BACKGROUND & AIMS: :HSP90 is a molecular chaperone that participates in folding, stabilization, activation, and assembly of several proteins, all of which are key regulators in cell signaling. In dimorphic pathogenic fungi such as Paracoccidioides brasiliensis, the adaptation to a higher temperature, acid pH and oxidative stress, is an essential event for fungal survival and also for the establishing of the infectious process. To further understand the role of this protein, we used antisense RNA technology to generate a P. brasiliensis isolate with reduced PbHSP90 gene expression (PbHSP90-aRNA). Reduced expression of HSP90 decreased yeast cell viability during batch culture growth and increased susceptibility to acid pH environments and imposed oxidative stress. Also, PbHSP90-aRNA yeast cells presented reduced viability upon interaction with macrophages. The findings presented here suggest a protective role for HSP90 during adaptation to hostile environments, one that promotes survival of the fungus during host-pathogen interactions.

背景与目标： : HSP90是一种分子伴侣，参与多种蛋白质的折叠，稳定，激活和组装，所有这些蛋白质都是细胞信号传导的关键调节剂。在双态致病性真菌 (例如巴西Paracoccidioides brasiliensis) 中，适应较高的温度，酸性pH和氧化应激是真菌存活以及建立感染过程的重要事件。为了进一步了解该蛋白的作用，我们使用反义RNA技术生成了具有降低PbHSP90基因表达 (PbHSP90-aRNA) 的巴西假单胞菌分离株。HSP90的表达降低了分批培养过程中酵母细胞的活力，并增加了对酸性pH环境的敏感性并施加了氧化应激。此外，PbHSP90-aRNA酵母细胞在与巨噬细胞相互作用时表现出降低的活力。此处提出的发现表明，HSP90在适应敌对环境期间具有保护作用，在宿主-病原体相互作用期间可促进真菌的存活。

BACKGROUND & AIMS: :We have previously shown in normal subjects that motor adaptation to imposed visual rotation is significantly enhanced when tested few days later. This occurs through a process of sleep-dependent memory consolidation. Here we ascertained whether patients with Parkinson's disease (PD) learn, improve, and retain new motor skills in the same way as normal subjects. We tested 16 patients in early stages of PD and 21 control subjects over two days. All subjects performed reaching movements on a digitizing tablet. Vision of the limb was precluded with an opaque screen; hand paths were shown on the screen with the targets' position. Unbeknownst to the subjects, the hand path on the screen was rotated by 30 degrees . In experiment 1, patients taking dopaminergic treatment and controls adapted to rotation with targets appearing in an unpredictable order. In experiment 2, drug-naïve patients and controls adapted to rotation in a less challenging task where target's appearance was predictable. Patients and controls made similar movements and adapted to rotation in the same way. However, when tested again over the following days, controls' performance significantly improved compared to training, while patients' performance did not. This lack of consolidation, which is present in the early stages of the disease and is independent from therapy, may be due to abnormal homeostatic processes that occur during sleep.

背景与目标： : 我们先前已经在正常受试者中表明，几天后进行测试时，对施加的视觉旋转的运动适应性显着增强。这是通过依赖睡眠的记忆巩固过程发生的。在这里，我们确定帕金森氏病 (PD) 患者是否以与正常人相同的方式学习，改善和保留新的运动技能。我们在两天内测试了16名PD早期患者和21名对照受试者。所有受试者都在数字化平板电脑上进行了伸手动作。不透明的屏幕阻止了肢体的视力; 屏幕上显示了目标位置的手路径。受试者不知道，屏幕上的手路径旋转了30度。在实验1中，接受多巴胺能治疗的患者和对照适应旋转，目标以不可预测的顺序出现。在实验2中，未接受药物治疗的患者和对照组适应了一项挑战性较小的任务，而目标的外观是可预测的。患者和对照组进行了类似的运动，并以相同的方式适应了旋转。但是，在接下来的几天中再次进行测试时，与训练相比，对照组的表现显着改善，而患者的表现却没有。这种缺乏巩固，存在于疾病的早期阶段，独立于治疗，可能是由于睡眠期间发生的异常稳态过程。

BACKGROUND & AIMS: :Dietary nutrients shape complex interactions between hosts and their commensal gut bacteria, further promoting flexibility in host-microbiota associations that can drive nutritional symbiosis. However, it remains less clear if diet-dependent host signaling mechanisms also influence these associations. Using Drosophila, we show here that nuclear factor κB (NF-κB)/Relish, an innate immune transcription factor emerging as a signaling node linking nutrient-immune-metabolic interactions, is vital to adapt gut microbiota species composition to host diet macronutrient composition. We find that Relish is required within midgut enterocytes to amplify host-Lactobacillus associations, an important bacterial mediator of nutritional symbiosis, and thus modulate microbiota composition in response to dietary adaptation. Relish limits diet-dependent transcriptional inducibility of the cap-dependent translation inhibitor 4E-BP/Thor to control microbiota composition. Furthermore, maintaining cap-dependent translation in response to dietary adaptation is critical to amplify host-Lactobacillus associations. These results highlight that NF-κB-dependent host signaling mechanisms, in coordination with host translation control, shape diet-microbiota interactions.

背景与目标： : 膳食营养素形成宿主与其共生肠道细菌之间复杂的相互作用，进一步促进宿主-微生物群关联的灵活性，从而推动营养共生。然而，尚不清楚依赖饮食的宿主信号传导机制是否也会影响这些关联。使用果蝇，我们在这里显示核因子 κ b (NF-κ b)/Relish，一种先天免疫转录因子，作为连接营养-免疫-代谢相互作用的信号节点出现，对于使肠道菌群物种组成适应宿主饮食中的大量营养素组成至关重要。我们发现，在中肠肠细胞中需要津津乐道来扩增宿主-乳酸菌的关联，这是营养共生的重要细菌介质，从而响应饮食适应来调节微生物群的组成。Relish限制了cap依赖性翻译抑制剂4E-BP/Thor的饮食依赖性转录诱导性，以控制微生物群组成。此外，保持对饮食适应的cap依赖性翻译对于扩增宿主-乳杆菌的关联至关重要。这些结果突出表明，NF-κ b依赖性宿主信号传导机制与宿主翻译控制相协调，塑造了饮食与微生物群的相互作用。

BACKGROUND & AIMS: :The genus Oryzias consists of 35 medaka-fish species each exhibiting various ecological, morphological and physiological peculiarities and adaptations. Beyond of being a comprehensive phylogenetic group for studying intra-genus evolution of several traits like sex determination, behavior, morphology or adaptation through comparative genomic approaches, all medaka species share many advantages of experimental model organisms including small size and short generation time, transparent embryos and genome editing tools for reverse and forward genetic studies. The Java medaka, Oryzias javanicus, is one of the two species of medaka perfectly adapted for living in brackish/sea-waters. Being an important component of the mangrove ecosystem, O. javanicus is also used as a valuable marine test-fish for ecotoxicology studies. Here, we sequenced and assembled the whole genome of O. javanicus, and anticipate this resource will be catalytic for a wide range of comparative genomic, phylogenetic and functional studies. Complementary sequencing approaches including long-read technology and data integration with a genetic map allowed the final assembly of 908 Mbp of the O. javanicus genome. Further analyses estimate that the O. javanicus genome contains 33% of repeat sequences and has a heterozygosity of 0.96%. The achieved draft assembly contains 525 scaffolds with a total length of 809.7 Mbp, a N50 of 6,3 Mbp and a L50 of 37 scaffolds. We identified 21454 predicted transcripts for a total transcriptome size of 57, 146, 583 bps. We provide here a high-quality chromosome scale draft genome assembly of the euryhaline Javafish medaka (321 scaffolds anchored on 24 chromosomes (representing 97.7% of the total bases)), and give emphasis on the evolutionary adaptation to salinity.

背景与目标： : Oryzias属由35种fish鱼组成，每种鱼都表现出各种生态，形态和生理特性以及适应性。除了通过比较基因组方法研究性别决定，行为，形态或适应性等多种性状的属内进化的综合系统发育组之外，所有的青the物种都具有许多实验模式生物的优势，包括体积小，世代时间短，用于反向和正向遗传研究的透明胚胎和基因组编辑工具。爪哇medaka，Oryzias javanicus，是两个非常适合生活在咸水/海水中的medaka物种之一。O. javanicus是红树林生态系统的重要组成部分，也被用作生态毒理学研究的有价值的海洋试验鱼。在这里，我们对O. javanicus的整个基因组进行了测序和组装，并预计该资源将对广泛的比较基因组，系统发育和功能研究具有催化作用。包括长读技术和与遗传图谱的数据集成在内的互补测序方法允许爪哇爪哇基因组的908 Mbp的最终组装。进一步的分析估计O. javanicus基因组包含重复序列的33% 并且具有0.96% 的杂合性。所实现的草稿组件包含总长度为809.7 Mbp的525支架、6,3 Mbp的N50和37支架的L50。对于57、146、583个bps的总转录组大小，我们确定了21454个预测转录本。我们在这里提供了一个高质量的染色体规模基因组草图组装的euryhaline Javafish medaka (321个支架锚定在24条染色体上 (代表总碱基的97.7%))，并强调了对盐度的进化适应。

BACKGROUND & AIMS: :Virtual rehabilitation has been used during decades to provide a more personalized, controlled, and enjoyable experience on upper-limb motor rehabilitation. Since novel virtual reality (VR) technologies are now accessible and highly immersive, the challenge for a wide dissemination of virtual rehabilitation in clinical scenarios has shifted from the hardware robustness to the software intelligence. A sophisticated technique that provides physiological intelligence to novel human-computer interaction (HCI) applications is biocybernetic adaptation. The concept emerges from the electrophysiological computing field, and it proposes using body signals to detect human states (e.g. workload or fatigue) and modulate the virtual activity accordingly. This paper evaluates the effects of using biocybernetic adaptation in a virtual rehabilitation game that aims to encourage users to exert at a desirable intensity level while interacting with the virtual environment. The system relies on surface-electromyography (sEMG) signals to detect fatigue levels in real-time and adapt the game challenge dynamically. Perceived fatigue levels, game user experience, and game performance parameters are assessed after playing the game, considering two different visualization modalities: non-immersive (conventional flat screen) and immersive (VR headset). Results revealed how the biocybernetic system in the immersive condition not only produced lower levels of perceived fatigue compared with the non-immersive, but also, created a more enjoyable and positive experience in a controlled experiment with 24 healthy subjects. Moreover, participants in the immersive condition showed a better performance in the virtual game and higher usability levels scored by users compared with the non-immersive condition. To conclude, we highlight the importance of combining novel immersive approaches with physiologically aware systems to enhance the benefits of virtual rehabilitation therapies.

背景与目标： : 虚拟康复在过去的几十年中一直被用来为上肢运动康复提供更加个性化，可控和愉快的体验。由于新颖的虚拟现实 (VR) 技术现在可以访问并且高度沉浸式，因此在临床场景中广泛传播虚拟康复的挑战已从硬件鲁棒性转向软件智能。生物细胞适应是一种为新型人机交互 (HCI) 应用提供生理智能的复杂技术。该概念来自电生理计算领域，它提出使用身体信号来检测人类状态 (例如工作量或乏力) 并相应地调节虚拟活动。本文评估了在虚拟康复游戏中使用生物细胞适应的效果，该游戏旨在鼓励用户在与虚拟环境交互的同时以理想的强度发挥作用。该系统依靠表面肌电图 (sEMG) 信号来实时检测乏力水平并动态适应游戏挑战。考虑两种不同的可视化方式: 非沉浸式 (常规平板屏幕) 和沉浸式 (VR耳机)，在玩游戏后评估感知乏力水平，游戏用户体验和游戏性能参数。结果表明，与非沉浸式相比，沉浸式生物细胞系统不仅产生了较低的感知乏力水平，而且在24位健康受试者的对照实验中创造了更愉快和积极的体验。此外，与非沉浸状态相比，沉浸状态的参与者在虚拟游戏中表现出更好的性能，并且用户获得了更高的可用性水平。最后，我们强调了将新颖的沉浸式方法与生理感知系统相结合以增强虚拟康复疗法的益处的重要性。

BACKGROUND & AIMS: OBJECTIVE:Orthorexia is a pathological fixation about the consumption of healthy food. The present study aimed to reveal the psychometric properties of the Turkish version of ORTO-15, which was developed to evaluate orthorexia, and to investigate the relationship betweenorthorexia, and eating attitude, obsessive-compulsive symptoms, and some demographic variables. METHOD:The study included 994 participants aged between 19 and 66 years. ORTO-15, the Maudsley Obsessive-Compulsive Inventory, and the Eating Attitude Test-40 were administered to the participants. RESULTS:A 3-factor solution with varimax rotation explained 40.62% of the variance. When 4 items with factor loadings below+/- 0.50 were eliminated from ORTO-15, the Cronbach's alpha coefficient was 0.62. The remaining 11 items were thought to have statistically satisfactory properties for the Turkish version of ORTO and were collectively referred to as ORTO-11. This version was used to investigate the relationship between orthorexia, and eating attitude and obsessive-compulsive symptoms. Pathological eating attitude and obsessive-compulsive symptoms were related to orthorexia. Women exhibited more orthorexic symptoms then men. In the present study high a body mass index was an important variable for orthorexia, but only together with gender (female), pathological eating attitude, and increased obsessive-compulsive symptoms. The results, implications, and limitations of the study are discussed. CONCLUSION:ORTO-11 demonstrated statistically satisfactory properties. Orthorexia was related to pathological eating attitude and obsessive-compulsive symptoms; however, caution should be used when generalizing the reported results.

背景与目标：

BACKGROUND & AIMS: :An amendment to this paper has been published and can be accessed via the original article.

背景与目标： : 本文的修正案已经发表，可以通过原始文章访问。

BACKGROUND & AIMS: :We showed recently that exposure to whisker vibrations enhances coding efficiency in rat barrel cortex despite increasing correlations in variability (Adibi et al., 2013). Here, to understand how adaptation achieves this improvement in sensory representation, we decomposed the stimulus information carried in neuronal population activity into its fundamental components in the framework of information theory. In the context of sensory coding, these components are the entropy of the responses across the entire stimulus set (response entropy) and the entropy of the responses conditional on the stimulus (conditional response entropy). We found that adaptation decreased response entropy and conditional response entropy at both the level of single neurons and the pooled activity of neuronal populations. However, the net effect of adaptation was to increase the mutual information because the drop in the conditional entropy outweighed the drop in the response entropy. The information transmitted by a single spike also increased under adaptation. As population size increased, the information content of individual spikes declined but the relative improvement attributable to adaptation was maintained.

背景与目标： : 我们最近表明，尽管变异性之间的相关性增加，但暴露于晶须振动仍可提高大鼠桶皮层中的编码效率 (Adibi等，2013)。在这里，为了了解适应如何实现感官表现的这种改善，我们在信息论的框架内将神经元群体活动中携带的刺激信息分解为其基本组成部分。在感官编码的上下文中，这些成分是整个刺激集的响应的熵 (响应熵) 和以刺激为条件的响应的熵 (条件响应熵)。我们发现，适应在单个神经元水平和神经元群体的合并活动上都降低了响应熵和条件响应熵。但是，适应的净效果是增加互信息，因为条件熵的下降超过了响应熵的下降。在适应的情况下，单个峰值传输的信息也会增加。随着人口规模的增加，单个峰值的信息含量下降，但归因于适应的相对改善得以保持。

BACKGROUND & AIMS: :The ability to appropriately respond to environmental conditions is critical for the survival of simple microbes and for development of complex multicellular organisms. Sensing and responding to a given environmental condition requires the integration of numerous signals through one or more signal transduction pathways. This leads to changes in gene expression, and potentially post-translational modifications, that favour growth in the given environment. In the fungus Candida albicans, an important opportunistic pathogen, environmental pH has profound effects on morphology and proper adaptation to extracellular pH is critical for pathogenesis. Here, we demonstrate that the Rim101/PacC pH-sensing pathway acts in parallel to Crz1, via calcineurin, to adapt to alkaline pH. We also show that the Rim101 pathway acts in parallel to Crz2, independent of calcineurin, to adapt to high lithium concentrations and to repress filamentation at acidic pH. Our studies also revealed a novel requirement for Crz1, Crz2 and calcineurin for growth at acidic pH. From these studies, we propose that the Crz1 homologue Crz2 is calcineurin-independent, but like Crz1, acts in parallel to promote specific Rim101-dependent processes. These results establish and begin to dissect the complex interactions between important signal transduction pathways in C. albicans, which are critical for virulence.

背景与目标： : 对环境条件做出适当反应的能力对于简单微生物的生存和复杂多细胞生物的发育至关重要。感测和响应给定的环境条件需要通过一个或多个信号转导途径整合众多信号。这会导致基因表达的变化，以及潜在的翻译后修饰，从而有利于在给定环境中生长。在重要的机会性病原体白色念珠菌中，环境pH对形态有深远的影响，对细胞外pH的适当适应对发病机理至关重要。在这里，我们证明了Rim101/PacC pH感应途径通过钙调神经磷酸酶与Crz1平行作用，以适应碱性pH。我们还表明，Rim101途径与Crz2平行，独立于钙调神经磷酸酶，以适应高锂浓度并抑制酸性pH下的丝化。我们的研究还揭示了Crz1，Crz2和钙调神经磷酸酶在酸性pH下生长的新需求。从这些研究中，我们建议Crz1同源物Crz2不依赖钙调神经磷酸酶，但与Crz1一样，平行作用以促进特定的Rim101-dependent过程。这些结果建立并开始剖析白色念珠菌重要信号转导途径之间的复杂相互作用，这对毒力至关重要。

BACKGROUND & AIMS: :Obesity and type II diabetes are characterized by insulin resistance in peripheral tissues. A high caloric intake combined with a sedentary lifestyle is the leading cause of these conditions. Whole-body insulin resistance and its improvement are the result of the combined actions of each insulin-sensitive organ. Among the fundamental molecular mechanisms by which each organ is able to communicate and engage in cross-talk are cytokines or peptides which stem from secretory organs. Recently, it was reported that several cytokines or peptides are secreted from muscle (myokines), adipose tissue (adipokines) and liver (hepatokines) in response to certain nutrition and/or physical activity conditions. Cytokines exert autocrine, paracrine or endocrine effects for the maintenance of energy homeostasis. The present review is focused on the relationship and cross-talk amongst muscle, adipose tissue and the liver as secretory organs in metabolic diseases.

背景与目标： : 肥胖和II型糖尿病的特征是外周组织的胰岛素抵抗。高热量摄入加上久坐的生活方式是这些疾病的主要原因。全身胰岛素抵抗及其改善是每个胰岛素敏感器官共同作用的结果。在每个器官能够交流和参与串扰的基本分子机制中，有来自分泌器官的细胞因子或肽。最近，据报道，响应某些营养和/或身体活动条件，从肌肉 (肌动因子)，脂肪组织 (脂肪因子) 和肝脏 (肝因子) 分泌了几种细胞因子或肽。细胞因子发挥自分泌，旁分泌或内分泌作用，以维持能量稳态。本综述主要集中在代谢性疾病中肌肉，脂肪组织和肝脏作为分泌器官之间的关系和串扰。

BACKGROUND & AIMS: :Biopsychosocial adaptation remains a multifaceted challenge for individuals with spinal cord injury, their families, and healthcare providers alike. The development of frequent medical complications necessitating healthcare interventions is an ongoing, debilitating, and costly problem for those living with spinal cord injuries. Although several demographic variables have been correlated with positive adaptation in individuals with spinal cord injury, the research outcome data present limitations in understanding and facilitating which coping techniques work best to augment biopsychosocial adaptation in this population. Coping facilitates adaptation and adjustment to stress and can help to increase quality of life in people living with spinal cord injury and reduce common complications. The purpose of this study was to determine the extent to which sociodemographic characteristics and hardiness explain coping in 243 adults living with a spinal cord injury. In addition, this study examined which predictors of coping explain biopsychosocial adaptation. A descriptive explanatory design was utilized. Standardized instruments were administered nationally to assess hardiness, coping, and physiological and psychosocial adaptation. Canonical correlation and multiple regression analyses indicated that less educated, less hardy, and recently injured participants were more likely to use escape-avoidance coping and less likely to use social support, problem solving, and positive reappraisal coping behaviors (p < .05). Individuals with paraplegia had a higher level of functional ability, spent less time in rehabilitation, had a greater sense of control, and experienced less frequent complications. The control dimension of hardiness was the only dimension that significantly related to biopsychosocial adaptation within this sample.

背景与目标： : 对于脊髓损伤的个人，他们的家人和医疗保健提供者来说，生物心理社会适应仍然是一个多方面的挑战。对于患有脊髓损伤的人来说，需要进行医疗干预的频繁医疗并发症的发展是一个持续，令人衰弱且代价高昂的问题。尽管一些人口统计学变量与脊髓损伤个体的积极适应相关，但研究结果数据在理解和促进哪种应对技术最能增强该人群的生物心理社会适应方面存在局限性。应对有助于适应和适应压力，并有助于提高脊髓损伤患者的生活质量并减少常见并发症。这项研究的目的是确定社会人口统计学特征和坚固性在多大程度上解释了243名患有脊髓损伤的成年人的应对方式。此外，这项研究考察了应对的哪些预测因素解释了生物心理社会适应。采用描述性解释性设计。在全国范围内使用标准化工具来评估硬度，应对能力以及生理和社会心理适应能力。典型相关和多元回归分析表明，受教育程度低、耐寒和最近受伤的参与者更有可能使用逃避应对，而不太可能使用社会支持、解决问题和积极的重新评估应对行为 (p <.05)。截瘫患者的功能能力较高，康复时间较少，控制意识较强，并发症发生率较低。在该样本中，硬度的控制维度是与生物心理社会适应显着相关的唯一维度。

BACKGROUND & AIMS: :Knowledge of the number and nature of genetic changes responsible for adaptation is essential for understanding and predicting evolutionary trajectories. Here, we study the genomic basis of compensatory adaptation to the fitness cost of fungicide resistance in experimentally evolved strains of the filamentous fungus Aspergillus nidulans The original selection experiment tracked the fitness recovery of lines founded by an ancestral strain that was resistant to fludioxonil, but paid a fitness cost in the absence of the fungicide. We obtained whole-genome sequence data for the ancestral A. nidulans strain and eight experimentally evolved strains. We find that fludioxonil resistance in the ancestor was likely conferred by a mutation in histidine kinase nikA, part of the two-component signal transduction system of the high-osmolarity glycerol (HOG) stress response pathway. To compensate for the pleiotropic negative effects of the resistance mutation, the subsequent fitness gains observed in the evolved lines were likely caused by secondary modification of HOG pathway activity. Candidate genes for the compensatory fitness increases were significantly overrepresented by stress response functions, and some were specifically associated with the HOG pathway itself. Parallel evolution at the gene level was rare among evolved lines. There was a positive relationship between the predicted number of adaptive steps, estimated from fitness data, and the number of genomic mutations, determined by whole-genome sequencing. However, the number of genomic mutations was, on average, 8.45 times greater than the number of adaptive steps inferred from fitness data. This research expands our understanding of the genetic basis of adaptation in multicellular eukaryotes and lays out a framework for future work on the genomics of compensatory adaptation in A. nidulans.

背景与目标： : 了解负责适应的遗传变化的数量和性质对于理解和预测进化轨迹至关重要。在这里，我们研究了在实验进化的丝状真菌构巢曲霉菌株中，对杀真菌剂抗性的适应性成本进行补偿性适应的基因组基础。最初的选择实验跟踪了由祖先菌株建立的品系的适应性恢复，该品系对氟二氧嘧啶具有抗性，但在没有杀真菌剂的情况下支付了健身费用。我们获得了祖先的A. nidulans菌株和八个实验进化菌株的全基因组序列数据。我们发现，祖先的氟二氧杂环素抗性可能是由组氨酸激酶nikA的突变赋予的，该突变是高渗透压甘油 (HOG) 应激反应途径的两组分信号转导系统的一部分。为了补偿抗性突变的多效性负面影响，在进化系中观察到的随后的适应性增益可能是由HOG途径活性的二次修饰引起的。代偿性适应性增加的候选基因显着被应激反应功能所代表，其中一些与HOG途径本身特别相关。在进化品系中，基因水平的平行进化很少见。根据适应性数据估算的自适应步骤的预测数量与通过全基因组测序确定的基因组突变数量之间存在正相关关系。然而，基因组突变的数量平均比从适应性数据推断的适应性步骤的数量大8.45倍。这项研究扩大了我们对多细胞真核生物适应的遗传基础的理解，并为未来在a.nidulans的补偿性适应基因组学方面的工作奠定了框架。

BACKGROUND & AIMS: :The spatial range of a species habitat is generally determined by the ability of the species to cope with biotic and abiotic variables that vary in space. Therefore, the species range is itself an evolvable property. Indeed, environmental gradients permit a mode of evolution in which range expansion and adaptation go hand in hand. This process can contribute to rapid evolution of drug resistant bacteria and viruses, because drug concentrations in humans and livestock treated with antibiotics are far from uniform. Here, we use a minimal stochastic model of discrete, interacting organisms evolving in continuous space to study how the rate of adaptation of a quantitative trait depends on the steepness of the gradient and various population parameters. We discuss analytical results for the mean-field limit as well as extensive stochastic simulations. These simulations were performed using an exact, event-driven simulation scheme that can deal with continuous time-, density- and coordinate-dependent reaction rates and could be used for a wide variety of stochastic systems. The results reveal two qualitative regimes. If the gradient is shallow, the rate of adaptation is limited by dispersion and increases linearly with the gradient slope. If the gradient is steep, the adaptation rate is limited by mutation. In this regime, the mean-field result is highly misleading: it predicts that the adaptation rate continues to increase with the gradient slope, whereas stochastic simulations show that it in fact decreases with the square root of the slope. This discrepancy underscores the importance of discreteness and stochasticity even at high population densities; mean-field results, including those routinely used in quantitative genetics, should be interpreted with care.

背景与目标： : 物种栖息地的空间范围通常取决于物种应对空间变化的生物和非生物变量的能力。因此，物种范围本身就是一种可进化的属性。实际上，环境梯度允许一种进化模式，在这种模式下，范围扩展和适应齐头并进。这个过程可以促进耐药细菌和病毒的快速进化，因为用抗生素治疗的人和牲畜的药物浓度远非均匀。在这里，我们使用在连续空间中进化的离散相互作用生物的最小随机模型来研究数量性状的适应速度如何取决于梯度的陡度和各种种群参数。我们讨论了平均场极限的分析结果以及广泛的随机模拟。这些模拟是使用精确的，事件驱动的模拟方案进行的，该方案可以处理连续的时间，密度和坐标相关的反应速率，并且可以用于各种随机系统。结果揭示了两种定性制度。如果梯度较浅，则适应率受色散限制，并随梯度斜率线性增加。如果梯度陡峭，则适应率受到突变的限制。在这种情况下，平均场结果具有很大的误导性: 它预测适应率随梯度斜率的增加而继续增加，而随机模拟表明，它实际上随斜率的平方根而减小。即使在高人口密度下，这种差异也强调了离散性和随机性的重要性; 平均场结果，包括定量遗传学中常规使用的结果，应谨慎解释。

BACKGROUND & AIMS: :The brain demands oxygen and glucose to fulfill its roles as the master regulator of body functions as diverse as bladder control and creative thinking. Chemical and electrical transmission in the nervous system is rapidly disrupted in stroke as a result of hypoxia and hypoglycemia. Despite being highly evolved in its architecture, the human brain appears to utilize phylogenetically conserved homeostatic strategies to combat hypoxia and ischemia. Specifically, several converging lines of inquiry have demonstrated that the transcription factor hypoxia-inducible factor-1 (HIF1-1) mediates the activation of a large cassette of genes involved in adaptation to hypoxia in surviving neurons after stroke. Accordingly, pharmacological or molecular approaches that engage hypoxic adaptation at the point of one of its sensors (e.g., inhibition of HIF prolyl 4 hydroxylases) leads to profound sparing of brain tissue and enhanced recovery of function. In this review, we discuss the potential mechanisms that could subserve protective and restorative effects of augmenting hypoxic adaptation in the brain. The strategy appears to involve HIF-dependent and HIF-independent pathways and more than 70 genes and proteins activated transcriptionally and post-transcriptionally that can act at cellular, local, and system levels to compensate for oxygen insufficiency. The breadth and depth of this homeostatic program offers a hopeful alternative to the current pessimism towards stroke therapeutics.

背景与目标： : 大脑需要氧气和葡萄糖来发挥其作为身体功能的主要调节剂的作用，如膀胱控制和创造性思维。由于缺氧和低血糖，神经系统中的化学和电传递会迅速中断。尽管其结构高度进化，但人脑似乎利用了系统发育保守的稳态策略来对抗缺氧和缺血。具体地说，几个会聚的研究线已经证明，转录因子缺氧诱导因子-1 (HIF1-1) 介导了中风后存活神经元适应缺氧的大量基因盒的激活。因此，在其传感器之一处进行低氧适应的药理学或分子方法 (例如，抑制HIF脯氨酰4羟化酶) 导致脑组织的深度保留和功能的增强恢复。在这篇综述中，我们讨论了可能对增强大脑缺氧适应的保护和恢复作用产生亚作用的潜在机制。该策略似乎涉及HIF依赖性和HIF依赖性途径，以及超过70个基因和蛋白质在转录和转录后激活，可以在细胞，局部和系统水平上起作用以补偿氧气不足。此稳态计划的广度和深度为当前对中风疗法的悲观主义提供了希望的替代方案。

BACKGROUND & AIMS: :Changes in co-receptor-use by human immunodeficiency virus type 1 (HIV-1) strains are relatively rare in vivo. Here we describe two variants derived from the CCR5-using strain SF162, selected for replication in the C8166 T-cell line. Amino acid substitutions in the V3 loop conferred CXCR4-use; however, the loss of macrophage-tropism by one variant was due to a single mutation in the start codon of vpu. We discuss how V3 loop and vpu mutations acquired by replication in T-cell lines in vitro correlate with similar changes reported for primary isolates and HIV-1 sequences in vivo.

背景与目标： : 人类免疫缺陷病毒1型 (HIV-1) 菌株在体内共同使用受体的变化相对罕见。在这里，我们描述了源自CCR5-using菌株SF162的两种变体，选择用于在C8166 T细胞系中复制。V3环中的氨基酸取代赋予了CXCR4-use; 然而，一个变体的巨噬细胞嗜性丧失是由于vpu起始密码子中的单个突变所致。我们讨论了在体外T细胞系中通过复制获得的V3环和vpu突变如何与体内原代分离株和HIV-1序列报道的类似变化相关。