Biology subjects

Park, J.-Y.

Publications and source records attributed to Park, J.-Y..

3 recordsLinked to original sources

bioRxiv2019

Unveiling the crucial role of type IV secretion system and motility of Helicobacter pylori in IL-1β production via NLRP3 inflammasome activation in neutrophils

Helicobacter pylori is a gram-negative, microaerophilic, and spiral-shaped bacterium and causes gastrointestinal diseases in human. IL-1{beta} is a representative cytokine produced in innate immune cells and is considered to be a key factor in the development of gastrointestinal malignancies. However, the mechanism of IL-1{beta} production by neutrophils during H. pylori infection is still unknown. We designed this study to identify host and bacterial factors involved in regulation of H. pylori-induced IL-1{beta} production in neutrophils. We found that H. pylori-induced IL-1{beta} production is abolished in NLRP3-, ASC-, and caspase-1/11-deficient neutrophils, suggesting essential role for NLRP3 inflammasome in IL-1{beta} response against H. pylori. Host TLR2, but not TLR4 and Nod2, was also required for transcription of NLRP3 and IL-1{beta} as well as secretion of IL-1{beta}. H. pylori lacking cagL, a key component of the type IV secretion system (T4SS), induced less IL-1{beta} production in neutrophils than did its isogenic WT strain, whereas vacA and ureA were dispensable. Moreover, T4SS was involved in caspase-1 activation and IL-1{beta} maturation in H. pylori-infected neutrophils. We also found that FlaA is essential for H. pylori-mediated IL-1{beta} production in neutrophils, but not dendritic cells. TLR5 and NLRC4 were not required for H. pylori-induced IL-1{beta} production in neutrophils. Instead, bacterial motility is essential for the production of IL-1{beta} in response to H. pylori. In conclusion, our study shows that host TLR2 and NLRP3 inflammasome and bacterial T4SS and motility are essential factors for IL-1{beta} production by neutrophils in response to H. pylori.\n\nIMPORTANCEIL-1{beta} is a representative pro-inflammatory cytokine and is considered to be a central host factor for the development of gastric cancers. Although neutrophils have been considered to be involved in H. pylori-induced gastric inflammation, the underlying mechanism by which H. pylori triggers IL-1{beta} production in neutrophils remains to be defined. In this study, our data suggested a critical role for the host TLR2 and NLRP3 inflammasome in IL-1{beta} production by neutrophil during H. pylori infection. Moreover, we found the bacterial factors, T4SS and FlaA, to be essential for IL-1{beta} production and NLRP3 activation during the course of H. pylori infection. Our current findings provide detailed molecular genetic mechanisms associated with IL-1{beta} production in neutrophils in response to H. pylori infection, which can serve as innovative anti-inflammatory targets to reduce H. pylori-induced gastric malignancies.

immunology↗

bioRxiv2019

High diagnostic yield and clinical utility of WES for patients with undiagnosed genetic disorder by automating variant interpretation

PurposeEVIDENCE, an automated interpretation system, has been developed to facilitate the entire process of whole exome sequencing (WES) analyses. This study investigated the diagnostic yield of EVIDENCE in patients suspected genetic disorders. MethodsDNA from 330 probands (age range, 0-68 years) with suspected genetic disorders were subjected to WES. Candidate variants were identified by EVIDENCE and confirmed by testing family members and/or clinical reassessments. ResultsThe average number of overlapping organ categories per patient was 4.5 {+/-} 5.0. EVIDENCE reported a total 244 variants in 215 (65.1%) of the 330 probands. After clinical reassessment and/or family member testing, 196 variants were identified in 171 probands (51.8%), including 115 novel variants. These variants were confirmed as being responsible for 146 genetic disorders. One hundred-seven (54.6%) of the 196 variants were categorized as pathogenic or likely pathogenic before, and 146 (74.6%) after, clinical assessment and/or family member testing. Factors associated with a variant being confirmed as causative include rules, such as PVS1, PS1, PM1, PM5, and PP5, and similar symptom scores between that variant and a patients phenotype. ConclusionThis new, automated variant interpretation system facilitated the diagnosis of various genetic diseases with a 51% improvement in diagnostic yield.

genetics↗

bioRxiv2019

Raptor genomes reveal evolutionary signatures of predatory and nocturnal lifestyles

BackgroundBirds of prey (raptors) are dominant apex predators in terrestrial communities, with hawks (Accipitriformes) and falcons (Falconiformes) hunting by day, and owls (Strigiformes) hunting by night.\n\nResultsHere, we report new genomes and transcriptomes for 20 species of birds, including 16 species of birds of prey, and high-quality reference genomes for the Eurasian eagle-owl (Bubo bubo), oriental scops-owl (Otus sunia), eastern buzzard (Buteo japonicus), and common kestrel (Falco tinnunculus). Our extensive genomic analysis and comparisons with non-raptor genomes identified common molecular signatures that underpin anatomical structure and sensory, muscle, circulatory, and respiratory systems related to a predatory lifestyle. Compared with diurnal birds, owls exhibit striking adaptations to the nocturnal environment, including functional trade-offs in the sensory systems (e.g., loss of color vision genes and selection for enhancement of nocturnal vision and other sensory systems) that are probably convergent with other nocturnal avian orders. Additionally, we found that a suite of genes associated with vision and circadian rhythm were differentially expressed between nocturnal and diurnal raptors, indicating adaptive expression change during the transition to nocturnality.\n\nConclusionsOverall, raptor genomes showed genomic signatures associated with the origin and maintenance of several specialized physiological and morphological features essential to be apex predators.

genomics↗