Biology subjects

Ichinose, T.

Publications and source records attributed to Ichinose, T..

8 recordsLinked to original sources

bioRxiv2025

Mouse pulmonary pathological characteristics induced by Asian-mineral dust transported with Coniothyrium fuckelii at a high altitude of 2,000 meters

Asian sand dust (ASD) events are known to transport not only mineral particles but also bioaerosols such as fungi across East Asia, posing complex respiratory health risks. Previously, we isolated Coniothyrium fuckelii (Strain Con-15H316)--a dematiaceous phytopathogenic fungus--from the ASD samples collected at an altitude of 2000 m over the Noto Peninsula, Japan. While Con-15H316 elicited potent immunological responses in our earlier cytokine-focused studies, its histopathological impact on mammalian lungs remained uncharacterized. Here, we re-evaluated formalin-fixed murine lung tissues from mice intratracheally administered heat-treated ASD (H-ASD: only mineral particles), Con-15H316, and Con-15H316 in combination with H-ASD. H-ASD alone induced macrophage-dominant alveolar granulomas, and Con-15H316 alone triggered peribronchiolitis with eosinophilic infiltration. Strikingly, co-exposure resulted in a qualitatively distinct and synergistically worsened phenotype, featuring neutrophil-rich suppurative alveolar pneumonia, granulomas, and peribronchiolitis. Bronchoalveolar lavage fluid (BALF) analysis revealed marked co-elevation of lactate dehydrogenase (LDH) and CCL2 (C-C motif chemokine 2, also known as monocyte chemoattractant protein-1, MCP-1), suggesting concurrent tissue injury and monocyte-driven immune activation. To elucidate the cellular origin of the CCL2 protein, we reanalyzed two publicly available single-cell RNA-seq datasets, identifying monocytes and interstitial macrophages as the dominant Ccl2-expressing populations in microbially injured lungs. Although C. fuckelii has been recognized generally as a plant pathogen, this study exhibited the first histological evidence of the potential of this fungus to induce or exacerbate mammalian lung injury, especially in combination with mineral dust. Our findings uncover a novel, non-allergic alveolar injury phenotype associated with microbial-particulate co-exposure, expanding current toxicological paradigms beyond pathologies associated with excessive immune reactions to inhaled particulates and bioaerosols.

pathology↗

bioRxiv2025

Rod photoreceptors control the ON vs OFF polarity of cone-signaling neurons

A fundamental feature of the visual system is its ability to detect image contrast. The contrast processing starts in the first synapse of the retina where parallel pathways are established to compute contrast to bright (ON pathway) and dark (OFF pathway) objects, separately transferred to morphologically identified ON and OFF cells throughout the visual system. Here, we found that response polarity in ON and OFF neurons is not fixed but rather switches dynamically to the opposite sign. The switch was not observed in rod-knockout mice, indicating that rods generate the polarity switch. We determined that neither horizontal cells nor rod-signaling pathways were responsible for the switch. Instead, we discovered that EAAT5 glutamate transporters located at photoreceptor terminals were required to produce the polarity switch. Our findings provide a new perspective on the adaptive properties of neural networks and their ability to encode contrast across the visual dynamic range.

neuroscience↗

bioRxiv2025

A characterization of mouse retinal ganglion cell types labeled with AAV tools

The mouse retina is made-up of approximately 150 types of neurons each with unique characteristics and functions in interpreting visual information. Recent efforts to categorize cell types using molecular markers, morphology, and electrophysiological response properties have provided a wealth of information and a host of tools for studying specific cell types. AAV-based approaches have several advantages over transgenic mouse lines, including ease of application to many different animal models without extensive crossing and their amenability to intersectional approaches. Here, we provide an in-depth characterization of retinal ganglion cell types labeled by two AAV vectors drawn from a recent panel of constructs with synthetic promoters. Each promoter analyzed here was derived from a gene expressed in a cell type specific manner. Using a combination of morphology, molecular markers, and electrophysiological measurement of light responses, we found that each vector labeled distinct subsets of RGCs. However, both labeled more cell types than expected from the expression pattern of the promoters endogenous gene. We then characterized the projection patterns of these RGC types to the brain, finding that each AAV type labeled distinct axonal populations. These tools provide new access to a unique subset of cells and will be instrumental to future studies analyzing their functions and connectivity.

neuroscience↗

bioRxiv2025

Chameau (HBO1) regulates starvation in a temperature-dependent manner in Drosophila melanogaster

The body temperature of Drosophila melanogaster depends on the extrinsic temperature. Numerous studies in fruit flies have shown that environmental temperature has an effect on metabolism, lifespan and starvation resilience. We have previously shown that Chameau (Chm), a MYST-domain acetyltransferase, promotes aging but also increases starvation resilience. As starvation resilience is highly temperature dependent, we explored the effect of temperature on starvation resilience in fruit flies with reduced chm expression. Strikingly, we found that an increase of 2{degrees}C was sufficient to restore starvation resilience in chm mutants. The increase in temperature rescued the dampened expression of genes involved in insulin, hormone and starvation response as well as a reduced rate of weight loss and misregulation of trehalose, which we observed in chm mutants at 23{degrees}C. Our data show that whereas Chm has an important role in regulating starvation at 23{degrees}C and below, it becomes obsolete at higher temperatures. Our finding that a gene plays an important role only under specific environmental conditions has important implications in light of the recent global change of climate conditions.

molecular biology↗

bioRxiv2024

Blue light toxicity drives the gut microbiota-mediated lipid accumulation in Drosophila

Human agriculture has always raced against insect adaptation, requiring updated pest control methods and knowledge of evolutionary processes. Excessive exposure to blue light (BL) kills a wide range of insect species and has attracted attention as an alternative to chemical pesticides. Here, to understand how insects adapt to BL toxicity, we investigated evolutionary responses to BL toxicity in Drosophila melanogaster over 70 generations using laboratory selection experiments. The selected line exhibited an obese phenotype accompanied by midgut elongation, with BL tolerance dependent on gut microbiota- mediated lipid accumulation. Whole-genome and transcriptome analyses consistently highlighted interactions between the microbiota and host lipid metabolism-related genes. Remarkably, manipulating genes associated with lipid accumulation conferred BL tolerance even in the absence of selection. We suggest that the acquisition of BL tolerance occurs through adaptive obesity. Our study introduces a mechanism of evolutionary adaptation of insects against BL-based selective pressure by maximising the benefits from the gut microbiota via midgut elongation. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=141 SRC="FIGDIR/small/608892v5_ufig1.gif" ALT="Figure 1"> View larger version (62K): org.highwire.dtl.DTLVardef@111c9d5org.highwire.dtl.DTLVardef@d9bf7forg.highwire.dtl.DTLVardef@1ab46fborg.highwire.dtl.DTLVardef@1c111cd_HPS_FORMAT_FIGEXP M_FIG C_FIG Brief summaryLaboratory selection for tolerance to blue light toxicity in Drosophila revealed that gut microbiota-mediated obesity, marked by midgut elongation and increased beneficial bacteria, is a key evolutionary adaptation.

evolutionary biology↗

bioRxiv2024

ZIP13 regulates lipid metabolism by changing intracellular iron and zinc balance

Metabolic diseases are caused by a prolonged energy imbalance, and adipose tissue is known to be the main contributor. We previously reported that ZIP13, an Slc39a transporter whose deficiency causes Ehlers-Danlos syndrome spondylocheirodysplastic type 3 associated with lipoatrophy, inhibits the adipocyte browning pathway by modulating intracellular zinc status. The precise mechanisms of how ZIP13 regulates the homeostasis of adipose tissue remain unclear and therefore, we investigated the role of ZIP13 in mature adipocytes using adipocyte-specific Zip13-deficient mice. We herein demonstrate that these mice show accelerated lipolysis and reduced respiratory exchange ratio. In addition, abundance of iron and zinc balance were altered during differentiation in normal adipocytes, whereas iron distribution was substantially affected in Zip13-deficient adipocytes, which downregulated PDE activity and enhanced {beta}-adrenergic receptor signaling pathways. Importantly, we confirmed that ZIP13 could transport both zinc and iron, using the Xenopus oocyte transport system and in silico structural dynamics simulations, and that the defect in iron distribution perturbs proper lipolysis. Together, these results illustrate that ZIP13 acts as a key regulator for lipolysis in adipocytes via the proper use of metals, and that the ZIP13-iron axis plays an important role in regulation of lipid metabolism.

cell biology↗

bioRxiv2024

Melanopsin ganglion cells in the mouse retina independently evoke pupillary light reflex

PurposeThe pupillary light reflex (PLR) is crucial for protecting the retina from bright light. The intrinsic photosensitive ganglion cells (ipRGCs) in the retina mediate the PLR, which directly sense light and receive inputs from rod/cone photoreceptors. Previous work used genetic knockout mice to reveal that rod/cone photoreceptors drive transient constriction, and ipRGCs drive the sustained component. We acutely ablated photoreceptors by a chemical injection to examine the role of rod and cone photoreceptors in PLR. MethodsPLR and the multiple electrode array (MEA) recording were conducted with C57BL6/J (wildtype: WT) and Cnga3-/-; Gnat1-/- (rod/cone dysfunctional) mice. n-Nitroso-n-methylurea (MNU) was applied to C57 mice by intraperitoneal injection, and PLR was conducted after 5-7 days of injection. Three different light levels (mesopic, low photopic, and high photopic) were tested. Immunohistochemistry was conducted using the anti-Gnat1 and anti-melanopsin antibodies with DAPI. ResultsPLR was induced by all light levels we tested, and the level of constriction increased as the light level increased. After the MNU injection, PLR was not induced at mesopic light stimulus, but was fully induced by high light. The level of PLR was identical between WT and MNU mice, suggesting that ipRGCs fully contributed to the PLR at this light level. Immunohistochemistry revealed that photoreceptors were ablated by the MNU injection, but ipRGCs were preserved. The MEA recording revealed that a population of ipRGCs generated fast and robust spikes in MNU-injected retinal tissues in ex vivo. ConclusionsContrary to previous observations, our results demonstrate that ipRGCs are the major contributor to the PLR induced by high light.

neuroscience↗

bioRxiv2023

Translational regulation enhances distinction of cell types in the nervous system

Multicellular organisms are composed of specialized cell types with distinct proteomes. While recent advances in single-cell transcriptome analyses have revealed differential expression of mRNAs, cellular diversity in translational profiles remains underinvestigated. By performing RNA-seq and Ribo-seq in genetically-defined cells in the Drosophila brain, we here revealed substantial posttranscriptional regulations that augment the cell-type distinctions at the level of protein expression. Specifically, we found that translational efficiency of proteins fundamental to neuronal functions, such as ion channels and neurotransmitter receptors, was maintained low in glia, leading to their preferential translation in neurons. Notably, distribution of ribosome footprints on these mRNAs exhibited a remarkable bias towards the 5' leaders in glia. Using transgenic reporter strains, we provide evidence that the small upstream open reading frames (uORFs) in the 5 leader confer selective translational suppression in glia. Overall, these findings underscore the profound impact of translational regulation in shaping the proteomics for cell-type distinction and provide new insights into the molecular mechanisms driving cell-type diversity.

neuroscience↗