近地面激光雷达点云密度对森林冠层结构参数提取准确性的影响

基于激光雷达技术获取冠层结构为森林生态学研究增加了新的维度。搭载于多旋翼无人机的近地面激光雷达相比于固定翼有人机的机载激光雷达,能够更加灵活高效地获取森林群落样地高密度点云。但在实际操作中,往往出现局部低密度点云数据,影响了冠层结构参数提取的准确性。使用4块森林动态样地的近地面激光雷达点云数据;利用航带分解方法分析各样地低密度样方成因;采用点云抽稀模拟算法计算并拟合偏差曲线,对比不同样地、参数和取样尺度间的点云密度对冠层结构参数提取准确性的影响;根据偏差曲线计算各条件下保证参数提取准确性的最低点云密度。结果发现：1)低密度区域主要受地形或(和)近地面遥感设计规划的影响。地形复杂的测区(西双版纳和古田山样地),遥感规划难度大,整体难以获取高密度点云(在30点/m²左右),容易在沟谷和高海拔处出现低密度样方。平坦测区(长白山两块样地)虽可获取高密度点云(均超过150点/m²),但欠佳的遥感规划设计导致长白山1测区北部出现1hm²低密度区域。2)冠层参数提取准确性随点云密度减少而迅速降低,呈负指数幂函数关系。这一变化趋势在不同...     

Binding of HIV-1 gp120 to DC-SIGN Promotes ASK-1-Dependent Activation-Induced Apoptosis of Human Dendritic Cells

During disease progression to AIDS, HIV-1 infected individuals become increasingly immunosuppressed and susceptible to opportunistic infections. It has also been demonstrated that multiple subsets of dendritic cells (DC), including DC-SIGN(+) cells, become significantly depleted in the blood and lymphoid tissues of AIDS patients, which may contribute to the failure in initiating effective host immune responses. The mechanism for DC depletion, however, is unclear. It is also known that vast quantities of viral envelope protein gp120 are shed from maturing HIV-1 virions and form circulating immune complexes in the serum of HIV-1-infected individuals, but the pathological role of gp120 in HIV-1 pathogenesis remains elusive. Here we describe a previously unrecognized mechanism of DC death in chronic HIV-1 infection, in which ligation of DC-SIGN by gp120 sensitizes DC to undergo accelerated apoptosis in response to a variety of activation stimuli. The cultured monocyte-derived DC and also freshly-isolated DC-SIGN(+) blood DC that were exposed to either cross-linked recombinant gp120 or immune-complex gp120 in HIV(+) serum underwent considerable apoptosis after CD40 ligation or exposure to bacterial lipopolysaccharide (LPS) or pro-inflammatory cytokines such as TNFα and IL-1β. Furthermore, circulating DC-SIGN(+) DC that were isolated directly from HIV-1(+) individuals had actually been pre-sensitized by serum gp120 for activation-induced exorbitant apoptosis. In all cases the DC apoptosis was substantially inhibited by DC-SIGN blockade. Finally, we showed that accelerated DC apoptosis was a direct consequence of excessive activation of the pro-apoptotic molecule ASK-1 and transfection of siRNA against ASK-1 significantly prevented the activation-induced excessive DC death. Our study discloses a previously unknown mechanism of immune modulation by envelope protein gp120, provides new insights into HIV immunopathogenesis, and suggests potential therapeutic approaches to prevent DC depletion in chronic HIV infection.     

CCR5 antagonist TD-0680 uses a novel mechanism for enhanced potency against HIV-1 entry, cell-mediated infection, and a resistant variant

Regardless of the route of transmission, R5-tropic HIV-1 predominates early in infection, rendering C-C chemokine receptor type 5 (CCR5) antagonists as attractive agents not only for antiretroviral therapy but also for prevention. Here, we report the specificity, potency, and underlying mechanism of action of a novel small molecule CCR5 antagonist, TD-0680. TD-0680 displayed the greatest potency against a diverse group of R5-tropic HIV-1 and SIV strains when compared with its prodrug, TD-0232, the Food and Drug Administration-approved CCR5 antagonist Maraviroc, and TAK-779, with EC(50) values in the subnanomolar range (0.09-2.29 nm). Importantly, TD-0680 was equally potent at blocking envelope-mediated cell-cell fusion and cell-mediated viral transmission as well as the replication of a TAK-779/Maraviroc-resistant HIV-1 variant. Interestingly, TD-0232 and TD-0680 functioned differently despite binding to a similar transmembrane pocket of CCR5. Site-directed mutagenesis, drug combination, and antibody blocking assays identified a novel mechanism of action of TD-0680. In addition to binding to the transmembrane pocket, the unique exo configuration of this molecule protrudes and sterically blocks access to the extracellular loop 2 (ECL2) region of CCR5, thereby interrupting the interaction between virus and its co-receptor more effectively. This mechanism of action was supported by the observations of similar TD-0680 potency against CD4-dependent and -independent SIV strains and by molecular docking analysis using a CCR5 model. TD-0680, therefore, merits development as an anti-HIV-1 agent for therapeutic purposes and/or as a topical microbicide for the prevention of sexual transmission of R5-tropic HIV-1.     

A systematic analysis of the resistance and sensitivity of HER2YVMA receptor tyrosine kinase mutant to tyrosine kinase inhibitors in HER2-positive lung cancer

Human epidermal growth factor receptor 2 (HER2) has become a well-established target for the treatment of HER2-positive lung cancer. However, a frequently observed in-frame mutation that inserts amino acid quadruplex Tyr776-Val777-Met778-Ala779 at G776 (G776^YVMA) in HER2 kinase domain can cause drug resistance and sensitivity, largely limiting the application of reversible tyrosine kinase inhibitors in lung cancer therapy. A systematic investigation of the intermolecular interactions between the HER2^YVMA mutant and clinical small-molecule inhibitors would help to establish a complete picture of drug response to HER2 G776^YVMA insertion in lung cancer, and to design new tyrosine kinase inhibitors with high potency and selectivity to target the lung cancer-related HER2^YVMA mutant. Here, we combined homology modeling, ligand grafting, structure minimization, molecular simulation and binding affinity analysis to profile a number of tyrosine kinase inhibitors against the G776^YVMA insertion in HER2. It is found that the insertion is far away from HER2 active pocket and thus cannot contact inhibitor ligand directly. However, the insertion is expected to induce marked allosteric effect on some regions around the pocket, including A-loop and hinges connecting between the N- and C-lobes of HER2 kinase domain, which may exert indirect influence to inhibitor binding. Most investigated inhibitors exhibit weak binding strength to both wild-type and mutant HER2, which can be attributed to steric hindrance that impairs ligand compatibility with HER2 active pocket. However, the cognate inhibitor lapatinib and the non-cognate inhibitor bosutinib were predicted to have low affinity for wild-type HER2 but high affinity for HER2^YVMA mutant, which was confirmed by subsequent kinase assay experiments; the inhibitory potencies of bosutinib against wild-type and mutant HER2 were determined to be IC₅₀?>?1000 and =27?nM, respectively, suggesting that the bosutinib might be exploited as a selective inhibitor for mutant over wild-type HER2. Structural examination revealed that formation of additional non-bonded interactions such as hydrogen bonds and hydrophobic contacts with HER2 A-loop region due to G776^YVMA insertion is the primary factor to improve bosutinib affinity upon the mutation.     

Adaptive evolution of chloroplast genomes in ancestral grasses

The grass family, Poaceae, is one of the most successful families among angiosperms. Although it has long been suggested that the chloroplast genomes of the Poaceae have undergone an elevated evolutionary rate compared to other angiosperms, little was known about the details of this phenomenon. By using chloroplast genome data from 31 seed plants species, we recently showed that episodic rate acceleration occurred in the common ancestral branch of the core Poaceae (a clade formed by rice Oryza sativa, wheat Triticum aestivum, maize Zea mays and their allies) accompanied by elevated non-synonymous/synonymous rate ratio, while the rate and the non-synonymous/synonymous rate ratio reverted to the low level typical of most monocot species in the terminal branches. It was further shown that positive selection or adaptive evolution operated in several chloroplast proteins during the evolution of ancestral grasses, and the amino acid sites which putatively experienced positive selection have been identified. These findings illustrate the importance of future works of structural biological research of chloroplasts to understand the background of the evolution of the successful group, Poaceae.Key words: rate acceleration, positive selection, non-synonymous/synonymous rate ratio, Poaceae, structural biologyThe grass family, Poaceae, is one of the largest plant families, comprising about 10,000 species including the most important agricultural plants, rice, wheat and maize, as well as grass-dominated ecosystems which comprise about one-third of Earth''s vegetative cover and support a vast number of animals.¹ The chloroplast genes of the grass family Poaceae are known to have undergone accelerations in their evolutionary rates,^2,3 yet little was known about the details of this acceleration. It has become increasingly feasible to estimate the phylogenetic tree of angiosperms and to clarify the tempo and model of molecular evolution by using chloroplast genome sequences.^4–6 By using chloroplast genome data from 13 monocot species and 18 species from dicots and gymnosperms (31 species in total), we recently examined the details of this phenomenon from several aspects.Figure 1 shows the Poales + Musa part of the chloroplast ML tree of the 31 species, and the elongated branches of Poaceae show the rate acceleration in that particular group. Moreover, longer distances of the Poaceae species from Musa than the Typha/Musa distance by more than two times both in terms of non-synonymous and synonymous substitutions (Fig. 1) indicate that both types of substitutions have undergone rate acceleration along the line leading to Poaceae. To explore the pattern of rate change during the course of grass evolution more in detail, we estimated the time-scale of Angiosperm phylogeny with a relaxed clock based on the Bayesian method implemented in MCMCTREE program of PAML.⁷ As is apparent from Figure 1, the molecular evolutionary rate (substitution rate) differs among different lineages, and therefore we used the relaxed clock method which takes account of the evolution of the evolutionary rate in estimating the divergence times and the pattern of rate change. Based on fossil evidence, we assumed the followings in calibrating the relaxed clock; (1) the Gymnosperm/Angiosperm divergence occurred at 280–310 Ma (million years ago),^5,6 (2) the divergence of Poales from other monocots occurred before 115 Ma,^8,9 and (3) the most basal divergence in eudicots occurred before 125 Ma.⁵Open in a separate windowFigure 1Poales + Musa part of the chloroplast genome tree from 31 seed plant species. The branch lengths are proportional to the estimated lengths by the ML with the codon-substitution model (CODEML in PAML⁷). Non-synonymous (d_N) and synonymous (d_S) distances of Poales from Musa and ω = d_N/d_S (along branches) were estimated by the same program.We further gave a constraint of >65 Ma for the Zea/Oryza divergence based on the recent finding of 65 Ma grass phytoliths in dinosaur coprolites which places the diversification of the grasses to the Cretaceous period.^10,11 As a result, it was found that the rate acceleration was limited to the common ancestral branch of Poaceae after they diverged from Musa and that the rate reverted to the slow rate typical of most monocot species in the terminal branches. Even when the constraint was removed, almost the same pattern of rate change was obtained, suggesting that our conclusion regarding accelerated rate in the ancestral grasses followed by the reverted slow rate in contemporary Poaceae is robust.Non-synonymous/synonymous rate ratio (ω = d_N/d_S) is widely used as an indicator of positive selection or adaptive evolution.¹² Figure 1 also indicates a pronounced increase of ω ratio in the common ancestral branch of Poaceae after their divergence from Typha, followed by reversion in the terminal branches to the lower level typical of basal lineages. The elevation of the ω ratio can be due either by adaptive evolution or by relaxation of selective constraints. An ω value higher than 1 is usually regarded as an evidence of adaptive evolution, but since the ω values shown in the figure averages over the entire protein-encoding genes, we would not obtain such a high value even if positive selection operated in some regions of some proteins. To identify positively selected sites, among 75 protein-encoding genes, we at first selected 14 genes, for which the model with higher ω in the ancestral grass branch than others is significantly better than the model with homogeneous ω, and by using the branch-site model,^13,14 we identified 5 genes (atpE, cemA, clpP, rpoB and rps11) which have p value of the branch-site likelihood ratio test less than 0.05 and contain positively selected sites. The amino acid sites and substitutions identified to have experienced positive selection are as follows; atpE (2T→K, 17S→C, 41A→N, 64M→W, 132V→W), cemA (55N→R, 76Y→K, 161W→F, 190I→F, 204I→C), clpP (26R→V, 48V→T, 86F→T, 112I→P, 134E→R, 182T→D), rpoB (90R→F, 338G→K, 1026G→N), rps11 (54V→P, 62A→S, 82A→R, 105L→S, 115R→A, 120L→R) where the numberings of amino acid sites are those of Zea mays.¹⁵ We anticipate that these amino acid substitutions might have relevance to the successful evolution of grasses. To clarify the implication of these findings, structural biological studies of chloroplast proteins on how the amino acid changes affect their functions are needed.Rates of molecular evolution can be potentially linked to life history of organisms. By comparing evolutionary rates of chloroplast, nuclear and mitochondrial genes across five groups of angiosperms, Smith and Donoghue¹⁶ found that the rates are generally low in trees/shrubs compared to related herbs. Our finding, however, suggests that the pattern of rate change during evolution is more complicated than has previously been anticipated, and highlights the need for distinguishing rates of internal branches and those of terminal branches rather than averaging along a lineage in addressing this complicated problem.As Theodosius Dobzhansky¹⁷ wrote, nothing in biology makes sense except in the light of evolution, and the functional background of the molecular machinery in chloroplasts should be interpreted in the light of evolution. We hope our molecular evolutionary analysis of the chloroplast genomes is the first step towards this goal, and hope collaboration of molecular evolutionists with structural biologists becomes fruitful in the future.     

植物子平台及中国数字植物标本馆(CVH)运维: 做法和经验

该文系统介绍了植物子平台所采取的以数字标本质量为导向的数字化技术规范和管理策略,以及CVH网站数据共享规则, 并指出存在的问题及今后努力方向。     

中国陆地生态系统净初级生产力时空变化特征及影响因素

为揭示气候变化背景下我国各陆地生态系统净初级生产力(NPP)的时空分布特征与驱动机制,引入重心模型分析2000—2017年我国NPP的空间分布格局变化,并利用相关分析方法结合Thornthwaite Memorial模型定量区分气候变化与人类活动影响NPP的相对作用。结果表明：(1)2000—2017年全国NPP均值为325.86 g C/m²,整体呈现出南方高北方低,东南向西北逐渐递减的特点。(2)近18年全国与各陆地生态系统NPP均呈现增长趋势,全国NPP增长速率为4.4597 g C m^-2 a^-1,总净增加约0.391 Pg C。空间上全国与森林、草地、荒漠生态系统的NPP重心向东北方向移动,农田与城市生态系统的NPP重心向西北方向移动,表明NPP在该方向上的增速和增量最大。(3)全国NPP在华北、西北地区与四川盆地主要受降水的影响,在青藏高原与云贵高原的东部主要受气温的影响,各陆地生态系统之间城市生态系统NPP对降水响应的敏感度相对最高,荒漠生态系统NPP对温度响应的敏感度相对最高。(4)气候变化和人类活动对全...     

Large-Scale Phylogenomic Analyses Reveal the Monophyly of Bryophytes and Neoproterozoic Origin of Land Plants

The relationships among the four major embryophyte lineages (mosses, liverworts, hornworts, vascular plants) and the timing of the origin of land plants are enigmatic problems in plant evolution. Here, we resolve the monophyly of bryophytes by improving taxon sampling of hornworts and eliminating the effect of synonymous substitutions. We then estimate the divergence time of crown embryophytes based on three fossil calibration strategies, and reveal that maximum calibration constraints have a major effect on estimating the time of origin of land plants. Moreover, comparison of priors and posteriors provides a guide for evaluating the optimal calibration strategy. By considering the reliability of fossil calibrations and the influences of molecular data, we estimate that land plants originated in the Precambrian (980–682 Ma), much older than widely recognized. Our study highlights the important contribution of molecular data when faced with contentious fossil evidence, and that fossil calibrations used in estimating the timescale of plant evolution require critical scrutiny.