Article
Biochemistry & Molecular Biology
Zuben P. Brown, Irina S. Abaeva, Swastik De, Christopher U. T. Hellen, Tatyana Pestova, Joachim Frank
Summary: This study presents cryo-EM structures of hepatitis C virus IRES initiation complexes, revealing the dynamic network of 40S/IRES contacts and the conformational changes during the transition from eIF2- to eIF5B-containing 48S complexes, providing important insights into the process of subunit joining.
Review
Microbiology
Sahibzada Waheed Abdullah, Jin'en Wu, Xuefei Wang, Huichen Guo, Shiqi Sun
Summary: This review discusses the various types of IRESs found in Picornaviridae and the past and present discoveries regarding ITAFs and their mechanism of action. It also summarizes the importance of herbal extracts, drugs, and chemicals in controlling picornavirus translation and replication. The movement of ITAFs from the nucleus to viral replication factories is also discussed.
Article
Microbiology
Shiv Kumar, Rohit Verma, Sandhini Saha, Ashish Kumar Agrahari, Shivangi Shukla, Oinam Ningthemmani Singh, Umang Berry, Tushar Kanti Maiti, Shailendra Asthana, C. T. Ranjith-Kumar, Milan Surjit
Summary: Multiple processes exist in a cell to ensure continuous production of essential proteins through different translation processes. Viruses have evolved strategies to use the host translation machinery for their protein synthesis. This study identifies the RNA-protein interactome of the HEV IRESl element and demonstrates the roles of ribosomal protein RPL5 and RNA helicase A (DHX9) in mediating HEV IRESl activity, establishing it as a bona fide internal translation initiation site.
MICROBIOLOGY SPECTRUM
(2023)
Article
Biochemistry & Molecular Biology
Benjamin Weiss, George Edward Allen, Joachim Kloehn, Karim Abid, Pascale Jaquier-Gubler, Joseph Alphonsus Curran
Summary: The eIF4E family of initiation factors regulate protein synthesis by binding to mRNA cap structures. Among them, eIF4E3 is recruited to the translation complex after mTOR inhibition by Torin1, reprogramming the translatome to enhance cellular stress resistance. Its interaction with diverse cellular proteins suggests potential additional functions beyond initiation factor roles.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Pharmacology & Pharmacy
Yongmei Feng, Stefan Grotegut, Predrag Jovanovic, Valentina Gandin, Steven H. Olson, Rabi Murad, Anne Beall, Sharon Colayco, Paul De-Jesus, Sumit Chanda, Brian P. English, Robert H. Singer, Michael Jackson, Ivan Topisirovic, Ze'ev A. Ronai
Summary: This study identified small molecules that can inhibit coronaviruses by disrupting protein synthesis, providing a potential basis for developing novel therapeutic modalities against coronaviruses.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Xinpu Tang, Yi Pu, Haoning Peng, Kaixiu Li, Sara Faouzi, Tianjian Lu, Dan Pu, Michael Cerezo, Jianguo Xu, Lu Li, Caroline Robert, Shensi Shen
Summary: As a central node of protein synthesis, the cap-binding complex, eukaryotic translation initiation factor 4 F (eIF4F), is involved in cell homeostasis, development and tumorigenesis. A large body of literature exists on the regulation and function of eIF4F in cancer cells, however the intracellular localization patterns of this complex are largely unknown. This study developed an in situ detection method for eIF4F at the single cell level and identified five distinct spatial patterns of the eIF4F translation initiation complex in human melanoma cells. The spatial patterns of eIF4F complexes at the single cell level could distinguish melanoma cells harboring different oncogenic driver mutations, suggesting their potential association with melanoma cell chemoresistance.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Su Wu, Gerhard Wagner
Summary: eIF4F plays diverse roles in human cancers, with overexpression of EIF4G1 being more selective than EIF4E, serving as a prognostic indicator in cancer patients. This expression imbalance affects housekeeping pathways and cancer-related pathways, leading to cap-independent initiation due to eIF4G1 hyperphosphorylation. These findings provide a novel model of dysregulated eIF4F function and highlight the clinical relevance of cap-(in)dependent initiation in cancer.
Article
Multidisciplinary Sciences
Yuri Frosi, Yen-Chu Lin, Jiang Shimin, Siti Radhiah Ramlan, Kelly Hew, Alf Henrik Engman, Anil Pillai, Kit Yeung, Yue Xiang Cheng, Tobias Cornvik, Par Nordlund, Megan Goh, Dilraj Lama, Zachary P. Gates, Chandra S. Verma, Dawn Thean, David P. Lane, Ignacio Asial, Christopher J. Brown
Summary: An attractive approach to target intracellular macromolecular interfaces and model putative drug interactions is to design small high-affinity proteins. Here, the authors engineer and optimize an autonomous and disulfide-free human VH domain for intracellular expression, and identify several VH domain binders against eIF4E, a protein commonly hyper-activated in cancer. These VH domains interact with eIF4E at the eIF4G binding site via a distinct structural pose, and their intracellular overexpression reduces cellular proliferation and expression of malignancy-related proteins in cancer cell lines. The linkage of high-diversity in vitro libraries with an intracellularly expressible miniprotein scaffold facilitates the discovery of VH domains suitable for intracellular applications.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Guowei Geng, Chengming Yu, Xuefeng Yuan
Summary: This study found that the IRES activity of RNA2 in wheat yellow mosaic virus varies. Through analysis of RNA structure and mutagenesis, it was found that certain structural elements in the LYJN isolate synergistically ensure higher IRES activity. Additionally, both the HC and LYJN isolates have conserved structural elements that ensure basic IRES activity. This study reveals a novel evolution pattern of IRES, regulating IRES activity by altering the number of eIF4E-binding sites.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2024)
Article
Neurosciences
Valeria Ruggiero, Claudio Fagioli, Stefano de Pretis, Valerio Di Carlo, Nicoletta Landsberger, Daniele Zacchetti
Summary: CDKL5 is an important kinase involved in neuronal development and synapse formation. Decreased expression or activity of CDKL5 leads to severe neurodevelopmental disorders. This study investigates the translational regulation of CDKL5 and identifies important elements and factors involved. The findings provide insights into the physiological processes and pathogenesis related to CDKL5 deficiency disorder.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Cell Biology
Ann Kari Grindheim, Sudarshan S. Patil, Canan G. Nebigil, Laurent Desaubry, Anni Vedeler
Summary: Annexin A2 (AnxA2) plays a critical role in cell transformation, immune response, and resistance to cancer therapy. It acts as a calcium- and lipid-binding protein as well as an mRNA-binding protein, involved in the regulation of certain cytoskeleton-associated mRNAs. A new inhibitor called FL3 can transiently increase the expression of AnxA2 and stimulate short-term transcription/translation of anxA2 mRNA. AnxA2 regulates its own mRNA translation via a feedback mechanism, which can be partially relieved by FL3.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Microbiology
Hui Li, Wenqian Li, Shuangling Zhang, Manman Qiu, Zhuoran Li, Yongquan Lin, Juan Tan, Wentao Qiao
Summary: This study reveals the interaction between the upregulated host protein GADD34 and EV71 and provides insights into the mechanisms by which EV71 non-structural precursor protein 3CD regulates host protein expression. GADD34 is important for EV71 replication, and its key functional domains, PEST 1, 2, and 3 regions, promote EV71 replication. Additionally, GADD34 is found to promote viral IRES independently of its eIF2α phosphatase activity.
MICROBIOLOGY SPECTRUM
(2022)
Review
Cell Biology
Sonja I. Buschow, Diahann T. S. L. Jansen
Summary: Research on the impaired T cell responses in chronic hepatitis B patients has mainly focused on CD8(+) T cells, while CD4(+) T cells are crucial in the development of long-lasting effector CD8(+) T cells. This review discusses the importance of including CD4(+) T cells in T cell-directed immunotherapeutic strategies to cure chronic HBV.
Article
Virology
Zhou Shen, Chen Chen, Yilin Yang, Zhenhua Xie, Qingying Ao, Lu Lv, Shoufeng Zhang, Huanchun Chen, Rongliang Hu, Hongjun Chen, Guiqing Peng
Summary: African swine fever virus (ASFV) is highly contagious and lethal in pigs, and understanding how ASFV proteins inhibit host translation through the transmembrane domain of pE66L sheds light on the mechanism of host translation shut-off induced by ASFV. This study provides important insights into the interaction between ASFV and its host cells, suggesting that ASFV pE66L plays a key role in modulating host gene expression.
JOURNAL OF VIROLOGY
(2021)
Article
Virology
Reina Sasaki-Tanaka, Ryota Masuzaki, Hiroaki Okamoto, Toshikatsu Shibata, Mitsuhiko Moriyama, Hirofumi Kogure, Tatsuo Kanda
Summary: This study identified nicotinamide as a potential therapeutic drug for HAV infection by inhibiting HAV replication through suppressing AP-1 activity and HAV IRES-mediated translation.
JOURNAL OF VIROLOGY
(2023)
Article
Allergy
M. Gil-Martinez, J. M. Rodrigo-Munoz, B. Sastre, J. A. Canas, R. Garcia-Latorre, N. Redondo, L. de la Fuente, P. Minguez, I Mahillo-Fernandez, J. Sastre, S. Quirce, M. L. Caballero, J. M. Olaguibel, V del Pozo
Summary: The aim of this study was to identify serum miRNAs that can phenotype asthma patients. Next-generation sequencing and RT-qPCR validation revealed that hsa-miR-26a-1-3p and hsa-miR-376a-3p were associated with eosinophilic and noneosinophilic asthma. Furthermore, the expression of these miRNAs was correlated with the pathogenesis of asthma.
JOURNAL OF INVESTIGATIONAL ALLERGOLOGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Immunology
Mario Fernandez-Ruiz, Lorena Forque, Eliseo Albert, Natalia Redondo, Estela Gimenez, Francisco Lopez-Medrano, Esther Gonzalez, Natalia Polanco, Tamara Ruiz-Merlo, Patricia Parra, Rafael San Juan, Amado Andres, Jose Maria Aguado, David Navarro
Summary: The study found that HPgV-1 infection does not appear to influence patient or graft outcomes after kidney transplantation. The infection rate is mainly influenced by the type of organ transplantation and donation method.
TRANSPLANT INFECTIOUS DISEASE
(2022)
Review
Immunology
Natalia Redondo, David Navarro, Jose Maria Aguado, Mario Fernandez-Ruiz
Summary: New reliable biomarkers are needed to predict immune-related complications after organ and stem cell transplantation. Torque Teno Virus (TTV) shows promise as a functional surrogate for monitoring immunosuppression, with high prevalence rates and stable viral loads. Studies suggest that increasing TTV DNA levels are associated with infectious complications, while decreasing levels are associated with acute rejection. However, the interpretation in stem cell transplant recipients is complicated by various factors. Standardization of PCR methods and ongoing trials evaluating a TTV load-guided strategy are expected in the future.
TRANSPLANT INFECTIOUS DISEASE
(2022)
Article
Immunology
Lorena Forque, Mario Fernandez-Ruiz, Eliseo Albert, Estela Gimenez, Carolina Monzo, Javier Chaves, Natalia Redondo, Isabel Rodriguez-Goncer, Tamara Ruiz-Merlo, Patricia Parra, Amado Andres, Jose Maria Aguado, David Navarro
Summary: This study investigates the genetic diversity and clinical correlates of the Anelloviridae family after kidney transplantation. The dominant genus was Alphatorquevirus, followed by Betatorquevirus and Gammatorquevirus. Changes in the predominant genus were observed in some patients. Overall, the levels of Anelloviridae DNA increased after transplantation and were associated with the use of T-cell depleting agents. However, there were no associations between the dominant genus or total Anelloviridae DNA levels and clinical outcomes.
Article
Hematology
Catia Simoes, Maria-Carmen Chillon, David Martinez-Cuadron, Maria-Jose Calasanz, Maria-Belen Vridiales, Iria Vazquez, Montserrat Hernandez-Ruano, Benat Ariceta, Paula Aguirre-Ruiz, Leire Burgos, Diego Alignani, Sarai Sarvide, Sara Villar, Ana Alfonso Pierola, Felipe Prosper, Rosa Ayala, Joaquin Martinez-Lopez, Juan Miguel Bergua Burgues, Susana Vives, Jose A. Perez-Simon, Maria Garcia-Fortes, Teresa Bernal del Castillo, Mercedes Colorado, Mayte Olave, Juan I. Rodriguez-Gutierrez, Jorge Labrador, Marcos Gonzalez, Jesus F. San-Miguel, Miguel angel Sanz, Pau Montesinos, Bruno Paiva
Summary: Clonal evolution in acute myeloid leukemia (AML) can be reconstructed using integrated multidimensional flow cytometry (MFC) immunophenotyping and fluorescence-activated cell sorting (FACS) with next-generation sequencing (NGS). Mutational analysis of dysplastic cells and leukemic blasts at the onset of AML identified stable, branching, and clonal evolution patterns. Techniques other than single-cell multiomics can be used to detect measurable residual disease (MRD) and genetic traits associated with treatment resistance in patients achieving complete response (CR). Whole-exome sequencing revealed different clonal involvement in dysplastic myeloerythropoiesis, leukemic transformation, and chemoresistance.
Article
Engineering, Civil
Ismael Ben-Yelun, Miguel Diaz-Lago, Luis Saucedo-Mora, Miguel Angel Sanz, Ricardo Callado, Francisco Javier Montans
Summary: Applications of Structural Health Monitoring (SHM) combined with Machine Learning (ML) techniques enhance real-time performance tracking and increase structural integrity awareness of civil, aerospace and automotive infrastructures. In this paper, a novel ML algorithm is developed to predict fatigue damage in composite materials using the signals of Lamb Waves and other meaningful features. The proposed algorithm achieves good accuracy and computation times comparable to other ML algorithms.
ENGINEERING STRUCTURES
(2023)
Article
Virology
Mario Fernandez-Ruiz, Natalia Redondo, Patricia Parra, Tamara Ruiz-Merlo, Isabel Rodriguez-Goncer, Natalia Polanco, Esther Gonzalez, Francisco Lopez-Medrano, Rafael San Juan, David Navarro, Amado Andres, Jose Maria Aguado
Summary: This study compares two methods (intracellular cytokine staining and interferon-gamma release assay) in predicting immune protection among kidney transplant recipients. The results suggest that intracellular cytokine staining performs slightly better in predicting immune protection at the time of discontinuation of prophylaxis.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Chemistry, Physical
Ismael Ben-Yelun, Guillermo Gomez-Carano, Francisco J. San Millan, Miguel Angel Sanz, Francisco Javier Montans, Luis Saucedo-Mora
Summary: The goal of this research is to introduce a novel tunable 3D metamaterial that can reproduce a wide spectrum of 3D auxetic and non-auxetic Poisson's ratios and Young's moduli. By changing the connectivity and position of the cell's internal nodes, this metamaterial can accommodate different spatial curvatures and boundaries. This wide range of variation is achieved through simple spatial triangularization and allows for better adaptability to component design boundaries and shapes.
Article
Mathematics, Applied
Luis Saucedo-Mora, Ismael Ben-Yelun, Hugo Garcia-Modet, Miguel Angel Sanz-Gomez, Francisco Javier Montans
Summary: 3D printing is changing the design and manufacturing of high value industrial components, pursuing a macro-micro structural optimization of architected metamaterials to customize mechanical properties. Topology optimization techniques facilitate the design of microstructures and overall component topology. A novel topology optimization algorithm is proposed, aiming to homogenize the strain level by minimizing its standard deviation, without imposing constraints and reducing external parameters. The proposed technique, working directly with moduli, is suitable for material-component design using functionally graded metamaterials and can be extended to non-linear isotropic materials.
FINITE ELEMENTS IN ANALYSIS AND DESIGN
(2023)
Article
Immunology
Mario Fernandez-Ruiz, Estefani Garcia-Rios, Natalia Redondo, Isabel Rodriguez-Goncer, Tamara Ruiz-Merlo, Patricia Parra, Virginia Sandonis, Francisco Lopez-Medrano, Rafael San Juan, Esther Gonzalez, Natalia Polanco, Amado Andres, David Navarro, Jose Maria Aguado, Pilar Perez-Romero
Summary: This study investigates the impact of cytomegalovirus (CMV)-specific antibodies on infection in kidney transplant recipients. The results suggest that CMV-AbNEIs do not have a protective role in preventing CMV infection.
JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Immunology
Mario Fernandez-Ruiz, Beatriz Sanchez Moreno, Javier Santiago Almeda, Isabel Rodriguez-Goncer, Tamara Ruiz-Merlo, Natalia Redondo, Francisco Lopez-Medrano, Rafael San Juan, Amado Andres, Jose Maria Aguado
Summary: Previous statin therapy had no apparent protective effect on the outcome of post-transplant bloodstream infection among kidney transplant recipients. The time to clinical cure and secondary outcomes such as fever resolution, ICU admission or renal replacement therapy requirement, and 30-day all-cause mortality did not differ significantly between statin and non-statin groups.
TRANSPLANT INFECTIOUS DISEASE
(2023)
Article
Immunology
Blanca D. Lopez-Ayllon, Ana de Lucas-Rius, Laura Mendoza-Garcia, Transito Garcia-Garcia, Raul Fernandez-Rodriguez, Jose M. Suarez-Cardenas, Fatima Milhano Santos, Fernando Corrales, Natalia Redondo, Federica Pedrucci, Sara Zaldivar-Lopez, Angeles Jimenez-Marin, Juan J. Garrido, Maria Montoya
Summary: The study found that SARS-CoV-2 encodes eleven accessory proteins in its genome, and their roles during infection are not fully understood. Transcriptomics analysis revealed that WNT5A and IL11 were significantly up-regulated in A549 cells expressing certain accessory proteins from SARS-CoV-2. Bioinformatics analysis and functional assays confirmed the involvement of WNT5A and IL11 in pulmonary fibrosis, and altered profibrotic gene expression was observed in lung cell lines infected with SARS-CoV-2 and COVID-19 patients' lung biopsies. These findings suggest that targeting these accessory proteins could be a potential therapeutic approach against COVID-19.
FRONTIERS IN IMMUNOLOGY
(2023)
Letter
Surgery
Mario Fernandez-Ruiz, Patricia Parra, Tamara Ruiz-Merlo, Natalia Redondo, Isabel Rodriguez-Goncer, Amado Andres, Jose Maria Aguado
TRANSPLANT INTERNATIONAL
(2023)
Article
Transplantation
Mario Fernandez-Ruiz, Patricia Almendro-Vazquez, Natalia Redondo, Tamara Ruiz-Merlo, Sandra Abella, Adan Somoza, Francisco Lopez-Medrano, Rafael San Juan, Carmelo Loinaz, Amado Andres, Estela Paz-Artal, Jose Maria Aguado
Summary: The BA.4/BA.5-adapted bivalent booster vaccine generated strong subvariant-specific responses among SOT recipients, but the booster-induced cell-mediated immunity remained lower than in immunocompetent individuals.
TRANSPLANTATION DIRECT
(2023)
Article
Peripheral Vascular Disease
Isabel Rodriguez-Goncer, Laura Corbella, David Lora, Natalia Redondo, Francisco Lopez-Medrano, Eduardo Gutierrez, Angel Sevillano, Ana Hernandez Vicente, Rafael San-Juan, Tamara Ruiz-Merlo, Patricia Parra, Esther Gonzalez, Maria Dolores Folgueira, Amado Andres, Jose Maria Aguado, Mario Fernandez-Ruiz
Summary: This study aimed to investigate whether cytomegalovirus (CMV) infection increases the risk of cardiovascular complications after kidney transplantation (KT). The analysis of 465 KT recipients revealed an association between CMV viremia and the incidence of post-transplant atherosclerotic (PAEs) and thrombotic events (PTEs), but this association was not significant after adjusting for various factors.
ATHEROSCLEROSIS PLUS
(2022)
