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  • 1
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    High-resolution mapping of meiotic crossovers and non-crossovers in yeast (2008)
    Nature Publishing Group (NPG)
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    Publication Date: 2008-07-11
    Description: Meiotic recombination has a central role in the evolution of sexually reproducing organisms. The two recombination outcomes, crossover and non-crossover, increase genetic diversity, but have the potential to homogenize alleles by gene conversion. Whereas crossover rates vary considerably across the genome, non-crossovers and gene conversions have only been identified in a handful of loci. To examine recombination genome wide and at high spatial resolution, we generated maps of crossovers, crossover-associated gene conversion and non-crossover gene conversion using dense genetic marker data collected from all four products of fifty-six yeast (Saccharomyces cerevisiae) meioses. Our maps reveal differences in the distributions of crossovers and non-crossovers, showing more regions where either crossovers or non-crossovers are favoured than expected by chance. Furthermore, we detect evidence for interference between crossovers and non-crossovers, a phenomenon previously only known to occur between crossovers. Up to 1% of the genome of each meiotic product is subject to gene conversion in a single meiosis, with detectable bias towards GC nucleotides. To our knowledge the maps represent the first high-resolution, genome-wide characterization of the multiple outcomes of recombination in any organism. In addition, because non-crossover hotspots create holes of reduced linkage within haplotype blocks, our results stress the need to incorporate non-crossovers into genetic linkage analysis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2780006/" 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/PMC2780006/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mancera, Eugenio -- Bourgon, Richard -- Brozzi, Alessandro -- Huber, Wolfgang -- Steinmetz, Lars M -- P01 HG000205/HG/NHGRI NIH HHS/ -- P01 HG000205-19/HG/NHGRI NIH HHS/ -- R01 GM068717/GM/NIGMS NIH HHS/ -- R01 GM068717-06/GM/NIGMS NIH HHS/ -- England -- Nature. 2008 Jul 24;454(7203):479-85. doi: 10.1038/nature07135. Epub 2008 Jul 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18615017" target="_blank"〉PubMed〈/a〉
    Keywords: *Chromosome Mapping ; Chromosomes, Fungal/genetics ; Crossing Over, Genetic/*genetics ; DNA Breaks, Double-Stranded ; DNA-Binding Proteins/genetics ; Flap Endonucleases ; Gene Conversion/*genetics ; Gene Expression Regulation, Fungal ; Genetic Linkage/genetics ; Genetic Markers/genetics ; Genome, Fungal/genetics ; Genotype ; Haplotypes/genetics ; Meiosis/*genetics ; Mutation/genetics ; Saccharomyces cerevisiae/cytology/*genetics ; Saccharomyces cerevisiae Proteins/genetics ; Trans-Activators/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
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    Bidirectional promoters generate pervasive transcription in yeast (2009)
    Nature Publishing Group (NPG)
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    Publication Date: 2009-01-27
    Description: Genome-wide pervasive transcription has been reported in many eukaryotic organisms, revealing a highly interleaved transcriptome organization that involves hundreds of previously unknown non-coding RNAs. These recently identified transcripts either exist stably in cells (stable unannotated transcripts, SUTs) or are rapidly degraded by the RNA surveillance pathway (cryptic unstable transcripts, CUTs). One characteristic of pervasive transcription is the extensive overlap of SUTs and CUTs with previously annotated features, which prompts questions regarding how these transcripts are generated, and whether they exert function. Single-gene studies have shown that transcription of SUTs and CUTs can be functional, through mechanisms involving the generated RNAs or their generation itself. So far, a complete transcriptome architecture including SUTs and CUTs has not been described in any organism. Knowledge about the position and genome-wide arrangement of these transcripts will be instrumental in understanding their function. Here we provide a comprehensive analysis of these transcripts in the context of multiple conditions, a mutant of the exosome machinery and different strain backgrounds of Saccharomyces cerevisiae. We show that both SUTs and CUTs display distinct patterns of distribution at specific locations. Most of the newly identified transcripts initiate from nucleosome-free regions (NFRs) associated with the promoters of other transcripts (mostly protein-coding genes), or from NFRs at the 3' ends of protein-coding genes. Likewise, about half of all coding transcripts initiate from NFRs associated with promoters of other transcripts. These data change our view of how a genome is transcribed, indicating that bidirectionality is an inherent feature of promoters. Such an arrangement of divergent and overlapping transcripts may provide a mechanism for local spreading of regulatory signals-that is, coupling the transcriptional regulation of neighbouring genes by means of transcriptional interference or histone modification.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2766638/" 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/PMC2766638/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xu, Zhenyu -- Wei, Wu -- Gagneur, Julien -- Perocchi, Fabiana -- Clauder-Munster, Sandra -- Camblong, Jurgi -- Guffanti, Elisa -- Stutz, Francoise -- Huber, Wolfgang -- Steinmetz, Lars M -- P01 HG000205/HG/NHGRI NIH HHS/ -- P01 HG000205-19/HG/NHGRI NIH HHS/ -- R01 GM068717/GM/NIGMS NIH HHS/ -- R01 GM068717-06/GM/NIGMS NIH HHS/ -- England -- Nature. 2009 Feb 19;457(7232):1033-7. doi: 10.1038/nature07728. Epub 2009 Jan 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19169243" target="_blank"〉PubMed〈/a〉
    Keywords: Gene Expression Profiling ; Gene Expression Regulation, Fungal/*genetics ; Genes, Fungal/genetics ; Genes, Overlapping/genetics ; Genome, Fungal/genetics ; Models, Genetic ; Nucleosomes ; Promoter Regions, Genetic/*genetics ; RNA Stability/genetics ; RNA, Fungal/*genetics ; RNA, Untranslated/genetics ; Saccharomyces cerevisiae/classification/*genetics ; Saccharomyces cerevisiae Proteins/genetics ; Transcription, Genetic/*genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
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    The role of black holes in galaxy formation and evolution (2009)
    Nature Publishing Group (NPG)
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    Publication Date: 2009-07-10
    Description: Virtually all massive galaxies, including our own, host central black holes ranging in mass from millions to billions of solar masses. The growth of these black holes releases vast amounts of energy that powers quasars and other weaker active galactic nuclei. A tiny fraction of this energy, if absorbed by the host galaxy, could halt star formation by heating and ejecting ambient gas. A central question in galaxy evolution is the degree to which this process has caused the decline of star formation in large elliptical galaxies, which typically have little cold gas and few young stars, unlike spiral galaxies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cattaneo, A -- Faber, S M -- Binney, J -- Dekel, A -- Kormendy, J -- Mushotzky, R -- Babul, A -- Best, P N -- Bruggen, M -- Fabian, A C -- Frenk, C S -- Khalatyan, A -- Netzer, H -- Mahdavi, A -- Silk, J -- Steinmetz, M -- Wisotzki, L -- England -- Nature. 2009 Jul 9;460(7252):213-9. doi: 10.1038/nature08135.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Astrophysikalisches Institut Potsdam, An der Sternwarte 16, 14482 Potsdam, Germany. acattaneo@aip.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19587763" target="_blank"〉PubMed〈/a〉
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
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    Widespread bidirectional promoters are the major source of cryptic transcripts in yeast (2009)
    Nature Publishing Group (NPG)
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    Publication Date: 2009-01-27
    Description: Pervasive and hidden transcription is widespread in eukaryotes, but its global level, the mechanisms from which it originates and its functional significance are unclear. Cryptic unstable transcripts (CUTs) were recently described as a principal class of RNA polymerase II transcripts in Saccharomyces cerevisiae. These transcripts are targeted for degradation immediately after synthesis by the action of the Nrd1-exosome-TRAMP complexes. Although CUT degradation mechanisms have been analysed in detail, the genome-wide distribution at the nucleotide resolution and the prevalence of CUTs are unknown. Here we report the first high-resolution genomic map of CUTs in yeast, revealing a class of potentially functional CUTs and the intrinsic bidirectional nature of eukaryotic promoters. An RNA fraction highly enriched in CUTs was analysed by a 3' Long-SAGE (serial analysis of gene expression) approach adapted to deep sequencing. The resulting detailed genomic map of CUTs revealed that they derive from extremely widespread and very well defined transcription units and do not result from unspecific transcriptional noise. Moreover, the transcription of CUTs predominantly arises within nucleosome-free regions, most of which correspond to promoter regions of bona fide genes. Some of the CUTs start upstream from messenger RNAs and overlap their 5' end. Our study of glycolysis genes, as well as recent results from the literature, indicate that such concurrent transcription is potentially associated with regulatory mechanisms. Our data reveal numerous new CUTs with such a potential regulatory role. However, most of the identified CUTs corresponded to transcripts divergent from the promoter regions of genes, indicating that they represent by-products of divergent transcription occurring at many and possibly most promoters. Eukaryotic promoter regions are thus intrinsically bidirectional, a fundamental property that escaped previous analyses because in most cases divergent transcription generates short-lived unstable transcripts present at very low steady-state levels.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Neil, Helen -- Malabat, Christophe -- d'Aubenton-Carafa, Yves -- Xu, Zhenyu -- Steinmetz, Lars M -- Jacquier, Alain -- England -- Nature. 2009 Feb 19;457(7232):1038-42. doi: 10.1038/nature07747. Epub 2009 Jan 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut Pasteur, Unite de Genetique des Interactions Macromoleculaires, CNRS, URA2171, 75015 Paris, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19169244" target="_blank"〉PubMed〈/a〉
    Keywords: 5' Untranslated Regions/genetics ; Gene Expression Regulation, Fungal/*genetics ; Genome, Fungal/genetics ; Glycolysis/genetics ; Promoter Regions, Genetic/*genetics ; RNA Polymerase II/metabolism ; RNA Stability/genetics ; RNA, Fungal/*genetics/metabolism ; Saccharomyces cerevisiae/*genetics ; Saccharomyces cerevisiae Proteins/genetics ; Transcription, Genetic/*genetics
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  • 5
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    The dynamic genome of Hydra (2010)
    Nature Publishing Group (NPG)
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    Publication Date: 2010-03-17
    Description: The freshwater cnidarian Hydra was first described in 1702 and has been the object of study for 300 years. Experimental studies of Hydra between 1736 and 1744 culminated in the discovery of asexual reproduction of an animal by budding, the first description of regeneration in an animal, and successful transplantation of tissue between animals. Today, Hydra is an important model for studies of axial patterning, stem cell biology and regeneration. Here we report the genome of Hydra magnipapillata and compare it to the genomes of the anthozoan Nematostella vectensis and other animals. The Hydra genome has been shaped by bursts of transposable element expansion, horizontal gene transfer, trans-splicing, and simplification of gene structure and gene content that parallel simplification of the Hydra life cycle. We also report the sequence of the genome of a novel bacterium stably associated with H. magnipapillata. Comparisons of the Hydra genome to the genomes of other animals shed light on the evolution of epithelia, contractile tissues, developmentally regulated transcription factors, the Spemann-Mangold organizer, pluripotency genes and the neuromuscular junction.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4479502/" 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/PMC4479502/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chapman, Jarrod A -- Kirkness, Ewen F -- Simakov, Oleg -- Hampson, Steven E -- Mitros, Therese -- Weinmaier, Thomas -- Rattei, Thomas -- Balasubramanian, Prakash G -- Borman, Jon -- Busam, Dana -- Disbennett, Kathryn -- Pfannkoch, Cynthia -- Sumin, Nadezhda -- Sutton, Granger G -- Viswanathan, Lakshmi Devi -- Walenz, Brian -- Goodstein, David M -- Hellsten, Uffe -- Kawashima, Takeshi -- Prochnik, Simon E -- Putnam, Nicholas H -- Shu, Shengquiang -- Blumberg, Bruce -- Dana, Catherine E -- Gee, Lydia -- Kibler, Dennis F -- Law, Lee -- Lindgens, Dirk -- Martinez, Daniel E -- Peng, Jisong -- Wigge, Philip A -- Bertulat, Bianca -- Guder, Corina -- Nakamura, Yukio -- Ozbek, Suat -- Watanabe, Hiroshi -- Khalturin, Konstantin -- Hemmrich, Georg -- Franke, Andre -- Augustin, Rene -- Fraune, Sebastian -- Hayakawa, Eisuke -- Hayakawa, Shiho -- Hirose, Mamiko -- Hwang, Jung Shan -- Ikeo, Kazuho -- Nishimiya-Fujisawa, Chiemi -- Ogura, Atshushi -- Takahashi, Toshio -- Steinmetz, Patrick R H -- Zhang, Xiaoming -- Aufschnaiter, Roland -- Eder, Marie-Kristin -- Gorny, Anne-Kathrin -- Salvenmoser, Willi -- Heimberg, Alysha M -- Wheeler, Benjamin M -- Peterson, Kevin J -- Bottger, Angelika -- Tischler, Patrick -- Wolf, Alexander -- Gojobori, Takashi -- Remington, Karin A -- Strausberg, Robert L -- Venter, J Craig -- Technau, Ulrich -- Hobmayer, Bert -- Bosch, Thomas C G -- Holstein, Thomas W -- Fujisawa, Toshitaka -- Bode, Hans R -- David, Charles N -- Rokhsar, Daniel S -- Steele, Robert E -- P 21108/Austrian Science Fund FWF/Austria -- R24 RR015088/RR/NCRR NIH HHS/ -- England -- Nature. 2010 Mar 25;464(7288):592-6. doi: 10.1038/nature08830. Epub 2010 Mar 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉US Department of Energy Joint Genome Institute, Walnut Creek, California 94598, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20228792" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anthozoa/genetics ; Comamonadaceae/genetics ; DNA Transposable Elements/genetics ; Gene Transfer, Horizontal/genetics ; Genome/*genetics ; Genome, Bacterial/genetics ; Hydra/*genetics/microbiology/ultrastructure ; Molecular Sequence Data ; Neuromuscular Junction/ultrastructure
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  • 6
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    Genetic analysis of variation in transcription factor binding in yeast (2010)
    Nature Publishing Group (NPG)
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    Publication Date: 2010-03-20
    Description: Variation in transcriptional regulation is thought to be a major cause of phenotypic diversity. Although widespread differences in gene expression among individuals of a species have been observed, studies to examine the variability of transcription factor binding on a global scale have not been performed, and thus the extent and underlying genetic basis of transcription factor binding diversity is unknown. By mapping differences in transcription factor binding among individuals, here we present the genetic basis of such variation on a genome-wide scale. Whole-genome Ste12-binding profiles were determined using chromatin immunoprecipitation coupled with DNA sequencing in pheromone-treated cells of 43 segregants of a cross between two highly diverged yeast strains and their parental lines. We identified extensive Ste12-binding variation among individuals, and mapped underlying cis- and trans-acting loci responsible for such variation. We showed that most transcription factor binding variation is cis-linked, and that many variations are associated with polymorphisms residing in the binding motifs of Ste12 as well as those of several proposed Ste12 cofactors. We also identified two trans-factors, AMN1 and FLO8, that modulate Ste12 binding to promoters of more than ten genes under alpha-factor treatment. Neither of these two genes was previously known to regulate Ste12, and we suggest that they may be mediators of gene activity and phenotypic diversity. Ste12 binding strongly correlates with gene expression for more than 200 genes, indicating that binding variation is functional. Many of the variable-bound genes are involved in cell wall organization and biogenesis. Overall, these studies identified genetic regulators of molecular diversity among individuals and provide new insights into mechanisms of gene regulation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2941147/" 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/PMC2941147/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zheng, Wei -- Zhao, Hongyu -- Mancera, Eugenio -- Steinmetz, Lars M -- Snyder, Michael -- P01 HG000205/HG/NHGRI NIH HHS/ -- P01 HG000205-10/HG/NHGRI NIH HHS/ -- R01 CA077808/CA/NCI NIH HHS/ -- R01 CA077808-09/CA/NCI NIH HHS/ -- R01 GM059507-09/GM/NIGMS NIH HHS/ -- R01 GM068717/GM/NIGMS NIH HHS/ -- R01 GM068717-08/GM/NIGMS NIH HHS/ -- RR19895/RR/NCRR NIH HHS/ -- England -- Nature. 2010 Apr 22;464(7292):1187-91. doi: 10.1038/nature08934. Epub 2010 Mar 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06520, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20237471" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs/genetics ; Binding Sites/genetics ; Cell Cycle Proteins/genetics/metabolism ; Cell Wall/genetics/metabolism ; Gene Expression Regulation, Fungal ; Genes, Fungal/genetics ; Genetic Variation/*genetics ; Genome, Fungal/genetics ; Nuclear Proteins/genetics/metabolism ; Oligonucleotide Array Sequence Analysis ; Peptides/pharmacology ; Pheromones/pharmacology ; Polymorphism, Genetic/genetics ; Promoter Regions, Genetic/genetics ; Protein Binding ; Quantitative Trait Loci/genetics ; Reproducibility of Results ; Saccharomyces cerevisiae/drug effects/*genetics/*metabolism ; Saccharomyces cerevisiae Proteins/chemistry/*genetics/*metabolism ; Trans-Activators/genetics/metabolism ; Transcription Factors/chemistry/*genetics/*metabolism
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  • 7
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    Structural basis for recognition of synaptic vesicle protein 2C by botulinum neurotoxin A (2013)
    Nature Publishing Group (NPG)
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    Publication Date: 2013-11-19
    Description: Botulinum neurotoxin A (BoNT/A) belongs to the most dangerous class of bioweapons. Despite this, BoNT/A is used to treat a wide range of common medical conditions such as migraines and a variety of ocular motility and movement disorders. BoNT/A is probably best known for its use as an antiwrinkle agent in cosmetic applications (including Botox and Dysport). BoNT/A application causes long-lasting flaccid paralysis of muscles through inhibiting the release of the neurotransmitter acetylcholine by cleaving synaptosomal-associated protein 25 (SNAP-25) within presynaptic nerve terminals. Two types of BoNT/A receptor have been identified, both of which are required for BoNT/A toxicity and are therefore likely to cooperate with each other: gangliosides and members of the synaptic vesicle glycoprotein 2 (SV2) family, which are putative transporter proteins that are predicted to have 12 transmembrane domains, associate with the receptor-binding domain of the toxin. Recently, fibroblast growth factor receptor 3 (FGFR3) has also been reported to be a potential BoNT/A receptor. In SV2 proteins, the BoNT/A-binding site has been mapped to the luminal domain, but the molecular details of the interaction between BoNT/A and SV2 are unknown. Here we determined the high-resolution crystal structure of the BoNT/A receptor-binding domain (BoNT/A-RBD) in complex with the SV2C luminal domain (SV2C-LD). SV2C-LD consists of a right-handed, quadrilateral beta-helix that associates with BoNT/A-RBD mainly through backbone-to-backbone interactions at open beta-strand edges, in a manner that resembles the inter-strand interactions in amyloid structures. Competition experiments identified a peptide that inhibits the formation of the complex. Our findings provide a strong platform for the development of novel antitoxin agents and for the rational design of BoNT/A variants with improved therapeutic properties.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Benoit, Roger M -- Frey, Daniel -- Hilbert, Manuel -- Kevenaar, Josta T -- Wieser, Mara M -- Stirnimann, Christian U -- McMillan, David -- Ceska, Tom -- Lebon, Florence -- Jaussi, Rolf -- Steinmetz, Michel O -- Schertler, Gebhard F X -- Hoogenraad, Casper C -- Capitani, Guido -- Kammerer, Richard A -- England -- Nature. 2014 Jan 2;505(7481):108-11. doi: 10.1038/nature12732. Epub 2013 Nov 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Biomolecular Research, Paul Scherrer Institut, CH-5232 Villigen PSI, Switzerland. ; 1] Laboratory of Biomolecular Research, Paul Scherrer Institut, CH-5232 Villigen PSI, Switzerland [2]. ; 1] Cell Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, The Netherlands [2]. ; Swiss Light Source, Paul Scherrer Institut, CH-5232 Villigen PSI, Switzerland. ; UCB Celltech, UCB Pharma, UCB NewMedicines, Slough SL1 4EN, UK. ; UCB Pharma, UCB NewMedicines, B-1420 Braine-L'Alleud, Belgium. ; 1] Laboratory of Biomolecular Research, Paul Scherrer Institut, CH-5232 Villigen PSI, Switzerland [2] Department of Biology, ETH Zurich, CH-8093 Zurich, Switzerland. ; Cell Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, The Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24240280" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Botulinum Toxins, Type A/*chemistry/*metabolism ; Crystallography, X-Ray ; Endocytosis/drug effects ; HEK293 Cells ; Humans ; Membrane Glycoproteins/*chemistry/*metabolism ; Models, Molecular ; Neostriatum/cytology ; Nerve Tissue Proteins/*chemistry/*metabolism ; Neurons/drug effects ; Peptide Fragments/chemistry/pharmacology ; Structure-Activity Relationship
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    Extensive transcriptional heterogeneity revealed by isoform profiling (2013)
    Nature Publishing Group (NPG)
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    Publication Date: 2013-04-26
    Description: Transcript function is determined by sequence elements arranged on an individual RNA molecule. Variation in transcripts can affect messenger RNA stability, localization and translation, or produce truncated proteins that differ in localization or function. Given the existence of overlapping, variable transcript isoforms, determining the functional impact of the transcriptome requires identification of full-length transcripts, rather than just the genomic regions that are transcribed. Here, by jointly determining both transcript ends for millions of RNA molecules, we reveal an extensive layer of isoform diversity previously hidden among overlapping RNA molecules. Variation in transcript boundaries seems to be the rule rather than the exception, even within a single population of yeast cells. Over 26 major transcript isoforms per protein-coding gene were expressed in yeast. Hundreds of short coding RNAs and truncated versions of proteins are concomitantly encoded by alternative transcript isoforms, increasing protein diversity. In addition, approximately 70% of genes express alternative isoforms that vary in post-transcriptional regulatory elements, and tandem genes frequently produce overlapping or even bicistronic transcripts. This extensive transcript diversity is generated by a relatively simple eukaryotic genome with limited splicing, and within a genetically homogeneous population of cells. Our findings have implications for genome compaction, evolution and phenotypic diversity between single cells. These data also indicate that isoform diversity as well as RNA abundance should be considered when assessing the functional repertoire of genomes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3705217/" 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/PMC3705217/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pelechano, Vicent -- Wei, Wu -- Steinmetz, Lars M -- P01 HG000205/HG/NHGRI NIH HHS/ -- R01 GM068717/GM/NIGMS NIH HHS/ -- England -- Nature. 2013 May 2;497(7447):127-31. doi: 10.1038/nature12121. Epub 2013 Apr 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genome Biology Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23615609" target="_blank"〉PubMed〈/a〉
    Keywords: Alternative Splicing/*genetics ; Fungal Proteins/genetics ; *Gene Expression Profiling ; Genes, Fungal/genetics ; Genome, Fungal/genetics ; Genomics ; Protein Isoforms/genetics ; RNA, Fungal/*analysis/*genetics ; RNA, Messenger/analysis/genetics ; Regulatory Sequences, Ribonucleic Acid/genetics ; Saccharomyces cerevisiae/*genetics ; Transcription, Genetic/*genetics ; Transcriptome/*genetics
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    Visual space is compressed in prefrontal cortex before eye movements (2014)
    Nature Publishing Group (NPG)
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    Publication Date: 2014-03-29
    Description: We experience the visual world through a series of saccadic eye movements, each one shifting our gaze to bring objects of interest to the fovea for further processing. Although such movements lead to frequent and substantial displacements of the retinal image, these displacements go unnoticed. It is widely assumed that a primary mechanism underlying this apparent stability is an anticipatory shifting of visual receptive fields (RFs) from their presaccadic to their postsaccadic locations before movement onset. Evidence of this predictive 'remapping' of RFs has been particularly apparent within brain structures involved in gaze control. However, critically absent among that evidence are detailed measurements of visual RFs before movement onset. Here we show that during saccade preparation, rather than remap, RFs of neurons in a prefrontal gaze control area massively converge towards the saccadic target. We mapped the visual RFs of prefrontal neurons during stable fixation and immediately before the onset of eye movements, using multi-electrode recordings in monkeys. Following movements from an initial fixation point to a target, RFs remained stationary in retinocentric space. However, in the period immediately before movement onset, RFs shifted by as much as 18 degrees of visual angle, and converged towards the target location. This convergence resulted in a threefold increase in the proportion of RFs responding to stimuli near the target region. In addition, like in human observers, the population of prefrontal neurons grossly mislocalized presaccadic stimuli as being closer to the target. Our results show that RF shifts do not predict the retinal displacements due to saccades, but instead reflect the overriding perception of target space during eye movements.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4064801/" 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/PMC4064801/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zirnsak, Marc -- Steinmetz, Nicholas A -- Noudoost, Behrad -- Xu, Kitty Z -- Moore, Tirin -- EY014924/EY/NEI NIH HHS/ -- R01 EY014924/EY/NEI NIH HHS/ -- T32 MH020016/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Mar 27;507(7493):504-7. doi: 10.1038/nature13149.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Neurobiology, Stanford University School of Medicine, Stanford, California 94305, USA [2] Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305, USA. ; Department of Neurobiology, Stanford University School of Medicine, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24670771" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Electrodes ; Fixation, Ocular/physiology ; Humans ; Macaca mulatta ; Male ; Models, Neurological ; Neurons/physiology ; Prefrontal Cortex/cytology/*physiology ; Retina/physiology ; Saccades/*physiology ; Visual Acuity/physiology ; Visual Fields/physiology ; Visual Perception/*physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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    A spectrograph for exoplanet observations calibrated at the centimetre-per-second level (2012)
    Nature Publishing Group (NPG)
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    Publication Date: 2012-06-05
    Description: The best spectrographs are limited in stability by their calibration light source. Laser frequency combs are the ideal calibrators for astronomical spectrographs. They emit a spectrum of lines that are equally spaced in frequency and that are as accurate and stable as the atomic clock relative to which the comb is stabilized. Absolute calibration provides the radial velocity of an astronomical object relative to the observer (on Earth). For the detection of Earth-mass exoplanets in Earth-like orbits around solar-type stars, or of cosmic acceleration, the observable is a tiny velocity change of less than 10 cm s(-1), where the repeatability of the calibration--the variation in stability across observations--is important. Hitherto, only laboratory systems or spectrograph calibrations of limited performance have been demonstrated. Here we report the calibration of an astronomical spectrograph with a short-term Doppler shift repeatability of 2.5 cm s(-1), and use it to monitor the star HD 75289 and recompute the orbit of its planet. This repeatability should make it possible to detect Earth-like planets in the habitable zone of star or even to measure the cosmic acceleration directly.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wilken, Tobias -- Curto, Gaspare Lo -- Probst, Rafael A -- Steinmetz, Tilo -- Manescau, Antonio -- Pasquini, Luca -- Gonzalez Hernandez, Jonay I -- Rebolo, Rafael -- Hansch, Theodor W -- Udem, Thomas -- Holzwarth, Ronald -- England -- Nature. 2012 May 30;485(7400):611-4. doi: 10.1038/nature11092.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max-Planck-Institut fur Quantenoptik, Hans-Kopfermann-Strasse 1, D-85748 Garching, Germany. tobias.wilken@mpq.mpg.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22660320" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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