Diffusion-driven instabilities and emerging spatial patterns in patchy landscapes

Spatial variation in population densities across a landscape is a feature of many ecological systems, from self-organised patterns on mussel beds to spatially restricted insect outbreaks. It occurs as a result of environmental variation in abiotic factors and/or biotic factors structuring the spatial distribution of populations. However the ways in which abiotic and biotic factors interact to determine the existence and nature of spatial patterns in population density remain poorly understood. Here we present a new approach to studying this question by analysing a predator–prey patch-model in a heterogenous landscape. We use analytical and numerical methods originally developed for studying nearest-neighbour (juxtacrine) signalling in epithelia to explore whether and under which conditions patterns emerge. We find that abiotic and biotic factors interact to promote pattern formation. In fact, we find a rich and highly complex array of coexisting stable patterns, located within an enormous number of unstable patterns. Our simulation results indicate that many of the stable patterns have appreciable basins of attraction, making them significant in applications. We are able to identify mechanisms for these patterns based on the classical ideas of long-range inhibition and short-range activation, whereby landscape heterogeneity can modulate the spatial scales at which these processes operate to structure the populations.     

Landscape-level gene flow in Lobaria pulmonaria, an epiphytic lichen

Epiphytes are strongly affected by the population dynamics of their host trees. Owing to the spatio-temporal dynamics of host tree populations, substantial dispersal rates--corresponding to high levels of gene flow--are needed for populations to persist in a landscape. However, several epiphytic lichens have been suggested to be dispersal-limited, which leads to the expectation of low gene flow at the landscape scale. Here, we study landscape-level genetic structure and gene flow of a putatively dispersal-limited epiphytic lichen, Lobaria pulmonaria. The genetic structure of L. pulmonaria was quantified at three hierarchical levels, based on 923 thalli collected from 41 plots situated within a pasture-woodland landscape and genotyped at six fungal microsatellite loci. We found significant isolation by distance, and significant genetic differentiation both among sampling plots and among trees. Landscape configuration, i.e. the effect of a large open area separating two forested regions, did not leave a traceable pattern in genetic structure, as assessed with partial Mantel tests and analysis of molecular variance. Gene pools were spatially intermingled in the pasture-woodland landscape, as determined by Bayesian analysis of population structure. Evidence for local gene flow was found in a disturbed area that was mainly colonized from nearby sources. Our analyses indicated high rates of gene flow of L. pulmonaria among forest patches, which may reflect the historical connectedness of the landscape through gene movement. These results support the conclusion that dispersal in L. pulmonaria is rather effective, but not spatially unrestricted.     

Effects of electric field on alamethicin bound at the lipid-water interface: a molecular mechanics study.

A systematic molecular mechanics study of the alamethicin molecule was made to determine a set of low-energy conformers in vacuo and in aqueous environment. The behavior of these conformers was investigated at the phase boundary which was modeled as a plane dividing two compartments with solvation properties of water and octanol with a constant electric field applied normal to the boundary. The calculations were performed with a molecular mechanics program for calculation of stable conformations at the phase boundary utilizing the Empiric Conformational Energy Program for Peptides force field and the Hopfinger-Scheraga solvation model. 371 minimum energy conformers of alamethicin, determined in vacuo with the build-up procedure, were used as starting conformations for energy minimization in aqueous environment and at the phase boundary. Only 49 interphase-bound structures were within 12 kcal/mol of the minima which was found. No helical structures having values close to the canonical parameters for an alpha- or 3(10)-helix were found despite the presence of eight alpha-methylalanine residues which favor the formation of these helices; four helix-like structures were found, having all negative phi, psi values. All the helical conformers have very high energies in water (approximately 14 kcal/mol), but are quite stable at the phase boundary (3.7-6.8 kcal/mol above the lowest minima found). The implications of these results for proposed mechanisms for membrane-binding and voltage-dependent gating are considered.     

Regression commonality analyses on hierarchical genetic distances

Landscape genetics is emerging as an important way of supporting decision‐making in landscape management, in response to the deterioration of matrix permeability due to habitat loss and fragmentation. In line with unremitting methodological developments in landscape genetics, a new analytical procedure was recently proposed as a way of evaluating the effects of landscape gradients on genetic structures. This procedure is based on the computation of inter‐individual hierarchical genetic distances (HGD), a metric of genetic differentiation taking into account the hierarchical structure in populations as inferred from clustering algorithms. HGD can be used as dependent variables in multivariate regressions to assess the effects of various landscape predictors on spatial patterns of genetic differentiation. However, multicollinearity may obscure the interpretation of multivariate regressions. We illustrate how regression commonality analyses (CA), a detailed variance partitioning procedure that can be used to deal with multicollinearity issues, can thoroughly improve our understanding of landscape connectivity when HGD are used as a dependent variable, with the red deer Cervus elaphus as an empirical example. Using logistic regression commonality analyses on HGD, we showed that semi‐natural open areas, transportation infrastructures and, to a lesser extent, urban areas and rivers, were associated with an increase in hierarchical genetic differentiation in red deer. Regressions based on HGD provided detailed results that could not have been obtained with regressions based on standard genetic distances, with notably additional insights as to the possible influence of linear features such as roads and highways on landscape connectivity. Furthermore, CA helped identify synergistic associations among variables as well as suppressors, thus resolving inconsistencies among hierarchical levels and revealing spurious correlations that may have gone unnoticed in the course of classical regression analyses. We thus recommend the use of regression commonality analysis on hierarchical genetic distances as a promising statistical tool for landscape geneticists.     

Amyloid beta-protein monomer folding: free-energy surfaces reveal alloform-specific differences

Alloform-specific differences in structural dynamics between amyloid β-protein (Aβ) 40 and Aβ42 appear to underlie the pathogenesis of Alzheimer's disease. To elucidate these differences, we performed microsecond timescale replica-exchange molecular dynamics simulations to sample the conformational space of the Aβ monomer and constructed its free-energy surface. We find that neither peptide monomer is unstructured, but rather that each may be described as a unique statistical coil in which five relatively independent folding units exist, comprising residues 1-5, 10-13, 17-22, 28-37, and 39-42, which are connected by four turn structures. The free-energy surfaces of both peptides are characterized by two large basins, comprising conformers with either substantial α-helix or β-sheet content. Conformational transitions within and between these basins are rapid. The two additional hydrophobic residues at the Aβ42 C-terminus, Ile41 and Ala42, significantly increase contacts within the C-terminus, and between the C-terminus and the central hydrophobic cluster (Leu17-Ala21). As a result, the β-structure of Aβ42 is more stable than that of Aβ40, and the conformational equilibrium in Aβ42 shifts towards β-structure. These results suggest that drugs stabilizing α-helical Aβ conformers (or destabilizing the β-sheet state) would block formation of neurotoxic oligomers. The atomic-resolution conformer structures determined in our simulations may serve as useful targets for this purpose. The conformers also provide starting points for simulations of Aβ oligomerization—a process postulated to be the key pathogenetic event in Alzheimer's disease.     

三峡库区低山丘陵区多尺度景观指数响应及适宜粒度

景观格局具有典型的空间异质性和尺度依赖性。在对景观格局进行分析研究时需跨越多个尺度,空间粒度大小在尺度聚合分析中至关重要。三峡库区低山丘陵区斑块破碎、景观格复杂性显著、景观格局特征及尺度变异规律仍待明确,本文以三峡库区秭归县为研究区,设定1—400m内23个粒度梯度水平,定量评估县域、乡镇以及小流域不同幅度上的景观格局指数以及拟合函数,探讨多空间幅度景观格局指数随粒度大小的变化特征。基于景观指数的粒度效应特征和拟合函数的曲线特征(最大曲率点、极值点),明确适宜不同幅度的山地景观格局指数研究的粒度阈值,以揭示库区低山丘陵区景观结构的复杂性和变异性。结果表明：不同景观指数对空间粒度变化和空间幅度变化的响应存在差异,不同景观指数的空间粒度响应主要呈现增加、降低、波动和无明显规律变化的趋势,其中斑块密度、最大斑块面积等指数对斑块形状和大小的变化敏感,而多样性指数的粒度变化敏感度较低;部分指数如斑块密度、边缘密度、周长面积分维数等对空间幅度的变化并不敏感,而最大斑块面积、景观形状指数、散布与并列指数、分离度等指数对空间幅度的变化敏感,适合进行不同幅度适宜粒度阈值的推定;边缘密度、平均斑块大小、景...     

景观生态恢复与重建是区域生态安全格局构建的关键途径

生态恢复与重建是跨尺度、多等级的问题,其主要表现层次应是生态系统（生物群落）、景观,甚至区域,而不能仅仅局限于生态系统。景观的恢复与重建是针对景观退化而言,景观退化从表现形式上可分为景观结构退化与景观功能退化。景观结构退化即景观破碎化,是指景观中各生态系统之间的各种功能联系断裂或连接度(connectivity)减少的现象;而鲜受重视的景观聚集（aggregation）在很多情况下同样具有造成景观退化的负面效应。景观功能退化是指与前一状态相比,由于景观异质性的改变导致景观的稳定性与服务功能等的衰退现象。景观恢复是指恢复原生生态系统间被人类活动终止或破坏的相互联系;景观生态建设应以景观单元空间结构的调整和重新构建为基本手段,包括调整原有的景观格局,引进新的景观组分等,以改善受胁或受损生态系统的功能,提高其基本生产力和稳定性,将人类活动对于景观演化的影响导入良性循环。二者的综合,统称为景观生态恢复与重建,是构建安全的区域生态格局的关键途径。其目标是建立一种由结构合理、功能高效、关系协调的模式生态系统（model ecosystem）组成的模式景观（model landscape）,以实现生态系统健康、生态格局安全和景观服务功能持续,以3S(RS,GPS,GIS)技术为支撑的GAP(ageographic approach to protect biological diversity)分析将为大尺度景观恢复的诊断、评价、规划提供重要的手段。景观中某些关键性点、位置或关系的破坏对整个生态安全具有毁灭性的后果,研究景观层次上的生态恢复模式及恢复技术、选择恢复的关键位置、构筑生态安全格局已成为景观生态学家关注的焦点。     

Intrinsically Disordered Protein Exhibits Both Compaction and Expansion under Macromolecular Crowding

Conformational malleability allows intrinsically disordered proteins (IDPs) to respond agilely to their environments, such as nonspecifically interacting with in vivo bystander macromolecules (or crowders). Previous studies have emphasized conformational compaction of IDPs due to steric repulsion by macromolecular crowders, but effects of soft attraction are largely unexplored. Here we studied the conformational ensembles of the IDP FlgM in both polymer and protein crowders by small-angle neutron scattering. As crowder concentrations increased, the mean radius of gyration of FlgM first decreased but then exhibited an uptick. Ensemble optimization modeling indicated that FlgM conformations under protein crowding segregated into two distinct populations, one compacted and one extended. Coarse-grained simulations showed that compacted conformers fit into an interstitial void and occasionally bind to a surrounding crowder, whereas extended conformers snake through interstitial crevices and bind multiple crowders simultaneously. Crowder-induced conformational segregation may facilitate various cellular functions of IDPs.     

基于3S技术的珠江三角洲景观格局动态变化述评

珠三角是一个景观格局与过程变化极为复杂的区域,近30年来,高速的经济增长与快速的城市化过程使珠三角的景观发生了剧烈的变化,随着全世界对生态环境发展的重视,该区域的景观变化研究也引起了众多专家和学者的关注。另外,随着遥感(RS)、地理信息系统(GIS)和全球定位系统(GPS)技术的发展和成熟,基于3S技术联合来监测和研究景观格局及其变化也成为研究的主流。因此,基于3S技术对珠江三角洲景观格局动态变化进行了大量的研究,并取得了一些成果。本文首先总结了基于3S技术监测景观格局动态变化;其次分析了这些方法在珠江三角洲地区中的应用;并提出几点展望,旨在为珠三角今后的景观格局变化监测研究提供一些必要的借鉴和支持。     

Scale‐dependent genetic structure of the Idaho giant salamander (Dicamptodon aterrimus) in stream networks

The network architecture of streams and rivers constrains evolutionary, demographic and ecological processes of freshwater organisms. This consistent architecture also makes stream networks useful for testing general models of population genetic structure and the scaling of gene flow. We examined genetic structure and gene flow in the facultatively paedomorphic Idaho giant salamander, Dicamptodon aterrimus, in stream networks of Idaho and Montana, USA. We used microsatellite data to test population structure models by (i) examining hierarchical partitioning of genetic variation in stream networks; and (ii) testing for genetic isolation by distance along stream corridors vs. overland pathways. Replicated sampling of streams within catchments within three river basins revealed that hierarchical scale had strong effects on genetic structure and gene flow. amova identified significant structure at all hierarchical scales (among streams, among catchments, among basins), but divergence among catchments had the greatest structural influence. Isolation by distance was detected within catchments, and in‐stream distance was a strong predictor of genetic divergence. Patterns of genetic divergence suggest that differentiation among streams within catchments was driven by limited migration, consistent with a stream hierarchy model of population structure. However, there was no evidence of migration among catchments within basins, or among basins, indicating that gene flow only counters the effects of genetic drift at smaller scales (within rather than among catchments). These results show the strong influence of stream networks on population structure and genetic divergence of a salamander, with contrasting effects at different hierarchical scales.     

Solution conformation of conotoxin GI determined by 1H nuclear magnetic resonance spectroscopy and distance geometry calculations

Conformational analysis of conotoxin GI, one of the neurotoxic peptides produced by a marine snail, genus Conus, was performed by a combination of nuclear magnetic resonance spectroscopy (NMR) and distance geometry calculations. The resulting conformers on minimization of the target function were classified into two groups. The difference in the structures of the conformers is mainly due to the difference in the orientation of the side chain of the tyrosyl residue. The results show that the solution structure of conotoxin GI satisfies the conformational requirements for the biological activity of an antagonist toward nicotinic cholinergic receptors elucidated in a series of studies on alkaloids. The structure is discussed on the basis of the results of comparison of the atomic arrangements of the active sites of snake venom peptides and molecular models based on the results of secondary structure prediction.     

MarkovHC: Markov hierarchical clustering for the topological structure of high-dimensional single-cell omics data with transition pathway and critical point detection

Clustering cells and depicting the lineage relationship among cell subpopulations are fundamental tasks in single-cell omics studies. However, existing analytical methods face challenges in stratifying cells, tracking cellular trajectories, and identifying critical points of cell transitions. To overcome these, we proposed a novel Markov hierarchical clustering algorithm (MarkovHC), a topological clustering method that leverages the metastability of exponentially perturbed Markov chains for systematically reconstructing the cellular landscape. Briefly, MarkovHC starts with local connectivity and density derived from the input and outputs a hierarchical structure for the data. We firstly benchmarked MarkovHC on five simulated datasets and ten public single-cell datasets with known labels. Then, we used MarkovHC to investigate the multi-level architectures and transition processes during human embryo preimplantation development and gastric cancer procession. MarkovHC found heterogeneous cell states and sub-cell types in lineage-specific progenitor cells and revealed the most possible transition paths and critical points in the cellular processes. These results demonstrated MarkovHC’s effectiveness in facilitating the stratification of cells, identification of cell populations, and characterization of cellular trajectories and critical points.     

Modeling conformational ensembles of slow functional motions in Pin1-WW

Protein-protein interactions are often mediated by flexible loops that experience conformational dynamics on the microsecond to millisecond time scales. NMR relaxation studies can map these dynamics. However, defining the network of inter-converting conformers that underlie the relaxation data remains generally challenging. Here, we combine NMR relaxation experiments with simulation to visualize networks of inter-converting conformers. We demonstrate our approach with the apo Pin1-WW domain, for which NMR has revealed conformational dynamics of a flexible loop in the millisecond range. We sample and cluster the free energy landscape using Markov State Models (MSM) with major and minor exchange states with high correlation with the NMR relaxation data and low NOE violations. These MSM are hierarchical ensembles of slowly interconverting, metastable macrostates and rapidly interconverting microstates. We found a low population state that consists primarily of holo-like conformations and is a "hub" visited by most pathways between macrostates. These results suggest that conformational equilibria between holo-like and alternative conformers pre-exist in the intrinsic dynamics of apo Pin1-WW. Analysis using MutInf, a mutual information method for quantifying correlated motions, reveals that WW dynamics not only play a role in substrate recognition, but also may help couple the substrate binding site on the WW domain to the one on the catalytic domain. Our work represents an important step towards building networks of inter-converting conformational states and is generally applicable.     

沈阳西郊景观格局变化的研究

景观格局变化的主要原因在于外界的干扰作用,其显著变化具有3种典型类型。本文对景观格局的研究,采用了几种计测指标:(1)各类嵌块体的数目和面积大小;(2)嵌块体的转移矩阵;(3)嵌块体的优势度指数;(4)景观的多样性指数。研究结果表明,沈阳西部景观在经历了30年的变化后,变得更加破碎,出现了较多的块状和岛状嵌块体。景观基质发生了改变,城市化现象较为明显,土地利用的经济效益也有所提高。但由于人口的剧增,人均土地面积在不断减少,荒地开发殆尽,这预示着土地承载能力的饱和与危机的开端。     

景观可持续性与景观可持续性科学

人类活动已经剧烈地改变了自然环境,全球气候变化、生物多样性丧失、环境污染等种种迹象表明当今世界正处在一个不可持续的运行轨迹上,实现可持续发展成为21世纪人类面临的巨大挑战。景观是理解与塑造人类社会和环境关系最具操作性的尺度,也是提供景观服务,实现人类福祉最重要的场所。景观可持续性研究对于人类具有重要意义。景观可持续性是指特定景观所具有的、能够长期而稳定地提供景观服务、维护和改善本区域人类福祉的综合能力。景观可持续性具有跨学科、多维度特征,强调景观弹性和可再生能力;景观服务是景观可持续性研究中的重要概念,它是连接自然资本与人类福祉的关键桥梁,也是将景观可持续性与景观生态学紧密联系在一起的纽带。格局-过程-设计新范式的产生是景观可持续性研究的新发展。在景观可持续性快速发展的同时,聚焦于景观和区域尺度的景观可持续性科学应运而生。景观可持续性科学以景观格局、景观服务、人类福祉三者之间的动态关系为主要研究内容,充分融合了景观生态学空间显示方法、可持续性指标体系和GISRS等方法技术,其理论框架和研究方法体系正在逐步形成和完善之中。景观可持续性科学是可持续性科学的重要组成部分,虽然处于刚刚起步阶段,它必将成为未来十多年可持续性科学的研究热点。     

Potential energy landscape and robustness of a gene regulatory network: toggle switch

Finding a multidimensional potential landscape is the key for addressing important global issues, such as the robustness of cellular networks. We have uncovered the underlying potential energy landscape of a simple gene regulatory network: a toggle switch. This was realized by explicitly constructing the steady state probability of the gene switch in the protein concentration space in the presence of the intrinsic statistical fluctuations due to the small number of proteins in the cell. We explored the global phase space for the system. We found that the protein synthesis rate and the unbinding rate of proteins to the gene were small relative to the protein degradation rate; the gene switch is monostable with only one stable basin of attraction. When both the protein synthesis rate and the unbinding rate of proteins to the gene are large compared with the protein degradation rate, two global basins of attraction emerge for a toggle switch. These basins correspond to the biologically stable functional states. The potential energy barrier between the two basins determines the time scale of conversion from one to the other. We found as the protein synthesis rate and protein unbinding rate to the gene relative to the protein degradation rate became larger, the potential energy barrier became larger. This also corresponded to systems with less noise or the fluctuations on the protein numbers. It leads to the robustness of the biological basins of the gene switches. The technique used here is general and can be applied to explore the potential energy landscape of the gene networks.     

A Nonquiescent “Idling” Population State in Drug-Treated,BRAF-Mutated Melanoma

Targeted therapy is an effective standard of care in BRAF-mutated malignant melanoma. However, the duration of tumor remission varies unpredictably among patients, and relapse is almost inevitable. Here, we examine the responses of several BRAF-mutated melanoma cell lines (including isogenic subclones) to BRAF inhibitors. We observe complex response dynamics across cell lines, with short-term responses (<100 h) varying from cell line to cell line. In the long term, however, we observe equilibration of all drug-treated populations into a nonquiescent state characterized by a balanced rate of death and division, which we term the “idling” state, and to our knowledge, this state has not been previously reported. Using mathematical modeling, we propose that the observed population-level dynamics are the result of cells transitioning between basins of attraction within a drug-modified phenotypic landscape. Each basin is associated with a drug-induced proliferation rate, a recently introduced metric of an antiproliferative drug effect. The idling population state represents a new dynamic equilibrium in which cells are distributed across the landscape such that the population achieves zero net growth. By fitting our model to experimental drug-response data, we infer the phenotypic landscapes of all considered melanoma cell lines and provide a unifying view of how BRAF-mutated melanomas respond to BRAF inhibition. We hypothesize that the residual disease observed in patients after targeted therapy is composed of a significant number of idling cells. Thus, defining molecular determinants of the phenotypic landscape that idling populations occupy may lead to “targeted landscaping” therapies based on rational modification of the landscape to favor basins with greater drug susceptibility.     

Common barriers,but temporal dissonance: Genomic tests suggest ecological and paleo‐landscape sieves structure a coastal riverine fish community

Assessments of spatial and temporal congruency across taxa from genetic data provide insights into the extent to which similar processes structure communities. However, for coastal regions that are affected continuously by cyclical sea‐level changes over the Pleistocene, congruent interspecific response will not only depend upon codistributions, but also on similar dispersal histories among taxa. Here, we use SNPs to test for concordant genetic structure among four codistributed taxa of freshwater fishes (Teleostei: Characidae) along the Brazilian Atlantic coastal drainages. Based on population relationships and hierarchical genetic structure analyses, we identify all taxa share the same geographic structure suggesting the fish utilized common passages in the past to move between river basins. In contrast to this strong spatial concordance, model‐based estimates of divergence times indicate that despite common routes for dispersal, these passages were traversed by each of the taxa at different times resulting in varying degrees of genetic differentiation across barriers with most divergences dating to the Upper Pleistocene, even when accounting for divergence with gene flow. Interestingly, when this temporal dissonance is viewed through the lens of the species‐specific ecologies, it suggests that an ecological sieve influenced whether species dispersed readily, with an ecological generalist showing the highest propensity for historical dispersal among the isolated rivers of the Brazilian coast (i.e., the most recent divergence times and frequent gene flow estimated for barriers). We discuss how our findings, and in particular what the temporal dissonance, despite common geographic passages, suggest about past dispersal structuring coastal communities as a function of ecological and paleo‐landscape sieves.