Evaluation of acyllysine isostere interactions with the aromatic pocket of the AF9 YEATS domain

Amide−π interactions, in which an amide interacts with an aromatic group, are ubiquitous in biology, yet remain understudied relative to other noncovalent interactions. Recently, we demonstrated that an electrostatically tunable amide−π interaction is key to recognition of histone acyllysine by the AF9 YEATS domain, a reader protein which has emerged as a therapeutic target due to its dysregulation in cancer. Amide isosteres are commonly employed in drug discovery, often to prevent degradation by proteases, and have proven valuable in achieving selectivity when targeting epigenetic proteins. However, like amide−π interactions, interactions of amide isosteres with aromatic rings have not been thoroughly studied despite widespread use. Herein, we evaluate the recognition of a series of amide isosteres by the AF9 YEATS domain using genetic code expansion to evaluate the amide isostere−π interaction. We show that compared to the amide−π interaction with the native ligand, each isostere exhibits similar electrostatic tunability with an aromatic residue in the binding pocket, demonstrating that the isosteres maintain similar interactions with the aromatic residue. We identify a urea-containing ligand that binds with enhanced affinity for the AF9 YEATS domain, offering a promising starting point for inhibitor development. Furthermore, we demonstrate that carbamate and urea isosteres of crotonyllysine are resistant to enzymatic removal by SIRT1, a protein that cleaves acyl post-translational modifications, further indicating the potential of amide isosteres in YEATS domain inhibitor development. These results also provide experimental precedent for interactions of these common drug discovery moieties with aromatic rings that can inform computational methods.     

Genome Analysis Traces Regional Dispersal of Rice in Taiwan and Southeast Asia

The dispersal of rice (Oryza sativa) following domestication influenced massive social and cultural changes across South, East, and Southeast (SE) Asia. The history of dispersal across islands of SE Asia, and the role of Taiwan and the Austronesian expansion in this process remain largely unresolved. Here, we reconstructed the routes of dispersal of O. sativa ssp. japonica rice to Taiwan and the northern Philippines using whole-genome resequencing of indigenous rice landraces coupled with archaeological and paleoclimate data. Our results indicate that japonica rice found in the northern Philippines diverged from Indonesian landraces as early as 3,500 years before present (BP). In contrast, rice cultivated by the indigenous peoples of the Taiwanese mountains has complex origins. It comprises two distinct populations, each best explained as a result of admixture between temperate japonica that presumably came from northeast Asia, and tropical japonica from the northern Philippines and mainland SE Asia, respectively. We find that the temperate japonica component of these indigenous Taiwan populations diverged from northeast Asia subpopulations at about 2,600 BP, whereas gene flow from the northern Philippines had begun before ∼1,300  BP. This coincides with a period of intensified trade established across the South China Sea. Finally, we find evidence for positive selection acting on distinct genomic regions in different rice subpopulations, indicating local adaptation associated with the spread of japonica rice.     

海口市江东新区30年来海岸带城市扩展与生态格局演变

基于GIS和RS技术,在最小累积阻力MCR模型基础上引入不同源地等级的相对阻力因子构建城市扩展生态阻力面UEER模型,并结合水文分析Hydrology模型利用多时相的研究方法对海口市江东新区五个时期(1988年、2001年、2009年、2017年和2019年)的建设用地扩展格局进行动态模拟分析,从生态安全的视角探讨海口市江东新区海岸带城市扩展与生态格局演变趋势。研究结果表明：(1)2018年前研究区重点建设区表现出“摊大饼”式蔓延格局,但在研究时域内重点建设区的面积从49.48 km~2增加到61.57 km~2,建设用地总体上是逐渐集聚的,表现出以重要交通枢纽、现有居民区和商业区为中心向外扩展的趋势。(2)城市扩展是沿着建设用地适宜扩展路径进行的,因受制于生态隔离带并不与相邻建设用地直接相连,由“适宜扩展路径”引导建设用地优化开发,避免建设用地盲目的向外扩展。另外,生态隔离带有逐渐向建设用地渗入,打破了建设用地适宜性区域集中连片的扩展态势。(3)东寨港自然保护区的存在,使得江东新区东海岸以东寨港红树林自然保护区为中心形成的片状区域是生态安全核心区域,虽在相关政策的支持下,研究区的生态...     

基于元胞自动机的城市空间动态模拟

城市空间动态的模拟与预测可以为城市可持续发展规划与管理提供重要的参考依据。SLEUTH元胞自动机模型在城市空间模拟中较强的适用性和可移植性,该模型通过对历史数据的蒙特卡洛迭代自动寻找城市增长误差最小的参数组合,解决了传统元胞自动机模型中转换规则不易确定的问题。以武汉市为研究案例,运用SLEUTH模型进行了城市空间动态模拟与情景预测。2007年至2011年的城市空间模拟结果显示,模拟结果与实际历史数据可以获得良好的空间匹配度,Lee-Sallee形状指数均在0.6以上,显示SLEUTH元胞自动机模型经过本地化校正后具有较强的适用性和满意的模拟精度。进而,设置了现状趋势、基本保护、严格保护等3种情景对武汉2025年城市空间动态进行了预测,结果显示,各情景模式下城市居住用地均明显增长,农业用地、林地、水域等均有所减少;现状趋势情景和基本保护情景下农田、林地、水域减少的幅度较大,会加剧区域的生境破碎、耕地功能下降、水资源匮乏、湖滨湿地萎缩等生态问题,说明这两种情景不能有效满足城市生态系统健康和可持续发展的需要。严格保护情景下,城市居住用地扩张的程度得到了明显的控制,水域和林地得到了有效的保护,对于重要的自然生态系统组分保护及其服务能力维持可以起到显著作用。     

Growth of newly established alien populations: comparison of North American gypsy moth colonies with invasion theory

A common characteristic observed in many biological invasions is the existence of a lag between the time of arrival by the alien population and the time when established populations are noticed. Considerable advances have been made in modeling the expansion of invading species, and there is often remarkable congruence between the behavior of these models with spread of actual populations. While these models have been used to characterize expansion of very newly founded colonies, there have been few attempts to compare the behavior predicted from theory with spread in actual newly founded populations, largely due to the difficulty of sampling sparse populations. Models predict that time lags in the radial expansion of newly invaded populations may be due to time requirements for the population to grow from founding to detectable levels. Models also indicate that these time lags can be predicted based upon population parameters such as the intrinsic rate of population growth and diffusion coefficient. In this paper, we compared the behavior of these models with historical data on gypsy moth, Lymantria dispar, establishment and spread to show similarities between model predictions and observed population spread, both of which exhibited temporal lags of expansion. However, actual populations exhibited certain behaviors that were not predicted, and this could be due, in part, to the existence of Allee effects and stochasticity. Further work that incorporates these effects is needed to more fully understand the growth of incipient colonies of invading species. Ultimately, this information can be of critical importance in the selection of effective strategies for their detection and eradication.     

Molecular phylogeography of four endemic Sagittaria species (Alismataceae) in the Sino‐Japanese Floristic Region of East Asia

To reveal the role of climate oscillations of the Quaternary in forming the contemporary plant diversity in the temperate Sino‐Japanese Floristic Region of mainland China, we assess the phylogeographical patterns of four Sagittaria species in the region using sequence data from plastid DNA non‐coding regions (psbA‐trnH, the rpl16 intron and trnC‐ycf6) and the internal transcribed spacers of nuclear ribosomal DNA (nrITS). Based on both datasets, the divergence time among the four studied species was estimated to fall in the Late Tertiary (plastid DNA: 7.1–13.7 Mya; ITS: 11.1–16.1 Mya). The ancestral distribution analyses revealed that regions with a great diversity in topography, climate and ecological conditions, e.g. the Hengduan Mountains, Central China and East China, were the areas where the endemics originated. Mismatch distribution analyses revealed that each species had experienced a range expansion in response to Quaternary climatic oscillations. Our findings contradict the hypothesis of Quaternary origins of the endemic Sagittaria spp.; we support the view that modern species in the Northern Hemisphere originated mostly during the Tertiary. Range expansion may have profoundly modified the current distribution ranges of Sagittaria species in the Sino‐Japanese Floristic Region. © 2015 The Linnean Society of London, Botanical Journal of the Linnean Society, 2016, 180 , 6–20.     

兔脊髓α受体对血量扩张引起肾交感神经活动抑制和促钠排泄的作用

在窦主动脉去神经麻醉兔观察阻断脊髓α受体对血量扩张引起肾交感神经活动（RSNA）抑制和促钠排泄反应的影响。兔脊髓蛛网膜下腔注射a肾上腺素能受体阻断剂酚妥拉明与人工脑脊液后,血量扩张引起RSNA抑制分别为（－25．4±5．4）％与（－42．5±5.2）％（P＜0.05）;兔脊髓蛛网膜下腔注射α1受体阻断剂哌唑嗪与人工脑脊液后血量扩张引起RSNA抑制分别为（－29．3±6.1）％与（－42．5±5.2）％（P＜005）。结果表明,阻断脊髓α受体或α1受体均可减弱血量扩张引起RSNA抑制。脊髓注射哌唑嗪后血量扩张引起促钠排泄与利尿反应也显著减弱（P＜005）。     

Agricultural intensification increases deforestation fire activity in Amazonia

Fire-driven deforestation is the major source of carbon emissions from Amazonia. Recent expansion of mechanized agriculture in forested regions of Amazonia has increased the average size of deforested areas, but related changes in fire dynamics remain poorly characterized. We estimated the contribution of fires from the deforestation process to total fire activity based on the local frequency of active fire detections from the Moderate Resolution Imaging Spectroradiometer (MODIS) sensors. High-confidence fire detections at the same ground location on 2 or more days per year are most common in areas of active deforestation, where trunks, branches, and stumps can be piled and burned many times before woody fuels are depleted. Across Amazonia, high-frequency fires typical of deforestation accounted for more than 40% of the MODIS fire detections during 2003–2007. Active deforestation frontiers in Bolivia and the Brazilian states of Mato Grosso, Pará, and Rondônia contributed 84% of these high-frequency fires during this period. Among deforested areas, the frequency and timing of fire activity vary according to postclearing land use. Fire usage for expansion of mechanized crop production in Mato Grosso is more intense and more evenly distributed throughout the dry season than forest clearing for cattle ranching (4.6 vs. 1.7 fire days per deforested area, respectively), even for clearings >200 ha in size. Fires for deforestation may continue for several years, increasing the combustion completeness of cropland deforestation to nearly 100% and pasture deforestation to 50–90% over 1–3-year timescales typical of forest conversion. Our results demonstrate that there is no uniform relation between satellite-based fire detections and carbon emissions. Improved understanding of deforestation carbon losses in Amazonia will require models that capture interannual variation in the deforested area that contributes to fire activity and variable combustion completeness of individual clearings as a function of fire frequency or other evidence of postclearing land use.     

Increased activity and growth rate in the non‐dispersive aquatic larval stage of a damselfly at an expanding range edge

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