The mitochondrial free radical theory of aging (mFRTA) implicates Reactive Oxygen Species (ROS)-induced mutations of mitochondrial DNA (mtDNA) as a major cause of aging. However, fifty years after its inception, several of its premises are intensely debated. Much of this uncertainty is due to the large range of values in the reported experimental data, for example on oxidative damage and mutational burden in mtDNA. This is in part due to limitations with available measurement technologies. Here we show that sample preparations in some assays necessitating high dilution of DNA (single molecule level) may introduce significant statistical variability. Adding to this complexity is the intrinsically stochastic nature of cellular processes, which manifests in cells from the same tissue harboring varying mutation load. In conjunction, these random elements make the determination of the underlying mutation dynamics extremely challenging. Our in silico stochastic study reveals the effect of coupling the experimental variability and the intrinsic stochasticity of aging process in some of the reported experimental data. We also show that the stochastic nature of a de novo point mutation generated during embryonic development is a major contributor of different mutation burdens in the individuals of mouse population. Analysis of simulation results leads to several new insights on the relevance of mutation stochasticity in the context of dividing tissues and the plausibility of ROS "vicious cycle" hypothesis.
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http://dx.doi.org/10.1371/journal.pcbi.1000572 | DOI Listing |
Proc Natl Acad Sci U S A
January 2025
Ministry of Education Key Laboratory of Environment Remediation and Ecological Health, Zhejiang Provincial Key Laboratory of Agricultural Resources and Environment, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058, China.
While iron (Fe) is essential for life and plays important roles for almost all growth related processes, it can trigger cell death in both animals and plants. However, the underlying mechanisms for Fe-induced cell death in plants remain largely unknown. S-nitrosoglutathione reductase (GSNOR) has previously been reported to regulate nitric oxide homeostasis to prevent Fe-induced cell death within root meristems.
View Article and Find Full Text PDFPLoS One
January 2025
Department of Ocean Integrated Science, Chonnam National University, Yeosu, Korea.
Ensuring the supply of safe and high-quality drinking water can be compromised by the presence of chironomid larvae in drinking water treatment plants (DWTPs), which may contaminate municipal water systems through freshwater resources. Chironomids are dominant species known for their resilience to a broad range of extreme aquatic environments. This study aimed to identify the morphological characteristics and obtain genetic information of the chironomid Paratanytarsus grimmii found in the water intake source and freshwater resource of DWTPs in Korea, highlighting the potential possibility of a parthenogenetic chironomid outbreak within DWTP networks.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, Jilin, 130062, China.
Staphylococcus aureus (S. aureus) is a major zoonotic pathogen, with mammary gland infections contributing to mastitis, a condition that poses significant health risks to lactating women and adversely affects the dairy industry. Therefore, understanding the immune mechanisms underlying mammary infections caused by S.
View Article and Find Full Text PDFVet Med Sci
January 2025
Department of Reproduction and Artificial Insemination, Faculty of Veterinary Medicine, İstanbul University-Cerrahpasa, Avcilar, İstanbul, Turkey.
Ram sperm are more vulnerable to freezing than those of most other farm animals. During sperm freezing, the cell membrane loses some of its cholesterol, which regulates signalling mechanisms and prevents premature capacitation. Resveratrol (RES) increases the fluidity of the cell membrane, which becomes peroxidized during freezing and reduces free radicals.
View Article and Find Full Text PDFBlood
December 2024
St. Jude Children's Research Hospital, Memphis, Tennessee, United States.
Inotuzumab Ozogamicin (InO) is an antibody-calicheamicin conjugate with striking efficacy in B-cell acute lymphoblastic leukemia (B-ALL). However, there is wide inter-patient variability in treatment response, and the genetic basis of this variation remains largely unknown. Using a genome-wide CRISPR screen, we discovered the loss of DNTT as a primary driver of InO resistance.
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