Biology subjects

Suzuki, S.

Publications and source records attributed to Suzuki, S..

78 records · Page 5Linked to original sources

bioRxiv2019

Plastidial (p)ppGpp synthesis by the Ca2+-dependent RelA-SpoT homolog regulates the adaptation of chloroplast gene expression to darkness in Arabidopsis

In bacteria, the hyper-phosphorylated nucleotides, guanosine 5-diphosphate 3-diphosphate (ppGpp) and guanosine 5-triphosphate 3-diphosphate (pppGpp), function as secondary messengers in the regulation of various metabolic processes of the cell, including transcription, translation, and enzymatic activities, especially under nutrient deficiency. The activity carried out by these nucleotide messengers is known as the stringent response. (p)ppGpp levels are controlled by two distinct enzymes, namely, RelA and SpoT, in Escherichia coli. RelA-SpoT homologs (RSHs) are also conserved in plants and algae where they function in the plastids. The model plant Arabidopsis thaliana contains four RSHs: RSH1, RSH2, RSH3, and Ca2+-dependent RSH (CRSH). Genetic characterizations of RSH1, RSH2, and RSH3 were undertaken, which showed that the (p)ppGpp-dependent plastidial stringent response significantly influences plant growth and stress acclimation. However, the physiological significance of CRSH-dependent (p)ppGpp synthesis remains unclear, as no crsh-null mutant has been available. Here to investigate the function of CRSH, a crsh-knockout mutant of Arabidopsis was constructed using a site-specific gene-editing technique, and its phenotype was characterized. A transient increase of ppGpp was observed for 30 min in the wild type (WT) after light-to-dark transition, but this increase was not observed in the crsh mutant. Similar analyzes were performed with the rsh2rsh3 double and rsh1rsh2rsh3 triple mutants of Arabidopsis and showed that the transient increments of ppGpp in the mutants were higher than those in the WT. The increase of (p)ppGpp in the WT and rsh2rsh3 accompanied decrements in the mRNA levels of psbD transcribed by the plastid-encoded plastid RNA polymerase. These results indicated that the transient increase of intracellular ppGpp at night is due to CRSH-dependent ppGpp synthesis and the (p)ppGpp level is maintained by the hydrolytic activities of RSH1, RSH2, and RSH3 to accustom plastidial gene expression to darkness.

plant biology↗

bioRxiv2019

Exploration-related strategy mediates negative coupling between decision-making performance and psychiatric symptoms

Various psychiatric symptoms are often accompanied by impairments in decision-making. Given the high comorbidity of psychiatric disorders, symptoms that specifically couple with the impairment remain unidentified. The computations involved in decision-making that mediate the coupling are also elusive. Here, we conducted an online experiment with healthy individuals (n=939), participating in a decision-making task and completing questionnaires about psychiatric symptoms. The questionnaire data identified two dimensions underlying various symptoms: the first is mainly associated with obsessive-compulsive traits whereas the second is associated with depression and anxiety. Furthermore, by model-based analysis, we found only the first dimension was negatively correlated with the overall performance of the decision-making task, and the negative correlation was mediated by choice stochasticity (random exploration) and propensity to choose options previously unchosen. Given that the preference for previously unchosen options can reflect uncertainty-driven exploration, our findings highlight a key role of exploration-related strategies in psychiatric deficits of decision-making.

neuroscience↗

bioRxiv2019

Neural, functional, and aesthetic impacts of spatially heterogeneous flicker: A potential role of natural flicker

Spatially heterogeneous flicker, characterized by probabilistic and locally independent luminance modulations, abounds in nature. It is generated by flames, water surfaces, rustling leaves, and so on, and it is pleasant to the senses. It affords spatiotemporal multistability that allows sensory activation conforming to the biases of the visual system, thereby generating the perception of spontaneous motion and likely facilitating the calibration of motion detectors. One may thus hypothesize that spatially heterogeneous flicker might potentially provide restoring stimuli to the visual system that engage fluent (requiring minimal top-down control) and self-calibrating processes. Here, we present some converging behavioral and electrophysiological evidence consistent with this idea. Spatially heterogeneous (multistable) flicker (relative to controls matched in temporal statistics) reduced posterior EEG (electroencephalography) beta power implicated in long-range neural interactions that impose top-down influences on sensory processing. Further, the degree of spatiotemporal multistability, the amount of posterior beta-power reduction, and the aesthetic responses to flicker were closely associated. These results are consistent with the idea that the pleasantness of natural flicker may derive from its spatiotemporal multistability that affords fluent and self-calibrating visual processing.

neuroscience↗

bioRxiv2019

Nuclear RNA export factor variant initiates piRNA-guided co-transcriptional silencing

The PIWI-interacting RNA (piRNA) pathway preserves genomic integrity by repressing transposable elements (TEs) in animal germ cells. Among PIWI-clade proteins in Drosophila, Piwi transcriptionally silences its targets through interactions with cofactors, including Panoramix (Panx) and forms heterochromatin characterized by H3K9me3 and H1. Here, we identified Nxf2, a nuclear RNA export factor (NXF) variant, as a protein that forms complexes with Piwi, Panx, and p15. Panx-Nxf2-p15 complex formation is necessary in the silencing by stabilizing protein levels of Nxf2 and Panx. Notably, ectopic targeting of Nxf2 initiates co-transcriptional repression of the target reporter in a manner independent of H3K9me3 marks or H1. However, continuous silencing requires HP1a and H1. In addition, Nxf2 directly interacts with target TE transcripts in a Piwi-dependent manner. These findings suggest a model in which the Nxf2-Panx-p15 complex enforces the association of Piwi with target transcripts to trigger co-transcriptional repression, prior to heterochromatin formation in the nuclear piRNA pathway.\n\nHighlightsO_LINxf2 plays an essential role in the Piwi-piRNA pathway\nC_LIO_LIFormation of Piwi-Panx-Nxf2-p15 (PPNP) complexes stabilizes both Panx and Nxf2\nC_LIO_LIThe PPNP complex triggers transcriptional silencing before heterochromatin formation\nC_LIO_LINxf2 directly binds to target transcripts in a Piwi-dependent manner\nC_LI

molecular biology↗

bioRxiv2018

Alopecia areata susceptibility variant identified by MHC risk haplotype sequencing reproduces symptomatic patched hair loss in mice

BackgroundAlopecia areata (AA) is a highly heritable multifactorial and complex disease. However, no convincing susceptibility gene has yet been pinpointed in the major histocompatibility complex (MHC), a region in the human genome known to be associated with AA as compared to other regions.\n\nResultsBy sequencing MHC risk haplotypes, we identified a variant (rs142986308, p.Arg587Trp) in the coiled-coil alpha-helical rod protein 1 (CCHCR1) gene as the only non-synonymous variant in the AA risk haplotype. Using CRISPR/Cas9 for allele-specific genome editing, we then phenocopied AA symptomatic patched hair loss in mice engineered to carry the Cchcr1 risk allele. Skin biopsies of these alopecic mice showed strong up-regulation of hair-related genes, including hair keratin and keratin-associated proteins (KRTAPs). Using transcriptomics findings, we further identified CCHCR1 as a novel component of hair shafts and cuticles in areas where the engineered alopecic mice displayed fragile and impaired hair.\n\nConclusionsThese results suggest an alternative mechanism for the aetiology of AA based on aberrant keratinization, in addition to generally well-known autoimmune events.

genomics↗

bioRxiv2017

High-Throughput Laboratory Evolution Of Escherichia coli Under Multiple Stress Environments

Bacterial cells have a remarkable capacity to adapt and to evolve to environmental changes. Although many mutations contributing to adaptive evolution have been identified, the relationship between the mutations and the phenotypic changes responsible for fitness gain has yet to be fully elucidated. For a better understanding of phenotype-genotype relationship in evolutionary dynamics, we performed high-throughput laboratory evolution of Escherichia coli under various stress conditions using an automated culture system. One measure of phenotype, transcriptome analysis, revealed that the expression changes which occurred during the evolution were generally similar among the strains evolved in the same stress environment. We also found several genes and gene functions for which mutations were commonly fixed in the strains resistant to the same stress, and whose effects on resistance were verified experimentally. We demonstrated that the integration of transcriptome and genome data enables us to extract the mechanisms for stress resistance.\n\nAuthor summaryUnderstanding the relationship between phenotypic and genetic changes is a fundamental goal in evolutionary biology, which can provide insights into the past and future evolutionary trajectories. Evolution of microorganisms in a laboratory has been the primary approach to clarify the mappings of phenotypic and genotypic changes. Here, we performed high-throughput laboratory evolution with bacteria using an automated culture system, to quantify phenotypic and genotypic changes occurred under various stress conditions. We identified various stress-specific gene expression changes and mutations, and contributions of them to fitness gain were validated. These results demonstrated that the integration of phenotypic and genotypic changes makes it possible to extract the mechanisms for stress resistance evolution, which will contribute to bioengineering applications.

evolutionary biology↗