Biology subjects

Yamauchi, H.

Publications and source records attributed to Yamauchi, H..

4 recordsLinked to original sources

bioRxiv2022

Determination of a target image of freshwater fishes composition in a mitigation project using eDNA metabarcoding methods

Establishing realistic targets for fish community composition is needed to assess the effectiveness of river restoration projects. We used environmental DNA (eDNA) metabarcoding with MiFish primers to obtain estimates of fish community composition across 17 sites upstream, downstream and within a restoration mitigation project area (Kaihotsu- Kasumi) located in the Shigenobu River system, Ehime Prefecture, Japan. We evaluate the benefits of using eDNA to quickly, sensitively, and extensively gather data to establish existing fish community composition in the restoration area, as well as potential future short-term, medium-term, and long-term targets of species assemblages that could realistically emerge following dispersal into the project area from upstream and downstream populations. We compare results from eDNA metabarcoding with species lists obtained from contemporaneous capture surveys and historical information. Nonmetric multidimensional scaling plots of community composition obtained from eDNA surveys showed that the Kaihotsu-Kasumi restoration area and surrounding river reaches were divided into three clusters: upper reaches, middle and lower reaches, and estuarine reaches. The Kaihotsu- Kasumi restoration area sites were included in the group containing the middle and lower reaches of the inflow and outflow rivers that were near the restoration area. We detected a total of twenty-six species in this group, twenty-one native species and five non-native species. Therefore, these native species were considered suitable as short-term target species with high potential for dispersal into Kaihotsu-Kasumi restoration area. By comparison, only 14 species would have been selected as target species based on capture surveys and historical literature. One factor increasing the resolution of our eDNA surveys was our ability to identify the presence of intraspecific lineages of Misgurnus anguillicaudatus (Clades A and B), which were missed by the capture surveys. These results indicate that the eDNA metabarcoding method can provide more comprehensive and realistic short-term target species estimates than capture surveys, as well as provide higher resolution monitoring through intraspecific lineage detection.

ecology↗

bioRxiv2022

Aberrant mechanosensitive signaling underlies activation of vascular endothelial xanthine oxidoreductase that promotes aortic aneurysm formation in Marfan syndrome

Marfan syndrome (MFS) is an inherited connective tissue disorder caused by mutations in the FBN1 gene encoding fibrillin-1, a matrix component of extracellular microfibrils. The main cause of morbidity and mortality in MFS is thoracic aortic aneurysm and dissection, but the underlying mechanisms remain undetermined. We found a significant increase in reactive oxygen species (ROS) generation in ascending aorta of MFS patients and MFS mice harboring the Fbn1 mutation (C1039G), which was associated with up-regulation of xanthine oxidoreductase (XOR) protein in aortic endothelial cells (ECs). Mechanosensitive signaling involving focal adhesion kinase (FAK)-p38 mitogen-activated protein kinase (MAPK) and early growth response-1 (Egr- 1) was aberrantly activated in ascending aorta of Fbn1C1039G/+ mice, and mechanical stress on human aortic ECs up-regulated XOR expression through FAK-p38 MAPK activation and Egr-1 up-regulation. Inhibition of XOR function by ECs-specific disruption of Xdh gene or by systemic administration of XOR inhibitor febuxostat in Fbn1C1039G/+ mice suppressed ROS generation, FAK-p38 MAPK activation, and Egr-1 up-regulation, leading to attenuation of aortic aneurysm formation. These findings unveil aberrant mechanosensitive signaling in vascular ECs triggering endothelial XOR activation and ROS generation as a culprit underlying the pathogenesis of aortic aneurysm formation in MFS, and highlight a drug repositioning approach using a uric acid lowering drug febuxostat as a potential therapy for MFS.

pathology↗

bioRxiv2021

Systematic identification of intron retention associated variants from massive publicly available transcriptome sequencing data

Many disease-associated genomic variants disrupt gene function through abnormal splicing. With the advancement of genomic medicine, identifying disease-associated splicing associated variants has become more important than ever. Most bioinformatics approaches to detect splicing associated variants require both genome and transcriptomic data. However, there are not many datasets where both of them are available. In this study, we developed a methodology to detect genomic variants that cause splicing changes (more specifically, intron retention), using transcriptome sequencing data alone. After demonstrating its high sensitivity and precision, we have applied it to 230,988 transcriptome sequencing data from the publicly available repository and identified 27,937 intron retention associated variants (IRAVs). In addition, by exploring positional relationships with variants registered in existing disease databases, we extracted 3,077 putative disease-associated IRAVs, which range from cancer drivers to variants linked with autosomal recessive disorders. The new in-silico screening framework proposed here provides a foundation for a platform that can automatically acquire medical knowledge making the most of massively accumulated publicly available sequencing data. Collections of IRAVs identified in this study are available through IRAVDB (https://iravdb.io/).

bioinformatics↗

bioRxiv2018

Engineering a model cell for rational tuning of GPCR signaling

G protein-coupled receptor (GPCR) signaling is the primary method eukaryotes use to respond to specific cues in their environment. However, the relationship between stimulus and response for each GPCR is difficult to predict due to diversity in natural signal transduction architecture and expression. Using genome engineering in yeast, we here constructed an insulated, modular GPCR signal transduction system to study how the response to stimuli can be predictably tuned using synthetic tools. We delineated the contributions of a minimal set of key components via computational and experimental refactoring, identifying simple design principles for rationally tuning the dose-response. Using four different receptors, we demonstrate how this enables cells and consortia to be engineered to respond to desired concentrations of peptides, metabolites and hormones relevant to human health. This work enables rational tuning of cell sensing, while providing a framework to guide reprogramming of GPCR-based signaling in more complex systems.

synthetic biology↗