Article
Neurosciences
Yujun Hou, Jae-Hyeon Park, Xiuli Dan, Xixia Chu, Beimeng Yang, Mansoor Hussain, Deborah L. Croteau, Vilhelm A. Bohr
Summary: RecQ helicase family proteins are essential for maintaining genome stability and their dysfunction is associated with genetic disorders and aging-related diseases. In this study, the effects of ionizing irradiation (IR) on RecQ-deficient mice were investigated, revealing abnormal cognitive behavior in the absence of IR and impairments in social ability and depressive-like behavior after exposure to IR. Transcriptomic and metabolomic analyses showed significant alterations in RecQ-deficient mice, with downregulation of pathways related to neuronal functions, DNA damage repair, and reactive oxygen responses. Increased DNA damage responses and differential expression of genes, including Aldolase Fructose-Bisphosphate B (Aldob) and NADPH Oxidase 4 (Nox4), were also observed. These findings suggest that RecQ dysfunction contributes to social and depressive-like behaviors in mice and highlight aldolase activity as a potential therapeutic target.
NEUROBIOLOGY OF DISEASE
(2023)
Review
Biochemistry & Molecular Biology
Jac A. Nickoloff, Aruna S. Jaiswal, Neelam Sharma, Elizabeth A. Williamson, Manh T. Tran, Dominic Arris, Ming Yang, Robert Hromas
Summary: Replicative DNA polymerases are obstructed by various DNA damage, leading to DNA replication stress that threatens genome stability. Cellular responses to replication stress include cell cycle arrest, replication fork collapse, DNA repair induction, and programmed cell death. Nucleases play critical roles in these responses, promoting repair and restart of stressed replication forks. Understanding biological responses to genome-wide replication stress can inform novel cancer treatment strategies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Yuriko Sorimachi, Daiki Karigane, Yukako Ootomo, Hiroshi Kobayashi, Takayuki Morikawa, Kinya Otsu, Yoshiaki Kubota, Shinichiro Okamoto, Nobuhito Goda, Keiyo Takubo
Summary: The study revealed that p38 alpha plays a multi-modal role in HSC aging, regulating differentiation bias and transplantation capacity at different stages of chronological aging. Furthermore, codeletion of p38 alpha exacerbated aging-related HSC phenotypes in mice deficient in ataxia-telangiectasia mutated, showing the complex role of p38MAPK in both promoting and suppressing HSC aging.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Yuanjiu Lei, Camila Guerra Martinez, Sylvia Torres-Odio, Samantha L. Bell, Christine E. Birdwell, Joshua D. Bryant, Carl W. Tong, Robert O. Watson, Laura Ciaccia West, A. Phillip West
Summary: In the mutator mouse model with mitochondrial DNA instability, aberrant activation of the IFN-I immune axis leads to immunometabolic dysfunction, shortened lifespan, and accelerated aging. Elevated IFN-I signaling suppresses activation of NRF2, increasing oxidative stress and proinflammatory responses, resulting in metabolic dysfunction.
Article
Biotechnology & Applied Microbiology
Martina Fiumara, Samuele Ferrari, Attya Omer-Javed, Stefano Beretta, Luisa Albano, Daniele Canarutto, Angelica Varesi, Chiara Gaddoni, Chiara Brombin, Federica Cugnata, Erika Zonari, Matteo Maria Naldini, Matteo Barcella, Bernhard Gentner, Ivan Merelli, Luigi Naldini
Summary: Base and prime editors have shown potential for precise genetic engineering, but their cellular responses and genotoxicity are not well understood. This study compared the efficiency, toxicity, and genotoxicity between base and prime editors and Cas9 in human hematopoietic cells. The findings suggest that these editors can induce harmful effects and genotoxicity, raising concerns for their clinical applications.
NATURE BIOTECHNOLOGY
(2023)
Article
Cell & Tissue Engineering
Zenghua Lin, Maile K. Hollinger, Zhijie Wu, Wanling Sun, Kaylind Batey, Jisoo Kim, Jichun Chen, Xingmin Feng, Neal S. Young
Summary: It was found that sirolimus enhanced the regeneration of hematopoietic stem and progenitor cells in mice exposed to sublethal total body irradiation and other regenerative stressors. The effects were associated with increased expression of hematopoietic genes, reduced DNA damage and clearance of cellular reactive oxygen species. Sirolimus also showed potential clinical applications for the treatment and prevention of hematopoietic injury.
Article
Cell Biology
Rui Jin, Chang Niu, Fengyun Wu, Sixin Zhou, Tao Han, Zhe Zhang, Entao Li, Xiaona Zhang, Shanrong Xu, Jiadong Wang, Shen Tian, Wei Chen, Qinong Ye, Cheng Cao, Long Cheng
Summary: DNA damage, a hallmark of aging, promotes SARS-CoV-2 infection, while inhibition of DNA damage response hampers viral entry. This study reveals the important role of DNA damage in SARS-CoV-2 infection and suggests that promoting DNA repair can alleviate viral infection and disease severity.
Article
Oncology
Yinghao Pan, Hongna Zuo, Fei Wen, Fei Huang, Yezhang Zhu, Lanrui Cao, Qian-Qian Sha, Yang Li, Huiying Zhang, Miao Shi, Chengzhen Liang, Jun Huang, Lin Zou, Heng-Yu Fan, Zhenyu Ju, Hu Wang, Li Shen
Summary: The gene HMCES plays a crucial role in maintaining DNA integrity during hematopoietic stress. Lack of HMCES leads to accumulation of DNA damage and downregulation of repair pathways in activated hematopoietic stem cells. The study also found that dysregulation of HMCES is associated with poor clinical outcomes in acute lymphocytic leukemia.
Editorial Material
Microbiology
Jacob L. Steenwyk
Summary: Cell cycle checkpoints and DNA repair pathways are crucial for maintaining genome integrity, but recent studies have revealed evolutionary diversity in eukaryotic DNA damage responses, with some fungi showing reduced activation of key kinases and downregulation of genome maintenance genes in response to DNA damage.
Article
Cell Biology
Shudong Zhu, Yan Zhu, Qiuwen Wang, Yi Zhang, Xialing Guo
Summary: DNA methylation at the promoter CpG islands of CHK gene is increased in colon cancer cells and human colon cancer tissues compared to normal healthy counterparts, leading to decreased expression of CHK mRNA. Enhanced levels of DNMT in colon cancer cells and tissues contribute to this process, resulting in increased oncogenic properties in colon cancer cells.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Oncology
Justin T. Avery, Ruowen Zhang, Rebecca J. Boohaker
Summary: GLI1, a transcriptional effector in the Hedgehog signaling pathway, is tightly regulated during normal tissue development but aberrant activation in cancer can promote hallmarks such as proliferation, metastasis, and chemoresistance. Its oncogenic activities mainly involve regulating cell cycle, DNA replication, and DNA damage repair processes. Understanding the mechanisms of GLI1 dysregulation can provide prognostic and diagnostic biomarkers for targeted therapy in cancer treatment.
FRONTIERS IN ONCOLOGY
(2021)
Article
Cell Biology
Tuo Zhang, Tianhe Ren, Huan Lin, Yuntong Tong, Jixian Zhang, Jie Nie, Yingjie Zhu, Yiting Wang, Bangming Jin, Chunlin Zhang, Tengxiang Chen, Meina He
Summary: ASH1L is an important epigenetic molecule that controls oocyte apoptosis during meiotic prophase I in mice. It regulates the capacity of the primordial follicle pool and plays a role in DNA double-strand break repair. Its expression also affects p63 and p-CHK2.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Microbiology
Kang Ning, Cagla Aksu Kuz, Fang Cheng, Zehua Feng, Ziying Yan, Jianming Qiu
Summary: This study demonstrates the significant role of Pol eta and Pol kappa in AAV DNA replication and rAAV production in HEK293T cells. Understanding the AAV DNA replication mechanism in HEK293T cells could help increase rAAV vector yield produced from the transfection method. The findings also provide insights into the ATR-mediated DNA repair process, which contributes to AAV genome amplification.
Article
Pharmacology & Pharmacy
Changyong Wu, Yang Shen, Lin Shi, Junhao Zhang, Tongxuan Guo, Lingni Zhou, Wanzhou Wang, Xu Zhang, Rutong Yu, Xuejiao Liu
Summary: Glioblastoma multiforme (GBM) is a highly deadly brain tumor. UBA1 inhibition by TAK-243 can increase the sensitivity of GBM to radiotherapy by impairing DNA double-strand break repair. This study provides a new therapeutic strategy for improving the radiation sensitivity of GBM and lays a foundation for further clinical trials.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Oncology
Alizhah J. Watson, Michaela L. Shaffer, Renee A. Bouley, Ruben C. Petreaca
Summary: This study investigated the relationship between mutations in the FBH1 gene and mutations in other DNA damage repair genes, such as BRCA2. The findings suggest that FBH1 mutations co-occur with mutations in BRCA2 and other genes, and that certain mutations destabilize the FBH1 protein structure. Overall, this research highlights the contribution of mutations in DNA damage repair genes to cellular transformation and immortalization.
Article
Health Care Sciences & Services
Marietta Hamberger, Nensi Ikonomi, Julian Schwab, Silke Werle, Axel Fuerstberger, Angelika M. R. Kestler, Martin Holderried, Udo X. Kaisers, Florian Steger, Hans A. Kestler
Summary: Empowerment in health care is implemented as a patient-centered approach, with many mHealth apps being developed for individual users. Integrating mHealth apps into the health care system can address challenges such as incomplete medical data and lack of communication. However, concerns about data security, regional differences in regulations, accessibility, and transparency hinder the successful integration. Rethinking the interpretation of empowerment could positively impact intersectoral communication and facilitate secure data sharing.
JMIR MHEALTH AND UHEALTH
(2022)
Editorial Material
Statistics & Probability
Maurizio Vichi, Andrea Ceroli, Hans A. Kestler, Akinori Okada, Claus Weihs
ADVANCES IN DATA ANALYSIS AND CLASSIFICATION
(2022)
Article
Biochemical Research Methods
Christoph Muessel, Nensi Ikonomi, Silke D. Werle, Felix M. Weidner, Markus Maucher, Julian D. Schwab, Hans A. Kestler
Summary: This article introduces a method called CANTATA, which supports the integration of information into regulatory networks and retrieves potential underlying regulations by optimizing the static and dynamic properties of these networks. The results show that the algorithm can predict missing interactions and the resulting models can be used to hypothesize the biological impact.
Article
Biochemistry & Molecular Biology
Sandra Classen, Elena Rahlf, Johannes Jungwirth, Nina Albers, Luca Philipp Hebestreit, Alexandra Zielinski, Lena Poole, Marco Groth, Philipp Koch, Thomas Liehr, Stefanie Kankel, Nils Cordes, Cordula Petersen, Kai Rothkamm, Helmut Pospiech, Kerstin Borgmann
Summary: By introducing BRCA1 mutations using CRISPR/Cas9, this study found that these mutations increased both sensitivity and resistance to exogenous DNA damage in breast cancer cells. Resistance was associated with improved DNA double-strand break repair and reduction in replication stress.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Mariateresa Mazzetto, Cinzia Caterino, Marco Groth, Elisa Ferrari, Martin Reichard, Mario Baumgart, Alessandro Cellerino
Summary: This study compared the aging patterns of wild and captive turquoise killifish. The majority of differentially expressed genes showed the same regulation direction in both populations, but there were also genes regulated in opposite directions. Additionally, the rate of age-dependent gene regulation was higher in wild animals, suggesting accelerated aging.
MOLECULAR BIOLOGY AND EVOLUTION
(2022)
Article
Clinical Neurology
Sonja Schoenecker, Verena Hoffmann, Fady Albashiti, Reinhard Thasler, Marlien Hagedorn, Marie-Luise Louiset, Anna Kopczak, Jennifer Roesler, Enayatullah Baki, Silke Wunderlich, Florian Kohlmayer, Klaus Kuhn, Martin Boeker, Johannes Tuennerhoff, Sven Poli, Ulf Ziemann, Oliver Kohlbacher, Katharina Althaus, Susanne Mueller, Albert Ludolph, Hans A. Kestler, Ulrich Mansmann, Marianne Dieterich, Lars Kellert
Summary: This study aims to validate a prediction score for the 3-month functional outcome after juvenile stroke or transient ischemic attack (TIA) in a multi-center observational cohort study. The prediction score has been derived from a retrospective analysis and will be compared to observed clinical outcomes. The importance of this study lies in its potential to personalize counseling and treatment for juvenile stroke patients.
Article
Computer Science, Interdisciplinary Applications
Matthias Ganzinger, Max Blumenstock, Axel Fuerstberger, Leonard Greulich, Hans A. Kestler, Michael Marschollek, Christian Niklas, Tim Schneider, Cord Spreckelsen, Erik Tute, Julian Varghese, Martin Dugas
Summary: Structured documentation of findings is important in clinical research and patient care. Integration of electronic case report forms (eCRF) with electronic health records (EHR) is challenging when researchers from different institutions collaborate. To address this issue, a novel architecture for a federated electronic data capture system (fEDC) was proposed.
JOURNAL OF BIOMEDICAL INFORMATICS
(2023)
Article
Virology
Alan Bareiss, Gunalp Uzun, Marco Mikus, Matthias Becker, Karina Althaus, Nicole Schneiderhan-Marra, Axel Fuerstberger, Julian D. D. Schwab, Hans A. A. Kestler, Martin Holderried, Peter Martus, Katja Schenke-Layland, Tamam Bakchoul
Summary: This study investigates self-reported side effects after COVID-19 vaccination and finds that the frequency of local and systemic side effects differs significantly between mRNA and vector-based vaccines, and is associated with vaccine type, age, and gender.
Article
Oncology
Lena Muehlenbruch, Tsima Abou-Kors, Marissa L. L. Dubbelaar, Leon Bichmann, Oliver Kohlbacher, Martin Bens, Jaya Thomas, Jasmin Ezic, Johann M. M. Kraus, Hans A. A. Kestler, Adrian von Witzleben, Joannis Mytilineos, Daniel Fuerst, Daphne Engelhardt, Johannes Doescher, Jens Greve, Patrick J. J. Schuler, Marie-Nicole Theodoraki, Cornelia Brunner, Thomas K. K. Hoffmann, Hans-Georg Rammensee, Juliane S. S. Walz, Simon Laban
Summary: HLA-presented peptides in OPSCC tumour tissue were identified through mass spectrometry analysis. A peptide warehouse of OPSCC-associated peptides was established, which can be used for immunogenicity testing and peptide-based immunotherapy.
BRITISH JOURNAL OF CANCER
(2023)
Article
Cell Biology
Monserrat Gerardo-Ramirez, Vanessa Giam, Diana Becker, Marco Groth, Nils Hartmann, Helen Morrison, Helen L. May-Simera, Markus P. Radsak, Jens U. Marquardt, Peter R. Galle, Peter Herrlich, Beate K. Straub, Monika Hartmann
Summary: Primary liver cancer is a major cause of cancer-related death globally. The Hippo tumor suppressor pathway and its upstream regulator Merlin have been found to play critical roles in cell proliferation and fate determination in the liver. This study evaluated the contribution of CD44 and Merlin-dependent processes to liver tumor development and progression. While Merlin deletion led to liver enlargement and the formation of various liver tumors, deletion of CD44 had no effect on primary liver tumor development but significantly inhibited metastasis formation. CD44 upregulates integrin beta 2 expression and promotes transendothelial migration of liver cancer cells, suggesting it as a potential target for intervention in liver cancer metastasis.
Article
Medicine, General & Internal
Una Ebong, Susanne Martina Buettner, Stefan A. Schmidt, Franziska Flack, Patrick Korf, Lynn Peters, Beate Gruener, Steffen Stenger, Thomas Stamminger, Hans Kestler, Meinrad Beer, Christopher Kloth
Summary: This study implemented an AI-based software prototype for the detection of COVID-19 pneumonia and differentiation between other types of pneumonia in lung CT datasets. The software achieved a sensitivity of 80.8% and a specificity of 50% for detecting COVID-19, but the human radiologist achieved a higher specificity of 97.2%.
Article
Computer Science, Artificial Intelligence
Felix M. Weidner, Julian D. Schwab, Sabine Woelk, Felix Rupprecht, Nensi Ikonomi, Silke D. Werle, Steve Hoffmann, Michael Kuehl, Hans A. Kestler
Summary: The dynamics of cellular mechanisms can be studied through network analysis. Logic-based models are a popular and simple modeling strategy, but their simulation complexity grows exponentially instead of linearly with the number of nodes. This study applies logic modeling to quantum computing to simulate cellular networks and demonstrates the benefits, such as complexity reduction and quantum algorithms for systems biology tasks. A model of mammalian cortical development is implemented to showcase the applicability of this approach, and results from quantum processing units and a noisy simulator are presented, along with discussions on current technical challenges.
Article
Computer Science, Interdisciplinary Applications
Axel Fuerstberger, Nensi Ikonomi, Angelika M. R. Kestler, Ralf Marienfeld, Julian D. Schwab, Peter Kuhn, Thomas Seufferlein, Hans A. Kestler
Summary: AMBAR is an interactive web application developed to support personalized decision-making in Molecular Tumor Boards (MTBs), improving the analysis and documentation of patients' data for therapeutic interventions.
COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE
(2023)
Article
Cell Biology
Gaojie Zhu, Fatima Khalid, Danhui Zhang, Zhouli Cao, Pallab Maity, Hans A. Kestler, Donata Orioli, Karin Scharffetter-Kochanek, Sebastian Iben
Summary: Mutations in various genes can cause the childhood disorder TTD, which is classified as a DNA repair disease or a transcription syndrome. Knockout/knockdown of TTDN1 and RNF113A resulted in consistent effects on ribosomal biogenesis and performance. Interference with these TTD factors led to downregulation of RNA polymerase I transcription, disrupted rRNA processing, reduced rRNA 18S backbone, impaired protein translation decoding, and accumulation of misfolded and carbonylated proteins, suggesting loss of protein homeostasis. This study proposes that ribosomal dysfunction is a common underlying mechanism in TTD.
Article
Biochemical Research Methods
Felix M. Weidner, Mirko Rossini, Joachim Ankerhold, Hans A. Kestler
Summary: This article presents a protocol for implementing Boolean network dynamics as quantum circuits. It provides steps for accessing cloud-based quantum processing units offered by IBM and IonQ, parsing logic for gene regulatory networks, performing simulations of quantum circuits on local devices, and visualizing measurement results. For complete details on the use and execution of this protocol, please refer to Weidner et al.1.
