Korea4K: whole genome sequences of 4,157 Koreans with 107 phenotypes derived from extensive health check-ups.

BACKGROUND: Phenome-wide association studies (PheWASs) have been conducted on Asian populations, including Koreans, but many were based on chip or exome genotyping data. Such studies have limitations regarding whole genome-wide association analysis, making it crucial to have genome-to-phenome association information with the largest possible whole genome and matched phenome data to conduct further population-genome studies and develop health care services based on population genomics. RESULTS: Here, we present 4,157 whole genome sequences (Korea4K) coupled with 107 health check-up parameters as the largest genomic resource of the Korean Genome Project. It encompasses most of the variants with allele frequency >0.001 in Koreans, indicating that it sufficiently covered most of the common and rare genetic variants with commonly measured phenotypes for Koreans. Korea4K provides 45,537,252 variants, and half of them were not present in Korea1K (1,094 samples). We also identified 1,356 new genotype-phenotype associations that were not found by the Korea1K dataset. Phenomics analyses further revealed 24 significant genetic correlations, 14 pleiotropic associations, and 127 causal relationships based on Mendelian randomization among 37 traits. In addition, the Korea4K imputation reference panel, the largest Korean variants reference to date, showed a superior imputation performance to Korea1K across all allele frequency categories. CONCLUSIONS: Collectively, Korea4K provides not only the largest Korean genome data but also corresponding health check-up parameters and novel genome-phenome associations. The large-scale pathological whole genome-wide omics data will become a powerful set for genome-phenome level association studies to discover causal markers for the prediction and diagnosis of health conditions in future studies.

Immune Activation Modulation via Magnetically Localized Bacteria Based Micro/Bio Robot (BBMBR).

Understanding tumor's microenvironment is one of the key factors in the cancer therapy. Especially, from the perspective of immunotherapy, immune desert or cold tumor is referred as significantly downregulated T cell in-filtration due to lack of immune surveillance in the tumor microenvironment. There are many studies are dedicated to convert cold tumor to hot tumor for enhancing the efficacy of immunotherapy. In this study, we suggested selective immune activation system through the spatiotemporal control of the bacteria as an immune boosting agent. To this end, we have developed bacteria-based micro/bio robot system (BBMBR) by attaching bacteria with magnetic nanoparticles (MNP) so that the localization can be controlled through the magnetic field. The biomanufacturing results showed that BBMBR includes 6.6 ± 1.54 MNP attached and the presence ratio of bacteria-MNP out of total bacteria population reached 75.2 ± 3.37%. Spatial controllability experiments have shown that rotational and translation localization has been controlled as intended. The function of the immune modulation system through BBMBR was confirmed through experiments that magnetically driven BBMBR localization induced localized immune activation. M1-phenotype differentiation of macrophage cells were quantified CD80 staining, and overall immune response level was evaluated through IL-6 measurements. As the distance from the activation point increased, the population of M1 differentiated macrophages decreased, and when the movement of BBMBR was magnetically restricted, overall immune activation was found to be regulated downward. Proposed BBMBR and immune modulation framework could introduce a powerful new paradigm in cancer treatment by improving the localization controllability of immune-boosting agent and the spatial immune activation strategies.

Effects of gas sparging and mechanical mixing on sonochemical oxidation activity.

The effects of air sparging (0-16 L min-1) and mechanical mixing (0-400 rpm) on enhancing the sonochemical degradation of rhodamine B (RhB) was investigated using a 28 kHz sonoreactor. The degradation of RhB followed pseudo first-order kinetics, where sparging or mixing induced a large sonochemical enhancement. The kinetic constant varied in three stages (gradually increased â†’ increased exponentially â†’ decreased slightly) as the rate of sparging or mixing increased, where the stages were similar for both processes. The highest sonochemical activity was obtained with sparging at 8 L min-1 or mixing at 200 rpm, where the standing wave field was significantly deformed by sparging and mixing, respectively. The cavitational oxidation activity was concentrated at the bottom of the sonicator when higher sparging or mixing rates were employed. Therefore, the large enhancement in the sonochemical oxidation was attributed mainly to the direct disturbance of the ultrasound transmission and the resulting change in the cavitation-active zone in this study. The effect of the position of air sparging and mixing was investigated. The indirect inhibition of the ultrasound transmission resulted in less enhancement of the sonochemical activity. Moreover, the effect of various sparging gases including air, N2, O2, Ar, CO2, and an Ar/O2 (8:2) mixture was compared, where all gases except CO2 induced an enhancement in the sonochemical activity, irrespective of the concentration of dissolved oxygen. The highest activity was obtained with the Ar/O2 (8:2) mixture. Therefore, it was revealed that the sonochemical oxidation activity could be further enhanced by applying gas sparging using the optimal gas.

p16Ink4a suppression of lung adenocarcinoma by Bmi-1 in the presence of p38 activation.

PURPOSE: Because evasion of tumor suppression is a critical step in cancer development, cancer cells have developed a variety of mechanisms to circumvent the influence of tumor suppressive pathways. Thus, genes that negatively regulate tumor suppressors could be considered novel types of oncogenes such as Bmi-1 repressing p16Ink4a and inhibiting p53 and were found to be frequently up-regulated in a variety of cancers. p38 mitogen-activated protein kinase (MAPK), which reportedly plays a crucial role as a tumor suppressor, is activated in number of lung adenocarcinomas, which is seemingly at odds with its role as a tumor suppressor. METHODS: We examined 10 lung adenocarcinomas and corresponding normal tissues and determined the expression levels of a variety of tumor suppressor proteins through real-time polymerase chain reaction and immunohistochemistry and measured p38 MAPK activity by immunoblotting or immunohistochemistry analysis. In the in vitro cellular model, p38 activation by H-Ras and consequent senescence induction was achieved through retro-viral gene transduction. Similarly, the suppression of p16Ink4a by Bmi-1 after the introduction of H-Ras was achieved through transient transfection with cationic liposome. RESULTS: We detected several lung adenocarcinomas that were positive for activated p38 MAPK but evidenced reduced levels of p16Ink4a expression. The suppression of p16Ink4a occurred in parallel with an increase in Bmi-1 and/or p16Ink4a promoter hypermethylation. Consistent with these observations, the H-Ras-stimulated induction of p16Ink4a was suppressed significantly through the coexpression of Bmi-1 in vitro. DISCUSSION: These results demonstrate that the suppression of p16Ink4a by either the induction of Bmi-1 or the hypermethylation of p16Ink4 may be an important step in avoiding tumor surveillance by p38 MAPK during the development of lung cancer.