Article
Biophysics
Julia Eckert, Jack J. W. A. van Loon, Lukas M. Eng, Thomas Schmidt
Summary: Studies show that microgravity and hypergravity impact cell shape, elasticity, and motility, with changes in cell traction forces under hypergravity conditions possibly linked to cytoskeleton reorganization and reinforcement.
BIOPHYSICAL JOURNAL
(2021)
Article
Pediatrics
Luping Chen, Bin Mu, Yalong Li, Fangjin Lu, Ping Mu
Summary: The DRR1-CREB axis plays a crucial role in the differentiation of neuroblastoma cells and is associated with the outcome of neuroblastoma patients.
PEDIATRIC RESEARCH
(2023)
Article
Cell Biology
Christian Vahlensieck, Cora S. Thiel, Daniel Poeschl, Timothy Bradley, Sonja Krammer, Beatrice Lauber, Jennifer Polzer, Oliver Ullrich
Summary: The transcriptome of human immune cells responds rapidly to altered gravity in a highly dynamic way, with profound adaptation seen in transcriptional patterns within seconds to minutes. In this study, human Jurkat T cells were exposed to 9xg hypergravity for 3 and 15 minutes, and RNA-Seq analysis revealed differential exon usage after 3 minutes, which became less pronounced after 15 minutes. Additionally, a shift in the transcript pool from coding to non-coding transcripts was observed. These findings suggest that gravity-sensitive differentially expressed genes follow a dynamic transcriptional rebound effect, with initial up-regulatory changes resulting from increased elongation rates. The direction of differential expression depended on the structural location in the genome. Furthermore, a correlation analysis identified a link between initially upregulated genes and specific transcription factors, providing further insight into the transcriptional response to altered gravity.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Plant Sciences
Mingming Dong, Shudan Xue, Ezra S. Bartholomew, Xuling Zhai, Lei Sun, Shuo Xu, Yaqi Zhang, Shuai Yin, Wenyue Ma, Shuying Chen, Zhongxuan Feng, Chao Geng, Xiangdong Li, Xingwang Liu, Huazhong Ren
Summary: This study provides insights into the molecular processes involved in multicellular trichome formation in cucumber and presents a framework for understanding the regulatory network of multicellular trichome formation.
Article
Chemistry, Multidisciplinary
Paul Mollenkopf, Dusan Prascevic, Thomas M. Bayerl, Josef A. Kaes, Joerg Schnauss
Summary: Heavy water, or deuterium oxide (D2O), has significant effects on various biological systems, particularly at the cellular level. It inhibits dynamic processes such as migration and invasion, as well as central processes of cell proliferation. D2O treatment also reduces individual cell deformabilities. Researchers discovered that D2O induces bundling in reconstituted entangled networks of filamentous actin, a novel and previously undescribed actin bundling mechanism.
Article
Multidisciplinary Sciences
Julian Knerr, Ralf Werner, Carsten Schwan, Hong Wang, Peter Gebhardt, Helga Groetsch, Almuth Caliebe, Malte Spielmann, Paul-Martin Holterhus, Robert Grosse, Nadine C. Hornig
Summary: Steroid hormone receptors are crucial for mammalian physiology and are involved in various conditions. Functional mutations in DAAM2 gene were found in patients with androgen insensitivity syndrome. DAAM2 is enriched in the nucleus and forms actin-dependent transcriptional droplets with AR in response to dihydrotestosterone, promoting gene expression and cellular functions. Our study reveals the signal-regulated nuclear actin assembly at a steroid hormone receptor, which is necessary for transcription.
Review
Immunology
Maksim V. Baranov, Manoj Kumar, Stefano Sacanna, Shashi Thutupalli, Geert van den Bogaart
Summary: The size, shape, rigidity, and surface roughness of pathogens are important parameters affecting cellular uptake and immune responses, particularly in inflammasome activation and T cell activation. Understanding how the physical properties of particles influence immune responses can assist in the design of more effective vaccines.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yuefen Cao, Hui Huang, Yanjun Yu, Huaqin Dai, Huanfeng Hao, Hua Zhang, Yurong Jiang, Mingquan Ding, Feifei Li, Lili Tu, Zhaosheng Kong, Junkang Rong
Summary: The dynamic remodeling of the actin cytoskeleton plays a central role in cotton fiber elongation. In the Li-1 mutant, over-expression of GhACT17DM disrupts actin polymerization, affecting the establishment and dynamics of the actin cytoskeleton, resulting in defective fiber elongation and the overall dwarf and twisted phenotype.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Nikolas Hundt, Daniel Cole, Max F. Hantke, Jack J. Miller, Weston B. Struwe, Philipp Kukura
Summary: This study uses mass photometry to investigate the polymerization process of actin and finds that the traditional nucleation-based models cannot explain the observed distribution of actin oligomers. Instead, the key step of filament formation is a slow transition between different states of an actin filament mediated by cation exchange or ATP hydrolysis. These findings have important implications for understanding the mechanism of actin nucleation and studying protein assembly at the molecular level.
Article
Biochemistry & Molecular Biology
Guang-Fei Wang, Qincai Dong, Yu Bai, Jing Gu, Qingping Tao, Junjie Yue, Rui Zhou, Xiayang Niu, Lin Zhu, Caiwei Song, Tong Zheng, Di Wang, Yanwen Jin, Hainan Liu, Cheng Cao, Xuan Liu
Summary: In this study, we found that the assembly and nucleation function of γ-tubulin, the essential component of the γ-tubulin ring complexes (γ TuRCs), are regulated by phosphorylation mediated by the nonreceptor tyrosine kinase c-Abl. This discovery provides a fundamental mechanism for maintaining the function of microtubules in the cytoskeleton.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Cell Biology
Qian-Ru He, Meng Cong, Fan-Hui Yu, Yu-Hua Ji, Shu Yu, Hai-Yan Shi, Fei Ding
Summary: Peripheral nerve fibroblasts play a critical role in nerve development and regeneration by promoting motoneuron neurite outgrowth. These fibroblasts exhibit different patterns of gene expression compared to cardiac fibroblasts.
NEURAL REGENERATION RESEARCH
(2022)
Article
Medicine, Research & Experimental
Doh Young Lee, Young Kang, Nu-Ri Im, Byoungjae Kim, Tack-Kyun Kwon, Kwang-Yoon Jung, Seung-Kuk Baek
Summary: In this study, the gene expression profile of tongue cancer associated with early lymph node metastasis was analyzed using TCGA data. A total of 225 differentially expressed genes were found, with 50 genes showing significant changes. The enrichment analysis revealed that most upregulated genes were associated with the actin cytoskeleton.
Review
Multidisciplinary Sciences
Riccardo Tassinari, Elena Olivi, Claudia Cavallini, Valentina Taglioli, Chiara Zannini, Martina Marcuzzi, Oleksandra Fedchenko, Carlo Ventura
Summary: Mechanical forces are crucial in cellular dynamics, from the molecular level to the complexity in somatic and stem cells. This article highlights the role of cytoskeletal mechanics and extracellular matrix in generating mechanical forces that lead to oscillatory synchronized patterns. It discusses how mechanical forces can modulate mechanosensing/-transduction to control tissue metabolism and enable nonpharmacologic tissue rescue. The importance of fine-tuning stem cell morphodynamics in bone anabolic activity, repair, obesity prevention, cardiovascular disease treatment, and heart failure is also emphasized. The use of specific mechanical stimuli to reprogram tissue-resident stem cells and enhance self-healing potential is explored, without the need for stem cell or tissue transplantation.
Article
Immunology
George F. Aranjuez, Jongeon Kim, Travis J. Jewett
Summary: In this study, the interaction between the Chlamydia trachomatis effector Tarp and F-actin was studied using a transgenic Drosophila melanogaster model. Results showed that Tarp expression disrupted F-actin dynamics during bristle development and competed with the host bundler Singed/Fascin. Additionally, Tarp partially rescued the morphological defects caused by the loss of the singed gene.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Immunology
Young-Su Yi, Han Gyung Kim, Ji Hye Kim, Woo Seok Yang, Eunji Kim, Deok Jeong, Jae Gwang Park, Nur Aziz, Suk Kim, Narayanan Parameswaran, Jae Youl Cho
Summary: The MyD88-Syk axis plays a critical role in macrophage-mediated inflammatory responses, and its function is enhanced by an upstream Src kinase activated by Rac1-generated filamentous actin (F-actin).
FRONTIERS IN IMMUNOLOGY
(2021)
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.
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.
Article
Ophthalmology
Thomas Stax Jakobsen, Jakob Appel ostergaard, Mads Kjolby, Elisa Lund Birch, Toke Bek, Anders Nykjaer, Thomas J. Corydon, Anne Louise Askou
Summary: The level and localization of the multifunctional receptor sortilin in the diabetic retina were investigated, and the effect of sortilin inhibition on retinal neurodegeneration in experimental diabetes was studied. Increased levels of sortilin were observed in human and murine diabetic retinas, and sortilin was highly localized to retinal Muller cells. Sortilin inhibition effectively protected against neuronal loss in diabetic mice by reducing inner retinal thickness and the count of retinal ganglion cells.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2023)
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)