Biology subjects

Yamanaka, T.

Publications and source records attributed to Yamanaka, T..

3 recordsLinked to original sources

bioRxiv2024

Extracellular disposal of nuclear waste by APP: a protective mechanism impaired in Alzheimer's disease

Although the amyloid beta (A{beta}) hypothesis1 has long been central to Alzheimers disease (AD) research, effective therapeutic strategies remain elusive2,3. Here we re-evaluate the functions of amyloid precursor protein (APP) and reveal its critical function in protecting against nuclear impairment-induced cell death and inflammation4,5. Overexpression of APP mitigated etoposide or lamin A knockdown-induced nuclear damage, while APP removal or mutations exacerbated these effects. Interestingly, neurons differentiated from induced pluripotent stem cells (iPSCs) exhibited similar patterns, and notably, familial AD-associated mutant APP failed to confer protection against nuclear impairment. We identify APPs interaction with a cytoplasmic structure of nuclear origin, termed "nuclear waste", and propose its role in extracellular waste disposal. Intriguingly, cells lacking APP showed impaired nuclear waste clearance, leading to abnormal cytoplasmic accumulation of the nuclear waste. Similarly, neuron-specific APP overexpression using adeno-associated virus (AAV) in mice reduced neuronal death and inflammation caused by nuclear damage. Conversely, shRNA-mediated APP exacerbated these effects, and mutant APP associated with familial AD lacked protective effects. Moreover, postmortem analysis of AD brains revealed accumulation of abnormal nuclear waste in the neurocytoplasm, irregular nuclear morphology, and reduced APP levels per neuron. Our data underscore APPs crucial role in disposing of nuclear waste, maintaining cellular homeostasis, and suggest its dysregulation as a potential contributor to AD pathogenesis. Restoring APP waste clearance in AD could be a promising target for disease-modifying therapies.

neuroscience↗

bioRxiv2024

Testosterone-Induced Metabolic Changes in Seminal Vesicle Epithelial cells Alter Plasma Components to Enhance Sperm Fertility

Male factors account for almost half of the causes of infertility. In rodents and humans, most of the components of semen are supplied by the seminal vesicles, and they support male reproductive ability, but there are many unknown details. In this study, the metabolic changes in the seminal vesicle epithelial cells were focused on, and the mechanisms by which testosterone affected the seminal plasma composition were investigated. A factor improving the linear motility of sperm was secreted from the seminal vesicles, and it was produced in an androgen-dependent manner. Bioassays, gene expression, and flux analysis studies demonstrated that testosterone promotes glucose uptake in seminal vesicle epithelial cells via GLUT4, resulting in fatty acid synthesis. ACLY was a critical factor in this metabolic change, which produced fatty acid, especially oleic acid. In conclusion, the critical role of testosterone-induced metabolic changes in the seminal vesicles is to ensure the synthesis of fatty acid. These findings suggest that testosterone-dependent lipid remodeling may contribute to sperm straight-line motility, and further functional verification is required. One Sentence Summary Testosterone promotes the conversion of glucose to fatty acid by increasing the expression of ACLY in seminal vesicle epithelial cells, thereby regulating the seminal plasma components.

cell biology↗

bioRxiv2023

Drivers of asymmetrical insect invasions between three world regions

The geographical exchange of non-native insects can be highly asymmetrical, with some world regions exporting or importing more species than others. Several hypotheses have been proposed to explain such asymmetries, including differences in propagule pressure, environmental features in recipient regions, or biological traits of invaders. We tested aspects of these hypotheses in the context of the exchange of non-native insects between North America, Europe, and Australasia. Europe was the dominant exporter of non-native insect species between the three regions, with most of this asymmetry arising prior to 1950. The European dominance could not be explained by differences in import value, source species pool sizes, or native plant richness in the recipient regions. We identified that the introduction of non-native plants, driven in part by European colonization, best explains the asymmetrical exchange of non-native insects between our focal regions.

ecology↗