Article
Multidisciplinary Sciences
You Yu, Shibai Li, Zheng Ser, Tanmoy Sanyal, Koyi Choi, Bingbing Wan, Huihui Kuang, Andrej Sali, Alex Kentsis, Dinshaw J. Patel, Xiaolan Zhao
Summary: This study investigated the structural features of the Smc5/6 complex and identified functional cooperation among its unique subunits, shedding light on the molecular basis for the distinct functions of Smc5/6.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Hematology
Michael D. Jain, Bachisio Ziccheddu, Caroline A. Coughlin, Rawan Faramand, Anthony J. Griswold, Kayla M. Reid, Meghan Menges, Yonghong Zhang, Ling Cen, Xuefeng Wang, Mohammad Hussaini, Ola Landgren, Marco L. Davila, Jonathan H. Schatz, Frederick L. Locke, Francesco Maura
Summary: This study revealed the mechanisms of resistance to CAR-19 T cell therapy for large B-cell lymphomas through whole-genome sequencing. Pretreatment complex structural variants, APOBEC mutational signatures, and genomic damage from reactive oxygen species were found to predict CAR-19 resistance. In addition, the loss of the RHOA tumor suppressor gene through recurrent 3p21.31 chromosomal deletion was commonly observed in patients who failed CAR T-cell therapy. The reduced expression or monoallelic loss of CD19 before treatment did not affect the efficacy, suggesting the success and resistance of CAR-19 therapy are related to multiple mechanisms.
Article
Chemistry, Applied
Zhenjun Liu, Jie Liu, Hua Zhong, Guohua Zhao, Yun Zhou
Summary: A fundamental understanding of the relationship between the structure and properties of konjac glucomannan (KGM) gels is important in designing food products. This study investigates the properties perceived by human subjects and the related structural features. The findings reveal that the crunchy property of KGM gels is dependent on a large gel architecture dimension (up to 1 mm) and is influenced by the inclusion of starch particles. The length scale of 0.5 to 1 μm plays a dominant role in conferring the crunchy mouthfeel to KGM gels.
FOOD HYDROCOLLOIDS
(2023)
Article
Multidisciplinary Sciences
Wei Fan, Xiaotang Wang, Shuhao Zeng, Na Li, Guoqing Wang, Ruonan Li, Siyuan He, Wanqian Li, Jiaxing Huang, Xingran Li, Jiangyi Liu, Shengping Hou
Summary: This study demonstrates that lactate-derived lactylation regulates CD4(+) T cell differentiation and plays an important role in autoimmune diseases. The levels of lactylation in CD4(+) T cells increase during the progression of experimental autoimmune uveitis. Inhibition of lactylation suppresses T(H)17 differentiation and attenuates inflammation.
Article
Multidisciplinary Sciences
Minghao Li, Zicheng Zhang, Qianrong Wang, Yan Yi, Baosheng Li
Summary: This study established the ESCC-META dataset to systematically evaluate the mutational features and clinical characteristics of esophageal squamous cell cancer (ESCC). They identified mutational signatures related to clinical features, detected significant mutated hotspots in TGFBR2 and IRF2BPL, and proposed a validated mutational score for prognosis prediction in ESCC.
NATURE COMMUNICATIONS
(2022)
Article
Biology
Stepfanie M. Aguillon, Jennifer Walsh, Irby J. Lovette
Summary: This study identified the genetic basis of six distinct plumage patches in North American woodpeckers, revealing that color differences could be created through selection acting on novel combinations of coloration genes.
PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Ahmed H. Hassan, Christian Ihling, Claudio Iacobucci, Panagiotis L. Kastritis, Andrea Sinz, Tobias Kruse
Summary: Within the cell, molybdenum (Mo) is biologically active when complexed within the FeMo cofactor or the molybdenum cofactor (Moco). The molybdenum insertase (Mo-insertase) catalyzes the formation of the Mo-center, consisting of the organic part molybdopterin (MPT) and the inorganic Mo-center. In this study, a structural model of the eukaryotic Mo-insertase Cnx1 complex was generated, revealing an asymmetric hexameric complex that allows the E- and G-domain active sites to align in a catalytically productive orientation.
Article
Biochemistry & Molecular Biology
Ahmed H. Hassan, Christian Ihling, Claudio Iacobucci, Panagiotis L. Kastritis, Andrea Sinz, Tobias Kruse
Summary: The trace element molybdenum (Mo) is biologically active within the cell when complexed with the nitrogenase-specific FeMo cofactor or the molybdenum cofactor (Moco). Moco consists of an organic part, molybdopterin (MPT), and an inorganic Mo-center. The molybdenum insertase (Mo-insertase) catalyzes the formation of the Mo-center, composed of two functional domains, G- and E-domains. In this study, a structural model of the eukaryotic Mo-insertase Cnx1 complex was generated, revealing an asymmetric hexameric complex that allows the active sites of the E- and G-domains to align for efficient catalysis.
Article
Multidisciplinary Sciences
Michelle M. Conti, Rui Li, Michelle A. Narvaez Ramos, Lihua Julie Zhu, Thomas G. Fazzio, Jennifer A. Benanti
Summary: The authors developed a high-throughput approach to quantitatively evaluate the contribution of each phosphosite within a multisite phosphorylated domain. They applied this method to study the yeast transcription factor Hcm1, revealing a complex CDK-regulatory circuit that mediates its activation.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Mark J. Margres, Rhett M. Rautsaw, Jason L. Strickland, Andrew J. Mason, Tristan D. Schramer, Erich P. Hofmann, Erin Stiers, Schyler A. Ellsworth, Gunnar S. Nystrom, Michael P. Hogan, Daniel A. Bartlett, Timothy J. Colston, David M. Gilbert, Darin R. Rokyta, Christopher L. Parkinson
Summary: The researchers sequenced the genome of the Tiger Rattlesnake and found that the simple venom phenotype is contributed to by gene loss, chromatin accessibility, and methylation levels. They provided the most complete characterization of the venom gene-regulatory network to date and identified key mechanisms mediating phenotypic variation across a polygenic regulatory network.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Min Zhang, Anna Jungblut, Franziska Kunert, Luis Hauptmann, Thomas Hoffmann, Olga Kolesnikova, Felix Metzner, Manuela Moldt, Felix Weis, Frank DiMaio, Karl-Peter Hopfner, Sebastian Eustermann
Summary: In this study, the authors reveal the structural mechanism for ATP-dependent chromatin remodeling of hexasomes by the INO80 complex. They demonstrate how INO80 recognizes noncanonical DNA and histone features of hexasomes that emerge from the loss of H2A-H2B. The researchers also find that the loss of H2A-H2B grants remodelers access to a different, yet unexplored layer of energy-driven chromatin regulation.
Article
Microbiology
Yunjie Chang, Hui Xu, Md A. Motaleb, Jun Liu
Summary: Researchers have discovered a multiprotein collar complex in Lyme disease spirochetes, which exhibits remarkable structural plasticity to accommodate the highly curved membrane and generate the high torque necessary for spirochete motility.
Article
Multidisciplinary Sciences
Erik Zupa, Martin Wurtz, Annett Neuner, Thomas Hoffmann, Mandy Rettel, Anna Boehler, Bram J. A. Vermeulen, Sebastian Eustermann, Elmar Schiebel, Stefan Pfeffer
Summary: This study elucidates the molecular architecture and conformational plasticity of the augmin complex, providing insights into its role in branched microtubule formation and advancing our understanding of spindle formation in mitosis.
NATURE COMMUNICATIONS
(2022)
Article
Neurosciences
Nicole F. Wong, Matthew A. Xu-Friedman
Summary: This study examines the time course of activity-dependent changes in auditory nerve synapses in mice after noise exposure and conductive hearing loss. The researchers found that EPSC amplitude and synaptic depression decrease shortly after noise exposure, followed by a gradual increase. Occlusion of the ear canal leads to a rapid decrease in EPSC amplitude, followed by an increase. Recovery to normal sound levels takes 1-2 days. Repeated exposure to noise for as little as 8 hours a day causes synaptic changes after 7 days. These findings suggest the presence of three activity-dependent mechanisms in auditory nerve synapses.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Microbiology
Bianca Vezzani, Margherita Neri, Stefano D'Errico, Alberto Papi, Marco Contoli, Carlotta Giorgi
Summary: A study has found that IL-1 beta plays a central role in lung inflammation after SARS-CoV-2 infection, while IFN-lambda is negatively affected by viral infection. These findings suggest that a promising approach to reverse the COVID-19-induced cytokine storm is the combined use of IFN-lambda and pharmaceutical blockade of IL-1 beta.
Article
Multidisciplinary Sciences
Tobias Lanz, R. Camille Brewer, Peggy P. Ho, Jae-Seung Moon, Kevin M. Jude, Daniel Fernandez, Ricardo A. Fernandes, Alejandro M. Gomez, Gabriel-Stefan Nadj, Christopher M. Bartley, Ryan D. Schubert, Isobel A. Hawes, Sara E. Vazquez, Manasi Iyer, J. Bradley Zuchero, Bianca Teegen, Jeffrey E. Dunn, Christopher B. Lock, Lucas B. Kipp, Victoria C. Cotham, Beatrix M. Ueberheide, Blake T. Aftab, Mark S. Anderson, Joseph L. DeRisi, Michael R. Wilson, Rachael J. M. Bashford-Rogers, Michael Platten, K. Christopher Garcia, Lawrence Steinman, William H. Robinson
Summary: Multiple sclerosis (MS) is an autoimmune disease where autoreactive lymphocytes attack the central nervous system. Epstein-Barr virus (EBV) infection has been linked to MS, with molecular mimicry between EBV nuclear antigen 1 (EBNA1) and central nervous system protein GlialCAM. EBNA1 immunization exacerbates disease in MS mouse models and anti-EBNA1 and anti-GlialCAM antibodies are prevalent in MS patients, providing a mechanistic link between MS and EBV and guiding the development of new MS therapies.
Article
Multidisciplinary Sciences
Naotaka Tsutsumi, Shoji Maeda, Qianhui Qu, Martin Vogele, Kevin M. Jude, Carl-Mikael Suomivuori, Ouliana Panova, Deepa Waghray, Hideaki E. Kato, Andrew Velasco, Ron O. Dror, Georgios Skiniotis, Brian K. Kobilka, K. Christopher Garcia
Summary: This study reports the cryo-electron microscopy structures of HCMV-encoded GPCRs US28 and US27 forming nonproductive and productive complexes with host G proteins, providing new insights into their functional mechanisms in viral pathogenesis.
Article
Biochemistry & Molecular Biology
Michelle Yen, Junming Ren, Qingxiang Liu, Caleb R. Glassman, Timothy P. Sheahan, Lora K. Picton, Fernando R. Moreira, Arjun Rustagi, Kevin M. Jude, Xiang Zhao, Catherine A. Blish, Ralph S. Baric, Leon L. Su, K. Christopher Garcia
Summary: This study presents a strategy to discover cytokine surrogate agonists by using modular ligands that exploit induced proximity and receptor dimer geometry as pharmacological metrics. The researchers generated combinatorial matrices of single-chain bispecific ligands and discovered that this approach can lead to the engineering of surrogate ligands that compel assembly of non-natural receptor heterodimers. The findings demonstrate the generalizability of this approach for the discovery of diversified agonists for various ligand-receptor systems.
Article
Multidisciplinary Sciences
Longxing Cao, Brian Coventry, Inna Goreshnik, Buwei Huang, William Sheffler, Joon Sung Park, Kevin M. Jude, Iva Markovic, Rameshwar U. Kadam, Koen H. G. Verschueren, Kenneth Verstraete, Scott Thomas Russell Walsh, Nathaniel Bennett, Ashish Phal, Aerin Yang, Lisa Kozodoy, Michelle DeWitt, Lora Picton, Lauren Miller, Eva-Maria Strauch, Nicholas D. DeBouver, Allison Pires, Asim K. Bera, Samer Halabiya, Bradley Hammerson, Wei Yang, Steffen Bernard, Lance Stewart, Ian A. Wilson, Hannele Ruohola-Baker, Joseph Schlessinger, Sangwon Lee, Savvas N. Savvides, K. Christopher Garcia, David Baker
Summary: This study presents a general solution to the challenge of designing proteins that can bind to specific sites on the surface of a target protein solely based on its three-dimensional structure. Through experimental validation, the method demonstrates broad applicability and successful de novo design of binding proteins for diverse protein targets. Detailed feedback from extensive experimental data guides improvements in both the method and our understanding of protein-protein interactions.
Letter
Urology & Nephrology
Laurens Liesenborghs, Veerle Huyst, Christophe Van Dijck, Jojanneke Rutgers, Irith De Baetselier, Chris Kenyon, Marjan Van Esbroeck, Koen Vercauteren
Article
Virology
Jasmine Coppens, Fien Vanroye, Isabel Brosius, Laurens Liesenborghs, Saskia van Henten, Thibaut Vanbaelen, Stefanie Bracke, Nicole Berens-Riha, Irith De Baetselier, Chris Kenyon, Patrick Soentjens, Eric Florence, Johan Van Griensven, Kevin K. Arien, Bart K. M. Jacobs, Dorien Van den Bossche, Marjan Van Esbroeck, Koen Vercauteren
Summary: This study verified the value of alternative specimen types, such as oropharyngeal swabs and saliva, for mpox laboratory confirmation. It found that saliva had higher diagnostic sensitivity and MPXV viral loads compared to oropharyngeal swabs and EDTA plasma. The recommendation to collect oropharyngeal swabs for mpox diagnosis may need to be revised to include saliva, and further research is needed to understand the potential role of saliva in disease transmission.
JOURNAL OF CLINICAL VIROLOGY
(2023)
Article
Infectious Diseases
Jef Vanhamel, Valeska Laisnez, Laurens Liesenborghs, Isabel Brosius, Nicole Berens-Riha, Thibaut Vanbaelen, Chris Kenyon, Koen Vercauteren, Marie Laga, Naima Hammami, Oriane Lambricht, Romain Mahieu, Amaryl Lecompte, Wim Vanden Berghe, Bea Vuylsteke
Summary: This study describes the initial phase of the monkeypox outbreak in Belgium and provides a detailed description of sexual behavior and transmission contexts. The results suggest that sexual contact and networks play a significant role in the transmission of monkeypox. Delayed detection of monkeypox infection may be attributed to the confusion of initial symptoms with other sexually transmitted infections or skin conditions, as well as low perception of risk.
SEXUALLY TRANSMITTED INFECTIONS
(2023)
Letter
Infectious Diseases
Christophe Van Dijck, Irith De Baetselier, Chris Kenyon, Laurens Liesenborghs, Koen Vercauteren, Marjan Van Esbroeck
Article
Virology
Isabel Brosius, Christophe Van Dijck, Jasmine Coppens, Leen Vandenhove, Eugene Bangwen, Fien Vanroye, Jacob Verschueren, Sabine Zange, Joachim Bugert, Johan Michiels, Emmanuel Bottieau, Patrick Soentjens, Johan van Griensven, Chris Kenyon, Kevin Arien, Marjan Van Esbroeck, Koen Vercauteren, Laurens Liesenborghs
Summary: A prospective longitudinal cohort study conducted on high-risk contacts of mpox patients in Antwerp, Belgium revealed that the risk of infection after exposure to clade IIb mpox virus (MPXV) is uncertain, and presymptomatic shedding of MPXV has been established. Out of the included participants, 66.0% of sexual contacts and 14.0% of non-sexual contacts showed evidence of MPXV infection by PCR testing. The study also found cases with typical mpox symptoms and confirmed the existence of presymptomatic shedding of replication-competent MPXV, highlighting the high transmission risk during sexual contact.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Huilin Yang, Umut Y. Ulge, Alfredo Quijano-Rubio, Zachary J. Bernstein, David R. Maestas, Jung-Ho Chun, Wentao Wang, Jian-Xin Lin, Kevin M. Jude, Srujan Singh, Brian T. Orcutt-Jahns, Peng Li, Jody Mou, Liam Chung, Yun-Huai Kuo, Yasmin H. Ali, Aaron S. Meyer, Warren L. Grayson, Nicola M. Heller, K. Christopher Garcia, Warren J. Leonard, Daniel-Adriano Silva, Jennifer H. Elisseeff, David Baker, Jamie B. Spangler
Summary: In this study, IL-4 cytokine mimetics called Neo-4 were designed based on a de novo engineered IL-2 mimetic scaffold. These cytokines can mimic the physiological functions of IL-4 and offer insights into differential IL-4 signaling through type I versus type II receptors. The design workflow of this study can inform the development of targeted cytokine therapeutics.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Naotaka Tsutsumi, Sunhee Hwang, Deepa Waghray, Simon Hansen, Kevin M. Jude, Nan Wang, Yi Miao, Caleb R. Glassman, Nathanael A. Caveney, Claudia Y. Janda, Rami N. Hannoush, K. Christopher Garcia
Summary: Wnt morphogens play critical roles in embryonic development and tissue regeneration. They initiate β-catenin signaling by forming ternary receptor complexes composed of tissue-specific Frizzled receptors and shared LRP5/6 coreceptors. The cryo-EM structure of an affinity-matured XWnt8-Frizzled8-LRP6 complex reveals the mechanism of coreceptor discrimination by canonical Wnts through their N termini and linker domains. Chimeric Wnts with modular linker grafts transfer LRP6 domain specificity and enable non-canonical Wnt5a to signal through the canonical pathway.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Microbiology
Ole Lagatie, Dax Lauwers, Harvinder Singh, Fien Vanroye, Daniel J. Stieh, Johan Vingerhoets, Ludo Lavreys, Valerie Oriol-Mathieu, Will Colon, Chris Verhofstede, Koen Vercauteren, Dorien Van den Bossche, Maria Grazia Pau
Summary: The use of current serological tests may pose challenges to the adoption of HIV vaccines due to the overlap between HIV antigens detected in these tests and those used in the vaccines. Our study aimed to identify target antigens that can be used in new serological tests to accurately diagnose HIV infections without interference from vaccine-induced antibodies.
MICROBIOLOGY SPECTRUM
(2023)
Article
Infectious Diseases
Matilde Hens, Isabel Brosius, Nicole Berens-Riha, Jasmine Coppens, Liesbeth Van Gestel, Jojanneke Rutgers, Chris Kenyon, Patrick Soentjens, Saskia van Henten, Stefanie Bracke, Thibaut Vanbaelen, Leen Vandenhoven, Emmanuel Bottieau, Koen Vercauteren, Marjan Van Esbroeck, Laurens Liesenborghs, Christophe Van Dijck
Summary: This study described the characteristics of mpox patients who sought care at a Belgian sexual health clinic and compared them to patients with a clinical suspicion of mpox but tested negative. The presence of skin lesions, lymphadenopathy, and proctitis were associated with the diagnosis of mpox. Age, HIV status, childhood smallpox vaccination, number of sexual partners, and international travel were not associated with mpox.
NEW MICROBES AND NEW INFECTIONS
(2023)
Article
Immunology
Alexandra Vujkovic, My Ha, Tessa de Block, Lida van Petersen, Isabel Brosius, Caroline Theunissen, Sabrina H. van Ierssel, Esther Bartholomeus, Wim Adriaensen, Guido Vanham, George Elias, Pierre Van Damme, Viggo Van Tendeloo, Philippe Beutels, Maartje van Frankenhuijsen, Erika Vlieghe, Benson Ogunjimi, Kris Laukens, Pieter Meysman, Koen Vercauteren
Summary: This study demonstrates that annotating TCR sequences of activated CD8+ T cells can be used to diagnose acute viral infections and differentiate them from historical exposures.
JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Multidisciplinary Sciences
Aerin Yang, Kevin M. Jude, Ben Lai, Mason Minot, Anna M. Kocyla, Caleb R. Glassman, Daisuke Nishimiya, Yoon Seok Kim, Sai T. Reddy, Aly A. Khan, K. Christopher Garcia
Summary: This article presents a synthetic protein-protein coevolution platform that can isolate matched pairs of interacting muteins from complex libraries. The large dataset of coevolved complexes enables a systems-level analysis of molecular recognition and the prediction of remodeled interfaces beyond the reach of the experimental library. The integration of these approaches allows for simulating protein coevolution and generating protein complexes with diverse molecular recognition properties.
