Biology subjects

Yoh, N.

Publications and source records attributed to Yoh, N..

6 recordsLinked to original sources

bioRxiv2026

Paired Tumor Biopsies Reveal Spatiotemporal Myeloid Remodeling After Local Chemotherapy in Glioblastoma

BackgroundStandard-of-care chemotherapy for glioblastoma induces inflammation that may contribute to disease recurrence. Although recurrent tumors are enriched with myeloid cells, the early cellular response to chemotherapy and the mechanisms that initiate this inflammatory remodeling remain poorly understood. In particular, it is unknown how neoplastic and tumor-associated myeloid populations respond during the immediate post-treatment period, and whether tumor-associated myeloid cells directly experience chemotherapy-induced genotoxic stress that contributes to inflammatory state transitions. MethodsWe performed sequencing-based analysis of neoplastic and immune populations following topotecan exposure using multiple complementary model systems and time points. We first analyzed MRI-localized, paired pre- and post-treatment biopsies from a first-in-human trial of 28-day convection enhanced delivery (CED) of topotecan (n=5) using cell-type-deconvolved bulk-RNA-sequencing and immunofluorescence. We then treated syngeneic murine gliomas using an in vivo model of CED-topotecan and measured acute 3-day and 7-day treatment responses by single cell RNA-sequencing. We additionally conducted sequencing analysis of patient-derived slice cultures and in vitro human microglial and glioma cell lines following 24-hour topotecan treatment. ResultsIn paired human biopsies, CED-topotecan induced spatially restricted transcriptional remodeling within the infusion zone, characterized by suppression of proliferative tumor programs and enrichment of inflammatory, interferon, hypoxia, and mesenchymal signatures. Cell-type deconvolution and immunofluorescence linked this response to myeloid remodeling, including enrichment of monocyte-derived tumor-associated macrophage states, increased MARCO-positive myeloid populations, and pH2AX-positive genotoxic stress within Iba1-positive myeloid cells. In the murine CED model, topotecan prolonged survival and reduced tumor cellularity, while also inducing inflammatory and DNA-damage programs in tumor-associated macrophages that evolved by 7-days toward hypoxia, angiogenesis, TGF-{beta} signaling, and mesenchymal/tissue-remodeling programs. Human slice culture and in vitro microglial systems confirmed stress-coupled inflammatory and DNA-damage responses in human myeloid cells. ConclusionsChemotherapy exposure induces a spatially structured inflammatory myeloid response characterized by early genotoxic stress and inflammatory activation, with later emergence of mesenchymal and tissue-remodeling macrophage programs. Across model systems, our analysis supports a model in which chemotherapy-associated damage in both tumor and myeloid cells contributes to an evolving inflammatory microenvironment after treatment.

neuroscience↗

bioRxiv2025

Convection-enhanced delivery of dexamethasone in glioma suppresses myeloid inflammation while avoiding systemic toxicities

Dexamethasone is widely used to control cerebral edema and inflammation in glioblastoma, but its benefits are limited by systemic toxicities and adverse prognostic associations. We evaluated local administration of dexamethasone via convection-enhanced delivery (CED) to maximize intratumoral anti-inflammatory effects by increasing local corticosteroid exposure while minimizing systemic exposure. In two glioma mouse models, continuous intraparenchymal infusion of dexamethasone was well tolerated with no adverse effects. Pharmacokinetic analyses supported preferential intratumoral distribution and reduced systemic exposure with CED compared with systemic dosing. Single-nucleus RNA sequencing (snRNA-seq) and immunohistochemistry showed attenuation of glioma-associated inflammation with downregulation of reactive microglial/macrophage programs and reduced tumor-infiltrating myeloid cells with a morphology consistent with a less activated state. Experiments in human induced pluripotent stem cell (iPSC)-derived microglia confirmed that dexamethasone directly suppresses inflammatory gene expression, indicating a conserved mechanism across species. This inflammatory suppression was recapitulated in both immortalized microglial (HMC3) and macrophage (THP1) cell lines. These findings suggest that localized dexamethasone delivered by CED reprograms the glioma immune microenvironment and achieves control of inflammation without the systemic adverse effects associated with standard systemic dexamethasone therapy. This clinically translatable strategy may improve symptom management and provide a platform for integrating local immunomodulation with future glioblastoma therapies.

cancer biology↗

bioRxiv2025

Habitat use and diel activity of insectivorous bats across land-use types on an Afrotropical oceanic island

Tropical island biodiversity is declining at alarming rates. Yet, understanding how species are coping with such disturbance is largely limited for afro-tropical islands. Here we examined habitat use and diel activity of insectivorous bats across different land-use types covering the endemic-rich Principe Island, Central West Africa. We acoustically surveyed insectivorous bats across 48 sites throughout old-growth forests, secondary re-growth forests, cocoa shaded plantations, and horticultures. Based on 17,527 bat-passes, we were able to record all four insectivorous bat species known to occur on Principe, including the recently described Pseudoromicia principis, the most frequently recorded species. Taphozous mauritianus, a data deficient open-space forager, was the least recorded species. Species activity was lowest in old-growth forests, as well as the activity of the edge-forager P. principis. The activity of the open-space forager Mops pumilus was lowest in forest habitats, whereas Hipposideros ruber, a forest forager, was restricted to these habitats. Diel activity patterns of M. pumilus varied between forests and non-forest habitats, whereas those of P. principis remained similar. Interspecific activity overlap decreased towards more altered land-use types. Our findings emphasize that conserving the remaining forests, along with the current mosaic of land-uses, is needed to maintain Principes complete insectivorous bat assemblages.

ecology↗

bioRxiv2024

Indirect effects of habitat amount mediated by habitat configuration determine bat diversity at the landscape-scale in Peninsular Malaysia

The impacts of fragmentation are often overlooked in landscape studies investigating how habitat loss impacts biodiversity, despite the casual relationship linking both processes. As habitat loss is the primary cause of fragmentation, understanding the inter-related effects of these twin processes on biodiversity is key to minimise biodiversity loss. Here we assess how habitat amount and configuration influence insectivorous bat assemblages, considering both the direct effects of these processes, as well as the indirect effects of habitat amount mediated through configuration. Bats were acoustically surveyed along independent gradients of habitat amount (forest cover) and configuration (number of patches and edge density) across 28 insular landscapes embedded within a Malaysian hydroelectric reservoir. Using Structural Equation Modelling, the direct and indirect effects of habitat amount were examined on bat sonotype richness, total, and guild-specific activity (forest, edge and open-space foragers). Forest cover had a direct and positive effect on sonotype richness and forest forager activity. The quadratic relationship linking edge density and forest cover was strong and overall positive, but while below 30% of forest cover, increasingly forested landscapes had increasingly high edge densities, the opposite pattern was observed in more forested landscapes. On the other hand, increasingly forested landscapes consistently harboured less patches. Owing to the overall low habitat amount in our landscapes and negative edge effects, the indirect effects of forest cover (mediated through edge density) were therefore negative on sonotype richness, outweighing any positive direct effect. The number of patches had little effect on the bat assemblage, except on total activity which was higher in landscapes harbouring more forest patches. As a result, negative indirect effects of forest cover mediated through number of patches were only observed on total activity. Our results highlight that, in natural settings, habitat amount can hardly be altered without influencing habitat configuration, thereby preventing any independent management of these threats. Minimising habitat loss is therefore essential to balance the associated prevailing negative effects of fragmentation on insectivorous bats across tropical forests.

ecology↗

bioRxiv2023

How do conservationists choose where to publish?

Conservation literature addresses a broad spectrum of interdisciplinary questions and benefits most by representing a diverse range of authors, particularly those from countries where much conservation work is focused. In other disciplines, it is well known that barriers and biases exist in the academic publishing sphere, which can impact research dissemination and an authors career development. Here, we used a Discrete Choice Experiment to determine how different journal attributes impact authors choices of where to publish in conservation. We identified three demographic groups across 1038 respondents who have previously published in conservation journals, each exhibiting different publishing preferences. Only two attributes showed a consistent response across groups: cost to publish negatively impacted journal choice, including for those in high-income countries, and authors had a consistent preference for double-blind review. Authors from middle-income countries were willing to pay more for society-owned journals, unlike authors from higher-income countries. Journals with a broad geographical scope, which were Open Access, and which had higher impact factors were preferable to two of the three demographic groups. However, we found journal scope and Open Access were more important in dictating journal choice than impact factor. Overall, our findings demonstrate that different demographics experience different preferences or limitations depending on attributes such as a journals Open Access policy. However, the scarcity of published authors from low-income countries highlights further, pervasive barriers to representation in conservation research. Based on our findings, we provide recommendations to conservation-related journals to reduce barriers to publishing and ultimately benefit conservation science.

scientific communication and education↗

bioRxiv2023

Foraging guild modulates insectivorous bat responses to habitat loss and insular fragmentation in peninsular Malaysia

Despite mounting evidence on the ecological impacts of damming for biodiversity, little is known regarding its consequences in the hyper-diverse Southeast Asian tropical forests. Here we assess the effects of habitat loss and fragmentation on the diversity and activity of insectivorous bats within the hydroelectric Kenyir Lake in peninsular Malaysia. We surveyed bat assemblages on 26 islands and two mainland continuous forest sites using passive acoustic monitoring. Echolocation calls were classified into sonotypes, each corresponding to either one or multiple species, and grouped into foraging guilds. We then examined bat overall assemblage (sonotype richness, activity, and composition), guild- and sonotype-specific activity. From 9360 hours of recordings, we identified 16 bat sonotypes, including 10 forest (2854 bat passes), three edge (13 703) and three open-space foragers (3651). Sonotype richness increased towards denser forest structures (higher Normalized Difference Vegetation Index - NDVI), while species composition varied across the gradient of forest area. Forest foragers were positively affected by NDVI and negatively affected by distance to the closest neighbour, whereas edge foragers activity increased in smaller islands. Of the six sonotypes analysed, the activity of one forest sonotype increased with forest area, while that of one edge sonotype decreased. Ensuring habitat quality within insular forest remnants, in addition to their functional connectivity, maximises bat diversity, including the persistence of forest foraging species. Future hydropower development should therefore avoid the creation of a myriad of small, isolated, and habitat-degraded islands further characterised by altered levels of bat diversity and guild-level activity. HighlightsO_LIWe assessed the diversity of insectivorous bats in dam-induced islands in Malaysia C_LIO_LISpecies persistence was modulated by island size and habitat quality C_LIO_LIForest foragers were negatively affected by island isolation and degradation C_LIO_LIEdge foragers benefited from fragmentation, increasing in activity on smaller islands C_LIO_LIBy creating multiple small, isolated, degraded islands, damming erodes bat diversity C_LI

ecology↗