The study of the mechanisms affecting single stress factor impact on long-term metabolic rearrangements is necessary for understanding the principles of plant protective reactions. The objective of the study was to assess the involvement of UV-C-induced genomic instability in induction рlant long-term protective reactions. The study was carried out on two genotypes of chamomile, Perlyna Lisostepu (PL) variety and its mutant, using UV-C pre-sowing seed radiation exposure at dose levels 5-15 kJ/m. Multiple DNA damages under different exposure doses were studied on plant tissues during the flowering stage using - ISSR-RAPD DNA marker PCR. In the cluster analysis of changes within the amplicon spectra as an integral group the Jacquard similarity index was used. The results of the study suggest that genomic instability is a link between the direct effects of UV-C exposure and stimulation of metabolic rearrangements at the final stages of ontogeny. A hypothetical scheme for the transformation of primary UV-C DNA damage into long-term maintenance of genomic instability signs has been proposed.
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http://dx.doi.org/10.1016/j.jplph.2024.154171 | DOI Listing |
Nat Genet
January 2025
Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
Understanding the molecular landscape of nonmuscle-invasive bladder cancer (NMIBC) is essential to improve risk assessment and treatment regimens. We performed a comprehensive genomic analysis of patients with NMIBC using whole-exome sequencing (n = 438), shallow whole-genome sequencing (n = 362) and total RNA sequencing (n = 414). A large genomic variation within NMIBC was observed and correlated with different molecular subtypes.
View Article and Find Full Text PDFCell Death Dis
January 2025
Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Molecular Cell Biology and Immunology, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
Aging of the brain vasculature plays a key role in the development of neurovascular and neurodegenerative diseases, thereby contributing to cognitive impairment. Among other factors, DNA damage strongly promotes cellular aging, however, the role of genomic instability in brain endothelial cells (EC) and its potential effect on brain homeostasis is still largely unclear. We here investigated how endothelial aging impacts blood-brain barrier (BBB) function by using excision repair cross complementation group 1 (ERCC1)-deficient human brain ECs and an EC-specific Ercc1 knock out (EC-KO) mouse model.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of Michigan Medical School, Ann Arbor, MI, USA.
Background: The transfer of mitochondrial DNA into the nuclear genomes of eukaryotes (Numts) has been linked to lifespan in non-human species and recently demonstrated to occur in rare instances from one human generation to the next.
Method: Here we investigated numtogenesis dynamics in humans in two ways. First, we quantified Numts in 1,187 post-mortem brain and blood samples from different individuals.
Cancer Immunol Immunother
January 2025
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China.
Microsatellite stable (MSS) colorectal cancer (CRC) is a subtype of CRC that generally exhibits resistance to immunotherapy, particularly immune checkpoint inhibitors such as PD-1 blockade. This study investigates the effects and underlying mechanisms of combining PD-1 blockade with IDO1 inhibition in MSS CRC. Bioinformatics analyses of TCGA-COAD and TCGA-READ cohorts revealed significantly elevated IDO1 expression in CRC tumors, correlating with tumor mutation burden across TCGA datasets.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Background: Studies of the genetics of Alzheimer's disease (AD) have largely focused on single nucleotide variants and short insertions/deletions. However, much of the disease heritability has yet to be uncovered, suggesting that other forms of genetic variation promote substantial portions of genetic risk. Uncovering the genetic basis of AD can lead to new disease biomarkers and delineate disease mechanisms.
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