JC Polyomavirus Uses Extracellular Vesicles To Infect Target Cells

The endemic human JC polyomavirus (JCPyV) causes progressive multifocal leukoencephalopathy in immune-suppressed patients. The mechanisms of virus infection in vivo are not understood because the major target cells for virus in the brain do not express virus receptors and do not bind virus. We found that JCPyV associates with extracellular vesicles (EVs) and can infect target cells independently of virus receptors. Virus particles were found packaged inside extracellular vesicles and attached to the outer side of vesicles. Anti-JCPyV antisera reduced infection by purified virus but had no effect on infection by EV-associated virus. Treatment of cells with the receptor-destroying enzyme neuraminidase inhibited infection with purified virus but did not inhibit infection by EV-associated virus. Mutant pseudoviruses defective in sialic acid receptor binding could not transduce cells as purified pseudovirions but could do so when associated with EVs. This alternative mechanism of infection likely plays a critical role in the dissemination and spread of JCPyV both to and within the central nervous system

Ecologies of dramaturgy in dance creation: a conversation

AW é Jamaicana, Preta, dançarina mulher cisgênero e dramaturga. Dois interesses paralelos emergiram gradualmente ao longo de sua carreira – a contribuição do performer ao processo criativo, e a dinâmica da operação necessariamente colaborativa que é a coreografia contemporânea. Esta entrevista com a artista-pesquisadora reporta sua experiência artística e o processo criativo da obra Confession Publique, ao qual ela ocupa a posição triádica de dramaturga, dançarina e pesquisadora auto-etnógrafa, compondo uma conversa dialógica entre artistas interdisciplinares e pesquisadores do projeto Dramaturgical Ecologies (sediado na Anonimo). Para além de uma entrevista, este projeto polivocal–centrado nos temas de agenciamento, dramaturgia, corporalização e movimento–migrou do físico para o virtual, respondendo a reconfiguração biopolítica causada pela pandemia do COVID-19. Esta transição ativou  tensões e ressonâncias no diálogo que se tornaram limitações facilitadoras, onde os corpos envolvidos na pesquisa se tornaram parte da co-composição dramatúrgica do processo de escrita deste texto. O resultado está distribuído nas páginas que seguem, tomando forma de uma escrita performativa dialógica-reflexiva, criada a partir de um processo de pensamento coletivo. Angelique Willkie é Jamaicana, Preta, dançarina mulher cisgênero e dramaturga. Dois interesses paralelos emergiram gradualmente ao longo de sua carreira – a contribuição do performer ao processo criativo, e a dinâmica da operação necessariamente colaborativa que é a coreografia contemporânea. Esta entrevista com a artista-pesquisadora reporta sua experiência artística e o processo criativo da obra Confession Publique, ao qual ela ocupa a posição triádica de dramaturga, dançarina e pesquisadora auto-etnógrafa, compondo uma conversa dialógica entre artistas interdisciplinares e pesquisadores do projeto Dramaturgical Ecologies (sediado na Concordia University, CA). Para além de uma entrevista, este projeto polivocal–centrado nos temas de agenciamento, dramaturgia, corporalização e movimento–migrou do físico para o virtual, respondendo a reconfiguração biopolítica causada pela pandemia do COVID-19. Esta transição ativou tensões e ressonâncias no diálogo que se tornaram limitações facilitadoras, onde os corpos envolvidos na pesquisa se tornaram parte da co-composição dramatúrgica do processo de escrita deste texto. O resultado está distribuído nas páginas que seguem, tomando forma de uma escrita performativa dialógica-reflexiva, criada a partir de um processo de pensamento coletivo.

Biogenesis of JC Polyomavirus Associated Extracellular Vesicles

JC polyomavirus (JCPyV) is a small, non-enveloped virus that persists in the kidney in about half the adult population. In severely immune-compromised individuals JCPyV causes the neurodegenerative disease progressive multifocal leukoencephalopathy (PML) in the brain. JCPyV has been shown to infect cells by both direct and indirect mechanisms, the latter involving extracellular vesicle (EV) mediated infection. While direct mechanisms of infection are well studied indirect EV mediated mechanisms are poorly understood. Using a combination of chemical and genetic approaches we show that several overlapping intracellular pathways are responsible for the biogenesis of virus containing EV. Here we show that targeting neutral sphingomyelinase 2 (nSMase2) with the drug cambinol decreased the spread of JCPyV over several viral life cycles. Genetic depletion of nSMase2 by either shRNA or CRISPR/Cas9 reduced EV-mediated infection. Individual knockdown of seven ESCRT-related proteins including HGS, ALIX, TSG101, VPS25, VPS20, CHMP4A, and VPS4A did not significantly reduce JCPyV associated EV (JCPyV(+) EV) infectivity, whereas knockdown of the tetraspanins CD9 and CD81 or trafficking and/or secretory autophagy-related proteins RAB8A, RAB27A, and GRASP65 all significantly reduced the spread of JCPyV and decreased EV-mediated infection. These findings point to a role for exosomes and secretory autophagosomes in the biogenesis of JCPyV associated EVs with specific roles for nSMase2, CD9, CD81, RAB8A, RAB27A, and GRASP65 proteins

The Lantern, 2011-2012

• Frangipani • A Shadow • Dear Anne, In this Place, Stringbean Girls • Back to a Dandelion • How to Plant a Room • Swimming Pool Poem 30 • The Naming of Daughters • Berman Museum Photographs • Truth or Dare • The Song of Remembrance, L\u27vov, Poland, 1940 • Headlights • Prayer of Thanks • Numbers Game • Pediment • Home Sick • Lust • Sand Lining Instructions • A-A-Ask a Question • Flash Cards • Columbus Day • Mr. Yoest Gives His Report to the Police Officers on Wednesday Night • Gender Trouble • The Internet Connection at Ursinus College • Assuming You\u27ll Still be Here • 10/28/11, Third Poem • October • Actions that Affirm and Confirm Us as a Community • Why I Hate The Lantern • Confessions of an Ex-Vegetarian • Run • Lunch at Caltort • Schemers • You Will Make Beautiful Babies in America • The Black Dirt Region • Il Travatore • Ghost Story • Blue Eyes and Sunny Skies • A Little Sincerity • The Bookstore • The Opposite of Serendipity • The Human Doll • Evil Deeds • Francesca • Sunday Morning • Jersey Aesthetic • Jump! • Behind Reimert • Seaweed in New Zealand • Tombee de L\u27elegance • The Window • Esperando • Rainbow to the Heavens • Encased • In Springtime • A Fiesolan Monk\u27s Room • Inside a Bone • Neon Indian • Moments of Clarity • OneFeral: A Feral Self-Portrait • Cover Image: The Conquerorhttps://digitalcommons.ursinus.edu/lantern/1177/thumbnail.jp

Immunogenicity of chimeric haemagglutinin-based, universal influenza virus vaccine candidates: interim results of a randomised, placebo-controlled, phase 1 clinical trial.

BackgroundInfluenza viruses cause substantial annual morbidity and mortality globally. Current vaccines protect against influenza only when well matched to the circulating strains. However, antigenic drift can cause considerable mismatches between vaccine and circulating strains, substantially reducing vaccine effectiveness. Moreover, current seasonal vaccines are ineffective against pandemic influenza, and production of a vaccine matched to a newly emerging virus strain takes months. Therefore, there is an unmet medical need for a broadly protective influenza virus vaccine. We aimed to test the ability of chimeric H1 haemagglutinin-based universal influenza virus vaccine candidates to induce broadly cross-reactive antibodies targeting the stalk domain of group 1 haemagglutinin-expressing influenza viruses.MethodsWe did a randomised, observer-blinded, phase 1 study in healthy adults in two centres in the USA. Participants were randomly assigned to one of three prime-boost, chimeric haemagglutinin-based vaccine regimens or one of two placebo groups. The vaccine regimens included a chimeric H8/1, intranasal, live-attenuated vaccine on day 1 followed by a non-adjuvanted, chimeric H5/1, intramuscular, inactivated vaccine on day 85; the same regimen but with the inactivated vaccine being adjuvanted with AS03; and an AS03-adjuvanted, chimeric H8/1, intramuscular, inactivated vaccine followed by an AS03-adjuvanted, chimeric H5/1, intramuscular, inactivated vaccine. In this planned interim analysis, the primary endpoints of reactogenicity and safety were assessed by blinded study group. We also assessed anti-H1 haemagglutinin stalk, anti-H2, anti-H9, and anti-H18 IgG antibody titres and plasmablast and memory B-cell responses in peripheral blood. This trial is registered with ClinicalTrials.gov, number NCT03300050.FindingsBetween Oct 10, 2017, and Nov 27, 2017, 65 participants were enrolled and randomly assigned. The adjuvanted inactivated vaccine, but not the live-attenuated vaccine, induced a substantial serum IgG antibody response after the prime immunisation, with a seven times increase in anti-H1 stalk antibody titres on day 29. After boost immunisation, all vaccine regimens induced detectable anti-H1 stalk antibody (2·2-5·6 times induction over baseline), cross-reactive serum IgG antibody, and peripheral blood plasmablast responses. An unsolicited adverse event was reported for 29 (48%) of 61 participants. Solicited local adverse events were reported in 12 (48%) of 25 participants following prime vaccination with intramuscular study product or placebo, in 12 (33%) of 36 after prime immunisation with intranasal study product or placebo, and in 18 (32%) of 56 following booster doses of study product or placebo. Solicited systemic adverse events were reported in 14 (56%) of 25 after prime immunisation with intramuscular study product or placebo, in 22 (61%) of 36 after immunisation with intranasal study product or placebo, and in 21 (38%) of 56 after booster doses of study product or placebo. Disaggregated safety data were not available at the time of this interim analysis.InterpretationThe tested chimeric haemagglutinin-based, universal influenza virus vaccine regimens elicited cross-reactive serum IgG antibodies that targeted the conserved haemagglutinin stalk domain. This is the first proof-of-principle study to show that high anti-stalk titres can be induced by a rationally designed vaccine in humans and opens up avenues for further development of universal influenza virus vaccines. On the basis of the blinded study group, the vaccine regimens were tolerable and no safety concerns were observed.FundingBill & Melinda Gates Foundation

Search for a new resonance decaying to a W or Z boson and a Higgs boson in the ll/lv/vv + bb final states with the ATLAS detector

A search for a new resonance decaying to a W or Z boson and a Higgs boson in the ll/lv/vv + bb final states is performed using 20.3 fb −1 of pp collision data recorded at √ s = 8 TeV with the ATLAS detector at the Large Hadron Collider. The search is conducted by examining the W H / Z H invariant mass distribution for a localized excess. No significant deviation from the Standard Model background prediction is observed. The results are interpreted in terms of constraints on the Minimal Walking Technicolor model and on a simplified approach based on a phenomenological Lagrangian of Heavy Vector Triplets

A search for tt̄ resonances using lepton-plus-jets events in proton-proton collisions at √s = 8 TeV with the ATLAS detector

A search for new particles that decay into top quark pairs is reported. The search is performed with the ATLAS experiment at the LHC using an integrated luminosity of 20.3 fb−¹ of proton-proton collision data collected at a centre-of-mass energy of √s=8 TeV. The lepton-plus-jets final state is used, where the top pair decays to W+bW−b̄, with one W boson decaying leptonically and the other hadronically. The invariant mass spectrum of top quark pairs is examined for local excesses or deficits that are inconsistent with the Standard Model predictions. No evidence for a top quark pair resonance is found, and 95% confidence-level limits on the production rate are determined for massive states in benchmark models. The upper limits on the cross-section times branching ratio of a narrow Z′ boson decaying to top pairs range from 4.2 pb to 0.03 pb for resonance masses from 0.4 TeV to 3.0 TeV. A narrow leptophobic topcolour Z′ boson with mass below 1.8 TeV is excluded. Upper limits are set on the cross-section times branching ratio for a broad colour-octet resonance with Γ/m = 15% decaying to tt̄. These range from 4.8 pb to 0.03 pb for masses from 0.4 TeV to 3.0 TeV. A Kaluza-Klein excitation of the gluon in a Randall-Sundrum model is excluded for masses below 2.2 TeV

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Search for single production of vector-like quarks decaying into Wb in pp collisions at √s = 8 TeV with the ATLAS detector

A search for singly produced vector-like Q quarks, where Q can be either a T quark with charge +2/3 or a Y quark with charge −4/3, is performed in proton–proton collisions recorded with the ATLAS detector at the LHC. The dataset corresponds to an integrated luminosity of 20.3 fb −1 and was produced with a centre-of-mass energy of √s = 8 TeV. This analysis targets Q→Wb decays where the W boson decays leptonically. A veto on massive large-radius jets is used to reject the dominant tt̄ background. The reconstructed Q-candidate mass, ranging from 0.4 to 1.2 TeV, is used in the search to discriminate signal from background processes. No significant deviation from the Standard Model expectation is observed, and limits are set on the Q→Wb cross-section times branching ratio. The results are also interpreted as limits on the QWb coupling and the mixing with the Standard Model sector for a singlet T quark or a Y quark from a doublet. T quarks with masses below 0.95 TeV are excluded at 95 % confidence level, assuming a unit coupling and a BR(T→Wb)=0.5, whereas the expected limit is 1.10 TeV

Search for W W/W Z resonance production in ℓνqq final states in pp collisions at √s=13 TeV with the ATLAS detector

A search is conducted for new resonances decaying into a W W or W Z boson pair, where one W boson decays leptonically and the other W or Z boson decays hadronically. It is based on proton-proton collision data with an integrated luminosity of 36.1 fb −1 collected with the ATLAS detector at the Large Hadron Collider at a centre-of-mass energy of s=13 TeV in 2015 and 2016. The search is sensitive to diboson resonance production via vector-boson fusion as well as quark-antiquark annihilation and gluon-gluon fusion mechanisms. No significant excess of events is observed with respect to the Standard Model backgrounds. Several benchmark models are used to interpret the results. Limits on the production cross section are set for a new narrow scalar resonance, a new heavy vector-boson and a spin-2 Kaluza-Klein graviton.[Figure not available: see fulltext.]