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Article ; Online: Genomic monitoring unveil the early detection of the SARS-CoV-2 B.1.351 (beta) variant (20H/501Y.V2) in Brazil.

Slavov, Svetoslav N / Patané, José S L / Bezerra, Rafael Dos Santos / Giovanetti, Marta / Fonseca, Vagner / Martins, Antonio J / Viala, Vincent L / Rodrigues, Evandra S / Santos, Elaine V / Barros, Claudia R S / Marqueze, Elaine C / Santos, Bibiana / Aburjaile, Flavia / Neto, Raul M / Moretti, Debora B / Haddad, Ricardo / Calado, Rodrigo T / Kitajima, João P / Freitas, Erika /

Schlesinger, David / Junior de Alcantara, Luiz C / Elias, Maria C / Sampaio, Sandra C / Kashima, Simone / Covas, Dimas T

Journal of medical virology

2021 Volume 93, Issue 12, Page(s) 6782–6787

Abstract: ... regional health departments we identified cocirculation of multiple SARS-CoV-2 lineages such as B.1.1 (0.5 ... B.1.1.28 (23.2%), B.1.1.7 (alpha variant, 6.2%), B.1.566 (1.4%), B.1.544 (0.5%), C.37 (0.5%) P.1 ... for the first time in Brazil, the South African B.1.351 (beta) variant of concern, B.1.351 (501Y.V2) (0.5 ...

Abstract	Sao Paulo State, currently experiences a second COVID-19 wave overwhelming the healthcare system. Due to the paucity of SARS-CoV-2 complete genome sequencing, we established a Network for Pandemic Alert of Emerging SARS-CoV-2 Variants to rapidly understand and monitor the spread of SARS-CoV-2 variants into the state. Through analysis of 210 SARS-CoV-2 complete genomes obtained from the largest regional health departments we identified cocirculation of multiple SARS-CoV-2 lineages such as B.1.1 (0.5%), B.1.1.28 (23.2%), B.1.1.7 (alpha variant, 6.2%), B.1.566 (1.4%), B.1.544 (0.5%), C.37 (0.5%) P.1 (gamma variant, 66.2%), and P.2 (zeta variant, 1.0%). Our analysis allowed also the detection, for the first time in Brazil, the South African B.1.351 (beta) variant of concern, B.1.351 (501Y.V2) (0.5%), characterized by the following mutations: ORF1ab: T265I, R724K, S1612L, K1655N, K3353R, SGF 3675_F3677del, P4715L, E5585D; spike: D80A, D215G, L242_L244del, A262D, K417N, E484K, N501Y, D614G, A701V, C1247F; ORF3a: Q57H, S171L, E: P71L; ORF7b: Y10F, N: T205I; ORF14: L52F. The most recent common ancestor of the identified strain was inferred to be mid-October to late December 2020. Our analysis demonstrated the P.1 lineage predominance and allowed the early detection of the South African strain for the first time in Brazil. We highlight the importance of SARS-CoV-2 active monitoring to ensure the rapid detection of potential variants for pandemic control and vaccination strategies. Highlights Identification of B.1.351 (beta) variant of concern in the Sao Paulo State. Dissemination of SARS-CoV-2 variants of concern and interest in the Sao Paulo State. Mutational Profile of the circulating variants of concern and interest.
MeSH term(s)	Antibodies, Neutralizing/immunology ; Antibodies, Viral/immunology ; Brazil ; COVID-19/immunology ; COVID-19/virology ; Genomics/methods ; Humans ; Mutation/genetics ; Mutation/immunology ; SARS-CoV-2/genetics ; SARS-CoV-2/immunology ; Spike Glycoprotein, Coronavirus/genetics ; Spike Glycoprotein, Coronavirus/immunology
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; Spike Glycoprotein, Coronavirus
Language	English
Publishing date	2021-07-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	752392-0
ISSN	1096-9071 ; 0146-6615
ISSN (online)	1096-9071
ISSN	0146-6615
DOI	10.1002/jmv.27190
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Article ; Online: Intestinal B cells license metabolic T-cell activation in NASH microbiota/antigen-independently and contribute to fibrosis by IgA-FcR signalling.

Kotsiliti, Elena / Leone, Valentina / Schuehle, Svenja / Govaere, Olivier / Li, Hai / Wolf, Monika J / Horvatic, Helena / Bierwirth, Sandra / Hundertmark, Jana / Inverso, Donato / Zizmare, Laimdota / Sarusi-Portuguez, Avital / Gupta, Revant / O'Connor, Tracy / Giannou, Anastasios D / Shiri, Ahmad Mustafa / Schlesinger, Yehuda / Beccaria, Maria Garcia / Rennert, Charlotte /

Pfister, Dominik / Öllinger, Rupert / Gadjalova, Iana / Ramadori, Pierluigi / Rahbari, Mohammad / Rahbari, Nuh / Healy, Marc E / Fernández-Vaquero, Mirian / Yahoo, Neda / Janzen, Jakob / Singh, Indrabahadur / Fan, Chaofan / Liu, Xinyuan / Rau, Monika / Feuchtenberger, Martin / Schwaneck, Eva / Wallace, Sebastian J / Cockell, Simon / Wilson-Kanamori, John / Ramachandran, Prakash / Kho, Celia / Kendall, Timothy J / Leblond, Anne-Laure / Keppler, Selina J / Bielecki, Piotr / Steiger, Katja / Hofmann, Maike / Rippe, Karsten / Zitzelsberger, Horst / Weber, Achim / Malek, Nisar / Luedde, Tom / Vucur, Mihael / Augustin, Hellmut G / Flavell, Richard / Parnas, Oren / Rad, Roland / Pabst, Olivier / Henderson, Neil C / Huber, Samuel / Macpherson, Andrew / Knolle, Percy / Claassen, Manfred / Geier, Andreas / Trautwein, Christoph / Unger, Kristian / Elinav, Eran / Waisman, Ari / Abdullah, Zeinab / Haller, Dirk / Tacke, Frank / Anstee, Quentin M / Heikenwalder, Mathias

Journal of hepatology

2023 Volume 79, Issue 2, Page(s) 296–313

Abstract: ... We investigated the role of gastrointestinal B cells in the development of NASH, fibrosis and NASH-induced HCC ... Methods: C57BL/6J wild-type (WT), B cell-deficient and different immunoglobulin-deficient or transgenic ... containing B cells only in the gastrointestinal tract) were fed a choline-deficient high-fat diet, and ...

Abstract	Background & aims: The progression of non-alcoholic steatohepatitis (NASH) to fibrosis and hepatocellular carcinoma (HCC) is aggravated by auto-aggressive T cells. The gut-liver axis contributes to NASH, but the mechanisms involved and the consequences for NASH-induced fibrosis and liver cancer remain unknown. We investigated the role of gastrointestinal B cells in the development of NASH, fibrosis and NASH-induced HCC. Methods: C57BL/6J wild-type (WT), B cell-deficient and different immunoglobulin-deficient or transgenic mice were fed distinct NASH-inducing diets or standard chow for 6 or 12 months, whereafter NASH, fibrosis, and NASH-induced HCC were assessed and analysed. Specific pathogen-free/germ-free WT and μMT mice (containing B cells only in the gastrointestinal tract) were fed a choline-deficient high-fat diet, and treated with an anti-CD20 antibody, whereafter NASH and fibrosis were assessed. Tissue biopsy samples from patients with simple steatosis, NASH and cirrhosis were analysed to correlate the secretion of immunoglobulins to clinicopathological features. Flow cytometry, immunohistochemistry and single-cell RNA-sequencing analysis were performed in liver and gastrointestinal tissue to characterise immune cells in mice and humans. Results: Activated intestinal B cells were increased in mouse and human NASH samples and licensed metabolic T-cell activation to induce NASH independently of antigen specificity and gut microbiota. Genetic or therapeutic depletion of systemic or gastrointestinal B cells prevented or reverted NASH and liver fibrosis. IgA secretion was necessary for fibrosis induction by activating CD11b+CCR2+F4/80+CD11c-FCGR1+ hepatic myeloid cells through an IgA-FcR signalling axis. Similarly, patients with NASH had increased numbers of activated intestinal B cells; additionally, we observed a positive correlation between IgA levels and activated FcRg+ hepatic myeloid cells, as well the extent of liver fibrosis. Conclusions: Intestinal B cells and the IgA-FcR signalling axis represent potential therapeutic targets for the treatment of NASH. Impact and implications: There is currently no effective treatment for non-alcoholic steatohepatitis (NASH), which is associated with a substantial healthcare burden and is a growing risk factor for hepatocellular carcinoma (HCC). We have previously shown that NASH is an auto-aggressive condition aggravated, amongst others, by T cells. Therefore, we hypothesized that B cells might have a role in disease induction and progression. Our present work highlights that B cells have a dual role in NASH pathogenesis, being implicated in the activation of auto-aggressive T cells and the development of fibrosis via activation of monocyte-derived macrophages by secreted immunoglobulins (e.g., IgA). Furthermore, we show that the absence of B cells prevented HCC development. B cell-intrinsic signalling pathways, secreted immunoglobulins, and interactions of B cells with other immune cells are potential targets for combinatorial NASH therapies against inflammation and fibrosis.
MeSH term(s)	Humans ; Mice ; Animals ; Non-alcoholic Fatty Liver Disease/complications ; Carcinoma, Hepatocellular/pathology ; Liver Neoplasms/genetics ; Mice, Inbred C57BL ; Liver/pathology ; Fibrosis ; Liver Cirrhosis/complications ; Mice, Transgenic ; Microbiota ; Immunoglobulin A/metabolism ; Immunoglobulin A/pharmacology ; Disease Models, Animal ; Diet, High-Fat/adverse effects
Chemical Substances	Immunoglobulin A
Language	English
Publishing date	2023-05-22
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	605953-3
ISSN	1600-0641 ; 0168-8278
ISSN (online)	1600-0641
ISSN	0168-8278
DOI	10.1016/j.jhep.2023.04.037
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Article ; Online: Genomic monitoring unveil the early detection of the SARS-CoV-2 B.1.351 lineage (20H/501Y.V2) in Brazil

Slavov, Svetoslav N / Patane, Jose / Bezerra, Rafael S / Giovanetti, Marta / Fonseca, Vagner / Martins, Antonio J / Viala, Vincent L / Rodrigues, Evandra S / Santos, Elaine V / Barros, Claudia R.S / Marqueze, Elaine C / Santos, Bibiana / Aburjaile, Flavia / Neto, Raul M / Moretti, Debora B / Haddad, Ricardo / Calado, Rodrigo T / Kitajima, Joao Paulo / Freitas, Erika /

Schlesinger, David / Alcantara, Luiz C.J / Elias, M. Carolina / Vessoni, Sandra C.S / Kashima, Simone / Covas, Dimas T

medRxiv

Abstract: ... lineages such as i) B.1.1 (0.92%), ii) B.1.1.1 (0.46%), iii) B.1.1.28 (25.34%), iv) B.1.1.7 (5.99%), v) B.1 ... for the first time in Brazil of the South African variant of concern (VOC), the B.1.351 (501Y.V2) (0.46 ...

Abstract	Sao Paulo State, the most populous area in Brazil, currently experiences a second wave of the COVID-19 pandemic which overwhelmed the healthcare system. Recently, due to the paucity of SARS-CoV-2 complete genome sequences, we established a Network for Pandemic Alert of Emerging SARS-CoV-2 Variants to rapidly understand the spread of SARS-CoV-2 and monitor in nearly real-time the circulating SARS-CoV-2 variants into the state. Through full genome analysis of 217 SARS-CoV-2 complete genome sequences obtained from the largest regional health departments we were able to identify the co-circulation of multiple SARS-CoV-2 lineages such as i) B.1.1 (0.92%), ii) B.1.1.1 (0.46%), iii) B.1.1.28 (25.34%), iv) B.1.1.7 (5.99%), v) B.1.566 (1.84%), vi) P.1 (64.05%), and P.2 (0.92%). Further our analysis allowed the detection, for the first time in Brazil of the South African variant of concern (VOC), the B.1.351 (501Y.V2) (0.46%). The identified lineage was characterized by the presence of the following mutations: ORF1ab: T265I, R724K, S1612L, K1655N, K3353R, SGF 3675_F3677del, P4715L, E5585D; Spike: D80A, D215G, L242_L244del, A262D, K417N, E484K, N501Y, D614G, A701V, C1247F; ORF3a: Q57H, S171L, E: P71L; ORF7b: Y10F, N: T205I; ORF14: L52F. Origin of the most recent common ancestor of this genomic variant was inferred to be between middle October to late December 2020. Analysis of generated sequences demonstrated the predominance of the P.1 lineage and allowed the early detection of the South African strain for the first time in Brazil. Our findings highlight the importance to increase active monitoring to ensure the rapid detection of new SARS-CoV-2 variants with a potential impact in pandemic control and vaccination strategies.
Keywords	covid19
Language	English
Publishing date	2021-04-04
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2021.03.30.21254591
Database	COVID19

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Article: Japanese B encephalitis in American soldiers in Korea.

SABIN, A B / SCHLESINGER, R W

American journal of hygiene

2008 Volume 46, Issue 3, Page(s) 356–375

MeSH term(s)	Encephalitis ; Encephalitis, Arbovirus/epidemiology ; Encephalitis, Arbovirus/statistics & numerical data ; Encephalitis, Japanese ; Epidemics ; Korea ; Military Personnel ; Republic of Korea ; Respiratory System ; Respiratory Tract Diseases ; United States
Language	English
Publishing date	2008-08-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	2938-5
ISSN	0096-5294
ISSN	0096-5294
DOI	10.1093/oxfordjournals.aje.a119174
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Book ; Online: Production and Comprehension of Utterances (RLE Linguistics B

Schlesinger, I.M

(Routledge Library Editions: Linguistics)

2014

Abstract: In this volume, the author reviews the results of research on language performance and proposes a model of production and comprehension. Although recent developments in linguistics are taken into account, consideration of other requirements of a ... ...

Series title	Routledge Library Editions: Linguistics
Abstract	In this volume, the author reviews the results of research on language performance and proposes a model of production and comprehension. Although recent developments in linguistics are taken into account, consideration of other requirements of a performance model leads to the conclusion that the grammar the speaker has in mind differs from the grammar as currently conceived of by most linguists. The author is also critical of recent computer simulations of language performance on the basis that they fall short of describing what goes on in human production and comprehension. The author therefo
Language	English
Size	Online-Ressource (248 p)
Publisher	Taylor and Francis
Publishing place	Hoboken
Document type	Book ; Online
Note	Description based upon print version of record
ISBN	1306320585 ; 9780415723763 ; 9781306320580 ; 9781317933533 ; 0415723760 ; 1317933532
Database	Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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Book: Environmental health science

Lippmann, Morton / Schlesinger, Richard B.

recognition, evaluation, and control of chemical health hazards

2018

Author's details	Morton Lippmann, Richard B. Schlesinger
Keywords	Environmental Health ; Environmental Pollution / prevention & control
Language	English
Size	x, 390 Seiten, Illustrationen
Edition	Second edition
Publisher	Oxford University Press
Publishing place	Oxford
Publishing country	Great Britain
Document type	Book
HBZ-ID	HT019531013
ISBN	978-0-19-068862-2 ; 0-19-068862-9
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Article ; Online: Light and pH-induced Changes in Structure and Accessibility of Transmembrane Helix B and Its Immediate Environment in Channelrhodopsin-2.

Volz, Pierre / Krause, Nils / Balke, Jens / Schneider, Constantin / Walter, Maria / Schneider, Franziska / Schlesinger, Ramona / Alexiev, Ulrike

The Journal of biological chemistry

2016 Volume 291, Issue 33, Page(s) 17382–17393

Abstract: ... of transmembrane helix B with the fluorescent dye fluorescein (acetamidofluorescein). We utilized (i) time-resolved ... experiments to observe the solvent accessibility of helix B at pH 6.0 and 7.4. The light-induced increase ... change at the cytoplasmic surface, consistent with an outward tilt of helix B. Furthermore, results ...

Abstract	A variant of the cation channel channelrhodopsin-2 from Chlamydomonas reinhardtii (CrChR2) was selectively labeled at position Cys-79 at the end of the first cytoplasmic loop and the beginning of transmembrane helix B with the fluorescent dye fluorescein (acetamidofluorescein). We utilized (i) time-resolved fluorescence anisotropy experiments to monitor the structural dynamics at the cytoplasmic surface close to the inner gate in the dark and after illumination in the open channel state and (ii) time-resolved fluorescence quenching experiments to observe the solvent accessibility of helix B at pH 6.0 and 7.4. The light-induced increase in final anisotropy for acetamidofluorescein bound to the channel variant with a prolonged conducting state clearly shows that the formation of the open channel state is associated with a large conformational change at the cytoplasmic surface, consistent with an outward tilt of helix B. Furthermore, results from solute accessibility studies of the cytoplasmic end of helix B suggest a pH-dependent structural heterogeneity that appears below pH 7. At pH 7.4 conformational homogeneity was observed, whereas at pH 6.0 two protein fractions exist, including one in which residue 79 is buried. This inaccessible fraction amounts to 66% in nanodiscs and 82% in micelles. Knowledge about pH-dependent structural heterogeneity may be important for CrChR2 applications in optogenetics.
MeSH term(s)	Chlamydomonas reinhardtii/chemistry ; Chlamydomonas reinhardtii/genetics ; Chlamydomonas reinhardtii/metabolism ; HEK293 Cells ; Humans ; Hydrogen-Ion Concentration ; Light ; Plant Proteins/chemistry ; Plant Proteins/genetics ; Plant Proteins/metabolism ; Protein Structure, Secondary ; Rhodopsin/chemistry ; Rhodopsin/genetics ; Rhodopsin/metabolism
Chemical Substances	Plant Proteins ; Rhodopsin (9009-81-8)
Language	English
Publishing date	2016-06-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.M115.711200
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Article: Clinically apparent and inapparent infection with Japanese B encephalitis virus in Shanghai and Tientsin.

SABIN, A B / SCHLESINGER, R W / GINDER, D R

Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.)

2010 Volume 65, Issue 2, Page(s) 183–187

MeSH term(s)	Asymptomatic Infections ; China ; Encephalitis ; Encephalitis Virus, Japanese ; Encephalitis, Arbovirus ; Epidemics ; Humans
Language	English
Publishing date	2010-03-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	4015-0
ISSN	1535-3699 ; 1525-1373 ; 0037-9727
ISSN (online)	1535-3699 ; 1525-1373
ISSN	0037-9727
DOI	10.3181/00379727-65-15903
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Article ; Online: Anti-HA Glycoforms Drive B Cell Affinity Selection and Determine Influenza Vaccine Efficacy.

Wang, Taia T / Maamary, Jad / Tan, Gene S / Bournazos, Stylianos / Davis, Carl W / Krammer, Florian / Schlesinger, Sarah J / Palese, Peter / Ahmed, Rafi / Ravetch, Jeffrey V

Cell

2015 Volume 162, Issue 1, Page(s) 160–169

Abstract: ... hypermutated B cell antigen receptors (BCR) on immune complexes (ICs). This implicates Fc-Fc receptor (FcR ... the inhibitory FcγRIIB on activated B cells. This elevates the threshold requirement for BCR signaling, resulting ... in B cell selection for higher affinity BCR. Immunization with sFc HA ICs elicited protective, high ...

Abstract	Protective vaccines elicit high-affinity, neutralizing antibodies by selection of somatically hypermutated B cell antigen receptors (BCR) on immune complexes (ICs). This implicates Fc-Fc receptor (FcR) interactions in affinity maturation, which, in turn, are determined by IgG subclass and Fc glycan composition within ICs. Trivalent influenza virus vaccination elicited regulation of anti-hemagglutinin (HA) IgG subclass and Fc glycans, with abundance of sialylated Fc glycans (sFc) predicting quality of vaccine response. We show that sFcs drive BCR affinity selection by binding the Type-II FcR CD23, thus upregulating the inhibitory FcγRIIB on activated B cells. This elevates the threshold requirement for BCR signaling, resulting in B cell selection for higher affinity BCR. Immunization with sFc HA ICs elicited protective, high-affinity IgGs against the conserved stalk of the HA. These results reveal a novel, endogenous pathway for affinity maturation that can be exploited for eliciting high-affinity, broadly neutralizing antibodies through immunization with sialylated immune complexes.
MeSH term(s)	Antibodies, Neutralizing/immunology ; Antigen-Antibody Complex/chemistry ; Hemagglutinin Glycoproteins, Influenza Virus/immunology ; Humans ; Immunoglobulin Fc Fragments ; Immunoglobulin G/immunology ; Influenza Vaccines/immunology ; Plasma Cells/immunology ; Receptors, Antigen, B-Cell/chemistry ; Receptors, Antigen, B-Cell/immunology ; Receptors, Fc/metabolism ; Sialic Acids/metabolism
Chemical Substances	Antibodies, Neutralizing ; Antigen-Antibody Complex ; Hemagglutinin Glycoproteins, Influenza Virus ; Immunoglobulin Fc Fragments ; Immunoglobulin G ; Influenza Vaccines ; Receptors, Antigen, B-Cell ; Receptors, Fc ; Sialic Acids
Language	English
Publishing date	2015-07-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2015.06.026
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Article: Expression of CD11a (LFA-1) on B-chronic Lymphocytic Leukemia and Lymphoma Cells: Correlation with Cell Surface Immunoglobulin Intensity and CD58 (LFA-3) Expression.

Rabinowitz, R / Polliack, A / Leizerowitz, R / Keren-Zur, Y / Schlesinger, M

Leukemia & lymphoma

2016 Volume 5 Suppl 1, Page(s) 59–64

Abstract: In the present study the expression of CD11a (LFA-1) was studied on B-chronic lymphocytic leukemia ... CLL) cells and B-non-Hodgkin's small lymphocytic lymphoma in leukemic phase (NHL). The expression ...

Abstract	In the present study the expression of CD11a (LFA-1) was studied on B-chronic lymphocytic leukemia (CLL) cells and B-non-Hodgkin's small lymphocytic lymphoma in leukemic phase (NHL). The expression of CD11a was correlated with that of surface immunoglobulin (Smig) and CD58 (LFA-3). Patients with CLL were found to have a significantly lower proportion of CD11a+ cells than NHL patients, and the intensity of the staining of Smig was lower in CLL when compared with NHL. The proportion of CD11a+ cells in CLL, but not in NHL, was inversely correlated with the total white blood cell count. In CLL patients the percentage of CD11a+ cells was significantly lower in Rai stages 2-4 compared with stages 0-1. There was a strong correlation between the proportion of CD11a+ and CD58+ cells in both CLL and NHL. In contrast, there was no correlation between the proportion of CD11a cells and Smig intensity in both of these diseases when studied separately. However, when the results in these two diseases were pooled, the proportion of CD11a cells correlated with Smig intensity. The present study indicates that Smig intensity and proportion of CD11a+ cells are important criteria for the differential diagnosis between CLL and NHL.
Language	English
Publishing date	2016-07-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	1042374-6
ISSN	1029-2403 ; 1042-8194
ISSN (online)	1029-2403
ISSN	1042-8194
DOI	10.3109/10428199109103380
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