Resilience provides a new way for communities to become more disaster-resistant and better able to recover.This study proposes a resilience-building risk framework for mountainous communities in Southwest China based ...Resilience provides a new way for communities to become more disaster-resistant and better able to recover.This study proposes a resilience-building risk framework for mountainous communities in Southwest China based on field theory and the baseline resilience indicator for communities.It calculated the resilience-building risk probability using Bayesian network modeling based on ten communities in the mountainous regions of Southwest China.The study obtained data from multiple sources,calculated conditional probabilities among factors and finally explored the risk of community resilience construction and its influencing factors based on Bayesian networks in three aspects:forward propagation,backward diagnosis,and significance analysis.We found that 1)the overall risk level of community resilience building in mountainous areas of Southwest China is low,only 26.8%;2)among the sub resilience fields,the organizational field has the lowest probability of risk(14.2%),and the economic field has the highest probability of risk(42.8%);3)when the overall resilience level decreases,the economic field changes the most,with the most significant magnitude of change in the level of income;and 4)improving residents'information accessibility and enhanced training exercises can reduce the overall resilience risk probability to a greater extent.This study can help local communities evaluate the level of resilience construction correctly,clarify the focus of resilience construction efforts,and provide a reference for resilience-building assessment efforts in other regions.展开更多
目的:THAP结构域蛋白6(THAP domain-containing protein 6,THAP6)是THAP家族成员之一,含保守的THAP锌指结构域,可作为转录因子调控基因表达。既往研究表明THAP6可能参与巨噬细胞激活及社会刺激相关的转录调控,但THAP6是否影响情绪和社...目的:THAP结构域蛋白6(THAP domain-containing protein 6,THAP6)是THAP家族成员之一,含保守的THAP锌指结构域,可作为转录因子调控基因表达。既往研究表明THAP6可能参与巨噬细胞激活及社会刺激相关的转录调控,但THAP6是否影响情绪和社交行为及脑组织结构,目前未见报道。本研究旨在明确Thap6基因缺失对小鼠情绪和社交行为的影响,初步探讨Thap6基因敲除对小鼠脑组织的影响,为揭示THAP6在神经精神疾病中的潜在作用提供实验依据。方法:采用CRISPR/Cas9技术构建Thap6基因全身敲除小鼠模型,通过基因型鉴定筛选Thap6基因敲除杂合子(Thap6+/-,n=8)和野生型(wild-type,WT;n=10)C57BL/6J雄性小鼠作为研究对象。在小鼠成年后,采用转棒实验评估运动和平衡能力,采用旷场实验评估一般活动性和探索能力,采用糖水偏好实验和悬尾实验评估抑郁样行为,采用高架十字迷宫实验评估焦虑样行为,采用三箱社交实验评估社交行为。在行为评估结束后,收集小鼠脑组织,采用苏木精-伊红(hematoxylin and eosin,HE)染色和尼氏染色观察脑组织微结构和神经元数量的改变情况。结果:行为学结果显示,与WT小鼠相比,Thap6+/-小鼠在高架十字迷宫中进入开放臂的次数百分比显著降低(t=2.516,P=0.024)、在开放臂中的平均运动速度显著增快(t=3.045,P=0.013);在三箱社交实验中,Thap6+/-小鼠的社交能力指数(t=4.350,P0.05)。脑组织HE染色结果显示,Thap6+/-小鼠皮质散在细胞形态异常、细胞质疏松、细胞核模糊;杏仁核神经元排列松散、细胞间隔增大、大量空泡形成;小脑浦肯野细胞排列不齐、边界不清、部分细胞核肿胀溶解、细胞缺失;黑质神经元核仁丢失、部分细胞固缩;Thap6+/-组小鼠海马神经元排列有序,细胞形态较好,数目较多,排列紧密。尼氏染色结果显示,Thap6+/-小鼠海马齿状回区域神经元数量显著增多(U=0,P=0.029),皮质、杏仁核、小脑、黑质4个脑区均出现形态异常和神经元数量减少(均U=0,P=0.029)。结论:Thap6基因敲除导致小鼠焦虑样行为和社交行为缺陷,同时导致小鼠多个脑区脑结构异常和神经元数量减少。本研究首次系统揭示了THAP6在情绪与社交行为调控中的重要作用,为理解THAP家族蛋白在中枢神经系统中的功能分化提供了新证据,并提示Thap6基因敲除小鼠可能作为研究焦虑和社交障碍相关神经精神疾病的新型动物模型。展开更多
基金supported by the National Natural Science Foundation of China(U20A20111)the Sichuan Youth Science and Technology Innovation Research Team Project(2020JDTD0006).
摘要Resilience provides a new way for communities to become more disaster-resistant and better able to recover.This study proposes a resilience-building risk framework for mountainous communities in Southwest China based on field theory and the baseline resilience indicator for communities.It calculated the resilience-building risk probability using Bayesian network modeling based on ten communities in the mountainous regions of Southwest China.The study obtained data from multiple sources,calculated conditional probabilities among factors and finally explored the risk of community resilience construction and its influencing factors based on Bayesian networks in three aspects:forward propagation,backward diagnosis,and significance analysis.We found that 1)the overall risk level of community resilience building in mountainous areas of Southwest China is low,only 26.8%;2)among the sub resilience fields,the organizational field has the lowest probability of risk(14.2%),and the economic field has the highest probability of risk(42.8%);3)when the overall resilience level decreases,the economic field changes the most,with the most significant magnitude of change in the level of income;and 4)improving residents'information accessibility and enhanced training exercises can reduce the overall resilience risk probability to a greater extent.This study can help local communities evaluate the level of resilience construction correctly,clarify the focus of resilience construction efforts,and provide a reference for resilience-building assessment efforts in other regions.
摘要目的:THAP结构域蛋白6(THAP domain-containing protein 6,THAP6)是THAP家族成员之一,含保守的THAP锌指结构域,可作为转录因子调控基因表达。既往研究表明THAP6可能参与巨噬细胞激活及社会刺激相关的转录调控,但THAP6是否影响情绪和社交行为及脑组织结构,目前未见报道。本研究旨在明确Thap6基因缺失对小鼠情绪和社交行为的影响,初步探讨Thap6基因敲除对小鼠脑组织的影响,为揭示THAP6在神经精神疾病中的潜在作用提供实验依据。方法:采用CRISPR/Cas9技术构建Thap6基因全身敲除小鼠模型,通过基因型鉴定筛选Thap6基因敲除杂合子(Thap6+/-,n=8)和野生型(wild-type,WT;n=10)C57BL/6J雄性小鼠作为研究对象。在小鼠成年后,采用转棒实验评估运动和平衡能力,采用旷场实验评估一般活动性和探索能力,采用糖水偏好实验和悬尾实验评估抑郁样行为,采用高架十字迷宫实验评估焦虑样行为,采用三箱社交实验评估社交行为。在行为评估结束后,收集小鼠脑组织,采用苏木精-伊红(hematoxylin and eosin,HE)染色和尼氏染色观察脑组织微结构和神经元数量的改变情况。结果:行为学结果显示,与WT小鼠相比,Thap6+/-小鼠在高架十字迷宫中进入开放臂的次数百分比显著降低(t=2.516,P=0.024)、在开放臂中的平均运动速度显著增快(t=3.045,P=0.013);在三箱社交实验中,Thap6+/-小鼠的社交能力指数(t=4.350,P0.05)。脑组织HE染色结果显示,Thap6+/-小鼠皮质散在细胞形态异常、细胞质疏松、细胞核模糊;杏仁核神经元排列松散、细胞间隔增大、大量空泡形成;小脑浦肯野细胞排列不齐、边界不清、部分细胞核肿胀溶解、细胞缺失;黑质神经元核仁丢失、部分细胞固缩;Thap6+/-组小鼠海马神经元排列有序,细胞形态较好,数目较多,排列紧密。尼氏染色结果显示,Thap6+/-小鼠海马齿状回区域神经元数量显著增多(U=0,P=0.029),皮质、杏仁核、小脑、黑质4个脑区均出现形态异常和神经元数量减少(均U=0,P=0.029)。结论:Thap6基因敲除导致小鼠焦虑样行为和社交行为缺陷,同时导致小鼠多个脑区脑结构异常和神经元数量减少。本研究首次系统揭示了THAP6在情绪与社交行为调控中的重要作用,为理解THAP家族蛋白在中枢神经系统中的功能分化提供了新证据,并提示Thap6基因敲除小鼠可能作为研究焦虑和社交障碍相关神经精神疾病的新型动物模型。