Article
Environmental Sciences
Elvis Ticiani, Jose A. Villegas, Carlos Murga-Zamalloa, Almudena Veiga-Lopez
Summary: BPS, as an endocrine disrupting chemical, interferes with EGF-induced EGFR activation by binding to EGFR in placenta cells. BPA and BPF do not bind to EGFR, demonstrating that BPS is the only substance with this ability to interfere with EGFR.
Article
Biochemistry & Molecular Biology
Gilles Thibault, Gilles Paintaud, Hsueh Cheng Sung, Laurie Lajoie, Edouard Louis, Celine Desvignes, Herve Watier, Valerie Gouilleux-Gruart, David Ternant
Summary: Fc gamma RIIA/CD32A is expressed on platelets and some endothelial cells, playing a role in binding IgG antibodies, which may contribute to their elimination. Platelet Fc gamma RIIA's affinity for different IgG subclasses influences the clearance of antibodies like infliximab.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Hideyuki Yone, Hiromitsu Kono, Hayato Hirai, Kunihiro Ohta
Summary: Phenotypic variation is caused by genome rearrangements and mutations, but systematic gene identification methods based on genome rearrangements are not fully established. This study used the TAQing system and compared it with a conventional mutagenesis method to explore the loci responsible for a specific phenotype. The results showed that TAQed mutants accurately identified key genes compared to the conventional mutagenesis approach.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Kate M. Crowther, Susanne M. Mesoy, Sarah C. R. Lummis
Summary: This study identified the important M1 residues in GABA(A rho) receptors using mutagenesis and functional assays. The results provide insights into the functional properties of these residues and their differences among subunits. These findings are significant for understanding the mechanism of GABA(A rho) receptor function.
Article
Biochemistry & Molecular Biology
Pau Castel, Ann Holtz-Morris, Yongwon Kwon, Bernhard P. Suter, Frank McCormick
Summary: DoMY-Seq is a novel protein domain mapping technique that combines yeast two-hybrid and next-generation sequencing technologies to rapidly and with high resolution identify protein-protein interaction domains. By optimizing traditional biochemical methods, it provides a new tool for studying challenging PPIs.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Masaru Takeshita, Hidehiro Fukuyama, Katsuhiko Kamada, Takehisa Matsumoto, Chieko Makino-Okamura, Tomomi Uchikubo-Kamo, Yuri Tomabechi, Kazuharu Hanada, Saya Moriyama, Yoshimasa Takahashi, Hirohito Ishigaki, Misako Nakayama, Cong Thanh Nguyen, Yoshinori Kitagawa, Yasushi Itoh, Masaki Imai, Tadashi Maemura, Yuri Furusawa, Hiroshi Ueki, Kiyoko Iwatsuki-Horimoto, Mutsumi Ito, Seiya Yamayoshi, Yoshihiro Kawaoka, Mikako Shirouzu, Makoto Ishii, Hideyuki Saya, Yasushi Kondo, Yuko Kaneko, Katsuya Suzuki, Koichi Fukunaga, Tsutomu Takeuchi
Summary: Therapeutic neutralizing antibodies against SARS-CoV-2 infection have been highly effective. In this study, monoclonal antibodies were created from COVID-19 convalescent patients and antibodies that exhibited comparable neutralizing ability to clinically used antibodies were identified. These antibodies have shown antiviral activity against various mutations and a modification was introduced to prevent antibody-dependent enhancement. Therapeutic administration of these antibodies in animal models resulted in reduction of viral load and tissue damage.
Article
Biochemistry & Molecular Biology
Monica Castro-Cruz, Frederique Lembo, Jean-Paul Borg, Gilles Trave, Renaud Vincentelli, Pascale Zimmermann
Summary: PSD95-disc large-zonula occludens (PDZ) domains are globular modules that bind to carboxy-terminal sequences of membrane-associated proteins and influence their trafficking and signaling. PDZome 2.0 is a library for Yeast two-hybrid, consisting of 305 individual clones, that outperforms the previous resource in identifying PDZ interactions. Its boundaries were designed based on available PDZ structures, and it has been shown to effectively interact with the E6 oncoprotein from HPV16.
Article
Physiology
Susanne M. Mesoy, Matthew Bridgland-Taylor, Sarah C. R. Lummis
Summary: The role of the M4 helix in the pLGIC family is not yet fully understood, but it is known to be involved in receptor assembly and signaling. This study compares the sensitivity of M4 in different expression systems and finds that the lipid content of the plasma membrane may explain the observed differences. Furthermore, the study shows that most of the identified nonfunctional M4 mutants are functional when expressed in oocytes, suggesting that the expression system used is important for studying the function of M4.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Cell Biology
Mitchell D. Meyer, Jasmine Winzeler, Sophia M. Taylor, Alex Kilgore, Kimberly Edicha, Chase Chitwood, Zachary Spearin, S. K. Nadia Rahman Silvia, Ronith Chakraborty, Jesse E. Smith, Bridget Kennedy, Carson Zois, Hayley Cawthon, Mukiri Gilruth, Steven K. Backues
Summary: Selective autophagy is a cellular process that degrades damaged or toxic cytoplasmic components, and Atg11 is a key adapter protein involved in this process. We identified three critical residues in the coiled-coil 2 domain of Atg11 that are required for its structure and function.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Chemistry, Applied
Zhaomin Zheng, Qilin Huang, Yu Kang, Yonggang Liu, Wei Luo
Summary: The study investigated the influence of molecular size and chain conformation of water-soluble yeast beta-glucan on its interaction with Dectin-1, revealing that higher molecular weight beta-glucan exhibited a spherical conformation while smaller molecular weight beta-glucan showed a stiff chain conformation. The interaction between beta-glucan and Dectin-1 was found to be easier for spherical beta-glucan with longer side chains.
CARBOHYDRATE POLYMERS
(2021)
Article
Genetics & Heredity
Zhiquan Wang, Longjie Ni, Liangqin Liu, Haiyan Yuan, Suzhen Huang, Chunsun Gu
Summary: This study identified the interaction between IlMT2a and IlMT3 in I. lactea var. chinensis plants, where IlMT2a provides cadmium tolerance in horsehair while IlMT3 does not offer significant protection in transgenic Arabidopsis thaliana.
Article
Multidisciplinary Sciences
Alicja Karabasz, Monika Bzowska, Joanna Bereta, Maria Czarnek, Maja Sochalska, Tomasz Klaus
Summary: The study confirmed glycan-dependent interactions between mouse IgG3 and J774A.1 and P388D1 cells, and revealed the involvement of additional unknown receptors in IgG3 binding, in addition to ITGB1, Fc gamma RII, and Fc gamma RIII.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Eileen Dahlke, Yaman Anan, Lea Maximiliane Klie, Ariane Elisabeth Hartkopf, Franziska Theilig
Summary: The neonatal Fc receptor (FcRn) is highly expressed in the renal proximal tubule and plays a crucial role in the reclamation of albumin by cellular transcytosis. The interaction between megalin and FcRn in the endosomal compartment was detected, which increased when endocytosis was induced. Megalin orchestrates the endocytosis and intracellular trafficking of FcRn as an early event in transcytosis.
Article
Biochemistry & Molecular Biology
Naveenchandra Suryadevara, Swathi Shrihari, Pavlo Gilchuk, Laura A. VanBlargan, Elad Binshtein, Seth J. Zost, Rachel S. Nargi, Rachel E. Sutton, Emma S. Winkler, Elaine C. Chen, Mallorie E. Fouch, Edgar Davidson, Benjamin J. Doranz, Rita E. Chen, Pei-Yong Shi, Robert H. Carnahan, Larissa B. Thackray, Michael S. Diamond, James E. Crowe
Summary: The study found that a subset of human monoclonal antibodies derived from convalescent SARS-CoV-2 patients possess neutralizing activity, with two antibodies capable of inhibiting infection. Mechanistic studies revealed these antibodies neutralize in part by inhibiting post-attachment steps in the infection cycle.
Article
Biochemistry & Molecular Biology
Susanne M. Mesoy, Sarah C. R. Lummis
Summary: This study investigated the role of M4 residues in the alpha 4 ss 2 nAChR using site-directed mutagenesis. Results showed that two mutant receptors had altered EC(50)s, 13 were nonfunctional, and coexpression with chaperones allowed 4 to respond to agonist. The remaining 9 mutants showed potential involvement in channel opening based on radioligand binding studies.
ACS CHEMICAL NEUROSCIENCE
(2021)
Review
Respiratory System
E. de Poel, J. W. Lefferts, J. M. Beekman
JOURNAL OF CYSTIC FIBROSIS
(2020)
Article
Respiratory System
Peter Van Mourik, Paul van Haaren, Evelien Kruisselbrink, Cemil Korkmaz, Hettie M. Janssens, Karin M. de Winter-de Groot, Cornelis K. van der Ent, Marne C. Hagemeijer, Jeffrey M. Beekman
JOURNAL OF CYSTIC FIBROSIS
(2020)
Article
Allergy
Inge Van de Walle, Karen Silence, Kevin Budding, Liesbeth Van de Ven, Kim Dijkxhoorn, Elisabeth de Zeeuw, Cafer Yildiz, Sofie Gabriels, Jean-Michel Percier, Johanna Wildemann, Jan Meeldijk, Peter J. Simons, Louis Boon, Linda Cox, Rob Holgate, Rolf Urbanus, Henny G. Otten, Jeanette H. W. Leusen, Christophe Blanchetot, Hans de Haard, C. Erik Hack, Peter Boross
Summary: ARGX-117 is a promising new complement inhibitor that uniquely targets both the classical and lectin pathways by binding to the Sushi-2 domain of C2. It prevents complement-mediated cytotoxicity in in vitro models for autoimmune hemolytic anemia and antibody-mediated rejection of organ transplants.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2021)
Article
Oncology
Niklas Baumann, Thies Roesner, J. H. Marco Jansen, Chilam Chan, Klara Marie Eichholz, Katja Klausz, Dorothee Winterberg, Kristina Mueller, Andreas Humpe, Renate Burger, Matthias Peipp, Denis M. Schewe, Christian Kellner, Jeanette H. W. Leusen, Thomas Valerius
Summary: The study shows that inhibiting glutaminyl cyclase can enhance the immunotherapeutic effects on tumor cells. Inhibition of glutaminyl cyclase reduces the specific signal of CD47 at the SIRP alpha binding site, leading to increased efficiency of tumor cell phagocytosis and ADCC reactions mediated by antibodies.
Article
Infectious Diseases
Arthur H. van Stigt, Katrien Oude Rengerink, Kitty W. M. Bloemenkamp, Wouter de Waal, Sabine M. P. J. Prevaes, Thuy-My Le, Femke van Wijk, Maaike Nederend, Anneke H. Hellinga, Christianne S. Lammers, Gerco den Hartog, Martijn J. C. van Herwijnen, Johan Garssen, Leon M. J. Knippels, Lilly M. Verhagen, Caroline G. M. de Theije, Alejandro Lopez-Rincon, Jeanette H. W. Leusen, Belinda Van't Land, Louis Bont
Summary: The PRIMA cohort aims to identify novel functions of components in human milk that are protective against respiratory tract infections and allergic diseases early in life through an observational, prospective, and multi-center birth study. It will provide new insights into immunomodulatory components in human milk by collecting and analyzing human milk samples in relation to clinical data.
BMC INFECTIOUS DISEASES
(2022)
Article
Oncology
Tassilo L. A. Wachsmann, Anne K. Wouters, Dennis F. G. Remst, Renate S. Hagedoorn, Miranda H. Meeuwsen, Eline van Diest, Jeanette Leusen, Jurgen Kuball, J. H. Frederik Falkenburg, Mirjam H. M. Heemskerk
Summary: This study compared the activity of CAR T cells and engineered TCR T cells in targeting CD20 antigen, and found that CAR T cells were more potent in the short term but their expansion was impaired with increased antigen exposure, while eTCR T cells performed better under high antigenic pressure.
Article
Medicine, Research & Experimental
Alexander H. Staudacher, Vasilios Liapis, Nicole L. Wittwer, William Tieu, Hiu Chun Lam, Jeanette Leusen, Michael P. Brown
Summary: The interaction between Fc and Fc gamma R is not essential for the diagnostic or therapeutic applications of chDAB4 conjugates, as tumor-associated macrophages mainly respond to endogenous signals rather than functional expression of Fc gamma R during phagocytosis.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Review
Immunology
Chilam Chan, Marta Lustig, Niklas Baumann, Thomas Valerius, Geert van Tetering, Jeanette H. W. Leusen
Summary: The expression of checkpoint molecules by tumor cells hampers the clinical responses to therapeutic antibodies. Myeloid checkpoint inhibition in combination with IgA-based treatment could significantly enhance IgA therapy.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Niklas Baumann, Christian Arndt, Judith Petersen, Marta Lustig, Thies Roesner, Katja Klausz, Christian Kellner, Miriam Bultmann, Lorenz Bastian, Fotini Vogiatzi, Jeanette H. W. Leusen, Renate Burger, Denis M. Schewe, Matthias Peipp, Thomas Valerius
Summary: Antibody-based immunotherapy is increasingly used to treat acute lymphoblastic leukemia (ALL) patients. This study investigates the effects of CD38 antibodies, targeting T-ALL cells expressing CD38, on tumor cell killing through antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cell-mediated cytotoxicity (ADCC). The study shows that IgA2 variants of CD38 antibodies are more effective in killing tumor cells through myeloid cells. The interactions between CD47 and SIRP alpha negatively regulate ADCP and ADCC. Additionally, treatment with all-trans retinoic acid (ATRA) enhances CD38 expression and further enhances ADCP and ADCC.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Biliana Todorova, Ophelie Godon, Eva Conde, Caitlin M. Gillis, Bruno Iannascoli, Odile Richard-Le Goff, Daniel Fiole, Lubka T. Roumenina, Jeanette H. W. Leusen, Andrew J. Murphy, Lynn E. Macdonald, Laurent L. Reber, Friederike Joensson, Pierre Bruhns
Summary: In mouse models of active systemic anaphylaxis, IgG-allergen immune complexes predominantly accumulate in the lungs. The accumulation of allergens in the lungs does not rely on IgG receptors, complement component C1q, neutrophils, or macrophages. Neutrophils and monocytes recruited to the lungs capture high amounts of allergens, leading to downregulation of surface IgG receptors and activation.
JOURNAL OF IMMUNOLOGY
(2022)
Correction
Immunology
Chilam Chan, Marta Lustig, Niklas Baumann, Thomas Valerius, Geert Van Tetering, Jeanette H. W. Leusen
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Firas Hamdan, Michaela Feodoroff, Salvatore Russo, Manlio Fusciello, Sara Feola, Jacopo Chiaro, Gabriella Antignani, Francesca Greco, Jeanette Leusen, Erkko Ylosmaki, Mikaela Gronholm, Vincenzo Cerullo
Summary: Immune checkpoint inhibitors have shown clinical success in cancer treatment, but there is room for improvement. Researchers have developed an oncolytic adenovirus, Ad-Cab, to enhance the efficacy of PD-L1 checkpoint inhibitors. By adding somatic mutations to increase natural killer (NK) cell activation, they further improved the effectiveness of the therapy. The modified adenovirus demonstrated targeted release in the tumor microenvironment and better tumor killing.
MOLECULAR THERAPY-ONCOLYTICS
(2023)
Article
Oncology
Marjolein C. Stip, J. H. Marco Jansen, Maaike Nederend, Maria Tsioumpekou, Mitchell Evers, Patricia A. Olofsen, Friederike Meyer-Wentrup, Jeanette H. W. Leusen
Summary: The transgenic mouse model expressing human Fc alpha RI is a valuable tool for studying the efficacy of IgA immunotherapy against infectious diseases and cancer.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Review
Cell Biology
Maria Tsioumpekou, Danielle Krijgsman, Jeanette H. W. Leusen, Patricia A. Olofsen
Summary: Neutrophils are important immune cells that make up 50-70% of the white blood cell population. In infection and cancer, neutrophil numbers increase due to the secretion of various substances by cells present in the inflamed tissue or tumor microenvironment. The function of neutrophils in cancer has gained attention, as they can have both pro-tumor and anti-tumor effects, depending on the cytokine environment in the tumor microenvironment.
Article
Medicine, Research & Experimental
Simone Mester, Mitchell Evers, Saskia Meyer, Jeannette Nilsen, Victor Greiff, Inger Sandlie, Jeanette Leusen, Jan Terje Andersen
Summary: In this study, it was demonstrated that ABD-fused IgA1 binds human FcRn pH-dependently and is rescued from cellular degradation in a receptor-specific manner in the presence of albumin. Furthermore, the presence of ABD led to an extended half-life of IgA1 in human FcRn transgenic mice, with the light chain fusion showing the longest half-life. The study suggests that an ABD, which does not interfere with albumin binding to human FcRn, may be used to extend the half-life of IgA.