Abstract DNA crosslinks are cytotoxic lesions caused by a variety of DNA reacting compounds. Some bacterial competitors and environmental organisms evolved the ability to synthesize and secrete alkylating molecules that bind to DNA, impairing replication and transcription and ultimately resulting in death of the target cells. Notwithstanding, environmental exposure, spontaneous chemical reactions and byproducts of the physiological metabolism can interfere with DNA, leading to toxic crosslinking damage. Hence, bacteria evolved repair systems capable of removing lesions and allowing cells to thrive even in harsh conditions. Base Excision Repair, Nucleotide Excision Repair, Homologous Recombination and Translesion Synthesis all combine to solve DNA monoadducts, Intrastrand, Interstrand, and DNA-Peptide Crosslinks. In this review, we address major stressors to which bacteria are exposed, their DNA-damaging capacities and how the prokaryotic cell responds.
Abstract Plant-microorganism interactions contribute to plant health by enhancing nutrient acquisition. The transcription factor OsASR5 regulates detoxification gene expression under aluminum stress in rice and is implicated as a positive regulator of responses to iron and phosphorus deficiency. Given its role in nutrient regulation, we investigated whether OsASR5 influences the assembly of the rice microbiome. In this study, we characterized the bacteria communities associated with the leaves and roots of OsASR5-RNAi rice plants compared to wild-type Oryza sativa cv. Nipponbare. Notably, OsASR5-RNAi plants showed altered bacterial beta diversity compared with wild type. The bacterial composition of OsASR5-RNAi plants differed in both organs, with decreased Desulfobacteriota and increased in Acidobacteria abundance in leaves. At the genus level, Methylobacterium, a known plant growth promoter, was less prevalent in leaves, while Magnetospirillum, associated with iron cycling, was less abundant in roots. Conversely, several bacteria were more abundant in OsASR5-RNAi plants, including Aneurinibacillus, Anaeromyxobacter, and Methylobacter, which are associated with nitrogen cycling and phosphorus solubilization. Additionally, Geobacter and Geothrix, both known for their role in metal reduction, particularly iron, were more abundant in OsASR5-RNAi plants. These suggest that OsASR5 affects plant-microbe interactions, potentially influencing nutrient cycling and plant stress responses through microbiome modulation.
Abstract 1α,25-(OH)2-D3 can promote autophagy of osteoclast precursors (OCPs), resulting in its pro-osteoclastogenic effect, which limits its anti-osteoporotic efficacy. To address the above challenges, we need to explore the targets of autophagy-enhancing effect of 1α,25-(OH)2-D3. These results showed that 1α,25-(OH)2-D3 promoted the expression of BECN1 mRNA and Beclin1 protein in OCPs under RANKL induction. Furthermore, 1α,25-(OH)2-D3 enhances p65 phosphorylation and nuclear translocation. The lentiviral-mediated silencing of both BECN1 and p65 impeded the facilitation of 1α,25-(OH)2-D3 on osteoclast differentiation and OCP autophagy. Moreover, p65 silencing blocked the enhancement of BECN1 mRNA expression and Beclin1 protein expression by 1α,25-(OH)2-D3. In conclusion, 1α,25-(OH)2-D3 enhances Beclin1-dependent autophagy in OCPs by promoting BECN1 transcription, thereby promoting osteoclast differentiation; this indicates that the therapeutic strategies for BECN1 or p65 targeted inhibition have the potential to optimize the anti-osteoporotic function of 1α,25-(OH)2-D3.
Abstract We developed the “HVSnp: Human Viruses SNP-related database, a curated database”.HVSnp is exclusive to the human SNPs studied and related to viral diseases, with manually mined and curated information from public SNP databases and scientific articles. We used MySQL (version 8.0) due to the easy management and the Looker Studio online availability. Among the output information, we have SNP identification, reference, alternative, and risk alleles, chromosome, gene, and gene function, summary, among others. In total, HVSnp contains eighteen viral diseases and 2020 records: Adenovirus (17 SNPs), Chikungunya (7), COVID-19 (314), Cytomegalovirus (54), Dengue (62), Epstein-Barr (54), Hepatitis A (3), Hepatitis B (380), Hepatitis C (166), Herpes (8), Human immunodeficiency virus (479), Papillomavirus (87), Influenza (74), Measles (68), Respiratory syncytial virus (50), Sars-CoV (80), West Nile (68), and Zika (49). As one SNP can be associated with more than one virus, the number of unique SNPs is 1691 and 651 genes. HVSnp has supplementary information obtained in articles for the summary elaboration, which contains the most significant results described in the literature about a possible relationship between SNPs and viruses. The database is available at URL: https://lookerstudio.google.com/s/pGUC7m538gQ.
Abstract For nearly 50 years, scientists have sought to exploit messenger RNA (mRNA) as a therapeutic tool, overcoming major challenges related to instability, delivery, and inflammatory reactions. A major breakthrough came with the incorporation of modified nucleosides, particularly pseudouridine, during in vitro mRNA synthesis, which markedly improved stability, translation efficiency, and tolerability. The clinical success of mRNA technology was demonstrated in 2020 with the development of highly effective and safe COVID-19 vaccines, administered to over a billion individuals worldwide. These achievements inaugurated a new era in molecular medicine. In this review, we revisit the historical development of mRNA delivery into human cells and discuss the emergence of mRNA as a gene-therapy approach. In fact, beyond vaccination, mRNA platforms are rapidly expanding toward protein replacement therapies for genetic disorders and innovative strategies for cancer treatment. We summarize advances in synthetic mRNA design and optimization, delivery vehicles, and administration strategies that enable therapeutic applications. Finally, we highlight current limitations, technological challenges, and future opportunities, emphasizing how mRNA-based technologies have become powerful tools for studying gene function and developing next-generation precision therapies.
