Article
Multidisciplinary Sciences
Yosuke Morodomi, Sachiko Kanaji, Brian M. Sullivan, Alessandro Zarpellon, Jennifer N. Orje, Eric Won, Ryan Shapiro, Xiang-Lei Yang, Wolfram Ruf, Paul Schimmel, Zaverio M. Ruggeri, Taisuke Kanaji
Summary: Platelets play a crucial role in hemostasis, thrombosis, inflammation, and innate immunity. A study found that an activated form of tyrosyl-tRNA synthetase (YRSACT) has extratranslational activity that enhances megakaryopoiesis and platelet production. This study discovered that YRSACT can mimic inflammatory stress and induce a unique population of megakaryocytes with stem cell and myeloid markers, relying on Toll-like receptor activation and type I interferon signaling.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Biljana Ermanoska, Bob Asselbergh, Laura Morant, Maria-Luise Petrovic-Erfurth, Seyyedmohsen Hosseinibarkooie, Ricardo Leitao-Goncalves, Leonardo Almeida-Souza, Sven Bervoets, Litao Sun, LaTasha Lee, Derek Atkinson, Akram Khanghahi, Ivaylo Tournev, Patrick Callaerts, Patrik Verstreken, Xiang-Lei Yang, Brunhilde Wirth, Avital A. Rodal, Vincent Timmerman, Bruce L. Goode, Tanja A. Godenschwege, Albena Jordanova
Summary: Mutations in tyrosyl-tRNA synthetase and other tRNA ligases cause Charcot-Marie-Tooth peripheral neuropathy, with dysregulation of F-actin organization playing a role. A gain-of-function mechanism is implicated in the pathogenicity. Genetic modulation of F-actin improves neuronal features in flies expressing the disease-causing mutations. This study reveals the evolutionary-conserved role of YARS1 as an F-actin organizer and its link to tRNA-synthetase-induced neurodegeneration.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Meriem Elkolli, Hayet Elkolli, Manawwer Alam, Yacine Benguerba
Summary: The misuse and overuse of antibiotics have led to antibiotic resistance. However, terpene-rich essential oils provide a potential alternative for antimicrobial agents. In this study, we demonstrated the antibacterial activity of three plant essential oils and identified their binding energies with a critical enzyme involved in bacterial protein synthesis through molecular docking.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biology
Manish Datt
Summary: Aminoacyl-tRNA synthetases are crucial components of ribosomal protein translational machinery, with Plasmodium Tyrosyl-tRNA synthetase (PfTyrRS) identified as a validated drug target. This study explores the dynamic conformational landscape of PfTyrRS in substrate binding, revealing diverse conformations and highlighting the importance of understanding allostery in designing structure-based inhibitors for PfTyrRS.
COMPUTATIONAL BIOLOGY AND CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Chong Dai, Adriana Reyes-Ordonez, Jae-Sung You, Jie Chen
Summary: Aminoacyl-tRNA synthetases play essential roles in protein synthesis, with some also exhibiting non-translational functions. Threonyl-tRNA synthetase (ThrRS) has been found to negatively regulate myoblast differentiation through a non-catalytic mechanism involving new domains UNE-T and TGS. ThrRS interacts with Axin1, inhibiting JNK signaling and affecting skeletal myogenesis through the MEKK4-MKK4-JNK pathway.
Article
Chemistry, Multidisciplinary
Zhongqiang Wang, Hayden Matthews, Guozhong Deng, Xiaojian Zhou, Yongzheng Chen
Summary: Using thermodynamic techniques, it was found that the non-proteinogenic amino acids m-fluorotyrosine and 2,4-dihydroxyphenylalanine exhibited higher binding affinity to the tyrosyl-tRNA synthetase from Escherichia coli than to that from human cytosol.
AUSTRALIAN JOURNAL OF CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Tatsuya Horikoshi, Hiroki Noguchi, Takuya Umehara, Hiromi Mutsuro-Aoki, Ryodai Kurihara, Ryohei Noguchi, Takahiro Hashimoto, Yuki Watanabe, Tadashi Ando, Kenichi Kamata, Sam-Yong Park, Koji Tamura
Summary: The tRNA(Tyr) of Nanoarchaeum equitans has a unique feature with an extra guanosine residue at the 5' terminus. Despite the absence of extra guanosine at the 5'-end, a mutant tRNA(Tyr) of N. equitans can still be tyrosylated by tyrosyl-tRNA synthase. A substitution mutant of N. equitans TyrRS at Ile200 was able to tyrosylate both wild-type tRNA(Tyr) and tRNA without the G-1 residue, with U35, A73, and C1:G72 identified as strong recognition sites through further analysis.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Ismail M. M. Othman, Mohamed A. M. Gad-Elkareem, El Hassane Anouar, Kaiss Aouadi, Mejdi Snoussi, Adel Kadri
Summary: Novel substituted pyrazolone and dipyrazolotriazine derivatives were synthesized and characterized as potential dual antimicrobial/antioxidant agents. The sulfonamide analogues demonstrated excellent antibacterial activity and ABTS scavenging capacity, with SAR revealing benzenesulfonamide as a crucial group for enhancing activity. Molecular docking studies confirmed stronger binding interactions of the potent analogues with target enzymes, suggesting potential as lead compounds for infectious disease treatment.
BIOORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Duan Bing-Ya, Sun Ying-Fei
Summary: Designing enzyme binding pockets to accommodate substrates with different chemical structures is a great challenge, traditionally requiring screening of thousands to millions of mutants. By integrating molecular modeling and data-driven machine learning, mutant libraries with high enrichment ratios can be generated to accelerate the screening process. This integrated workflow is expected to significantly benefit Mj. tyrRS mutant screening and reduce time and cost of wet-lab experiments.
PROGRESS IN BIOCHEMISTRY AND BIOPHYSICS
(2021)
Article
Medicine, Research & Experimental
Abubucker Peer Mohideen
Summary: The ongoing issue of multidrug resistance (MDR) among bacterial pathogens has worsened during the COVID-19 pandemic. This study focused on identifying phytochemical compounds in Leucas aspera that inhibit antibacterial targets. Through analysis, four compounds - Chrysoeriol, Apigenin, Acacetin, and (-)-Chicanine - were identified as potential novel antibacterial drugs for MDR infections.
JOURNAL OF RESEARCH IN MEDICAL AND DENTAL SCIENCE
(2022)
Article
Cell Biology
Miguel A. Del Pozo, Fidel-Nicolas Lolo, Asier Echarri
Summary: Caveolae are nanodomains with specific lipid and protein composition that flatten upon increased plasma membrane tension, critical for force sensing and accommodation in mechanically challenged tissues. They play a key role in protecting cells from mechanical stress damage and are highly plastic structures that interact with mechanotransduction pathways, with components capable of translocating to the nucleus to convey stress information. Additionally, caveolae regulate membrane traffic in response to environmental mechanical forces, highlighting their relevance in mechanoadaption in different physiological and pathological processes.
CURRENT OPINION IN CELL BIOLOGY
(2021)
Article
Biochemical Research Methods
Martina Conte, Sergio Casas-Tinto, Juan Soler
Summary: Glioblastoma is a highly invasive tumor of the central nervous system that expands and infiltrates uncontaminated brain regions through a complex interplay of metalloproteases expression, extracellular matrix degradation, and integrin activity. A novel multidisciplinary approach, based on in vivo experiments in Drosophila and mathematical models, has been proposed to describe the dynamics of active and inactive integrins in relation to matrix metalloprotease concentration and tumor density at the Glioblastoma invasion front, capturing the formation of patterns that drive tumor front evolution.
PLOS COMPUTATIONAL BIOLOGY
(2021)
Article
Biology
Patricia Jarabo, Carmen de Pablo, Hector Herranz, Francisco Antonio Martin, Sergio Casas-Tinto
Summary: Cell to cell communication is crucial for tissue development and physiology, but in pathological conditions such as glioblastoma, disruptions in glia-neuron communication can lead to tumor expansion at the expense of healthy tissue. Glioblastoma cells produce ImpL2, an antagonist of the insulin pathway, which targets neighboring neurons and causes early symptoms of neurodegeneration such as mitochondrial disruption and synapse loss. Restoring neuronal insulin activity may help rescue synapse loss and delay premature death caused by glioma, indicating a potential avenue for anti-tumoral strategies.
LIFE SCIENCE ALLIANCE
(2021)
Article
Cell Biology
Maria Losada-Perez, Nuria Garcia-Guillen, Sergio Casas-Tinto
Summary: The article introduces a new experimental design to damage the mammalian central nervous system through a contusion injury paradigm. It demonstrates that adult Drosophila melanogaster glial cells undergo spontaneous functional recovery after injury and analyzes the role of immune cells in functional regeneration.
DISEASE MODELS & MECHANISMS
(2021)
Review
Biochemistry & Molecular Biology
Teresa de los Reyes Corrales, Maria Losada-Perez, Sergio Casas-Tinto
Summary: The JNK signaling pathway is crucial in the central nervous system, playing a central role in combating pathophysiological insults during development and adulthood. It is involved in various diseases such as glioblastoma, regeneration/repair after injury, neurodegeneration, and neuronal cell death.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Genetics & Heredity
Sergio Casas-Tinto, Alberto Ferrus
Summary: The study found that haplolethals associated with the gene wupA result from the combined insufficiency of a large number of Troponin I isoforms. These findings reveal novel aspects of gene expression and may have implications for evolutionary gene splitting.
Article
Biochemistry & Molecular Biology
Patricia Jarabo, Carmen de Pablo, Amanda Gonzalez-Blanco, Sergio Casas-Tinto
Summary: This study identified the upregulation of the circadian gene cry in glioblastoma (GB) patients and a Drosophila GB model. It determined that cry is required for GB progression and that the PI3K pathway regulates cry expression in GB cells. These findings contribute to understanding the mechanisms underlying GB malignancy and lethality and provide a new role for Cry in GB cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cell Biology
Suresh Kumar, Miguel Sanchez-alvarez, Fidel-Nicolas Lolo, Flavia Trionfetti, Raffaele Strippoli, Marco Cordani
Summary: Autophagy and the lysosomal system, known together as the autophagolysosomal system, play a crucial role in maintaining cellular health and homeostasis by clearing cellular waste. TFEB regulates this system by driving the expression of multiple genes, including components of the autophagolysosomal system. Reactive Oxygen Species (ROS) are key in the physiological and pathological roles of this system.
Article
Multidisciplinary Sciences
Maria Garcia-Garcia, Sara Sanchez-Perales, Patricia Jarabo, Enrique Calvo, Trevor Huyton, Liran Fu, Sheung Chun Ng, Laura Sotodosos-Alonso, Jesus Vazquez, Sergio Casas-Tinto, Dirk Gorlich, Asier Echarri, Miguel A. Del Pozo
Summary: The nuclear import of YAP, a mechanoresponsive transcriptional regulator, is driven by Importin-7. YAP then controls Importin-7 response to mechanical cues and restricts Importin-7 binding to other cargoes, demonstrating a regulatory layer indirectly regulated by mechanical cues.
NATURE COMMUNICATIONS
(2022)
Article
Genetics & Heredity
Maria Losada-Perez, Mamen Hernandez Garcia-Moreno, Irene Garcia-Ricote, Sergio Casas-Tinto
Summary: Glioblastoma is an aggressive and lethal brain tumor that interacts with healthy surrounding tissues through cell communication and synapses, promoting tumor expansion and neurodegeneration.
Article
Biology
Patricia Jarabo, Celia G. Barredo, Carmen de Pablo, Sergio Casas-Tinto, Francisco A. Martin
Summary: Neurodegeneration induced by glioblastoma disrupts circadian rhythms in Drosophila, and aligning these rhythms with the external period can lead to a longer lifespan, suggesting a potential therapeutic approach for human glioblastoma.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biology
Fidel-Nicolas Lolo, Dacil Maria Pavon, Araceli Grande, Alberto Elosegui Artola, Valeria Ines Segatori, Sara Sanchez, Xavier Trepat, Pere Roca-Cusachs, Miguel A. del Pozo
Summary: Cells can sense mechanical stress and regulate cellular mechanosensing response through the cycling and activation of integrins. Cavolae play a crucial role in the early regulation of integrin mechanosensing.
Article
Cell Biology
Fidel-Nicolas Lolo, Nikhil Walani, Eric Seemann, Dobryna Zalvidea, Dacil Maria Pavon, Gheorghe Cojoc, Moreno Zamai, Christine Viaris de Lesegno, Fernando Martinez de Benito, Miguel Sanchez-Alvarez, Juan Jose Uriarte, Asier Echarri, Daniel Jimenez-Carretero, Joan-Carles Escolano, Susana A. Sanchez, Valeria R. Caiolfa, Daniel Navajas, Xavier Trepat, Jochen Guck, Christophe Lamaze, Pere Roca-Cusachs, Michael M. Kessels, Britta Qualmann, Marino Arroyo, Miguel A. Del Pozo
Summary: Cells modulate their physical properties and adapt their plasma membrane in response to different types and intensities of mechanical force. Caveolin-1, independently from caveolae, confers deformability and mechanoprotection to cells through modulation of plasma membrane curvature, impacting downstream mechanotransduction.
NATURE CELL BIOLOGY
(2023)
Article
Entomology
Ana Guillem-Amat, Elena Lopez-Errasquin, Irene Garcia-Ricote, Jose Luis Barbero, Lucas Sanchez, Sergio Casas-Tinto, Felix Ortego
Summary: The alpha 6 subunit of nicotinic acetylcholine receptor (nAChR) has been identified as the target for spinosad in insects. This study shows that point mutations in the alpha 6 gene of resistant flies result in truncated proteins that fail to reach the cell membrane, leading to spinosad resistance.
Review
Cell Biology
Carolina Costa-Rodrigues, Joana Couceiro, Eduardo Moreno
Summary: Cell competition is a process that senses differences in cell fitness status through various modes and benefits cells with higher fitness. It recognizes isoforms of transmembrane protein Flower and translates relative fitness into distinct fates, while impairments in cell competition can potentiate disease development. In diseases like cancer, malignant cells exhibit supercompetitor behavior by killing neighboring cells, while in neurodegenerative disorders such as Alzheimer's disease, the cellular processes involved remain unclear. Research using Drosophila melanogaster as a model has identified fitness markers in neurons, establishing a link between cell competition and Alzheimer's disease.
DISEASE MODELS & MECHANISMS
(2021)
