Cytoskeleton stiffness regulates cellular senescence and innate immune response in Hutchinson–Gilford Progeria Syndrome

Hutchinson–Gilford progeria syndrome (HGPS) is caused by the accumulation of mutant prelamin A (progerin) in the nuclear lamina, resulting in increased nuclear stiffness and abnormal nuclear architecture. Nuclear mechanics are tightly coupled to cytoskeletal mechanics via lamin A/C. However, the role of cytoskeletal/nuclear mechanical properties in mediating cellular senescence and the relationship between cytoskeletal stiffness, nuclear abnormalities, and senescent phenotypes remain largely unknown. Here, using muscle‐derived mesenchymal stromal/stem cells (MSCs) from the Zmpste24^?/? (Z24^?/?) mouse (a model for HGPS) and human HGPS fibroblasts, we investigated the mechanical mechanism of progerin‐induced cellular senescence, involving the role and interaction of mechanical sensors RhoA and Sun1/2 in regulating F‐actin cytoskeleton stiffness, nuclear blebbing, micronuclei formation, and the innate immune response. We observed that increased cytoskeletal stiffness and RhoA activation in progeria cells were directly coupled with increased nuclear blebbing, Sun2 expression, and micronuclei‐induced cGAS‐Sting activation, part of the innate immune response. Expression of constitutively active RhoA promoted, while the inhibition of RhoA/ROCK reduced cytoskeletal stiffness, Sun2 expression, the innate immune response, and cellular senescence. Silencing of Sun2 expression by siRNA also repressed RhoA activation, cytoskeletal stiffness and cellular senescence. Treatment of Zmpste24^?/? mice with a RhoA inhibitor repressed cellular senescence and improved muscle regeneration. These results reveal novel mechanical roles and correlation of cytoskeletal/nuclear stiffness, RhoA, Sun2, and the innate immune response in promoting aging and cellular senescence in HGPS progeria.     

Age attenuates the T‐type CaV3.2‐RyR axis in vascular smooth muscle

Caveolae position Ca_V3.2 (T‐type Ca²⁺ channel encoded by the α‐3.2 subunit) sufficiently close to RyR (ryanodine receptors) for extracellular Ca²⁺ influx to trigger Ca²⁺ sparks and large‐conductance Ca²⁺‐activated K⁺ channel feedback in vascular smooth muscle. We hypothesize that this mechanism of Ca²⁺ spark generation is affected by age. Using smooth muscle cells (VSMCs) from mouse mesenteric arteries, we found that both Ca_v3.2 channel inhibition by Ni²⁺ (50 µM) and caveolae disruption by methyl‐ß‐cyclodextrin or genetic abolition of Eps15 homology domain‐containing protein (EHD2) inhibited Ca²⁺ sparks in cells from young (4 months) but not old (12 months) mice. In accordance, expression of Ca_v3.2 channel was higher in mesenteric arteries from young than old mice. Similar effects were observed for caveolae density. Using SMAKO Ca_v1.2^?/? mice, caffeine (RyR activator) and thapsigargin (Ca²⁺ transport ATPase inhibitor), we found that sufficient SR Ca²⁺ load is a prerequisite for the Ca_V3.2‐RyR axis to generate Ca²⁺ sparks. We identified a fraction of Ca²⁺ sparks in aged VSMCs, which is sensitive to the TRP channel blocker Gd³⁺ (100 µM), but insensitive to Ca_V1.2 and Ca_V3.2 channel blockade. Our data demonstrate that the VSMC Ca_V3.2‐RyR axis is down‐regulated by aging. This defective Ca_V3.2‐RyR coupling is counterbalanced by a Gd³⁺ sensitive Ca²⁺ pathway providing compensatory Ca²⁺ influx for triggering Ca²⁺ sparks in aged VSMCs.     

Psoralen attenuates bleomycin‐induced pulmonary fibrosis in mice through inhibiting myofibroblast activation and collagen deposition

Idiopathic pulmonary fibrosis (IPF) is a progressive disease characterized by excessive deposition of extracellular matrix (ECM) and chronic inflammation with limited therapeutic options. Psoralen, a major active component extracted from Psoralea corylifolia L. seed, has several biological effects. However, the role of psoralen in IPF is still unclear. Here, we hypothesized that psoralen played an essential role in IPF in the inhibition of fibroblast proliferation and inflammatory response. A murine model of IPF was established by injecting bleomycin (BLM) intratracheally, and psoralen was administered for 14 days from the 7^th to 21^st day after BLM injection. Our results demonstrated that psoralen treatment reduced body weight loss and improved the survival rate of mice with IPF. Histological and immunofluorescent examination showed that psoralen alleviated BLM‐induced lung parenchymal inflammatory and fibrotic alteration. Furthermore, psoralen inhibited proliferation and collagen synthesis of mouse fibroblasts and partially reversed BLM‐induced expression of α‐smooth muscle actin at both the tissue and cell level. Moreover, psoralen decreased the expression of transforming growth factor‐β1, interleukin‐1β, and tumor necrosis factor‐α in the lungs of BLM‐stimulated mice. Our results reveale for the first time that psoralen exerts therapeutic effects against IPF in a BLM‐induced murine model.     

The asymmetric relationships of the distribution of conspecific saplings and adults in forest fragments

随着土地利用方式变化的加剧,生境片段化已成为影响植物多样性的主要因子之一。通常,当成年树个体的密度越高,其周边同种幼树个体的存活率可能会下降,从而为其它物种提供了空间和资源,进而可以维持较高的局域物种多样性。因此,同种成年树和幼树个体的空间分布格局关系和作用强度可以调节植物多样性。然而,对于在片段化森林中,同种成年树和幼树个体空间分布关系的研究却很少报道,迄今尚不清楚片段化景观中同种个体的空间分布关系与物种多样性之间的联系。本研究选择千岛湖陆桥岛屿系统中的27个岛屿,基于岛屿上幼树和成年树个体的空间分布数据,利用混合效应模型分析它们之间的作用强度。同种幼树和成年树个体的空间作用强度越大,说明它们之间的负相互作用越强,即幼树和成年树个体空间分布越分散。此外,本研究分析了岛屿属性(岛屿面积、与大陆的距离和与最近岛屿的距离)与同种个体空间作用强度及物种多样性之间的关系。结果表明,同种个体的空间作用强度随着与最近岛屿距离的增加而增加。同时,物种多样性随着同种个体的空间作用强度的增加而显著增加,且岛屿面积和同种个体的空间作用强度分别解释了岛屿间物种多样性差异的26%和6%,共同解释了8%。耐阴种和非常见种比非耐阴种和常见种的同种幼树和成年树的空间分布更为分散。本研究表明,同种个体的空间分布可能会影响多度较低物种在片段化森林中的生存,反映了生物相互作用对于维持片段化森林中的植物多样性具有重要作用。 本研究也强调在检验同种密度制约时应考虑森林之间的连接度。     

新疆吉木萨尔县蝴蝶群落多样性

蝴蝶作为指示生物, 被广泛地应用于生物多样性监测及环境质量评估。探究新疆吉木萨尔县蝴蝶群落多样性, 可为当地蝴蝶多样性的保护及环境监测提供基础数据。本研究采用样线法在新疆吉木萨尔县选取山前荒漠、农田、山地草原、山地森林、亚高山草甸5种不同的生境类型, 对蝴蝶种类和群落多样性进行调查。共记录蝴蝶4,401号, 隶属于7科26属38种。其中蛱蝶科有9属12种, 为优势科; 粉蝶科的个体数最多, 占比55.01%; 绢蝶科、凤蝶科和弄蝶科的种类数和个体数最少, 均为单科种, 是该地区的稀有类群。对不同生境蝴蝶群落多样性和相似度分析比较的结果显示: 5种生境中多样性指数从高到低依次为亚高山草甸、山地森林、山地草原、农田及山前荒漠, 其中山地森林和亚高山草甸的相似性系数较高, 达到0.77, 山前荒漠和山地草原的相似性系数最低, 为0.37。蝴蝶物种数及多样性指数随海拔的增加呈上升趋势。蝴蝶群落随月份发生变化, 蝴蝶种类和数量在5月发生、7月达到峰值。蝶类个体数在3年内呈下降趋势。研究结果表明, 蝴蝶物种的组成和多样性与生境类型具有密切联系, 保护生态环境, 维持该地区植物群落的多样性、降低人为干扰程度是保护蝶类多样性的关键。     

Balancing selection in Pattern Recognition Receptor signalling pathways is associated with gene function and pleiotropy in a wild rodent

Pathogen‐mediated balancing selection is commonly considered to play an important role in the maintenance of genetic diversity, in particular in immune genes. However, the factors that may influence which immune genes are the targets of such selection are largely unknown. To address this, here we focus on Pattern Recognition Receptor (PRR) signalling pathways, which play a key role in innate immunity. We used whole‐genome resequencing data from a population of bank voles (Myodes glareolus) to test for associations between balancing selection, pleiotropy and gene function in a set of 123 PRR signalling pathway genes. To investigate the effect of gene function, we compared genes encoding (a) receptors for microbial ligands versus downstream signalling proteins, and (b) receptors recognizing components of microbial cell walls, flagella and capsids versus receptors recognizing features of microbial nucleic acids. Analyses based on the nucleotide diversity of full coding sequences showed that balancing selection primarily targeted receptor genes with a low degree of pleiotropy. Moreover, genes encoding receptors recognizing components of microbial cell walls etc. were more important targets of balancing selection than receptors recognizing nucleic acids. Tests for localized signatures of balancing selection in coding and noncoding sequences showed that such signatures were mostly located in introns, and more evenly distributed among different functional categories of PRR pathway genes. The finding that signatures of balancing selection in full coding sequences primarily occur in receptor genes, in particular those encoding receptors for components of microbial cell walls etc., is consistent with the idea that coevolution between hosts and pathogens is an important cause of balancing selection on immune genes.     

台风“山竹”对深圳城市绿地及生物量的影响

台风是影响沿海城市绿地生态系统最主要、最频繁的自然干扰因子。2018年9月的台风"山竹"以强台风等级袭击深圳,陆地最大阵风达46.5 m/s(15级)。以深圳市区绿地(公园绿地、居民区绿地、行道树)中的乔木为研究对象,通过灾后实地调研,采用相关统计方法以及生物量评估方法,探讨了台风"山竹"对深圳市区绿地的影响。结果表明:(1)深圳市区调查树木受损比例高达21.4%,其中以轻度受损(枝干折断)为主;市区树冠生物量总量较台风之前下降了8.44%。(2)南部地区受损程度明显高于内陆,东南地区受损程度高于西北地区;福田区、龙岗区以及坪山新区受损情况最为严重,受损树木比例均超过30%。中东部树冠生物量损失程度高于西部地区。(3)公园绿地受损最为严重,居民区绿地的受损情况最轻。(4)行道树中黄金榕、腊肠树受损比例均超过50%,而棕榈科植物受损程度较轻。研究结果可为深圳市抗风树种的选择、不同类型绿地针对台风的减灾防灾策略提供科学依据。     

市县级限制开发区环境功能区划研究——以河北省张家口市为例

限制开发地区是我国主体功能区划中划定的提供重要生态功能和农产品的地区,对其进行环境功能区划对于推动环境功能区划制度落地与实施,以及限制开发区的保护与发展有着重要意义。当前国家及省级的环境功能区划研究已经相对成熟,而市县尺度的限制开发地区环境功能区划相关研究较少。在总结现有环境功能区划研究方法的基础上,以河北省张家口市为例,探讨了市县级限制开发地区环境功能区划体系设计和技术方法,提出了以公里格网作为分析单元,结合县域行政边界,基于环境功能综合评价的结果,从自然生态安全、维护人群健康和区域环境支撑能力等3个方面,开展环境功能区划。基于该方法,将张家口市分为自然生态保留区、生态功能保持区、生态功能恢复区、农产品安全保障区、环境开发准入区、聚居发展维护区6类环境功能区,并根据各环境功能区的主要功能及生态环境特点提出相应的发展建议,以期为该区域管理提供可行的操作手段。本文提出的方法也可为其他限制开发地区的环境功能区划提供参考。