fixation time

固定时间
  • 文章类型: Journal Article
    群体中有益等位基因固定的速率取决于固定此类等位基因的概率和时间。这两个数量都可能受到人口细分和有限基因流的显着影响。这里,我们研究了有限的分散如何影响有益的从头突变的固定率,以及站立遗传变异的固定时间。我们针对根据扩散岛模型构造的种群进行研究,允许我们使用扩散近似,我们用模拟来补充。我们发现,在选择适度的情况下,在有限的分散下,固定的时间平均比在panmixia下少。如果适应发生于从头隐性突变,情况尤其如此,和分散没有太受限制(使得大约FST<0.2)。原因是轻度有限的分散只会导致有效种群规模的适度增加(这会减慢固定速度),但由于近亲繁殖而足以导致纯合性相对过量,从而将罕见的隐性等位基因暴露于选择(加速固定)。我们还探索了通过局部灭绝然后重新定居的种群动态的影响,发现这种动态总是加速固定的遗传变异,而从头突变显示出更快的固定,并伴随着更长的等待时间。最后,我们讨论了我们的结果对扫描检测的影响,这表明有限的分散减轻了涉及隐性和显性等位基因的扫描的遗传特征之间的预期差异。
    The rate at which beneficial alleles fix in a population depends on the probability of and time to fixation of such alleles. Both of these quantities can be significantly impacted by population subdivision and limited gene flow. Here, we investigate how limited dispersal influences the rate of fixation of beneficial de novo mutations, as well as fixation time from standing genetic variation. We investigate this for a population structured according to the island model of dispersal allowing us to use the diffusion approximation, which we complement with simulations. We find that fixation may take on average fewer generations under limited dispersal than under panmixia when selection is moderate. This is especially the case if adaptation occurs from de novo recessive mutations, and dispersal is not too limited (such that approximately FST<0.2). The reason is that mildly limited dispersal leads to only a moderate increase in effective population size (which slows down fixation), but is sufficient to cause a relative excess of homozygosity due to inbreeding, thereby exposing rare recessive alleles to selection (which accelerates fixation). We also explore the effect of metapopulation dynamics through local extinction followed by recolonization, finding that such dynamics always accelerate fixation from standing genetic variation, while de novo mutations show faster fixation interspersed with longer waiting times. Finally, we discuss the implications of our results for the detection of sweeps, suggesting that limited dispersal mitigates the expected differences between the genetic signatures of sweeps involving recessive and dominant alleles.
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  • 文章类型: Journal Article
    当前的食物环境变得越来越肥胖,随着肥胖率和相关疾病的不断上升。能量密集食品的广告丰富,并通过利用人们对食物线索的注意力偏见来促进不健康的饮食行为,由于高度增强食物的敏化而产生的认知过程。提高对食物线索的认识可能会促进对能量密集食物的过度消费。当前的研究采用了新颖的眼动追踪方法来捕获持续的,或后期,对食物线索的注意力偏见。后期注意偏差是有意识控制下的注意偏差,与初始/早期注意偏差相比,可能更容易改变。它反映了自动过程。本研究假设被分类为超重/肥胖的个体对食物线索的后期注意偏见大于被分类为正常体重的个体。30名被分类为超重/肥胖(BMI≥25)的参与者和47名被分类为正常体重(BMI<25)的参与者被评估了对食物提示的后期注意偏见。概念化为在特定于食物的视觉探针程序任务中同时呈现食物和中性图像时,固定在食物提示上的时间百分比。在被分类为超重至肥胖的个体中,固定在食物提示上的时间百分比为51.25±1.27(平均值SE),而被分类为正常体重的个体的固定百分比为47.26±0.87(P=0.03)。总之,被分类为超重至肥胖的个体对食物提示有更大的后期注意偏差.这建立了影响能量摄入的重要因素,可能会在未来的临床试验中进行修改。
    The Current food environment has become increasingly obesogenic, with rates of obesity and related conditions continually rising. Advertisements for energy-dense foods are abundant and promote unhealthy eating behaviors by capitalizing on one\'s attentional bias towards food cues, a cognitive process resulting from the sensitization of highly reinforcing food. A heightened awareness towards food cues may promote overconsumption of energy-dense foods. The current study employed novel eye-tracking methodology to capture sustained, or late-stage, attentional bias towards food cues. Late-stage attentional bias is the aspect of attentional bias under conscious control and likely more prone to modification compared to initial/ early-stage attentional bias, which reflects automatic processes. The present study hypothesized late-stage attentional bias towards food cues is greater among individuals classified as overweight/obese than those classified as normal weight. Thirty (30) participants classified as overweight/obese (BMI ≥25) and 47 classified as normal weight (BMI <25) were assessed for late-stage attentional bias towards food cues, conceptualized as the percentage of time fixated on food cues when both food and neutral images were presented during a food-specific visual probe procedure task. Percentage of time fixated on food cues was 51.25 ± 1.27 (mean + SE) among individuals classified as overweight to obese while those classified as normal weight had a percent fixation of 47.26 ± 0.87 (P=0.03). In conclusion, individuals classified as overweight to obese have greater late-stage attentional bias towards food cues. This establishes an important factor influencing energy intake that may be modified in future clinical trials.
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  • 文章类型: Journal Article
    在中性Wright-Fisher模型的扩散近似中,中性等位基因固定或丢失的预期时间与等位基因在群体中分布的初始熵成正比。对于这种巧合没有任何解释。在本文中,我们表明,熵耗散率与分离等位基因的数量成正比。由于最终固定状态的熵为零,分离等位基因的预期寿命与系统中的初始熵成正比。我们表明,关于分离等位基因丢失的平均时间和最后一个分离等位基因固定的预期时间的经典公式源于扩散过程的这些特性。我们还将我们的结果扩展到人口规模随时间变化的情况。杂合性和熵的耗散表明,超线性种群增长导致无限的预期固定时间,即,快速增长的种群中的中性等位基因可以永远隔离,而不会因遗传漂移而变得固定或消失。
    In the diffusion approximation of the neutral Wright-Fisher model, the expected time until fixation or loss of a neutral allele is proportional to the initial entropy of the distribution of the allele in the population. No explanation is known for this coincidence. In this paper, we show that the rate of entropy dissipation is proportional to the number of segregating alleles. Since the final fixed state has zero entropy, the expected lifetime of segregating alleles is proportional to the initial entropy in the system. We show that classical formulae on the average time to loss of segregating alleles and the expected time to fixation of the last segregating allele stem from these properties of the diffusion process. We also extend our results to the case of population size changing in time. The dissipation of heterozygosity and entropy shows that superlinear population growth leads to infinite expected fixation times, i.e., neutral alleles in fast-growing populations could segregate forever without ever becoming fixed or disappearing by genetic drift.
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  • 文章类型: Journal Article
    种子库(或休眠)是一种普遍的押注对冲策略,产生一种形式的人口重叠,这降低了遗传漂移的程度。集成此特性的方法复杂性意味着在开发用于检测选择性扫描的工具时将其忽略。但是,随着休眠延长祖先重组图(ARG),固定时间越来越长,它可以改变选择的基因组特征。为了在种子库物种中检测正选择下的基因,重要的是(1)确定选择的功效是否受到影响,(2)预测正选择等位基因及其周围的核苷酸多样性模式。我们提出了第一个基于树序列的模拟程序,该程序集成了弱种子库,以检查有限种群中有益等位基因的动态和基因组足迹。我们发现种子库不会影响固定的可能性,并证实了固定时间增加的预期。我们还证实了先前的发现,对于强大的选择,在种子库存在的情况下,近交有效种群规模不会扩大固定时间,但比预期的要短。随着种子库提高有效重组率,扫描的足迹在选定的站点周围显得更窄,并且由于ARG的缩放,可以在更长的时间内检测到。开发的模拟工具可用于预测选择的足迹,并得出植物过去进化事件的统计推断,无脊椎动物,或带有种子库的真菌。
    Seed banking (or dormancy) is a widespread bet-hedging strategy, generating a form of population overlap, which decreases the magnitude of genetic drift. The methodological complexity of integrating this trait implies it is ignored when developing tools to detect selective sweeps. But, as dormancy lengthens the ancestral recombination graph (ARG), increasing times to fixation, it can change the genomic signatures of selection. To detect genes under positive selection in seed banking species it is important to (1) determine whether the efficacy of selection is affected, and (2) predict the patterns of nucleotide diversity at and around positively selected alleles. We present the first tree sequence-based simulation program integrating a weak seed bank to examine the dynamics and genomic footprints of beneficial alleles in a finite population. We find that seed banking does not affect the probability of fixation and confirm expectations of increased times to fixation. We also confirm earlier findings that, for strong selection, the times to fixation are not scaled by the inbreeding effective population size in the presence of seed banks, but are shorter than would be expected. As seed banking increases the effective recombination rate, footprints of sweeps appear narrower around the selected sites and due to the scaling of the ARG are detectable for longer periods of time. The developed simulation tool can be used to predict the footprints of selection and draw statistical inference of past evolutionary events in plants, invertebrates, or fungi with seed banks.
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  • 文章类型: Journal Article
    标准化的预分析代码(SPREC)聚集了热缺血(WIT),冷缺血(CIT),和固定时间(FIT)在一个精确的格式。尽管在欧洲体外诊断法规或美国国立卫生研究院广泛的分析前计划的支持下,其重要性日益提高,鲜为人知的是,它在生物样本手术标本中的经验发生。在几个步骤中,组织银行伯尔尼实现了一个完全翔实的SPREC代码,具有来自10,555CIT的见解,4,740WIT,和3,121FIT值。在根据精益六西格玛原则进行工艺优化时,我们确定了SPREC代码作为样本特征和可追溯过程参数的双重作用。通过这项分析前研究,我们概述了各种器官的真实数据,这些器官在WIT方面存在特定差异,CIT,和FIT值。此外,我们的FIT数据表明,由于周末延误,SPREC固定有可能适应混凝土石蜡包埋时间点,并将其类别扩展到72小时以上。此外,我们从工作负载中确定了分析前变量的依赖关系,白天,和诊所是可行的精益流程管理。因此,白天简化的生物作业工作流程对工作负载高峰具有显著的弹性,在重应力条件下,将天然组织处理(即CIT)的周转时间从74.6分钟减少到46.1分钟。总之,即使在过程优化下,也有手术特定的预分析在手术病理上受到限制,这可能会影响生物标志物从一个实体转移到另一个实体。除了样本特征之外,SPREC编码对于组织库和病理学研究所跟踪WIT非常有益,CIT,和适合过程优化和监测测量。
    The standardized preanalytical code (SPREC) aggregates warm ischemia (WIT), cold ischemia (CIT), and fixation times (FIT) in a precise format. Despite its growing importance underpinned by the European in vitro diagnostics regulation or broad preanalytical programs by the National Institutes of Health, little is known about its empirical occurrence in biobanked surgical specimen. In several steps, the Tissue Bank Bern achieved a fully informative SPREC code with insights from 10,555 CIT, 4,740 WIT, and 3,121 FIT values. During process optimization according to LEAN six sigma principles, we identified a dual role of the SPREC code as a sample characteristic and a traceable process parameter. With this preanalytical study, we outlined real-life data in a variety of organs with specific differences in WIT, CIT, and FIT values. Furthermore, our FIT data indicate the potential to adapt the SPREC fixation toward concrete paraffin-embedding time points and to extend its categories beyond 72 h due to weekend delays. Additionally, we identified dependencies of preanalytical variables from workload, daytime, and clinics that were actionable with LEAN process management. Thus, streamlined biobanking workflows during the day were significantly resilient to workload peaks, diminishing the turnaround times of native tissue processing (i.e. CIT) from 74.6 to 46.1 min under heavily stressed conditions. In conclusion, there are surgery-specific preanalytics that are surgico-pathologically limited even under process optimization, which might affect biomarker transfer from one entity to another. Beyond sample characteristics, SPREC coding is highly beneficial for tissue banks and Institutes of Pathology to track WIT, CIT, and FIT for process optimization and monitoring measurements.
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  • 文章类型: Journal Article
    虚拟运动景观的树密度是决定广泛性焦虑症(GAD)患者在虚拟环境下运动时可以获得的收益的主要因素。通过使用瞳孔大小,固定计数和时间作为度量,本研究旨在阐明虚拟环境中树木覆盖密度与应力之间的关系。将90例GAD患者随机分为36-60%树密度(高树密度,HTDS),20-35%树密度(中等树密度,MTDS),或对照组(n=30)。研究人员使用眼动追踪技术来分析注视时间,固定计数和瞳孔大小的变化,以评估参与者在虚拟环境中进行20分钟有氧运动后的压力变化。结果表明,在虚拟环境中锻炼后,GAD患者的瞳孔大小扩大。此外,MTDS组中的GAD患者循环可以显示出比HTDS中更小的瞳孔大小。这些结果表明,MTDS组中GAD患者循环20分钟可以感觉到较低的压力。眼动追踪分析的结果表明,GAD患者花费更多的时间和计数观察HTDS和MTDS运动场景中的树元素。具体来说,在HTDS条件和MTDS条件下,他们在树木和绿色植物上花费了更多48%和27%的时间,分别,而不是非自然的体育节目。虽然36-60%树密度的虚拟自然运动景观可以从GAD患者那里获得更多的视觉关注,虚拟自然体育景观的20-35%树木密度更能减轻他们的压力。
    The tree density of virtual sportscape is the main factor that determines the benefits that generalized anxiety disorder (GAD) patients can obtain when they exercise with virtual environment. By using pupil size, fixation count and time as metrics, this research aimed to clarify the relationship between tree cover density and stress in the virtual environment. Ninety GAD patients were randomly grouped into the 36-60% tree density (high tree density, HTDS), 20-35% tree density (medium tree density, MTDS), or control groups (n = 30). Researchers used eye-tracking technology to analyze fixation time, fixation count and changes in pupil size to evaluate the stress changes of participants after 20 min of aerobic exercise in a virtual environment. The results showed that pupil size expanded in GAD patients after exercising in the virtual environment. Furthermore, GAD patient cycling in the MTDS group can show smaller pupil size than those in HTDS. Those results suggest that GAD patient cycling 20 min in the MTDS group can perceived lower stress. The results of eye tracking analysis showed that GAD patients spend more time and counts observing tree elements in HTDS and MTDS sportscapes. Specifically, they spent more 48% and 27% time on tree and green plants in the HTDS condition and MTDS condition, respectively, than in non-natural sportsscapes. Although 36-60% tree density of virtual natural sportscape can get more visual attention from GAD patients, 20-35% tree density of virtual natural sportscape is more capable of reducing their stress.
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  • 文章类型: Journal Article
    进化图论(EGT)研究了图约束下的Moran生死过程。它的两个主要目标是在图上找到一些初始突变体种群的固定概率和时间。图的固定概率受到了相当多的关注。关于固定时间的分布知之甚少。我们获得干净,固定和灭绝时间的紧密代理的完整条件特征函数(CCF)的精确表达式。该代理是在固定或灭绝之前突变体种群大小变化的次数。我们从乘积martingale中得出这些CCF,我们为具有任意数量分区的进化图识别。该句的存在只要求这些分区之间的连接是某种类型的。我们的结果是具有任意数量分区的图上任何代理固定时间的CCF的第一个表达式。我们的CCF的参数依赖性是明确的,所以我们可以探索它们如何依赖于图结构。Martingales是研究EGT主要问题的有力方法。它们的适用性对于图中的分区数量是不变的,所以我们可以同时研究整个系列的图形。
    Evolutionary graph theory (EGT) investigates the Moran birth-death process constrained by graphs. Its two principal goals are to find the fixation probability and time for some initial population of mutants on the graph. The fixation probability of graphs has received considerable attention. Less is known about the distribution of fixation time. We derive clean, exact expressions for the full conditional characteristic functions (CCFs) of a close proxy to fixation and extinction times. That proxy is the number of times that the mutant population size changes before fixation or extinction. We derive these CCFs from a product martingale that we identify for an evolutionary graph with any number of partitions. The existence of that martingale only requires that the connections between those partitions are of a certain type. Our results are the first expressions for the CCFs of any proxy to fixation time on a graph with any number of partitions. The parameter dependence of our CCFs is explicit, so we can explore how they depend on graph structure. Martingales are a powerful approach to study principal problems of EGT. Their applicability is invariant to the number of partitions in a graph, so we can study entire families of graphs simultaneously.
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  • 文章类型: Journal Article
    Although many experimental and theoretical studies on natural selection have been carried out in a constant environment, as natural environments typically vary in time, it is important to ask if and how the results of these investigations are affected by a changing environment. Here, we study the properties of the conditional fixation time defined as the time to fixation of a new mutant that is destined to fix in a finite, randomly mating diploid population with intermediate dominance that is evolving in a periodically changing environment. It is known that in a static environment, the conditional mean fixation time of a co-dominant beneficial mutant is equal to that of a deleterious mutant with the same magnitude of selection coefficient. We find that this symmetry is not preserved, even when the environment is changing slowly. More generally, we find that the conditional mean fixation time of an initially beneficial mutant in a slowly changing environment depends weakly on the dominance coefficient and remains close to the corresponding result in the static environment. However, for an initially deleterious mutant under moderate and slowly varying selection, the fixation time differs substantially from that in a constant environment when the mutant is recessive. As fixation times are intimately related to the levels and patterns of genetic diversity, our results suggest that for beneficial sweeps, these quantities are only mildly affected by temporal variation in environment. In contrast, environmental change is likely to impact the patterns due to recessive deleterious sweeps strongly.
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  • 文章类型: Journal Article
    Evolutionary graph theory investigates how spatial constraints affect processes that model evolutionary selection, e.g. the Moran process. Its principal goals are to find the fixation probability and the conditional distributions of fixation time, and show how they are affected by different graphs that impose spatial constraints. Fixation probabilities have generated significant attention, but much less is known about the conditional time distributions, even for simple graphs. Those conditional time distributions are difficult to calculate, so we consider a close proxy to it: the number of times the mutant population size changes before absorption. We employ martingales to obtain the conditional characteristic functions (CCFs) of that proxy for the Moran process on the complete bipartite graph. We consider the Moran process on the complete bipartite graph as an absorbing random walk in two dimensions. We then extend Wald\'s martingale approach to sequential analysis from one dimension to two. Our expressions for the CCFs are novel, compact, exact, and their parameter dependence is explicit. We show that our CCFs closely approximate those of absorption time. Martingales provide an elegant framework to solve principal problems of evolutionary graph theory. It should be possible to extend our analysis to more complex graphs than we show here.
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  • 文章类型: Journal Article
    The time taken for a selectively favorable allele to spread through a single population was investigated early in the history of population genetics. The resulting formulas are based on deterministic dynamics, leading to inaccuracies at allele frequencies close to 0 or 1. To remedy this problem, the properties of the stochastic phases at either end point of allele frequency need to be analyzed. This article uses a heuristic approach to determining the expected times spent in the stochastic and deterministic phases of allele frequency trajectories, for a model of weak selection at a single locus that is valid for inbreeding populations and for autosomal and sex-linked inheritance. The net fixation time is surprisingly insensitive to the level of dominance of a favorable mutation, even with random mating. Approximate expressions for the variance of the net fixation time are also obtained, which imply that there can be substantial stochastic effects even in very large populations. The accuracy of the approximations was evaluated by comparisons with computer simulations. The results reveal some areas that need further investigation if a full understanding of selective sweeps is to be obtained, notably the possibility that fixations of slightly deleterious mutations may be affecting variability at closely linked sites.
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