Biology subjects

Wu, H.-M.

Publications and source records attributed to Wu, H.-M..

5 recordsLinked to original sources

bioRxiv2025

Phylogenetic Insights into Antifungal Susceptibility: Comparing Environmental and Clinical Scedosporium and Lomentospora Isolates from Taiwan

ObjectivesScedosporium and Lomentospora species are intrinsically resistant molds increasingly implicated in invasive infections with poor outcomes. Olorofim, a novel orotomide antifungal, has demonstrated potent activity against various molds. This study evaluated the antifungal susceptibility of clinical and environmental isolates, focusing on olorofim, and examined these data in a phylogenetic context. MethodsA total of 216 isolates (Scedosporium spp., n=205; L. prolificans, n=11) were collected from clinical and environmental sources across Taiwan. Species identification was confirmed by sequencing of the ITS and {beta}-tubulin regions, followed by maximum-likelihood phylogenetic analysis. Antifungal susceptibility was determined using CLSI M38-A3 method. Cross-resistance was evaluated using correlation analyses. Phylogenetic signal, Mantel tests, and variance partitioning were applied to assess the evolutionary structuring of minimum inhibitory concentrations (MICs). ResultsScedosporium apiospermum (46.3%) and S. boydii (15.7%) were the predominant species, exhibiting comparable triazole susceptibility profiles (MIC90: voriconazole 1-2 mg/L, posaconazole 4 mg/L, and isavuconazole 8 mg/L). L. prolificans displayed pan-resistance to all agents except olorofim. Among triazoles, voriconazole yielded the lowest MICs for most Scedosporium isolates. Olorofim exhibited the lowest MICs across Scedosporium spp. and L. prolificans (all MIC90 [≤]0.12 mg/L). Rare taxa (S. marinum, S. haikouense, S. multisporum, S. minutisporum, S. sp. nov.1) were also identified, exhibiting variable triazole MICs but consistently low olorofim MICs. The association between antifungal susceptibility and species relatedness varied by drug: moderate for posaconazole, amphotericin B, and voriconazole; intermediate for olorofim; weak for isavuconazole; and absent for itraconazole. Most MIC variability (72.5-89.2%) occurred within rather than between species. ConclusionsAntifungal susceptibility among Scedosporium spp. and L. prolificans was drug dependent. Olorofim demonstrated consistently low MICs across species, whereas amphotericin B and triazoles showed variable, species-specific activity. These findings highlight olorofim as a promising therapeutic option and emphasize the need for target gene-based investigations to elucidate the evolutionary basis of antifungal resistance.

microbiology↗

bioRxiv2024

Human activity, not environmental factors, drives Scedosporium and Lomentospora distribution in Taiwan

Scedosporium and Lomentospora species are emerging fungal pathogens capable of causing severe infections in both immunocompetent and immunocompromised individuals. Previous environmental surveys have suggested potential associations between these fungi and various soil chemical parameters, though the relative influence of human activity versus environmental factors has not been systematically evaluated. Here, we conducted a comprehensive survey of 406 soil samples from 132 locations across Taiwan, analyzing fungal abundance alongside soil physicochemical parameters and the Human Footprint Index (HFI). We recovered 236 fungal isolates comprising 10 species, with S. boydii (32.2%), S. apiospermum (30.9%), and S. dehoogii (14.4%) being the most prevalent. The highest fungal burdens were observed in urban environments (up to 1293 CFU/g), particularly in public spaces and healthcare facilities. Statistical analysis revealed a significant positive correlation between fungal abundance and HFI (r = 0.125, p = 0.013), while soil chemical parameters including nitrogen, carbon, pH, electrical conductivity, and various base cations showed no significant associations despite their wide ranges. These findings indicate that anthropogenic disturbance of environments, rather than soil chemistry, is the primary driver of Scedosporium and Lomentospora distribution in Taiwan. This understanding holds important implications for predicting infection risks and developing targeted public health strategies, particularly in rapidly urbanizing regions. Future studies incorporating more specific indicators of human impact may further elucidate the mechanisms underlying these distribution patterns. Lay AbstractWe found that human activities, rather than soil properties, determine where Scedosporium/Lomentospora fungi distribute in Taiwan. These fungi are more abundant in urban areas than less-human-disturbed environments, suggesting increased infection risks in densely populated regions.

ecology↗

bioRxiv2023

SELENOT regulates endoplasmic reticulum calcium flux via SERCA2 and maintains dopaminergic DAT to protect against attention deficit hyperactivity disorder in mice

Attention deficit and hyperactivity disorder (ADHD) is a prevalent developmental disorder. SELENOT is an endoplasmic reticulum-resident selenocysteine-containing protein. We aimed to investigate the role of SELENOT in dopaminergic neurons. Results from Selenotfl/fl;Dat-cre mice showed that SELENOT deficiency in dopaminergic neurons resulted in ADHD-like behaviors including hyperlocomotion, recognition memory deficit, repetitive movement, and impulsivity. Dopamine metabolism, extrasynaptic dopamine, spontaneous excitatory postsynaptic currents in the striatum and electroencephalogram theta power were enhanced in Selenotfl/fl;Dat-cre mice, whereas dopaminergic neurons in the substantia nigra were slightly reduced but exhibited normal neuronal firing and little cellular stress. Among dopamine- associated proteins, dopamine transporter (DAT) level was remarkably reduced and monoamine oxidase A increased mildly in the striatum and/or midbrain of Selenotfl/fl;Dat-cre mice. The ADHD-like phenotype and DAT ablation were corroborated in Selenotfl/fl;Nestin- cre mice, but not in Selenotfl/fl;Gfap-cre mice. In vitro overexpression and knockdown analyses and RNA-sequencing data revealed that SELENOT causatively regulated DAT mRNA and protein expression through Ca2+ signaling and NURR1. SELENOT maintained cellular Ca2+ levels via interaction with endoplasmic reticulum SERCA2, but not IP3Rs and RYRs, as demonstrated by Ca2+ imaging, co-immunoprecipitation coupled with mass spectrometry, and colocalization analyses. Treatment with psychostimulants, amphetamine or methylphenidate, rescued the hyperactivity in Selenotfl/fl;Dat-cre mice. In conclusion, SELENOT in dopaminergic neurons is indispensable to maintain proper dopamine signaling in the midbrain against ADHD.

neuroscience↗

bioRxiv2023

Brassinosteroid recruits FERONIA to safeguard cell expansion in Arabidopsis

Plant cell expansion is driven by turgor pressure and regulated by hormones. How plant cells avoid cell wall rupture during hormone-induced cell expansion remains a mystery. Here we show that brassinosteroid (BR), while stimulating cell elongation, promotes the plasma membrane (PM) accumulation of the receptor kinase FERONIA (FER), which monitors cell wall damage and in turn attenuates BR-induced cell elongation to prevent cell rupture. The GSK3-like kinase BIN2 phosphorylates FER, resulting in reduced FER accumulation and translocation from endoplasmic reticulum to PM. By inactivating BIN2, BR signaling promotes dephosphorylation and increases PM accumulation of FER, thereby enhancing the surveillance of cell wall integrity. Our study reveals a vital signaling circuit that coordinates hormone signaling with mechanical sensing to prevent cell bursting during hormone-induced cell expansion. One-Sentence SummaryBrassinosteroid recruits a cell wall integrity monitor to prevent growth-induced cell wall damage.

plant biology↗

bioRxiv2023

Probucol mitigates high-fat diet-induced cognitive and social impairments through disruption of redox-inflammation association

Obesity and its detrimental metabolic consequences are commonly recognized as risk factors for impairments in the central nervous system (CNS). However, the direct link between metabolic abnormalities and brain functions during high-fat feeding remains unclear. Here, we show that treatment with probucol, a cholesterol-lowering drug, counteracts the cognitive and social impairments induced by a high-fat diet in mice, while having no effect on mood disorders. Unexpectedly, the beneficial effects of probucol do not result from rectifying obesity or restoring glucose and lipid homeostasis, as evidenced by the lack of change in body weight, blood glucose and serum cholesterol levels. Interestingly, high-fat feeding led to association among the levels of redox factors, including oxidized low-density lipoprotein, glutathione and malondialdehyde, as well as a significant negative correlation between malondialdehyde levels and behavioral performance. Probucol treatment interrupts these linkages and differentially regulates the proteins for the generation of reactive oxygen species and reactive nitrogen species in the brain. These findings prompt a reconsideration of the mechanism of action of probucol, as well as the roles of altered metabolic profiles and free radicals in brain function.

animal behavior and cognition↗