Negative Self-Regulation of TLR9 Signaling by Its N-Terminal Proteolytic Cleavage Product

TLR signaling is essential to innate immunity against microbial invaders and must be tightly controlled. We have previously shown that TLR9 undergoes proteolytic cleavage processing by lysosomal proteases to generate two distinct fragments. The C-terminal cleavage product plays a critical role in activating TLR9 signaling; however, the precise role of the N-terminal fragment, which remains in lysosomes, in the TLR9 response is still unclear. In this article, we report that the N-terminal cleavage product negatively regulates TLR9 signaling. Notably, the N-terminal fragment promotes the aspartic protease-mediated degradation of the C-terminal fragment in endolysosomes. Furthermore, the N-terminal TLR9 fragment physically interacts with the C-terminal product, thereby inhibiting the formation of homodimers of the C-terminal fragment; this suggests that the monomeric C-terminal product is more susceptible to attack by aspartic proteases. Together, these results suggest that the N-terminal TLR9 proteolytic cleavage product is a negative self-regulator that prevents excessive TLR9 signaling activity.Korea (South). Ministry of Education, Science and Technology (MEST) (National Research Foundation of Korea. Grant 2011-0015372)Korea (South). Ministry of Education, Science and Technology (MEST) (National Research Foundation of Korea. Grant 2010-0009203)Korea. Ministry of Health and Welfare. National Research and Development Program for Cancer Contro

Increased viral load in patients infected with severe acute respiratory syndrome coronavirus 2 Omicron variant in the Republic of Korea

Objectives Coronavirus disease 2019 (COVID-19) has been declared a global pandemic owing to the rapid spread of the causative agent, severe acute respiratory syndrome coronavirus 2. Its Delta and Omicron variants are more transmissible and pathogenic than other variants. Some debates have emerged on the mechanism of variants of concern. In the COVID-19 wave that began in December 2021, the Omicron variant, first reported in South Africa, became identifiable in most cases globally. The aim of this study was to provide data to inform effective responses to the transmission of the Omicron variant. Methods The Delta variant and the spike protein D614G mutant were compared with the Omicron variant. Viral loads from 5 days after symptom onset were compared using epidemiological data collected at the time of diagnosis. Results The Omicron variant exhibited a higher viral load than other variants, resulting in greater transmissibility within 5 days of symptom onset. Conclusion Future research should focus on vaccine efficacy against the Omicron variant and compare trends in disease severity associated with its high viral load

Genetic diagnosis of inborn errors of immunity using clinical exome sequencing

Inborn errors of immunity (IEI) include a variety of heterogeneous genetic disorders in which defects in the immune system lead to an increased susceptibility to infections and other complications. Accurate, prompt diagnosis of IEI is crucial for treatment plan and prognostication. In this study, clinical utility of clinical exome sequencing (CES) for diagnosis of IEI was evaluated. For 37 Korean patients with suspected symptoms, signs, or laboratory abnormalities associated with IEI, CES that covers 4,894 genes including genes related to IEI was performed. Their clinical diagnosis, clinical characteristics, family history of infection, and laboratory results, as well as detected variants, were reviewed. With CES, genetic diagnosis of IEI was made in 15 out of 37 patients (40.5%). Seventeen pathogenic variants were detected from IEI-related genes, BTK, UNC13D, STAT3, IL2RG, IL10RA, NRAS, SH2D1A, GATA2, TET2, PRF1, and UBA1, of which four variants were previously unreported. Among them, somatic causative variants were identified from GATA2, TET2, and UBA1. In addition, we identified two patients incidentally diagnosed IEI by CES, which was performed to diagnose other diseases of patients with unrecognized IEI. Taken together, these results demonstrate the utility of CES for the diagnosis of IEI, which contributes to accurate diagnosis and proper treatments

Replication data for: Replication for Decommodification and Activation in Social Democratic Policy: Resolving the Paradox

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Investigation of Epoxidized Palm Oils as Green Processing Aids and Activators in Rubber Composites

Epoxidized palm oil (EPO) is environmentally friendly, biodegradable, and a relatively less costly processing aid. In this study, we investigated the suitability of EPO in place of aromatic processing oils in styrene butadiene rubber. The curing properties, mechanical properties, abrasion resistance, and heat buildup properties of rubber composites with EPO were compared with those of the standard with aromatic oils. The rubber composites with EPO showed enhanced mechanical properties including modulus, tensile strength, and elongation at break. This is ascribed to the improved dispersion of fillers in the rubber matrix and interaction between the filler and the polymer. Furthermore, EPO in the rubber matrix showed remarkable abrasion resistance, rebound resilience, and heat buildup at low loadings. EPO in a rubber composite presents feasibility as a renewable raw material that can serve as an alternative to petrochemical oils in various applications