Unlabelled: The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the pandemic and post-pandemic periods has been characterized by rapid adaptive changes that confer immune escape and enhanced human-to-human transmissibility. Sequence change is additionally marked by an excess number of C→U transitions suggested as being due to host-mediated genome editing. To investigate how these influence the evolutionary trajectory of SARS-CoV-2, 2,000 high-quality, coding complete genome sequences of SARS-CoV-2 variants collected pre-September 2020 and from each subsequently appearing alpha, delta, BA.1, BA.2, BA.5, XBB, EG, HK, and JN.1 lineages were downloaded from NCBI Virus in April 2024. C→U transitions were the most common substitution during the diversification of SARS-CoV-2 lineages over the 4-year observation period. A net loss of C bases and accumulation of U's occurred at a constant rate of approximately 0.2%-0.25%/decade. C→U transitions occurred in over a quarter of all sites with a C (26.5%; range 20.0%-37.2%) around five times more than observed for the other transitions (5.3%-6.8%). In contrast to an approximately random distribution of other transitions across the genome, most C→U substitutions occurred at statistically preferred sites in each lineage. However, only the most C→U polymorphic sites showed evidence for a preferred 5'U context previously associated with APOBEC 3A editing. There was a similarly weak preference for unpaired bases suggesting much less stringent targeting of RNA than mediated by A3 deaminases in DNA editing. Future functional studies are required to determine editing preferences, impacts on replication fitness of SARS-CoV-2 and other RNA viruses, and impact on host tropism.
Importance: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the pandemic and post-pandemic periods has shown a remarkable capacity to adapt and evade human immune responses and increase its human-to-human transmissibility. The genome of SARS-CoV-2 is also increasingly scarred by the effects of multiple C→U mutations from host genome editing as a cellular defense mechanism akin to restriction factors for retroviruses. Through the analysis of large data sets of SARS-CoV-2 isolate sequences collected throughout the pandemic period and beyond, we show that C→U transitions have driven a base compositional change over time amounting to a net loss of C bases and accumulation of U's at a rate of approximately 0.2%-0.25%/decade. Most C→U substitutions occurred in the absence of the preferred upstream-base context or targeting of unpaired RNA bases previously associated with the host RNA editing protein, APOBEC 3A. The analyses provide a series of testable hypotheses that can be experimentally investigated in the future.
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http://dx.doi.org/10.1128/mbio.02493-24 | DOI Listing |
Open Life Sci
December 2024
Department of Gastroenterology, The Ninth People's Hospital of Chongqing, No. 69, Jialing Village, Beibei District, Chognqing, 400700, China.
Colorectal cancer (CRC) is a common malignant tumor characterized by a high degree of invasiveness, and since zinc-α2 glycoprotein (ZAG) has been implicated in the progression of several malignancies, this study was designed to investigate the role of ZAG in CRC. Its expression was assessed using the GEPIA database, and short hairpin RNA (shRNA) interference was conducted to create ZAG knockdown in CRC cell lines. We also conducted lipid synthesis, cell proliferation, apoptosis, and epithelial-mesenchymal transition (EMT) experiments to elucidate the effects of ZAG expression on CRC, as well as explored the potential underlying mechanistic pathways.
View Article and Find Full Text PDFEvol Med Public Health
November 2024
Department of Obstetrics and Gynaecology, Medical University of Graz, Graz, Austria.
Evolutionary perspectives on obesity have been dominated by genetic frameworks, but plastic responses are also central to its aetiology. While often considered a relatively modern phenomenon, obesity was recorded during the Palaeolithic through small statuettes of the female form (Venus figurines). Even if the phenotype was rare, these statuettes indicate that some women achieved large body sizes during the last glacial maximum, a period of nutritional stress.
View Article and Find Full Text PDFFront Oncol
December 2024
Department of Oncology, Binzhou Medical University Hospital, Binzhou, Shandong, China.
Objective: To assess the cost-effectiveness of combining camrelizumab with rivoceranib versus sorafenib as initial treatment options for advanced hepatocellular carcinoma (HCC) across different developmental regions in China.
Methods: Utilizing TreeAge Pro and data from the phase III randomized CARES-310 clinical trial, a model based on Markov state transitions was developed. Health state utility values were derived from the CARES-310 trial, and direct medical costs were obtained from relevant literature and local pricing data.
Cureus
December 2024
College of Medicine, Alfaisal University, Riyadh, SAU.
Smell and taste sensations have been linked to positive outcomes in the feeding of premature infants, though the impact on the time required to transition to oral feeding remains unclear. This study aimed to evaluate the beneficial effects of smell and taste interventions on clinical outcomes in preterm infants. We conducted a search in PubMed, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials from inception through September 2024 for randomized controlled trials (RCTs) examining the effects of smell and taste on clinical outcomes in preterm infants with a gestational age of less than 34 weeks.
View Article and Find Full Text PDFSAGE Open Nurs
December 2024
Faculty of Nursing, Universitas Airlangga, Surabaya, Indonesia.
Introduction: Pregnancy can cause various physical and physiological changes. It affects confidence, resulting in depression and disturbing health not only for a mother but also for her fetus. These will also determine the ability of the mother to take care of her baby after delivery.
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