These data show macula-specific increases in mtDNA damage, heteroplasmic mutations, and diminished repair that are associated with aging and AMD severity.
Dental caries and periodontitis are common bacterial mouth infections. As a potentially attractive substitute for conventional antibiotics, antimicrobial peptides have been widely tested and used for controlling bacterial infections. In this study, we tested the efficacy of the peptides from the skin secretions of Rana chensinensis for killing several major cariogenic and periodontic pathogens as well as Candida albicans. L-K6, a temporin-1CEb analog, exhibited high antimicrobial activity against the tested oral pathogens and was able to inhibit Streptococcus mutans biofilm formation and reduce 1-day-old S. mutans biofilms with a minimum biofilm inhibitory concentration and reducing concentration of 3.13 and 6.25 μM, respectively. The results of confocal laser scanning microscopy demonstrated that the peptide significantly reduced cell viability within oral biofilms. Furthermore, as little as 5 μM L-K6 significantly inhibited lipopolysaccharide (LPS)- and interleukin-1β-induced productions of interleukin-8 and tumor necrosis factor-α from THP-1 monocytic cells. This anti-inflammatory activity is associated with the binding of L-K6 to LPS and neutralizing LPS-induced proinflammatory responses in THP-1 cells, as well as dissociating LPS aggregates. Our results suggest that L-K6 may have potential clinical applications in treating dental caries by killing S. mutans within dental plaque and acting as anti-inflammatory agents in infected tissues.
Decades of artificial selection have significantly improved performance and efficiency of animal production systems. However, little is known about the microevolution of genomes due to intensive breeding. Using whole-genome sequencing, we document dynamic changes of chicken genomes under divergent selection on adiposity over 19 generations. Directional selection reduced withinline but increased between-line genomic differences. We observed that artificial selection tended to result in recruitment of preexisting variations of genes related to adipose tissue growth. In addition, novel mutations contributed to divergence of phenotypes under selection but contributed significantly less than preexisting genomic variants. Integration of 15 generations genome sequencing, genome-wide association study, and multi-omics data further identified that genes involved in signaling pathways important to adipogenesis, such as autophagy and lysosome (URI1, MBL2), neural system (CHAT), and endocrine (PCSK1) pathways, were under strong selection. Our study provides insights into the microevolutionary dynamics of domestic animal genomes under artificial selection.
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