Neural induction: Historical views and application to pluripotent stem cells

Embryonic stem (ES) cells are a useful experimental material to recapitulate the differentiation steps of early embryos, which are usually invisible and inaccessible from outside of the body, especially in mammals. ES cells have greatly facilitated the analyses of gene expression profiles and cell characteristics. In addition, understanding the mechanisms during neural differentiation is important for clinical purposes, such as developing new therapeutic methods or regenerative medicine. As neurons have very limited regenerative ability, neurodegenerative diseases are usually intractable, and patients suffer from the disease throughout their lifetimes. The functional cells generated from ES cells in vitro could replace degenerative areas by transplantation. In this review, we will first demonstrate the historical views and widely accepted concepts regarding the molecular mechanisms of neural induction and positional information to produce the specific types of neurons in model animals. Next, we will describe how these concepts have recently been applied to the research in the establishment of the methodology of neural differentiation from mammalian ES cells. Finally, we will focus on examples of the applications of differentiation systems to clinical purposes. Overall, the discussion will focus on how historical developmental studies are applied to state‐of‐the‐art stem cell research.     

Strategic Habitat Conservation for Beach Mice: Estimating Management Scenario Efficiencies

The Perdido Key beach mouse (Peromyscus polionotus trissyllepsis), Choctawhatchee beach mouse (P. p. allophrys), and St. Andrew beach mouse (P. p. peninsularis) are 3 federally endangered subspecies that inhabit coastal dunes of Alabama and Florida, USA. Conservation opportunities for these subspecies are limited and costly. Consequently, well-targeted efforts are required to achieve their downlisting criteria. To aid the development of targeted management scenarios that are designed to achieve downlisting criteria, we developed a Bayesian network model that uses habitat characteristics to predict the probability of beach mouse presence at a 30-m resolution across a portion of the Florida Panhandle. We then designed alternative management scenarios for a variety of habitat conditions for coastal dunes. Finally, we estimated how much area is needed to achieve the established downlisting criterion (i.e., habitat objective) and the amount of effort needed to achieve the habitat objective (i.e., management efficiency). The results suggest that after 7 years of post-storm recolonization, habitat objectives were met for Perdido Key (within its Florida critical habitat) and Choctawhatchee beach mice. The St. Andrew beach mouse required 5.14 km² of additional critical habitat to be protected and occupied. The St. Andrew beach mouse habitat objective might be achieved by first restoring protected critical habitat to good dune conditions and then protecting or restoring the unprotected critical habitat with the highest predicted probability of beach mouse presence. This scenario provided a 28% increase in management efficiency compared to a scenario that randomly protected or restored undeveloped unprotected critical habitat. In total, when coupled with established downlisting criteria, these quantitative and spatial decision support tools could provide insight into how much habitat is available, how much more is needed, and targeted conservation or restoration efforts that might efficiently achieve habitat objectives. © 2020 The Wildlife Society.     

Socially Defined Subpopulations Reveal Demographic Variation in a Giraffe Metapopulation

Populations are typically defined as spatially contiguous sets of individuals, but large populations of social species can be composed of discrete social communities that often overlap in space. Masai giraffes (Giraffa camelopardalis tippelskirchi) of Tanzania live in distinct social subpopulations that overlap spatially, enabling us to simultaneously explore environmental and social factors correlated with demographic variation in a metapopulation of >1,400 adult females and calves. We considered statistically distinct communities in the social network as subpopulations and tested for variation among the 10 subpopulations in adult female survival, calf survival, and reproductive rate (calf-to-adult female ratio). We then related variation in demographic rates among subpopulations to differences in vegetation, soil type, proximity to 2 types of human settlements, local giraffe population density, and social metrics of relationship strength and exclusivity among adult females. We did not find any among-subpopulation effects on adult female survival, suggesting adult female survival is buffered against environmental heterogeneity among subpopulations. Variation in calf demographic rates among subpopulations were correlated with vegetation, soils, anthropogenic factors, and giraffe population density but not with adult female relationship metrics, despite substantial spatial overlap. Subpopulations with more dense bushlands in their ranges had lower calf survival probabilities, and those closer to human settlements had higher reproductive rates, possibly because of spatial gradients in natural predation. Reproductive rates were higher in subpopulations with more volcanic soils, and calf survival probabilities were greater in subpopulations with higher local adult female densities, possibly related to higher-quality habitat associated with fertile soils or lower predation risk, or to greater competitive ability. The variation in fitness among subpopulations suggests that giraffes do not move unhindered among resource patches to equalize reproductive success, as expected according to an ideal free distribution. The differences in calf survival and reproductive rates could rather indicate intercommunity differences in competitive ability, perception, learning, or experience. Our approach of comparing demography among spatially overlapping yet distinct socially defined subpopulations provides a biologically meaningful way to quantify environmental and social factors influencing fine-scale demographic variation for social species. © 2021 The Wildlife Society.     

基于网络药理学探讨“黄芪-白术-熟地黄”组方防治肾病综合征的作用机制

本研究旨在通过网络药理学方法和分子对接技术探讨黄芪-白术-熟地黄组方(HBS)治疗肾病综合征的作用机制。通过多个数据库获取肾病综合征基因并进行功能模块分解,找出肾病综合征基因参与的主要生物学过程。通过文献以及数据库查找HBS活性成分和基因靶点,筛选出HBS治疗肾病综合征的有效靶点。通过有效靶点的KEGG和GO富集分析,找出其参与的主要生物学过程和信号通路,并以此构建靶点-生物功能(TF)网络和靶点-信号通路(TP)网络,综合分析后得到HBS治疗肾病综合征的机制网络,最后使用分子对接技术将HBS化合物和关键靶蛋白进行对接验证。肾病综合征基因主要与细胞增殖、凋亡以及肾脏发育有关。共筛选出18个有效靶点,有效靶点主要与免疫反应、炎症反应、细胞增殖和凋亡的调节有关,主要富集在IL-17、NF-κB、PI3K/Akt、FoxO、p53和Jak/STAT等信号通路上,这些信号通路是HBS调节免疫反应、炎症反应、细胞增殖和凋亡的主要途径。此外,分子对接结果证实HBS化合物与TGFβ1、PTGS2、IL1B、IL2、IL4、IL10、TNF和CD40LG等炎性细胞因子具有较好的结合活性。本研究表明HBS调控IL-17、NF-κB、PI3K/Akt、FoxO、p53和Jak/STAT信号通路上关键蛋白的表达,可能通过调节免疫反应和炎症反应,改善系膜细胞和足细胞的增殖、凋亡水平,进而对包括蛋白尿和肾小球硬化在内的肾病综合征病理改变发挥治疗作用。     

基于网络药理学与分子对接技术的清瘟护肺颗粒防治新型冠状病毒肺炎(COVID-19)的潜在药效物质研究

本文通过网络药理学和分子对接技术探讨清瘟护肺颗粒防治新型冠状病毒肺炎(COVID-19)的潜在药效物质。首先,通过TCMSP数据库,BATMAN-TCM数据库及TCMIP数据库检索清瘟护肺颗粒中十六味药的化学成分及作用靶点,利用GeneCards和OMIM数据库检索COVID-19的相关疾病靶点。然后,通过venny2.1.0获取清瘟护肺颗粒防治COVID-19的潜在靶点,利用R语言对潜在靶点进行GO功能和KEGG通路富集分析,并结合文献对富集所得通路进行分析。最后,利用Cytoscape3.7.1软件构建网络图,采用AutoDock4.2.1软件评价清瘟护肺颗粒中潜在药效成分和新型冠状病毒SARS-CoV-23CL水解酶、血管紧张素转化酶II(ACE2)和RNA依赖的RNA聚合酶(RdRp)的结合作用。网络药理学得到清瘟护肺颗粒防治COVID-19的473个活性成分和123个靶点,KEGG结果及文献分析预测到清瘟护肺颗粒可通过调控MAPK、小细胞肺癌、肺结核、PI3K-AKT等多条信号通路而发挥作用,分子对接结果显示清瘟护肺颗粒中潜在药效成分和SARS-CoV-23CL水解酶、ACE2及RdRp具有良好的亲和性。本研究较为全面揭示了清瘟护肺颗粒治疗COVID-19“多成分、多靶点、多通路”的特点,为深入探讨清瘟护肺颗粒治疗COVID-19的作用机制提供参考依据。