Biology subjects

Wu, M.-F.

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

7 recordsLinked to original sources

bioRxiv2026

Establishment of a Long-Term Germ-Free Medaka Model Reveals Microbiota-Dependent Regulation of Growth, Immunity, and Metabolism

Germ-free (GF) animal models are indispensable for dissecting host-microbiota interactions and their roles in health and disease. The small teleost fish medaka (Oryzias latipes) provides unique advantages for establishing GF models across developmental stages, yet the functions of its intestinal microbiota and metabolites remain poorly characterized. Here, we developed both early-life and chronic GF medaka models to systematically characterize host biology in the absence of microbiota and evaluate the contribution of gut-derived metabolites to growth and immune development. Using a refined sterile feeding and verification protocol, we successfully maintained GF medaka for up to 57 days post-fertilization (dpf). As anticipated, GF fish displayed developmental delays, impaired organogenesis, reduced immune competence, and metabolic dysregulation. Supplementation with sterile gut-derived metabolites partially alleviated these deficits, as evidenced by enhanced locomotor activity and immune responses. Mechanistically, recovery was associated with improved ribosome biogenesis, tricarboxylic acid cycle activity, and histidine and pyruvate metabolism, suggesting enhanced protein synthesis and immune maturation. However, metabolite supplementation also elevated oxidative stress and inflammatory responses and failed to fully restore long-term survival or organ development. Our findings support the use of GF medaka as a versatile platform for investigating microbiota-host interactions across life stages. By integrating metabolite interventions, this model provides critical insights into the functional roles of gut microbiota and offers a valuable tool for advancing microbiome research in health and disease.

microbiology↗

bioRxiv2025

Brainstem pathology in human narcolepsy: Neurodegeneration in the locus coeruleus in narcoleptic humans, but not in genetically narcoleptic mice or dogs

Our earlier study led to the conclusion that human narcolepsy with cataplexy was caused by the loss of forebrain hypocretin (orexin) neurons in the hypothalamus. We now report that humans having narcolepsy with cataplexy also have a 46% decrease in the number and an 18% increase in the size of brainstem neuromelanin-pigmented locus coeruleus (LC) neurons and increased microglial activity in LC. However, no such changes are observed in the LC of hypocretin peptide depleted narcoleptic mice, hypocretin neuron depleted orexin-tTA/TetO-DTA (orexin-DTA) narcoleptic mice or in narcoleptic dogs. Sodium oxybate, an effective treatment for narcolepsy, decreased the size of LC norepinephrine neurons and increased the number and size of LC microglial cells in mice. Our results indicate that the autoimmune process believed to cause human narcolepsy affects both forebrain Hcrt neurons and brainstem LC norepinephrine cells. Addressing both forebrain and brainstem pathologies may improve understanding of, and treatments for, human narcolepsy.

neuroscience↗

bioRxiv2023

Opiate anticipation,opiate induced anatomical changes in hypocretin (Hcrt, orexin) neurons and opiate induced microglial activation are blocked by the dual Hcrt receptor antagonist suvorexant, while opiate analgesia is maintained

We previously found that heroin addiction in humans is accompanied by an increase in the number of detected Hcrt neurons and a decrease in their soma size. We now show that the increased number of Hcrt cells visible after morphine treatment is likely the result of increased Hcrt production in neurons having sub-detection levels of the peptides. We find that morphine increases Hcrt projections to the ventral tegmental area (VTA), the level of tyrosine hydroxylase enzyme (TH) and the number of TH positive cells in VTA, with no changes in the adjacent substantia nigra. We find that the dual Hcrt receptor antagonist suvorexant prevents morphine-induced changes in the number and size of Hcrt neurons, microglial activation and morphine anticipatory behavior, but does not diminish morphine analgesia. These findings suggest that combined administration of opiates and suvorexant may be a less addictive way of administering opiates for pain relief in humans.

neuroscience↗

bioRxiv2022

The tau oligomer antibody APNmAb005 detects early-stage pathological tau enriched at synapses and rescues neuronal loss in long-term treatments

Numerous tau immunotherapies are being developed against Alzheimers disease (AD), but it has been challenging to specifically target early-stage tau aggregates using conformation-dependent antibodies. Here, we report a monoclonal antibody, APNmAb005, that recognized a conformational epitope associated with tau oligomers. In AD brain extracts, mAb005 preferentially recognized oligomeric tau in the synapse over monomeric tau in the cytosol. In the prefrontal cortex and hippocampus, mAb005 immunoreactivity was strongly present in early-stage AD but surprisingly diminished in late-stage AD (Braak stage VI). mAb005 also recognized aggregates in 3R tauopathies (Picks disease) and 4R tauopathies (corticobasal degeneration and progressive supranuclear palsy), including those in astrocytes and oligodendrocytes. In rTg4510 mice (P301L tau), mAb005 immunoreactivity first appeared in distal neurites but much later in neuronal somas. Thus, the mAb005 epitope appears to be associated with early-stage oligomers of tau (esoTau) that accumulate around synapses in AD, which is also detectable in both 3R and 4R tauopathies. In cellular uptake models of tauopathy transmission, mAb005 blocked the formation of intracellular inclusions induced by incubation with rTg4510 mouse brain extracts. Long-term treatments with mAb005 in rTg4510 mice partially rescued synaptic and neuronal loss in the hippocampus without promoting overall tau clearance. Our data suggest that immunotherapies targeting esoTau enriched around synaptic sites may alleviate tau toxicity against synapses and neurons, which may be a promising treatment strategy against AD. One Sentence SummaryA tau-conformer antibody recognizing synaptic oligomers and 3R, 4R, and mixed aggregates in humans rescues neuronal loss in mouse tauopathy models.

neuroscience↗

bioRxiv2020

Plagues of Desert Locust: No invasion risk to China

Recently, the most serious upsurge of desert locust (Schistocerca gregaria) in the last 25 years is spreading across eastern Africa and southwestern Asia. Parts of the desert locust invasion area, namely the northern border areas of Pakistan and India are very close to China, and whether locust swarms will invade China is of wide concern. To answer this question, we identified areas of potentially suitable habitat for the desert locust within China based on historical precipitation and temperature data, and found that parts of Xinjiang and Inner Mongolia provinces could provide ephemeral habitat in summer, but these places are remote from any other desert locust breeding area. Presently, the desert locust populations in Pakistan and India are mature and have laid eggs, and are less likely to spread long distances. The next generation of adults will appear in April and May, and so we examined twenty years historical wind data (2000-2019) for this period. Our results showed that winds at the height of locust swarm flight blew eastward during April and May, but the wind speeds were quite slow and would not facilitate desert locust eastward migration over large distances. Furthermore, simulated trajectories of desert locust swarms with 10 days migration mostly ended within India. The most easterly point of these trajectories just reached eastern India, close to the border between India and Myanmar, and this is very close to the eastern border of the invasion area of desert locust described in previous studies. In conclusion, the risk that the desert locust will invade China is very low.

ecology↗

bioRxiv2019

High risk of the Fall Armyworm invading into Japan and the Korean Peninsula via overseas migration

The fall armyworm, Spodoptera frugiperda (J.E. Smith) is an emerging and most severe pest species in the Old World. It is originally native in the Americas. Since 2016 it has spread widely and rapidly to throughout Africa, the Middle East, India, Southeast Asia and most recently southern China. By May 2019 it has appeared in 13 provinces in most southern China and would spread further to northern China. It is highly likely that S. frugiperda would enter into Japan and Korea via overseas migrations as many other migratory pests did before. To evaluate the invasion risk of S. frugiperda into Japan and Korean Peninsula, we modelled the rate of expansion and future potential migratory range of the insect by a trajectory analytical approach with flight behaviour of S. frugiperda implemented, and meteorological data of past five years (2014-2018) used. Our results predicted that S. frugiperda would migrate from southern and eastern China into Japan and Korea soon. Most likely, Japan would be invaded from Fujian and Zhejiang on 1 June - 15 July, and Kyushu, Shikoku and south-western Honshu could face the highest risk of S. frugiperdas invasion. Korea would be most possibly reached by S. frugiperda from northern Zhejiang, Jiangsu, Anhui, and Shandong on 1 June - 15 July and later. Our results indicated a very high risk that S. frugiperda would annually invade Japan and the Korean Peninsula and cause a possible significant decrease in agricultural productivity.

animal behavior and cognition↗

bioRxiv2019

Prediction of migratory routes of the invasive fall armyworm in eastern China using a trajectory analytical approach

BACKGROUNDThe fall armyworm (FAW), an invasive pest from the Americas, is rapidly spreading through the Old World, and has recently invaded the Indochinese Peninsula and southern China. In the Americas, FAW migrates from winter-breeding areas in the south into summer-breeding areas throughout North America where it is a major pest of corn. Asian populations are also likely to evolve migrations into the corn-producing regions of eastern China, where they will pose a serious threat to food security.\n\nRESULTSTo evaluate the invasion risk in eastern China, the rate of expansion and future migratory range was modelled by a trajectory simulation approach, combined with flight behaviour and meteorological data. Our results predict that FAW will migrate from its new year-round breeding regions into the two main corn-producing regions of eastern China (the North China and Northeast China Plains), via two pathways. The western pathway originates in Myanmar and Yunnan, and FAW will take four migration steps to reach the North China Plain by July. Migration along the eastern pathway from Indochina and southern China progresses faster, with FAW reaching the North China Plain in three steps by June and reaching the Northeast China Plain in July.\n\nCONCLUSIONOur results indicate that there is a high risk that FAW will invade the major corn-producing areas of eastern China via two migration pathways, and cause significant impacts to agricultural productivity. Information on migration pathways and timings can be used to inform integrated pest management strategies for this emerging pest.

animal behavior and cognition↗