Biology subjects

Kawashima, H.

Publications and source records attributed to Kawashima, H..

6 recordsLinked to original sources

bioRxiv2025

Speed-controlled visual stimuli modulate fish collective dynamics

Fish navigation is modulated by visual stimulation and associated parameters, such as size, speed, and orientation, yet the regulatory mechanisms remain unclear. Here, we experimentally investigate how systematically controlled stimulus speed influences the temporal and spatial collective dynamics of Hemigrammus bleheri. Using a simple and customisable top-down projection setup, we displayed clockwise-rotating black-dot patterns at three distinct speeds to simulate complex environmental motion cues. We quantified individual temporal responsiveness through angular movements, and evaluated group-level spatial organisation. Fish angular movements positively tracked the rotation direction of the visual patterns. Lower stimulus speeds elicited predominantly exploratory behaviour, while higher speeds induced a transition to strong motion-tracking behaviour, aligning fish orientation with the rotating patterns. Increasing stimulus speed also corresponded with greater nearest-neighbour distance, indicating reduced spatial cohesion. Notably, we observed transient schooling episodes not aligned with the rotational stimulus, reflecting periods in which internal social interactions outweighed stimulus-driven coordination. Using a newly defined free-schooling index, we show that such internally driven episodes were frequent at lower stimulus speeds but markedly reduced at higher speeds. Overall, these results demonstrate that speed-controlled visual stimuli modulate both individual navigation and group coherence, offering new insights into how visual cues shape fish collective behaviour dynamics.

animal behavior and cognition↗

bioRxiv2022

A detailed landscape of genomic alterations in malignant peripheral nerve sheath tumor cell lines challenges the current MPNST diagnosis

BackgroundMalignant peripheral nerve sheath tumors (MPNSTs) are soft tissue sarcomas that arise from the peripheral nervous system. Half of the tumors develop in the context of the genetic disease Neurofibromatosis type 1 (NF1) and the rest are sporadic sarcomas. MPNSTs have a dismal prognosis due to their aggressiveness and tendency to metastasize, and new treatment options are needed. The diagnosis of MPNSTs can be challenging, especially outside of the NF1 context since specific histological criteria have not been completely established. Genomic analysis may both facilitate differential diagnoses and suggest precision medicine strategies. MethodsWe generated a complete genomic resource of a set of widely used human NF1-related and sporadic MPNST cell lines by applying ploidy analysis, whole genome and whole exome sequencing and SNP-array analysis, complemented by methylome-based classification and immunofluorescence of cell identity markers (SOX9, SOX10, S100B). ResultsNF1 MPNST cell lines faithfully recapitulated the genomic copy number profile of primary MPNSTs. Structural variants were key players in the complete inactivation of most recurrently altered tumor suppressor genes (TSGs) (NF1, CDKN2A, SUZ12/EED), while small variants played a minor role in the NF1 context, both concerning TSG inactivation and due to the absence of gain-of-function mutations. In clear contrast, the sporadic cell lines (STS-26T, HS-Sch-2, HS-PSS) did not recapitulate the copy number profile of primary MPNSTs. They carried different TSG inactivation and exhibited gain-of-function mutations by predicted kinase activation or generation of fusion genes. Mutational frequencies and signatures emerged as promising informative tools for aiding in MPNST differential diagnosis. Due to the multiple genomic differences exhibited, we complemented their characterization using a methylome-based classifier. All NF1-related cell lines were assigned within the MPNST group, while sporadic cell lines clustered either with melanomas or with an uncertain MPNST-like sarcoma group. The staining of cell identity markers reinforced the idea of a potential misdiagnose of the MPNSTs used to derive the sporadic cell lines analyzed. ConclusionsDeep genomic analysis, together with methylome-based sarcoma classification and cell identity marker analysis, challenged the MPNST identity of sporadic cell lines. Results presented here open an opportunity to revise MPNST differential diagnosis and classification.

genomics↗

bioRxiv2021

Cancer malignancy is correlated with up-regulation of PCYT2-mediated glycerol phosphate modification of α-dystroglycan

The dystrophin-glycoprotein complex connects the cytoskeleton with base membrane components such as laminin through unique O-glycans displayed on -dystroglycan (-DG). Genetic impairment of elongation of these glycans causes congenital muscular dystrophies. We previously identified that glycerol phosphate (GroP) can cap the core part of the -DG O-glycans and terminate their further elongation. This study examined the possible roles of the GroP modification in cancer malignancy, focusing on colorectal cancer. We found that the GroP modification critically depends on PCYT2, which serves as CDP-Gro synthase. Furthermore, we identified a significant positive correlation between cancer progression and GroP modification, which also correlated positively with PCYT2 expression. Moreover, we demonstrate that GroP modification promotes the migration of cancer cells. Based on these findings, we propose that the GroP modification by PCYT2 disrupts the glycan-mediated cell adhesion to the extracellular matrix and thereby enhances cancer metastasis. Thus, the present study suggests the possibility of novel approaches for cancer treatment by targeting the PCYT2-mediated GroP modification.

biochemistry↗

bioRxiv2021

Conversion of cancer-associated fibroblasts from pro- to antitumor improves the sensitivity of pancreatic cancer to chemotherapeutics

Previous therapeutic attempts to deplete cancer-associated fibroblasts (CAFs) or inhibit their proliferation in pancreatic ductal adenocarcinoma (PDAC) were not successful in mice or patients. Thus, CAFs may be tumor suppressive or heterogeneous, with distinct cancer-restraining and -promoting CAFs (rCAFs and pCAFs, respectively). Here, we show that induced expression of the glycosylphosphatidylinositol-anchored protein Meflin, a rCAF-specific marker, in CAFs by genetic and pharmacological approaches improved the chemosensitivity of mouse PDAC. A chemical library screen identified Am80, a synthetic, non-natural retinoid, as a reagent that effectively induced Meflin expression in CAFs. Am80 administration improved the sensitivity of PDAC to chemotherapeutics, accompanied by increases in tumor vessel area and intratumoral drug delivery. Mechanistically, Meflin was involved in the suppression of tissue stiffening by interacting with lysyl oxidase to inhibit its collagen crosslinking activity. These data suggested that modulation of CAF heterogeneity may represent a strategy for PDAC treatment.

cancer biology↗

bioRxiv2020

Ribosome profiling in Streptococcus pneumoniae reveals the role of methylation of 23S rRNA nucleotide G748 on ribosome stalling.

2.(1) BackgroundMany nucleotides in 23S rRNA are methylated post-transcriptionally by methyltransferases and cluster around the peptidyltransferase center (PTC) and the nascent peptidyl exit tunnel (NPET) located in 50S subunit of 70S ribosome. Biochemical interactions between a nascent peptide and the tunnel may stall ribosome movement and affect expression levels of the protein. However, no studies have shown a role for NPET on ribosome stalling using an NPET mutant. (2) ResultsA ribosome profiling assay in Streptococcus pneumoniae demonstrates for the first time that an NPET mutant exhibits completely different ribosome occupancy compared to wild-type. We demonstrate, using RNA footprinting, that changes in ribosome occupancy correlate with changes in ribosome stalling. Further, statistical analysis shows that short peptide sequences that cause ribosome stalling are species-specific and evolutionarily selected. NPET structure is required to realize these specie-specific ribosome stalling. (3) ConclusionsResults support the role of NPET on ribosome stalling. NPET structure is required to realize the species-specific and evolutionary conserved ribosome stalling. These findings clarify the role of NPET structure on the translation process.

genomics↗

bioRxiv2020

A molecular map of lymph node blood vascular endothelium at single cell resolution

Blood vascular endothelial cells (BECs) control the immune response by regulating immune cell recruitment, metabolite exchange and blood flow in lymphoid tissues. However, the diversity of BEC and their origins during immune angiogenesis remain poorly understood. Here we profile transcriptomes of BEC from mouse peripheral lymph nodes and map key phenotypes to the vasculature. Our analysis identifies multiple novel subsets including a venous population whose gene signature predicts an unexpectedly selective role in myeloid cell (vs lymphocyte) recruitment to the medulla, confirmed by 2 photon videomicroscopy. We define five phenotypes of capillary lining BEC including a capillary resident regenerative population (CRP) that displays stem cell and migratory gene signatures and contributes to homeostatic BEC turnover and to vascular neogenesis after immunization. Trajectory analyses reveal retention of developmental programs along a progression of cellular phenotypes from CRP to mature venous and arterial BEC subsets. Overall, our single cell atlas provides a molecular blueprint of the lymph node blood vasculature and defines subset specialization for immune cell recruitment and vascular homeostasis.

immunology↗