Article
Cell Biology
Jayashree Sahana, Thomas J. Corydon, Markus Wehland, Marcus Krueger, Sascha Kopp, Daniela Melnik, Stefan Kahlert, Borna Relja, Manfred Infanger, Daniela Grimm
Summary: The study evaluated changes in focal adhesions in breast cancer cells exposed to simulated microgravity. The findings suggest that genes related to cytoskeleton, extracellular matrix, and focal adhesions are altered in response to microgravity. Fibronectin, vinculin, and E-cadherin play central roles in the formation of multicellular spheroids in breast cancer cells under such conditions.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Zeynab Mousavikhamene, Daniel J. Sykora, Milan Mrksich, Neda Bagheri
Summary: This research successfully introduced an algorithm that could distinguish cancer from non-cancer cells in high-resolution single cell images by exploiting structural differences in the cytoskeleton. Overcoming the barrier of insufficient data in machine learning methodologies, the study identified the most discriminatory features to predict cell type accurately with as few as 100 cells per line. Furthermore, normalizing cell shape improved discrimination of cell lines with difficult-to-distinguish phenotypes, demonstrating the generalizability of the algorithm across various tissue origins.
SCIENTIFIC REPORTS
(2021)
Article
Gastroenterology & Hepatology
Letao Fan, Aslihan Gokaltun, Sarah Maggipinto, Yoshinori Kitagawa, Jeevendra Martyn, Heidi Yeh, Basak E. Uygun, Martin L. Yarmush, O. Berk Usta
Summary: Alterations in mitochondrial morphology and function are well established in nonalcoholic fatty liver disease (NAFLD). Little is known about whether mitochondrial function and injuries recover upon disease reversal. This study investigates the interplays between the cytoskeletal network and mitochondria in the development and reversal of steatosis.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Evan Ja-Yang Wang, I-Hsuan Chen, Brian Yu-Ting Kuo, Chia-Cheng Yu, Ming-Tsung Lai, Jen-Tai Lin, Leo Yen-Ting Lin, Chih-Mei Chen, Tritium Hwang, Jim Jinn-Chyuan Sheu
Summary: Cytoskeleton proteins provide mechanical support for cell development and tissue homeostasis. Mutated genes associated with cytoskeletal proteins have been found in cancer, some of which have clinical implications. Cytoskeleton-associated proteins also play important signaling roles in cancer development. Mutations in cytoskeleton components can change the physical/mechanical properties of cells and determine cell fate during cancer development.
Article
Biochemistry & Molecular Biology
Ivana Barravecchia, Chiara De Cesari, Mattia Forcato, Francesca Scebba, Olga Pyankova, Joanna M. Bridger, Helen A. Foster, Giovanni Signore, Andrea Borghini, Mariagrazia Andreassi, Massimiliano Andreazzoli, Silvio Bicciato, Mario Enrico Pe, Debora Angeloni
Summary: Microgravity and space radiation have distinct effects on human endothelial cells in space flight, triggering different molecular pathways and leading to specific changes in cell structure and function. Tailored countermeasures should be developed separately for microgravity and space radiation to protect astronauts' health effectively.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Xin-Tong Wu, Xiao Yang, Ran Tian, Ying-Hui Li, Chun-Yan Wang, Yu-Bo Fan, Lian-Wen Sun
Summary: Decades of spaceflight studies have shown that cells are capable of sensing and responding to microgravity in space through cytoskeletal reorganization. The disruption of cytoskeletal equilibrium by the shift from ground to space gravity leads to cellular changes in morphology, mechanical properties, extracellular matrix, and signaling pathways, ultimately affecting cell functionality in microgravity.
Article
Cell Biology
Yolla German, Loan Vulliard, Anton Kamnev, Laurene Pfajfer, Jakob Huemer, Anna-Katharina Mautner, Aude Rubio, Artem Kalinichenko, Kaan Boztug, Audrey Ferrand, Joerg Menche, Loic Dupre
Summary: The immunological synapse decodes stimulatory signals into adapted lymphocyte responses, and high-content imaging is used to analyze T and NK cells. The study demonstrates how actin cytoskeleton remodeling shapes synapse architecture and affects lytic granule positioning. Analysis of immunodeficient individuals' CD8(+) T cells reveals the roles of ARPC1B and WASP in synapse assembly.
Article
Biochemistry & Molecular Biology
Liyong Zhang, Delanie McEvoy, Yen Le, Chris Ambrose
Summary: Leaf spongy mesophyll cells form an interconnected network to maximize light capture and gas exchange, with cells enlarging by selectively expanding cell wall regions in contact with intercellular spaces. Stable MT bundles cue the position of intercellular spaces, promoting efficient dilation and cell branching.
Article
Oncology
Kirsten H. Walen
Summary: This study presents an in vitro trackable model system derived from our genome's conservation, which is highly applicable to the initiation and evolution of tumorigenesis. The induction of death signals to proliferating normal human cells resulted in a unique tetraploidization response and cell cycle stress, leading to mitotic slippage and the formation of diploid cells with decreased genome content, displaying increased fitness. This response was associated with a distinct characteristic of the 4n nucleus, involving a 90-degree turn perpendicular to the cell's cytoskeleton axis. The resulting changes in cell shape resembled the morphology of diagnostic cancer cells seen today.
SEMINARS IN CANCER BIOLOGY
(2022)
Review
Cell Biology
Evelyn Garlick, Steven G. Thomas, Dylan M. Owen
Summary: Immune cells consist of a diverse set of cells that undergo complex biological processes, with the cellular cytoskeleton playing a key role in regulating these processes. Optical microscopy is well-suited for imaging and quantitatively describing the structure and dynamics of the cytoskeleton. The latest methodology, hardware, and software for labeling and analyzing cytoskeletal structures are reviewed, with highlighted challenges and areas for future development.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Medicine, Research & Experimental
Lorena Rodriguez, Gabriela Di Venosa, Martin A. Rivas, Angeles Juarranz, Francisco Sanz-Rodriguez, Adriana Casas
Summary: The study found that Ras transfection affects cell morphology, extracellular matrix, and cell-cell adhesion, resulting in increased resistance to photodynamic therapy (PDT).
Article
Medicine, Research & Experimental
Yuan Xie, Liqun He, Roberta Lugano, Yanyu Zhang, Haiyan Cao, Qiyuan He, Min Chao, Boxuan Liu, Qingze Cao, Jianhao Wang, Yang Jiao, Yaqin Hu, Liying Han, Yong Zhang, Hua Huang, Lene Uhrbom, Christer Betsholtz, Liang Wang, Anna Dimberg, Lei Zhang
Summary: By analyzing single-cell RNA sequencing data, researchers discovered different endothelial cell phenotypes in tumor vessels of human glioblastoma, which exhibit varying levels of activation and blood-brain barrier impairment. These findings are associated with different anatomical locations within and around the tumor.
Article
Environmental Sciences
Huan Wu, Yuexin Wei, Yu Zhou, Chunlan Long, Yifan Hong, Yan Fu, Tianxin Zhao, Junke Wang, Yuhao Wu, Shengde Wu, Lianju Shen, Guanghui Wei
Summary: The study revealed that BPS caused male reproductive dysfunction by affecting the integrity of the blood-testis barrier and apical ectoplasmic specialization, predominantly through disruption of F-actin and microtubules, and modulating the balance of mTORC1 and mTORC2.
SCIENCE OF THE TOTAL ENVIRONMENT
(2021)
Article
Multidisciplinary Sciences
Odmaa Bayaraa, Claire K. Inman, Sneha A. Thomas, Fatima Al Jallaf, Manar Alshaikh, Youssef Idaghdour, Louise Ashall
Summary: Hyperglycemia-induced transcriptomic changes in human aortic endothelial cells were analyzed using deep time-series RNA-seq profiling. The study revealed significant pathway activation/inhibition events during the 1-4 hour transition, and identified unique clusters of genes underlying coordinated transcriptional events under high glucose conditions. The results provide insights into the rapid molecular alterations promoting endothelial cell dysfunction.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Aneesh Chandrasekharan, Shankara Narayanan Varadarajan, Asha Lekshmi, T. R. Santhoshkumar
Summary: Cytosolic and organelle redox play critical roles in both physiological and pathological cell states, and the mitochondrion is the major source of cellular ROS and contributes to cell death. The alteration of redox is evident in cells undergoing different forms of cell death. The hierarchical profiling of redox signaling in a single cell is important to understand the contribution of each species in cell death.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Linnea Hojer Wang, Markus Wehland, Petra M. M. Wise, Manfred Infanger, Daniela Grimm, Michael C. C. Kreissl
Summary: This manuscript investigates four tyrosine kinase inhibitors (TKIs), cabozantinib, vandetanib, pralsetinib, and selpercatinib, used for treating advanced and/or metastatic medullary thyroid cancer (MTC). The focus is on treatment-related hypertension, a well-known adverse effect (AE) of these TKIs. While TKI-induced hypertension is rarely a dose-limiting side effect, complications associated with hypertension can increase with longer patient survival without proper medication.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cell Biology
Silja Hansen, Michelle E. McClements, Thomas J. Corydon, Robert E. MacLaren
Summary: Inherited retinal diseases (IRD) are a group of clinically and genetically diverse diseases that cause blindness in the working-age population. Gene augmentation therapies have limitations in treating IRDs, but DNA editing, particularly prime editing, shows potential in correcting different types of mutations. This review provides an overview of recent advancements in prime editing technology and discusses its potential as a treatment option for IRDs.
Article
Biochemistry & Molecular Biology
Justina Joksiene, Jayashree Sahana, Markus Wehland, Herbert Schulz, Jose Luis Cortes-Sanchez, Judit Prat-Duran, Daniela Grimm, Ulf Simonsen
Summary: A diabetogenic state induced by spaceflight causes stress and health problems in astronauts. Microgravity is a main stressor in space that leads to hyperglycaemia. The molecular pathways and synergistic effects of microgravity and hyperglycaemia are not fully understood.
Article
Anatomy & Morphology
Claudia R. Cecchi, Sidsel Alsing, Gustavo P. P. Jesus, Enio A. Zacarias, Lisbeth Kjaer, Michelle S. Clement, Makiko Kumagai-Braesch, Thomas J. Corydon, Paolo Bartolini, Cibele N. Peroni, Lars Aagaard
Summary: Growth hormone (GH) deficiency is currently treated with recombinant human GH (hGH), but encapsulated cell therapy (ECT) may provide a more convenient long-term treatment strategy. This study used PiggyBac-based (PB) transposon delivery to engineer retinal pigment epithelial cells (ARPE-19) with various promoters and codon-optimization methods, and tested the secretion of GH. The results showed that ARPE-19 cells could be encapsulated in TheraCyte devices and secrete GH for at least 60 days in vitro, demonstrating the potential for further in vivo studies.
Review
Cell Biology
Thomas J. Corydon, Herbert Schulz, Peter Richter, Sebastian M. Strauch, Maik Boehmer, Dario A. Ricciardi, Markus Wehland, Marcus Krueger, Gilmar S. Erzinger, Michael Lebert, Manfred Infanger, Petra M. Wise, Daniela Grimm
Summary: Microgravity has a significant impact on the health of space explorers, affecting cell proliferation, differentiation, and growth. With the planning of deep space exploration and the commercialization of space travel, researchers are focusing on gene regulation in cells and organisms exposed to real and simulated microgravity. Cancer and metastasis research in particular benefit from these findings.
Review
Biochemistry & Molecular Biology
Urjosee Sahana, Markus Wehland, Ulf Simonsen, Herbert Schulz, Daniela Grimm
Summary: Despite recent advances in HF therapy, CV mortality, morbidity, and HFH remain challenges. Vericiguat activates sGC to improve CV function and has shown efficacy in reducing CV death and HFH in HFrEF patients. However, it has no therapeutic effect on HFpEF. Common adverse events of vericiguat include hypotension, syncope, and anemia. Larger studies are needed to investigate the potential effect in HFpEF patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Jakob Haldrup, Sofie Andersen, Alexander Rafael LaVilla Labial, Jonas Holst Wolff, Frederik Plum Frandsen, Thomas Wisbech Skov, Anne Bruun Rovsing, Ian Nielsen, Thomas Stax Jakobsen, Anne Louise Askou, Martin K. Thomsen, Thomas J. Corydon, Emil Aagaard Thomsen, Jacob Giehm Mikkelsen
Summary: Effective delivery of gene editing tools in therapeutic in vivo gene editing using CRISPR/Cas can be achieved by engineering lentivirus-derived nanoparticles (LVNPs) as carriers for Cas protein and single guide RNA (sgRNA). LVNPs facilitate precise and efficient gene editing with reduced off-target cleavage activity, making them promising vehicles for in vivo gene disruption. The proof-of-concept study in mice demonstrates the potential of LVNPs for donor-free base and prime editing without double-stranded DNA breaks.
NUCLEIC ACIDS RESEARCH
(2023)
Review
Medicine, Research & Experimental
Ida Juhl Corydon, Bjorn Kristensen Fabian-Jessing, Thomas Stax Jakobsen, Asbjorn Cortnum Jorgensen, Emilie Grarup Jensen, Anne Louise Askou, Lars Aagaard, Thomas Juhl Corydon
Summary: The year 2023 is the 25th anniversary of the discovery of RNAi. RNAi-based therapeutics have gained significant momentum in the past decade, with five approved therapeutics targeting the liver and ongoing trials indicating the availability of more RNAi-based medicines for extra-hepatic tissues in the future. This systematic review identified a total of 90 trials published in 81 articles and 48 ongoing trials, investigating the maturation of RNAi-based therapeutics and developments in delivery platforms, administration routes, and potential targets.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2023)
Article
Multidisciplinary Sciences
Francesca Cialdai, Austin M. Brown, Cory W. Baumann, Debora Angeloni, Sarah Baatout, Alexandra Benchoua, Juergen Bereiter-Hahn, Daniele Bottai, Judith-Irina Buchheim, Marco Calvaruso, Eugenie Carnero-Diaz, Sara Castiglioni, Duccio Cavalieri, Gabriele Ceccarelli, Alexander Chouker, Gianni Ciofani, Giuseppe Coppola, Gabriella Cusella, Andrea Degl'Innocenti, Jean-Francois Desaphy, Jean-Pol Frippiat, Michael Gelinsky, Giada Genchi, Maria Grano, Daniela Grimm, Alain Guignandon, Christiane Hahn, Jason Hatton, Raul Herranz, Christine E. Hellweg, Carlo Saverio Iorio, Thodoris Karapantsios, Jack van Loon, Matteo Lulli, Jeanette Maier, Jos Malda, Emina Mamaca, Lucia Morbidelli, Angelique van Ombergen, Andreas Osterman, Aleksandr Ovsianikov, Francesco Pampaloni, Elizabeth Pavezlorie, Veronica Pereda-Campos, Cyrille Przybyla, Christopher Puhl, Petra Rettberg, Chiara Risaliti, Angela Maria Rizzo, Kate Robson-Brown, Leonardo Rossi, Giorgio Russo, Alessandra Salvetti, Daniela Santucci, Matthias Sperl, Felice Strollo, Kevin Tabury, Sara Tavella, Christiane Thielemann, Ronnie Willaert, Nathaniel J. Szewczyk, Monica Monici
Summary: This white paper presents the indications and recommendations of the SciSpacE Science Community on filling the gaps of knowledge regarding the effects of gravity alterations on animal and human systems at a cellular and tissue level. Despite previous studies, a comprehensive integrated model of the changes occurring at different system and functional levels is still lacking, making it difficult to predict the long-term consequences of human adaptation to the space environment and implement effective medical support plans.
Review
Biochemistry & Molecular Biology
Silvana Miranda, Shannon Marchal, Lina Cumps, Jenne Dierckx, Marcus Kruger, Daniela Grimm, Sarah Baatout, Kevin Tabury, Bjorn Baselet
Summary: The lunar dust problem arose from NASA's Apollo missions in 1969, as exposure to lunar dust became unavoidable. Several astronauts suffered allergy-like symptoms due to lunar dust inhalation. Research into the toxic effects of lunar dust gained significant interest and expanded to include other organ systems. With plans for future moon missions and potentially Mars missions, dust mitigation strategies are crucial for sustainable space exploration.
Review
Biochemistry & Molecular Biology
Niklas S. Jensen, Markus Wehland, Petra M. Wise, Daniela Grimm
Summary: Hypertension is a major global health burden, with an increasing prevalence due to aging populations and sedentary lifestyles. While there is evidence of the role of vitamin D in regulating blood pressure, its direct antihypertensive effect remains unclear. However, supplementing vitamin D in combination with other antihypertensive agents may have promising results.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Jayashree Sahana, Jose Luis Cortes-Sanchez, Viviann Sandt, Daniela Melnik, Thomas J. Corydon, Herbert Schulz, Zexi Cai, Katja Evert, Daniela Grimm, Markus Wehland
Summary: This study cultured breast cancer cell lines MCF-7 and MDA-MB-231 under simulated microgravity conditions and investigated the gene expression pattern and cellular signaling pathways involved. The results showed that the engineered three-dimensional multicellular spheroid model can be used to study breast cancer cell behavior and evaluate the efficacy of drugs against breast cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)