Article
Immunology
Eric J. Allenspach, Frank Soveg, Laura S. Finn, Lomon So, Jacquelyn A. Gorman, Aaron B. Rosen, Suzanne Skoda-Smith, Marsha M. Wheeler, Kaitlyn A. Barrow, Lucille M. Rich, Jason S. Debley, Michael J. Bamshad, Deborah A. Nickerson, Ram Savan, Troy R. Torgerson, David J. Rawlings
Summary: SAMD9L is an interferon-induced tumor suppressor associated with a spectrum of multisystem disorders. A frameshift variant led to expression of a truncated protein that exhibited a gain-of-function phenotype, interfering with global protein synthesis by inhibiting translational elongation. Variants in SAMD9L that globally suppress translation had no effect or increased mRNA transcription, suggesting lineage-dominant sensitivities to this translation block.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Cell Biology
Yufeng Luo, Shuo Liu, Jiguo Xue, Ye Yang, Junxuan Zhao, Ying Sun, Bolun Wang, Shenyi Yin, Juan Li, Yuchao Xia, Feixiang Ge, Jiqiao Dong, Lvze Guo, Buqing Ye, Weijin Huang, Youchun Wang, Jianzhong Jeff Xi
Summary: This study established a robust mammalian cell-surface-display platform to study the interactions between SARS-CoV-2 variants, cellular receptor ACE2, and monoclonal antibodies on a large scale. By analyzing the mutational landscape, it was found that certain key mutations in the spike protein can increase infectivity and confer resistance to specific monoclonal antibodies. These methods have significant implications for the precise control of SARS-CoV-2 in the future.
Article
Genetics & Heredity
Kathleen M. Chen, Aaron K. Wong, Olga G. Troyanskaya, Jian Zhou
Summary: Sei is a new framework for integrating human genetics data with a sequence-based mapping of predicted regulatory activities to elucidate mechanisms contributing to complex traits and diseases.
Article
Environmental Sciences
Licheng Wang, Xihui Gu, Louise J. Slater, Jianfeng Li, Dongdong Kong, Xiang Zhang, Jianyu Liu
Summary: Decadal changes in the translation distance of tropical cyclones (TC) have been observed from 1975 to 2020, with a long-term decrease in global TC translation distance. This decrease is attributed to an abrupt change point around 1997, marking a shift from increasing translation distance during 1975-1997 to decreasing translation distance during 1998-2020. The shift is driven by changes in the distance between TC genesis location and land, as well as the percentage of landfalling TCs to all TCs, influenced by the Pacific Decadal Oscillation (PDO) and Atlantic Multidecadal Oscillation (AMO) phase switch in the mid-1990s.
Article
Multidisciplinary Sciences
Takashi Ohgita, Norihiro Namba, Hiroki Kono, Toshinori Shimanouchi, Hiroyuki Saito
Summary: The A53T mutation and C-terminal truncation enhance the aggregation of α-synuclein by reducing the unfavorable activation enthalpy of nucleation, and the truncation further triggers the autocatalytic fibril elongation on the fibril surfaces.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Sarah Kearns, Frank M. Mason, W. Kimryn Rathmell, In Young Park, Cheryl Walker, Kristen J. Verhey, Michael A. Cianfrocco
Summary: The study reveals the critical role of SETD2 in dual methylation of both tubulin and histones inside cells, with mutations in different domains affecting its binding and catalytic abilities towards different substrates.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Wen-Qiang Zheng, Signe Vandal Pedersen, Kyle Thompson, Emanuele Bellacchio, Courtney E. French, Benjamin Munro, Toni S. Pearson, Julie Vogt, Daria Diodato, Tue Diemer, Anja Ernst, Rita Horvath, Manali Chitre, Jakob Ek, Flemming Wibrand, Dorothy K. Grange, Lucy Raymond, Xiao-Long Zhou, Robert W. Taylor, Elsebet Ostergaard
Summary: TARS2 gene encodes a mitochondrial enzyme crucial for mitochondrial protein synthesis, and its pathogenic variants can lead to mitochondrial diseases. New cases reported in this study have expanded the clinical spectrum of TARS2-related mitochondrial diseases, demonstrating the pathogenic nature of these variants.
HUMAN MOLECULAR GENETICS
(2022)
Review
Multidisciplinary Sciences
Juan Li, Shengjie Lai, George F. Gao, Weifeng Shi
Summary: Since the emergence of COVID-19 in Wuhan in 2019, the world has faced a devastating pandemic with millions of cases and fatalities. This article provides insights into the spread and genetic variations of the SARS-CoV-2 virus, emphasizes the importance of genomic surveillance, and highlights the international transmission of major variants identified late in 2020.
Article
Biochemistry & Molecular Biology
Xuesong Wang, Willem Jespers, Just J. de Waal, Kim A. N. Wolff, Liedeke van Uden, Adriaan P. IJzerman, Gerard J. P. van Westen, Laura H. Heitman
Summary: This study examines the role of the adenosine A(1) receptor (A(1)AR) in tumor development and explores the effects of mutations on receptor activity and pharmacology. Results reveal that mutations in the extracellular loops generally decrease receptor activity and agonist potency, while some contradictory effects are observed for mutations in the intracellular loops. This research enriches our understanding of A(1)AR structure and function, providing insights into the consequences of these mutations in cancer.
Article
Mathematics, Applied
Lin Tang, Qian Zhang
Summary: In this paper, we establish global C-1+alpha,C-1+alpha/2 estimates for solutions of the linearized parabolic Monge-Ampere equation L(phi)u(x,t):=-u(t)detD(2)phi(x) + tr[(Phi x)D(2)u] = f(x,t) under appropriate conditions on the domain, Monge-Ampere measures, boundary data and f, where Phi:=det(D-2 phi)(D-2 phi)(-1) is the cofactor of the Hessian of D2 phi.
RESULTS IN MATHEMATICS
(2022)
Article
Genetics & Heredity
Mika Saotome, Deepak Balakrishnan Poduval, Renju Nair, Mikhala Cooper, Motoki Takaku
Summary: GATA3 is a frequently mutated gene in breast cancer, with more than 10% of breast tumors carrying mutations in this gene. In this study, researchers established breast cancer cell lines expressing different truncation mutants of GATA3 and identified common and distinct gene expression patterns. The impact on epithelial-to-mesenchymal transition (EMT) related genes was similar across the mutants, and chromatin localization showed non-canonical motif enrichment. The A333 frameshift mutant had the most significant impact on GATA3 binding compared to other mutants.
FRONTIERS IN GENETICS
(2022)
Article
Mathematics, Applied
Xiaoguang You, Aibin Zang, Yin Li
Summary: By casting Euler-alpha equations into vorticity-stream function formula and obtaining useful estimates from the properties of the vorticity formula in exterior domain, one can establish the global existence and uniqueness of solutions to Euler-alpha equations in 2D exterior domain, with the condition of regular enough initial data.
Article
Biochemistry & Molecular Biology
Alexandra M. Whiteley, Miguel A. Prado, Stefanie A. H. de Poot, Joao A. Paulo, Marissa Ashton, Sara Dominguez, Martin Weber, Hai Ngu, John Szpyt, Mark P. Jedrychowski, Amy Easton, Steven P. Gygi, Thimo Kurz, Mervyn J. Monteiro, Eric J. Brown, Daniel Finley
Summary: This study provides an unbiased and global analysis of Ubqln2's role in controlling the proteome composition, showing impacts on various physiological pathways and identifying specific proteins linked to UBQLN2 function. The research also reveals candidate client proteins whose degradation is promoted by UBQLN2 in disease models.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Kristine Degn, Ludovica Beltrame, Freja Dahl Hede, Valentina Sora, Vincenzo Nicolaci, Marina Vabistsevits, Kjeld Schmiegelow, Karin Wadt, Matteo Tiberti, Matteo Lambrughi, Elena Papaleo
Summary: This study characterizes somatic and germline variants of p53, focusing on their effects on protein stability and their interactions with the 207-213 region. The methods used in this study can be applied to other p53 variants and proteins where conformational changes in loop regions are important for function.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Genetics & Heredity
Ilse Van Gucht, Josephina A. N. Meester, Jotte Rodrigues Bento, Maaike Bastiaansen, Jarl Bastianen, Ilse Luyckx, Lotte Van den Heuvel, Cedric H. G. Neutel, Pieter-Jan Guns, Mandy Vermont, Erik Fransen, Melanie H. A. M. Perik, Joe Davis Velchev, Maaike Alaerts, Dorien Schepers, Silke Peeters, Isabel Pintelon, Abdulrahman Almesned, Matteo P. Ferla, Jenny C. Taylor, Anthony R. Dallosso, Maggie Williams, Julie Evans, Jill A. Rosenfeld, Thierry Sluysmans, Desiderio Rodrigues, Ashish Chikermane, Gangadhara Bharmappanavara, Kayal Vijayakumar, Hassan Mottaghi Moghaddam Shahri, Narges Hashemi, Paria Najarzadeh Torbati, Mehran B. Toosi, Zuhair N. Al-Hassnan, Julie Vogt, Nicole Revencu, Isabelle Maystadt, Erin M. Miller, K. Nicole Weaver, Amber Begtrup, Henry Houlden, David Murphy, Reza Maroofian, Alistair T. Pagnamenta, Lut Van Laer, Bart L. Loeys, Aline Verstraeten
Summary: Importin 8, encoded by IPO8, is crucial for the development of thoracic aortic aneurysm (TAA) and its loss-of-function variants may cause a syndromic form of TAA with clinical overlap with other syndromes. Importin 8 plays a role in dysregulation of the TGF-beta signaling pathway, providing potential for future mechanistic studies and drug targeting in TAA.
AMERICAN JOURNAL OF HUMAN GENETICS
(2021)
Article
Biochemistry & Molecular Biology
Annika Bartsch, Callum M. Ives, Christof Kattner, Florian Pein, Manuel Diehn, Mikio Tanabe, Axel Munk, Ulrich Zachariae, Claudia Steinem, Salome Llabres
Summary: This study highlights the importance of a single point mutation in the porin PorB from Neisseria meningitidis in affecting the binding and permeation of beta-lactam antibiotics, shedding light on the molecular basis of drug resistance in Gram-negative bacteria. Through various techniques including X-ray crystallography, electrophysiology, biomolecular simulation, and liposome swelling experiments, differences in drug interaction with PorB were identified, providing insights into potential broader applications in drug-porin interactions. This research improves the understanding of how mutations in porins contribute to drug resistance mechanisms.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2021)
Article
Biology
Matthew T. Parker, Katarzyna Knop, Vasiliki Zacharaki, Anna Sherwood, Daniel Tome, Xuhong Yu, Pascal Gp Martin, Jim Beynon, Scott D. Michaels, Geoffrey J. Barton, Gordon G. Simpson
Summary: Genes involved in disease resistance, such as the nucleotide-binding, leucine-rich repeat (NLR) genes in plant genomes, play crucial roles but can also have negative impacts. Research shows that the RNA-binding protein FPA controls NLR transcript processing and gene annotation, revealing a co-transcriptional layer of NLR regulation with implications for plant immune responses.
Article
Biochemical Research Methods
Javier S. Utges, Maxim Tsenkov, Noah J. M. Dietrich, Stuart A. MacGowan, Geoffrey J. Barton
Summary: The study combines genetic differences between over 100,000 individuals and in-depth analysis of Ankyrin repeats to identify critical sites for ankyrin stability and substrate interactions. Highly conserved positions with low missense variants in the human population were found, while evolutionarily divergent positions were enriched in protein-protein interactions. The research suggests the domain has three surfaces with different enrichment patterns in interactions and variants.
PLOS COMPUTATIONAL BIOLOGY
(2021)
Article
Biology
Michael Barton, Stuart A. MacGowan, Mikhail A. Kutuzov, Omer Dushek, Geoffrey John Barton, P. Anton van der Merwe
Summary: The study analyzed the effects of mutations in the Spike protein of SARS-CoV-2 on its interaction with ACE2, finding that most mutations increased affinity with ACE2. Two ACE2 mutations were also found to enhance binding with the Spike protein.
Article
Biochemistry & Molecular Biology
Mihaly Varadi, Stephen Anyango, David Armstrong, John Berrisford, Preeti Choudhary, Mandar Deshpande, Nurul Nadzirin, Sreenath S. Nair, Lukas Pravda, Ahsan Tanweer, Bissan Al-Lazikani, Claudia Andreini, Geoffrey J. Barton, David Bednar, Karel Berka, Tom Blundell, Kelly P. Brock, Jose Maria Carazo, Jiri Damborsky, Alessia David, Sucharita Dey, Roland Dunbrack, Juan Fernandez Recio, Franca Fraternali, Toby Gibson, Manuela Helmer-Citterich, David Hoksza, Thomas Hopf, David Jakubec, Natarajan Kannan, Radoslav Krivak, Manjeet Kumar, Emmanuel D. Levy, Nir London, Jose Ramon Macias, Madhusudhan M. Srivatsan, Debora S. Marks, Lennart Martens, Stuart A. McGowan, Jake E. McGreig, Vivek Modi, R. Gonzalo Parra, Gerardo Pepe, Damiano Piovesan, Jaime Prilusky, Valeria Putignano, Leandro G. Radusky, Pathmanaban Ramasamy, Atilio O. Rausch, Nathalie Reuter, Luis A. Rodriguez, Nathan J. Rollins, Antonio Rosato, Luis Serrano, Gulzar Singh, Petr Skoda, Carlos Oscar S. Sorzano, Jan Stourac, Joanna Sulkowska, Radka Svobodova, Natalia Tichshenko, Silvio C. E. Tosatto, Wim Vranken, Mark N. Wass, Dandan Xue, Daniel Zaidman, Janet Thornton, Michael Sternberg, Christine Orengo, Sameer Velankar
Summary: PDBe-KB is an open collaboration platform that aims to integrate functional and biophysical annotations from world-leading specialist data resources, serving the Protein Data Bank. By developing standardized data exchange formats and integrating functional annotations from partner resources, PDBe-KB aims to place macromolecular structure data in a biological context and provide valuable biological insights.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Multidisciplinary Sciences
Jessen Bredeson, Jessica B. Lyons, Ibukun O. Oniyinde, Nneka R. Okereke, Olufisayo Kolade, Ikenna Nnabue, Christian O. Nwadili, Eva Hribova, Matthew Parker, Jeremiah Nwogha, Shengqiang Shu, Joseph Carlson, Robert Kariba, Samuel Muthemba, Katarzyna Knop, Geoffrey J. Barton, Anna Sherwood, Antonio Lopez-Montes, Robert Asiedu, Ramni Jamnadass, Alice Muchugi, David Goodstein, Chiedozie N. Egesi, Jonathan Featherston, Asrat Asfaw, Gordon G. Simpson, Jaroslav Dolezel, Prasad S. Hendre, Allen Van Deynze, Pullikanti Lava Kumar, Jude E. Obidiegwu, Ranjana Bhattacharjee, Daniel S. Rokhsar
Summary: This study presents a chromosome-scale genome assembly of Dioscorea alata and a genetic map derived from African breeding populations. It reveals the genome structure and genetic traits of the greater yam, including genes related to disease resistance and tuber quality. The study also highlights the presence of inbreeding and interspecific introgression during domestication. These findings provide important insights for yam breeding.
NATURE COMMUNICATIONS
(2022)
Article
Biochemical Research Methods
Stuart MacGowan, Michael Barton, Mikhail Kutuzov, Omer Dushek, P. Anton van der Merwe, Geoffrey Barton
Summary: This study investigated the impact of ACE2 gene variants on SARS-CoV-2 infection. The research found that certain ACE2 variants can reduce the binding capability between the virus and host cells, thus protecting cells from infection, while other variants enhance the binding capability, potentially leading to wider viral spreading across tissues and cell types.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Carmen Escudero-Martinez, Max Coulter, Rodrigo Alegria Terrazas, Alexandre Foito, Rumana Kapadia, Laura Pietrangelo, Mauro Maver, Rajiv Sharma, Alessio Aprile, Jenny Morris, Pete E. Hedley, Andreas Maurer, Klaus Pillen, Gino Naclerio, Tanja Mimmo, Geoffrey J. Barton, Robbie Waugh, James Abbott, Davide Bulgarelli
Summary: This study utilizes metagenomics information to uncover QTLs and candidate genes underlying rhizosphere microbiome composition in barley.
NATURE COMMUNICATIONS
(2022)
Article
Biology
Matthew T. Parker, Beth K. Soanes, Jelena Kusakina, Antoine Larrieu, Katarzyna Knop, Nisha Joy, Friedrich Breidenbach, Anna Sherwood, Geoffrey J. Barton, Sebastian M. Fica, Brendan H. Davies, Gordon G. Simpson, Jonathan P. Staley
Summary: Alternative splicing is associated with the evolution of complex eukaryotes. The m(6)A modification of U6 snRNA plays a crucial role in splicing accuracy and efficiency. The sequence composition of splice sites and the cooperative roles of U5 and U6 snRNA are important in splice site selection. U6 snRNA m(6)A modification influences the usage of 3' splice sites. Two major classes of 5' splice site were identified in diverse eukaryotes.
Article
Chemistry, Medicinal
Laura A. T. Cleghorn, Richard J. Wall, Seibastien Albrecht, Stuart A. MacGowan, Suzanne Norval, Manu De Rycker, Andrew Woodland, Daniel Spinks, Stephen Thompson, Stephen Patterson, Victoriano Corpas Lopez, Gourav Dey, Iain T. Collie, Irene Hallyburton, Robert Kime, Frederick R. C. Simeons, Laste Stojanovski, Julie A. Frearson, Paul G. Wyatt, Kevin D. Read, Ian H. Gilbert, Susan Wyllie
Summary: Despite advancements in treatment options, there is a need for new drugs to eradicate human African trypanosomiasis (HAT). In this study, potent 2,4-diaminothiazoles were developed as drug-like inhibitors against Trypanosoma brucei. Animal testing confirmed the efficacy in the hemolymphatic stage, but optimization for brain penetration did not achieve the desired in vivo efficacy due to a shift in mechanism of action. Subsequent studies identified a nonessential kinase as the target and emphasized the importance of cytotoxic drugs for HAT treatment.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biotechnology & Applied Microbiology
Matthew T. Parker, Katarzyna Knop, Geoffrey J. Barton, Gordon G. Simpson
Summary: This study introduces a method to improve the accuracy of long-read RNA sequencing using alignment metrics and machine-learning-derived sequence information, effectively filtering out spurious splice junctions and guiding realignment in a two-pass approach. This method enhances the accuracy of spliced alignment and transcriptome assembly for species with and without high-quality annotations.