HP1a-mediated heterochromatin formation promotes antimicrobial responses against Pseudomonas aeruginosa infection.

BACKGROUND: Pseudomonas aeruginosa is a Gram-negative bacterium that causes severe infectious disease in diverse host organisms, including humans. Effective therapeutic options for P. aeruginosa infection are limited due to increasing multidrug resistance and it is therefore critical to understand the regulation of host innate immune responses to guide development of effective therapeutic options. The epigenetic mechanisms by which hosts regulate their antimicrobial responses against P. aeruginosa infection remain unclear. Here, we used Drosophila melanogaster to investigate the role of heterochromatin protein 1a (HP1a), a key epigenetic regulator, and its mediation of heterochromatin formation in antimicrobial responses against PA14, a highly virulent P. aeruginosa strain. RESULTS: Animals with decreased heterochromatin levels showed less resistance to P. aeruginosa infection. In contrast, flies with increased heterochromatin formation, either in the whole organism or specifically in the fat body-an organ important in humoral immune response-showed greater resistance to P. aeruginosa infection, as demonstrated by increased host survival and reduced bacterial load. Increased heterochromatin formation in the fat body promoted the antimicrobial responses via upregulation of fat body immune deficiency (imd) pathway-mediated antimicrobial peptides (AMPs) before and in the middle stage of P. aeruginosa infection. The fat body AMPs were required to elicit HP1a-mediated antimicrobial responses against P. aeruginosa infection. Moreover, the levels of heterochromatin in the fat body were downregulated in the early stage, but upregulated in the middle stage, of P. aeruginosa infection. CONCLUSIONS: These data indicate that HP1a-mediated heterochromatin formation in the fat body promotes antimicrobial responses by epigenetically upregulating AMPs of the imd pathway. Our study provides novel molecular, cellular, and organismal insights into new epigenetic strategies targeting heterochromatin that have the potential to combat P. aeruginosa infection.

Phenolic compositions and antioxidant properties of leaves of eight persimmon varieties harvested in different periods.

The compositions and contents of antioxidant components and antioxidant attributes (scavenging DPPH radicals, TEAC, ferric reducing power and inhibiting Cu2+-induced human LDL oxidation) for the leaves of eight persimmon varieties harvested from Sep. to Nov. were determined. Harvest time and variety were important factors affecting the compositions and contents of phenolic compounds in persimmon leaves; moreover, phenolic contents (polyphenol, flavonoid, condensed tannin and phenolic acid) of the leaves were significantly correlated with their antioxidant activities. For each variety, the leaves harvested in months with higher temperature, solar radiation and sunshine duration had higher phenolic contents contributing to better antioxidant properties (ranking: Sep. > Oct. > Nov.). In addition, the compositions and contents of phenolic components and antioxidant capacities for the leaves from various persimmon varieties were also different. The leaves of persimmon varieties belonging to pollination constant and astringent (PCA) had higher phenolic contents and also presented better antioxidant effects.

Insights into structural properties of denatured human prion 121-230 at melting temperature studied by replica exchange molecular dynamics.

Misfolding and aggregation of the prion protein (PrP) is responsible for the development of fatal transmissible neurodegenerative diseases. PrP undergoes structural conversion from a natively folded state into a misfolded state, resulting in aggregated amyloid fibrils. Partial unfolding has been recognized as an essential step in fibrillation, especially at the middle point of unfolding. To study the possible aggregation-prone states, we characterized the structure of the C-terminal globular domain of human prion (huPrP) 121-230 near extended conformation at melting temperature by replica exchange molecular dynamics (REMD) simulation, as the REMD method is the most suited generalized-ensemble algorithm that performs random walk in energy space and promotes a system to escape from local energy traps. Our results revealed that denatured huPrP is partially folded with α-helical structure at melting temperature. The simulation results provide further insight into the unfolding of prion, which is essential in pathogenesis of prion diseases.