Biology subjects

Hosokawa, K.

Publications and source records attributed to Hosokawa, K..

6 recordsLinked to original sources

bioRxiv2026

HPV-Associated Tonsillar Intraepithelial Neoplasia and Oral High-Risk HPV mRNA as a Candidate Biomarker

Early detection of human papillomavirus (HPV)-associated oropharyngeal cancer is an unmet need, as its premalignant lesions remain unestablished. We hypothesized that such lesions exist in individuals with oral high-risk HPV (HR-HPV) mRNA. We preoperatively screened 1,180 individuals undergoing tonsillectomy due to benign conditions and detected five with oral HR-HPV mRNA. Serial sectioning of the entire excised tonsils identified HPV-associated intraepithelial lesions in three of these five individuals. A similar lesion was identified in an additional individual with oral HPV16 infection with unknown oral HR-HPV mRNA status. Intraepithelial lesions in two individuals were HPV16-associated and showed moderate-to-severe atypia, whereas those in the other two individuals were associated with other HR-HPV and showed minimal-to-mild atypia. Based on HPV life cycle, the former were classified as transforming lesions and the latter as productive-to-intermediate lesions. Spatial transcriptomic analysis revealed molecular profiles intermediate between those of normal epithelium and HPV-associated oropharyngeal cancer. These findings establish the first evidence for HPV-associated tonsillar premalignant lesions and suggest oral HR-HPV mRNA as a candidate biomarker.

cancer biology↗

bioRxiv2025

Curvature-sensing peptide functions as a membrane interfactant that glues small extracellular vesicles to cell membranes and enhances vesicle cellular uptake

Small extracellular vesicles (sEVs) are lipid nanoparticles secreted from mammalian cells that are involved in the transfer of informational or therapeutically effective substances between cells. Although the scope of research on sEVs as biocompatible carriers for drug delivery to diseased tissues and cells is expanding, several challenges remain, such as low cellular uptake efficiency and difficulty in loading drugs. It is desirable to alleviate the energy barriers associated with the cellular uptake of sEVs and minimize perturbation of sEVs when loading drugs onto them. In this study, we developed a simple drug-loading system for sEVs using a dimeric curvature-sensing peptide, which enhances sEV accumulation on the cell surface by acting as an adhesive, subsequently inducing endocytic uptake of sEVs through a clathrin-mediated pathway. The dimeric curvature-sensing peptide selectively binds to the sEV surface within 10 min, even in the presence of serum proteins, and functions as a membrane interfactant to reduce the energy barriers for the cellular uptake of sEVs. The cellular uptake of sEVs and the dimeric curvature-sensing peptide under coexisting conditions increased to over fivefold and 20-fold, respectively, compared with those administered alone. Furthermore, the dimeric curvature-sensing peptide can efficiently load anticancer drugs onto the surface of sEVs, and the system effectively induces apoptosis in two types of cancer cells. Dimeric curvature-sensing peptide is a novel technique with potential applications in drug delivery.

biochemistry↗

bioRxiv2023

Laser-induced auditory perception: transtympanic laser irradiation of the cochlea from the outer ear evokes an auditory-related neural and behavioral response

Brain-machine interfaces are emerging devices that act as a medium for communication between the neural system and external software and hardware. Over the last decade, there has been a discussion on applying infrared laser stimulation to the brain-machine interfaces, including cochlear implants. Infrared lasers can selectively activate neural populations without introducing exogenous agents to tissues. This study presents the first demonstration that laser irradiation of the cochlea, a peripheral sensory organ, can elicit a clear behavioral auditory response. Mongolian gerbils (Meriones unguiculatus) were divided into two groups, each subjected to classical conditioning where a reward water delivery was predicted by either cochlear laser stimulation or sound stimulus. Laser-conditioned animals successfully learned licking behavior, with conditioned responses and behavioral properties comparable to auditory-conditioned animals. The laser-evoked response was significantly inhibited by auditory masking, and auditory-conditioned animals demonstrated stimulus generalization to laser stimulation. In a subsequent experiment, simultaneous presentation of auditory and laser stimulation induced nonlinear amplification in both auditory cortical and behavioral responses, suggesting that combining auditory and laser stimulation can enhance auditory perception beyond the effects of each stimulus alone. These findings indicate that infrared laser irradiation of the cochlea can potentially evoke and enhance auditory perception, making it a promising candidate for implementation in auditory prostheses.

neuroscience↗

bioRxiv2019

Visual discrimination of optical material properties: a large-scale study

Complex visual processing involved in perceiving the object materials can be better elucidated by taking a variety of research approaches. Sharing stimulus and response data is an effective strategy to make the results of different studies directly comparable and can assist researchers with different backgrounds to jump into the field. Here, we constructed a database containing several sets of material images annotated with visual discrimination performance. We created the material images using physically-based computer graphics techniques and conducted psychophysical experiments with them in both laboratory and crowdsourcing settings. The observers task was to discriminate materials on one of six dimensions (gloss contrast, gloss distinctness-of-image, translucent vs. opaque, metal vs. plastic, metal vs. glass, and glossy vs. painted). The illumination consistency and object geometry were also varied. We used a non-verbal procedure (an oddity task) applicable for diverse use-cases such as cross-cultural, cross-species, clinical, or developmental studies. Results showed that the material discrimination depended on the illuminations and geometries and that the ability to discriminate the spatial consistency of specular highlights in glossiness perception showed larger individual differences than in other tasks. In addition, analysis of visual features showed that the parameters of higher-order color texture statistics can partially, but not completely, explain task performance. The results obtained through crowdsourcing were highly correlated with those obtained in the laboratory, suggesting that our database can be used even when the experimental conditions are not strictly controlled in the laboratory. Several projects using our dataset are underway.

neuroscience↗

bioRxiv2019

Kaposi’s sarcoma-associated herpesvirus ORF66 is essential for late gene expression and virus production via interaction with ORF34

Kaposis sarcoma-associated herpesvirus (KSHV) is closely associated with B-cell and endothelial cell malignancies. After the initial infection, KSHV retains its viral genome in the nucleus of the host cell and establishes a lifelong latency. During lytic infection, KSHV encoded lytic-related proteins are expressed in a sequential manner and are classified as immediate early, early, and late gene transcripts. The transcriptional initiation of KSHV late genes is thought to require the complex formation of the virus specific pre-initiation complex (vPIC), which may consist of at least 6 transcription factors (ORF18, 24, 30, 31, 34, and 66). However, the functional role of ORF66 in vPIC during KSHV replication remains largely unclear. Here, we generated ORF66-deficient KSHV using a BAC system to evaluate its role during viral replication. While ORF66-deficient KSHV demonstrated mainly attenuated late gene expression and decreased viral production, viral DNA replication was unaffected. CHIP analysis showed that ORF66 bound to the promoters of late gene (K8.1), but did not to those of latent gene (ORF72), immediate early gene (ORF16) and early gene (ORF46/47). Furthermore, we found that three highly conserved C-X-X-C sequences and a conserved leucine-repeat in the C-terminal region of ORF66 were essential for interaction with ORF34 and viral production. The interaction between ORF66 and ORF34 occurred in a zinc-dependent manner. Our data support a model, in which ORF66 serves as a critical vPIC component to promote late viral gene expression and viral production.\n\nIMPORTANCEKSHV ORF66, a late gene product, and vPIC are thought to contribute significantly to late gene expression during the lytic replication. However, the physiological importance of ORF66 in terms of viral replication and vPIC formation remains poorly understood. Therfore, we generated a ORF66-deficient BAC clone and evaluated its viral replication. Results showed that ORF66 played a critical role in virus production and the transcription of L genes. To our knowledge, this is the first report showing ORF66 function in virus replication using ORF66-deficient KSHV. We also clarified that ORF66 interacted with the transcription start site of K8.1 gene, a late gene. Furthermore, we identified the ORF34-binding motifs in the ORF66 C-terminus: three C-X-X-C sequences and a leucine-repeat sequence, which are highly conserved among {beta}- and {gamma}-herpesviruses. Our study provides insights into the regulatory mechanisms of not only the late gene expression of KSHV but also those of other herpesviruses.

microbiology↗

bioRxiv2018

Cell division history determines hematopoietic stem cell potency

Loss of stem cell self-renewal may underpin aging. Here, we combined single cell profiling, deep-learning, mathematical modelling and in vivo functional studies to explore how hematopoietic stem cell (HSC) division patterns evolve with age. We trained an artificial neural network (ANN) to accurately identify cell types in the hematopoietic hierarchy and predict their age from their gene expression patterns. We then used this ANN to compare daughter cell identities immediately after HSC divisions, and found that HSC self-renewal declines sharply with age. Furthermore, while HSC cell divisions are deterministic and intrinsically-regulated in young and old age, they become stochastic and niche-sensitive in mid-life. Analysis of evolving division patterns indicated that the self-renewal ability an individual HSC depends upon number times it has divided previously. We propose a model of HSC proliferation that accurately predicts the accumulation of HSCs with age, and reconciles the stochastic and instructive views of fate commitment.

cell biology↗