1126/science.1229159.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23520111" target="_blank"〉PubMed〈/a〉

Description: The processes that shaped modern European mitochondrial DNA (mtDNA) variation remain unclear. The initial peopling by Palaeolithic hunter-gatherers ~42,000 years ago and the immigration of Neolithic farmers into Europe ~8000 years ago appear to have played important roles but do not explain present-day mtDNA diversity. We generated mtDNA profiles of 364 individuals from prehistoric cultures in Central Europe to perform a chronological study, spanning the Early Neolithic to the Early Bronze Age (5500 to 1550 calibrated years before the common era). We used this transect through time to identify four marked shifts in genetic composition during the Neolithic period, revealing a key role for Late Neolithic cultures in shaping modern Central European genetic diversity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4039305/" 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/PMC4039305/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brandt, Guido -- Haak, Wolfgang -- Adler, Christina J -- Roth, Christina -- Szecsenyi-Nagy, Anna -- Karimnia, Sarah -- Moller-Rieker, Sabine -- Meller, Harald -- Ganslmeier, Robert -- Friederich, Susanne -- Dresely, Veit -- Nicklisch, Nicole -- Pickrell, Joseph K -- Sirocko, Frank -- Reich, David -- Cooper, Alan -- Alt, Kurt W -- Genographic Consortium -- R01 GM100233/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Oct 11;342(6155):257-61. doi: 10.1126/science.1241844.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Anthropology, Johannes Gutenberg University of Mainz, Mainz, Germany. brandtg@uni-mainz.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24115443" target="_blank"〉PubMed〈/a〉

Description: Host cell factor-1 (HCF-1), a transcriptional co-regulator of human cell-cycle progression, undergoes proteolytic maturation in which any of six repeated sequences is cleaved by the nutrient-responsive glycosyltransferase, O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT). We report that the tetratricopeptide-repeat domain of O-GlcNAc transferase binds the carboxyl-terminal portion of an HCF-1 proteolytic repeat such that the cleavage region lies in the glycosyltransferase active site above uridine diphosphate-GlcNAc. The conformation is similar to that of a glycosylation-competent peptide substrate. Cleavage occurs between cysteine and glutamate residues and results in a pyroglutamate product. Conversion of the cleavage site glutamate into serine converts an HCF-1 proteolytic repeat into a glycosylation substrate. Thus, protein glycosylation and HCF-1 cleavage occur in the same active site.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3930058/" 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/PMC3930058/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lazarus, Michael B -- Jiang, Jiaoyang -- Kapuria, Vaibhav -- Bhuiyan, Tanja -- Janetzko, John -- Zandberg, Wesley F -- Vocadlo, David J -- Herr, Winship -- Walker, Suzanne -- R01 GM094263/GM/NIGMS NIH HHS/ -- R01GM094263/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Dec 6;342(6163):1235-9. doi: 10.1126/science.1243990.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24311690" target="_blank"〉PubMed〈/a〉

Description: Instances in which natural selection maintains genetic variation in a population over millions of years are thought to be extremely rare. We conducted a genome-wide scan for long-lived balancing selection by looking for combinations of SNPs shared between humans and chimpanzees. In addition to the major histocompatibility complex, we identified 125 regions in which the same haplotypes are segregating in the two species, all but two of which are noncoding. In six cases, there is evidence for an ancestral polymorphism that persisted to the present in humans and chimpanzees. Regions with shared haplotypes are significantly enriched for membrane glycoproteins, and a similar trend is seen among shared coding polymorphisms. These findings indicate that ancient balancing selection has shaped human variation and point to genes involved in host-pathogen interactions as common targets.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3612375/" 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/PMC3612375/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Leffler, Ellen M -- Gao, Ziyue -- Pfeifer, Susanne -- Segurel, Laure -- Auton, Adam -- Venn, Oliver -- Bowden, Rory -- Bontrop, Ronald -- Wall, Jeffrey D -- Sella, Guy -- Donnelly, Peter -- McVean, Gilean -- Przeworski, Molly -- 075491/Z/04/B/Wellcome Trust/United Kingdom -- 086084/Z/08/Z/Wellcome Trust/United Kingdom -- 090532/Wellcome Trust/United Kingdom -- 090532/Z/09/Z/Wellcome Trust/United Kingdom -- 095552/Wellcome Trust/United Kingdom -- 095552/Z/11/Z/Wellcome Trust/United Kingdom -- GM72861/GM/NIGMS NIH HHS/ -- HG005226/HG/NHGRI NIH HHS/ -- R01 GM072861/GM/NIGMS NIH HHS/ -- T32 GM007197/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Mar 29;339(6127):1578-82. doi: 10.1126/science.1234070. Epub 2013 Feb 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA. emleffler@uchicago.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23413192" target="_blank"〉PubMed〈/a〉

Description: An ability to mimic the boundaries of biological compartments would improve our understanding of self-assembly and provide routes to new materials for the delivery of drugs and biologicals and the development of protocells. We show that short designed peptides can be combined to form unilamellar spheres approximately 100 nanometers in diameter. The design comprises two, noncovalent, heterodimeric and homotrimeric coiled-coil bundles. These are joined back to back to render two complementary hubs, which when mixed form hexagonal networks that close to form cages. This design strategy offers control over chemistry, self-assembly, reversibility, and size of such particles.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fletcher, Jordan M -- Harniman, Robert L -- Barnes, Frederick R H -- Boyle, Aimee L -- Collins, Andrew -- Mantell, Judith -- Sharp, Thomas H -- Antognozzi, Massimo -- Booth, Paula J -- Linden, Noah -- Miles, Mervyn J -- Sessions, Richard B -- Verkade, Paul -- Woolfson, Derek N -- BB/G008833/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2013 May 3;340(6132):595-9. doi: 10.1126/science.1233936. Epub 2013 Apr 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Chemistry, Cantock's Close, University of Bristol, Bristol BS8 1TS, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23579496" target="_blank"〉PubMed〈/a〉