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Gleicher N, Kushnir VA, Albertini DA, Barad DH
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First birth following spindle transfer
REPRODUCTIVE BIOMEDICINE ONLINE 2017 NOV; 35(5):542-543
Astorga G, Li DD, Therreau L, Kassa M, Marty A, Llano I
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Concerted Interneuron Activity in the Cerebellar Molecular Layer During Rhythmic Oromotor Behaviors
JOURNAL OF NEUROSCIENCE 2017 NOV 22; 37(47):11455-11468
Molecular layer interneurons (MLIs, stellate and basket cells) of the cerebellar cortex are linked together by chemical and electrical synapses and exert a potent feedforward inhibition on Purkinje cells. The functional role of MLIs during specific motor tasks is uncertain. Here, we used two-photon imaging to study the patterns of activity of neighboring individual MLIs in the Crus II region of awake female mice during two types of oromotor activity, licking and bruxing, using specific expression of the genetically encoded calcium indicator protein GCaMP6s. We found that both stellate and basket cells engaged in synchronized waves of calcium activity during licking and bruxing, with high degrees of correlation among the signals collected in individual MLIs. In contrast, no calcium activity was observed during whisking. MLI activity tended to lag behind the onset of sustained licking episodes, indicating a regulatory action of MLIs during licking. Furthermore, during licking, stellate cell activity was anisotropic: the coordination was constant along the direction of parallel fibers (PFs), but fell off with distance along the orthogonal direction. These results suggest a PF drive for Ca2+ signals during licking. In contrast, during bruxing, MLI activity was neither clearly organized spatially nor temporally correlated with oromotor activity. In conclusion, MLI activity exhibits a high degree of correlation both in licking and in bruxing, but spatiotemporal patterns of activity display significant differences for the two types of behavior.
Martel J, Ko YF, Ojcius DM, Lu CC, Chang CJ, Lin CS, Lai HC, Young JD
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Immunomodulatory Properties of Plants and Mushrooms
TRENDS IN PHARMACOLOGICAL SCIENCES 2017 NOV; 38(11):967-981
Plants and mushrooms are used for medicinal purposes and the screening of molecules possessing biological activities. A single plant or mushroom may produce both stimulatory and inhibitory effects on immune cells, depending on experimental conditions, but the reason behind this dichotomy remains obscure. We present here a large body of experimental data showing that water extracts of plants and mushrooms usually activate immune cells, whereas ethanol extracts inhibit immune cells. The mode of extraction of plants and mushrooms may thus determine the effects produced on immune cells, possibly due to differential solubility and potency of stimulatory and inhibitory compounds. We also examine the possibility of using such plant and mushroom extracts to treat immune system disorders.
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GM, Chen HS, Chen M, Chen Y, Jiang CH, Leggat D, Liao H, Liu Z, Romeo F, Shaheen SM, Spiezia A, Tao J, Wang C, Wang Z, Yazgan E, Zhang H, Zhao J, Ban Y, Chen G, Li Q, Liu S, Mao Y, Qian SJ, Wang D, Xu Z, Avila C, Cabrera A, Sierra LFC, Florez C, Hernandez CFG, Alvarez JDR, Courbon B, Godinovic N, Lelas D, Puljak I, Cipriano PMR, Sculac T, Antunovic Z, Kovac M, Brigljevic V, Ferencek D, Kadija K, Mesic B, Starodumov A, Susa T, Ather MW, Attikis A, Mavromanolakis G, Mousa J, Nicolaou C, Ptochos F, Razis PA, Rykaczewski H, Finger M, Finger M, Jarrin EC, Abdelalim AA, Aly R, Mohammed Y, Dewanjee RK, Kadastik M, Perrini L, Raidal M, Tiko A, Veelken C, Eerola P, Pekkanen J, Voutilainen M, Harkonen J, Jarvinen T, Karimaki V, Kinnunen R, Lampen T, Lassila-Perini K, Lehti S, Linden T, Luukka P, Tuominen E, Tuominiemi J, Tuovinen E, Talvitie J, Tuuva T, Besancon M, Couderc F, Dejardin M, Denegri D, Faure JL, Ferri F, Ganjour S, Ghosh S, Givernaud A, Gras P, de Monchenault GH, Jarry P, Kucher I, 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A, Lacaprara S, Lujan P, Margoni M, Maron G, Meneguzzo AT, Pozzobon N, Ronchese P, Rossin R, Simonetto F, Torassa E, Ventura S, Zanetti M, Zotto P, Braghieri A, Fallavollita F, Magnani A, Montagna P, Ratti SP, Re V, Ressegotti M, Riccardi C, Salvini P, Vai I, Vitulo P, Solestizi LA, Biasini M, Bilei GM, Cecchi C, Ciangottini D, Fano L, Lariccia P, Leonardi R, Manoni E, Mantovani G, Mariani V, Menichelli M, Rossi A, Santocchia A, Spiga D, Androsov K, Azzurri P, Bagliesi G, Bernardini J, Boccali T, Borrello L, Castaldi R, Ciocci MA, Dell'Orso R, Fedi G, Giannini L, Giassi A, Grippo MT, Ligabue F, Lomtadze T, Manca E, Mandorli G, Martini L, Messineo A, Palla F, Rizzi A, Savoy-Navarro A, Spagnolo P, Tenchini R, Tonelli G, Venturi A, Verdini PC, Barone L, Cavallari F, Cipriani M, Del Re D, Diemoz M, Gelli S, Longo E, Margaroli F, Marzocchi B, Meridiani P, Organtini G, Paramatti R, Preiato F, Rahatlou S, Rovelli C, Santanastasio F, Amapane N, Arcidiacono R, Argiro S, Arneodo M, Bartosik N, 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H, De La Cruz-Burelo E, Heredia-De La Cruz I, Rabadan-Trejo RI, Lopez-Fernandez R, Guisao JM, Sanchez-Hernandez A, Moreno SC, Barrera CO, Valencia FV, Pedraza I, Ibarguen HAS, Estrada CU, Pineda AM, Krofcheck D, Butler PH, Ahmad A, Ahmad M, Hassan Q, Hoorani HR, Saddique A, Shah MA, Shoaib M, Waqas M, Bialkowska H, Bluj M, Boimska B, Frueboes T, Gorski M, Kazana M, Nawrocki K, Romanowska-Rybinska K, Szleper M, Zalewski P, Bunkowski K, Byszuk A, Doroba K, Kalinowski A, Konecki M, Krolikowski J, Misiura M, Olszewski M, Pyskir A, Walczak M, Bargassa P, Silva CBDE, Calpas B, Di Francesco A, Faccioli P, Gallinaro M, Hollar J, Leonardo N, Iglesias LL, Nemallapudi MV, Seixas J, Toldaiev O, Vadruccio D, Varela J, Afanasiev S, Bunin P, Gavrilenko M, Golutvin I, Gorbunov I, Kamenev A, Karjavin V, Lanev A, Malakhov A, Matveev V, Palichik V, Perelygin V, Shmatov S, Shulha S, Skatchkov N, Smirnov V, Voytishin N, Zarubin A, Ivanov Y, Kim V, Kuznetsova E, Levchenko P, Murzin V, Oreshkin V, Smirnov I, 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Measurements of properties of the Higgs boson decaying into the four-lepton final state in pp collisions at root s=13 TeV
JOURNAL OF HIGH ENERGY PHYSICS 2017 NOV 9; ?(11):? Article 047
Properties of the Higgs boson are measured in the H -> ZZ -> 4l (l = e, mu) decay channel. A data sample of proton-proton collisions at root s = 13 TeV, collected with the CMS detector at the LHC and corresponding to an integrated luminosity of 35.9 fb(-1) is used. The signal strength modifier mu, defined as the ratio of the observed Higgs boson rate in the H -> ZZ -> 4l decay channel to the standard model expectation, is measured to be mu = 1.05(-0.17)(+0.19) at m(H) = 125.09 GeV, the combined ATLAS and CMS measurement of the Higgs boson mass. The signal strength modifiers for the individual Higgs boson production modes are also measured. The cross section in the fiducial phase space defined by the requirements on lepton kinematics and event topology is measured to be 2.92(-0.44)(+0.48)(stat) (+0.28)(-0.24)(syst) fb, which is compatible with the standard model prediction of 2.76 +/- 0.14 fb. Differential cross sections are reported as a function of the transverse momentum of the Higgs boson, the number of associated jets, and the transverse momentum of the leading associated jet. The Higgs boson mass is measured to be m(H) = 125.26 +/- 0.21 GeV and the width is constrained using the on-shell invariant mass distribution to be Gamma(H) < 1.10 GeV, at 95% confidence level.
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Gurpinar E, Kunori S, Lamichhane K, Lee SW, Libeiro T, Peltola T, Undleeb S, Volobouev I, Wang Z, Greene S, Gurrola A, Janjam R, Johns W, Maguire C, Melo A, Ni H, Sheldon P, Tuo S, Velkovska J, Xu Q, Arenton MW, Barria P, Cox B, Hirosky R, Ledovskoy A, Li H, Neu C, Sinthuprasith T, Sun X, Wang Y, Wolfe E, Xia F, Harr R, Karchin PE, Sturdy J, Zaleski S, Brodski M, Buchanan J, Caillol C, Dasu S, Dodd L, Duric S, Gomber B, Grothe M, Herndon M, Herve A, Hussain U, Klabbers P, Lanaro A, Levine A, Long K, Loveless R, Pierro GA, Polese G, Ruggles T, Savin A, Smith N, Smith WH, Taylor D, Woods N
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Search for a light pseudoscalar Higgs boson produced in association with bottom quarks in pp collisions at root s=8 TeV
JOURNAL OF HIGH ENERGY PHYSICS 2017 NOV 6; ?(11):? Article 010
A search for a light pseudoscalar Higgs boson (A) produced in association with bottom quarks and decaying into a muon pair is reported. The search uses 19.7 fb(-1) of proton-proton collisions at a center-of-mass energy of 8TeV, collected by the CMS experiment. No signal is observed in the dimuon mass range from 25 to 60 GeV. Upper limits on the cross section times branching fraction, sigma(pp -> b $(b) over bar $A) B(A -> mu mu), are set.
Janovitz T, Wong SS, Young NS, Oliveira T, Falck-Pedersen E
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Parvovirus B19 integration into human CD36+erythroid progenitor cells
VIROLOGY 2017 NOV; 511(?):40-48
The pathogenic autonomous human parvovirus B19 (B19V) productively infects erythroid progenitor cells (EPCs). Functional similarities between B19V nonstructural protein (NS1), a DNA binding endonuclease, and the Rep proteins of Adeno-Associated Virus (AAV) led us to hypothesize that NS1 may facilitate targeted nicking of the human genome and B19 vDNA integration. We adapted an integration capture sequencing protocol (IC-Seq) to screen B19V infected human CD36+ EPCs for viral integrants, and discovered 40,000 unique B19V integration events distributed throughout the human genome. Computational analysis of integration patterns revealed strong correlations with gene intronic regions, H3K9me3 sites, and the identification of 41 base pair consensus sequence with an octanucleotide core motif. The octanucleotide core has homology to a single region of B19V, adjacent to the P6 promoter TATA box. We present the first direct evidence that B19V infection of erythroid progenitor cells disrupts the human genome and facilitates viral DNA integration.
Rubsam M, Mertz AF, Kubo A, Marg S, Jungst C, Goranci-Buzhala G, Schauss AC, Horsley V, Dufresne ER, Moser M, Ziegler W, Amagai M, Wickstrom SA, Niessen CM
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E-cadherin integrates mechanotransduction and EGFR signaling to control junctional tissue polarization and tight junction positioning
NATURE COMMUNICATIONS 2017 NOV 1; 8(?):? Article 1250
Generation of a barrier in multi-layered epithelia like the epidermis requires restricted positioning of functional tight junctions (TJ) to the most suprabasal viable layer. This positioning necessitates tissue-level polarization of junctions and the cytoskeleton through unknown mechanisms. Using quantitative whole-mount imaging, genetic ablation, and traction force microscopy and atomic force microscopy, we find that ubiquitously localized E-cadherin coordinates tissue polarization of tension-bearing adherens junction (AJ) and F-actin organization to allow formation of an apical TJ network only in the uppermost viable layer. Molecularly, E-cadherin localizes and tunes EGFR activity and junctional tension to inhibit premature TJ complex formation in lower layers while promoting increased tension and TJ stability in the granular layer 2. In conclusion, our data identify an E-cadherin-dependent mechanical circuit that integrates adhesion, contractile forces and biochemical signaling to drive the polarized organization of junctional tension necessary to build an in vivo epithelial barrier.
Ait-Bouziad N, Lv GH, Mahul-Mellier AL, Xiao SF, Zorludemir G, Eliezer D, Walz T, Lashuel HA
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Discovery and characterization of stable and toxic Tau/phospholipid oligomeric complexes
NATURE COMMUNICATIONS 2017 NOV 22; 8(?):? Article 1678
The microtubule-associated protein Tau plays a central role in the pathogenesis of Alzheimer's disease. Although Tau interaction with membranes is thought to affect some of its physiological functions and its aggregation properties, the sequence determinants and the structural and functional consequences of such interactions remain poorly understood. Here, we report that the interaction of Tau with vesicles results in the formation of highly stable protein/phospholipid complexes. These complexes are toxic to primary hippocampal cultures and are detected by MC-1, an antibody recognizing pathological Tau conformations. The core of these complexes is comprised of the PHF6* and PHF6 hexapeptide motifs, the latter in a beta-strand conformation. Studies using Tau-derived peptides enabled the design of mutants that disrupt Tau interactions with phospholipids without interfering with its ability to form fibrils, thus providing powerful tools for uncoupling these processes and investigating the role of membrane interactions in regulating Tau function, aggregation and toxicity.
Yu JS, Liao HX, Pritchett J, Bowman C, Vivian C, Parks R, Xia SM, Cooper M, Williams WB, Bonsignori M, Reed SG, Chen M, Vandergrift N, Rice CM, Haynes BF
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Development of a recombinant yellow fever vector expressing a HIV Glade C founder envelope gp120
JOURNAL OF VIROLOGICAL METHODS 2017 NOV; 249(?):85-93
Development of a HIV-1 vaccine is a major global priority. The yellow fever virus (YFV) attenuated vaccine 17D is among the most effective of currently used vaccines. However, the stability of the YFV17D vector when carrying non-flavivirus genes has been problematic. We have constructed and expressed HIV-1 Env in YFV17D with either single transmembrane (STM) or double transmembrane (DTM) YFV E protein domains for the development of anti-HIV antibodies. Here we describe modifications of the YFV17D vector such that HIV-1 Env gp120 is expressed in up to 5 passages in Vero cells. Immunization with recombinant YFV17D vector prime followed by HIV-1 CH505 TF gp120 protein boosts were able to induce neutralizing antibodies for a HIV-1 tier 1 isolate in mice. This modified YFV vector may be a starting point for constructing HIV-1 vaccine candidate priming vectors.
Swaminathan V, Alushin GM, Waterman CM
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Mechanosensation: A Catch Bond That Only Hooks One Way
CURRENT BIOLOGY 2017 NOV 6; 27(21):R1158-R1160
Single-molecule force spectroscopy and modeling have revealed that the adhesion molecule vinculin and F-actin form a catch bond that is dependent on the direction of forces along the actin filament. This may underlie the mechanisms by which cells sense directional physical cues.