Article
Multidisciplinary Sciences
Aji Alex M. Raynold, Danyang Li, Lan Chang, Julien E. Gautrot
Summary: Authors report on mechanisms of RNA release from polycationic gene delivery vectors, highlighting the role of competitive binding, and characterise the interactome associated with vectors upon cytosolic entry.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Edward L. Huttlin, Raphael J. Bruckner, Jose Navarrete-Perea, Joe R. Cannon, Kurt Baltier, Fana Gebreab, Melanie P. Gygi, Alexandra Thornock, Gabriela Zarraga, Stanley Tam, John Szpyt, Brandon M. Gassaway, Alexandra Panov, Hannah Parzen, Sipei Fu, Arvene Golbazi, Eila Maenpaa, Keegan Stricker, Sanjukta Guha Thakurta, Tian Zhang, Ramin Rad, Joshua Pan, David P. Nusinow, Joao A. Paulo, Devin K. Schweppe, Laura Pontano Vaites, J. Wade Harper, Steven P. Gygi
Summary: This study explores thousands of interactions between proteins, creating two essential cell-line specific interaction networks that help researchers understand the principles of proteome organization and unknown protein characteristics. Comparing different cell lines revealed extensive customization, linking core complexes with essential proteins and rewiring subnetworks to produce each cell's phenotype.
Article
Infectious Diseases
Loraine V. Fabri, Kristy I. Azzopardi, Joshua Osowicki, Hannah R. Frost, Pierre R. Smeesters, Andrew C. Steer
Summary: A reliable molecular method has been developed for measuring Streptococcus pyogenes bacterial load from throat swabs collected in a controlled human infection model of S. pyogenes pharyngitis.
BMC INFECTIOUS DISEASES
(2021)
Article
Biochemistry & Molecular Biology
Sylvain D. Vallet, Martin N. Davis, Anna Barque, Ali H. Thahab, Sylvie Ricard-Blum, Alexandra Naba
Summary: This study presents a novel ECM protein, SNED1, which promotes breast cancer metastasis and regulates craniofacial development. By combining computational predictions and experimental approaches, the physico-chemical properties of SNED1 were characterized, and its potential functions were inferred, shedding light on its pathophysiological roles.
BIOCHEMICAL JOURNAL
(2021)
Article
Nanoscience & Nanotechnology
Marta Broto, Michael M. Kaminski, Christopher Adrianus, Nayoung Kim, Robert Greensmith, Schan Dissanayake-Perera, Alexander J. Schubert, Xiao Tan, Hyemin Kim, Anand S. Dighe, James J. Collins, Molly M. Stevens
Summary: This study combines CRISPR-Cas reaction with nanozyme-linked ELISA to achieve quantitative detection of Cas13-mediated RNA detection through catalytic metallic nanoparticles at room temperature (CrisprZyme). The study shows that CrisprZyme is adaptable to lateral flow reading and different Cas enzymes, and can detect various non-coding RNAs. The platform can be used to identify disease patients and monitor cellular differentiation. CrisprZyme can serve as a universally applicable signal catalyst for CRISPR-based diagnostics, expanding the target range of preamplification-free, quantitative detection.
NATURE NANOTECHNOLOGY
(2022)
Article
Chemistry, Physical
Weiwei He, Nawavi Naleem, Diego Kleiman, Serdal Kirmizialtin
Summary: This article highlights the growing recognition of RNA's functional and therapeutic roles and the difficulties in gaining atomic-level insights through experiments. It explores the use of all-atom simulations to overcome these challenges and assesses the performance of different force fields against small-angle X-ray scattering experiments. The study identifies inconsistencies in existing force fields and proposes a modified force field, HB-CUFIX, which exhibits improved performance in studying the thermodynamics and structural properties of realistic RNA motifs.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2022)
Article
Oncology
Margaret C. Steiner, Jez L. Marston, Luis P. Iniguez, Matthew L. Bendall, Katherine B. Chiappinelli, Douglas F. Nixon, Keith A. Crandall
Summary: Research implicates that HERVs are involved in various cancers, with differential expression identified in prostate, breast, and colon cancers. The study highlights potential biomarkers and therapeutic targets in these cancers, providing insights into the role of HERVs in cancer pathogenesis.
Article
Multidisciplinary Sciences
Anna Nemudraia, Artem Nemudryi, Murat Buyukyoruk, Andrew M. Scherffius, Trevor Zahl, Tanner Wiegand, Shishir Pandey, Joseph E. Nichols, Laina N. Hall, Aidan McVey, Helen H. Lee, Royce A. Wilkinson, Laura R. Snyder, Joshua D. Jones, Kristin S. Koutmou, Andrew Santiago-Frangos, Blake Wiedenheft
Summary: This study applies type-III CRISPR-based RNA capture and concentration technology to the detection of SARS-CoV-2, with advantages of rapidity, high sensitivity, and low cost.
NATURE COMMUNICATIONS
(2022)
Article
Biophysics
Yuanyuan Zhu, Jian Wu, Qingli Zhou
Summary: Functional DNA (fDNA) refers to DNA molecules that have specific binding ability or catalytic function, with advantages of simple synthesis, low cost, low toxicity, high chemical stability, recognition specificity, and biocompatibility. However, the limited sensitivity of fDNA sensors to trace targets is a major challenge, especially when there is low affinity between fDNA and the targets. Various nucleic acid signal amplification strategies (NASAS) have been explored to improve the limit of detection of fDNA. This review summarizes four NASAS (hybridization chain reaction, entropy-driven catalysis, rolling circle amplification, CRISPR/Cas system) and their corresponding design principles, as well as the principle and application of fDNA sensors integrated with signal amplification strategies for the detection of non-nucleic acid targets. The main challenges and application prospects of NASAS-integrated fDNA biosensing system are also discussed.
BIOSENSORS & BIOELECTRONICS
(2023)
Letter
Biotechnology & Applied Microbiology
Long-Can Mei, Ge-Fei Hao, Guang-Fu Yang
Summary: This article reviews the existing thermodynamic databases for protein-nucleic acid interactions and provides general comments to enhance browsing and exploration.
TRENDS IN BIOTECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Samir Rahman, Pengfei Dong, Pasha Apontes, Michael B. Fernando, Roman Kosoy, Kayla G. Townsley, Kiran Girdhar, Jaroslav Bendl, Zhiping Shao, Ruth Misir, Nadia Tsankova, Steven P. Kleopoulos, Kristen J. Brennand, John F. Fullard, Panos Roussos
Summary: This study provides multi-scale insights into the 3D genome in the human brain, revealing differences in genome compartmentalization and topologically associated domains between neurons and glia, and highlighting the association between rewiring of chromatin loops and neural development as well as neurodevelopmental disorders such as autism.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Oncology
Antonella Falconieri, Giovanni Minervini, Federica Quaglia, Geppo Sartori, Silvio C. E. Tosatto
Summary: The von Hippel-Lindau (pVHL) tumor suppressor plays a crucial role in regulating cell adaptation to low oxygen concentrations and is also involved in testis development and sperm maturation. Through a testis-specific library screening, 55 novel proteins that interact with pVHL were identified, many of which are involved in metabolic pathways frequently altered in cancer. The findings suggest that pVHL may be important for normal gonadal development in humans.
Article
Biochemical Research Methods
Shayne D. Wierbowski, Siqi Liang, Yuan Liu, You Chen, Shagun Gupta, Nicole M. Andre, Steven M. Lipkin, Gary R. Whittaker, Haiyuan Yu
Summary: The emergence of new viral agents is driven by evolution of interactions between viral proteins and host targets, leading to increased infectivity of viruses such as SARS-CoV-2 through rapid evolution. State-of-the-art interface prediction and molecular docking were used to construct a three-dimensional structural interactome between SARS-CoV-2 and human, facilitating the study of how pathogen-host interactions impact transmission and virulence. The resource provided aims to aid in the development and testing of informed hypotheses for understanding the etiology and treatments of SARS-CoV-2.
Article
Biochemistry & Molecular Biology
Zupeng Wang, Caihong Zhong
Summary: Cas12c-DETECTOR is a new nucleic acid detection platform with high sensitivity and specificity, capable of specifically identifying SNPs through coupling with sgRNAs, and can be used for diagnosing human and plant pathogens in conjunction with other techniques.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Biochemical Research Methods
Dalin He, Gang Liu, Jing Yang, Xiaoning Jiang, Hongzhi Wang, Yaru Fan, Shangyu Gong, Feng Wei, Youxiang Diao, Yi Tang
Summary: This study developed a recombinase polymerase amplification (RPA)-based CRISPR-Cas13a method for fast detection of TMUV infection. The method showed high specificity and sensitivity, and performed comparably to the standard method in clinical samples.
BIOCONJUGATE CHEMISTRY
(2022)
Article
Infectious Diseases
Lena M. M. Sauer, Rodrigo Canovas, Daniel Roche, Hosam Shams-Eldin, Patrice Ravel, Jacques Colinge, Ralph T. T. Schwarz, Choukri Ben Mamoun, Eric Rivals, Emmanuel Cornillot
Summary: Protozoan parasites attach specific and diverse proteins to their plasma membrane via a GPI anchor. The FT-GPI software can detect GPI-anchored proteins and identify new candidates for vaccines against malaria and other parasitic diseases.
Review
Biochemistry & Molecular Biology
Jiahui Huang, Gerhard F. Ecker
Summary: The discovery of the first ATP-binding cassette (ABC) transporter has led to extensive research efforts in overcoming tumor cell multidrug resistance (MDR) by inhibiting the ABC-transporter. This review focuses on the structural aspects of this important group of transmembrane transport proteins and includes a summary of available structures and recent structure-based studies. The use of artificial intelligence (AI) predictions from AlphaFold-2 is also discussed.
Article
Multidisciplinary Sciences
Katherine M. Kennedy, Marcus C. de Goffau, Maria Elisa Perez-Munoz, Marie-Claire Arrieta, Fredrik Backhed, Peer Bork, Thorsten Braun, Frederic D. Bushman, Joel Dore, Willem M. de Vos, Ashlee M. Earl, Jonathan A. Eisen, Michal A. Elovitz, Stephanie C. Ganal-Vonarburg, Michael G. Ganzle, Wendy S. Garrett, Lindsay J. Hall, Mathias W. Hornef, Curtis Huttenhower, Liza Konnikova, Sarah Lebeer, Andrew J. Macpherson, Ruth C. Massey, Alice Carolyn McHardy, Omry Koren, Trevor D. Lawley, Ruth E. Ley, Liam O'Mahony, Paul W. O'Toole, Eric G. Pamer, Julian Parkhill, Jeroen Raes, Thomas Rattei, Anne Salonen, Eran Segal, Nicola Segata, Fergus Shanahan, Deborah M. Sloboda, Gordon C. S. Smith, Harry Sokol, Tim D. Spector, Michael G. Surette, Gerald W. Tannock, Alan W. Walker, Moran Yassour, Jens Walter
Summary: The colonization of microbial communities in the human fetus and the prenatal intrauterine environment is still controversial. Recent studies analyzing microbial populations in human fetuses indicate that the detected signals might be due to contamination during sample collection or DNA sequencing processes. The presence of live and replicating microbial populations in healthy fetal tissues contradicts fundamental concepts in immunology and clinical microbiology. This has significant implications for our understanding of human immune development and highlights the challenges in studying microbial communities in low-biomass environments.
Article
Biochemistry & Molecular Biology
Typhaine Paysan-Lafosse, Matthias Blum, Sara Chuguransky, Tiago Grego, Beatriz Lazaro Pinto, Gustavo A. Salazar, Maxwell L. Bileschi, Peer Bork, Alan Bridge, Lucy Colwell, Julian Gough, Daniel H. Haft, Ivica Letunic, Aron Marchler-Bauer, Huaiyu Mi, Darren A. Natale, Christine A. Orengo, Arun P. Pandurangan, Catherine Rivoire, Christian J. A. Sigrist, Ian Sillitoe, Narmada Thanki, Paul D. Thomas, Silvio C. E. Tosatto, Cathy H. Wu, Alex Bateman
Summary: The InterPro database has been updated with new data content and website features, providing a more user-friendly access to protein sequence classification and functional domain identification. It has also integrated features from the retiring Pfam website and developed a card game to engage the non-scientific community. Furthermore, the database explores the benefits and challenges of using artificial intelligence for protein structure prediction.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biology
Patrick Essletzbichler, Vitaly Sedlyarov, Fabian Frommelt, Didier Soulat, Leonhard X. Heinz, Adrijana Stefanovic, Benedikt Neumayer, Giulio Superti-Furga
Summary: Phagocytosis is a crucial process for tissue clearance and host defense, but its dysregulation is linked to various diseases. This study used a genome-wide CRISPRko FACS screen to identify 716 genes involved in phagocytosis. By mapping the hits to a protein-protein interaction network, novel phagocytosis regulators were discovered and validated. This comprehensive network provides insights into cargo uptake and transformation, and can aid in the identification of potential drivers for endo-lysosomal diseases.
LIFE SCIENCE ALLIANCE
(2023)
Review
Pharmacology & Pharmacy
Esra Balikci, Anne-Sophie M. C. Marques, Jesper S. Hansen, Kilian V. M. Huber
Summary: The rational development of new therapeutics requires a thorough understanding of how aberrant signaling affects cellular homeostasis and causes human disease. Chemical probes are powerful tools for drug discovery that have led to fundamental insights into biological processes and have paved the way for the development of first-in-class drugs.
EXPERT OPINION ON DRUG DISCOVERY
(2023)
Article
Biochemistry & Molecular Biology
Emanuele Mocciaro, Roberto Giambruno, Stefano Micheloni, Filippo M. Cernilogar, Annapaola Andolfo, Cristina Consonni, Maria Pannese, Giulia Ferri, Valeria Runfola, Gunnar Schotta, Davide Gabellini
Summary: FSHD is a prevalent neuromuscular disorder associated with copy number reduction and epigenetic alterations of the D4Z4 macrosatellite on chromosome 4q35. Aberrant expression of the transcription factor DUX4 plays a key role in this disease. In this study, the authors identified the chromatin remodeling protein WDR5 as an interactor of the long non protein-coding RNA DBE-T and demonstrated its requirement for the expression of DUX4 and its targets. Targeting WDR5 rescued cell viability and myogenic differentiation of FSHD patient cells, suggesting it as a potential therapeutic target for FSHD.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Jean-Philippe Villemin, Laia Bassaganyas, Didier Pourquier, Florence Boissiere, Simon Cabello-Aguilar, Evelyne Crapez, Rita Tanos, Emmanuel Cornillot, Andrei Turtoi, Jacques Colinge
Summary: The study of cellular networks mediated by ligand-receptor interactions has been a hot topic recently due to single-cell omics. However, there is a lack of comparable bulk data and clinical information in single-cell studies. Spatial transcriptomic analyses offer a revolutionary tool in biology, particularly those relying on multicellular resolution. In this study, we introduce BulkSignalR, an R package that infers ligand-receptor networks from bulk data, integrates downstream pathways, and provides statistical significance estimation and visualization methods, including those specific to spatial data. Our results demonstrate the relevance and superior quality of BulkSignalR inferences compared to other spatial transcriptomic packages.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Immunology
Emilia Rabia, Veronique Garambois, Christine Dhommee, Christel Larbouret, Laurie Lajoie, Yoan Buscail, Gabriel Jimenez-Dominguez, Sylvie Choblet-Thery, Emmanuelle Liaudet-Coopman, Martine Cerutti, Marta Jarlier, Patrice Ravel, Laurent Gros, Nelly Pirot, Gilles Thibault, Eugene A. A. Zhukovsky, Pierre-Emmanuel Gerard, Andre Pelegrin, Jacques Colinge, Thierry Chardes
Summary: Using the BiXAb(TM) tetravalent platform, we generated bispecific antibodies against EGFR, HER2, or HER3 and compared them with single antibodies and antibody pair combinations. We selected 3Patri-1Cetu-Fc, 3Patri-1Matu-Fc, and 3Patri-2Trastu-Fc as lead candidates and tested their efficacy in mouse models of pancreatic cancer. This semi-rational/semi-empirical approach represents the first attempt to identify potent bispecific antibodies against ErbB family members in pancreatic cancer.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Markus Blatter, Charlotte Meylan, Antoine Clery, Roberto Giambruno, Yaroslav Nikolaev, Michel Heidecker, Jessica Arvindbhai Solanki, Manuel O. Diaz, Davide Gabellini, Frederic H. -T. Allain
Summary: The study found that Mixed-lineage leukemia 1 (MLL1) is a transcription activator of the HOX family and its activity is repressed by cyclophilin 33 (Cyp33), which binds to MLL1 PHD3. The researchers determined the solution structures of Cyp33 in different binding states and identified that conformational changes triggered by Cyp33 binding to RNA facilitate the release of MLL1 from the histone mark. These findings provide a mechanistic understanding of how Cyp33 binding to MLL1 switches chromatin to a transcriptional repressive state through a negative feedback loop triggered by RNA binding.
Article
Chemistry, Medicinal
Aljosa Smajic, Iris Rami, Sergey Sosnin, Gerhard F. Ecker
Summary: This study investigates the distribution of positive and nonpositive entries within the ChEMBL database and its impact on the performance of classification models. The results indicate that models trained on publicly available data tend to overpredict positives, while models based on industry data sets predict negatives more often. The visualization of the prediction space further strengthens these findings by identifying regions where predictions converge. Furthermore, the utilization of these models for consensus modeling for potential adverse events prediction is highlighted.
CHEMICAL RESEARCH IN TOXICOLOGY
(2023)
Review
Pharmacology & Pharmacy
Vojtech Dvorak, Giulio Superti-Furga
Summary: Solute carriers (SLCs) are the largest group of membrane transporters in the human genome, and they are central in controlling metabolism compartmentalization, with most of this superfamily being linked to human diseases. Despite being considered attractive therapeutic targets, many SLCs still lack functional and structural annotations.
EXPERT OPINION ON DRUG DISCOVERY
(2023)
Article
Biochemistry & Molecular Biology
Karin Grillberger, Eike Collen, Claudia Immacolata Trivisani, Jonathan Blum, Marcel Leist, Gerhard F. Ecker
Summary: Toxic effects of neonicotinoids and their metabolites on human neurons were investigated using a combination of in silico and in vitro methods. Calcium imaging on neurons confirmed a key event predicted by molecular simulations, providing a new approach for next-generation risk assessments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Chuqing Sun, Jingchao Chen, Menglu Jin, Xueyang Zhao, Yun Li, Yanqi Dong, Na Gao, Zhi Liu, Peer Bork, Xing-Ming Zhao, Wei-Hua Chen
Summary: In this study, DNA methylation patterns in 8848 high-quality phages from 104 fecal samples were analyzed using single-molecule real-time sequencing. The results show that 97.60% of gut phages exhibit methylation, and certain factors correlate with methylation densities. Phages with higher methylation densities have potential viability advantages. More than one-third of the phages possess their own DNA methyltransferases (MTases), and increased MTase copies are associated with higher genome methylation densities and specific methylation motifs. These findings indicate the widespread utilization of DNA methylation by gut DNA phages as an evasion mechanism against host defense systems.
Article
Biochemical Research Methods
Jean-Pierre Borg, Jacques Colinge, Patrice Ravel
Summary: The traditional method of modular response analysis (MRA) is difficult to apply to networks with 10 or more nodes due to sensitivity to noise in the data and perturbation intensities. We propose a new formulation of MRA as a multilinear regression problem, which allows for integration of all replicates and potential additional perturbations in a larger and more stable system of equations. This approach provides more relevant confidence intervals for network parameters and shows competitive performance for networks up to size 1000. Integration of known null edges further improves the results.