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Doctoral Dissertation Research: Identifying Plastic Responses in Human Skeletal Tissues through a Sensitive Developmental Windows Framework

博士论文研究：通过敏感的发育窗口框架识别人体骨骼组织的塑性反应

基本信息

批准号：
2018997
负责人：
James Watson
金额：
$ 3.06万
依托单位：
University of Arizona
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2022-08-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=2018997&HistoricalAwards=false
关键词：
Doctoral Dissertation Research Identifying Plastic

项目摘要

Environmental factors exert considerable influence over processes of growth and development, and stress experienced in early life can have long-term consequences for health and mortality risk. It is therefore critical to understand when individuals are most vulnerable to stress exposures. Sensitive developmental windows (SDW) are periods in early life when energy needs are high, and developing tissues exhibit greater plasticity in response to stress. This doctoral dissertation project will examine evidence of plasticity in the human skeletal system using a SDW framework, in order to better understand how the timing of stress exposures in early life influence patterns of disease susceptibility and mortality risk over the lifespan. The intellectual impacts of this project will be the production of a novel framework in which to more clearly define the relationship between early life environments, biology, and health outcomes across the lifespan. Insights derived from this project about the lifetime impacts of developmental stress may inform research in human development and public health. The project will also facilitate training of undergraduate and graduate students in non-destructive methods of skeletal analysis that are broadly applicable across modern, historical, and archaeological contexts. This project will improve existing methods of identifying and interpreting evidence of plasticity in the skeletal system by examining a set of asymmetries in skeletal elements that capture an extended period of early child development. Evidence for plasticity will be measured through the SDW framework by calculating asymmetry indices in three skeletal samples that represent human populations engaged in different modes of subsistence, social organization, and diet (early farmers, prehistoric agriculturalists, and historic preindustrialists). These asymmetry indices will be compared across populations and assessed using childhood mortality rates, age-at-death and adult stature as covariates, so that the impact of plasticity on mortality risk over the lifespan can be evaluated. The methodology employed in this project involves non-destructive analysis of skeletal elements, providing an accessible approach to examining plasticity.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

环境因素对生长和发育过程有相当大的影响，生命早期经历的压力可能对健康和死亡风险产生长期影响。因此，了解个人何时最容易受到压力的影响至关重要。敏感发育窗口（SDW）是生命早期能量需求高的时期，发育中的组织对压力表现出更大的可塑性。这个博士论文项目将使用SDW框架研究人类骨骼系统可塑性的证据，以便更好地了解早期生活中压力暴露的时间如何影响疾病易感性和死亡风险的模式。该项目的智力影响将是产生一个新的框架，在其中更清楚地定义早期生命环境，生物学和整个生命周期的健康结果之间的关系。从这个项目中获得的关于发展压力对一生影响的见解可能会为人类发展和公共卫生研究提供信息。该项目还将促进对本科生和研究生进行非破坏性骨骼分析方法的培训，这些方法广泛适用于现代，历史和考古背景。该项目将通过检查一组骨骼元素的不对称性来改进现有的识别和解释骨骼系统可塑性证据的方法，这些骨骼元素捕获了儿童早期发育的延长期。可塑性的证据将通过SDW框架来测量，通过计算三个骨骼样本的不对称指数，这些样本代表了从事不同生存模式，社会组织和饮食的人类（早期农民，史前农业家和历史上的前工业化）。这些不对称指数将在不同人群中进行比较，并使用儿童死亡率、死亡年龄和成年身高作为协变量进行评估，以便评估可塑性对整个生命周期死亡风险的影响。该项目采用的方法包括对骨骼元素进行非破坏性分析，提供了一种检查可塑性的方法。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。