Through their life cycles, bacteria experience many different environments in which the relationship between available energy resources and the frequency and the nature of various stresses is highly variable. In order to survive in such changeable environments, bacteria must balance the need for nutritional competence with stress resistance. In Escherichia coli natural populations, this is most frequently achieved by changing the regulation of the RpoS sigma factor-dependent general stress response. One important secondary consequence of altered regulation of the RpoS regulon is the modification of mutation rates. For example, under nutrient limitation during stationary phase, the high intracellular concentration of RpoS diminishes nutritional competence, increases stress resistance, and, by downregulating the mismatch repair system and upregulating [corrected] the expression of the dinB gene (coding for PolIV translesion synthesis polymerase) increases mutation rates. The reduction of the intracellular concentration of RpoS has exactly opposite effects on nutritional competence, stress resistance and mutation rates. Therefore, the natural selection that favours variants having the highest fitness under different environmental conditions results in high variability of stress-associated mutation rates in those variants.
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http://dx.doi.org/10.1111/j.1462-2920.2005.00968.x | DOI Listing |
Acta Neuropathol Commun
January 2025
Department of Neurology, Peking Union Medical College Hospital, Peking Union Medical College (PUMC) and Chinese Academy of Medical Science (CAMS), Beijing, China.
Mutations in the ANXA11 gene, encoding an RNA-binding protein, have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS), but the underlying in vivo mechanisms remain unclear. This study examines the clinical features of ALS patients harboring the ANXA11 hotspot mutation p.P36R, characterized by late-onset motor neuron disease and occasional multi-system involvement.
View Article and Find Full Text PDFNat Commun
January 2025
State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing, China.
The relative contributions of mutation rate variation, selection, and recombination in shaping genomic variation in bacterial populations remain poorly understood. Here we analyze 3318 Yersinia pestis genomes, spanning nearly a century and including 2336 newly sequenced strains, to shed light on the patterns of genetic diversity and variation distribution at the population level. We identify 45 genomic regions ("hot regions", HRs) that, although comprising a minor fraction of the genome, are hotbeds of genetic variation.
View Article and Find Full Text PDFJ Thorac Oncol
January 2025
Department of Respiratory Medicine and Medical Oncology, Yokohama Municipal Citizen's Hospital, 1-1 Mitsuzawa-Nishi-machi, Kanagawa-ku, Yokohama 221-0855, Japan.
Introduction: Osimertinib is the first-line treatment for patients with non-small cell lung cancer (NSCLC) who have EGFR mutations and favorable performance status (PS). Despite increasing clinical data on osimertinib, evidence in patients with an impaired PS remains limited. Therefore, a multicenter phase II trial (OPEN/TORG2040) was conducted to evaluate the efficacy and safety of first-line osimertinib for patients with EGFR mutation-positive NSCLC and poor PS.
View Article and Find Full Text PDFHum Immunol
January 2025
Department of Urology, Jiaxing Second Hospital, Jiaxing 314000, China. Electronic address:
Previous studies have revealed the essential role of lysosomes in human diseases, including cancer. However, there is a lack of in-depth systematic research on its function in kidney renal clear cell carcinoma (KIRC). In this project, we collected the public dataset of KIRC and selected lysosomal genes tightly linked with survival.
View Article and Find Full Text PDFMol Oncol
January 2025
Analysis of Circulating Tumor Cells Lab, Laboratory of Analytical Chemistry, Department of Chemistry, University of Athens, Greece.
Plasma cell-free DNA (cfDNA) analysis to track estrogen receptor 1 (ESR1) mutations is highly beneficial for the identification of tumor molecular dynamics and the improvement of personalized treatments for patients with metastatic breast cancer (MBC). Plasma-cfDNA is, up to now, the most frequent liquid biopsy analyte used to evaluate ESR1 mutational status. Circulating tumor cell (CTC) enumeration and molecular characterization analysis provides important clinical information in patients with MBC.
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