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Korlach J, Gedman G, Kingan SB, Chin CS, Howard JT, Audet JN, Cantin L, Jarvis ED
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De novo PacBio long-read and phased avian genome assemblies correct and add to reference genes generated with intermediate and short reads (opens in new window)

GIGASCIENCE 2017 AUG 23; 6(10):?
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Reference-quality genomes are expected to provide a resource for studying gene structure, function, and evolution. However, often genes of interest are not completely or accurately assembled, leading to unknown errors in analyses or additional cloning efforts for the correct sequences. A promising solution is long-read sequencing. Here we tested PacBio-based long-read sequencing and diploid assembly for potential improvements to the Sanger-based intermediate-read zebra finch reference and Illumina-based short-read Anna's hummingbird reference, 2 vocal learning avian species widely studied in neuroscience and genomics. With DNA of the same individuals used to generate the reference genomes, we generated diploid assemblies with the FALCON-Unzip assembler, resulting in contigs with no gaps in the megabase range, representing 150-fold and 200-fold improvements over the current zebra finch and hummingbird references, respectively. These long-read and phased assemblies corrected and resolved what we discovered to be numerous misassemblies in the references, including missing sequences in gaps, erroneous sequences flanking gaps, base call errors in difficult-to-sequence regions, complex repeat structure errors, and allelic differences between the 2 haplotypes. These improvements were validated by single long-genome and transcriptome reads and resulted for the first time in completely resolved protein-coding genes widely studied in neuroscience and specialized in vocal learning species. These findings demonstrate the impact of long reads, sequencing of previously difficult-to-sequence regions, and phasing of haplotypes on generating the high-quality assemblies necessary for understanding gene structure, function, and evolution.
Sani I, Santandrea E, Morrone MC, Chelazzi L
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Temporally evolving gain mechanisms of attention in macaque area V4 (opens in new window)

JOURNAL OF NEUROPHYSIOLOGY 2017 AUG; 118(2):964-985
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Cognitive attention and perceptual saliency jointly govern our interaction with the environment. Yet, we still lack a universally accepted account of the interplay between attention and luminance contrast, a fundamental dimension of saliency. We measured the attentional modulation of V4 neurons' contrast response functions (CRFs) in awake, behaving macaque monkeys and applied a new approach that emphasizes the temporal dynamics of cell responses. We found that attention modulates CRFs via different gain mechanisms during subsequent epochs of visually driven activity: an early contrast-gain, strongly dependent on prestimulus activity changes (baseline shift); a time-limited stimulus-dependent multiplicative modulation, reaching its maximal expression around 150 ms after stimulus onset; and a late resurgence of contrast-gain modulation. Attention produced comparable time-dependent attentional gain changes on cells heterogeneously coding contrast, supporting the notion that the same circuits mediate attention mechanisms in V4 regardless of the form of contrast selectivity expressed by the given neuron. Surprisingly, attention was also sometimes capable of inducing radical transformations in the shape of CRFs. These findings offer important insights into the mechanisms that underlie contrast coding and attention in primate visual cortex and a new perspective on their interplay, one in which time becomes a fundamental factor. NEW & NOTEWORTHY We offer an innovative perspective on the interplay between attention and luminance contrast in macaque area V4, one in which time becomes a fundamental factor. We place emphasis on the temporal dynamics of attentional effects, pioneering the notion that attention modulates contrast response functions of V4 neurons via the sequential engagement of distinct gain mechanisms. These findings advance understanding of attentional influences on visual processing and help reconcile divergent results in the literature.
Nogueira RT, Sahi V, Huang J, Tsuji M
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Human IgG repertoire of malaria antigen-immunized human immune system (HIS) mice (opens in new window)

IMMUNOLOGY LETTERS 2017 AUG; 188(?):46-52
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Humanized mouse models present an important tool for preclinical evaluation of new vaccines and therapeutics. Here we show the human variable repertoire of antibody sequences cloned from a previously described human immune system (HIS) mouse model that possesses functional human CD4 + T cells and B cells, namely HIS-CD4/B mice. We sequenced variable IgG genes from single memory B-cell and plasma-cell sorted from splenocytes or whole blood lymphocytes of HIS-CD4/B mice that were vaccinated with a human plasmodial antigen, a recombinant Plasmodiun falciparun circumsporozoite protein (rPfCSP). We demonstrate that rPfCSP immunization triggers a diverse B-cell IgG repertoire composed of various human VH family genes and distinct V(D)J recombinations that constitute diverse CDR3 sequences similar to humans, although low hypermutated sequences were generated. These results demonstrate the substantial genetic diversity of responding human B cells of HIS-CD4/B mice and their capacity to mount human IgG class-switched antibody response upon vaccination.
Chen TF, Sazinsky SL, Houde D, DiLillo DJ, Bird J, Li KK, Cheng GT, Qiu HW, Engen JR, Ravetch JV, Wittrup KD
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Engineering Aglycosylated IgG Variants with Wild-Type or Improved Binding Affinity to Human Fc Gamma RIIA and Fc Gamma RIIIAs (opens in new window)

JOURNAL OF MOLECULAR BIOLOGY 2017 AUG 4; 429(16):2528-2541
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The binding of human IgG1 to human Fc gamma receptors (hFc gamma Rs) is highly sensitive to the presence of a single N-linked glycosylation site at asparagine 297 of the Fc, with deglycosylation resulting in a complete loss of hFc gamma R binding. Previously, we demonstrated that aglycosylated human IgG1 Fc variants can engage the human Fc gamma RII class of the low-affinity hFc gamma Rs, demonstrating that N-linked glycosylation of the Fc is not a strict requirement for hFc gamma R engagement. In the present study, we demonstrate that aglycosylated IgG variants can be engineered to productively engage with Fc gamma RIIIA, as well as the human Fc gamma RII subset. We also assess the biophysical properties and serum half-life of the aglycosylated IgG variants to measure stability. Aglycosylated constructs N297D/S298T (DTT)-K326I/A327Y/L328G (IYG) and N297D/S298A IYG optimally drove tumor cell phagocytosis. A mathematical model of phagocytosis suggests that hFc gamma R) and hFc gamma RIIIA dimers were the main drivers of phagocytosis. In vivo tumor control of B16F10 lung metastases further confirmed the variant DTT IYG to be the best at restoring wild-type-like properties in prevention of lung metastases. While deuterium incorporation was similar across most of the protein, several peptides within the CH2 domain of DTT IYG showed differential deuterium uptake in the peptide region of the FG loop as compared to the aglycosylated N297Q. Thus, in this study, we have found an aglycosylated variant that may effectively substitute for wild-type Fc. These aglycosylated variants have the potential to allow therapeutic antibodies to be produced in virtually any expression system and still maintain effector function. (C) 2017 Elsevier Ltd. All rights reserved.
Aaltonen T, Gonzalez BA, Amerio S, Amidei D, Anastassov A, Annovi A, Antos J, Apollinari G, Appel JA, Apresyan A, Arisawa T, Artikov A, Asaadi J, Ashmanskas W, Auerbach B, Aurisano A, Azfar F, Badgett W, Barbaro-Galtieri A, Barnes VE, Barnett BA, Barria P, Bartos P, Bauce M, Bauer G, Bedeschi F, Beecher D, Behari S, Bellettini G, Bellinger J, Benjamin D, Beretvas A, Bhatti A, Binkley M, Bisello D, Bizjak I, Bland KR, Blumenfeld B, Bocci A, Bodek A, Bortoletto D, Boudreau J, Boveia A, Brau B, Brigliadori L, Brisuda A, Bromberg C, Brucken E, Bucciantonio M, Budagov J, Budd HS, Budd S, Burkett K, Busetto G, Bussey P, Buzatu A, Calancha C, Camarda S, Campanelli M, Campbell M, Canelli F, Canepa A, Carls B, Carlsmith D, Carosi R, Carrillo S, Carron S, Casal B, Castro A, Catastini P, Cauz D, Cavaliere V, Cavalli-Sforza M, Cerri A, Cerrito L, Chen YC, Chertok M, Chlachidze G, Chlebana F, Cho K, Chokheli D, Chou JP, Chung WH, Chung YS, Ciobanu CI, Ciocci MA, Clark A, Compostella G, Convery ME, Conway J, Corbo M, Cordelli M, Cox CA, Cox DJ, Crescioli F, Almenar CC, Cuevas J, Culbertson R, Dagenhart D, d'Ascenzo N, Datta M, de Barbaro P, De Cecco S, De Lorenzo G, Dell'Orso M, Deluca C, Demortier L, Deng J, Deninno M, Devoto F, d'Errico M, Di Canto A, Di Ruzza B, Dittmann JR, D'Onofrio M, Donati S, Dong P, Dorigo M, Dorigo T, Ebina K, Elagin A, Eppig A, Erbacher R, Errede D, Errede S, Ershaidat N, Eusebi R, Fang HC, Farrington S, Feindt M, Fernandez JP, Ferrazza C, Field R, Flanagan G, Forrest R, Frank MJ, Franklin M, Freeman JC, Funakoshi Y, Furic I, Gallinaro M, Galyardt J, Garcia JE, Garfinkel AF, Garosi P, Gerberich H, Gerchtein E, Giagu S, Giakoumopoulou V, Giannetti P, Gibson K, Ginsburg CM, Giokaris N, Giromini P, Giunta M, Giurgiu G, Glagolev V, Glenzinski D, Gold M, Goldin D, Goldschmidt N, Golossanov A, Gomez G, Gomez-Ceballos G, Goncharov M, Gonzalez O, Gorelov I, Goshaw AT, Goulianos K, Gresele A, Grinstein S, Grosso-Pilcher C, Group RC, da Costa JG, Gunay-Unalan Z, Haber C, Hahn SR, Halkiadakis E, Hamaguchi A, Han JY, Happacher F, Hara K, Hare D, Hare M, Harr RF, Hatakeyama K, Hays C, Heck M, Heinrich J, Hewamanage S, Hidas D, Hocker A, Hopkins W, Horn D, Hou S, Hughes RE, Hurwitz M, Husemann U, Hussain N, Hussein M, Huston J, Introzzi G, Iori M, Ivanov A, James E, Jang D, Jayatilaka B, Jeon EJ, Jha MK, Jindariani S, Johnson W, Jones M, Joo KK, Jun SY, Junk TR, Kamon T, Karchin PE, Kato Y, Ketchum W, Keung J, Khotilovich V, Kilminster B, Kim DH, Kim HS, Kim HW, Kim JE, Kim MJ, Kim SB, Kim SH, Kim YK, Kimura N, Kirby M, Klimenko S, Kondo K, Kong DJ, Konigsberg J, Kotwal AV, Kreps M, Kroll J, Krop D, Krumnack N, Kruse M, Krutelyov V, Kuhr T, Kurata M, Kwang S, Laasanen AT, Lami S, Lammel S, Lancaster M, Lander RL, Lannon K, Lath A, Latino G, Lazzizzera I, LeCompte T, Lee E, Lee HS, Lee JS, Lee SW, Leo S, Leone S, Lin CJ, Linacre J, Lindgren M, Lipeles E, Lister A, Litvintsev DO, Liu C, Liu Q, Liu T, Lockwitz S, Lockyer NS, Loginov A, Lucchesi D, Lueck J, Lujan P, Lungu G, Lys J, Lysak R, Madrak R, Maeshima K, Makhoul K, Maksimovic P, Malik S, Manca G, Manousakis-Katsikakis A, Margaroli F, Marino C, Martinez M, Martinez-Ballarin R, Mastrandrea P, Mathis M, Mattson ME, Mazzanti P, McFarland KS, McIntyre P, McNulty R, Mehta A, Mehtala P, Menzione A, Mesropian C, Miao T, Mietlicki D, Mitra A, Miyake H, Moed S, Moggi N, Mondragon MN, Moon CS, Moore R, Morello MJ, Morlock J, Fernandez PM, Mukherjee A, Muller T, Murat P, Mussini M, Nachtman J, Nagai Y, Naganoma J, Nakano I, Napier A, Nett J, Neu C, Neubauer MS, Nielsen J, Nodulman L, Norniella O, Nurse E, Oakes L, Oh SH, Oh YD, Oksuzian I, Okusawa T, Orava R, Ortolan L, Griso SP, Pagliarone C, Palencia E, Papadimitriou V, Paramonov AA, Patrick J, Pauletta G, Paulini M, Paus C, Pellett DE, Penzo A, Phillips TJ, Piacentino G, Pianori E, Pilot J, Plager C, Pondrom L, Potamianos K, Poukhov O, Prokoshin F, Pronko A, Ptohos F, Pueschel E, Punzi G, Pursley J, Rahaman A, Ramakrishnan V, Ranjan N, Redondo I, Renton P, Rescigno M, Rimondi F, Ristori L, Robson A, Rodrigo T, Rodriguez T, Rogers E, Rolli S, Roser R, Rossi M, Rubbo F, Ruffini F, Ruiz A, Russ J, Rusu V, Safonov A, Sakumoto WK, Sakurai Y, Santi L, Sartori L, Sato K, Saveliev V, Savoy-Navarro A, Schlabach P, Schmidt A, Schmidt EE, Schmidt MP, Schmitt M, Schwarz T, Scodellaro L, Scribano A, Scuri F, Sedov A, Seidel S, Seiya Y, Semenov A, Sforza F, Sfyrla A, Shalhout SZ, Shears T, Shepard PF, Shimojima M, Shiraishi S, Shochet M, Shreyber I, Simonenko A, Sinervo P, Sissakian A, Sliwa K, Smith JR, Snider FD, Soha A, Somalwar S, Sorin V, Squillacioti P, Stancari M, Stanitzki M, St Denis R, Stelzer B, Stelzer-Chilton O, Stentz D, Strologas J, Strycker GL, Sudo Y, Sukhanov A, Suslov I, Takemasa K, Takeuchi Y, Tang J, Tecchio M, Teng PK, Thom J, Thome J, Thompson GA, Thomson E, Ttito-Guzman P, Tkaczyk S, Tokar S, Tollefson K, Tomura T, Torre S, Torretta D, Totaro P, Trovato M, Tu Y, Ukegawa F, Uozumi S, Varganov A, Vazquez F, Velev G, Vellidis C, Vidal M, Vila I, Vilar R, Vizan J, Vogel M, Volpi G, Wagner P, Wagner RL, Wakisaka T, Wallny R, Wang SM, Warburton A, Waters D, Weinberger M, Whitehouse B, Whiteson D, Wicklund E, Wilbur S, Wick F, Williams HH, Wilson JS, Wilson P, Winer BL, Wittich P, Wolfe H, Wright T, Wu X, Wu Z, Yamamoto K, Yamaoka J, Yang T, Yang UK, Yang YC, Yao WM, Yeh GP, Yi K, Yoh J, Yorita K, Yoshida T, Yu GB, Yu I, Yu SS, Yun JC, Zanetti A, Zeng Y, Zucchelli S
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Observation of the Y (4140) structure in the J/psi phi mass spectrum in B-+/- -> J/psi phi K-+/- decays (opens in new window)

MODERN PHYSICS LETTERS A 2017 AUG 30; 32(26):? Article 1750139
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The observation of the Y ( 4140) structure in B-+/- -> J/psi phi K-+/- decays produced in (p) over barp collisions at root s = 1.96 TeV is reported with a statistical significance greater than 5 standard deviations. A fit to the J/psi phi mass spectrum is performed assuming the presence of a Breit-Wigner resonance. The fit yields a signal of 19 +/- 6 (stat) +/- 3 (syst) resonance events, and resonance mass and width of 4143.4(-3.0)(+2.9) ( stat) +/- 0.6 (syst) MeV/c(2) and 15.3(-6.1)(+10.4) (stat) +/- 2.5 (syst) MeV/c(2), respectively. The parameters of this resonance-like structure are consistent with values reported from an earlier CDF analysis.
Abramowicz H, Abt I, Adamczyk L, Adamus M, Antonelli S, Aushev V, Aushev Y, Behnke O, Behrens U, Bertolin A, Bloch I, Brock I, Brook NH, Brugnera R, Bruni A, Bussey PJ, Caldwell A, Capua M, Catterall CD, Chwastowski J, Ciborowski J, Ciesielski R, Cooper-Sarkar AM, Corradi M, Dementiev RK, Devenish RCE, Dusini S, Foster B, Gach G, Gallo E, Garfagnini A, Geiser A, Gizhko A, Gladilin LK, Golubkov YA, Grzelak G, Guzik M, Gwenlan C, Hlushchenko O, Hochman D, Hori R, Ibrahim ZA, Iga Y, Ishitsuka M, Jomhari NZ, Kadenko I, Kananov S, Karshon U, Kaur P, Kisielewska D, Klanner R, Klein U, Korzhavina IA, Kotanski A, Kovalchuk N, Kowalski H, Krupa B, Kuprash O, Kuze M, Levchenko BB, Levy A, Lisovyi M, Lobodzinska E, Lohr B, Lohrmann E, Longhin A, Lukina OY, Malka J, Mastroberardino A, Idris FM, Nasir NM, Myronenko V, Nagano K, Onishchuk Y, Paul E, Perlanski W, Pokrovskiy NS, Polini A, Przybycien M, Ruspa M, Saxon DH, Schioppa M, Schneekloth U, Schorner-Sadenius T, Shcheglova LM, Shkola O, Shyrma Y, Skillicorn IO, Slominski W, Solano A, Stanco L, Stefaniuk N, Stern A, Stopa P, Sztuk-Dambietz J, Tassi E, Tokushuku K, Tomaszewska J, Tsurugai T, Turcato M, Turkot O, Tymieniecka T, Verbytskyi A, Abdullah WATW, Wichmann K, Wing M, Yamada S, Yamazaki Y, Zarnecki AF, Zawiejski L, Zenaiev O, Zhautykov BO
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Studies of the diffractive photoproduction of isolated photons at HERA (opens in new window)

PHYSICAL REVIEW D 2017 AUG 31; 96(3):? Article 032006
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The photoproduction of isolated photons has been measured in diffractive events recorded by the ZEUS detector at HERA. Cross sections are evaluated in the photon transverse- energy and pseudorapidity ranges 5 < E-T(gamma) < 15 GeV and -0.7 < eta(gamma) < 0.9, inclusively, and also with a jet with transverse energy and pseudorapidity in the ranges 4 < E-T(jet) < 35 GeV and -1.5 0.9, where z(P)(meas) is the fraction of the longitudinal momentum of the colorless "Pomeron" exchange that is transferred to the photon- jet final state, giving evidence for direct Pomeron interactions.
Medrihan L, Sagi Y, Inde Z, Krupa O, Daniels C, Peyrache A, Greengard P
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Initiation of Behavioral Response to Antidepressants by Cholecystokinin Neurons of the Dentate Gyrus (opens in new window)

NEURON 2017 AUG 2; 95(3):564-576.e4
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Selective serotonin reuptake inhibitors (SSRIs) are the most commonly used class of antidepressant drugs, but the cellular and molecular mechanisms by which their therapeutic action is initiated are poorly understood. Here we show that serotonin 5-HT1B receptors in cholecystokinin (CCK) inhibitory interneurons of the mammalian dentate gyrus (DG) initiate the therapeutic response to antidepressants. In these neurons, 5-HT1B receptors are expressed presynaptically, and their activation inhibits GABA release. Inhibition of GABA release from CCK neurons disinhibits parvalbumin (PV) interneurons and, as a consequence, reduces the neuronal activity of the granule cells. Finally, inhibition of CCK neurons mimics the antidepressant behavioral effects of SSRIs, suggesting that these cells may represent a novel cellular target for the development of fast-acting antidepressant drugs.
Weitzhandler I, Dzuricky M, Hoffmann I, Quiroz FG, Gradzielski M, Chilkoti A
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Micellar Self-Assembly of Recombinant Resilin-/Elastin-Like Block Copolypeptides (opens in new window)

BIOMACROMOLECULES 2017 AUG; 18(8):2419-2426
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Reported here is the synthesis of perfectly sequence defined, monodisperse diblock copolypeptides of hydrophilic elastin-like and hydrophobic resilin-like polypeptide blocks and characterization of their self-assembly as a function of structural parameters by light scattering, cryo-TEM, and small-angle neutron scattering. A subset of these diblock copolypeptides exhibit lower critical solution temperature and upper critical solution temperature phase behavior and self-assemble into spherical or cylindrical micelles. Their morphologies are dictated by their chain length, degree of hydrophilicity, and hydrophilic weight fraction of the ELP block. We find that (1) independent of the length of the corona-forming ELP block there is a minimum threshold in the length of the RLP block below which self-assembly does not occur, but that once that threshold is crossed, (2) the RLP block length is a unique molecular parameter to independently tune self-assembly and (3) increasing the hydrophobicity of the corona-forming ELP drives a transition from spherical to cylindrical morphology. Unlike the self-assembly of purely ELP-based block copolymers, the self-assembly of RLP ELPs can be understood by simple principles of polymer physics relating hydrophilic weight fraction and polymer polymer and polymer solvent interactions to micellar morphology, which is important as it provides a route for the de novo design of desired nanoscale morphologies from first principles.
Belousov R, Cohen EGD, Rondoni L
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Nonequilibrium Langevin dynamics: A demonstration study of shear flow fluctuations in a simple fluid (opens in new window)

PHYSICAL REVIEW E 2017 AUG 14; 96(2):? Article 022125
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The present paper is based on a recent success of the second-order stochastic fluctuation theory in describing time autocorrelations of equilibrium and nonequilibrium physical systems. In particular, it was shown to yield values of the related deterministic parameters of the Langevin equation for a Couette flow in a microscopic molecular dynamics model of a simple fluid. In this paper we find all the remaining constants of the stochastic dynamics, which then is simulated numerically and compared directly with the original physical system. By using these data, we study in detail the accuracy and precision of a second-order Langevin model for nonequilibrium physical systems theoretically and computationally. We find an intriguing relation between an applied external force and cumulants of the resulting flow fluctuations. This is characterized by a linear dependence of an athermal cumulant ratio, an apposite quantity introduced here. In addition, we discuss how the order of a given Langevin dynamics can be raised systematically by introducing colored noise.
Theofanopoulou C, Boeckx C, Jarvis ED
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A hypothesis on a role of oxytocin in the social mechanisms of speech and vocal learning (opens in new window)

PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES 2017 AUG 30; 284(1861):? Article 20170988
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Language acquisition in humans and song learning in songbirds naturally happen as a social learning experience, providing an excellent opportunity to reveal social motivation and reward mechanisms that boost sensorimotor learning. Our knowledge about the molecules and circuits that control these social mechanisms for vocal learning and language is limited. Here we propose a hypothesis of a role for oxytocin (OT) in the social motivation and evolution of vocal learning and language. Building upon existing evidence, we suggest specific neural pathways and mechanisms through which OT might modulate vocal learning circuits in specific developmental stages.