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Biology subjects

Goda, N.

Publications and source records attributed to Goda, N..

5 recordsLinked to original sources

Left-right asymmetry of the microminipig brain.

Left-right asymmetry of the brain is well recognized in various animals including C. elegans, drosophila and zebrafish. In primates, most of the brain studies describe side of the brain. However, in spite of huge amounts of accumulating rodent studies on neuroscience, most of rodent studies do not distinguish the brain side. The pig brain is considered to occupy an intermediate position between primates and rodents in terms of structural complexity and brain function. Moreover, the numbers of studies using genetic manipulation of pigs are drastically increasing. So, we investigated microminipig (MMP) brain mesoscopic anatomy focusing on left-right differences of its morphology. Here, we show the anterior cingulate cortex, perirhinal cortex, and cerebellum of male and female MMPs, are structurally asymmetrical. The cerebellar vermis, paravermis is tilted from the midline and the consequently the cerebellar cortex exhibits asymmetrical morphology. The anterior cingulate gurus exhibited protrusion and invagination toward the midline on the right and left side, respectively. The left perirhinal lobe exhibited distinct patterns of cortical gyration between left and right side. These data demonstrate that MMPs are one of the suitable model animals for investigating cerebral and cerebellar asymmetry.

neuroscience↗

Epithelial cells induce the polar migration via the MHC-I-AltR interaction to eliminate transformed cells

In epithelial tissues, adjacent normal cells recognize and eliminate transformed cells, maintaining tissue homeostasis. We have demonstrated that the interaction between MHC-I (Major Histocompatibility Complex Class I) on transformed cells and the receptor AltR (Suboptimal Alteration Recognizing Protein) on the normal epithelial cell plays a central role in triggering the elimination ability within normal cells. Moreover, previous reports have suggested that the collective movement of surrounding normal cells including "non-adjacent peripheral normal cells" which are located further out from transformed cells also contributes to the elimination of transformed cells. However, how the direct interaction mediated by MHC-I-AltR affects the behavior of these peripheral normal cells remained unclear. In this study, we aimed to analyze the relationship between the collective movement of normal cells and the elimination of transformed cells. To achieve this, we visualized the two-dimensional movement of individual epithelial cells using the PIV (Particle Image Velocimetry) analysis and quantified the behavior of transformed cells and surrounding normal cells as vectors composed of speed and direction. As a result, we observed that a subset of normal cells near the transformed cells exhibited the unidirectional migration toward the transformed cells (polar migration), which ultimately led to their elimination. Furthermore, this polar migration was suggested to be induced by the MHC-I-AltR interaction. Additional analyses suggest that MHC-I-stimulated AltR induces Ca2+ signaling between normal cells, which in turn triggers the polar migration. Based on these findings, we conclude that the core molecules involved in transformed recognition, MHC-I and AltR, not only trigger the elimination ability in adjacent normal cells but also regulate the behavior of non-adjacent peripheral normal cells, contributing to the elimination of transformed cells.

molecular biology↗

GRable version 1.0: A software tool for site-specific glycoform analysis using the improved Glyco-RIDGE method with parallel clustering and MS2 information

High-throughput intact glycopeptide analysis is crucial for elucidating the physiological and pathological status of the glycans attached to each glycoprotein. Mass spectrometry-based glycoproteomic methods are challenging because of the diversity and heterogeneity of glycan structures. Therefore, we have developed an MS1-based site-specific glycoform analysis method named "Glycan heterogeneity-based Relational IDentification of Glycopeptide signals on Elution profile (Glyco-RIDGE)" for a more comprehensive analysis. This method detects glycopeptide signals as a cluster based on the mass and chromatographic properties of glycopeptides and then searches for each combination of core peptides and glycan compositions by matching their mass and retention time differences. Here we developed a novel browser-based software named GRable for semi-automated Glyco-RIDGE analysis with significant improvements in glycopeptide detection algorithms, including "parallel clustering." This unique function improved the comprehensiveness of glycopeptide detection and allowed the analysis to focus on specific glycan structures, such as pauci-mannose. The other notable improvement is evaluating the "confidence level" of the GRable results, especially using MS2 information. This function facilitated reduced misassignment of the core peptide and glycan composition and improved the interpretation of the results. Additional improved points are: "correction function" for accurate monoisotopic peak picking; one-to-one correspondence of clusters and core peptides even for multiply sialylated glycopeptides; and "inter-cluster analysis" function for understanding the reason for detected but unmatched clusters. The significance of these improvements was demonstrated using purified and crude glycoprotein samples, showing that GRable allowed site-specific glycoform analysis of intact sialylated glycoproteins on a large scale and in depth. Therefore, this software will help to analyze the status and changes in glycans to obtain biological and clinical insights into protein glycosylation by complementing the comprehensiveness of MS2-based glycoproteomics. GRable can run freely online using a web browser via the GlyCosmos Portal (https://glycosmos.org/grable). Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=105 SRC="FIGDIR/small/564073v2_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@12ae798org.highwire.dtl.DTLVardef@1cac352org.highwire.dtl.DTLVardef@dd6b92org.highwire.dtl.DTLVardef@c16ddf_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

Context-Dependent Modification of PFKFB3 in Hematopoietic Stem Cells Promotes Anaerobic Glycolysis and Ensures Stress Hematopoiesis

Metabolic pathways are plastic and rapidly change in response to stress or perturbation. Current metabolic profiling techniques require lysis of many cells, complicating the tracking of metabolic changes over time after stress in rare cells such as hematopoietic stem cells (HSCs). Here, we aimed to identify the key metabolic enzymes that define differences in glycolytic metabolism between steady-state and stress conditions in HSCs and elucidate their regulatory mechanisms. Through quantitative 13C metabolic flux analysis of glucose metabolism using high-sensitivity glucose tracing and mathematical modeling, we found that HSCs activate the glycolytic rate-limiting enzyme phosphofructokinase (PFK) during proliferation and oxidative phosphorylation (OXPHOS) inhibition. Real-time measurement of adenosine triphosphate (ATP) levels in single HSCs demonstrated that proliferative stress or OXPHOS inhibition led to accelerated glycolysis via increased activity of PFKFB3, the enzyme regulating an allosteric PFK activator, within seconds to meet ATP requirements. Furthermore, varying stresses differentially activated PFKFB3 via PRMT1-dependent methylation during proliferative stress and via AMPK-dependent phosphorylation during OXPHOS inhibition. Overexpression of Pfkfb3 induced HSC proliferation and promoted differentiated cell production, whereas inhibition or loss of Pfkfb3 suppressed them. This study reveals the flexible and multilayered regulation of HSC glycolytic metabolism to sustain hematopoiesis under stress and provides techniques to better understand the physiological metabolism of rare hematopoietic cells. Key PointsO_LICombined isotope tracing, mathematical modeling, and single cell ATP analysis enable high-resolution evaluation of blood cell metabolism. C_LIO_LIUnder stress, HSCs quickly accelerate glycolysis to meet ATP demands and maintain hematopoiesis via context-dependent PFKFB3 activation. C_LI

cell biology↗

Development of a new 3D tracking system for multiple marmosets under free-moving conditions

Assessment of social interactions and behavioral changes in nonhuman primates is useful for understanding brain function changes during life events and pathogenesis of neurological diseases. The common marmoset (Callithrix jacchus), that lives in a nuclear family like humans, is a useful model, but long-term automated behavioral observation of multiple animals has not been achieved. Here, we developed a Full Monitoring and Animal Identification (FulMAI) system for long-term detection of three-dimensional (3D) trajectories of each individual in multiple marmosets under free-moving conditions by combining video tracking, Light Detection And Ranging, and deep learning. Using this system, identification of each animal was more than 97% accurate. Location preferences and inter-individual distance could be calculated, and deep learning could detect grooming behavior. The FulMAI system allows us to analyze the natural behavior of individuals in a family over their lifetime and understand how behavior changes due to life events together with other data.

animal behavior and cognition↗