Article
Oncology
Jiemiao Hu, Xueqing Xia, Qingnan Zhao, Shulin Li
Summary: The acetylation of Rae-1 protein at lysines 80 and 87 by acetyltransferases GCN5 and PCAF protects it from shedding, activating NKG2D-dependent immune surveillance and potentially serving as a new target for NKG2D immunotherapy in cancer treatment.
Article
Virology
Robert Ehret, Kudor Harb, Stefan Breuer, Martin Obermeier
Summary: This study evaluated the performance of a redesigned HIV-1 RNA quantitative assay. The results demonstrated high sensitivity, good linearity, and accuracy of this assay in HIV-1 positive patients of different subtypes. Additionally, the assay showed simplicity and fast turnaround time.
JOURNAL OF CLINICAL VIROLOGY
(2022)
Article
Oncology
Weijie Liao, Naihan Xu, Haowei Zhang, Weifang Liao, Yanzhi Wang, Songmao Wang, Shikuan Zhang, Yuyang Jiang, Weidong Xie, Yaou Zhang
Summary: Our study reveals that EPB41L4A-AS1/GCN5 complex inhibits glucose uptake by regulating histone and nonhistone acetylation or crotonylation, targeting GLUT4/2 and TXNIP. Inhibition of EPB41L4A-AS1 expression may be an effective strategy for the treatment of type 2 diabetes mellitus, as weaker glucose uptake ability is one of its major clinical features.
CLINICAL AND TRANSLATIONAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Alan N. Engelman, Peter Cherepanov
Summary: Recent high-resolution structures of HIV-1 intasomes and intasomes from a closely related strain of simian immunodeficiency virus (SIV) have revealed the binding modes of several advanced INSTI compounds to the HIV/SIV integrase active site, critically informing the structural basis of drug resistance and providing important guidance for the continued development of this class of antiretroviral therapeutics.
Review
Virology
Alan N. Engelman, Mamuka Kvaratskhelia
Summary: Integrase is a crucial protein in retroviruses responsible for inserting reverse transcripts into cellular genomes. Recent studies have found that integrase binds to viral RNA, and disruption of this binding leads to defective viral particles unable to undergo reverse transcription. Class II integrase mutant viruses also exhibit similar defects, but with variations in their underlying mechanisms.
Article
Virology
Clemence Richetta, Frederic Subra, Isabelle Malet, Herve Leh, Charlotte Charpentier, Angela Corona, Gilles Collin, Diane Descamps, Eric Deprez, Vincent Parissi, Vincent Calvez, Enzo Tramontano, Anne-Genevieve Marcelin, Olivier Delelis
Summary: This study discovered a drug-resistant virus to strand-transfer inhibitors with a mutation in the 3'-PPT region instead of the integrase gene. This mutation altered the reverse transcription process, leading to the accumulation of 1-LTR circular structures instead of linear DNA. The accumulation of 1-LTR circles enabled viral replication without integration of the viral genome.
JOURNAL OF VIROLOGY
(2022)
Article
Cell Biology
Anne Monette, Meijuan Niu, Maya Nijhoff Asser, Robert J. Gorelick, Andrew J. Mouland
Summary: This study reveals that HIV-1 core proteins can condense with viral genomic RNA to form membraneless biomolecular condensates (BMCs), and investigates the characteristics and drug sensitivity of these BMCs in living cells. The findings demonstrate that HIV-1 core BMCs exhibit similar features to other biomolecular condensates and can be further formed into visible condensates through protease-mediated maturation, playing a crucial role in the viral ingress process.
Article
Microbiology
Kirsten L. White, Nathan Osman, Ernesto Cuadra-Foy, Bluma G. Brenner, Devleena Shivakumar, Federico Campigotto, Manuel Tsiang, Philip A. Morganelli, Nikolai Novikov, Scott E. Lazerwith, Haolun Jin, Anita Niedziela-Majka
Summary: The HIV integrase strand transfer inhibitor bictegravir has a longer dissociation half-life and more durable antiviral activity against wild-type HIV compared to other drugs like dolutegravir, raltegravir, and elvitegravir. Bictegravir makes more contacts with the IN-DNA complex than dolutegravir, contributing to its prolonged residence time and resilience against many resistance mutations.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Virology
Tomozumi Imamichi, John G. Bernbaum, Sylvain Laverdure, Jun Yang, Qian Chen, Helene Highbarger, Ming Hao, Hongyan Sui, Robin Dewar, Weizhong Chang, H. Clifford Lane
Summary: A genome-wide association study identified 14 naturally occurring SNPs in HIV associated with virus load, with a variant containing a Met-to-Ile change in integrase found to be impaired in replication. The study also showed that GagPol assembly, virus release, and autoprocessing are regulated not only by integrase but also by RNase H.
JOURNAL OF VIROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Longfei Liu, Wen Ge, Zhiwei Zhang, Ya Li, Mengxiao Xie, Chenhui Zhao, Chunlei Yao, Can Luo, Zhijiao Wu, Wenbo Wang, Dan Zhao, Jing Zhang, Wen Qiu, Yingwei Wang
Summary: In this study, elevated levels of SOX9, GCN5, FGF1, and PDGF alpha were observed in the renal tissues of Thy-1N rats and GMCs stimulated with sublytic C5b-9. It was found that sublytic C5b-9 induced GMC proliferation by increasing the expression of SOX9, GCN5, FGF1, and PDGF alpha, and GCN5 mediated SOX9 acetylation to enhance FGF1 or PDGF alpha synthesis and GMC proliferation. Silencing renal SOX9, GCN5, FGF1, or PDGF alpha genes significantly reduced FGF1 and PDGF alpha expression, GMC proliferation, and urinary protein secretion in Thy-1N rats. Additionally, positive expression of these genes was also observed in the renal tissues of MsPGN patients.
Article
Virology
Ishak D. Irwan, Bryan R. Cullen
Summary: The study reveals that HTLV-1 Tax protein can rescue the replication of IN-HIV-1 in T cells by activating the LTR promoter on HIV-1 DNA. Recruitment of NF-kappa B to unintegrated viral DNA is a prerequisite for Tax-induced changes in epigenetic marks, and induction of Tax expression can reverse the epigenetic silencing of unintegrated HIV 1 DNA. Introducing heterologous promoters into IN-deficient HIV-1-based vectors can maintain transcriptional activity even in the absence of Tax.
JOURNAL OF VIROLOGY
(2021)
Article
Virology
Takao Masuda, Osamu Kotani, Masaru Yokoyama, Yuya Abe, Gota Kawai, Hironori Sato
Summary: HIV-1 RT and IN function efficiently in reverse transcription as the fusion form RTIN, which exhibits increased affinity to dNTPs and alters the structure and enzymatic activity of RT.
Article
Biochemistry & Molecular Biology
Wen Ge, Yajuan Gong, Ya Li, Ningxia Wu, Yuting Ruan, Tongpeng Xu, Yongqian Shu, Wen Qiu, Yingwei Wang, Chenhui Zhao
Summary: In this study, the researchers found that interleukin-17 (IL-17) is able to promote metastasis in non-small cell lung cancer (NSCLC). They also identified the potential mechanism behind IL-17-induced NSCLC cell metastasis. The results showed that IL-17, IL-17RA, GCN5, SOX4, and MMP9 were all increased in NSCLC tissues and IL-17-stimulated NSCLC cells, and IL-17 treatment enhanced cell migration and invasion. Further exploration revealed that IL-17-upregulated GCN5 and SOX4 could bind to the same region of the downstream MMP9 gene promoter, driving its transcription and promoting cell migration and invasion. By inhibiting the expression of GCN5, SOX4, or MMP9, the researchers observed reduced SOX4 acetylation, MMP9 induction, and metastatic nodule formation in NSCLC cells. Overall, this study suggests that the IL-17-GCN5-SOX4-MMP9 axis is closely associated with NSCLC metastasis.
MOLECULAR CARCINOGENESIS
(2023)
Article
Chemistry, Multidisciplinary
Marina Toplak, Adelheid Nagel, Britta Frensch, Thorsten Lechtenberg, Robin Teufel
Summary: We report a novel regulatory principle for natural product biosynthesis involving an acetyltransferase. The acetyltransferase modifies a redox-tailoring enzyme, enabling pathway furcation and alternating pharmacophore assembly in rubromycin polyketide biosynthesis. This discovery provides new perspectives for improving enzyme activities and natural product titers.
Review
Biochemistry & Molecular Biology
Chao Zhang, Qian Xie, Chi Cheong Wan, Zhe Jin, Chun Hu
Summary: HIV-1 integrase plays a crucial role in HIV-1 treatment, but issues like drug resistance require further research. This review discussed the structure, function, and recent advances in small-molecule inhibitors of HIV-1 integrase.
CURRENT MEDICINAL CHEMISTRY
(2021)
Article
Cardiac & Cardiovascular Systems
Cornelis J. Boogerd, Gregory P. A. Lacraz, Abel Vertesy, Sebastiaan J. van Kampen, Ilaria Perini, Hesther de Ruiter, Danielle Versteeg, Andreas Brodehl, Petra van der Kraak, Mauro Giacca, Nicolaas de Jonge, Jan Philipp Junker, Alexander van Oudenaarden, Aryan Vink, Eva van Rooij
Summary: This study used Tomo-Seq technology to create a gene expression atlas of explanted ACM hearts, allowing the identification of new genes and pathways involved in specific remodeling processes. The study found that Zinc finger and BTB domain-containing protein 11 (ZBTB11) is specifically enriched at sites of active fibro-fatty replacement of myocardium, and its overexpression induces autophagy and cell death-related gene programs in human cardiomyocytes. ZBTB11 is identified as a novel driver of cardiomyocyte loss.
CARDIOVASCULAR RESEARCH
(2023)
Article
Medicine, Research & Experimental
Paola Valentini, Bianca Pierattini, Elsa Zacco, Damiano Mangoni, Stefano Espinoza, Natalie A. Webster, Byron Andrews, Piero Carninci, Gian Gaetano Tartaglia, Luca Pandolfini, Stefano Gustincich
Summary: SINEUPs are a novel class of natural and synthetic non-coding antisense RNA molecules that can increase the translation of a target mRNA, with a modular organization. Through chemical modifications, SINEUP activity can be realized, with the m6A and psi combination showing the best performance and improved stability.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)
Article
Materials Science, Multidisciplinary
Sehmus Ozden, Susanna Monti, Valentina Tozzini, Nikita S. Dutta, Stefania Gili, Nick Caggiano, A. James Link, Nicola M. Pugno, John Higgins, Rodney D. Priestley, Craig B. Arnold
Summary: The integration of 2D graphitic carbon with 1D carbon nanofiber allows for the development of an ultralightweight G-CF aerogel with a hierarchical structure, which exhibits low density and high surface area and shows excellent water purification performance.
Article
Chemistry, Multidisciplinary
Zacharias G. Fthenakis, Ioannis D. Petsalakis, Valentina Tozzini, Nektarios N. Lathiotakis
Summary: This study analyzes the performance of eleven reactive force fields (ReaxFF) for studying carbon systems, and discusses the advantages of a new hybrid ReaxFF. While seven of them provide unrealistic predictions for graphene, the remaining four ReaxFFs show reasonable results for graphene, carbon nanotubes, and fullerenes, in accordance with density functional theory (DFT) calculations and/or experimental data.
FRONTIERS IN CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Melissa S. Carroll, Mauro Giacca
Summary: CRISPR activation and interference technology has the potential for regulated gene expression, which can be applied for both investigative purposes and therapeutic development. However, the application of this technology is still in its early stage and requires improvements in transcriptional regulators selection, delivery and expression in vivo.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2023)
Article
Oncology
Rossana Bussani, Lorena Zentilin, Ricardo Correa, Andrea Colliva, Furio Silvestri, Serena Zacchigna, Chiara Collesi, Mauro Giacca
Summary: This study found that recovered COVID-19 patients may still experience worsening of their condition and eventually die, despite negative test results. Post-mortem analysis showed that the lung pathology of these patients was similar to that of acute COVID-19 cases, despite negative viral tests. These findings suggest that SARS-CoV-2 infection can persist longer than suggested by standard tests, with specific cell types in the lung being infected.
JOURNAL OF PATHOLOGY
(2023)
Article
Materials Science, Multidisciplinary
Luca Basta, Federica Bianco, Aldo Moscardini, Filippo Fabbri, Luca Bellucci, Valentina Tozzini, Stefan Heun, Stefano Veronesi
Summary: Spatially-resolved organic functionalization of monolayer graphene is achieved via low-energy electron beam irradiation, resulting in a local increase of the graphene chemical reactivity. The functionalization pattern is designed in a well-controlled way by creating structural defects using electron beam irradiation. The spatial distribution of the defects is investigated using atomic force microscopy and their effects on the graphene are studied using Raman spectroscopy and simulations.
JOURNAL OF MATERIALS CHEMISTRY C
(2023)
Article
Chemistry, Multidisciplinary
Domenic Prete, Alessia Colosimo, Valeria Demontis, Luca Medda, Valentina Zannier, Luca Bellucci, Valentina Tozzini, Lucia Sorba, Fabio Beltram, Dario Pisignano, Francesco Rossella
Summary: Thermoelectric polyelectrolytes are considered as an excellent material platform for bio-compatible electronic devices and sensors that generate their own power. However, there has been a lack of evidence for direct probing of ionic diffusion at the nanoscale in these materials. In this study, heat-driven hybrid nanotransistors based on InAs nanowires embedded in thermally biased Na+-functionalized (poly)ethyleneoxide were developed, enabling the investigation of ionic diffusions and nanoscale resolution. The microscopic parameters of the polyelectrolyte were extracted, providing a framework for the design of next-generation polymer-based thermoelectric materials.
Article
Cell Biology
Stefania Cane, Roza Maria Barouni, Marina Fabbi, John Cuozzo, Giulio Fracasso, Annalisa Adamo, Stefano Ugel, Rosalinda Trovato, Francesco De Sanctis, Mauro Giacca, Rita Lawlor, Aldo Scarpa, Borislav Rusev, Gabriella Lionetto, Salvatore Paiella, Roberto Salvia, Claudio Bassi, Susanna Mandruzzato, Silvano Ferrini, Vincenzo Bronte
Summary: Preclinical studies have shown that myeloid cells can suppress antitumor immunity by degrading L-arginine, but differences in ARG1 expression and function in rodents and humans have hindered clinical translation. This study discovered that neutrophil extracellular traps (NETs) released by activated neutrophils in patients with PDAC create a microdomain where cathepsin S (CTSS) cleaves human ARG1 (hARG1) into different forms with enhanced enzymatic activity. These NET-associated hARG1 molecules suppress T lymphocytes, but their proliferation can be restored by blocking CTSS cleavage or using hARG1-specific monoclonal antibodies, suggesting potential therapeutic strategies for PDAC.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Chemistry, Physical
Margherita Bini, Valentina Tozzini, Giorgia Brancolini
Summary: Gold nanoparticles with different surface functionalizations have selective interactions with specific proteins, making them useful in various biotechnology and biomedicine applications. To manipulate their interactions with charged biomolecules or substrates, the nanoparticles can be functionalized with charged groups. This study uses atomistic molecular dynamics simulations to analyze the conformational dynamics of ligand-coated gold nanoparticles and proposes a general representation of their electrostatic properties. The results provide insights into the role of nanoparticle features and ionic strength in determining interparticle interactions.
JOURNAL OF PHYSICAL CHEMISTRY B
(2023)
Review
Cell & Tissue Engineering
Mauro Giacca
Summary: The realization that various types of RNAs play a crucial role in tissue function opens up new possibilities for RNA-based therapies. For heart-related conditions, RNA therapies can stimulate cardiac repair, protect against ischemic damage or chemotherapy-induced cardiotoxicity, promote therapeutic angiogenesis, regenerate cardiac mass, and cure inherited cardiac diseases through mutation editing. However, the field of RNA therapeutics is still in its early stages and faces challenges in delivering RNA medicines to cells and specifically targeting the heart.
STEM CELLS TRANSLATIONAL MEDICINE
(2023)
Article
Immunology
Deborah Lecuyer, Roberta Nardacci, Desiree Tannous, Emie Gutierrez-Mateyron, Aurelia Deva Nathan, Frederic Subra, Cristina Di Primio, Paola Quaranta, Vanessa Petit, Clemence Richetta, Ali Mostefa-Kara, Franca Del Nonno, Laura Falasca, Romain Marlin, Pauline Maisonnasse, Julia Delahousse, Juliette Pascaud, Eric Deprez, Marie Naigeon, Nathalie Chaput, Angelo Paci, Veronique Saada, David Ghez, Xavier Mariette, Mario Costa, Mauro Pistello, Awatef Allouch, Olivier Delelis, Mauro Piacentini, Roger Le Grand, Jean-Luc Perfettini
Summary: The purinergic receptor P2X7 and NLRP3 inflammasome are found to be cellular host factors required for SARS-CoV-2 infection, and their activation promotes viral replication and inflammation.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Roman Roy, Antonio Cannata, Mohammad Al-Agil, Emma Ferone, Antonio Jordan, Brian To-Dang, Matthew Sadler, Aamir Shamsi, Mohammad Albarjas, Susan Piper, Mauro Giacca, Ajay M. Shah, Theresa Mcdonagh, Daniel Bromage, Paul A. Scott
Summary: This study aimed to investigate the diagnostic accuracy of different approaches for the diagnosis of acute myocarditis (AM). The findings indicate that ICD-10 codes have poor accuracy in identifying AM cases and should be used with caution in clinical research. The selection criteria used to diagnose AM can have important implications for patient management and outcomes. Standardization of inclusion criteria for AM studies is necessary.
EUROPEAN HEART JOURNAL-QUALITY OF CARE AND CLINICAL OUTCOMES
(2023)
Article
Multidisciplinary Sciences
Cristina Di Primio, Paola Quaranta, Marianna Mignanelli, Giacomo Siano, Matteo Bimbati, Arianna Scarlatti, Carmen Rita Piazza, Piero Giorgio Spezia, Paola Perrera, Fulvio Basolo, Anello Marcello Poma, Mario Costa, Mauro Pistello, Antonino Cattaneo
Summary: COVID-19 infection is associated with the aggravation of Alzheimer's disease, and this study provides evidence that SARS-CoV-2 infection induces phosphorylation of Tau protein at pathological epitopes, leading to aggregation and altered subcellular localization.
Article
Astronomy & Astrophysics
A. Apponi, M. G. Betti, M. Borghesi, A. Boyarsky, N. Canci, G. Cavoto, C. Chang, V Cheianov, Y. Cheipesh, W. Chung, A. G. Cocco, A. P. Colijn, N. D'Ambrosio, N. de Groot, A. Esposito, M. Faverzani, A. Ferella, E. Ferri, L. Ficcadenti, T. Frederico, S. Gariazzo, F. Gatti, C. Gentile, A. Giachero, Y. Hochberg, Y. Kahn, M. Lisanti, G. Mangano, L. E. Marcucci, C. Mariani, M. Marques, G. Menichetti, M. Messina, O. Mikulenko, E. Monticone, A. Nucciotti, D. Orlandi, F. Pandolfi, S. Parlati, C. Pepe, C. Perez de los Heros, O. Pisanti, M. Polini, A. D. Polosa, A. Puiu, I Rago, Y. Raitses, M. Rajteri, N. Rossi, K. Rozwadowska, I Rucandio, A. Ruocco, C. F. Strid, A. Tan, L. K. Teles, V Tozzini, C. G. Tully, M. Viviani, U. Zeitler, F. Zhao
Summary: We discuss the consequences of quantum uncertainty on the spectrum of electrons emitted by the beta-processes of a tritium atom bound to a graphene sheet. We propose possible avenues to mitigate the effect of quantum uncertainty.
