Biology subjects

Yang, J.-H.

Publications and source records attributed to Yang, J.-H..

5 recordsLinked to original sources

bioRxiv2018

Association of Prevotella enterotype with polysomnographic data in obstructive sleep apnea/hypopnea syndrome patients

Intermittent hypoxia and sleep fragmentation are critical pathophysiological processes involved in obstructive sleep apnea/hypopnea syndrome (OSAHS). These manifestation independently affect similar brain regions and contribute to OSAHS-related comorbidities that are known to be related to the host gut alteration microbiota. We hypothesized that microbiota disruption influences the pathophysiological processes of OSAHS through a microbiota-gut-brain axis. Thus, we aim to survey enterotypes and polysomnographic data of OSAHS patients. Subjects were diagnosed by polysomnography, from whom fecal samples were obtained and analyzed for the microbiome composition by variable regions 3-4 of 16S rRNA pyrosequencing and bioinformatic analyses. We examined blood cytokines level of all subjects. Three enterotypes Bacteroides (n=73), Ruminococcus (n=14), and Prevotella (n=26) were identified. Central apnea indices, mixed apnea indices, N1 sleep stage, mean apnea-hypopnea duration, and arousal indices were increased in apnea-hypopnea indices (AHI) [≥]15 patients with the Prevotella enterotype. However, for AHI<15 subjects, obstructive apnea indices and systolic blood pressure were significantly observed in Ruminococcus and Prevotella enterotypes, respectively. The present study indicates the possibility of pathophysiological interplay between enterotypes and sleep structure disruption in sleep apnea through a microbiota-gut-brain axis and offers some new insight toward the pathogenesis of OSAHS.\n\nImportanceIntermittent hypoxia (IH) and sleep fragmentation (SF) are hallmarks of are the predominant mechanism underlying obstructive sleep apnea/hypopnea syndrome (OSAHS). Moreover, IH and SF of pathophysiological roles in the gut microbiota dysbiosis in OSAHS have been demonstrated. We hypothesized that gut microbiota disruption may cross-talk the brain function via microbiota-gut-brain axis. Indeed, we observed central apnea indices and other parameters of disturbances during sleep were significantly elevated in AHI[≥]15 patients with the Prevotella enterotype. This enterotype prone to endotoxin production, driving systemic inflammation, ultimately contributes to OSAHS-linked comorbidities. Vice versa, increasing the arousal index leads to systemic inflammatory changes and accompanies metabolic dysfunction. We highlight that the possibility that the microbiota-gut-brain axis operates a bidirectional effect on the development of OSAHS pathology.

microbiology↗

bioRxiv2018

Widespread and polymorphous noncoding amino acid residues in human sperm proteome

Proteins are usually deciphered by translation of the coding genome; however, their amino acid residues are seldom determined directly across the proteome. Herein, we describe a systematic workflow for identifying all possible protein residues that differ from the coding genome, termed noncoded amino acids (ncAAs). By measuring the mass differences between the coding amino acids and the actual protein residues in human spermatozoa, over a million nonzero delta masses were detected, fallen into 424 high-quality Gaussian clusters and 571 high-confidence ncAAs spanning 29,053 protein sites. Most ncAAs are novel with unresolved side-chains and discriminative between healthy individuals and patients with oligoasthenospermia. For validation, 40 out of 98 ncAAs that matched with amino acid substitutions were confirmed by exon sequencing. This workflow revealed the widespread existence of previously unreported ncAAs in the sperm proteome, which represents a new dimension on the understanding of amino acid polymorphisms at the proteomic level.\n\nHighlightsO_LI571 ncAAs spanning 108,000 protein sites were identified in human sperm proteome.\nC_LIO_LIMost ncAAs are novel with unresolved sidechains and found at unreported protein sites.\nC_LIO_LIExon sequencing confirmed 40 of 98 ncAAs that matched with amino acid substitutions.\nC_LIO_LIMany ncAAs are linked with disease and have potential for diagnosis and targeting.\nC_LI\n\neTOC BlurbWe describe a systematic identification of all possible protein residues that were not encoded by their genomic sequences. A total of 571 high-confidence most novel noncoded amino acids were identified in human sperm proteome, corresponding to over 108,000 ncAA-containing protein sites. For validation, 40 out of 98 ncAAs that matched to amino acid substitutions were confirmed by exon sequencing. These ncAAs are discriminative between individuals and expand our understanding of amino acid polymorphisms in human proteomes and diseases.

molecular biology↗

bioRxiv2018

Variability and compensation of cardiomycoyte ionic conductances at the population level

Conductances of ion channels and transporters controlling cardiac excitation may vary in a population of subjects with different cardiac gene expression patterns. However, the amount of variability and its origin are not quantitatively known. We propose a new computational method to predict this variability that consists of finding combinations of conductances generating a normal intracellular Ca2+ transient without any constraint on the action potential. Furthermore, we validate experimentally its predictions using the Hybrid Mouse Diversity Panel, a model system of genetically diverse mouse strains that allows us to quantify inter-subject versus intra-subject variability. The method predicts that conductances of inward Ca2+ and outward K+ currents compensate each other to generate a normal Ca2+ transient in good quantitative agreement with current measurements in ventricular myocytes from hearts of different isogenic strains. Our results suggest that a feedback mechanism sensing the aggregate Ca2+ transient of the heart suffices to regulate ionic conductances.

biophysics↗

bioRxiv2018

MicroRNA-122 supports robust innate immunity in hepatocytes by suppressing STAT3 phosphorylation

The intrinsic innate immunity of hepatocytes is essential for the control of hepatitis viruses and influences the outcome of antiviral therapy. MicroRNA-122 (miR-122) is the most abundant microRNA in hepatocytes and is a central player in liver biology and disease. However, little is known about the role of miR-122 in hepatocyte innate immunity. Herein, we show that restoring miR-122 levels in hepatoma cells markedly increased the activation of both type III and type I interferons (IFNs) in response to hepatitis C virus (HCV) RNA or poly(I:C). We determined that miR-122 promotes IFN production through down-regulating the tyrosine (Tyr705) phosphorylation of STAT3. We show that STAT3 represses IFN activation by inhibiting interferon regulatory factor 1 (IRF1), which is rate-limiting for maximal IFN expression, especially type III IFNs. Through large-scale screening, we identified that miR-122 targets MERTK, FGFR1 and IGF1R, three oncogenic receptor tyrosine kinases that directly promote STAT3 phosphorylation. These findings reveal a previously unknown role for miR-122 in hepatic immunity and indicate a new potential strategy for treating hepatic infections through targeting STAT3.

molecular biology↗

bioRxiv2017

Discovering the Interactions between Circular RNAs and RNA-binding Proteins from CLIP-seq Data using circScan

Although tens of thousands of circular RNAs (circRNAs) have been identified in mammalian genomes, only few of them have been characterized with biological functions. Here, we report a new approach, circScan, to identify regulatory interactions between circRNAs and RNA-binding proteins (RBPs) by discovering back-splicing reads from Cross-Linking and Immunoprecipitation followed by high-throughput sequencing (CLIP-seq) data. By using our method, we have systematically scanned ~1500 CLIP-seq datasets, and identified ~12540 and ~1090 novel circRNA-RBP interactions in human and mouse genomes, respectively, which include all known interactions between circRNAs and Argonaute (AGO) proteins. More than twenty novel interactions were further experimentally confirmed by RNA Immunoprecipitation quantitative PCR (RIP-qPCR). Importantly, we uncovered that some natural circRNAs interacted with cap-independent translation factors eukaryotic initiation factor 3 (eIF3) and N6-Methyladenosine (m6A), indicating they can be translated into proteins. These findings demonstrate that circRNAs are regulated by various RBPs, suggesting they may play important roles in diverse biological processes.

molecular biology↗