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Biology subjects

Ge, N.

Publications and source records attributed to Ge, N..

4 recordsLinked to original sources

Domain-specific Schema Reuse Supports Flexible Learning to Learn in Primate Brain

Prior knowledge accelerates subsequent learning of similarly structured problems - a phenomenon termed "learning to learn" - by forming and reusing generalizable neural representations, i.e., the schemas. However, the stability-plasticity dilemma, i.e., how to exploit stable schemas to facilitate learning while remaining flexible towards possible changes, is not well understood. We hypothesize that restricting schemas to specific functional, e.g., decision-making, subspace and making it orthogonal to other subspaces allows the brain to balance stability and plasticity. To test it, we trained three macaques on visuomotor mapping tasks and recorded neural activity in the dorsolateral premotor cortex. By delineating decision and stimulus subspaces, we identified a schema-like manifold within only the decision subspace. The reuse of decision schemas significantly facilitated subsequent learning. In addition, the decision subspace exhibited a trend to be orthogonal to the stimulus subspace, minimizing interference between these two domains. Our results revealed that restricting schemas to specific functional domains can preserve useful knowledge while maintaining orthogonality with other subspaces, allowing for flexible adaptation to new environments, thereby resolving the stability-plasticity dilemma. This finding provides new insights into the mechanisms underlying brains capability to learn both fast and flexibly, which can also inspire more efficient learning algorithms for artificial intelligence systems towards working in open, dynamic environments.

neuroscience↗

Castration Model Illuminates Sex Differences in Healthy Aging: Insights from Metabolome and Transcriptome Analyses

BackgroundSex, as a critical biological variable, has historically been underappreciated, despite the pervasive influence of sexual dimorphism across physiological and pathological processes. A significant obstacle to advancing sex-biased biological research is the absence of an effective animal model. In recent years, castration has emerged as a potential model for elucidating sex-based differences in the context of healthy aging, where it has been shown to equalize lifespan and growth trajectories in genetically diverse mice. However, the molecular shifts induced by castration in common laboratory models, such as C57BL/6 mice, and the broader applicability of this model to other sex-related biological contexts remain largely unexplored. MethodsWe employed multi-omics and observational analyses to investigate the molecular changes associated with sex and sex hormones following castration. We analyzed serum, kidney, and liver samples from 12-week-old and 18-month-old castrated male C57BL/6 mice, alongside intact male and female counterparts. The castration model was further applied to assess differences in cisplatin-induced toxicity and age-related cognitive decline in comparison to unaltered controls. ResultsLC-MS/MS metabolomics revealed that castrated males exhibited substantial alterations in steroid hormone levels and increased concentrations of antioxidant compounds, such as taurine, despite identical diets. Integrated metabolome-transcriptome analysis confirmed distinct patterns of lipid peroxidation and oxidative stress across sham-operated female, male, and castrated male mice. Histopathological evaluations following cisplatin treatment and aging-related behavioral tests demonstrated the models utility in investigating sex-dependent drug toxicity and cognitive decline. These findings underscored the critical role of sex hormones in modulating both toxicity defense mechanisms and cognitive performance. ConclusionThis study provides a systematic multi-omics spectrum on the castration model and demonstrates its capacity to feminize metabolic and transcriptomic profiles, establishing it as a valuable tool for exploring sex hormone-driven biological differences. Our findings lay the groundwork for further mechanistic studies and broaden the potential applications of the castration model in diverse biomedical research domains.

systems biology↗

A genome-wide survey of DNA methylation in Panax notoginseng reveals CHH hyper-methylation regulates the after-ripening and dormancy of recalcitrant seeds

DNA methylation plays a crucial role in regulating fruit ripening and seed development. It remains unknown about the dynamic characteristics of DNA methylation and its regulation mechanisms in morpho-physiological dormancy (MPD)-typed seeds with recalcitrant characteristics. The P. notoginseng seeds are defined by the MPD and are characterized by a strong sensitivity to dehydration during the after-ripening process. We performed DNA methylomes, siRNA profiles, and transcriptomes of embryo and endosperm in P. notoginseng seeds at different after-ripening stages. Herein, we find that the CHH hyper-methylation contributes to the global increase in DNA methylation during the after-ripening process of P. notoginseng seeds. The endosperm genome is hyper-methylated compared to the embryo genome. The CHH hyper-methylation is caused by the high expression level of DNA methyltransferase PnCMT2 in the embryo, and PnDRM2 in the endosperm, respectively. The CHH hyper-methylation alters gene transcription levels to regulate the after-ripening and dormancy of recalcitrant seeds. For example, it inhibits the expression of genes in embryo development to make seeds maintain a dormant status, whereas it activates the expression of genes in the hormone-mediated signaling pathway, and energy metabolism to accomplish the MPD-typed seed after-ripening process. Together, our findings reveal a global increase in DNA methylation and its vital driver in gene expression, and thus elucidate how global CHH hyper-methylation regulates the after-ripening in recalcitrant MPD-typed seeds. This work establishes a key role for epigenetics in regulating the dormancy of MPD-typed seeds with recalcitrant characteristics.

developmental biology↗

A single nonsynonymous mutation on gene encoding E protein of Zika virus leads to increased neurovirulence in vivo

Zika virus can infect a wide range of tissues including the developmental brain of human fetuses, causing from mild to severe clinical diseases. Whether its genetic characteristics impacts on viral pathogenesis is incompletely understood. We have obtained viral variants through serially passage of a clinical Zika virus isolate (SW01) in neonatal mice in vivo and found some of which exhibited markedly increased virulence and neurotropism. By deep sequencing analysis, the more pathogenic viral variants were found to contain four dominant nonsynonymous nucleotide mutations on genes encoding E and NS2A proteins. Further investigation using molecularly cloned viruses revealed that a single 67D (Aspatic acid) to N (Asparagine) substitution on E protein is sufficient to confer the increased virulence and neurotropism. These findings provide new insight into Zika virus pathogenesis and suggest novel targets for the development of therapeutics. Author SummaryRecent large outbreaks of Zika virus infection worldwide have revealed an association between the viral infection and increased cases of specific neurological problems including Congenital Zika Syndrome (including microcephaly) and adult Guillain-Barre Syndrome. However, the determinants of the increased neurovirulence of Zika virus remain uncertain. One hypothesis is that some unique changes across the Zika viral genome have led to the occurrence of these neurological diseases. To test this hypothesis, we continuously propagated a clinical isolate of contemporary Zika virus (SW01) in neonatal mice brain for 11 times to obtain an mouse central nervous system (CNS) adapted Zika virus (MA-SW01) that showed significantly increased neurovirulence in vivo. We then discovered that a single G to A nucleotide substitution at the 1069 site of Zika virus open reading frame leading to a D (aspartic acid) to N (asparagine) in viral Envelope protein is responsible for the increased neurovirulence. These findings improve our understanding of the neurological pathogenesis of Zika virus and provide clues for the development of antiviral strategy.

microbiology↗