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Zaki MS, Masri A, Gregor A, Gleeson JG, Rosti RO
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Dandy-Walker malformation, genitourinary abnormalities, and intellectual disability in two families
AMERICAN JOURNAL OF MEDICAL GENETICS PART A 2015 NOV; 167(11):2503-2507
We report on two families, each with documented consanguinity and two affected with overlapping features of Dandy-Walker malformation, genitourinary abnormalities, intellectual disability, and hearing deficit. This phenotype shares similar findings with many well-known syndromes. However, the clinical findings of this syndrome categorize this as a new syndrome as compared with the phenotype of already established syndromes. Due to parental consanguinity, occurrence in siblings of both genders and the absence of manifestations in obligate carrier parents, an autosomal recessive pattern of inheritance is more likely. The authors believe that these families suggest a novel autosomal recessive cerebello-genital syndrome. Array CGH analyses of an affected did not show pathological deletions or duplications. (c) 2015 Wiley Periodicals, Inc.
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Teo WD, Thom J, Thompson J, Tucker J, Weng Y, Winstrom L, Wittich P, Winn D, Abdullin S, Albrow M, Anderson J, Apollinari G, Bauerdick LAT, Beretvas A, Berryhill J, Bhat PC, Bolla G, Burkett K, Butler JN, Cheung HWK, Chlebana F, Cihangir S, Elvira VD, Fisk I, Freeman J, Gottschalk E, Gray L, Green D, Grunendahl S, Gutsche O, Hanlon J, Hare D, Harris RM, Hirschauer J, Hooberman B, Jindariani S, Johnson M, Joshi U, Klima B, Kreis B, Kwan S, Linacre J, Lincoln D, Lipton R, Liu T, Lykken J, Maeshima K, Marraffino JM, Outschoorn VIM, Maruyama S, Mason D, McBride P, Merkel P, Mishra K, Mrenna S, Nahn S, Newman-Holmes C, O'Dell V, Prokofyev O, Sexton-Kennedy E, Sharma S, Soha A, Spalding WJ, Spiegel L, Taylor L, Tkaczyk S, Tran NV, Uplegger L, Vaandering EW, Vidal R, Whitbeck A, Whitmore J, Yang F, Acosta D, Avery P, Bortignon P, Bourilkov D, Carver M, Curry D, Das S, De Gruttola M, Di Giovanni GP, Field RD, Fisher M, Furic IK, Hugon J, Konigsberg J, Korytov A, Kypreos T, Low JF, Matchev K, 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Chakaberia I, Ivanov A, Kaadze K, Khalil S, Makouski M, Maravin Y, Saini LK, Skhirtladze N, Svintradze I, Gronberg J, Lange D, Rebassoo F, Wright D, Baden A, Belloni A, Calvert B, Eno SC, Gomez JA, Hadley NJ, Jabeen S, Kellogg RG, Kolberg T, Lu Y, Mignerey AC, Pedro K, Skuja A, Tonjes MB, Tonwar SC, Apyan A, Barbieri R, Bierwagen K, Busza W, Cali IA, Di Matteo L, Ceballos GG, Goncharov M, Gulhan D, Klute M, Lai YS, Lee YJ, Levin A, Luckey PD, Paus C, Ralph D, Roland C, Roland G, Stephans GSF, Sumorok K, Velicanu D, Veverka J, Wyslouch B, Yang M, Zanetti M, Zhukova V, Dahmes B, Gude A, Kao SC, Klapoetke K, Kubota Y, Mans J, Nourbakhsh S, Pastika N, Rusack R, Singovsky A, Tambe N, Turkewitz J, Acosta JG, Oliveros S, Avdeeva E, Bloom K, Bose S, Claes DR, Dominguez A, Suarez RG, Keller J, Knowlton D, Kravchenko I, Lazo-Flores J, Meier F, Ratnikov F, Snow GR, Zvada M, Dolen J, Godshalk A, Iashvili I, Kharchilava A, Kumar A, Rappoccio S, Alverson G, Barberis E, Baumgartel D, Chasco M, Massironi A, Morse DM, Nash D, Orimoto T, Trocino D, Wang RJ, Wood D, Zhang J, Hahn KA, Kubik A, Mucia N, Odell N, Pollack B, Pozdnyakov A, Schmitt M, Stoynev S, Sung K, Velasco M, Won S, Brinkerhoff A, Chan KM, Drozdetskiy A, Hildreth M, Jessop C, Karmgard DJ, Kellams N, Lannon K, Lynch S, Marinelli N, Musienko Y, Pearson T, Planer M, Ruchti R, Smith G, Valls N, Wayne M, Wolf M, Woodard A, Antonelli L, Brinson J, Bylsma B, Durkin LS, Flowers S, Hart A, Hill C, Hughes R, Kotov K, Ling TY, Luo W, Puigh D, Rodenburg M, Winer BL, Wolfe H, Wulsin HW, Driga O, Elmer P, Hardenbrook J, Hebda P, Koay SA, Lujan P, Marlow D, Medvedeva T, Mooney M, Olsen J, Piroue P, Quan X, Saka H, Stickland D, Tully C, Werner JS, Zuranski A, Brownson E, Malik S, Mendez H, Vargas JER, Barnes VE, Benedetti D, Bortoletto D, De Mattia M, Gutay L, Hu Z, Jha MK, Jones M, Jung K, Kress M, Leonardo N, Miller DH, Neumeister N, Primavera F, Radburn-Smith BC, Shi X, Shipsey I, Silvers D, Svyatkovskiy A, Wang F, Xie W, Xu L, Zablocki J, Parashar N, Stupak J, Adair A, Akgun B, Ecklund KM, Geurts FJM, Li W, Michlin B, Padley BP, Redjimi R, Roberts J, Zabel J, Betchart B, Bodek A, de Barbaro P, Demina R, Eshaq Y, Ferbel T, Galanti M, Garcia-Bellido A, Goldenzweig P, Han J, Harel A, Hindrichs O, Khukhunaishvili A, Korjenevski S, Petrillo G, Vishnevskiy D, Ciesielski R, Demortier L, Goulianos K, Mesropian C, Arora S, Barker A, Chou JP, Contreras-Campana C, Contreras-Campana E, Duggan D, Ferencek D, Gershtein Y, Gray R, Halkiadakis E, Hidas D, Kaplan S, Lath A, Panwalkar S, Park M, Patel R, Salur S, Schnetzer S, Sheffield D, Somalwar S, Stone R, Thomas S, Thomassen P, Walker M, Rose K, Spanier S, York A, Bouhali O, Hernandez AC, Eusebi R, Flanagan W, Gilmore J, Kamon T, Khotilovich V, Krutelyov V, Montalvo R, Osipenkov I, Pakhotin Y, Perloff A, Roe J, Rose A, Safonov A, Suarez I, Tatarinov A, Ulmer KA, Akchurin N, Cowden C, Damgov J, Dragoiu C, Dudero PR, Faulkner J, Kovitanggoon K, Kunori S, Lee SW, Libeiro T, Volobouev I, Appelt E, Delannoy AG, Greene S, Gurrola A, Johns W, Maguire C, Mao Y, Melo A, Sharma M, Sheldon P, Snook B, Tuo S, Velkovska J, Arenton MW, Boutle S, Cox B, Francis B, Goodell J, Hirosky R, Ledovskoy A, Li H, Lin C, Neu C, Wood J, Clarke C, Harr R, Karchin PE, Don CKK, Lamichhane P, Sturdy J, Belknap DA, Carlsmith D, Cepeda M, Dasu S, Dodd L, Duric S, Friis E, Hall-Wilton R, Herndon M, Herve A, Klabbers P, Lanaro A, Lazaridis C, Levine A, Loveless R, Mohapatra A, Ojalvo I, Perry T, Pierro GA, Polese G, Ross I, Sarangi T, Savin A, Smith WH, Taylor D, Vuosalo C, Woods N
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Study of W boson production in pPb collisions at root(NN)-N-S=5.02 TeV
PHYSICS LETTERS B 2015 NOV 12; 750(?):565-586
The first study of W boson production in pPb collisions is presented, for bosons decaying to a muon or electron, and a neutrino. The measurements are based on a data sample corresponding to an integrated luminosity of 34.6 nb(-1) at a nucleon-nucleon centre-of-mass energy of root(NN)-N-S = 5.02 TeV, collected by the CMS experiment. The W boson differential cross sections, lepton charge asymmetry, and forward-backward asymmetries are measured for leptons of transverse momentum exceeding 25 GeV/c, and as a function of the lepton pseudorapidity in the vertical bar eta(lab)vertical bar < 2.4 range. Deviations from the expectations based on currently available parton distribution functions are observed, showing the need for including W boson data in nuclear parton distribution global fits. (C) 2015 CERN for the benefit of the CMS Collaboration. Published by Elsevier B.V.
Park M, Sivertsen BB, Els-Heindl S, Huber T, Holst B, Beck-Sickinger AG, Schwartz TW, Sakmar TP
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Bioorthogonal Labeling of Ghrelin Receptor to Facilitate Studies of Ligand-Dependent Conformational Dynamics
CHEMISTRY & BIOLOGY 2015 NOV 19; 22(11):1431-1436
Ghrelin receptor (GhrR) is a promising drug target because of its central role in energy homeostasis. GhrR, known for high constitutive activity, is thought to display multi-state conformations during activation and signaling. We used genetically encoded unnatural amino acids and bioorthogonal labeling reactions to engineer multiple fluorescent donor-acceptor pairs to probe ligand-directed structural changes in GhrR. We demonstrate how conformational dynamics of a G-protein-coupled receptor can be measured in reconstituted systems.
Lottersberger F, Karssemeijer RA, Dimitrova N, de Lange T
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53BP1 and the LINC Complex Promote Microtubule-Dependent DSB Mobility and DNA Repair
CELL 2015 NOV 5; 163(4):880-893
Increased mobility of chromatin surrounding doublestrand breaks (DSBs) has been noted in yeast and mammalian cells but the underlying mechanism and its contribution to DSB repair remain unclear. Here, we use a telomere-based system to track DNA damage foci with high resolution in living cells. We find that the greater mobility of damaged chromatin requires 53BP1, SUN1/2 in the linker of the nucleoskeleton, and cytoskeleton (LINC) complex and dynamic microtubules. The data further demonstrate that the excursions promote non-homologous end joining of dysfunctional telomeres and implicated Nesprin-4 and kinesins in telomere fusion. 53BP1/LINC/ microtubule-dependent mobility is also evident at irradiation-induced DSBs and contributes to the mis-rejoining of drug-induced DSBs in BRCA1-deficient cells showing that DSB mobility can be detrimental in cells with numerous DSBs. In contrast, under physiological conditions where cells have only one or a few lesions, DSB mobility is proposed to prevent errors in DNA repair.
Scull MA, Schneider WM, Flatley BR, Hayden R, Fung C, Jones CT, van de Belt M, Penin F, Rice CM
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The N-terminal Helical Region of the Hepatitis C Virus p7 Ion Channel Protein Is Critical for Infectious Virus Production
PLOS PATHOGENS 2015 NOV; 11(11):? Article e1005297
The hepatitis C virus (HCV) p7 protein is required for infectious virus production via its role in assembly and ion channel activity. Although NMR structures of p7 have been reported, the location of secondary structural elements and orientation of the p7 transmembrane domains differ among models. Furthermore, the p7 structure-function relationship remains unclear. Here, extensive mutagenesis, coupled with infectious virus production phenotyping and molecular modeling, demonstrates that the N-terminal helical region plays a previously underappreciated yet critical functional role, especially with respect to E2/p7 cleavage efficiency. Interrogation of specific N-terminal helix residues identified as having p7-specific defects and predicted to point toward the channel pore, in a context of independent E2/p7 cleavage, further supports p7 as a structurally plastic, minimalist ion channel. Together, our findings indicate that the p7 N-terminal helical region is critical for E2/p7 processing, protein-protein interactions, ion channel activity, and infectious HCV production.
Levran O, Peles E, Randesi M, da Rosa JC, Ott J, Rotrosen J, Adelson M, Kreek MJ
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Synaptic Plasticity and Signal Transduction Gene Polymorphisms and Vulnerability to Drug Addictions in Populations of European or African Ancestry
CNS NEUROSCIENCE & THERAPEUTICS 2015 NOV; 21(11):898-904
AimDrug addiction is characterized, in part, by deregulation of synaptic plasticity in circuits involved in reward, stress, cue learning, and memory. This study was designed to assess whether 185 variants in 32 genes central to synaptic plasticity and signal transduction contribute to vulnerability to develop heroin and/or cocaine addiction. MethodsAnalyses were conducted in a sample of 1860 subjects divided according to ancestry (African and European) and drug of abuse (heroin or cocaine). ResultsEighteen SNPs in 11 genes (CDK5R1, EPHA4, EPHA6, FOSL2, MAPK3, MBP, MPDZ, NFKB1, NTRK2, NTSR1, and PRKCE) showed significant associations (P < 0.01), but the signals did not survive correction for multiple testing. SNP rs230530 in the NFKB1 gene, encoding the transcription regulator NF-kappa-B, was the only SNP indicated in both ancestry groups and both addictions. This SNP was previously identified in association with alcohol addiction. SNP rs3915568 in NTSR1, which encodes neurotensin receptor, and SNP rs1389752 in MPDZ, which encodes the multiple PDZ domain protein, were previously associated with heroin addiction or alcohol addiction, respectively. ConclusionsThe study supports the involvement of genetic variation in signal transduction pathways in heroin and cocaine addiction and provides preliminary evidence suggesting several new risk or protective loci that may be relevant for diagnosis and treatment success.
Kang HC, Baek ST, Song S, Gleeson JG
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Clinical and Genetic Aspects of the Segmental Overgrowth Spectrum Due to Somatic Mutations in PIK3CA
JOURNAL OF PEDIATRICS 2015 NOV; 167(5):957-962
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Mercadante PG, Moon CS, Novaes SF, Padula SS, Abad DR, Vargas JCR, Aleksandrov A, Hadjiiska R, Iaydjiev P, Rodozov M, Stoykova S, Sultanov G, Vutova M, Dimitrov A, Glushkov I, Litov L, Pavlov B, Petkov P, Ahmad M, Bian JG, Chen GM, Chen HS, Chen M, Cheng T, Du R, Jiang CH, Plestina R, Romeo F, Shaheen SM, Tao J, Wang C, Wang Z, Zhang H, Asawatangtrakuldee C, Ban Y, Li Q, Liu S, Mao Y, Qian SJ, Wang D, Xu Z, Avila C, Cabrera A, Sierra LFC, Florez C, Gomez JP, Moreno BG, Sanabria JC, Godinovic N, Lelas D, Puljak I, Cipriano PMR, Antunovic Z, Kovac M, Brigljevic V, Kadija K, Luetic J, Micanovic S, Sudic L, Attikis A, Mavromanolakis G, Mousa J, Nicolaou C, Ptochos F, Razis PA, Rykaczewski H, Bodlak M, Finger M, Finger M, El-khateeb E, Elkafrawy T, Mohamed A, Radi A, Salama E, Calpas B, Kadastik M, Murumaa M, Raidal M, Tiko A, Veelken C, Eerola P, Pekkanen J, Voutilainen M, Harkonen J, Karimaki V, Kinnunen R, Lampen T, Lassila-Perini K, Laurila S, Lehti S, Linden T, Luukka P, Maenpaa T, 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Search for a charged Higgs boson in pp collisions at root s=8 TeV
JOURNAL OF HIGH ENERGY PHYSICS 2015 NOV 4; ?(11):? Article 018
A search for a charged Higgs boson is performed with a data sample corresponding to an integrated luminosity of 19.7 +/- 0.5 fb(-1) collected with the CMS detector in proton-proton collisions at root s = 8,TeV. The charged Higgs boson is searched for in top quark decays for m(H +/-) < m(t) - m(b), and in the direct production pp -> t(b)H-+/- for m(H +/-) > m(t) - m(b). The H-+/- -> tau(+/-)nu(tau) and H-+/- -> tb decay modes in the final states tau(h)+jets, mu tau(h), l+jets, and ll' (l =e, mu) are considered in the search. No signal is observed and 95% confidence level upper limits are set on the charged Higgs boson production. A model-independent upper limit on the product branching fraction B(t -> H(+/-)b) B(H-+/- -> tau(+/-)nu(tau)) = 1.2-0.15% is obtained in the mass range m(H +/-) = 80-160 GeV, while the upper limit on the cross section times branching fraction sigma(pp -> t(b)H-+/-) B(H-+/- -> tau(+/-)nu(tau)) = 0.38-0.025 pb is set in the mass range m(H)+ = 180-600 GeV. Here, sigma(pp -> t(b)H-+/-) stands for the cross section sum sigma(pp -> (t) over bar H+) + sigma(pp -> t (b) over bar H-). Assuming B(t -> H(+/-)b) = 1, an upper limit on sigma(pp -> t(b)H-+/-) of 2.0-0.13 pb is set for m(H +/-) = 180-600 GeV. The combination of all considered decay modes and final states is used to set exclusion limits in the m(H +/-)-tan beta parameter space in different MSSM benchmark scenarios.
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Search for diphoton resonances in the mass range from 150 to 850 GeV in pp collisions at root s=8 TeV
PHYSICS LETTERS B 2015 NOV 12; 750(?):494-519
Results are presented of a search for heavy particles decaying into two photons. The analysis is based on a 19.7 fb(-1) sample of proton-proton collisions at root s = 8 TeV collected with the CMS detector at the CERN LHC. The diphoton mass spectrum from 150 to 850 GeV is used to search for an excess of events over the background. The search is extended to new resonances with natural widths of up to 10% of the mass value. No evidence for new particle production is observed and limits at 95% confidence level on the production cross section times branching fraction to diphotons are determined. These limits are interpreted in terms of two-Higgs-doublet model parameters. (C) 2015 CERN for the benefit of the CMS Collaboration. Published by Elsevier B.V.
Doring TF, Knapp S, Cohen JE
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Taylor's power law and the stability of crop yields
FIELD CROPS RESEARCH 2015 NOV; 183(?):294-302
Taylor's power law (TPL) describes the empirical relationship sigma(2)=a mu(b) where sigma(2) are sample variances and mu are sample means in subsets of data in a data set. Equivalently, TPL states that the logarithm of the sample variance is a linear function of the logarithm of the sample mean across different subsets of data. Here we show that crop yields follow this relationship in several published data sets from varied situations. We show that TPL is frequently, but not always, valid for various factors structuring the data including varieties, crop species, trial environments or countries. We propose that the residuals from the linear regression of log(sigma(2)) against log(mu) can be used as a measure of stability, called POLAR (Power Law Residuals). We compare POLAR stability with other commonly used measures of stability, and show that POLAR stability offers an advantage over some frequently used stability measures. (C) 2015 Elsevier B.V. All rights reserved.