Biology subjects

Arakawa, Y.

Publications and source records attributed to Arakawa, Y..

7 recordsLinked to original sources

bioRxiv2026

Multidimensional semantic representations emerge from multi-frequency representational similarity learning

Current theories of semantic representation are agnostic about how fine-grained neurophysiological activity corresponds to representation of multidimensional semantic information. By applying an innovative multivariate technique (representational similarity learning; RSL), we adjudicated three hypotheses: (1) that multidimensional semantic structure is represented within a single frequency range (e.g., gamma/high gamma); (2) that each semantic dimension is independently represented within a different frequency range; and (3) that multidimensional semantic information is "transfrequency" (at least some information emerges only when multiple frequencies are considered together). RSL was applied to time-frequency power and phase data extracted from electrocorticography (ECoG) grid electrodes on the surface of human ventral anterior temporal lobe (vATL). We found significant decoding of graded, multidimensional semantic information from a wide range of frequencies (4 - 200 Hz), but not from individual frequency bands, providing clear evidence that multidimensional semantic information is coded in a transfrequency fashion.

neuroscience↗

bioRxiv2026

Density-Dependent Rearrangement of Desmoplakin in Epithelial Junctions: Insights from Expansion Microscopy

Desmosomes mechanically couple neighboring epithelial cells to the intermediate filament cytoskeleton. However, how the nanoscale organization changes with epithelial cell density remains incompletely understood. Here, we used expansion microscopy (ExM) to examine Madin-Darby canine kidney epithelial monolayers. ExM revealed density-associated differences in the relative apicobasal organization of epithelial junctions, with increased separation between occludin-positive tight junctions and desmoglein 2-positive desmosomes in confluent monolayers. A comparison of subconfluent and confluent cultures revealed a density-associated reorganization of desmoplakin (DSP) within opposing desmosomal plaques, with a more pronounced change in C-terminal spacing than in N-terminal spacing. Independent STED analysis of non-expanded samples confirmed the density-associated increase in DSP C-terminal spacing. In keratin filament-deficient cells, this spacing was elevated in subconfluent cultures and did not increase with cell density. Pharmacological inhibition of myosin II or ROCK reduced this elevated spacing, indicating that keratin loss-associated reorganization of DSP is sensitive to actomyosin contractility. These findings show that epithelial cell density is associated with the remodeling of epithelial junction organization and DSP plaque architecture, demonstrating the utility of ExM for quantitative analysis of junctional architecture.

cell biology↗

bioRxiv2026

Schlafen 11 (SLFN11) overexpression and nucleolar localization in response to bortezomib in multiple myeloma

Proteins belonging to the Schlafen family are interferon-inducible and participate in the regulation of antiviral responses, immune signaling and proteotoxic stress. SLFN11 also kills cells with replicative damage, serving as a predictive biomarker for chemotherapeutic response. Here we examined SLFN11 expression and significance in multiple myeloma (MM). The TCGA and MMRF CoMMpass datasets were analyzed for SLFN11 expression. Bone marrow and cell lines samples were analyzed for SLFN11 protein. SLFN11-knockout MM cell lines were used to explore how SLFN11 affects bortezomib response. Retrospective analysis of the HOVON-65/GMMG-HD4 phase III trial (n=327) assessed clinical relevance. SLFN11 is consistently highly expressed across MM subtypes (except CD1 and MAF/MAFB) and in normal plasma cells, and its expression strongly correlates with super-enhancer-driven plasma cell transcriptional programs. CD138-positive normal and myeloma plasma cells retain SLFN11 expression even when proliferative activity (MKI67/Ki-67) increases with disease progression. Bortezomib, a first-line MM treatment, induces SLFN11 nucleolar translocation with suppression of ribosomal RNA synthesis. Knocking out SLFN11 in MM cells enhances bortezomib sensitivity and exatecan resistance, supporting SLFN11s protective role in proteotoxic stress and sensitizing role in replication stress. In the HOVON-65/GMMG-HD4 trial, SLFN11-low patients showed selective benefit from bortezomib-based therapy, suggesting that SLFN11 expression may guide therapeutic stratification in MM. SignificanceSLFN11 is highly expressed in normal and malignant plasma cells. Bortezomib induces SLFN11 nucleolar translocation, suppressing ribosomal RNA synthesis and global translation. SLFN11 confers bortezomib resistance while sensitizing to topoisomerase I inhibitors. Clinical analysis supports that low SLFN11 expression predicts bortezomib benefit, providing a mechanistic basis for SLFN11-guided therapeutic stratification.

cancer biology↗

bioRxiv2025

Lamin A/C Deficiency Drives Genomic Instability and Poor Survival in Small-Cell Lung Cancer through Increased R-loop Accumulation

Lamin A/C (LMNA), a key component of the nuclear envelope, is essential for maintaining nuclear integrity and genome organization [1]. While LMNA dysregulation has been implicated in genomic instability across cancer and aging, the underlying mechanisms remain poorly understood [2]. Here, we investigate LMNAs role in small-cell lung cancer (SCLC), a highly aggressive malignancy characterized by extreme genomic instability [3, 4]. We demonstrate that LMNA depletion promotes R-loop accumulation, transcription-replication conflicts, replication stress, DNA breaks, and micronuclei formation. Mechanistically, LMNA loss disrupts nuclear pore complex distribution, reducing phenylalanine-glycine (FG)-nucleoporin incorporation and impairing RNA export efficiency. Furthermore, we show that LMNA expression is epigenetically repressed by EZH2 during SCLC differentiation from neuroendocrine (NE) to non-NE states. Clinically, low LMNA levels correlate with significantly worse survival in SCLC patients. These findings uncover a novel role for LMNA in safeguarding genome integrity and shaping tumor heterogeneity, with broad implications for cancer and aging. Significance StatementLamin A/C, a key structural component of the nuclear envelope, is frequently lost or mutated in cancer, laminopathies, and aging-related disorders. Lamin A/C loss is associated with genomic instability, but the underlying mechanisms remain incompletely understood. We demonstrate that LMNA loss drives genomic instability by promoting R-loop accumulation through disrupted nuclear pore dynamics and impaired RNA export. These findings reveal a previously unrecognized link between LMNA loss, nuclear envelope dysfunction, and genome instability. Targeting this pathway could help mitigate genomic instability in aging and laminopathies, while leveraging R-loop accumulation may enhance the efficacy of DNA-damaging therapies in cancer.

cancer biology↗

bioRxiv2025

All spectral frequencies of neural activity reveal semantic representation in the human anterior ventral temporal cortex

Intracranial electrophysiology offers a unique insight into the nature of information representation in the brain - it can be used to disentangle information encoded in local neuronal activity (gamma and high gamma frequencies) from information encoded via long-range interactions (lower frequencies). We used regularised logistic regression to decode animacy from time-frequency power and phase extracted from electrocorticography (ECoG) grid electrode data recorded on the surface of human vATL. Power in gamma (30 - 60 Hz) and high gamma (60 - 200 Hz) produced reliable decoding, indicating that semantic information is indeed expressed by local populations in vATL. However, power from a wide range of frequencies (4 - 200 Hz) produced significantly higher decoding accuracy and also exhibited the same rapidly-changing dynamic code previously observed when decoding voltage. These findings support the theory that semantic information is encoded by a local vATL "hub" that interacts with distributed cortical "spokes".

neuroscience↗

bioRxiv2021

Dissecting the clonality of I1 plasmids using ORF-based binarized structure network analysis of plasmids (OSNAp)

Phylogenetic relationship of 97 I1 plasmids harboring blaCTX-M genes encoding extended-spectrum beta-lactamase (ESBL) was analyzed using the ORF-based binarized structure network analysis of plasmids (OSNAp). The majority of plasmids carrying blaCTX-M-1 or blaCTX-M-8, ESBL genes primarily associated with domestic animals, were clonal. On the other hand, plasmids carrying blaCTX-M-14 or blaCTX-M-15, identified from both humans and domestic animals, were diverse in their contents. The findings suggest that circulation of I1 plasmids among humans and animals may contribute to their diversity.

microbiology↗

bioRxiv2019

Connectivity Gradient in the Human Left Inferior Frontal Gyrus: Intraoperative Cortico-Cortical Evoked Potential Study

In the dual-stream model of language processing, the exact connectivity of the ventral stream to the anterior temporal lobe remains elusive. To investigate the connectivity among the inferior frontal gyrus (IFG) and the lateral part of the temporal and parietal lobes, we integrated spatiotemporal profiles of cortico-cortical evoked potentials (CCEPs) recorded intraoperatively from 14 patients who had had resective surgeries for brain tumor or epileptic focus. The 4D visualization of the combined CCEP data showed that the pars opercularis (Brocas area) connected to the posterior temporal cortices and the supramarginal gyrus, while the pars orbitalis connected to the anterior lateral temporal cortices and the angular gyrus. Quantitative topographical analysis of CCEP connectivity confirmed an anterior-posterior gradient of connectivity from IFG stimulus sites to the temporal response sites. Reciprocality analysis indicated that the anterior part of the IFG is bi-directionally connected to the temporal or parietal area. The present study revealed that each IFG subdivision has a different connectivity to the temporal lobe with an anterior-posterior gradient and supports the classical connectivity concept of Dejerine that the frontal lobe is connected to the temporal lobe through the arcuate fasciculus and also a double-fan-shaped structure, anchored at the limen insulae.

neuroscience↗