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Dysregulated biodynamics in metabolic attractor systems precede the emergence of amyotrophic lateral sclerosis.

在肌萎缩侧索硬化症出现之前,代谢吸引子系统中的生物动力学失调。

  • 影响因子:4.35
  • DOI:10.1371/journal.pcbi.1007773
  • 作者列表:"Curtin P","Austin C","Curtin A","Gennings C","Figueroa-Romero C","Mikhail KA","Botero TM","Goutman SA","Feldman EL","Arora M
  • 发表时间:2020-04-15
Abstract

:Evolutionarily conserved mechanisms maintain homeostasis of essential elements, and are believed to be highly time-variant. However, current approaches measure elemental biomarkers at a few discrete time-points, ignoring complex higher-order dynamical features. To study dynamical properties of elemental homeostasis, we apply laser ablation inductively-coupled plasma mass spectrometry (LA-ICP-MS) to tooth samples to generate 500 temporally sequential measurements of elemental concentrations from birth to 10 years. We applied dynamical system and Information Theory-based analyses to reveal the longest-known attractor system in mammalian biology underlying the metabolism of nutrient elements, and identify distinct and consistent transitions between stable and unstable states throughout development. Extending these dynamical features to disease prediction, we find that attractor topography of nutrient metabolism is altered in amyotrophic lateral sclerosis (ALS), as early as childhood, suggesting these pathways are involved in disease risk. Mechanistic analysis was undertaken in a transgenic mouse model of ALS, where we find similar marked disruptions in elemental attractor systems as in humans. Our results demonstrate the application of a phenomological analysis of dynamical systems underlying elemental metabolism, and emphasize the utility of these measures in characterizing risk of disease.

摘要

: 进化保守机制维持必需元件的稳态,并且被认为是高度时变的。然而,目前的方法在几个离散的时间点测量元素生物标志物,忽略了复杂的高阶动力学特征。为了研究元素稳态的动力学性质,我们将激光烧蚀电感耦合等离子体质谱 (la-icp-ms) 应用于牙齿样品,以产生从出生到10年的元素浓度的500个时间顺序测量。我们应用动力系统和基于信息理论的分析,揭示了哺乳动物生物学中已知最长的吸引子系统,它是营养元素代谢的基础,并在整个发育过程中识别稳定和不稳定状态之间的明显和一致的转变。将这些动力学特征扩展到疾病预测,我们发现营养代谢的吸引子形貌早在儿童期就在肌萎缩侧索硬化 (ALS) 中发生了改变,表明这些途径与疾病风险有关。在ALS的转基因小鼠模型中进行了机理分析,其中我们发现元素吸引子系统中的显著破坏与人类相似。我们的研究结果证明了对元素代谢动力系统的物候分析的应用,并强调了这些措施在表征疾病风险方面的效用。

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DOI:10.1016/j.ajog.2019.07.015
作者列表:["Tarasoff LA","Ravindran S","Malik H","Salaeva D","Brown HK"]

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影响因子:1.81
发表时间:2020-01-01
DOI:10.1080/13696998.2019.1646263
作者列表:["Droege M","Sproule D","Arjunji R","Gauthier-Loiselle M","Cloutier M","Dabbous O"]

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脊髓疾病方向

包括脊髓肿瘤、脊髓非肿瘤样病变和脊髓发育异常。脊髓病变可引起脊髓压迫症。脊髓压迫症是由各种性质的病变引起脊髓、脊神经根及其血管受压的一组病症,可导致患者瘫痪等。

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