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Article ; Online: T.B. Wyller responds.

Wyller, Torgeir Bruun

Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke

2021 Volume 141, Issue 2021-14

Title translation	T.B. Wyller svarer.
Language	Norwegian
Publishing date	2021-10-11
Publishing country	Norway
Document type	Journal Article ; Comment
ZDB-ID	603504-8
ISSN	0807-7096 ; 0029-2001
ISSN (online)	0807-7096
ISSN	0029-2001
DOI	10.4045/tidsskr.21.0662
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Article ; Online: Cholesterol not particle concentration mediates the atherogenic risk conferred by apolipoprotein B particles: a Mendelian randomization analysis.

Helgadottir, Anna / Thorleifsson, Gudmar / Snaebjarnarson, Audunn / Stefansdottir, Lilja / Sveinbjornsson, Gardar / Tragante, Vinicius / Björnsson, Eyþór / Steinthorsdottir, Valgerdur / Gretarsdottir, Solveig / Helgason, Hannes / Saemundsdottir, Jona / Olafsson, Isleifur / Thune, Jens Jakob / Raja, Anna Axelsson / Ghouse, Jonas / Olesen, Morten Salling / Christensen, Alex / Jacobsen, Rikke Louise / Dowsett, Joseph /

Bruun, Mie Topholm / Nielsen, Kaspar / Knowlton, Kirk / Nadauld, Lincoln / Benediktsson, Rafn / Erikstrup, Christian / Pedersen, Ole B / Banasik, Karina / Brunak, Søren / Bundgaard, Henning / Ostrowski, Sisse R / Sulem, Patrick / Arnar, David O / Thorgeirsson, Gudmundur / Thorsteinsdottir, Unnur / Gudbjartsson, Daniel F / Stefansson, Kari / Holm, Hilma

European journal of preventive cardiology

2022 Volume 29, Issue 18, Page(s) 2374–2385

Abstract: Background and aims: The causal contribution of apolipoprotein B (apoB) particles ... apolipoprotein B particles and CAD is more associated with non-HDL-C than apoB particle concentration. ...

Abstract	Background and aims: The causal contribution of apolipoprotein B (apoB) particles to coronary artery disease (CAD) is established. We examined whether this atherogenic contribution is better reflected by non-high-density lipoprotein cholesterol (non-HDL-C) or apoB particle concentration. Method and results: We performed Mendelian randomization (MR) analysis using 235 variants as genetic instruments; testing the relationship between their effects on the exposures, non-HDL-C and apoB, and on the outcome CAD using weighted regression. Variant effect estimates on the exposures came from the UK Biobank (N = 376 336) and on the outcome from a meta-analysis of five CAD datasets (187 451 cases and 793 315 controls). Subsequently, we carried out sensitivity and replication analyses.In univariate MR analysis, both exposures associated with CAD (βnon-HDL-C = 0.40, P = 2.8 × 10-48 and βapoB = 0.38, P = 1.3 × 10-44). Adding effects on non-HDL-C into a model that already included those on apoB significantly improved the genetically predicted CAD effects (P = 3.9 × 10-5), while adding apoB into the model including non-HDL-C did not (P = 0.69). Thirty-five per cent (82/235) of the variants used as genetic instruments had discordant effects on the exposures, associating with non-HDL-C/apoB ratio at P < 2.1 × 10-4 (0.05/235). Fifty-one variants associated at genome-wide significance. Conclusion: Many sequence variants have discordant effects on non-HDL-C and apoB. These variants allowed us to show that the causal mechanism underlying the relationship between apolipoprotein B particles and CAD is more associated with non-HDL-C than apoB particle concentration.
MeSH term(s)	Humans ; Mendelian Randomization Analysis ; Cholesterol, LDL ; Risk Factors ; Cholesterol ; Apolipoproteins B/genetics ; Coronary Artery Disease/genetics ; Atherosclerosis ; Lipoproteins ; Cholesterol, HDL ; Apolipoprotein B-100/genetics
Chemical Substances	Cholesterol, LDL ; Cholesterol (97C5T2UQ7J) ; Apolipoproteins B ; Lipoproteins ; Cholesterol, HDL ; Apolipoprotein B-100
Language	English
Publishing date	2022-09-18
Publishing country	England
Document type	Meta-Analysis ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2626011-6
ISSN	2047-4881 ; 2047-4873
ISSN (online)	2047-4881
ISSN	2047-4873
DOI	10.1093/eurjpc/zwac219
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Article: Combining Cell-Intrinsic and -Extrinsic Resistance to HIV-1 By Engineering Hematopoietic Stem Cells for CCR5 Knockout and B Cell Secretion of Therapeutic Antibodies.

Feist, William N / Luna, Sofia E / Ben-Efraim, Kaya / Filsinger Interrante, Maria V / Amorin, Nelson A / Johnston, Nicole M / Bruun, Theodora U J / Ghanim, Hana Y / Lesch, Benjamin J / Dudek, Amanda M / Porteus, Matthew H

bioRxiv : the preprint server for biology

2024

Abstract: Autologous transplantation ... ...

Abstract	Autologous transplantation of
Language	English
Publishing date	2024-03-09
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.03.08.583956
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Article ; Online: T.B. Wyller svarer.

Wyller, Torgeir Bruun

Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke

2014 Volume 134, Issue 5, Page(s) 500

Title translation	T.B. Wyller replies.
MeSH term(s)	Antibodies, Monoclonal/economics ; Antineoplastic Agents/economics ; Health Policy ; Humans ; Melanoma/economics
Chemical Substances	Antibodies, Monoclonal ; Antineoplastic Agents
Language	Norwegian
Publishing date	2014-03-11
Publishing country	Norway
Document type	Comment ; Letter
ZDB-ID	603504-8
ISSN	0807-7096 ; 0029-2001
ISSN (online)	0807-7096
ISSN	0029-2001
DOI	10.4045/tidsskr.14.0226
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Article ; Online: Functional Effects of Receptor-Binding Domain Mutations of SARS-CoV-2 B.1.351 and P.1 Variants.

Bayarri-Olmos, Rafael / Jarlhelt, Ida / Johnsen, Laust Bruun / Hansen, Cecilie Bo / Helgstrand, Charlotte / Rose Bjelke, Jais / Matthiesen, Finn / Nielsen, Susanne Dam / Iversen, Kasper Karmark / Ostrowski, Sisse Rye / Bundgaard, Henning / Frikke-Schmidt, Ruth / Garred, Peter / Skjoedt, Mikkel-Ole

Frontiers in immunology

2021 Volume 12, Page(s) 757197

Abstract: The recent identification and rise to dominance of the P.1 and B.1.351 SARS-CoV-2 variants have ... immune evasive consequences of the P.1 and B.1.351 RBD mutations. E484K and N501Y result in gain-of-function ... the two different 417 substitutions severely impair the RBD/ACE-2 affinity, but in the combined P.1 and B ...

Abstract	The recent identification and rise to dominance of the P.1 and B.1.351 SARS-CoV-2 variants have brought international concern because they may confer fitness advantages. The same three positions in the receptor-binding domain (RBD) are affected in both variants, but where the 417 substitution differs, the E484K/N501Y have co-evolved by convergent evolution. Here we characterize the functional and immune evasive consequences of the P.1 and B.1.351 RBD mutations. E484K and N501Y result in gain-of-function with two different outcomes: The N501Y confers a ten-fold affinity increase towards ACE-2, but a modest antibody evasion potential of plasma from convalescent or vaccinated individuals, whereas the E484K displays a significant antibody evasion capacity without a major impact on affinity. On the other hand, the two different 417 substitutions severely impair the RBD/ACE-2 affinity, but in the combined P.1 and B.1.351 RBD variants, this effect is partly counterbalanced by the effect of the E484K and N501Y. Our results suggest that the combination of these three mutations is a two-step forward and one step back in terms of viral fitness.
MeSH term(s)	Adult ; Amino Acid Substitution ; Angiotensin-Converting Enzyme 2/immunology ; Antibodies, Viral/immunology ; BNT162 Vaccine ; COVID-19 Vaccines/administration & dosage ; COVID-19 Vaccines/immunology ; Female ; Humans ; Male ; Mutation, Missense ; Protein Domains ; SARS-CoV-2/genetics ; SARS-CoV-2/immunology ; Spike Glycoprotein, Coronavirus/genetics ; Spike Glycoprotein, Coronavirus/immunology ; Vaccination
Chemical Substances	Antibodies, Viral ; COVID-19 Vaccines ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; BNT162 Vaccine (N38TVC63NU)
Language	English
Publishing date	2021-10-07
Publishing country	Switzerland
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.757197
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Article ; Online: Identification of BLNK and BTK as mediators of rituximab-induced programmed cell death by CRISPR screens in GCB-subtype diffuse large B-cell lymphoma.

Thomsen, Emil Aagaard / Rovsing, Anne Bruun / Anderson, Mads Valdemar / Due, Hanne / Huang, Jinrong / Luo, Yonglun / Dybkaer, Karen / Mikkelsen, Jacob Giehm

Molecular oncology

2020 Volume 14, Issue 9, Page(s) 1978–1997

Abstract: Diffuse large B-cell lymphoma (DLBCL) is characterized by extensive genetic heterogeneity, and ... to identify genes involved in facilitating the rituximab response in cancerous B cells. Along with the CD20 ... encoding MS4A1 gene, we identify genes related to B-cell receptor (BCR) signaling as mediators ...

Abstract	Diffuse large B-cell lymphoma (DLBCL) is characterized by extensive genetic heterogeneity, and this results in unpredictable responses to the current treatment, R-CHOP, which consists of a cancer drug combination supplemented with the humanized CD20-targeting monoclonal antibody rituximab. Despite improvements in the patient response rate through rituximab addition to the treatment plan, up to 40% of DLBCL patients end in a relapsed or refractory state due to inherent or acquired resistance to the regimen. Here, we employ a lentiviral genome-wide clustered regularly interspaced short palindromic repeats library screening approach to identify genes involved in facilitating the rituximab response in cancerous B cells. Along with the CD20-encoding MS4A1 gene, we identify genes related to B-cell receptor (BCR) signaling as mediators of the intracellular signaling response to rituximab. More specifically, the B-cell linker protein (BLNK) and Bruton's tyrosine kinase (BTK) genes stand out as pivotal genes in facilitating direct rituximab-induced apoptosis through mechanisms that occur alongside complement-dependent cytotoxicity (CDC). Our findings demonstrate that rituximab triggers BCR signaling in a BLNK- and BTK-dependent manner and support the existing notion that intertwined CD20 and BCR signaling pathways in germinal center B-cell-like-subtype DLBCL lead to programmed cell death.
MeSH term(s)	Adaptor Proteins, Signal Transducing/genetics ; Adaptor Proteins, Signal Transducing/metabolism ; Agammaglobulinaemia Tyrosine Kinase/genetics ; Agammaglobulinaemia Tyrosine Kinase/metabolism ; Alleles ; Antigens, CD20/metabolism ; Apoptosis/drug effects ; Apoptosis/genetics ; CRISPR-Cas Systems/genetics ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics ; Germinal Center/drug effects ; Germinal Center/pathology ; HEK293 Cells ; Humans ; Lymphoma, Large B-Cell, Diffuse/drug therapy ; Lymphoma, Large B-Cell, Diffuse/genetics ; Mutation/genetics ; Rituximab/pharmacology ; Rituximab/therapeutic use ; Serum/metabolism
Chemical Substances	Adaptor Proteins, Signal Transducing ; Antigens, CD20 ; B cell linker protein ; Rituximab (4F4X42SYQ6) ; Agammaglobulinaemia Tyrosine Kinase (EC 2.7.10.2)
Language	English
Publishing date	2020-07-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2415106-3
ISSN	1878-0261 ; 1574-7891
ISSN (online)	1878-0261
ISSN	1574-7891
DOI	10.1002/1878-0261.12753
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Article ; Online: The alpha/B.1.1.7 SARS-CoV-2 variant exhibits significantly higher affinity for ACE-2 and requires lower inoculation doses to cause disease in K18-hACE2 mice.

Bayarri-Olmos, Rafael / Johnsen, Laust Bruun / Idorn, Manja / Reinert, Line S / Rosbjerg, Anne / Vang, Søren / Hansen, Cecilie Bo / Helgstrand, Charlotte / Bjelke, Jais Rose / Bak-Thomsen, Theresa / Paludan, Søren R / Garred, Peter / Skjoedt, Mikkel-Ole

eLife

2021 Volume 10

Abstract: The alpha/B.1.1.7 SARS-CoV-2 lineage emerged in autumn 2020 in the United Kingdom and transmitted ... such as the beta/B.1.351 and gamma/P.1 strains. Here, we present a functional characterization of the alpha/B.1.1.7 ... with a low dose of B.1.1.7, compared to an early 2020 SARS-CoV-2 isolate. When challenged with sera ...

Abstract	The alpha/B.1.1.7 SARS-CoV-2 lineage emerged in autumn 2020 in the United Kingdom and transmitted rapidly until winter 2021 when it was responsible for most new COVID-19 cases in many European countries. The incidence domination was likely due to a fitness advantage that could be driven by the receptor-binding domain (RBD) residue change (N501Y), which also emerged independently in other variants of concern such as the beta/B.1.351 and gamma/P.1 strains. Here, we present a functional characterization of the alpha/B.1.1.7 variant and show an eightfold affinity increase towards human angiotensin-converting enzyme-2 (ACE-2). In accordance with this, transgenic hACE2 mice showed a faster disease progression and severity after infection with a low dose of B.1.1.7, compared to an early 2020 SARS-CoV-2 isolate. When challenged with sera from convalescent individuals or anti-RBD monoclonal antibodies, the N501Y variant showed a minor, but significant elevated evasion potential of ACE-2/RBD antibody neutralization. The data suggest that the single asparagine to tyrosine substitution remarkable rise in affinity may be responsible for the higher transmission rate and severity of the B.1.1.7 variant.
MeSH term(s)	Angiotensin-Converting Enzyme 2/immunology ; Angiotensin-Converting Enzyme 2/metabolism ; Animals ; Antibodies, Monoclonal/metabolism ; Antibodies, Neutralizing/metabolism ; Antibodies, Viral/metabolism ; COVID-19/genetics ; COVID-19/metabolism ; COVID-19/virology ; Disease Progression ; Female ; Humans ; Male ; Mice ; Mutation, Missense ; Protein Binding ; SARS-CoV-2/genetics ; SARS-CoV-2/immunology ; SARS-CoV-2/metabolism ; Severity of Illness Index ; Spike Glycoprotein, Coronavirus/genetics ; Spike Glycoprotein, Coronavirus/immunology ; Spike Glycoprotein, Coronavirus/metabolism ; United Kingdom
Chemical Substances	Antibodies, Monoclonal ; Antibodies, Neutralizing ; Antibodies, Viral ; Spike Glycoprotein, Coronavirus ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
Language	English
Publishing date	2021-11-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.70002
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Article ; Online: UPLC-MS/MS determination of ptaquiloside and pterosin B in preserved natural water.

Clauson-Kaas, Frederik / Hansen, Hans Christian Bruun / Strobel, Bjarne W

Analytical and bioanalytical chemistry

2016 Volume 408, Issue 28, Page(s) 7981–7990

Abstract: The naturally occurring carcinogen ptaquiloside and its degradation product pterosin B are found ... preservation method and a fast UPLC-MS/MS method for quantification of ptaquiloside and pterosin B in environmental ... for isolation of high purity ptaquiloside and pterosin B from plant material for use as analytical standards ...

Abstract	The naturally occurring carcinogen ptaquiloside and its degradation product pterosin B are found in water leaching from bracken stands. The objective of this work is to present a new sample preservation method and a fast UPLC-MS/MS method for quantification of ptaquiloside and pterosin B in environmental water samples, employing a novel internal standard. A faster, reliable, and efficient method was developed for isolation of high purity ptaquiloside and pterosin B from plant material for use as analytical standards, with purity verified by
Language	English
Publishing date	2016-11
Publishing country	Germany
Document type	Journal Article
ZDB-ID	201093-8
ISSN	1618-2650 ; 0016-1152 ; 0372-7920
ISSN (online)	1618-2650
ISSN	0016-1152 ; 0372-7920
DOI	10.1007/s00216-016-9895-z
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Article ; Online: Dissipation of pterosin B in acid soils - Tracking the fate of the bracken fern carcinogen ptaquiloside.

Skourti-Stathaki, Eirini / Clauson-Kaas, Frederik / Brandt, Kristian Koefoed / Rasmussen, Lars Holm / Hansen, Hans Christian Bruun

Chemosphere

2016 Volume 165, Page(s) 453–459

Abstract: ... contamination of drinking water. Pterosin B is formed by hydrolysis of ptaquiloside. In soil, Pterosin B is ... that pterosin B may serve as an indicator for any past presence of ptaquiloside. Pterosin B degradation was ... with pterosin B at 3 and 8 μg g ...

Abstract	Bracken ferns (Pteridium spp.) are well-known for their carcinogenic properties, which are ascribed to the content of ptaquiloside and ptaquiloside-like substances. Ptaquiloside leach from the ferns and may cause contamination of drinking water. Pterosin B is formed by hydrolysis of ptaquiloside. In soil, Pterosin B is adsorbed more strongly and it is expected to have a slower turnover than ptaquiloside. We thus hypothesized that pterosin B may serve as an indicator for any past presence of ptaquiloside. Pterosin B degradation was studied in acid forest soils from bracken-covered and bracken-free areas. Soil samples were incubated with pterosin B at 3 and 8 μg g
MeSH term(s)	Carcinogens/chemistry ; Hydrogen-Ion Concentration ; Hydrolysis ; Indans/chemistry ; Pteridium/chemistry ; Sesquiterpenes/chemistry ; Soil Pollutants/chemistry
Chemical Substances	Carcinogens ; Indans ; Sesquiterpenes ; Soil Pollutants ; pterosin B ; ptaquiloside (F0MN9S5699)
Language	English
Publishing date	2016-12
Publishing country	England
Document type	Journal Article
ZDB-ID	120089-6
ISSN	1879-1298 ; 0045-6535 ; 0366-7111
ISSN (online)	1879-1298
ISSN	0045-6535 ; 0366-7111
DOI	10.1016/j.chemosphere.2016.09.050
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Article ; Online: The alpha/B.1.1.7 SARS-CoV-2 variant exhibits significantly higher affinity for ACE-2 and requires lower inoculation doses to cause disease in K18-hACE2 mice

Rafael Bayarri-Olmos / Laust Bruun Johnsen / Manja Idorn / Line S Reinert / Anne Rosbjerg / Søren Vang / Cecilie Bo Hansen / Charlotte Helgstrand / Jais Rose Bjelke / Theresa Bak-Thomsen / Søren R Paludan / Peter Garred / Mikkel-Ole Skjoedt

eLife, Vol

2021 Volume 10

Abstract	The alpha/B.1.1.7 SARS-CoV-2 lineage emerged in autumn 2020 in the United Kingdom and transmitted rapidly until winter 2021 when it was responsible for most new COVID-19 cases in many European countries. The incidence domination was likely due to a fitness advantage that could be driven by the receptor-binding domain (RBD) residue change (N501Y), which also emerged independently in other variants of concern such as the beta/B.1.351 and gamma/P.1 strains. Here, we present a functional characterization of the alpha/B.1.1.7 variant and show an eightfold affinity increase towards human angiotensin-converting enzyme-2 (ACE-2). In accordance with this, transgenic hACE2 mice showed a faster disease progression and severity after infection with a low dose of B.1.1.7, compared to an early 2020 SARS-CoV-2 isolate. When challenged with sera from convalescent individuals or anti-RBD monoclonal antibodies, the N501Y variant showed a minor, but significant elevated evasion potential of ACE-2/RBD antibody neutralization. The data suggest that the single asparagine to tyrosine substitution remarkable rise in affinity may be responsible for the higher transmission rate and severity of the B.1.1.7 variant.
Keywords	immunology ; epidemiology ; SARS-CoV-2 ; mouse model ; human ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2021-11-01T00:00:00Z
Publisher	eLife Sciences Publications Ltd
Document type	Article ; Online
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