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  1. Article ; Online: B cell characteristics define HCV reinfection outcome.

    Underwood, Alexander P / Gupta, Money / Wu, Bing-Ru / Eltahla, Auda A / Boo, Irene / Wang, Jing Jing / Agapiou, David / Abayasingam, Arunasingam / Reynaldi, Arnold / Keoshkerian, Elizabeth / Zhao, Yanran / Brasher, Nicholas / Walker, Melanie R / Bukh, Jens / Maher, Lisa / Gordon, Tom / Davenport, Miles P / Luciani, Fabio / Drummer, Heidi E /
    Lloyd, Andrew R / Bull, Rowena A

    Journal of hepatology

    2024  

    Abstract: ... and Envelope 2 (E2)-specific memory B cell (MBCs) responses were examined longitudinally in 15 ... but not with reinfection clearance. Strong evidence of antigen imprinting was found, and the B cell ... an activated transcriptomic profile in HCV-specific B cells that rapidly expanded upon reinfection.: Conclusions: MBC ...

    Abstract Background and aims: In individuals highly exposed to hepatitis C virus (HCV), reinfection is common, suggesting that natural development of sterilising immunity is difficult. In those that are reinfected, some will develop a persistent infection, while a small proportion repeatedly clear the virus, suggesting natural protection is possible. The aim of this study was to characterise immune responses associated with rapid natural clearance of HCV reinfection.
    Methods: Broad neutralising antibodies (BnAbs) and Envelope 2 (E2)-specific memory B cell (MBCs) responses were examined longitudinally in 15 subjects with varied reinfection outcomes.
    Results: BnAb responses were associated with MBC recall, but not with reinfection clearance. Strong evidence of antigen imprinting was found, and the B cell receptor repertoire showed a high level of clonality with ongoing somatic hypermutation of many clones over subsequent reinfection events. Single cell transcriptomic analyses showed that cleared reinfections featured an activated transcriptomic profile in HCV-specific B cells that rapidly expanded upon reinfection.
    Conclusions: MBC quality, but not necessarily breadth of nAb responses, is important for protection against antigenically diverse variants, which is encouraging for HCV vaccine development.
    Language English
    Publishing date 2024-04-09
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 605953-3
    ISSN 1600-0641 ; 0168-8278
    ISSN (online) 1600-0641
    ISSN 0168-8278
    DOI 10.1016/j.jhep.2024.04.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: SIRT3, a metabolic target linked to ataxia-telangiectasia mutated (ATM) gene deficiency in diffuse large B-cell lymphoma.

    Bhalla, Kavita / Jaber, Sausan / Reagan, Kayla / Hamburg, Arielle / Underwood, Karen F / Jhajharia, Aditya / Singh, Maninder / Bhandary, Binny / Bhat, Shambhu / Nanaji, Nahid M / Hisa, Ruching / McCracken, Carrie / Creasy, Heather Huot / Lapidus, Rena G / Kingsbury, Tami / Mayer, Dirk / Polster, Brian / Gartenhaus, Ronald B

    Scientific reports

    2020  Volume 10, Issue 1, Page(s) 21159

    Abstract: ... cancer. We show that ATM deficiency in diffuse large B-cell lymphoma (DLBCL) significantly induce ...

    Abstract Inactivation of Ataxia-telangiectasia mutated (ATM) gene results in an increased risk to develop cancer. We show that ATM deficiency in diffuse large B-cell lymphoma (DLBCL) significantly induce mitochondrial deacetylase sirtuin-3 (SIRT3) activity, disrupted mitochondrial structure, decreased mitochondrial respiration, and compromised TCA flux compared with DLBCL cells expressing wild type (WT)-ATM. This corresponded to enrichment of glutamate receptor and glutamine pathways in ATM deficient background compared to WT-ATM DLBCL cells. ATM
    MeSH term(s) Ataxia Telangiectasia Mutated Proteins/antagonists & inhibitors ; Ataxia Telangiectasia Mutated Proteins/deficiency ; Ataxia Telangiectasia Mutated Proteins/genetics ; Cell Line, Tumor ; Citric Acid Cycle ; Forkhead Box Protein O3/metabolism ; Humans ; Lymphoma, Large B-Cell, Diffuse/genetics ; Mitochondria/metabolism ; Mitochondria/ultrastructure ; Models, Biological ; Oxygen Consumption ; Sirtuin 1/metabolism ; Sirtuin 3/metabolism
    Chemical Substances FOXO3 protein, human ; Forkhead Box Protein O3 ; Ataxia Telangiectasia Mutated Proteins (EC 2.7.11.1) ; Sirtuin 1 (EC 3.5.1.-) ; Sirtuin 3 (EC 3.5.1.-)
    Language English
    Publishing date 2020-12-03
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-020-78193-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: The serogroup B meningococcal outer membrane vesicle-based vaccine 4CMenB induces cross-species protection against Neisseria gonorrhoeae.

    Leduc, Isabelle / Connolly, Kristie L / Begum, Afrin / Underwood, Knashka / Darnell, Stephen / Shafer, William M / Balthazar, Jacqueline T / Macintyre, Andrew N / Sempowski, Gregory D / Duncan, Joseph A / Little, Marguerite B / Rahman, Nazia / Garges, Eric C / Jerse, Ann E

    PLoS pathogens

    2020  Volume 16, Issue 12, Page(s) e1008602

    Abstract: ... however, it was reported in a retrospective case-control study that vaccination of humans with a serogroup B ...

    Abstract There is a pressing need for a gonorrhea vaccine due to the high disease burden associated with gonococcal infections globally and the rapid evolution of antibiotic resistance in Neisseria gonorrhoeae (Ng). Current gonorrhea vaccine research is in the stages of antigen discovery and the identification of protective immune responses, and no vaccine has been tested in clinical trials in over 30 years. Recently, however, it was reported in a retrospective case-control study that vaccination of humans with a serogroup B Neisseria meningitidis (Nm) outer membrane vesicle (OMV) vaccine (MeNZB) was associated with reduced rates of gonorrhea. Here we directly tested the hypothesis that Nm OMVs induce cross-protection against gonorrhea in a well-characterized female mouse model of Ng genital tract infection. We found that immunization with the licensed Nm OMV-based vaccine 4CMenB (Bexsero) significantly accelerated clearance and reduced the Ng bacterial burden compared to administration of alum or PBS. Serum IgG and vaginal IgA and IgG that cross-reacted with Ng OMVs were induced by 4CMenB vaccination by either the subcutaneous or intraperitoneal routes. Antibodies from vaccinated mice recognized several Ng surface proteins, including PilQ, BamA, MtrE, NHBA (known to be recognized by humans), PorB, and Opa. Immune sera from both mice and humans recognized Ng PilQ and several proteins of similar apparent molecular weight, but MtrE was only recognized by mouse serum. Pooled sera from 4CMenB-immunized mice showed a 4-fold increase in serum bactericidal50 titers against the challenge strain; in contrast, no significant difference in bactericidal activity was detected when sera from 4CMenB-immunized and unimmunized subjects were compared. Our findings directly support epidemiological evidence that Nm OMVs confer cross-species protection against gonorrhea, and implicate several Ng surface antigens as potentially protective targets. Additionally, this study further defines the usefulness of murine infection model as a relevant experimental system for gonorrhea vaccine development.
    MeSH term(s) Animals ; Antigens, Bacterial/immunology ; Bacterial Outer Membrane Proteins/immunology ; Bacterial Vaccines/immunology ; Case-Control Studies ; Cross Protection/immunology ; Cross Reactions/immunology ; Female ; Gonorrhea/immunology ; Humans ; Immune Sera/immunology ; Immunization/methods ; Male ; Meningococcal Infections/microbiology ; Meningococcal Vaccines/immunology ; Meningococcal Vaccines/metabolism ; Meningococcal Vaccines/pharmacology ; Mice ; Mice, Inbred BALB C ; Neisseria gonorrhoeae/immunology ; Neisseria meningitidis/immunology ; Neisseria meningitidis, Serogroup B/immunology ; Retrospective Studies ; Serogroup ; Vaccination/methods
    Chemical Substances 4CMenB vaccine ; Antigens, Bacterial ; Bacterial Outer Membrane Proteins ; Bacterial Vaccines ; Immune Sera ; Meningococcal Vaccines
    Language English
    Publishing date 2020-12-08
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7366
    ISSN (online) 1553-7374
    ISSN 1553-7366
    DOI 10.1371/journal.ppat.1008602
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Deletion in chromosome 6 spanning alpha-synuclein and multimerin1 loci in the Rab27a/b double knockout mouse.

    Pattanayak, Rudradip / Underwood, Rachel / Crowley, Michael R / Crossman, David K / Morgan, Jennifer R / Yacoubian, Talene A

    Scientific reports

    2022  Volume 12, Issue 1, Page(s) 9837

    Abstract: ... at either the mRNA or protein level in Rab27a/b DKO mice. PCR of genomic DNA from Rab27a/b DKO mice demonstrated ... Given this deletion involving several genes, the Rab27a/b DKO mouse line should be used with caution or ...

    Abstract We report an incidental 358.5 kb deletion spanning the region encoding for alpha-synuclein (αsyn) and multimerin1 (Mmrn1) in the Rab27a/Rab27b double knockout (DKO) mouse line previously developed by Tolmachova and colleagues in 2007. Western blot and RT-PCR studies revealed lack of αsyn expression at either the mRNA or protein level in Rab27a/b DKO mice. PCR of genomic DNA from Rab27a/b DKO mice demonstrated at least partial deletion of the Snca locus using primers targeted to exon 4 and exon 6. Most genes located in proximity to the Snca locus, including Atoh1, Atoh2, Gm5570, Gm4410, Gm43894, and Grid2, were shown not to be deleted by PCR except for Mmrn1. Using whole genomic sequencing, the complete deletion was mapped to chromosome 6 (60,678,870-61,037,354), a slightly smaller deletion region than that previously reported in the C57BL/6J substrain maintained by Envigo. Electron microscopy of cortex from these mice demonstrates abnormally enlarged synaptic terminals with reduced synaptic vesicle density, suggesting potential interplay between Rab27 isoforms and αsyn, which are all highly expressed at the synaptic terminal. Given this deletion involving several genes, the Rab27a/b DKO mouse line should be used with caution or with appropriate back-crossing to other C57BL/6J mouse substrain lines without this deletion.
    MeSH term(s) Animals ; Chromosomes, Mammalian ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Protein Isoforms ; alpha-Synuclein/genetics ; alpha-Synuclein/metabolism ; rab27 GTP-Binding Proteins/genetics ; rab27 GTP-Binding Proteins/metabolism
    Chemical Substances Protein Isoforms ; alpha-Synuclein ; rab27 GTP-Binding Proteins ; Rab27a protein, mouse (EC 3.6.1.-.)
    Language English
    Publishing date 2022-06-14
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-022-13557-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Role of hypoxia in Diffuse Large B-cell Lymphoma: Metabolic repression and selective translation of HK2 facilitates development of DLBCL.

    Bhalla, Kavita / Jaber, Sausan / Nahid M, Nanaji / Underwood, Karen / Beheshti, Afshin / Landon, Ari / Bhandary, Binny / Bastian, Paul / Evens, Andrew M / Haley, John / Polster, Brian / Gartenhaus, Ronald B

    Scientific reports

    2018  Volume 8, Issue 1, Page(s) 744

    Abstract: Published molecular profiling studies in patients with lymphoma suggested the influence of hypoxia inducible factor-1 alpha (HIF1α) targets in prognosis of DLBCL. Yet, the role of hypoxia in hematological malignancies remains unclear. We observed that ... ...

    Abstract Published molecular profiling studies in patients with lymphoma suggested the influence of hypoxia inducible factor-1 alpha (HIF1α) targets in prognosis of DLBCL. Yet, the role of hypoxia in hematological malignancies remains unclear. We observed that activation of HIF1α resulted in global translation repression during hypoxic stress in DLBCL. Protein translation efficiency as measured using
    MeSH term(s) Animals ; Gene Expression Regulation ; Humans ; Hypoxia ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Kinesins/biosynthesis ; Lymphoma, Large B-Cell, Diffuse/physiopathology ; Protein Biosynthesis ; Tumor Cells, Cultured
    Chemical Substances HIF1A protein, human ; Hypoxia-Inducible Factor 1, alpha Subunit ; KIF2A protein, human ; Kinesins (EC 3.6.4.4)
    Language English
    Publishing date 2018-01-15
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-018-19182-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Changes in symptomatology, reinfection, and transmissibility associated with the SARS-CoV-2 variant B.1.1.7

    Mark S Graham, PhD / Carole H Sudre, PhD / Anna May, MA / Michela Antonelli, PhD / Benjamin Murray, MSc / Thomas Varsavsky, MSc / Kerstin Kläser, MSc / Liane S Canas, PhD / Erika Molteni, PhD / Marc Modat, PhD / David A Drew, PhD / Long H Nguyen, MD / Lorenzo Polidori, MSc / Somesh Selvachandran, MSc / Christina Hu, MA / Joan Capdevila, PhD / Alexander Hammers, ProfPhD / Andrew T Chan, ProfMD / Jonathan Wolf, MA /
    Tim D Spector, ProfPhD / Claire J Steves, PhD / Sebastien Ourselin, ProfPhD / Cherian Koshy / Amy Ash / Emma Wise / Nathan Moore / Matilde Mori / Nick Cortes / Jessica Lynch / Stephen Kidd / Derek J Fairley / Tanya Curran / James P McKenna / Helen Adams / Christophe Fraser / Tanya Golubchik / David Bonsall / Mohammed O Hassan-Ibrahim / Cassandra S Malone / Benjamin J Cogger / Michelle Wantoch / Nicola Reynolds / Ben Warne / Joshua Maksimovic / Karla Spellman / Kathryn McCluggage / Michaela John / Robert Beer / Safiah Afifi / Sian Morgan / Angela Marchbank / Anna Price / Christine Kitchen / Huw Gulliver / Ian Merrick / Joel Southgate / Martyn Guest / Robert Munn / Trudy Workman / Thomas R Connor / William Fuller / Catherine Bresner / Luke B Snell / Amita Patel / Themoula Charalampous / Gaia Nebbia / Rahul Batra / Jonathan Edgeworth / Samuel C Robson / Angela H Beckett / David M Aanensen / Anthony P Underwood / Corin A Yeats / Khalil Abudahab / Ben EW Taylor / Mirko Menegazzo / Gemma Clark / Wendy Smith / Manjinder Khakh / Vicki M Fleming / Michelle M Lister / Hannah C Howson-Wells / Louise Berry / Tim Boswell / Amelia Joseph / Iona Willingham / Carl Jones / Christopher Holmes / Paul Bird / Thomas Helmer / Karlie Fallon / Julian Tang / Veena Raviprakash / Sharon Campbell / Nicola Sheriff / Victoria Blakey / Lesley-Anne Williams / Matthew W Loose / Nadine Holmes / Christopher Moore / Matthew Carlile / Victoria Wright / Fei Sang / Johnny Debebe / Francesc Coll / Adrian W Signell / Gilberto Betancor / Harry D Wilson / Sahar Eldirdiri / Anita Kenyon / Thomas Davis / Oliver G Pybus / Louis du Plessis / Alex E Zarebski / Jayna Raghwani / Moritz UG Kraemer / Sarah Francois / Stephen W Attwood / Tetyana I Vasylyeva / Marina Escalera Zamudio / Bernardo Gutierrez / M. Estee Torok / William L Hamilton / Ian G Goodfellow / Grant Hall / Aminu S Jahun / Yasmin Chaudhry / Myra Hosmillo / Malte L Pinckert / Iliana Georgana / Samuel Moses / Hannah Lowe / Luke Bedford / Jonathan Moore / Susanne Stonehouse / Chloe L Fisher / Ali R Awan / John BoYes / Judith Breuer / Kathryn Ann Harris / Julianne Rose Brown / Divya Shah / Laura Atkinson / Jack CD Lee / Nathaniel Storey / Flavia Flaviani / Adela Alcolea-Medina / Rebecca Williams / Gabrielle Vernet / Michael R Chapman / Lisa J Levett / Judith Heaney / Wendy Chatterton / Monika Pusok / Li Xu-McCrae / Darren L Smith / Matthew Bashton / Gregory R Young / Alison Holmes / Paul Anthony Randell / Alison Cox / Pinglawathee Madona / Frances Bolt / James Price / Siddharth Mookerjee / Manon Ragonnet-Cronin / Fabricia F. Nascimento / David Jorgensen / Igor Siveroni / Rob Johnson / Olivia Boyd / Lily Geidelberg / Erik M Volz / Aileen Rowan / Graham P Taylor / Katherine L Smollett / Nicholas J Loman / Joshua Quick / Claire McMurray / Joanne Stockton / Sam Nicholls / Will Rowe / Radoslaw Poplawski / Alan McNally / Rocio T Martinez Nunez / Jenifer Mason / Trevor I Robinson / Elaine O'Toole / Joanne Watts / Cassie Breen / Angela Cowell / Graciela Sluga / Nicholas W Machin / Shazaad S Y Ahmad / Ryan P George / Fenella Halstead / Venkat Sivaprakasam / Wendy Hogsden / Chris J Illingworth / Chris Jackson / Emma C Thomson / James G Shepherd / Patawee Asamaphan / Marc O Niebel / Kathy K Li / Rajiv N Shah / Natasha G Jesudason / Lily Tong / Alice Broos / Daniel Mair / Jenna Nichols / Stephen N Carmichael / Kyriaki Nomikou / Elihu Aranday-Cortes / Natasha Johnson / Igor Starinskij / Ana da Silva Filipe / David L Robertson / Richard J Orton / Joseph Hughes / Sreenu Vattipally / Joshua B Singer / Seema Nickbakhsh / Antony D Hale / Louissa R Macfarlane-Smith / Katherine L Harper / Holli Carden / Yusri Taha / Brendan AI Payne / Shirelle Burton-Fanning / Sheila Waugh / Jennifer Collins / Gary Eltringham / Steven Rushton / Sarah O'Brien / Amanda Bradley / Alasdair Maclean / Guy Mollett / Rachel Blacow / Kate E Templeton / Martin P McHugh / Rebecca Dewar / Elizabeth Wastenge / Samir Dervisevic / Rachael Stanley / Emma J Meader / Lindsay Coupland / Louise Smith / Clive Graham / Edward Barton / Debra Padgett / Garren Scott / Emma Swindells / Jane Greenaway / Andrew Nelson / Clare M McCann / Wen C Yew / Monique Andersson / Timothy Peto / Anita Justice / David Eyre / Derrick Crook / Tim J Sloan / Nichola Duckworth / Sarah Walsh / Anoop J Chauhan / Sharon Glaysher / Kelly Bicknell / Sarah Wyllie / Scott Elliott / Allyson Lloyd / Robert Impey / Nick Levene / Lynn Monaghan / Declan T Bradley / Tim Wyatt / Elias Allara / Clare Pearson / Husam Osman / Andrew Bosworth / Esther Robinson / Peter Muir / Ian B Vipond / Richard Hopes / Hannah M Pymont / Stephanie Hutchings / Martin D Curran / Surendra Parmar / Angie Lackenby / Tamyo Mbisa / Steven Platt / Shahjahan Miah / David Bibby / Carmen Manso / Jonathan Hubb / Meera Chand / Gavin Dabrera / Mary Ramsay / Daniel Bradshaw / Alicia Thornton / Richard Myers / Ulf Schaefer / Natalie Groves / Eileen Gallagher / David Lee / David Williams / Nicholas Ellaby / Ian Harrison / Hassan Hartman / Nikos Manesis / Vineet Patel / Chloe Bishop / Vicki Chalker / Juan Ledesma / Katherine A Twohig / Matthew T.G. Holden / Sharif Shaaban / Alec Birchley / Alexander Adams / Alisha Davies / Amy Gaskin / Amy Plimmer / Bree Gatica-Wilcox / Caoimhe McKerr / Catherine Moore / Chris Williams / David Heyburn / Elen De Lacy / Ember Hilvers / Fatima Downing / Giri Shankar / Hannah Jones / Hibo Asad / Jason Coombes / Joanne Watkins / Johnathan M Evans / Laia Fina / Laura Gifford / Lauren Gilbert / Lee Graham / Malorie Perry / Mari Morgan / Matthew Bull / Michelle Cronin / Nicole Pacchiarini / Noel Craine / Rachel Jones / Robin Howe / Sally Corden / Sara Rey / Sara Kumziene-SummerhaYes / Sarah Taylor / Simon Cottrell / Sophie Jones / Sue Edwards / Justin O'Grady / Andrew J Page / Alison E Mather / David J Baker / Steven Rudder / Alp Aydin / Gemma L Kay / Alexander J Trotter / Nabil-Fareed Alikhan / Leonardo de Oliveira Martins / Thanh Le-Viet / Lizzie Meadows / Anna Casey / Liz Ratcliffe / David A Simpson / Zoltan Molnar / Thomas Thompson / Erwan Acheson / Jane AH Masoli / Bridget A Knight / Sian Ellard / Cressida Auckland / Christopher R Jones / Tabitha W Mahungu / Dianne Irish-Tavares / Tanzina Haque / Jennifer Hart / Eric Witele / Melisa Louise Fenton / Ashok Dadrah / Amanda Symmonds / Tranprit Saluja / Yann Bourgeois / Garry P Scarlett / Katie F Loveson / Salman Goudarzi / Christopher Fearn / Kate Cook / Hannah Dent / Hannah Paul / David G Partridge / Mohammad Raza / Cariad Evans / Kate Johnson / Steven Liggett / Paul Baker / Stephen Bonner / Sarah Essex / Ronan A Lyons / Kordo Saeed / Adhyana I.K Mahanama / Buddhini Samaraweera / Siona Silveira / Emanuela Pelosi / Eleri Wilson-Davies / Rachel J Williams / Mark Kristiansen / Sunando Roy / Charlotte A Williams / Marius Cotic / Nadua Bayzid / Adam P Westhorpe / John A Hartley / Riaz Jannoo / Helen L Lowe / Angeliki Karamani / Leah Ensell / Jacqui A Prieto / Sarah Jeremiah / Dimitris Grammatopoulos / Sarojini Pandey / Lisa Berry / Katie Jones / Alex Richter / Andrew Beggs / Angus Best / Benita Percival / Jeremy Mirza / Oliver Megram / Megan Mayhew / Liam Crawford / Fiona Ashcroft / Emma Moles-Garcia / Nicola Cumley / Colin P Smith / Giselda Bucca / Andrew R Hesketh / Beth Blane / Sophia T Girgis / Danielle Leek / Sushmita Sridhar / Sally Forrest / Claire Cormie / Harmeet K Gill / Joana Dias / Ellen E Higginson / Mailis Maes / Jamie Young / Leanne M Kermack / Ravi Kumar Gupta / Catherine Ludden / Sharon J Peacock / Sophie Palmer / Carol M Churcher / Nazreen F Hadjirin / Alessandro M Carabelli / Ellena Brooks / Kim S Smith / Katerina Galai / Georgina M McManus / Chris Ruis / Rose K Davidson / Andrew Rambaut / Thomas Williams / Carlos E Balcazar / Michael D Gallagher / Áine O'Toole / Stefan Rooke / Verity Hill / Kathleen A Williamson / Thomas D Stanton / Stephen L Michell / Claire M Bewshea / Ben Temperton / Michelle L Michelsen / Joanna Warwick-Dugdale / Robin Manley / Audrey Farbos / James W Harrison / Christine M Sambles / David J Studholme / Aaron R Jeffries / Alistair C Darby / Julian A Hiscox / Steve Paterson / Miren Iturriza-Gomara / Kathryn A Jackson / Anita O Lucaci / Edith E Vamos / Margaret Hughes / Lucille Rainbow / Richard Eccles / Charlotte Nelson / Mark Whitehead / Lance Turtle / Sam T Haldenby / Richard Gregory / Matthew Gemmell / Claudia Wierzbicki / Hermione J Webster / Thushan I de Silva / Nikki Smith / Adrienn Angyal / Benjamin B Lindsey / Danielle C Groves / Luke R Green / Dennis Wang / Timothy M Freeman / Matthew D Parker / Alexander J Keeley / Paul J Parsons / Rachel M Tucker / Rebecca Brown / Matthew Wyles / Max Whiteley / Peijun Zhang / Marta Gallis / Stavroula F Louka / Chrystala Constantinidou / Meera Unnikrishnan / Sascha Ott / Jeffrey K.J. Cheng / Hannah E. Bridgewater / Lucy R. Frost / Grace Taylor-Joyce / Richard Stark / Laura Baxter / Mohammad T. Alam / Paul E Brown / Dinesh Aggarwal / Alberto C Cerda / Tammy V Merrill / Rebekah E Wilson / Patrick C McClure / Joseph G Chappell / Theocharis Tsoleridis / Jonathan Ball / David Buck / John A Todd / Angie Green / Amy Trebes / George MacIntyre-Cockett / Mariateresa de Cesare / Alex Alderton / Roberto Amato / Cristina V Ariani / Mathew A Beale / Charlotte Beaver / Katherine L Bellis / Emma Betteridge / James Bonfield / John Danesh / Matthew J Dorman / Eleanor Drury / Ben W Farr / Luke Foulser / Sonia Goncalves / Scott Goodwin / Marina Gourtovaia / Ewan M Harrison / David K Jackson / Dorota Jamrozy / Ian Johnston / Leanne Kane / Sally Kay / Jon-Paul Keatley / Dominic Kwiatkowski / Cordelia F Langford / Mara Lawniczak / Laura Letchford / Rich Livett / Stephanie Lo / Inigo Martincorena / Samantha McGuigan / Rachel Nelson / Steve Palmer / Naomi R Park / Minal Patel / Liam Prestwood / Christoph Puethe / Michael A Quail / Shavanthi Rajatileka / Carol Scott / Lesley Shirley / John Sillitoe / Michael H Spencer Chapman / Scott AJ Thurston / Gerry Tonkin-Hill / Danni Weldon / Diana Rajan / Iraad F Bronner / Louise Aigrain / Nicholas M Redshaw / Stefanie V Lensing / Robert Davies / Andrew Whitwham / Jennifier Liddle / Kevin Lewis / Jaime M Tovar-Corona / Steven Leonard / Jillian Durham / Andrew R Bassett / Shane McCarthy / Robin J Moll / Keith James / Karen Oliver / Alex Makunin / Jeff Barrett / Rory N Gunson

    The Lancet Public Health, Vol 6, Iss 5, Pp e335-e

    an ecological study

    2021  Volume 345

    Abstract: Summary: Background: The SARS-CoV-2 variant B.1.1.7 was first identified in December, 2020 ... with the SARS-CoV-2 B.1.1.7 variant and reported symptoms, disease course, rates of reinfection, and ... during which the prevalence of B.1.1.7 increased most notably in parts of the UK). From this dataset ...

    Abstract Summary: Background: The SARS-CoV-2 variant B.1.1.7 was first identified in December, 2020, in England. We aimed to investigate whether increases in the proportion of infections with this variant are associated with differences in symptoms or disease course, reinfection rates, or transmissibility. Methods: We did an ecological study to examine the association between the regional proportion of infections with the SARS-CoV-2 B.1.1.7 variant and reported symptoms, disease course, rates of reinfection, and transmissibility. Data on types and duration of symptoms were obtained from longitudinal reports from users of the COVID Symptom Study app who reported a positive test for COVID-19 between Sept 28 and Dec 27, 2020 (during which the prevalence of B.1.1.7 increased most notably in parts of the UK). From this dataset, we also estimated the frequency of possible reinfection, defined as the presence of two reported positive tests separated by more than 90 days with a period of reporting no symptoms for more than 7 days before the second positive test. The proportion of SARS-CoV-2 infections with the B.1.1.7 variant across the UK was estimated with use of genomic data from the COVID-19 Genomics UK Consortium and data from Public Health England on spike-gene target failure (a non-specific indicator of the B.1.1.7 variant) in community cases in England. We used linear regression to examine the association between reported symptoms and proportion of B.1.1.7. We assessed the Spearman correlation between the proportion of B.1.1.7 cases and number of reinfections over time, and between the number of positive tests and reinfections. We estimated incidence for B.1.1.7 and previous variants, and compared the effective reproduction number, Rt, for the two incidence estimates. Findings: From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7. For the same period, possible reinfections were identified in 249 (0·7% [95% CI 0·6–0·8]) of 36 509 app users who reported a positive swab test before Oct 1, 2020, but there was no evidence that the frequency of reinfections was higher for the B.1.1.7 variant than for pre-existing variants. Reinfection occurrences were more positively correlated with the overall regional rise in cases (Spearman correlation 0·56–0·69 for South East, London, and East of England) than with the regional increase in the proportion of infections with the B.1.1.7 variant (Spearman correlation 0·38–0·56 in the same regions), suggesting B.1.1.7 does not substantially alter the risk of reinfection. We found a multiplicative increase in the Rt of B.1.1.7 by a factor of 1·35 (95% CI 1·02–1·69) relative to pre-existing variants. However, Rt fell below 1 during regional and national lockdowns, even in regions with high proportions of infections with the B.1.1.7 variant. Interpretation: The lack of change in symptoms identified in this study indicates that existing testing and surveillance infrastructure do not need to change specifically for the B.1.1.7 variant. In addition, given that there was no apparent increase in the reinfection rate, vaccines are likely to remain effective against the B.1.1.7 variant. Funding: Zoe Global, Department of Health (UK), Wellcome Trust, Engineering and Physical Sciences Research Council (UK), National Institute for Health Research (UK), Medical Research Council (UK), Alzheimer's Society.
    Keywords Public aspects of medicine ; RA1-1270
    Subject code 150
    Language English
    Publishing date 2021-05-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
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  7. Article ; Online: The serogroup B meningococcal outer membrane vesicle-based vaccine 4CMenB induces cross-species protection against Neisseria gonorrhoeae.

    Isabelle Leduc / Kristie L Connolly / Afrin Begum / Knashka Underwood / Stephen Darnell / William M Shafer / Jacqueline T Balthazar / Andrew N Macintyre / Gregory D Sempowski / Joseph A Duncan / Marguerite B Little / Nazia Rahman / Eric C Garges / Ann E Jerse

    PLoS Pathogens, Vol 16, Iss 12, p e

    2020  Volume 1008602

    Abstract: ... however, it was reported in a retrospective case-control study that vaccination of humans with a serogroup B ...

    Abstract There is a pressing need for a gonorrhea vaccine due to the high disease burden associated with gonococcal infections globally and the rapid evolution of antibiotic resistance in Neisseria gonorrhoeae (Ng). Current gonorrhea vaccine research is in the stages of antigen discovery and the identification of protective immune responses, and no vaccine has been tested in clinical trials in over 30 years. Recently, however, it was reported in a retrospective case-control study that vaccination of humans with a serogroup B Neisseria meningitidis (Nm) outer membrane vesicle (OMV) vaccine (MeNZB) was associated with reduced rates of gonorrhea. Here we directly tested the hypothesis that Nm OMVs induce cross-protection against gonorrhea in a well-characterized female mouse model of Ng genital tract infection. We found that immunization with the licensed Nm OMV-based vaccine 4CMenB (Bexsero) significantly accelerated clearance and reduced the Ng bacterial burden compared to administration of alum or PBS. Serum IgG and vaginal IgA and IgG that cross-reacted with Ng OMVs were induced by 4CMenB vaccination by either the subcutaneous or intraperitoneal routes. Antibodies from vaccinated mice recognized several Ng surface proteins, including PilQ, BamA, MtrE, NHBA (known to be recognized by humans), PorB, and Opa. Immune sera from both mice and humans recognized Ng PilQ and several proteins of similar apparent molecular weight, but MtrE was only recognized by mouse serum. Pooled sera from 4CMenB-immunized mice showed a 4-fold increase in serum bactericidal50 titers against the challenge strain; in contrast, no significant difference in bactericidal activity was detected when sera from 4CMenB-immunized and unimmunized subjects were compared. Our findings directly support epidemiological evidence that Nm OMVs confer cross-species protection against gonorrhea, and implicate several Ng surface antigens as potentially protective targets. Additionally, this study further defines the usefulness of murine infection model as a relevant ...
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Subject code 630
    Language English
    Publishing date 2020-12-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
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  8. Article ; Online: Early probiotic supplementation with B. infantis in breastfed infants leads to persistent colonization at 1 year.

    O'Brien, Claire E / Meier, Anna K / Cernioglo, Karina / Mitchell, Ryan D / Casaburi, Giorgio / Frese, Steven A / Henrick, Bethany M / Underwood, Mark A / Smilowitz, Jennifer T

    Pediatric research

    2021  Volume 91, Issue 3, Page(s) 627–636

    Abstract: ... 10: Results: Fecal B. infantis was 2.5-3.5 log units higher at 6-12 months in the EVC group ... conditions between the two groups.: Conclusions: Probiotic supplementation with B. infantis ... to show that early probiotic supplementation with B. infantis with breast milk results in stable ...

    Abstract Background: Recent studies have reported a dysfunctional gut microbiome in breastfed infants. Probiotics have been used in an attempt to restore the gut microbiome; however, colonization has been transient, inconsistent among individuals, or has not positively impacted the host's gut.
    Methods: This is a 2-year follow-up study to a randomized controlled trial wherein 7-day-old infants received 1.8 × 10
    Results: Fecal B. infantis was 2.5-3.5 log units higher at 6-12 months in the EVC group compared with the UNS group (P < 0.01) and this relationship strengthened with the exclusion of infants who consumed infant formula and antibiotics. Infants in the EVC group had significantly higher Bifidobacteriaceae and lower Bacteroidaceae and Lachnospiraceae (P < 0.05). There were no differences in any health conditions between the two groups.
    Conclusions: Probiotic supplementation with B. infantis within the first month postnatal, in combination with breast milk, resulted in stable colonization that persisted until at least 1 year postnatal.
    Impact: A dysfunctional gut microbiome in breastfed infants is common in resource-rich nations and associated with an increased risk of immune diseases. Probiotics only transiently exist in the gut without persistent colonization or altering the gut microbiome. This is the first study to show that early probiotic supplementation with B. infantis with breast milk results in stable colonization of B. infantis and improvements to the gut microbiome 1 year postnatal. This study addresses a key gap in the literature whereby probiotics can restore the gut microbiome if biologically selected microorganisms are matched with their specific food in an open ecological niche.
    MeSH term(s) Bifidobacterium longum subspecies infantis ; Breast Feeding ; Feces/microbiology ; Female ; Follow-Up Studies ; Gastrointestinal Microbiome ; Humans ; Infant ; Milk, Human ; Probiotics
    Language English
    Publishing date 2021-03-24
    Publishing country United States
    Document type Journal Article ; Randomized Controlled Trial ; Research Support, N.I.H., Extramural
    ZDB-ID 4411-8
    ISSN 1530-0447 ; 0031-3998
    ISSN (online) 1530-0447
    ISSN 0031-3998
    DOI 10.1038/s41390-020-01350-0
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  9. Article ; Online: Colonization by B. infantis EVC001 modulates enteric inflammation in exclusively breastfed infants.

    Henrick, Bethany M / Chew, Stephanie / Casaburi, Giorgio / Brown, Heather K / Frese, Steven A / Zhou, You / Underwood, Mark A / Smilowitz, Jennifer T

    Pediatric research

    2019  Volume 86, Issue 6, Page(s) 749–757

    Abstract: ... diseases. We investigated the impact of B. infantis EVC001 colonization on enteric inflammation in a subset ... indicate that gut dysbiosis (absence of B. infantis) is associated with increased intestinal inflammation ...

    Abstract Background: Infant gut dysbiosis, often associated with low abundance of bifidobacteria, is linked to impaired immune development and inflammation-a risk factor for increased incidence of several childhood diseases. We investigated the impact of B. infantis EVC001 colonization on enteric inflammation in a subset of exclusively breastfed term infants from a larger clinical study.
    Methods: Stool samples (n = 120) were collected from infants randomly selected to receive either 1.8 × 10
    Results: Fecal calprotectin concentration negatively correlated with Bifidobacterium abundance (P < 0.0001; ρ = -0.72), and proinflammatory cytokines correlated with Clostridiaceae and Enterobacteriaceae, yet negatively correlated with Bifidobacteriaceae abundance. Proinflammatory cytokines were significantly lower in EVC001-fed infants on days 40 and 60 postnatally compared to baseline and compared to control infants.
    Conclusion: Our findings indicate that gut dysbiosis (absence of B. infantis) is associated with increased intestinal inflammation. Early addition of EVC001 to diet represents a novel strategy to prevent enteric inflammation during a critical developmental phase.
    MeSH term(s) Bifidobacterium longum subspecies infantis/growth & development ; Breast Feeding ; Cytokines/metabolism ; Enteritis/metabolism ; Enteritis/microbiology ; Enteritis/prevention & control ; Feces/chemistry ; Feces/microbiology ; Female ; Gastrointestinal Microbiome ; Humans ; Infant, Newborn ; Inflammation Mediators/metabolism ; Leukocyte L1 Antigen Complex/analysis ; Male ; Prospective Studies
    Chemical Substances Cytokines ; Inflammation Mediators ; Leukocyte L1 Antigen Complex
    Language English
    Publishing date 2019-08-23
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 4411-8
    ISSN 1530-0447 ; 0031-3998
    ISSN (online) 1530-0447
    ISSN 0031-3998
    DOI 10.1038/s41390-019-0533-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Author Correction: Role of hypoxia in Diffuse Large B-cell Lymphoma: Metabolic repression and selective translation of HK2 facilitates development of DLBCL.

    Bhalla, Kavita / Jaber, Sausan / Nahid M, Nanaji / Underwood, Karen / Beheshti, Afshin / Landon, Ari / Bhandary, Binny / Bastian, Paul / Evens, Andrew M / Haley, John / Polster, Brian / Gartenhaus, Ronald B

    Scientific reports

    2018  Volume 8, Issue 1, Page(s) 7221

    Abstract: A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper. ...

    Abstract A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
    Language English
    Publishing date 2018-05-03
    Publishing country England
    Document type Published Erratum
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-018-25251-9
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