Extinction

灭绝
  • 文章类型: Journal Article
    通过表达正确的行为来回应社会信号不仅在自闭症中受到挑战,而且在自闭症患病率高的疾病中,比如Prader-Willi综合征(PWS).临床证据表明,鼻内催产素(OXT)或加压素(AVP)可以调节患者的异常亲社会行为。然而,在社会厌恶的背景下,受损的行为反应背后的神经元机制是什么,以及如何纠正它们,仍然很大程度上未知。
    使用PWS的Magel2敲除(KO)小鼠模型(与CRE依赖性转基因品系杂交),我们设计了光遗传学,社会恐惧条件范式中的生理和药理策略。OXT和AVP信号传导的通路特异性作用在侧隔(LS)上进行了研究,接收密集下丘脑输入的区域。
    OXT和AVP信号在LS中促进抑制性突触传递,Magel2KO小鼠的失败抑制了生长抑素(SST)神经元并破坏了社交恐惧的灭绝。OXT和AVP缺陷的来源特别定位在Magel2KO小鼠的视上核→LS途径中,破坏了社交恐惧灭绝,可以通过LS中SST神经元的光遗传学或药理学抑制来纠正。有趣的是,LSSST神经元也门控了攻击行为的表达,可能作为超出局部间隔电路的功能单元的一部分。
    SST细胞在孤独症中整合和表达破坏的神经肽信号中起着至关重要的作用,从而改变表达安全与恐惧的平衡。我们的结果揭示了在社会厌恶的背景下功能障碍的新机制,并为自闭症谱系障碍的未来治疗提供了新的框架。
    UNASSIGNED: Responding to social signals by expressing the correct behavior is not only challenged in autism, but also in diseases with high prevalence of autism, like Prader-Willi Syndrome (PWS). Clinical evidence suggests aberrant pro-social behavior in patients can be regulated by intranasal oxytocin (OXT) or vasopressin (AVP). However, what neuronal mechanisms underlie impaired behavioral responses in a socially-aversive context, and how can they be corrected, remains largely unknown.
    UNASSIGNED: Using the Magel2 knocked-out (KO) mouse model of PWS (crossed with CRE-dependent transgenic lines), we devised optogenetic, physiological and pharmacological strategies in a social-fear-conditioning paradigm. Pathway specific roles of OXT and AVP signaling were investigated converging on the lateral septum (LS), a region which receives dense hypothalamic inputs.
    UNASSIGNED: OXT and AVP signaling promoted inhibitory synaptic transmission in the LS, which failure in Magel2KO mice disinhibited somatostatin (SST) neurons and disrupted social-fear extinction. The source of OXT and AVP deficits mapped specifically in the supraoptic nucleus→LS pathway of Magel2KO mice disrupting social-fear extinction, which could be corrected by optogenetic or pharmacological inhibition of SST-neurons in the LS. Interestingly, LS SST-neurons also gated the expression of aggressive behavior, possibly as part of functional units operating beyond local septal circuits.
    UNASSIGNED: SST cells in the LS play a crucial role in integration and expression of disrupted neuropeptide signals in autism, thereby altering the balance in expression of safety versus fear. Our results uncover novel mechanisms underlying dysfunction in a socially-aversive context, and provides a new framework for future treatments in autism-spectrum disorders.
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  • 文章类型: Journal Article
    许多物种最近从濒临灭绝中恢复过来。尽管这些物种避免了直接的灭绝威胁,由于人口下降的潜在遗传后果,它们的长期生存能力仍然不稳定,在几代人以外的时间尺度上,人们对此知之甚少。大约10,000年前,猛犸象(Mammuthprimigenius)在Wrangel岛上与世隔绝,并持续了200多代,直到大约4,000年前灭绝。为了研究导致猛犸象灭绝的进化过程,我们分析了21个西伯利亚猛犸象的基因组.我们的结果表明,在随后的六千年中,人口迅速从严重的瓶颈中恢复过来,并在人口统计学上保持稳定。我们发现轻度有害突变逐渐积累,而高度有害的突变被清除,表明近亲繁殖的抑郁症持续了数百代。人口统计学和遗传恢复之间的时滞对最近出现瓶颈的种群的保护管理具有广泛的影响。
    A number of species have recently recovered from near-extinction. Although these species have avoided the immediate extinction threat, their long-term viability remains precarious due to the potential genetic consequences of population declines, which are poorly understood on a timescale beyond a few generations. Woolly mammoths (Mammuthus primigenius) became isolated on Wrangel Island around 10,000 years ago and persisted for over 200 generations before becoming extinct around 4,000 years ago. To study the evolutionary processes leading up to the mammoths\' extinction, we analyzed 21 Siberian woolly mammoth genomes. Our results show that the population recovered quickly from a severe bottleneck and remained demographically stable during the ensuing six millennia. We find that mildly deleterious mutations gradually accumulated, whereas highly deleterious mutations were purged, suggesting ongoing inbreeding depression that lasted for hundreds of generations. The time-lag between demographic and genetic recovery has wide-ranging implications for conservation management of recently bottlenecked populations.
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  • 文章类型: Journal Article
    显示灭绝的更新效应的趋势表现为个体内稳定,与海马BOLD激活的差异模式相关的可重复加工策略,iFG和vmPFC,以及前额叶区域和背侧注意网络之间的静息状态功能连接差异。此外,影响注意力处理的去甲肾上腺素能系统的药理学调节对具有(REN)和没有(NoREN)更新倾向的个体具有部分不同的影响。然而,目前尚不清楚REN和NoREN个体在注意力相关白质(WM)区域的微结构特性方面是否存在差异,以及这种差异是否与去甲肾上腺素能处理有关。在此扩散张量成像(DTI)分析中,我们研究了与注意力相关的WM束的微观结构特性与ABA更新倾向之间的关系,在通过去甲肾上腺素能再摄取抑制剂托莫西汀刺激去甲肾上腺素能的条件下,与安慰剂相比。与安慰剂(PLAC)相比,接受去甲肾上腺素能刺激(ATO)的参与者的各向异性分数(FA)更高,基于ATOREN和PLACREN参与者的比较,效应主要为左侧.在两个治疗组的REN参与者中,几个WM束的FA与ABA更新水平呈正相关,提示较高的更新水平与较高的微结构完整性相关.这些发现指出了与注意力相关的WM束的微观结构特性与更新倾向之间的关系,该关系并不特别依赖于去甲肾上腺素能的处理。
    The tendency to show the renewal effect of extinction appears as an intra-individually stable, reproducible processing strategy associated with differential patterns of BOLD activation in hippocampus, iFG and vmPFC, as well as differential resting-state functional connectivity between prefrontal regions and the dorsal attention network. Also, pharmacological modulations of the noradrenergic system that influence attentional processing have partially different effects upon individuals with (REN) and without (NoREN) a propensity for renewal. However, it is as yet unknown whether REN and NoREN individuals differ regarding microstructural properties in attention-related white matter (WM) regions, and whether such differences are related to noradrenergic processing. In this diffusion tensor imaging (DTI) analysis we investigated the relation between microstructural properties of attention-related WM tracts and ABA renewal propensity, under conditions of noradrenergic stimulation by means of the noradrenergic reuptake inhibitor atomoxetine, compared to placebo. Fractional anisotropy (FA) was higher in participants with noradrenergic stimulation (ATO) compared to placebo (PLAC), the effect was predominantly left-lateralized and based on the comparison of ATO REN and PLAC REN participants. In REN participants of both treatment groups, FA in several WM tracts showed a positive correlation with the ABA renewal level, suggesting higher renewal levels were associated with higher microstructural integrity. These findings point towards a relation between microstructural properties of attention-related WM tracts and the propensity for renewal that is not specifically dependent on noradrenergic processing.
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  • 文章类型: Journal Article
    许多分类学研究都集中在粪甲虫属Helictopleurusd'Orbigny,1915年,马达加斯加特有。然而,这个属stilll需要彻底修改。语义技术,比如纳米烧蚀,通过改变数据的发布和分析方式,保持增强分类法的潜力。本文评估了纳米消融在Helictopleurus属中建立同义词的有效性。
    在这项研究中,我们确定了Helictopleurus中的四个新同义词:H.rudicollis(Fairmaire,1898)=H.hypocritaBalthasar,1941syn。11月。H.VadoniLebis,1960=H.perpunctatusBalthasar,1963syn。11月。H.halffteriBalthasar,1964=H.dorbignyiMontreuil,2005syn.11月。;H.clouei(哈罗德,1869)=H.gibbicollis(Fairmaire,1895)syn。11月。Helictopleurus的同义词数量可能比目前已知的要多得多,表明对其最近灭绝的估计可能不准确。我们还将新建立的同义词发布为纳米化,它们是可在线访问的机器可读的数据片段。此外,我们探索了纳米ublitations在分类学中的实用性,并通过数据提取的示例查询演示了它们的实际用途。
    UNASSIGNED: Numerous taxonomic studies have focused on the dung beetle genus Helictopleurus d\'Orbigny, 1915, endemic to Madagascar. However, this genus stilll needs a thorough revision. Semantic technologies, such as nanopublications, hold the potential to enhance taxonomy by transforming how data are published and analysed. This paper evaluates the effectiveness of nanopublications in establishing synonyms within the genus Helictopleurus.
    UNASSIGNED: In this study, we identify four new synonyms within Helictopleurus: H.rudicollis (Fairmaire, 1898) = H.hypocrita Balthasar, 1941 syn. nov.; H.vadoni Lebis, 1960 = H.perpunctatus Balthasar, 1963 syn. nov.; H.halffteri Balthasar, 1964 = H.dorbignyi Montreuil, 2005 syn. nov.; H.clouei (Harold, 1869) = H.gibbicollis (Fairmaire, 1895) syn. nov. Helictopleurus may have a significantly larger number of synonyms than currently known, indicating potentially inaccurate estimates about its recent extinction.We also publish the newly-established synonyms as nanopublications, which are machine-readable data snippets accessible online. Additionally, we explore the utility of nanopublications in taxonomy and demonstrate their practical use with an example query for data extraction.
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  • 文章类型: Journal Article
    创伤记忆的灭绝,创伤后应激障碍(PTSD)的主要治疗方法(称为暴露疗法),通过重新学习发生,并且可能通过相关电路的长期增强(LTP)在分子水平上被保留。并行,重复经颅磁刺激(rTMS)被认为是通过LTP-like机制工作的,安全,和创伤后应激障碍的有效治疗。我们最近失败的随机对照试验(1)强调正确识别皮质目标的必要性,TMS协议的方向性,和记忆激活的作用。在这里,我们提供了对创伤后应激障碍的系统评价,以进一步确定如何,where,以及何时应进行TMS治疗以缓解PTSD症状。我们对涉及PTSD患者和结局的rTMS临床试验的文献进行了系统回顾。我们搜索了MEDLINE直到10月25日,2023年用于“TMS和PTSD”和“经颅磁刺激和创伤后应激障碍”。“31篇出版物符合我们的纳入标准(k=17项随机对照试验(RCT),k=14开放标签)。RCT协议在TMS协议中有所不同,皮层TMS目标,和内存激活协议。在低频方案中没有明显的优势(k=5)与高频协议(k=6),或通过刺激位置。记忆激发或暴露方案(k=7)似乎可以增强反应。总的来说,TMS似乎可以有效治疗各种TMS频率的PTSD症状,半球目标差异,和暴露协议。当被视为增强提出的抗焦虑网络或抑制抗焦虑网络时,不同的协议在概念上可能是统一的。
    Extinction of traumatic memory, a primary treatment approach (termed exposure therapy) in post-traumatic stress disorder (PTSD), occurs through relearning and may be subserved at the molecular level by long-term potentiation (LTP) of relevant circuits. In parallel, repetitive transcranial magnetic stimulation (rTMS) is thought to work through LTP-like mechanisms and may provide a novel, safe, and effective treatment for PTSD. Our recent failed randomized controlled trial (1) emphasizes the necessity of correctly identifying cortical targets, directionality of TMS protocol, and role of memory activation. Here we provide a systematic review of TMS for PTSD to further identify how, where, and when TMS treatment should be delivered to alleviate PTSD symptoms. We conducted a systematic review of the literature searching for rTMS clinical trials involving PTSD patients and outcomes. We searched MEDLINE through October 25th, 2023 for \"TMS and PTSD\" and \"transcranial magnetic stimulation and posttraumatic stress disorder.\" Thirty-one publications met our inclusion criteria (k=17 randomized controlled trials (RCTs), k=14 open label). RCT protocols were varied in TMS protocols, cortical TMS targets, and memory activation protocols. There was no clear superiority across protocols of low-frequency (k=5) vs. high-frequency protocols (k=6), or by stimulation location. Memory provocation or exposure protocols (k=7) appear to enhance response. Overall, TMS appears to be effective in treating PTSD symptoms across a variety of TMS frequencies, hemispheric target differences, and exposure protocols. Disparate protocols may be conceptually harmonized when viewed as potentiating proposed anxiolytic networks or suppressing anxiogenic networks.
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  • 文章类型: Journal Article
    器质性食欲灭绝涉及以前增强的反应的减少,当它的发生不再得到回报时。使用陆生蟾蜍(Rhinellaarenarum)进行的两项实验通过改变各组暴露于无回报的目标盒刺激的时间来测试非增强反应的发生是否对于反应灭绝是必要的。在实验1中,接受相同习得训练的蟾蜍(15次,1次/天,在目标框中获取水的300s)被随机分配到两组。在600组中(n=12),动物在8个每日灭绝会议中在目标箱中度过了600秒(水存在但无法进入)。在第0组(n=11)中,蟾蜍执行跑道响应(即,从开始走到目标框),但一进入目标框就被移除,因此,对无回报的目标框刺激的暴露量最小。在灭绝试验中,600组的跑道反应减弱了,但在第0组中几乎没有变化。在实验2中,在相同的习得训练后,将蟾蜍随机分配到两组。组0(n=7)与先前实验中的组0相同地处理。在RI组中(保留间隔,n=7),蟾蜍在笼子里呆了13天。最后,所有的动物都在空的球门框中接受了4次灭绝,时间为300秒。在13个疗程中,第0组的行为变化很小,对目标框的暴露量最小。在灭绝中,两组均以相似的速率降低跑道响应。尽管程序是有帮助的,蟾蜍跑道反应的灭绝可以通过对刺激的巴甫洛夫进近反应以及目标框中的奖励和非奖励来解释。
    Instrumental appetitive extinction involves the reduction of a previously reinforced response when its occurrence is no longer rewarded. Two experiments with terrestrial toads (Rhinella arenarum) tested whether the occurrence of a nonreinforced response is necessary for response extinction by varying the time of exposure to nonrewarded goal-box stimuli across groups. In Experiment 1, toads that received the same acquisition training (15 sessions, 1 session/day, 300 s of access to water in the goal box) were randomly assigned to two groups. In Group 600 (n=12), animals spent 600 s in the goal box in 8 daily extinction sessions (water present but inaccessible). In Group 0 (n=11), toads performed the runway response (i.e., walking from the start to the goal box) but were removed as soon as they entered the goal box, thus having minimal exposure to nonrewarded goal-box stimuli. The runway response was weakened in Group 600 across extinction trials, but exhibited little change in Group 0. In Experiment 2, toads were randomly assigned to two groups after the same acquisition training. Group 0 (n=7) was treated the same as Group 0 in the previous experiment. In Group RI (retention interval, n=7), toads remained in their home cage for 13 days. Finally, all animals received 4 extinction sessions with 300 s in the empty goal box. There was little behavioral change in Group 0 during the 13 sessions with minimal exposure to the goal box. In extinction, both groups reduced their runway response at similar rates. Although the procedures were instrumental, extinction of the runway response in toads can be accounted for in terms of a Pavlovian approach response to stimuli paired with reward and nonreward in the goal box.
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  • 文章类型: Journal Article
    在本文中,我们考虑了具有修改Leslie-Gower的随机两物种捕食者-食饵系统。同时,我们假设捕食者中发生了狩猎合作。通过运用IT公式构造一个合适的Lyapunov函数,我们首先证明,对于任何给定的正初始值,都有一个唯一的全局正解。此外,基于切比雪夫不等式,讨论了随机最终有界性和随机持久性。然后,在某些条件下,我们证明了系统的均值和灭绝的持久性。最后,我们通过数值模拟验证了我们的结果。
    In this paper, we consider a stochastic two-species predator-prey system with modified Leslie-Gower. Meanwhile, we assume that hunting cooperation occurs in the predators. By using Itô formula and constructing a proper Lyapunov function, we first show that there is a unique global positive solution for any given positive initial value. Furthermore, based on Chebyshev inequality, the stochastic ultimate boundedness and stochastic permanence are discussed. Then, under some conditions, we prove the persistence in mean and extinction of system. Finally, we verify our results by numerical simulations.
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  • 文章类型: Journal Article
    在链霉菌科(Bryophyta)中,分形进化显然可以有效地选择性保留环境适应性特征超过8000万年。分析模拟了该大谱系中祖先特征的最大破坏。实施的约束是保留最新的祖先特征,所有直系后代物种都获得了不同的新性状。祖先性状的最大性状状态变化是任何一个子谱系中所有可能性状的16%,或整个血统的73%。结果显示,然而,在任何一个谱系或亚谱系中,只有四个祖先性状被永久消除。对于所研究的小组,谱系在8800万年的地质时间内以最低的恢复力费用保持了时间和区域生存有效特征的最大生物多样性。类似的过程会产生现存的标点平衡,因为在其他生命群体中,每个属大约四个后代和每1-2个时期一个属的爆发是可能的。该机制被认为是复杂性相关的,谱系是一种自组织的新兴现象,通过分形属的自然选择,在生态圈中得到了强烈的维持。
    Fractal evolution is apparently effective in selectively preserving environmentally resilient traits for more than 80 million years in Streptotrichaceae (Bryophyta). An analysis simulated maximum destruction of ancestral traits in that large lineage. The constraints enforced were the preservation of newest ancestral traits, and all immediate descendant species obtained different new traits. Maximum character state changes in ancestral traits were 16 percent of all possible traits in any one sub-lineage, or 73 percent total of the entire lineage. Results showed, however, that only four ancestral traits were permanently eliminated in any one lineage or sub-lineage. A lineage maintains maximum biodiversity of temporally and regionally survival-effective traits at minimum expense to resilience across a geologic time of 88 million years for the group studied. Similar processes generating an extant punctuated equilibrium as bursts of about four descendants per genus and one genus per 1-2 epochs are possible in other living groups given similar emergent processes. The mechanism is considered complexity-related, the lineage being a self-organized emergent phenomenon strongly maintained in the ecosphere by natural selection on fractal genera.
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  • 文章类型: Journal Article
    在深入调查全球生物多样性模式时,已经提出了许多大规模的多样化驱动因素,生物和非生物。然而,关于这些假设的效应子或它们的作用,几乎没有得出可靠的结论。这里,在检查特定的假设驱动因素之前,我们使用线性随机微分方程(SDE)框架来测试多元化模式的潜在驱动因素的存在。使用全球骨骼化海洋化石观测数据集,我们推断起源,使用捕获-标记-重新捕获方法,整个显生代的灭绝和采样率(统称为化石时间序列)。使用线性SDE,然后,我们比较模型,包括和排除这些化石时间序列的隐藏(即未测量)驱动因素。我们发现了海洋显生代多样化率的大规模潜在驱动因素的证据,并提出了这些因素的定量特征。然后我们测试全球温度是否变化,海平面,海洋沉积物区域或大陆碎片可能是化石时间序列的驱动因素。我们表明,这四个非生物因素中的任何一个都不可能是我们确定的隐藏驱动因素,尽管有证据表明沉积物面积与起源/灭绝率之间存在相关联系。我们对显生代多样化和采样的隐藏驱动因素的描述将有助于寻找他们的最终身份。
    In investigating global patterns of biodiversity through deep time, many large-scale drivers of diversification have been proposed, both biotic and abiotic. However, few robust conclusions about these hypothesized effectors or their roles have been drawn. Here, we use a linear stochastic differential equation (SDE) framework to test for the presence of underlying drivers of diversification patterns before examining specific hypothesized drivers. Using a global dataset of observations of skeletonized marine fossils, we infer origination, extinction and sampling rates (collectively called fossil time series) throughout the Phanerozoic using a capture-mark-recapture approach. Using linear SDEs, we then compare models including and excluding hidden (i.e. unmeasured) drivers of these fossil time series. We find evidence of large-scale underlying drivers of marine Phanerozoic diversification rates and present quantitative characterizations of these. We then test whether changing global temperature, sea-level, marine sediment area or continental fragmentation could act as drivers of the fossil time series. We show that it is unlikely any of these four abiotic factors are the hidden drivers we identified, though there is evidence for correlative links between sediment area and origination/extinction rates. Our characterization of the hidden drivers of Phanerozoic diversification and sampling will aid in the search for their ultimate identities.
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  • 文章类型: Journal Article
    暴露疗法是一线疗法,对焦虑症的经验验证治疗,强迫症,和创伤相关的疾病。灭绝学习是暴露疗法的主要理论框架,因此,随着时间的推移,对恐惧结果的反复不确认会导致恐惧减少。尽管该框架具有强大的经验支持和大量的转化效用,灭绝学习不太可能是暴露疗法治疗效果的唯一基础过程。在我们的诊所里,我们通常治疗强迫症(OCD)患者成功地与暴露疗法,即使当他们的部分或全部的恐惧的结果是不能接受不确认,通过延伸,灭绝学习在这里,我们提供了一个通用的临床小插图,说明了强迫症中常见的恐惧结局,该结局无法通过暴露(亵渎思想造成的诅咒)得到证实。我们描述了在这种情况下我们通常采用的两种特定的非灭绝策略,我们将这些策略与已知的改变机制联系起来,这些机制可能解释了它们的有效性:(1)对厌恶刺激的非关联习惯,(2)恐惧记忆启发和随后的再巩固。我们讨论了所采用的反向翻译方法固有的局限性及其扩展暴露疗法框架的机会。
    Exposure therapy is a first-line, empirically validated treatment for anxiety, obsessive-compulsive, and trauma-related disorders. Extinction learning is the predominant theoretical framework for exposure therapy, whereby repeated disconfirmation of a feared outcome yields fear reduction over time. Although this framework has strong empirical support and substantial translational utility, extinction learning is unlikely to be the sole process underlying the therapeutic effects of exposure therapy. In our clinic, we commonly treat obsessive-compulsive disorder (OCD) patients successfully with exposure therapy even when some or all of their feared outcomes are not amenable to disconfirmation and, by extension, to extinction learning. Herein, we present a generic clinical vignette illustrating a commonly encountered feared outcome in OCD that cannot be disconfirmed through exposure (damnation resulting from blasphemous thoughts). We describe two specific non-extinction-based strategies we commonly employ in such cases, and we associate these strategies with known change mechanisms that might account for their effectiveness: (1) non-associative habituation to aversive stimuli, and (2) fear-memory elicitation and subsequent reconsolidation. We discuss the limitations inherent in the reverse-translational approach taken and its opportunities for expanding the framework of exposure therapy.
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