Article
Immunology
Lisa Sandner, Marlis Alteneder, Ramona Rica, Barbara Woller, Eleonora Sala, Tobias Frey, Anela Tosevska, Ci Zhu, Moritz Madern, Matarr Khan, Pol Hoffmann, Alexandra Schebesta, Ichiro Taniuchi, Michael Bonelli, Klaus Schmetterer, Matteo Iannacone, Mirela Kuka, Wilfried Ellmeier, Shinya Sakaguchi, Ruth Herbst, Nicole Boucheron
Summary: This study identifies the guanine nucleotide exchange factor Rin-like (Rinl) as a negative regulator of Tfh cell development. Loss of Rinl leads to an increase in Tfh cells and affects CD28 internalization and signaling pathways in CD4(+) T cells.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Christopher Hubner, Hajo Haase
Summary: Zinc and ROS play roles in various physiological functions and are connected through their interaction with sulfur, forming a triad. Zinc can translate redox signals into zinc signals by binding to and releasing from thiols, affecting thiol oxidation and protein activity. The reciprocal interaction between zinc and redox-signaling involves shared molecular targets like active site cysteine thiols in PTP, showcasing their complex interplay on multiple levels.
Review
Oncology
Ainaz Mihanfar, Bahman Yousefi, Bita Azizzadeh, Maryam Majidinia
Summary: Melatonin has a regulatory role in multiple signaling pathways involved in cancer progression, making it a potential therapeutic approach for malignancies.
CANCER CELL INTERNATIONAL
(2022)
Article
Plant Sciences
Ressin Varghese, C. George Priya Doss, Raju Suresh Kumar, Abdulrahman Almansour, Natarajan Arumugam, Thomas Efferth, Siva Ramamoorthy
Summary: Phytopigments exhibit pleiotropic cardioprotective effects through various signaling pathways to alleviate cardiovascular diseases, suggesting their potential as novel and effective therapeutic candidates. More randomized, placebo-controlled clinical studies are recommended to establish the clinical efficacy of phytopigments.
Review
Nutrition & Dietetics
Izabela Berdowska, Malgorzata Matusiewicz, Izabela Fecka
Summary: Pomegranate extract has been used in medicine for its health-beneficial properties, with punicalagin identified as a key compound responsible for its anti-cancer effects. Recent studies have shown that punicalagin can impact cancer cells by redirecting signaling pathways towards apoptosis, senescence, and autophagy, thus hindering neoplastic progression.
Article
Biochemistry & Molecular Biology
Xiaoli Liu, Yan Gu, Yaoyao Bian, Danhong Cai, Yu Li, Ye Zhao, Zhaofeng Zhang, Mei Xue, Liang Zhang
Summary: HNK reduces the viability of human APL cell line (NB4 cells) by inducing paraptosis-like cell death. This process is associated with excessive reactive oxygen species (ROS), mitochondrial damage, endoplasmic reticulum stress, and increased microtubule-associated protein 1 light chain 3 (LC3) processing. It was found that the mTOR signaling pathway participated in paraptosis-like cell death induced by HNK, providing novel insights into the potential mechanism of paraptosis-like cell death.
Article
Biotechnology & Applied Microbiology
Aimin Liu, Buxin Zhang, Wei Zhao, Yuanhui Tu, Qingxing Wang, Jing Li
Summary: This study aims to investigate the therapeutic role of catalpol in psoriasis, and the results suggest that catalpol may ameliorate psoriasis symptoms by reducing oxidative stress and inflammation, possibly through SIRT1-mediated suppression of NF-.B and MAPKs pathways.
Review
Cell Biology
Flurina Boehi, Patrick Manetsch, Michael O. Hottiger
Summary: Signaling cascades play a crucial role in cellular responses to signals, with protein post-translational modifications such as ADP-ribosylation impacting a variety of cellular processes. The interplay between intracellular ADP-ribosyltransferases and selected signaling pathways is significant for understanding cellular responses.
Article
Biology
Manon Destalminil-Letourneau, Ismael Morin-Poulard, Yushun Tian, Nathalie Vanzo, Michele Crozatier
Summary: In adult mammals, hematopoiesis is tightly regulated by signals from the microenvironment called niche. The vascular system acts as a second niche to control lymph gland homeostasis by regulating intracellular calcium levels through the FGF signaling pathway. This study shows that two niches contribute to the control of Drosophila blood cell homeostasis through differential regulation of progenitors.
Article
Chemistry, Multidisciplinary
Zhiqiang Chen, Xinyi Zhou, Xiaojun Zhou, Yi Tang, Mingzhu Lu, Jianhong Zhao, Chenhui Tian, Mingzhi Wu, Yanliang Liu, Edward V. Prochownik, Fubing Wang, Youjun Li
Summary: This study discovers the role of the enzyme PMVK in stabilizing beta-catenin signaling by screening a human genome-wide library. PMVK-produced MVA-5PP competitively binds to CKI alpha to prevent beta-catenin Ser45 phosphorylation and degradation, while PMVK functions as a protein kinase to directly phosphorylate beta-catenin Ser184, increasing its nuclear localization. This non-canonical function of PMVK and its link to the mevalonate pathway reveal a potential target for cancer therapy.
Article
Biochemical Research Methods
Lujing Zheng, Zhenhuan Liu, Yang Yang, Hong-Bin Shen
Summary: This study introduces a new method, ConGRI, for identifying gene regulatory interactions from gene expression images using contrastive learning and deep neural network technology. The method outperforms traditional and deep learning methods on a Drosophila embryogenesis dataset, achieving high prediction accuracy.
Review
Cell Biology
Ioanna Mourkioti, Andriani Angelopoulou, Konstantinos Belogiannis, Nefeli Lagopati, Spyridon Potamianos, Efthymios Kyrodimos, Vassilis Gorgoulis, Angelos Papaspyropoulos
Summary: Prostate cancer is a hormone-dependent cancer that is a major cause of cancer incidence in men worldwide. The primary treatment approach is androgen deprivation therapy, but resistance often develops, leading to castration-resistant prostate cancer. Understanding the molecular mechanisms and signaling pathways involved in the progression of early-stage prostate cancer towards castration-resistant prostate cancer is crucial.
Article
Multidisciplinary Sciences
Luca Guglielmi, Claire Heliot, Sunil Kumar, Yuriy Alexandrov, Ilaria Gori, Foteini Papaleonidopoulou, Christopher Barrington, Philip East, Andrew D. Economou, Paul M. W. French, James McGinty, Caroline S. Hill
Summary: The absence of the transcriptional effector SMAD4 disrupts dorsal/ventral embryo patterning due to loss of BMP signaling, while Nodal signaling is maintained but lacks robustness. This highlights the differential requirement of SMAD4 for signaling by different TGF-beta family ligands, with implications for diseases where SMAD4 is mutated or deleted.
NATURE COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
Ching-Yi Liao, Ping Wang, Yanhai Yin, Diane C. Bassham
Summary: This article reviews the important functions of autophagy in plant growth, development, and stress responses, and discusses the interaction mechanisms between autophagy and phytohormone signaling pathways. It highlights recent insights into how autophagy regulates hormone signaling, particularly with stress hormone abscisic acid, brassinosteroid, and cytokinin, and briefly mentions potential connections between autophagy and other phytohormones.
Review
Biochemistry & Molecular Biology
Rezan Ashayeri Ahmadabad, Zahra Mirzaasgari, Ali Gorji, Maryam Khaleghi Ghadiri
Summary: Toll-like receptors are important in modulating inflammatory responses, particularly in neuroinflammation induced by cerebrovascular diseases. The TLR signaling pathway triggers immune responses through the production of inflammatory mediators. Modulating different TLRs may have potential benefits in improving functional outcomes after brain ischemia.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Tehmina Masud, Charles Soong, Hong Xu, Justina Biele, Saelin Bjornson, Steven McKinney, Samuel Aparicio
Summary: We have identified several genetic vulnerabilities to CX-5461 through experiments, including members of the homologous recombination repair pathway, Fanconi Anemia pathway, and the polymerase POLQ that plays a crucial role in resolving G4 structures. This could have potential significance for patient selection in future clinical trials.
SCIENTIFIC REPORTS
(2021)
Article
Genetics & Heredity
Esther Danenberg, Helen Bardwell, Vito R. T. Zanotelli, Elena Provenzano, Suet-Feung Chin, Oscar M. Rueda, Andrew Green, Emad Rakha, Samuel Aparicio, Ian O. Ellis, Bernd Bodenmiller, Carlos Caldas, H. Raza Ali
Summary: Imaging mass cytometry profiling of 693 breast tumors revealed 10 recurrent tumor microenvironment spatial structures, associated with genomic profiles and outcomes. These multicellular structures within the TME, varying in vascular content, stromal activation, and leukocyte composition, could improve patient stratification and link spatial organization to local TME function.
Article
Multidisciplinary Sciences
John Hilton, Karen Gelmon, Philippe L. Bedard, Dongsheng Tu, Hong Xu, Anna V. Tinker, Rachel Goodwin, Scott A. Laurie, Derek Jonker, Aaron R. Hansen, Zachary W. Veitch, Daniel J. Renouf, Linda Hagerman, Hongbo Lui, Bingshu Chen, Deb Kellar, Irene Li, Sung-Eun Lee, Takako Kono, Brian Y. C. Cheng, Damian Yap, Daniel Lai, Sean Beatty, John Soong, Kathleen I. Pritchard, Isabel Soria-Bretones, Eric Chen, Harriet Feilotter, Moira Rushton, Lesley Seymour, Samuel Aparicio, David W. Cescon
Summary: CX-5461, a G-quadruplex stabilizer, exhibits synthetic lethality in homologous recombination-deficient models. This multicentre phase I trial in patients with solid tumors demonstrates the clinical proof-of-concept for CX-5461, with a recommended phase II dose of 475 mg/m(2) in patients with defective homologous recombination. Responses are observed in 14% of patients, primarily in those with defective homologous recombination.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Peter Eirew, Ciara O'Flanagan, Jerome Ting, Sohrab Salehi, Jazmine Brimhall, Beixi Wang, Justina Biele, Teresa Algara, So Ra Lee, Corey Hoang, Damian Yap, Steven McKinney, Cherie Bates, Esther Kong, Daniel Lai, Sean Beatty, Mirela Andronescu, Elena Zaikova, Tyler Funnell, Nicholas Ceglia, Stephen Chia, Karen Gelmon, Colin Mar, Sohrab Shah, Andrew Roth, Alexandre Bouchard-Cote, Samuel Aparicio
Summary: This paper develops a quantitative approach to study gene fitness in breast cancer and analyzes the factors that influence uncertainty in fitness estimation. The results show that the gene fitness landscape in breast cancer patient-derived xenografts is dominated by inter-patient differences.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
George Hunt, Ann Boija, Mattias Mannervik
Summary: Maintenance of appropriate cell states involves epigenetic mechanisms, including Polycomb-group (PcG)-mediated transcriptional repression. This study reveals the association between the p300/CREB-binding protein (CBP) co-activator and PcG regions in Drosophila and mouse cells. CBP stabilizes Pol II at PcG-bound repressive sites and promotes Pol II pausing, which are necessary for R-loop formation and nucleosome depletion at Polycomb Response Elements (PREs), thereby supporting PcG-mediated silencing.
Article
Multidisciplinary Sciences
Tyler Funnell, Ciara H. O'Flanagan, Marc J. Williams, Andrew McPherson, Steven McKinney, Farhia Kabeer, Hakwoo Lee, Sohrab Salehi, Ignacio Vazquez-Garcia, Hongyu Shi, Emily Leventhal, Tehmina Masud, Peter Eirew, Damian Yap, Allen W. Zhang, Jamie L. P. Lim, Beixi Wang, Jazmine Brimhall, Justina Biele, Jerome Ting, Vinci Au, Michael Van Vliet, Yi Fei Liu, Sean Beatty, Daniel Lai, Jenifer Pham, Diljot Grewal, Douglas Abrams, Eliyahu Havasov, Samantha Leung, Viktoria Bojilova, Richard A. Moore, Nicole Rusk, Florian Uhlitz, Nicholas Ceglia, Adam C. Weiner, Elena Zaikova, J. Maxwell Douglas, Dmitriy Zamarin, Britta Weigelt, Sarah H. Kim, Arnaud Da Cruz Paula, Jorge S. Reis-Filho, Spencer D. Martin, Yangguang Li, Hong Xu, Teresa Ruiz de Algara, So Ra Lee, Viviana Cerda Llanos, David G. Huntsman, Jessica N. McAlpine, Sohrab P. Shah, Samuel Aparicio
Summary: This study reveals the contribution of cell-to-cell structural variation to the phenotypic and evolutionary diversity in human breast cancer and ovarian cancer, and provides insights into the genomic and mutational states of individual cancer cells.
Article
Biochemistry & Molecular Biology
Didier Hodzic, Jun Wu, Karen Krchma, Andrea Jurisicova, Yonit Tsatskis, Yijie Liu, Peng Ji, Kyunghee Choi, Helen McNeill
Summary: This study reveals for the first time the crucial role of nuclear envelope protein NEMP1 in erythropoiesis. The researchers found that NEMP1 plays an important regulatory role in nuclear envelope openings and enucleation process of red blood cells. The results provide a valuable mouse model for studying defective erythropoiesis.
Article
Oncology
Alexander Pfab, Sergey Belikov, Michaela Keuper, Martin Jastroch, Mattias Mannervik
Summary: This study found that the neurotoxin symbolscript can trigger cell death of dopamine neurons, leading to Parkinson's disease symptoms. Additionally, the neurotoxin directly affects mitochondrial function and transcription, resulting in reduced ATP production. These findings reveal the direct effects of symbolscript on cellular processes, while other gene expression or epigenetic changes are secondary effects reflecting cellular adaptation.
EXPERIMENTAL CELL RESEARCH
(2023)
Article
Multidisciplinary Sciences
Seong-Hwan Jun, Hosein Toosi, Jeff Mold, Camilla Engblom, Xinsong Chen, Ciara O'Flanagan, Michael Hagemann-Jensen, Rickard Sandberg, Samuel Aparicio, Johan Hartman, Andrew Roth, Jens Lagergren
Summary: Functional characterization of cancer clones is important for understanding cancer's evolutionary mechanisms. The authors introduce PhylEx, a method that combines bulk genomics and single-cell RNA sequencing data to reconstruct clonal trees and identify clones. PhylEx outperforms other methods and allows for accurate inference of clonal trees and analysis of cancer.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Nicholas Ceglia, Zachary Sethna, Samuel S. Freeman, Florian Uhlitz, Viktoria Bojilova, Nicole Rusk, Bharat Burman, Andrew Chow, Sohrab Salehi, Farhia Kabeer, Samuel Aparicio, Benjamin D. Greenbaum, Sohrab P. Shah, Andrew McPherson
Summary: To decipher individual cell phenotypes, high dimensional single-cell RNA sequencing is required. GeneVector is a scalable framework that uses gene co-expression to perform dimensionality reduction, allowing for the identification of transcriptional programs and cell type classification. GeneVector has been shown to capture phenotype-specific pathways and identify pathway variation in response to treatment.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Yi Cui, Gaojie Yang, Daniel R. Goodwin, Ciara H. O'Flanagan, Anubhav Sinha, Chi Zhang, Kristina E. Kitko, Tay Won Shin, Demian Park, Samuel Aparicio, Edward S. Boyden
Summary: Expansion microscopy (ExM) enlarges specimens physically for nanoimaging on standard light microscopes. The multifunctional anchor simplifies ExM protocols, reduces cost, and enables the preservation and visualization of RNA transcripts, proteins, and other biomolecular species.
Article
Multidisciplinary Sciences
Ha-Linh Nguyen, Tatjana Geukens, Marion Maetens, Samuel Aparicio, Ayse Bassez, Ake Borg, Jane Brock, Annegien Broeks, Carlos Caldas, Fatima Cardoso, Maxim De Schepper, Mauro Delorenzi, Caroline A. Drukker, Annuska M. Glas, Andrew R. Green, Edoardo Isnaldi, Jorunn Eyfjoro, Hazem Khout, Stian Knappskog, Savitri Krishnamurthy, Sunil R. Lakhani, Anita Langerod, John W. M. Martens, Amy E. McCart Reed, Leigh Murphy, Stefan Naulaerts, Serena Nik-Zainal, Ines Nevelsteen, Patrick Neven, Martine Piccart, Coralie Poncet, Kevin Punie, Colin Purdie, Emad A. Rakha, Andrea Richardson, Emiel Rutgers, Anne Vincent-Salomon, Peter T. Simpson, Marjanka K. Schmidt, Christos Sotiriou, Paul N. Span, Kiat Tee Benita Tan, Alastair Thompson, Stefania Tommasi, Karen Van Baelen, Marc Van de Vijver, Steven Van Laere, Laura van't Veer, Giuseppe Viale, Alain Viari, Hanne Vos, Anke T. Witteveen, Hans Wildiers, Giuseppe Floris, Abhishek D. Garg, Ann Smeets, Diether Lambrechts, Elia Biganzoli, Francois Richard, Christine Desmedt
Summary: Obesity is associated with an increased risk of developing breast cancer and worse prognosis in breast cancer patients. This study investigates the biological differences in untreated primary breast cancer according to patients' body mass index (BMI). The study finds several genomic alterations that are differentially prevalent in overweight or obese patients compared to lean patients. It also reveals an elevated and unresolved inflammation of the breast cancer tumor microenvironment associated with obesity. The findings suggest that patient adiposity may play a significant role in the heterogeneity of breast cancer and should be considered for tailored treatment.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Hareth Nahi, Michael Chrobok, Stephan Meinke, Charlotte Gran, Nicole Marquardt, Gabriel Afram, Tolga Sutlu, Mari Gilljam, Birgitta Stellan, Arnika K. Wagner, Pontus Blomberg, Per-Henrik Holmqvist, Lilian Walther-Jallow, Karin Mellstrom, Johan Liwing, Charlotte Gustafsson, Robert Mansson, Monika Klimkowska, Gosta Gahrton, Johan Lund, Per Ljungman, Hans-Gustaf Ljunggren, Evren Alici
Summary: This study demonstrates the feasibility of autologous NK cell-based immunotherapy in consolidation therapy for multiple myeloma and opens up the possibility for the usage of autologous NK cells in clinical settings where patients are not eligible for allogeneic NK cell-based immunotherapies.
CELL REPORTS MEDICINE
(2022)
Article
Oncology
Laura Kuett, Raul Catena, Alaz Ozcan, Alex Pluss, Peter Schraml, Holger Moch, Natalie de Souza, Bernd Bodenmiller
Summary: The article introduces a new imaging mass cytometry technology that allows for multiplexed tissue analysis in three dimensions. The study shows that this technology can reveal the complexity of cells and microenvironments, as well as phenomena occurring in three-dimensional space, such as tumor cell invasion.