Epigenetic alteration of imprinted genes during neural differentiation of germline-derived pluripotent stem cells

Spermatogonial stem cells (SSCs), which are unipotent stem cells in the testes that give rise to sperm, can be converted into germline-derived pluripotent stem (gPS) by self-induction. The androgenetic imprinting pattern of SSCs is maintained even after their reprogramming into gPS cells. In this study, we used an in vitro neural differentiation model to investigate whether the imprinting patterns are maintained or altered during differentiation. The androgenetic patterns of H19, Snrpn, and Mest were maintained even after differentiation of gPS cells into NSCs (gPS-NSCs), whereas the fully unmethylated status of Ndn in SSCs was altered to somatic patterns in gPS cells and gPS-NSCs. Thus, our study demonstrates epigenetic alteration of genomic imprinting during the induction of pluripotency in SSCs and neural differentiation, suggesting that gPS-NSCs can be a useful model to study the roles of imprinted genes in brain development and human neurodevelopmental disorders.     

Nitrous oxide emissions during establishment of eight alternative cellulosic bioenergy cropping systems in the North Central United States

Greenhouse gas (GHG) emissions from soils are a key sustainability metric of cropping systems. During crop establishment, disruptive land‐use change is known to be a critical, but under reported period, for determining GHG emissions. We measured soil N₂O emissions and potential environmental drivers of these fluxes from a three‐year establishment‐phase bioenergy cropping systems experiment replicated in southcentral Wisconsin (ARL) and southwestern Michigan (KBS). Cropping systems treatments were annual monocultures (continuous corn, corn–soybean–canola rotation), perennial monocultures (switchgrass, miscanthus, and poplar), and perennial polycultures (native grass mixture, early successional community, and restored prairie) all grown using best management practices specific to the system. Cumulative three‐year N₂O emissions from annuals were 142% higher than from perennials, with fertilized perennials 190% higher than unfertilized perennials. Emissions ranged from 3.1 to 19.1 kg N₂O‐N ha^?1 yr^?1 for the annuals with continuous corn > corn–soybean–canola rotation and 1.1 to 6.3 kg N₂O‐N ha^?1 yr^?1 for perennials. Nitrous oxide peak fluxes typically were associated with precipitation events that closely followed fertilization. Bayesian modeling of N₂O fluxes based on measured environmental factors explained 33% of variability across all systems. Models trained on single systems performed well in most monocultures (e.g., R² = 0.52 for poplar) but notably worse in polycultures (e.g., R² = 0.17 for early successional, R² = 0.06 for restored prairie), indicating that simulation models that include N₂O emissions should be parameterized specific to particular plant communities. Our results indicate that perennial bioenergy crops in their establishment phase emit less N₂O than annual crops, especially when not fertilized. These findings should be considered further alongside yield and other metrics contributing to important ecosystem services.     

不同电针方法对慢性应激抑郁模型大鼠下丘脑TRH表达的影响

目的:研究分析两种不同电针方法对慢性应激抑郁模型大鼠(CUMS)下丘脑中促甲状腺激素释放激素(TRH)表达的影响。方法:选取60只健康雄性SPF级SD大鼠编号后采用随机数字表法分为对照组(正常喂养)、模型组(仅建立CUMS模型,不予治疗)、观察组A(建立CUMS模型后,脉冲电针治疗)、观察组B(建立CUMS模型后,音乐电针治疗)、氟西汀组(建立CUMS模型后,氟西汀治疗)各12只,对除对照组之外的其他各组大鼠进行1只/笼的孤养结合方式建造CUMS模型,利用开野实验观察各组大鼠行为学改变,采用实时荧光定量(PCR)法测定各组大鼠下丘脑组织中TRH m RNA的表达,采用免疫组化法测定TRH蛋白的表达。结果:在刺激21 d后,模型组大鼠的水平运动次数、垂直运动次数显著的低于对照组、实验组A、实验组B、氟西汀组,且差异均具有统计学意义(P0.05),实验组A、实验组B、氟西汀组大鼠的水平运动次数、垂直运动次数显著低于对照组,且差异均具有统计学意义(P0.05),实验组A、实验组B、氟西汀组大鼠的水平运动次数、垂直运动次数差异无统计学意义(P0.05);模型组大鼠的下丘脑TRH m RNA、TRH蛋白水平低于对照组、实验组A、实验组B、氟西汀组,且差异均具有统计学意义(P0.05),实验组A、实验组B、氟西汀组大鼠的大鼠的下丘脑TRH m RNA、TRH蛋白水平显著低于对照组,且差异均具有统计学意义(P0.05);实验组A、实验组B、氟西汀组大鼠的大鼠的下丘脑TRH m RNA、TRH蛋白水平差异无统计学意义(P0.05)。结论:CUMS大鼠下丘脑中促甲状腺激素释放激素表达水平降低,脉冲电针与音乐电针能有效逆转这一现象,效果相当。     

A proteomics approach to identifying key protein targets involved in VEGF inhibitor mediated attenuation of bleomycin‐induced pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with a life expectancy of less than 5 years post diagnosis for most patients. Poor molecular characterization of IPF has led to insufficient understanding of the pathogenesis of the disease, resulting in lack of effective therapies. In this study, we have integrated a label‐free LC‐MS based approach with systems biology to identify signaling pathways and regulatory nodes within protein interaction networks that govern phenotypic changes that may lead to IPF. Ingenuity Pathway Analysis of proteins modulated in response to bleomycin treatment identified PI3K/Akt and Wnt signaling as the most significant profibrotic pathways. Similar analysis of proteins modulated in response to vascular endothelial growth factor (VEGF) inhibitor (CBO‐P11) treatment identified natural killer cell signaling and PTEN signaling as the most significant antifibrotic pathways. Mechanistic/mammalian target of rapamycin (mTOR) and extracellular signal‐regulated kinase (ERK) were identified to be key mediators of pro‐ and antifibrotic response, where bleomycin (BLM) treatment resulted in increased expression and VEGF inhibitor treatment attenuated expression of mTOR and ERK. Using a BLM mouse model of pulmonary fibrosis and VEGF inhibitor CBO‐P11 as a therapeutic measure, we identified a comprehensive set of signaling pathways and proteins that contribute to the pathogenesis of pulmonary fibrosis that can be targeted for therapy against this fatal disease.     

Plant functional diversity enhances associations of soil fungal diversity with vegetation and soil in the restoration of semiarid sandy grassland

The trait‐based approach shows that plant functional diversity strongly affects ecosystem properties. However, few empirical studies show the relationship between soil fungal diversity and plant functional diversity in natural ecosystems. We investigated soil fungal diversity along a restoration gradient of sandy grassland (mobile dune, semifixed dune, fixed dune, and grassland) in Horqin Sand Land, northern China, using the denaturing gradient gel electrophoresis of 18S rRNA and gene sequencing. We also examined associations of soil fungal diversity with plant functional diversity reflected by the dominant species' traits in community (community‐weighted mean, CWM) and the dispersion of functional trait values (FD_is). We further used the structure equation model (SEM) to evaluate how plant richness, biomass, functional diversity, and soil properties affect soil fungal diversity in sandy grassland restoration. Soil fungal richness in mobile dune and semifixed dune was markedly lower than those of fixed dune and grassland (P < 0.05). Soil fungal richness was positively associated with plant richness, biomass, CWM plant height, and soil gradient aggregated from the principal component analysis, but SEM results showed that plant richness and CWM plant height determined by soil properties were the main factors exerting direct effects. Soil gradient increased fungal richness through indirect effect on vegetation rather than direct effect. The negative indirect effect of FDis on soil fungal richness was through its effect on plant biomass. Our final SEM model based on plant functional diversity explained nearly 70% variances of soil fungal richness. Strong association of soil fungal richness with the dominant species in the community supported the mass ratio hypothesis. Our results clearly highlight the role of plant functional diversity in enhancing associations of soil fungal diversity with community structure and soil properties in sandy grassland ecosystems.     

Microhabitat selection in the common lizard: implications of biotic interactions,age, sex,local processes,and model transferability among populations

Modeling species' habitat requirements are crucial to assess impacts of global change, for conservation efforts and to test mechanisms driving species presence. While the influence of abiotic factors has been widely examined, the importance of biotic factors and biotic interactions, and the potential implications of local processes are not well understood. Testing their importance requires additional knowledge and analyses at local habitat scale. Here, we recorded the locations of species presence at the microhabitat scale and measured abiotic and biotic parameters in three different common lizard (Zootoca vivipara) populations using a standardized sampling protocol. Thereafter, space use models and cross‐evaluations among populations were run to infer local processes and estimate the importance of biotic parameters, biotic interactions, sex, and age. Biotic parameters explained more variation than abiotic parameters, and intraspecific interactions significantly predicted the spatial distribution. Significant differences among populations in the relationship between abiotic parameters and lizard distribution, and the greater model transferability within populations than between populations are in line with effects predicted by local adaptation and/or phenotypic plasticity. These results underline the importance of including biotic parameters and biotic interactions in space use models at the population level. There were significant differences in space use between sexes, and between adults and yearlings, the latter showing no association with the measured parameters. Consequently, predictive habitat models at the population level taking into account different sexes and age classes are required to understand a specie's ecological requirements and to allow for precise conservation strategies. Our study therefore stresses that future predictive habitat models at the population level and their transferability should take these parameters into account.     

Balancing competition for resources with multiple pest regulation in diversified agroecosystems: a process‐based approach to reconcile diversification and productivity

Agroecosystem plant diversification can enhance pest biological regulation and is a promising alternative to pesticide application. However, the costs of competition for resources between plants may exceed the benefits gained by pest regulation. To disentangle the interactions between pest regulation and competition, we developed a generic process‐based approach that accounts for the effects of an associated plant and leaf and root pests on biomass production. We considered three crop–plant associations that differ in competition profiles, and we simulated biomass production under wide ranges of both pest regulation rates and resources’ availability. We analyzed outputs to quantify the pest regulation service level that would be required to attain monoculture yield and other production goals. Results showed that pest regulation requirements were highly dependent on the profile of resource interception of the associated plant and on resources’ availability. Pest regulation and the magnitude of competition between plants interacted in determining the balance between nitrogen and radiation uptake by the crop. Our findings suggest that productivity of diversified agroecosystems relative to monoculture should be optimized by assembling plants whose characteristics balance crops’ resource acquisition. The theoretical insights from our study draw generic rules for vegetation assemblage to optimize trade‐offs between pest regulation and production. Our findings and approach may have implications in understanding, theorizing and implementing agroecosystem diversification. By its generic and adaptable structure, our approach should be useful for studying the effects of diversification in many agroecosystems.     

Evolutionary potential in the Alpine: trait heritabilities and performance variation of the dwarf willow Salix herbacea from different elevations and microhabitats

Alpine ecosystems are seriously threatened by climate change. One of the key mechanisms by which plants can adapt to changing environmental conditions is through evolutionary change. However, we still know little about the evolutionary potential in wild populations of long‐lived alpine plants. Here, we investigated heritabilities of phenological traits, leaf size, and performance traits in natural populations of the long‐lived alpine dwarf shrub Salix herbacea using relatedness estimates inferred from SSR (Simple Sequence Repeat) markers. Salix herbacea occurs in early‐ and late‐snowmelt microhabitats (ridges and snowbeds), and we assessed how performance consequences of phenological traits and leaf size differ between these microhabitats in order to infer potential for evolutionary responses. Salix herbacea showed low, but significant, heritabilities of leaf size, clonal and sexual reproduction, and moderate heritabilities of phenological traits. In both microhabitats, we found that larger leaves, longer intervals between snowmelt and leaf expansion, and longer GDD (growing‐degree days) until leaf expansion resulted in a stronger increase in the number of stems (clonal reproduction). In snowbeds, clonal reproduction increased with a shorter GDD until flowering, while the opposite was found on ridges. Furthermore, the proportion of flowering stems increased with GDD until flowering in both microhabitats. Our results suggest that the presence of significant heritable variation in morphology and phenology might help S. herbacea to adapt to changing environmental conditions. However, it remains to be seen if the rate of such an evolutionary response can keep pace with the rapid rate of climate change.     

Acute stress is detrimental to heart regeneration in zebrafish

Psychological stress is one of the factors associated with human cardiovascular disease. Here, we demonstrate that acute perceived stress impairs the natural capacity of heart regeneration in zebrafish. Beside physical and chemical disturbances, intermittent crowding triggered an increase in cortisol secretion and blocked the replacement of fibrotic tissue with new myocardium. Pharmacological simulation of stress by pulse treatment with dexamethasone/adrenaline reproduced the regeneration failure, while inhibition of the stress response with anxiolytic drugs partially rescued the regenerative process. Impaired heart regeneration in stressed animals was associated with a reduced cardiomyocyte proliferation and with the downregulation of several genes, including igfbp1b, a modulator of IGF signalling. Notably, daily stress induced a decrease in Igf1r phosphorylation. As cardiomyocyte proliferation was decreased in response to IGF-1 receptor inhibition, we propose that the stress-induced cardiac regenerative failure is partially caused by the attenuation of IGF signalling. These findings indicate that the natural regenerative ability of the zebrafish heart is vulnerable to the systemic paracrine stress response.