Review
Biochemistry & Molecular Biology
Vincent E. Provasek, Joy Mitra, Vikas H. Malojirao, Muralidhar L. Hegde
Summary: The continuous process of DNA damage and repair is crucial for maintaining genomic integrity. Among different types of DNA damage, double-strand breaks (DSBs) are the most dangerous and require timely repair. DSB repair is particularly important for nondividing, post-mitotic cells in the central nervous system (CNS), as failure in these mechanisms can lead to disruptions in neural networks and motor functions. In addition to repair pathways, DNA damage response (DDR) signaling and hnRNP proteins have been found to play important roles in neuronal DSB repair and are linked to age-associated neurological disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biology
Nadia Vertti-Quintero, Ethan Levien, Lucie Poggi, Ariel Amir, Guy-Franck Richard, Charles N. N. Baroud
Summary: This study demonstrates the use of microfluidic device to study DSBR at a single-cell level in yeast. The dynamics of DSBR were analyzed and a differential equation model was developed to obtain repair process rates. The study identified three types of DSB repair events that were previously unrecognized.
Article
Biochemistry & Molecular Biology
Ioannis Emmanouilidis, Natalia Fili, Alexander W. Cook, Yukti Hari-Gupta, Alia dos Santos, Lin Wang, Marisa L. Martin-Fernandez, Peter J. I. Ellis, Christopher P. Toseland
Summary: Mammalian cells are constantly exposed to various DNA damaging events, leading to the activation of DNA repair pathways. Cas9-based genomic intervention allows for induced DSBs at defined quantities and locations across the human genome, utilizing custom-designed promiscuous guide RNAs based on in silico predictions. This provides a generic, low-cost, and rapid methodology for inducing controlled DNA damage in cell culture models.
Article
Geriatrics & Gerontology
Evrydiki Kravvariti, Panagiotis A. Ntouros, Nikolaos Vlachogiannis, Maria Pappa, Vassilis L. Souliotis, Petros P. Sfikakis
Summary: Defects in the DNA damage response and repair network accumulate during aging, leading to physical frailty. This study found that older individuals had increased levels of oxidative stress and DNA damage, as well as reduced DNA repair capacity, compared to younger controls. These abnormalities were more pronounced in frail older adults and were associated with individual frailty levels, suggesting their potential as biomarkers for frailty.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2023)
Article
Multidisciplinary Sciences
Rizky Mutiara Fatimah, Nikko Adhitama, Yasuhiko Kato, Hajime Watanabe
Summary: In this study, a transgenic D. magna line was developed and a reporter gene system expressing mCherry and eGFP was established using CRISPR/Cas technology to evaluate homology-directed repair (HDR). This system can expand our understanding of HDR mechanisms and improve the HDR-based gene-editing system in this species.
SCIENTIFIC REPORTS
(2022)
Review
Genetics & Heredity
Leonhard Andreas Karl, Martina Peritore, Lorenzo Galanti, Boris Pfander
Summary: DNA double strand breaks (DSBs) are repaired in eukaryotes by various cellular mechanisms. Nucleosome remodelers, which have the ability to slide, evict, position, or edit nucleosomes, have emerged as key regulators of DSB repair. The activities of nucleosome remodelers at DSBs have been found to impact the decision-making process of DSB repair.
FRONTIERS IN GENETICS
(2022)
Article
Multidisciplinary Sciences
Ye Cai, Huifen Cao, Fang Wang, Yufei Zhang, Philipp Kapranov
Summary: This study presents a high-resolution method, SSiNGLe-AP, to map abasic (AP) sites in mammalian genomes. The results show that AP sites are nonrandomly distributed in the genome and are influenced by gene expression, age, and tissue type.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Benjamin B. Morris, Jason P. Smith, Qi Zhang, Zhijie Jiang, Oliver A. Hampton, Michelle L. Churchman, Susanne M. Arnold, Dwight H. Owen, Jhanelle E. Gray, Patrick M. Dillon, Hatem H. Soliman, Daniel G. Stover, Howard Colman, Arnab Chakravarti, Kenneth H. Shain, Ariosto S. Silva, John L. Villano, Michael A. Vogelbaum, Virginia F. Borges, Wallace L. Akerley, Ryan D. Gentzler, Richard D. Hall, Cindy B. Matsen, C. M. Ulrich, Andrew R. Post, David A. Nix, Eric A. Singer, James M. Larner, Peter Todd Stukenberg, David R. Jones, Marty W. Mayo
Summary: This study identified a new pan-cancer class of tumors, replicative instability (RIN), characterized by intra-chromosomal gene-level gain and loss events at replication stress sensitive genome sites. RIN was found to drive therapy resistance and distant metastases across multiple tumor types, indicating its significant importance in cancer research.
Article
Multidisciplinary Sciences
Anika Kuster, Nour L. Mozaffari, Oliver J. Wilkinson, Jessica L. Wojtaszek, Christina Zurfluh, Sara Przetocka, Dawid Zyla, Christine von Aesch, Mark S. Dillingham, R. Scott Williams, Alessandro A. Sartori
Summary: A peptide mimetic targeting CtIP was developed, which effectively inhibits CtIP activity, leading to impaired DNA repair and replication fork degradation, with selective toxicity to BRCA1-mutated cancer cells. This study provides a theoretical basis for the future development of CtIP-targeting compounds for cancer treatment.
Editorial Material
Biotechnology & Applied Microbiology
Megumi Ishii, Tetsuya Ishii
Summary: This passage discusses whether genome-edited agricultural products should be considered genetically modified organisms (GMOs) and how to prove definitively that a genome-edited organism does not contain exogenous DNA, taking social aspects into account.
TRENDS IN BIOTECHNOLOGY
(2022)
Review
Cell Biology
Huiming Lu, Anthony J. Davis
Summary: RecQ DNA helicases are a conserved protein family found in various organisms, playing important roles in cellular functions and potentially contributing to autosomal disorders.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biology
Laure Bobyk, Francois Vianna, Juan S. Martinez, Gaetan Gruel, Marc Benderitter, Celine Baldeyron
Summary: In this study, we investigated the dynamics of DNA repair pathways in response to alpha-particle irradiation, and found that different mechanisms are recruited at DNA damage sites. This research is important for assessing the risk associated with radiation exposure and improving the efficacy of radiation treatment.
Article
Cell Biology
Jong-Hyuk Lee, Raghavendra A. Shamanna, Tomasz Kulikowicz, Nima Borhan Fakouri, Edward W. Kim, Louise S. Christiansen, Deborah L. Croteau, Vilhelm A. Bohr
Summary: Werner syndrome (WS) is an accelerated aging disorder characterized by genomic instability caused by WRN protein deficiency. The phosphorylation of WRN by CDK2 on serine residue 426 is critical for WRN to choose between non-homologous end joining (NHEJ) and homologous recombination (HR) pathways. The phosphorylation stabilizes WRN's affinity for RPA and enhances its role in long-range resection, a crucial step for HR.
Review
Cell Biology
Damian Jaworski, Bartosz Brzoszczyk, Lukasz Szylberg
Summary: This review provides a comprehensive overview of the critical roles of mismatch repair (MMR) and double-strand break (DSB) defects in prostate cancer, as well as their clinical implications. It discusses the promising potential of immune checkpoint inhibitors and PARP inhibitors as targeted therapies, particularly in personalized medicine. Recent clinical trials have shown the efficacy of these novel treatments, leading to FDA approvals, offering hope for improved outcomes for patients.
Article
Cell Biology
You-hong Wang, Zhen Guo, Liang An, Yong Zhou, Heng Xu, Jing Xiong, Zhao-qian Liu, Xiao-ping Chen, Hong-hao Zhou, Xiong Li, Tao Liu, Wei-hua Huang, Wei Zhang
Summary: This study found that LINC-PINT is significantly downregulated in nasopharyngeal cancer tissues compared to rhinitis tissues, and low LINC-PINT expressions are associated with poorer prognosis in patients receiving radiotherapy. LINC-PINT plays a functional role in inhibiting malignant phenotypes and sensitizing cancer cells to irradiation in vitro and in vivo. Mechanistically, LINC-PINT inhibits DNA damage repair through the ATM/ATR-Chk1/Chk2 signaling pathways and increases radiosensitivity by interacting with DNA-PKcs.
CELL DEATH & DISEASE
(2021)
Article
Cell Biology
Wilhelmina E. Radstake, Kiran Gautam, Silvana Miranda, Randy Vermeesen, Kevin Tabury, Emil Rehnberg, Jasmine Buset, Ann Janssen, Liselotte Leysen, Mieke Neefs, Mieke Verslegers, Jurgen Claesen, Marc-Jan van Goethem, Uli Weber, Claudia Fournier, Alessio Parisi, Sytze Brandenburg, Marco Durante, Bjorn Baselet, Sarah Baatout
Summary: Human spaceflight is associated with various health issues including skin problems and delayed wound healing due to long-term exposure to microgravity, ionizing radiation, and psychological stress. Limited sample sizes in space research restrict the generalization of results. In this study, an in vitro model was used to investigate the combined effect of simulated microgravity, ionizing radiation, and stress hormones on wound healing capacity. The results showed that spaceflight stressors can interfere with wound healing at any phase and exhibit interactions, emphasizing the complexity of studying the effects of spaceflight stressors on biological processes and countermeasure development.
Article
Multidisciplinary Sciences
Anna Fogtman, Sarah Baatout, Bjorn Baselet, Thomas Berger, Christine E. Hellweg, Piers Jiggens, Chiara La Tessa, Livio Narici, Petteri Nieminen, Laure Sabatier, Giovanni Santin, Uwe Schneider, Ulrich Straube, Kevin Tabury, Walter Tinganelli, Linda Walsh, Marco Durante
Summary: Human spaceflight is evolving into sustainable space exploration, with plans to regularly visit the Moon and prepare for manned missions to Mars by 2030. However, the exposure to space radiation poses a major challenge that needs to be addressed for the safety of astronauts. Quantifying and managing the health risks and electronics damage caused by space radiation are urgent priorities for further research and development. The ESA/SciSpacE Space Radiation White Paper identifies these topics and emphasizes the need for understanding the complex radiation environment and developing effective countermeasures.
Article
Engineering, Biomedical
Racell Nabha, Marijke De Saint-Hubert, Joachim Marichal, Johannes Esser, Olivier Van Hoey, Christian Baeumer, Nico Verbeek, Lara Struelens, Edmond Sterpin, Kevin Tabury, Lukas Marek, Carlos Granja, Beate Timmermann, Filip Vanhavere
Summary: This study characterized the radiation fields produced by collimated and uncollimated proton beams. The results showed that combining proton beam scanning with an aperture can reduce the absorbed dose in the lateral fall-off and out-of-field by 60%. However, the increase in linear energy transfer (LET) caused by collimated fields did not result in higher DNA damage yields due to the large dose reduction.
PHYSICS IN MEDICINE AND BIOLOGY
(2023)
Review
Multidisciplinary Sciences
Rik H. G. Olde Engberink, Paula J. van Oosten, Tobias Weber, Kevin Tabury, Sarah Baatout, Giovanna Valenti, Alexander Chouker, Pierre Boutouyrie, Martina Heer, Jens Jordan, Nandu Goswami
Summary: Despite having sent humans into space for more than 50 years, crucial questions regarding kidney physiology, volume regulation, and osmoregulation remain unanswered. The complex interactions between various systems and environmental factors in microgravity make it challenging to determine the exact effects on these parameters. Better understanding of these effects is needed for long-term deep space missions and planetary surface explorations. In this review, the current understandings and knowledge gaps regarding the effects of microgravity on kidney function, volume regulation, and osmoregulation are summarized and discussed.
Review
Multidisciplinary Sciences
Katie M. Harris, Roopen Arya, Antoine Elias, Tobias Weber, David A. Green, Danielle K. Greaves, Lonnie G. Petersen, Lara Roberts, Tovy Haber Kamine, Lucia Mazzolai, Andrej Bergauer, David S. Kim, Rik H. Olde H. Engberink, Peter zu Eulenberg, Bruno Grassi, Lucrezia Zuccarelli, Giovanni Baldassarre, Kevin Tabury, Sarah Baatout, Jens Jordan, Andrew P. Blaber, Alexander Chouker, Thais Russomano, Nandu Goswami
Summary: The discovery of an asymptomatic venous thrombosis in an astronaut on the International Space Station has prompted a response from the space medicine community. The European Space Agency formed a team to review the pathophysiology, risk, clinical presentation, prevention, diagnosis, mitigation, and management strategies of venous thrombosis in spaceflight. This article discusses the findings of the ESA VT Topical Team, identifies key gaps hindering understanding of VT in space, and provides research recommendations and initial steps for further evaluation of this medical risk.
Article
Multidisciplinary Sciences
Eric B. Emanuelsson, Bjorn Baselet, Mieke Neefs, Sarah Baatout, Brit Proesmans, Lisa Daenen, Carl Johan Sundberg, Helene Rundqvist, Rodrigo Fernandez-Gonzalo
Summary: This study determined the nature of immune cell changes in the murine skeletal muscle following hindlimb unloading combined with an acute session of irradiation. The findings show that 14 days of hindlimb unloading induces a significant increase of myeloid immune cell infiltration in skeletal muscle.
Article
Multidisciplinary Sciences
Wilhelmina E. E. Radstake, Kiran Gautam, Silvana Miranda, Cynthia Van Rompay, Randy Vermeesen, Kevin Tabury, Mieke Verslegers, Alan Dowson, Jeffrey Gorissen, Jack J. W. A. van Loon, Nigel D. L. Savage, Sarah Baatout, Bjorn Baselet
Summary: The spaceflight environment poses risks to maintaining healthy skin function due to delayed wound healing, increasing the risk of infection. To understand how altered gravity levels affect fibroblast reactions, experiments were conducted using the Large Diameter Centrifuge. Dermal fibroblasts were exposed to different gravity levels, and the addition of cortisol showed impacts on cell behavior and secretion of cytokines and extracellular matrix proteins.
Article
Biochemistry & Molecular Biology
Charlotte Segers, Mohamed Mysara, Amelie Coolkens, Shari Wouters, Sarah Baatout, Natalie Leys, Sarah Lebeer, Mieke Verslegers, Felice Mastroleo
Summary: We investigated the protective effects of Limnospira indica PCC 8005 against radiation-induced mucositis and dysbiosis. Our results showed that both L. indica PCC 8005 and L. rhamnosus GG could prevent radiation-induced dysbiosis. This study suggests that L. indica PCC 8005 is a potential radiomitigator for pelvic irradiation-induced dysbiosis.
Article
Chemistry, Medicinal
Nathalie Heynickx, Charlotte Segers, Amelie Coolkens, Sarah Baatout, Koen Vermeulen
Summary: The study aimed to elucidate the uptake patterns of [Lu-177]Lu-PSMA-617 in salivary gland tissue and cells. The results showed that Monosodium Glutamate and glutamate receptor antagonists (Kynurenic acid and (RS)-MCPG) could reduce the non-specific binding of [Lu-177]Lu-PSMA-617, thereby decreasing the risk of salivary gland toxicity.
Article
Biochemistry & Molecular Biology
Wilhelmina E. Radstake, Kiran Gautam, Cynthia Van Rompay, Randy Vermeesen, Kevin Tabury, Mieke Verslegers, Sarah Baatout, Bjorn Baselet
Summary: In this study, two wound creation techniques were compared, as well as the influence of analysis software and cortisol on fibroblast migration behavior. Results showed that using a cell exclusion method significantly reduced fibroblast migration, while addition of cortisol only affected migration in scratched fibroblast monolayers. The potential relationship to cytokine expression was discussed.
BIOCHEMISTRY AND BIOPHYSICS REPORTS
(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
Multidisciplinary Sciences
Pauline Jacob, Christian Oertlin, Bjorn Baselet, Lisa S. Westerberg, Jean-Pol Frippiat, Sarah Baatout
Summary: Despite more than 50 years of sending humans into space, there are still crucial unanswered questions regarding the immune response in space conditions. The complex interactions between the immune system and other physiological systems in the human body make it challenging to study the long-term effects of space stressors such as radiation and microgravity. Exposure to microgravity and cosmic radiation can lead to changes in the immune system at the cellular and molecular levels, as well as in the major physiological systems of the body. Future long-term space missions may face serious health consequences due to abnormal immune responses induced in the space environment, including reduced ability to respond to injuries, infections, and vaccines, and increased risk of chronic diseases.
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.