ALBERT

Description: Author(s): Y. J. Ko, B. R. Kim, J. Y. Kim, B. Y. Han, C. H. Jang, E. J. Jeon, K. K. Joo, H. J. Kim, H. S. Kim, Y. D. Kim, Jaison Lee, J. Y. Lee, M. H. Lee, Y. M. Oh, H. K. Park, H. S. Park, K. S. Park, K. M. Seo, Kim Siyeon, and G. M. Sun (NEOS Collaboration) An experiment to search for light sterile neutrinos is conducted at a reactor with a thermal power of 2.8 GW located at the Hanbit nuclear power complex. The search is done with a detector consisting of a ton of Gd-loaded liquid scintillator in a tendon gallery approximately 24 m from the reactor co… [Phys. Rev. Lett. 118, 121802] Published Tue Mar 21, 2017

Description: Z-DNA binding proteins (ZBPs) play important roles in RNA editing, innate immune response and viral infection. Structural and biophysical studies show that ZBPs initially form an intermediate complex with B-DNA for B–Z conversion. However, a comprehensive understanding of the mechanism of Z-DNA binding and B–Z transition is still lacking, due to the absence of structural information on the intermediate complex. Here, we report the solution structure of the Zα domain of the ZBP-containing protein kinase from Carassius auratus (caZα PKZ ). We quantitatively determined the binding affinity of caZα PKZ for both B-DNA and Z-DNA and characterized its B–Z transition activity, which is modulated by varying the salt concentration. Our results suggest that the intermediate complex formed by caZα PKZ and B-DNA can be used as molecular ruler, to measure the degree to which DNA transitions to the Z isoform.

Description: Palmitate induces ER calcium depletion and apoptosis in mouse podocytes subsequent to mitochondrial oxidative stress Cell Death and Disease 6, e1976 (November 2015). doi:10.1038/cddis.2015.331 Authors: S Xu, S M Nam, J-H Kim, R Das, S-K Choi, T T Nguyen, X Quan, S J Choi, C H Chung, E Y Lee, I-K Lee, A Wiederkehr, C B Wollheim, S-K Cha & K-S Park

Description: For ultrasensitive magnetic resonance imaging (MRI), magnetic nanoparticles with extremely high r2 relaxivity are strongly desired. Magnetosome-like nanoparticles were prepared by coating polyethylene glycol-phospholipid (PEG-phospholipid) onto ferrimagnetic iron oxide nanocubes (FIONs). FIONs exhibited a very high relaxivity (r2) of 324 mM-1 s-1, allowing efficient labeling of various kinds of cells. The magnetic resonance (MR) imaging of single cells labeled with FIONs is demonstrated not only in vitro but also in vivo. Pancreatic islet grafts and their rejection could be imaged using FIONs on a 1.5 T clinical MRI scanner. The strong contrast effect of FIONs enabled MR imaging of transplanted islets in small rodents as well as in large animals. Therefore, we expect that MR imaging of pancreatic islet grafts using FIONs has the potentials for clinical applications. Furthermore, FIONs will enable highly sensitive noninvasive assessment after cell transplantation.

Description: In the large-quantity production of α2,3- and α2,6-sialyllactose (Neu5Ac(α2,3)Galβ1,4Glc (3'-SL) and Neu5Ac(α2,6)Galβ1,4Glc (6'-SL)) using sialyltransferases (STs), there are major hurdles to overcome for further improvement in yield and productivity of the enzyme reactions. Specifically, Pasteurella multocida α2,3-sialyltransferase (α2,3PST) forms a by-product to a certain extent, owing to its multifunctional activity at pH below 7.0, and Photobacterium damselae α2,6-sialyltransferase (α2,6PdST) shows relatively low ST activity. In this study, α2,3PST and α2,6PdST were successfully engineered using a hybrid approach that combines rational design with site-saturation mutagenesis. Narrowly focused on the substrate-binding pocket of the STs, putative functional residues were selected by multiple sequence alignment and alanine scanning, and subsequently subjected to site-saturation mutagenesis. In the case of α2,3PST, R313N single mutation improved its activity slightly (by a factor of 1.5), and further improvement was obtained by making the double mutants (R313N/T265S and R313H/T265S) resulting in an overall 2-fold improvement in its specific α2,3 ST activity, which is mainly caused by the increase in k cat . It was revealed that the R313 mutations to N, D, Y, H or T greatly reduced the α2,6 ST side-reaction activity of α2,3PST at below pH 7.0. In the case of α2,6PdST, single-mutation L433S/T and double-mutation I411T/L433T exhibited 3- and 5-fold enhancement of the α2,6 ST-specific activity compared with the wild-type, respectively, via increase in k cat values. Our results show a very good model system for enhancing ST activity and demonstrate that the generated mutants could be used efficiently for the mass production of 3'-SL and 6'-SL with enhanced productivity and yield.

Description: Dynamic modulation of ion channels by phosphorylation underlies neuronal plasticity. The Kv2.1 potassium channel is highly phosphorylated in resting mammalian neurons. Activity-dependent Kv2.1 dephosphorylation by calcineurin induces graded hyperpolarizing shifts in voltage-dependent activation, causing suppression of neuronal excitability. Mass spectrometry-SILAC (stable isotope labeling with amino acids in cell culture) identified 16 Kv2.1 phosphorylation sites, of which 7 were dephosphorylated by calcineurin. Mutation of individual calcineurin-regulated sites to alanine produced incremental shifts mimicking dephosphorylation, whereas mutation to aspartate yielded equivalent resistance to calcineurin. Mutations at multiple sites were additive, showing that variable phosphorylation of Kv2.1 at a large number of sites allows graded activity-dependent regulation of channel gating and neuronal firing properties.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Park, Kang-Sik -- Mohapatra, Durga P -- Misonou, Hiroaki -- Trimmer, James S -- NS42225/NS/NINDS NIH HHS/ -- R01 NS042225/NS/NINDS NIH HHS/ -- R01 NS042225-06/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2006 Aug 18;313(5789):976-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, School of Medicine, University of California, Davis, CA 95616, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16917065" target="_blank"〉PubMed〈/a〉

Description: Author(s): Y-G. Son, J.-Y. Kim, C. Mitsuda, K. Kobayashi, J. Ko, T-Y. Lee, J-Y. Choi, D-E. Kim, H-S. Seo, H-S. Han, K-S. Park, C-D. Park, and S. Shin This paper describes a start-to-end study of the suppression of stored-beam oscillation during top-up injection at the Pohang Light Source (PLS-II) beam line. The fast counterkicker implemented in PLS-II suppresses stored-beam oscillations in the vertical plane. During top-up injection in the magnet... [Phys. Rev. Accel. Beams 20, 082803] Published Wed Aug 30, 2017

Description: We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Deltaex2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉George, Julie -- Lim, Jing Shan -- Jang, Se Jin -- Cun, Yupeng -- Ozretic, Luka -- Kong, Gu -- Leenders, Frauke -- Lu, Xin -- Fernandez-Cuesta, Lynnette -- Bosco, Graziella -- Muller, Christian -- Dahmen, Ilona -- Jahchan, Nadine S -- Park, Kwon-Sik -- Yang, Dian -- Karnezis, Anthony N -- Vaka, Dedeepya -- Torres, Angela -- Wang, Maia Segura -- Korbel, Jan O -- Menon, Roopika -- Chun, Sung-Min -- Kim, Deokhoon -- Wilkerson, Matt -- Hayes, Neil -- Engelmann, David -- Putzer, Brigitte -- Bos, Marc -- Michels, Sebastian -- Vlasic, Ignacija -- Seidel, Danila -- Pinther, Berit -- Schaub, Philipp -- Becker, Christian -- Altmuller, Janine -- Yokota, Jun -- Kohno, Takashi -- Iwakawa, Reika -- Tsuta, Koji -- Noguchi, Masayuki -- Muley, Thomas -- Hoffmann, Hans -- Schnabel, Philipp A -- Petersen, Iver -- Chen, Yuan -- Soltermann, Alex -- Tischler, Verena -- Choi, Chang-min -- Kim, Yong-Hee -- Massion, Pierre P -- Zou, Yong -- Jovanovic, Dragana -- Kontic, Milica -- Wright, Gavin M -- Russell, Prudence A -- Solomon, Benjamin -- Koch, Ina -- Lindner, Michael -- Muscarella, Lucia A -- la Torre, Annamaria -- Field, John K -- Jakopovic, Marko -- Knezevic, Jelena -- Castanos-Velez, Esmeralda -- Roz, Luca -- Pastorino, Ugo -- Brustugun, Odd-Terje -- Lund-Iversen, Marius -- Thunnissen, Erik -- Kohler, Jens -- Schuler, Martin -- Botling, Johan -- Sandelin, Martin -- Sanchez-Cespedes, Montserrat -- Salvesen, Helga B -- Achter, Viktor -- Lang, Ulrich -- Bogus, Magdalena -- Schneider, Peter M -- Zander, Thomas -- Ansen, Sascha -- Hallek, Michael -- Wolf, Jurgen -- Vingron, Martin -- Yatabe, Yasushi -- Travis, William D -- Nurnberg, Peter -- Reinhardt, Christian -- Perner, Sven -- Heukamp, Lukas -- Buttner, Reinhard -- Haas, Stefan A -- Brambilla, Elisabeth -- Peifer, Martin -- Sage, Julien -- Thomas, Roman K -- 5R01CA114102-08/CA/NCI NIH HHS/ -- England -- Nature. 2015 Aug 6;524(7563):47-53. doi: 10.1038/nature14664. Epub 2015 Jul 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, Medical Faculty, University of Cologne, 50931 Cologne, Germany. ; Departments of Pediatrics and Genetics, Stanford University, Stanford, California 94305, USA. ; Department of Pathology and Center for Cancer Genome Discovery, University of Ulsan College of Medicine, Asan Medical Center 88, Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea. ; Department of Pathology, University Hospital Cologne, 50937 Cologne, Germany. ; Department of Pathology, College of Medicine, Hanyang University. 222 Wangsimniro, Seongdong-gu, Seoul 133-791, Korea. ; Vancouver General Hospital, Terry Fox laboratory, Vancouver, British Columbia V5Z 1L3, Canada. ; European Molecular Biology Laboratory, Genome Biology Unit, 69117 Heidelberg, Germany. ; Institute of Pathology, Center of Integrated Oncology Cologne-Bonn, University Hospital of Bonn, 53127 Bonn, Germany. ; Center for Cancer Genome Discovery, University of Ulsan College of Medicine, Asan Medical Center 88, Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea. ; Department of Genetics, Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, North Carolina 27599-7295, USA. ; UNC Lineberger Comprehensive Cancer Center School of Medicine, University of North Carolina at Chapel Hill, North Carolina 27599-7295, USA. ; Institute of Experimental Gene Therapy and Cancer Research, Rostock University Medical Center, 18057 Rostock, Germany. ; Department I of Internal Medicine, Center of Integrated Oncology Cologne-Bonn, University Hospital Cologne, 50937 Cologne, Germany. ; Department of Internal Medicine, University Hospital of Cologne, 50931 Cologne, Germany. ; Cologne Center for Genomics (CCG), University of Cologne, 50931 Cologne, Germany. ; 1] Cologne Center for Genomics (CCG), University of Cologne, 50931 Cologne, Germany. [2] Institute of Human Genetics, University Hospital Cologne, 50931 Cologne, Germany. ; 1] Division of Genome Biology, National Cancer Center Research Institute, Chuo-ku, Tokyo 1040045, Japan. [2] Genomics and Epigenomics of Cancer Prediction Program, Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Barcelona 08916, Spain. ; Division of Genome Biology, National Cancer Center Research Institute, Chuo-ku, Tokyo 1040045, Japan. ; Department of Pathology and Clinical Laboratories, National Cancer Center Hospital Chuo-ku, Tokyo 1040045, Japan. ; Department of Pathology, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8575, Japan. ; 1] Thoraxklinik at University Hospital Heidelberg, Amalienstrasse 5, 69126 Heidelberg, Germany. [2] Translational Lung Research Center Heidelberg (TLRC-H), Member of German Center for Lung Research (DZL), Amalienstrasse 5, 69126 Heidelberg, Germany. ; Thoraxklinik at University Hospital Heidelberg, Amalienstrasse 5, 69126 Heidelberg, Germany. ; 1] Translational Lung Research Center Heidelberg (TLRC-H), Member of German Center for Lung Research (DZL), Amalienstrasse 5, 69126 Heidelberg, Germany. [2] Institute of Pathology, University of Heidelberg, Im Neuenheimer Feld 220, 69120 Heidelberg, Germany. ; Institute of Pathology, Jena University Hospital, Friedrich-Schiller-University, 07743 Jena, Germany. ; Institute of Surgical Pathology, University Hospital Zurich, 8091 Zurich, Switzerland. ; Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea. ; Department of Thoracic and Cardiovascular Surgery, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea. ; Thoracic Program, Vanderbilt-Ingram Cancer Center PRB 640, 2220 Pierce Avenue, Nashville, Tennessee 37232, USA. ; University Hospital of Pulmonology, Clinical Center of Serbia, Medical School, University of Belgrade, 11000 Belgrade, Serbia. ; Department of Surgery, St. Vincent's Hospital, Peter MacCallum Cancer Centre, 3065 Melbourne, Victoria, Australia. ; Department of Pathology, St. Vincent's Hospital, Peter MacCallum Cancer Centre, 3065 Melbourne, Victoria, Australia. ; Department of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, 3065 Melbourne, Victoria, Australia. ; Asklepios Biobank fur Lungenerkrankungen, Comprehensive Pneumology Center Munich, Member of the German Center for Lung Research (DZL), Asklepios Fachkliniken Munchen-Gauting 82131, Germany. ; Laboratory of Oncology, IRCCS Casa Sollievo della Sofferenza, Viale Cappuccini, 71013 San Giovanni, Rotondo, Italy. ; Roy Castle Lung Cancer Research Programme, Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, The University of Liverpool Cancer Research Centre, 200 London Road, L69 3GA Liverpool, UK. ; University of Zagreb, School of Medicine, Department for Respiratory Diseases Jordanovac, University Hospital Center Zagreb, 10000 Zagreb, Croatia. ; Laboratory for Translational Medicine, Rudjer Boskovic Institute, 10000 Zagreb, Croatia. ; Charite Comprehensive Cancer Center, Charite Campus Mitte, 10115 Berlin, Germany. ; Tumor Genomics Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS - Istituto Nazionale Tumori, Via Venezian 1, 20133 Milan, Italy. ; Thoracic Surgery Unit, Department of Surgery, Fondazione IRCCS Istituto Nazionale Tumori, 20133 Milan, Italy. ; 1] Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, N-0424 Oslo, Norway. [2] Department of Oncology, Norwegian Radium Hospital, Oslo University Hospital, N-0310 Oslo, Norway. ; Department of Pathology, Norwegian Radium Hospital, Oslo University Hospital, N-0310 Oslo, Norway. ; Department of Pathology, VU University Medical Center, 1007 MB Amsterdam, The Netherlands. ; 1] West German Cancer Center, Department of Medical Oncology, University Hospital Essen, 45147 Essen, Germany. [2] German Cancer Consortium (DKTK), 69120 Heidelberg, Germany. ; Departments of Immunology, Genetics and Pathology, and Medical Sciences, Respiratory, Allergy and Sleep Research, Uppsala University, 75185 Uppsala, Sweden. ; Genes and Cancer Group, Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), 08908 Hospitalet de Llobregat, Barcelona, Spain. ; 1] Department of Clinical Science, Center for Cancer Biomarkers, University of Bergen, N-5058 Bergen, Norway. [2] Department of Gynecology and Obstetrics, Haukeland University Hospital, N-5058 Bergen, Norway. ; Computing Center, University of Cologne, 50931 Cologne, Germany. ; 1] Computing Center, University of Cologne, 50931 Cologne, Germany. [2] Department of Informatics, University of Cologne, 50931 Cologne, Germany. ; Institute of Legal Medicine, University of Cologne, 50823 Cologne, Germany. ; Gastrointestinal Cancer Group Cologne, Center of Integrated Oncology Cologne-Bonn, Department I for Internal Medicine, University Hospital of Cologne, 50937 Cologne, Germany. ; 1] Department I of Internal Medicine, Center of Integrated Oncology Cologne-Bonn, University Hospital Cologne, 50937 Cologne, Germany. [2] Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany. ; Computational Molecular Biology Group, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany. ; Department of Pathology and Molecular Diagnostics, Aichi Cancer Center, 464-8681 Nagoya, Japan. ; Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York 10065, USA. ; 1] Cologne Center for Genomics (CCG), University of Cologne, 50931 Cologne, Germany. [2] Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany. [3] Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany. ; Department of Pathology, CHU Grenoble INSERM U823, University Joseph Fourier, Institute Albert Bonniot 38043, CS10217 Grenoble, France. ; 1] Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, Medical Faculty, University of Cologne, 50931 Cologne, Germany. [2] Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany. ; 1] Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, Medical Faculty, University of Cologne, 50931 Cologne, Germany. [2] Department of Pathology, University Hospital Cologne, 50937 Cologne, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26168399" target="_blank"〉PubMed〈/a〉

Description: Substorms are known to sometimes occur even under northward interplanetary magnetic field (IMF) conditions. In this paper, we perform three-dimensional global magnetohydrodynamic (MHD) simulations to examine dayside reconnection, tail and ionospheric signatures for two cases of substorm observations under prolonged northward and dawnward IMF conditions: (1) A strongly northward/dawnward IMF case with B IMF  = (0, −20, 20) nT; (2) A weakley northward/dawnward IMF case with B IMF  = (0, −2, 2) nT. Thoughout the simulations, we used the constant solar wind conditions to reflect the prolonged solar wind conditions around the substorm times. We found that, in both cases, the tail reconnection occurred after the usual high-latitude reconnection on the dayside, providing a possible energy source for later triggered substorm observations under northward IMF conditions. The presence of an equal amount of IMF B y allows the high-latitude reconnected magnetic field lines to transport to the tail lobe, eventually leading to the tail reconnection. The simulation results also revealed the following major differences between the two cases: First, the reconnection onset (both on dayside and in the tail) occurs earlier in the strongly northward IMF case than in the weakly northward IMF case. Secondly, the polar cap size, which is finite in both cases despite the northward IMF conditions and thus supports the lobe energy build up needed for the substorm occurrences, is larger in the strongly northward IMF case. Accordingly the polar cap potential is far larger in the strongly northward IMF case (100 s of kV) than in the weakly northward IMF case (10s of kV). Thirdly, in the strongly northward IMF case, the strong earthward tail plasma flow appears to be caused by the enhanced convection (so, enhanced duskward E y ) due to the tail reconnection. In contrast, in the weakly northward IMF case, the earthward tail plasma flow increases gradually in association with a modestly increased duskward electric field. In addition, the inner plasma pressure and the cross tail current near the reconnection site increase significantly in the strongly northward IMF case but less significantly in the weakly northward IMF case after the onset of the tail reconnection. In conclusion, the simulation results support observations of the substorms under northward IMF conditions in the presence of an equal amount of IMF B y by demonstrating the energy input via dayside reconnection and the subsequent occurrence of the tail reconnection.