Article
Multidisciplinary Sciences
Felicia N. New, Benjamin R. Baer, Andrew G. Clark, Martin T. Wells, Ilana L. Brito
Summary: This study examines the interactions between host genetics and gut microbiome by analyzing the gut microbiomes and human variants of 250 individuals. The findings reveal associations between host genetics and microbiome-related metabolic traits, disorders, and certain cancers. The study also identifies common and rare microbial functions that are associated with host genetics.
SCIENTIFIC REPORTS
(2022)
Review
Biochemistry & Molecular Biology
Laura Veschetti, Mirko Treccani, Elisa De Tomi, Giovanni Malerba
Summary: This study proposes a comprehensive perspective on genomic instability, encompassing mutation accumulation, telomeric shortening, epigenetic alterations, and other mechanisms that can affect genomic information conservation or corruption. It examines the mechanisms of genomic instability across different species and its impact on human evolutionary history and contemporary health, particularly in aging and complex disorders. The study also explores the role of non-coding RNAs and future approaches for improved living and extended healthy lifespan.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Laurel A. Keefer, James R. White, Derrick E. Wood, Kelly M. R. Gerding, Kenneth C. Valkenburg, David Riley, Christopher Gault, Eniko Papp, Christine M. Vollmer, Amy Greer, James Hernandez, Paul M. McGregor, Adriana Zingone, Brid M. Ryan, Kristen Deak, Shannon J. McCall, Michael B. Datto, James L. Prescott, John F. Thompson, Gustavo C. Cerqueira, Sian Jones, John K. Simmons, Abigail McElhinny, Jennifer Dickey, Samuel Angiuoli, Luis A. Diaz, Victor E. Velculescu, Mark Sausen
Summary: This study describes a comprehensive genomic profiling assay with high analytical performance and provides validation of its accuracy and reliability using clinically and biologically relevant samples.
NATURE COMMUNICATIONS
(2022)
Article
Biology
Jack A. Brand, Winston K. W. Yee, Ian J. Aitkenhead, Jake M. Martin, Giovanni Polverino, Steven L. Chown, Bob B. M. Wong, Damian K. Dowling
Summary: Temperature is a crucial factor that affects organismal fitness and has significant ecological implications. The influence of temperature on behavioral variation among individuals and between sexes in ectotherms is still not well understood. This study investigates the effects of temperature on behavioral variation and metabolism in adult male and female Drosophila melanogaster. The results show that males are more responsive to temperature change in mean activity levels, but no sex differences were found in thermal metabolic plasticity. Higher temperatures increased variation in male locomotor activity, but not in females. Further research is needed to explore whether sex differences in behavioral variation in response to temperature change may lead to sex-specific vulnerabilities to a warming climate.
PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2023)
Article
Agronomy
Ming-Zhu Chen, Li-Jun Cao, Bing-Yan Li, Jin-Cui Chen, Ya-Jun Gong, Qiong Yang, Thomas L. Schmidt, Lei Yue, Jia-Ying Zhu, Hu Li, Xue-Xin Chen, Ary Anthony Hoffmann, Shu-Jun Wei
Summary: Temporal genetic differentiation among populations was low, indicating stable sources of recipient populations and migration trajectories. Southern populations were found to be sources of northern immigrants, specifically from the Sichuan cluster, while central-eastern populations originated from southern and Yunnan clusters. This study reveals seasonal migration patterns in the diamondback moth and highlights the importance of population genomic analysis in understanding insect migration.
PEST MANAGEMENT SCIENCE
(2021)
Article
Pharmacology & Pharmacy
Rhea Desai, Colin Seymour, Carmel Mothersill
Summary: This study investigated the correlation between shoulder width and the size of the bystander effect using clonal lineages derived from a cultured cell line. The results suggest that shoulder size is related to the radiosensitivity of mammalian cell lines and may have implications for out-of-field effects in radiotherapy.
Review
Genetics & Heredity
Tania Fabo, Paul Khavari
Summary: The burden of human disease lies primarily in polygenic diseases. Genome-wide association studies (GWAS) have identified genetic variants and loci associated with complex traits since the early 2000s. Recent advances in genetics have utilized computational techniques and genome editing to functionally characterize the extensive genomic variants associated with polygenic disease risk.
TRENDS IN GENETICS
(2023)
Article
Biology
Yoichiro Harada, Yu Mizote, Takehiro Suzuki, Akiyoshi Hirayama, Satsuki Ikeda, Mikako Nishida, Toru Hiratsuka, Ayaka Ueda, Yusuke Imagawa, Kento Maeda, Yuki Ohkawa, Junko Murai, Hudson H. Freeze, Eiji Miyoshi, Shigeki Higashiyama, Heiichiro Udono, Naoshi Dohmae, Hideaki Tahara, Naoyuki Taniguchi
Summary: Mannose has anticancer activity by regulating cell metabolism and inducing dNTP loss, affecting cell cycle and chemotherapy efficacy.
Review
Immunology
Ana Cheong, Zachary D. Nagel
Summary: The relationship between individual variation in DNA repair capacity and immune function and cancer risk is not fully explored. This review proposes a research paradigm that incorporates functional studies of genome integrity and the immune system to predict cancer risk and establish the foundation for personalized prevention.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Neus Font-Porterias, Rocio Caro-Consuegra, Marcel Lucas-Sanchez, Marie Lopez, Aaron Gimenez, Annabel Carballo-Mesa, Elena Bosch, Francesc Calafell, Lluis Quintana-Murci, David Comas
Summary: The study reveals that the Roma genomes exhibit a long-term balance under the effects of founder effects and gene flow, providing insights into the genetic variation in admixed populations.
MOLECULAR BIOLOGY AND EVOLUTION
(2021)
Article
Health Care Sciences & Services
Jared J. Luxton, Miles J. McKenna, Aidan M. Lewis, Lynn E. Taylor, Sameer G. Jhavar, Gregory P. Swanson, Susan M. Bailey
Summary: The study utilized telomere length data and chromosome aberrations assessment to evaluate cancer patients' sensitivity and risk to radiotherapy, providing important information for personalized treatment.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Oncology
Elizabeth A. Bloom, Pamela N. Peters, Regina Whitaker, Shonagh Russell, Benjamin Albright, Shelly Cummings, Kirsten M. Timms, Thomas Slavin, Braden Probst, Kyle C. Strickland, Rebecca A. Previs
Summary: Uterine serous carcinomas (USC) is a rare and aggressive subtype of uterine cancer. This study evaluated the genomic instability score (GIS), tumor mutational burden (TMB), and tumor-infiltrating lymphocytes (TILs) in USC patients and found that TMB > 1.35 mt/Mb was associated with improved survival, while higher GIS and increased immune cell infiltration were not.
Article
Hematology
Linping Hu, Xiuxiu Yin, Yawen Zhang, Aiming Pang, Xiaowei Xie, Shangda Yang, Caiying Zhu, Yapu Li, Biao Zhang, Yaojin Huang, Yunhong Tian, Mei Wang, Wenbin Cao, Shulian Chen, Yawei Zheng, Shihui Ma, Fang Dong, Sha Hao, Sizhou Feng, Yongxin Ru, Hui Cheng, Erlie Jiang, Tao Cheng
Summary: This study demonstrates that radiation-induced bystander effects impair the long-term hematopoietic reconstitution of human HSCs and affect the colony-forming ability of human hematopoietic progenitor cells. Additionally, the affected human hematopoietic cells show enhanced DNA damage responses and oxidative stress due to bystander effects. Various antioxidants can mitigate these effects, with differing efficacies in vitro and in vivo.
Article
Medicine, Research & Experimental
Xin Qin, Jing Wang, Xing Wang, Tao Huang, Zhiqing Fang, Lei Yan, Yidong Fan, Dawei Xu
Summary: DNA helicases play a crucial role in maintaining genomic stability, and mutations in these genes can lead to genomic instability and cancer susceptibility. Interestingly, overexpression of DNA helicases is observed in certain cancers. In this study, genomic and molecular alterations in 12 important DNA helicases were analyzed across various types of cancers. The study revealed significant expression heterogeneity among these helicases, and tumors were classified into subtypes based on their DNA helicase score. The high DNA helicase score subtypes were associated with stemness, proliferation, oncogenic signaling, longer telomeres, more mutations, copy number alterations, and shorter survival. Furthermore, high DNA helicase scores were linked to sensitivity to chemo- and radio-therapies, as well as defects in DNA repair pathways like homologous recombination deficiency. Importantly, a potential DNA helicase inhibitor, Danusertib, was identified in this study. These findings highlight the dysregulation of DNA helicases in cancer and their potential as therapeutic targets.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Genetics & Heredity
Foad J. Rouhani, Xueqing Zou, Petr Danecek, Tauanne Dias Amarante, Gene Koh, Qianxin Wu, Yasin Memari, Richard Durbin, Inigo Martincorena, Andrew R. Bassett, Daniel Gaffney, Serena Nik-Zainal
Summary: The study explores human induced pluripotent stem cells derived from different tissues, finding UV-related damage and mutations in skin fibroblast-derived cells, while blood-derived cells show a high prevalence of acquired mutations.
Article
Oncology
Conor Hanna, Victoria L. Dunne, Steven M. Walker, Karl T. Butterworth, Nuala McCabe, David J. J. Waugh, Richard D. Kennedy, Kevin M. Prise
Summary: Prostate cancer is the most frequently diagnosed cancer in men, with the role of the PTEN gene being complex but important in its treatment. Studies suggest that in the absence of PTEN, combined treatment using radiotherapy and the ATM inhibitor KU-60019 has a greater therapeutic effect.
Article
Multidisciplinary Sciences
Francesca Amoroso, Kimberley Glass, Reema Singh, Francisco Liberal, Rebecca E. Steele, Sarah Maguire, Rohinton Tarapore, Joshua E. Allen, Sandra Van Schaeybroeck, Karl T. Butterworth, Kevin Prise, Joe M. O'Sullivan, Suneil Jain, David J. Waugh, Ian G. Mills
Summary: The study demonstrated that ONC201 can enhance the radiation response of prostate cancer cells by suppressing the expression of cell cycle and DNA repair factors.
SCIENTIFIC REPORTS
(2021)
Article
Engineering, Biomedical
Yusuke Matsuya, Stephen J. McMahon, Karl T. Butterworth, Shingo Naijo, Isshi Nara, Yoshie Yachi, Ryo Saga, Masayori Ishikawa, Tatsuhiko Sato, Hiroyuki Date, Kevin M. Prise
Summary: The study explores the impact of hypoxia on in-field and out-of-field (OF) radio-sensitivities in cancer cells. Results show that hypoxia affects OF cells, although the effects on cell survival are dose-dependent and smaller compared to in-field and uniformly irradiated cells. This decreased radio-sensitivity of OF cells, seen as a consistent tendency for both double-strand breaks (DSB) and cell death endpoints, highlights the importance of radiation-induced intercellular communication in advanced radiotherapy dose-distributions such as with intensity-modulated radiotherapy.
PHYSICS IN MEDICINE AND BIOLOGY
(2021)
Review
Physics, Multidisciplinary
Pankaj Chaudhary, Giuliana Milluzzo, Hamad Ahmed, Boris Odlozilik, Aaron McMurray, Kevin M. Prise, Marco Borghesi
Summary: The use of particle accelerators in radiotherapy has improved therapeutic outcomes for solid tumors, with protons being well known for sparing normal tissues. Laser-accelerated proton beams offer unique temporal emission properties that can deliver high doses at rates exceeding those currently used in FLASH approaches. Further research on laser-driven protons not only advances clinical applications but also opens up unexplored realms in radiobiology.
FRONTIERS IN PHYSICS
(2021)
Article
Oncology
Philip G. Turner, Suneil Jain, Aidan Cole, Arthur Grey, Darren Mitchell, Kevin M. Prise, Alan R. Hounsell, Conor K. McGarry, Sandra Biggart, Joe M. O'Sullivan
Summary: This study investigated the safety and efficacy of combination therapy with radium-223 and pelvic EBRT for de novo bone metastatic mHSPC patients, showing a safe treatment option with promising efficacy signals, a high overall tumor response or stability rate among patients.
CLINICAL CANCER RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Hisanori Fukunaga, Kiichi Kaminaga, Eri Hirose, Ritsuko Watanabe, Noriko Usami, Kevin M. Prise, Akinari Yokoya
Summary: The study investigated the non-targeted effects on the regulation of the cell cycle in HeLa-FUCCI cells and found that malignant tumors lack a regulated cell growth system, suggesting differences between normal tissue and tumor characteristics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Oncology
Hisanori Fukunaga, Akinari Yokoya, Kevin M. Prise
Summary: Translation: Effects of radiation on spermatogenesis and transgenerational effects are reviewed in this article. The review explores novel radiobiological approaches for male fertility preservation during radiotherapy. The genotoxicity of radiation on germ cells and its potential transgenerational effects are discussed. The clinical importance of preserving male fertility during radiation treatment is also addressed. Further research in this field is needed to better understand the potential role of transgenerational effects.
Article
Oncology
Shannon J. Thompson, Aoife Rooney, Kevin M. Prise, Stephen J. McMahon
Summary: This study evaluates the performance of different Monte Carlo nanoscale physics models using a dataset on strand breaking in a single DNA strand. The models had similar energy distributions but made significantly different predictions for other endpoints. Multi-endpoint analysis is necessary to fully validate these models.
Article
Engineering, Biomedical
Shannon J. Thompson, Kevin M. Prise, Stephen J. McMahon
Summary: Laser-accelerated protons offer an alternative delivery mechanism for proton therapy. This study investigates the possibility of inter-track interactions between successive protons within a pulse delivered at ultra-high dose-rates. The results suggest that such interactions would not play a role in any potential changes in biological response between laser-accelerated and conventional proton therapy.
PHYSICS IN MEDICINE AND BIOLOGY
(2023)
Article
Engineering, Biomedical
Yusuke Matsuya, Stephen J. McMahon, Karl T. Butterworth, Yoshie Yachi, Ryo Saga, Tatsuhiko Sato, Kevin M. Prise
Summary: This study aimed to understand the mechanisms of intercellular communication under hypoxic conditions by modeling the cell-killing effects. The developed IMK model successfully predicted the dose-response curves for survival and lethal lesions, and demonstrated that the probability of releasing cell-killing signals depends on oxygen. The study also suggests that residual DNA double-strand breaks correlate with logarithmic survival fraction for in- and out-of-field cells, and the oxygen enhancement ratio determined using uniform-field exposure can predict the radiosensitivity of cells to intensity-modulated beams.
PHYSICS IN MEDICINE AND BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Aideen C. Roddy, Caitriona E. McInerney, Tom Flannery, Estelle G. Healy, James P. Stewart, Veronica J. Spence, Jamie Walsh, Manuel Salto-Tellez, Darragh G. McArt, Kevin M. Prise
Summary: Glioblastoma is a common and aggressive brain tumor, and therapy resistance may stem from glioma-stem cells. Transcriptome profiling revealed that angiogenesis and immune-related processes dominate the recurrence of glioblastoma. By using connectivity mapping analysis, FDA-approved repurposing drugs including rosiglitazone, nizatidine, pantoprazole, and tolmetin were identified as potential treatments against glioma-stem cells and glioblastoma recurrence. This translational bioinformatics pipeline offers a promising approach for identifying target compounds to overcome therapy resistance in cancers like glioblastoma.
Article
Biochemistry & Molecular Biology
Brianna N. Kerr, Daniel Duffy, Caitriona E. McInerney, Ashton Hutchinson, Inaya Dabaja, Rana Bazzi, Stephane Roux, Kevin M. Prise, Karl T. Butterworth
Summary: This study aimed to evaluate the radiosensitizing and immunomodulatory properties of differentially PEGylated GNPs in GBM cells. The results showed that PEGylation improved the radiobiological efficacy, with double-strand break induction being identified as a mechanism. PEGylated GNPs also enhanced the immunogenicity of radiotherapy, correlating with upregulation of inflammatory cytokines. These findings suggest that ID11 and ID12 could be potential candidates for RT-drug combination in future GBM preclinical investigations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Caitriona E. McInerney, Joanna A. Lynn, Alan R. Gilmore, Tom Flannery, Kevin M. Prise
Summary: The study characterized IDH1 expression and associated genes and pathways in adult gliomas, identifying 90 genes overexpressed in different signaling pathways related to IDH1. Potential prognostic and diagnostic biomarkers were discovered, showing correlations with IDH1 expression, and highlighting metabolic vulnerabilities and therapeutic targets for future clinical trials._IDS with mechanistic links were involved in neuronal development, cell proliferation, tumor suppression, and anaplerosis.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
A. Stupnikov, C. E. McInerney, K. I. Savage, S. A. McIntosh, F. Emmert-Streib, R. Kennedy, M. Salto-Tellez, K. M. Prise, D. G. McArt
Summary: RNA-seq technology poses challenges in the analysis of differential gene expression, but five models have been found to demonstrate robustness to sequencing alterations. The study indicates that the robustness of these models is dataset-agnostic and reliable for drawing conclusions when sample sizes are sufficiently large.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Francisco D. C. Guerra Liberal, Stephen J. McMahon, Kevin M. Prise
Summary: The study found that cellular geometry has a significant impact on the dosimetry of alpha particles, with different cellular configurations resulting in variations in dosimetry outcomes. However, the effects of different radionuclides on dosimetry outcomes are generally similar.
BIOMEDICAL PHYSICS & ENGINEERING EXPRESS
(2021)
Article
Biotechnology & Applied Microbiology
C. F. M. Menck, R. S. Galhardo, A. Quinet
Summary: Studies have shown that xeroderma pigmentosum variant (XP-V) patients have mutations in the POLH gene, resulting in a high frequency of skin tumors. However, it is paradoxical that the translesion synthesis DNA polymerase eta (Pol η) in these patients can actually suppress mutations, and the mechanism behind this is still unclear. Recent evidence suggests that cyclobutane pyrimidine dimers (CPDs) play an instructional role for Pol η, enabling accurate replication of these lesions, and the mutagenic effects induced by UV radiation are caused by the deamination of C-containing CPDs. This process leads to C>T transitions, which are the most common mutations in skin cancers. The delayed replication in XP-V cells amplifies the deamination of C in CPDs and increases the burden of C>T mutations through the activity of backup TLS polymerases.
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
(2024)