Biology subjects

Yamamoto, S.

Publications and source records attributed to Yamamoto, S..

82 records · Page 5Linked to original sources

bioRxiv2020

ChiS is a noncanonical DNA-binding hybrid sensor kinase that directly regulates the chitin utilization program in Vibrio cholerae

Two-component signal transduction systems (TCSs) represent a major mechanism that bacteria use to sense and respond to their environment. Prototypical TCSs are composed of a membrane-embedded histidine kinase (HK), which senses an environmental stimulus and subsequently phosphorylates a cognate partner protein called a response regulator (RR) that regulates gene expression in a phosphorylation-dependent manner. Vibrio cholerae uses the hybrid HK ChiS to activate the expression of the chitin utilization program, which is critical for the survival of this facultative pathogen in its aquatic reservoir. A cognate RR for ChiS has not been identified and the mechanism of ChiS-dependent signal transduction remains unclear. Here, we show that ChiS is a noncanonical membrane-embedded one-component system that can both sense chitin and directly regulate gene expression via a cryptic DNA binding domain. Unlike prototypical TCSs, we find that ChiS DNA binding is diminished, rather than stimulated, by phosphorylation. Finally, we provide evidence that ChiS likely activates gene expression by directly recruiting RNA polymerase. Together, this work addresses the mechanism of action for a major transcription factor in V. cholerae and highlights the versatility of signal transduction systems in bacterial species. Significance StatementFrom bacteria to humans, the ability to properly respond to environmental cues is critical for survival. The cholera pathogen Vibrio cholerae uses one protein, ChiS, to sense chitin in its environmental reservoir to regulate the expression of genes that are critical for the survival and evolution of this pathogen in this niche. Here, we study how the chitin sensor ChiS works, and discover that it regulates gene expression in an unexpected and unorthodox manner. Thus, this study uncovers how the major regulator ChiS works in this important human pathogen and highlights the versatile mechanisms that living systems use to respond to their environment.

microbiology↗

bioRxiv2019

Short-term effects on brain functional network caused by focused-attention meditation revealed by Tucker3 clustering on graph theoretical metrics

This study examines the short-term effects of focused-attention meditation on functional brain state in novice meditators. There are a number of feature metrics for functional brain states, such as functional connectivity, graph theoretical metrics, and amplitude of low frequency fluctuation (ALFF). It is necessary to choose appropriate metrics and also to specify the region of interests (ROIs) from a number of brain regions. Here, we use a Tucker3 clustering method, which simultaneously selects the feature vectors (graph theoretical metrics and fractional ALFF) and the ROIs that can discriminate between resting and meditative states based on the characteristics of the given data. In this study, breath-counting meditation, one of the most popular forms of focused-attention meditation, was used and brain activities during resting and meditation states were measured by functional magnetic resonance imaging. The results indicated that the clustering coefficients of eight brain regions tended to increase through the meditation. Our results reveal that short-term effects of breath-counting meditation can be explained by network density changes in these eight brain regions.

neuroscience↗

bioRxiv2019

A genetic screen for genes that impact peroxisomes in Drosophila identifies candidate genes for human disease

Peroxisomes are sub-cellular organelles that are essential for proper function of eukaryotic cells. In addition to being the sites of a variety of oxidative reactions, they are crucial regulators of lipid metabolism. Peroxisome loss or dysfunction leads to multisystem diseases in humans that strongly affects the nervous system. In order to uncover previously unidentified genes and mechanisms that impact peroxisomes, we conducted a genetic screen on a collection of lethal mutations on the X chromosome in Drosophila. Using the number, size and morphology of GFP tagged peroxisomes as a readout, we screened for mutations that altered the number and morphology of peroxisomes based on clonal analysis and confocal microscopy. From this screen, we identified 18 genes that cause increases in peroxisome number or altered morphology when mutated. We examined the human homologs of these genes and found that they are involved in a diverse array of cellular processes. Interestingly, the human homologs from the X-chromosome collection are under selective constraint in human populations and are good candidate genes particularly for dominant genetic disease. This in vivo screening approach for peroxisome defects allows identification of novel genes that impact peroxisomes in vivo in a multicellular organism and is a valuable platform to discover genes potentially involved in dominant disease that could affect peroxisomes.

genetics↗

bioRxiv2018

Estimating fish population abundance by integrating quantitative data on environmental DNA and hydrodynamic modelling

We propose a general framework of abundance estimation based on spatially replicated quantitative measurements of environmental DNA in which production, transport, and degradation of DNA are explicitly accounted for. Application to a Japanese jack mackerel (Trachurus japonicus) population in Maizuru Bay revealed that the method gives an estimate of population abundance comparable to that of a quantitative echo sounder method. These findings indicate the ability of environmental DNA to reliably reflect population abundance of aquatic macroorganisms and may o[ff]er a new avenue for population monitoring based on the fast, cost-e[ff]ective, and non-invasive sampling of genetic information.

ecology↗

bioRxiv2018

A theory of centriole duplication based on self-organized spatial pattern formation

In each cell cycle, centrioles are duplicated to produce a single copy of each pre-existing centriole. At the onset of centriole duplication, the master regulator Polo-like kinase 4 (Plk4) undergoes a dynamic change in its spatial pattern on the periphery of the pre-existing centriole, forming a single duplication site. However, the significance and mechanisms of this pattern transition remain largely unknown. Using super-resolution imaging, we found that centriolar Plk4 exhibits periodic discrete patterns resembling pearl necklaces, frequently with single prominent foci. We constructed mathematical models that simulated the pattern formation of Plk4 to gain insight into the discrete ring patterns. The simulations incorporating the self-organization properties of Plk4 successfully generated the experimentally observed patterns. We therefore propose that the self-patterning of Plk4 is crucial for the regulation of centriole duplication. These results, defining the mechanisms of self-organized regulation, provide a fundamental principle for understanding centriole duplication.

cell biology↗

bioRxiv2018

Loss-of-function in IRF2BPL is associated with neurological phenotypes

The Interferon Regulatory Factor 2 Binding Protein Like (IRF2BPL) gene encodes a member of the IRF2BP family of transcriptional regulators. Currently the biological function of this gene is obscure, and the gene has not been associated with a Mendelian disease. Here we describe seven individuals affected with neurological symptoms who carry damaging heterozygous variants in IRF2BPL. Five cases carrying nonsense variants in IRF2BPL resulting in a premature stop codon display severe neurodevelopmental regression, hypotonia, progressive ataxia, seizures, and a lack of coordination. Two additional individuals, both with missense variants, display global developmental delay and seizures and a relatively milder phenotype than those with nonsense alleles. The bioinformatics signature for IRF2BPL based on population genomics is consistent with a gene that is intolerant to variation. We show that the IRF2BPL ortholog in the fruit fly, called pits (protein interacting with Ttk69 and Sin3A), is broadly expressed including the nervous system. Complete loss of pits is lethal early in development, whereas partial knock-down with RNA interference in neurons leads to neurodegeneration, revealing requirement for this gene in proper neuronal function and maintenance. The nonsense variants in IRF2BPL identified in patients behave as severe loss-of-function alleles in this model organism, while ectopic expression of the missense variants leads to a range of phenotypes. Taken together, IRF2BPL and pits are required in the nervous system in humans and flies, and their loss leads to a range of neurological phenotypes in both species.

genetics↗

bioRxiv2018

Self-organization of Plk4 regulates symmetry breaking in centriole duplication.

During centriole duplication, a single daughter centriole is formed near the mother centriole. The mechanism that determines a single duplication site is unknown. Here, we demonstrate that intrinsic self-organization of Plk4 underlies symmetry breaking in centriole duplication. We show that in its nonphosphorylated state, Plk4 preferentially self-assembles via a disordered linker and that this self-assembly is prevented by autophosphorylation. Consistently, the dissociation dynamics of centriolar Plk4 are controlled by autophosphorylation. We further found that autophophorylated Plk4 is localized as a single focus around the mother centriole before procentriole formation, and is subsequently targeted for STIL-HsSAS6 loading. Perturbing Plk4 self-organization affects the asymmetry of centriolar Plk4 distribution and centriole duplication. We propose that the spatial patterning of Plk4 directs a single duplication site per mother centriole.

cell biology↗

bioRxiv2018

Structural diversity across arbuscular mycorrhizal, ectomycorrhizal, and endophytic plant-fungus networks

BackgroundBelow-ground linkage between plant and fungal communities is one of the major drivers of terrestrial ecosystem dynamics. However, we still have limited knowledge of how such plant-fungus associations vary in their community-scale properties depending on fungal functional groups and geographic locations.\n\nMethodsBased on high-throughput sequencing of root-associated fungi in eight forests along the Japanese Archipelago, we performed a comparative analysis of arbuscular mycorrhizal, ectomycorrhizal, and saprotrophic/endophytic associations across a latitudinal gradient from cool-temperate to subtropical regions.\n\nResultsIn most of the plant-fungus networks analyzed, host-symbiont associations were significantly specialized but lacked \"nested\" architecture, which has been commonly reported in plant-pollinator and plant-seed disperser networks. Meanwhile, the structure of arbuscular mycorrhizal networks was differentiated from that of ectomycorrhizal and saprotrophic/endophytic networks, characterized by high connectance. Our data also suggested that geographic factors affected the organization of plant-fungus network structure. For example, the southernmost subtropical site analyzed in this study displayed lower network-level specificity of host-symbiont associations and higher (but still low) nestedness than northern localities.\n\nConclusionsOur comparative analyses suggest that arbuscular mycorrhizal, ectomycorrhizal, and saprotrophic/endophytic plant-fungus associations often lack nested network architecture, while those associations can vary, to some extent, in their community-scale properties along a latitudinal gradient. Overall, this study provides a basis for future studies that will examine how different types of plant-fungus associations collectively structure terrestrial ecosystems.

microbiology↗

bioRxiv2017

Plant-soil feedbacks between arbuscular- and ecto-mycorrhizal communities

Soil microbiomes of adult trees exert species-specific effects on the survival and growth of seedlings1-6, yet empirical evidence that such plant-soil microbiome interaction drives seedling community assembly remains scarce. Here we show that mycorrhizal fungal communities determine seedling community assembly by controlling how resident plant communities alter the growth of newly established seedlings. We reciprocally introduced seedling communities of arbuscular-and ecto-mycorrhizal plant species to replicated mesocosms to follow the effects of mycorrhizal type match/mismatch with resident plant communities on seedling growth rates. The growth rates of recruited seedlings were generally higher under resident trees of the same mycorrhizal types than under those of different mycorrhizal types, generating positive plant-soil feedbacks through mycorrhizal-type matching. Such positive effects of matching were linked with seedlings greater acquisition rates of mycorrhizal symbionts from matched resident plants than from mismatched plants, and such linkage was pronounced for ecto-mycorrhizal plant species. In contrast, under the condition of mycorrhizal-type matching between resident plants and seedlings (i.e., within-mycorrhizal-type comparison), plant-soil feedback effects varied considerably in their sign and strength among resident-seedling species combinations. Consequently, the assembly of a temperate tree seedling community is driven by a combination of species-specific plant-soil feedbacks and the match/mismatch of mycorrhizal type between resident plants and seedlings.

ecology↗

bioRxiv2017

A systems approach to the characterization and classification of T-cell responses

Types of T-cell responses are categorized on the basis of a limited number of molecular markers selected using a priori knowledge about T-cell immunobiology. We sought to develop a novel systems-based approach for the creation of an unbiased framework enabling assessment of antigenic-peptide specific T-cell responses in vitro. A meta-analysis of transcriptome data from PBMCs stimulated with a wide range of peptides identified patterns of gene regulation that provided an unbiased classification of types of antigen-specific responses. Further analysis yielded new insight about the molecular processes engaged following antigenic stimulation. This led for instance to the identification of transcription factors not previously studied in the context of T-cell differentiation. Taken together this profiling approach can serve as a basis for the unbiased characterization of antigen-specific responses and as a foundation for the development of novel systems-based immune profiling assays.

genomics↗