ALBERT

Description: The kinetochore is the crucial apparatus regulating chromosome segregation in mitosis and meiosis. Particularly in meiosis I, unlike in mitosis, sister kinetochores are captured by microtubules emanating from the same spindle pole (mono-orientation) and centromeric cohesion mediated by cohesin is protected in the following anaphase. Although meiotic kinetochore factors have been identified only in budding and fission yeasts, these molecules and their functions are thought to have diverged earlier. Therefore, a conserved mechanism for meiotic kinetochore regulation remains elusive. Here we have identified in mouse a meiosis-specific kinetochore factor that we termed MEIKIN, which functions in meiosis I but not in meiosis II or mitosis. MEIKIN plays a crucial role in both mono-orientation and centromeric cohesion protection, partly by stabilizing the localization of the cohesin protector shugoshin. These functions are mediated mainly by the activity of Polo-like kinase PLK1, which is enriched to kinetochores in a MEIKIN-dependent manner. Our integrative analysis indicates that the long-awaited key regulator of meiotic kinetochore function is Meikin, which is conserved from yeasts to humans.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Jihye -- Ishiguro, Kei-ichiro -- Nambu, Aya -- Akiyoshi, Bungo -- Yokobayashi, Shihori -- Kagami, Ayano -- Ishiguro, Tadashi -- Pendas, Alberto M -- Takeda, Naoki -- Sakakibara, Yogo -- Kitajima, Tomoya S -- Tanno, Yuji -- Sakuno, Takeshi -- Watanabe, Yoshinori -- England -- Nature. 2015 Jan 22;517(7535):466-71. doi: 10.1038/nature14097. Epub 2014 Dec 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1Yayoi, Tokyo 113-0032, Japan. ; Instituto de Biologia Molecular y Celular del Cancer (CSIC-USAL), 37007 Salamanca, Spain. ; Center for Animal Resources and Development, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811 Japan. ; Laboratory for Chromosome Segregation, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25533956" target="_blank"〉PubMed〈/a〉

Description: Tubulin is a major component of the eukaryotic cytoskeleton, controlling cell shape, structure and dynamics, whereas its bacterial homologue FtsZ establishes the cytokinetic ring that constricts during cell division. How such different roles of tubulin and FtsZ evolved is unknown. Studying Archaea may provide clues as these organisms share characteristics with Eukarya and Bacteria. Here we report the structure and function of proteins from a distinct family related to tubulin and FtsZ, named CetZ, which co-exists with FtsZ in many archaea. CetZ X-ray crystal structures showed the FtsZ/tubulin superfamily fold, and one crystal form contained sheets of protofilaments, suggesting a structural role. However, inactivation of CetZ proteins in Haloferax volcanii did not affect cell division. Instead, CetZ1 was required for differentiation of the irregular plate-shaped cells into a rod-shaped cell type that was essential for normal swimming motility. CetZ1 formed dynamic cytoskeletal structures in vivo, relating to its capacity to remodel the cell envelope and direct rod formation. CetZ2 was also implicated in H. volcanii cell shape control. Our findings expand the known roles of the FtsZ/tubulin superfamily to include archaeal cell shape dynamics, suggesting that a cytoskeletal role might predate eukaryotic cell evolution, and they support the premise that a major function of the microbial rod shape is to facilitate swimming.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4369195/" 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/PMC4369195/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Duggin, Iain G -- Aylett, Christopher H S -- Walsh, James C -- Michie, Katharine A -- Wang, Qing -- Turnbull, Lynne -- Dawson, Emma M -- Harry, Elizabeth J -- Whitchurch, Cynthia B -- Amos, Linda A -- Lowe, Jan -- MC_U105184326/Medical Research Council/United Kingdom -- U105184326/Medical Research Council/United Kingdom -- England -- Nature. 2015 Mar 19;519(7543):362-5. doi: 10.1038/nature13983. Epub 2014 Dec 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK [2] The ithree institute, University of Technology Sydney, New South Wales 2007, Australia. ; Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK. ; 1] The ithree institute, University of Technology Sydney, New South Wales 2007, Australia [2] School of Physics, University of New South Wales, Sydney, New South Wales 2052, Australia. ; The ithree institute, University of Technology Sydney, New South Wales 2007, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25533961" target="_blank"〉PubMed〈/a〉

Description: To provide context for the diversification of archosaurs--the group that includes crocodilians, dinosaurs, and birds--we generated draft genomes of three crocodilians: Alligator mississippiensis (the American alligator), Crocodylus porosus (the saltwater crocodile), and Gavialis gangeticus (the Indian gharial). We observed an exceptionally slow rate of genome evolution within crocodilians at all levels, including nucleotide substitutions, indels, transposable element content and movement, gene family evolution, and chromosomal synteny. When placed within the context of related taxa including birds and turtles, this suggests that the common ancestor of all of these taxa also exhibited slow genome evolution and that the comparatively rapid evolution is derived in birds. The data also provided the opportunity to analyze heterozygosity in crocodilians, which indicates a likely reduction in population size for all three taxa through the Pleistocene. Finally, these data combined with newly published bird genomes allowed us to reconstruct the partial genome of the common ancestor of archosaurs, thereby providing a tool to investigate the genetic starting material of crocodilians, birds, and dinosaurs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4386873/" 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/PMC4386873/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Green, Richard E -- Braun, Edward L -- Armstrong, Joel -- Earl, Dent -- Nguyen, Ngan -- Hickey, Glenn -- Vandewege, Michael W -- St John, John A -- Capella-Gutierrez, Salvador -- Castoe, Todd A -- Kern, Colin -- Fujita, Matthew K -- Opazo, Juan C -- Jurka, Jerzy -- Kojima, Kenji K -- Caballero, Juan -- Hubley, Robert M -- Smit, Arian F -- Platt, Roy N -- Lavoie, Christine A -- Ramakodi, Meganathan P -- Finger, John W Jr -- Suh, Alexander -- Isberg, Sally R -- Miles, Lee -- Chong, Amanda Y -- Jaratlerdsiri, Weerachai -- Gongora, Jaime -- Moran, Christopher -- Iriarte, Andres -- McCormack, John -- Burgess, Shane C -- Edwards, Scott V -- Lyons, Eric -- Williams, Christina -- Breen, Matthew -- Howard, Jason T -- Gresham, Cathy R -- Peterson, Daniel G -- Schmitz, Jurgen -- Pollock, David D -- Haussler, David -- Triplett, Eric W -- Zhang, Guojie -- Irie, Naoki -- Jarvis, Erich D -- Brochu, Christopher A -- Schmidt, Carl J -- McCarthy, Fiona M -- Faircloth, Brant C -- Hoffmann, Federico G -- Glenn, Travis C -- Gabaldon, Toni -- Paten, Benedict -- Ray, David A -- 1U41HG006992-2/HG/NHGRI NIH HHS/ -- 1U41HG007234-01/HG/NHGRI NIH HHS/ -- 5U01HG004695/HG/NHGRI NIH HHS/ -- R01 HG002939/HG/NHGRI NIH HHS/ -- U41 HG006992/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Dec 12;346(6215):1254449. doi: 10.1126/science.1254449. Epub 2014 Dec 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biomolecular Engineering, University of California, Santa Cruz, CA 95064, USA. ed@soe.ucsc.edu david.a.ray@ttu.edu. ; Department of Biology and Genetics Institute, University of Florida, Gainesville, FL 32611, USA. ; Department of Biomolecular Engineering, University of California, Santa Cruz, CA 95064, USA. Center for Biomolecular Science and Engineering, University of California, Santa Cruz, CA 95064, USA. ; Department of Biochemistry, Molecular Biology, Entomology and Plant Pathology, Mississippi State University, Mississippi State, MS 39762, USA. ; Department of Biomolecular Engineering, University of California, Santa Cruz, CA 95064, USA. ; Bioinformatics and Genomics Programme, Centre for Genomic Regulation, 08003 Barcelona, Spain. Universitat Pompeu Fabra, 08003 Barcelona, Spain. ; Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO 80045, USA. Department of Biology, University of Texas, Arlington, TX 76019, USA. ; Department of Computer and Information Sciences, University of Delaware, Newark, DE 19717, USA. ; Department of Biology, University of Texas, Arlington, TX 76019, USA. ; Instituto de Ciencias Ambientales y Evolutivas, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile. ; Genetic Information Research Institute, Mountain View, CA 94043, USA. ; Institute for Systems Biology, Seattle, WA 98109, 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 Environmental Health Science, University of Georgia, Athens, GA 30602, USA. ; Institute of Experimental Pathology (ZMBE), University of Munster, D-48149 Munster, Germany. Department of Evolutionary Biology (EBC), Uppsala University, SE-752 36 Uppsala, Sweden. ; Porosus Pty. Ltd., Palmerston, NT 0831, Australia. Faculty of Veterinary Science, University of Sydney, Sydney, NSW 2006, Australia. Centre for Crocodile Research, Noonamah, NT 0837, Australia. ; Faculty of Veterinary Science, University of Sydney, Sydney, NSW 2006, Australia. ; Departamento de Desarrollo Biotecnologico, Instituto de Higiene, Facultad de Medicina, Universidad de la Republica, Montevideo, Uruguay. ; Moore Laboratory of Zoology, Occidental College, Los Angeles, CA 90041, USA. ; College of Agriculture and Life Sciences, University of Arizona, Tucson, AZ 85721, USA. ; Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA. ; School of Plant Sciences, University of Arizona, Tucson, AZ 85721, USA. ; Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh, NC 27607, USA. ; Howard Hughes Medical Institute, Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA. ; Institute for Genomics, Biocomputing and Biotechnology, Mississippi State University, Mississippi State, MS 39762, USA. ; Institute for Genomics, Biocomputing and Biotechnology, Mississippi State University, Mississippi State, MS 39762, USA. Department of Plant and Soil Sciences, Mississippi State University, Mississippi State, MS 39762, USA. ; Institute of Experimental Pathology (ZMBE), University of Munster, D-48149 Munster, Germany. ; Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO 80045, USA. ; Center for Biomolecular Science and Engineering, University of California, Santa Cruz, CA 95064, USA. Howard Hughes Medical Institute, Bethesda, MD 20814, USA. ; Department of Microbiology and Cell Science, University of Florida, Gainesville, FL 32611, USA. ; China National GeneBank, BGI-Shenzhen, Shenzhen, China. Center for Social Evolution, Department of Biology, University of Copenhagen, Copenhagen, Denmark. ; Department of Biological Sciences, Graduate School of Science, University of Tokyo, Tokyo, Japan. ; Department of Earth and Environmental Sciences, University of Iowa, Iowa City, IA 52242, USA. ; Department of Animal and Food Sciences, University of Delaware, Newark, DE 19717, USA. ; School of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, AZ 85721, USA. ; Department of Ecology and Evolutionary Biology, University of California, Los Angeles, CA 90019, USA. Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA. ; Bioinformatics and Genomics Programme, Centre for Genomic Regulation, 08003 Barcelona, Spain. Universitat Pompeu Fabra, 08003 Barcelona, Spain. Institucio Catalana de Recerca i Estudis Avancats, 08010 Barcelona, Spain. ; Center for Biomolecular Science and Engineering, University of California, Santa Cruz, CA 95064, 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. ed@soe.ucsc.edu david.a.ray@ttu.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25504731" 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: The emergence of artemisinin resistance in Southeast Asia imperils efforts to reduce the global malaria burden. We genetically modified the Plasmodium falciparum K13 locus using zinc-finger nucleases and measured ring-stage survival rates after drug exposure in vitro; these rates correlate with parasite clearance half-lives in artemisinin-treated patients. With isolates from Cambodia, where resistance first emerged, survival rates decreased from 13 to 49% to 0.3 to 2.4% after the removal of K13 mutations. Conversely, survival rates in wild-type parasites increased from 〈/=0.6% to 2 to 29% after the insertion of K13 mutations. These mutations conferred elevated resistance to recent Cambodian isolates compared with that of reference lines, suggesting a contemporary contribution of additional genetic factors. Our data provide a conclusive rationale for worldwide K13-propeller sequencing to identify and eliminate artemisinin-resistant parasites.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4349400/" 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/PMC4349400/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Straimer, Judith -- Gnadig, Nina F -- Witkowski, Benoit -- Amaratunga, Chanaki -- Duru, Valentine -- Ramadani, Arba Pramundita -- Dacheux, Melanie -- Khim, Nimol -- Zhang, Lei -- Lam, Stephen -- Gregory, Philip D -- Urnov, Fyodor D -- Mercereau-Puijalon, Odile -- Benoit-Vical, Francoise -- Fairhurst, Rick M -- Menard, Didier -- Fidock, David A -- R01 AI109023/AI/NIAID NIH HHS/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2015 Jan 23;347(6220):428-31. doi: 10.1126/science.1260867. Epub 2014 Dec 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, New York, NY, USA. ; Malaria Molecular Epidemiology Unit, Institut Pasteur du Cambodge, Phnom Penh, Cambodia. ; Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. ; Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie de Coordination UPR8241, Toulouse, France. Universite de Toulouse, UPS, Institut National Polytechnique de Toulouse, Toulouse, France. ; Sangamo BioSciences, Richmond, CA, USA. ; Institut Pasteur, Parasite Molecular Immunology Unit, Paris, France. ; Department of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, New York, NY, USA. Division of Infectious Diseases, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA. df2260@columbia.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25502314" target="_blank"〉PubMed〈/a〉

Description: The widespread reorganization of cellular architecture in mitosis is achieved through extensive protein phosphorylation, driven by the coordinated activation of a mitotic kinase network and repression of counteracting phosphatases. Phosphatase activity must subsequently be restored to promote mitotic exit. Although Cdc14 phosphatase drives this reversal in budding yeast, protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A) activities have each been independently linked to mitotic exit control in other eukaryotes. Here we describe a mitotic phosphatase relay in which PP1 reactivation is required for the reactivation of both PP2A-B55 and PP2A-B56 to coordinate mitotic progression and exit in fission yeast. The staged recruitment of PP1 (the Dis2 isoform) to the regulatory subunits of the PP2A-B55 and PP2A-B56 (B55 also known as Pab1; B56 also known as Par1) holoenzymes sequentially activates each phosphatase. The pathway is blocked in early mitosis because the Cdk1-cyclin B kinase (Cdk1 also known as Cdc2) inhibits PP1 activity, but declining cyclin B levels later in mitosis permit PP1 to auto-reactivate. PP1 first reactivates PP2A-B55; this enables PP2A-B55 in turn to promote the reactivation of PP2A-B56 by dephosphorylating a PP1-docking site in PP2A-B56, thereby promoting the recruitment of PP1. PP1 recruitment to human, mitotic PP2A-B56 holoenzymes and the sequences of these conserved PP1-docking motifs suggest that PP1 regulates PP2A-B55 and PP2A-B56 activities in a variety of signalling contexts throughout eukaryotes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338534/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338534/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grallert, Agnes -- Boke, Elvan -- Hagting, Anja -- Hodgson, Ben -- Connolly, Yvonne -- Griffiths, John R -- Smith, Duncan L -- Pines, Jonathon -- Hagan, Iain M -- 092096/Wellcome Trust/United Kingdom -- A13678/Cancer Research UK/United Kingdom -- A16406/Cancer Research UK/United Kingdom -- C147/A16406/Cancer Research UK/United Kingdom -- C29/A13678/Cancer Research UK/United Kingdom -- England -- Nature. 2015 Jan 1;517(7532):94-8. doi: 10.1038/nature14019. Epub 2014 Dec 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cell Division Group, CRUK Manchester Institute, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK. ; The Gurdon Institute, Tennis Court Road, University of Cambridge, Cambridge, CB2 1QN, UK. ; Biological Mass Spectrometry, CRUK Manchester Institute, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25487150" target="_blank"〉PubMed〈/a〉

Description: Distinct types of CD4(+) T cells protect the host against different classes of pathogens. However, it is unclear whether a given pathogen induces a single type of polarized T cell. By combining antigenic stimulation and T cell receptor deep sequencing, we found that human pathogen- and vaccine-specific T helper 1 (T(H)1), T(H)2, and T(H)17 memory cells have different frequencies but comparable diversity and comprise not only clones polarized toward a single fate, but also clones whose progeny have acquired multiple fates. Single naive T cells primed by a pathogen in vitro could also give rise to multiple fates. Our results unravel an unexpected degree of interclonal and intraclonal functional heterogeneity of the human T cell response and suggest that polarized responses result from preferential expansion rather than priming.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Becattini, Simone -- Latorre, Daniela -- Mele, Federico -- Foglierini, Mathilde -- De Gregorio, Corinne -- Cassotta, Antonino -- Fernandez, Blanca -- Kelderman, Sander -- Schumacher, Ton N -- Corti, Davide -- Lanzavecchia, Antonio -- Sallusto, Federica -- New York, N.Y. -- Science. 2015 Jan 23;347(6220):400-6. doi: 10.1126/science.1260668. Epub 2014 Dec 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Research in Biomedicine, Bellinzona, Universita della Svizzera Italiana, Lugano, Switzerland. Institute of Microbiology, ETH Zurich, Zurich, Switzerland. ; Institute for Research in Biomedicine, Bellinzona, Universita della Svizzera Italiana, Lugano, Switzerland. ; Division of Immunology, Netherlands Cancer Institute, Amsterdam, Netherlands. ; Institute for Research in Biomedicine, Bellinzona, Universita della Svizzera Italiana, Lugano, Switzerland. federica.sallusto@irb.usi.ch.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25477212" target="_blank"〉PubMed〈/a〉

Description: Contusive spinal cord injury leads to a variety of disabilities owing to limited neuronal regeneration and functional plasticity. It is well established that an upregulation of glial-derived chondroitin sulphate proteoglycans (CSPGs) within the glial scar and perineuronal net creates a barrier to axonal regrowth and sprouting. Protein tyrosine phosphatase sigma (PTPsigma), along with its sister phosphatase leukocyte common antigen-related (LAR) and the nogo receptors 1 and 3 (NgR), have recently been identified as receptors for the inhibitory glycosylated side chains of CSPGs. Here we find in rats that PTPsigma has a critical role in converting growth cones into a dystrophic state by tightly stabilizing them within CSPG-rich substrates. We generated a membrane-permeable peptide mimetic of the PTPsigma wedge domain that binds to PTPsigma and relieves CSPG-mediated inhibition. Systemic delivery of this peptide over weeks restored substantial serotonergic innervation to the spinal cord below the level of injury and facilitated functional recovery of both locomotor and urinary systems. Our results add a new layer of understanding to the critical role of PTPsigma in mediating the growth-inhibited state of neurons due to CSPGs within the injured adult spinal cord.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4336236/" 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/PMC4336236/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lang, Bradley T -- Cregg, Jared M -- DePaul, Marc A -- Tran, Amanda P -- Xu, Kui -- Dyck, Scott M -- Madalena, Kathryn M -- Brown, Benjamin P -- Weng, Yi-Lan -- Li, Shuxin -- Karimi-Abdolrezaee, Soheila -- Busch, Sarah A -- Shen, Yingjie -- Silver, Jerry -- NS025713/NS/NINDS NIH HHS/ -- R01 EY024575/EY/NEI NIH HHS/ -- R01 NS025713/NS/NINDS NIH HHS/ -- R01 NS079432/NS/NINDS NIH HHS/ -- England -- Nature. 2015 Feb 19;518(7539):404-8. doi: 10.1038/nature13974. Epub 2014 Dec 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA. ; Center for Brain and Spinal Cord Repair, Department of Neuroscience, Wexner Medical Center at The Ohio State University, Columbus, Ohio 43210, USA. ; Regenerative Medicine Program and Department of Physiology, University of Manitoba, Winnipeg, Manitoba R3E 0J9, Canada. ; Baldwin Wallace University, Berea, Ohio 44017, USA. ; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, USA. ; Shriners Hospital's Pediatric Research Center (Center for Neural Repair and Rehabilitation), Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25470046" 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: Chromosome segregation depends on sister chromatid cohesion mediated by cohesin. The cohesin subunits Smc1, Smc3, and Scc1 form tripartite rings that are thought to open at distinct sites to allow entry and exit of DNA. However, direct evidence for the existence of open forms of cohesin is lacking. We found that cohesin's proposed DNA exit gate is formed by interactions between Scc1 and the coiled-coil region of Smc3. Mutation of this interface abolished cohesin's ability to stably associate with chromatin and to mediate cohesion. Electron microscopy revealed that weakening of the Smc3-Scc1 interface resulted in opening of cohesin rings, as did proteolytic cleavage of Scc1. These open forms may resemble intermediate states of cohesin normally generated by the release factor Wapl and the protease separase, respectively.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Huis in 't Veld, Pim J -- Herzog, Franz -- Ladurner, Rene -- Davidson, Iain F -- Piric, Sabina -- Kreidl, Emanuel -- Bhaskara, Venugopal -- Aebersold, Ruedi -- Peters, Jan-Michael -- New York, N.Y. -- Science. 2014 Nov 21;346(6212):968-72. doi: 10.1126/science.1256904.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), 1030 Vienna, Austria. ; Department of Biology, Institute of Molecular Systems Biology, Eidgenossische Technische Hochschule (ETH) Zurich, 8093 Zurich, Switzerland. Department of Biochemistry, Gene Center, Ludwig-Maximilian University, 81377 Munich, Germany. ; Department of Biology, Institute of Molecular Systems Biology, Eidgenossische Technische Hochschule (ETH) Zurich, 8093 Zurich, Switzerland. ; Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), 1030 Vienna, Austria. peters@imp.ac.at.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25414306" target="_blank"〉PubMed〈/a〉