Wiley Interdisciplinary Reviews-Systems Biology and Medicine最新文献_第10页

Computational models of the neural control of breathing 呼吸神经控制的计算模型

IF 7.9 Q1 Medicine

Wiley Interdisciplinary Reviews-Systems Biology and Medicine

Pub Date : 2017-03-01 DOI: 10.1002/wsbm.1371

Y. Molkov, J. Rubin, I. Rybak, Jeffrey C. Smith

The ongoing process of breathing underlies the gas exchange essential for mammalian life. Each respiratory cycle ensues from the activity of rhythmic neural circuits in the brainstem, shaped by various modulatory signals, including mechanoreceptor feedback sensitive to lung inflation and chemoreceptor feedback dependent on gas composition in blood and tissues. This paper reviews a variety of computational models designed to reproduce experimental findings related to the neural control of breathing and generate predictions for future experimental testing. The review starts from the description of the core respiratory network in the brainstem, representing the central pattern generator (CPG) responsible for producing rhythmic respiratory activity, and progresses to encompass additional complexities needed to simulate different metabolic challenges, closed‐loop feedback control including the lungs, and interactions between the respiratory and autonomic nervous systems. The integrated models considered in this review share a common framework including a distributed CPG core network responsible for generating the baseline three‐phase pattern of rhythmic neural activity underlying normal breathing. WIREs Syst Biol Med 2017, 9:e1371. doi: 10.1002/wsbm.1371

持续的呼吸过程是哺乳动物生命所必需的气体交换的基础。每个呼吸周期都是由脑干中节律性神经回路的活动引起的，由各种调节信号形成，包括对肺膨胀敏感的机械受体反馈和依赖于血液和组织中气体成分的化学受体反馈。本文回顾了各种计算模型，旨在重现与呼吸神经控制相关的实验结果，并为未来的实验测试做出预测。该综述从描述脑干中的核心呼吸网络开始，代表负责产生有节奏的呼吸活动的中枢模式发生器(CPG)，并逐步涵盖模拟不同代谢挑战所需的额外复杂性，包括肺在内的闭环反馈控制，以及呼吸和自主神经系统之间的相互作用。本综述中考虑的综合模型共享一个共同的框架，包括一个分布式CPG核心网络，负责产生正常呼吸下节律性神经活动的基线三相模式。中国生物医学工程学报，2017,39(4):571 - 571。doi: 10.1002 / wsbm.1371

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引用次数: 53

Cancer and inflammation 癌症和炎症

IF 7.9 Q1 Medicine

Wiley Interdisciplinary Reviews-Systems Biology and Medicine

Pub Date : 2017-03-01 DOI: 10.1002/wsbm.1370

L. Munn

The relationship between inflammation and cancer has been recognized since the 17th century,1 and we now know much about the cells, cytokines and physiological processes that are central to both inflammation and cancer.2-9 Chronic inflammation can induce certain cancers,10-17 and solid tumors, in turn, can initiate and perpetuate local inflammatory processes that foster tumor growth and dissemination.5,18-20 Consequently, inflammatory pathways have been targeted in attempts to control cancer.21-23 Inflammation is a central aspect of the innate immune system's response to tissue damage or infection, and also facilitates the recruitment of circulating cells and antibodies of the adaptive immune response to the tissue. Components of the innate immune response carry out a robust, but sometimes overly‐conservative response, sacrificing specificity for the sake of preservation. Thus, when innate immunity goes awry, it can have profound implications. How the innate and adaptive immune systems cooperate to neutralize pathogens and repair damaged tissues is still an area of intense investigation. Further, how these systems can respond to cancer, which arises from normal ‘self’ cells that undergo an oncogenic transformation, has profound implications for cancer therapy. Recently, immunotherapies that activate adaptive immunity have shown unprecedented promise in the clinic, producing durable responses and dramatic increases in survival rate in patients with advanced stage melanoma.24-26 Consequently, the relationship between cancer and inflammation has now returned to the forefront of clinical oncology. WIREs Syst Biol Med 2017, 9:e1370. doi: 10.1002/wsbm.1370

炎症和癌症之间的关系自17世纪以来就已被认识到，现在我们对炎症和癌症的核心细胞、细胞因子和生理过程了解得很多。2-9慢性炎症可以诱发某些癌症，10-17和实体瘤，反过来，可以启动和延续局部炎症过程，促进肿瘤的生长和传播。5,18-20因此，炎症途径已成为控制癌症的目标。21-23炎症是先天免疫系统对组织损伤或感染反应的一个核心方面，也促进了循环细胞和适应性免疫反应抗体对组织的招募。先天免疫反应的组成部分进行稳健的，但有时过于保守的反应，牺牲特异性为了保存。因此，当先天免疫出现问题时，可能会产生深远的影响。先天免疫系统和适应性免疫系统如何合作来中和病原体和修复受损组织仍然是一个深入研究的领域。此外，这些系统如何对癌症做出反应，癌症是由正常的“自我”细胞经历致癌转化而产生的，这对癌症治疗具有深远的意义。最近，激活适应性免疫的免疫疗法在临床中显示出前所未有的希望，在晚期黑色素瘤患者中产生持久的反应并显着提高生存率。因此，癌症和炎症之间的关系现在又回到了临床肿瘤学的前沿。中国生物医学工程学报，2017,32(1):444 - 444。doi: 10.1002 / wsbm.1370

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引用次数: 181

Toward modeling locomotion using electromyography‐informed 3D models: application to cerebral palsy 利用肌电图三维模型建模运动:在脑瘫中的应用

IF 7.9 Q1 Medicine

Wiley Interdisciplinary Reviews-Systems Biology and Medicine

Pub Date : 2017-03-01 DOI: 10.1002/wsbm.1368

Massimo Sartori, J. Fernàndez, L. Modenese, C. Carty, L. Barber, K. Oberhofer, Jianwei Zhang, G. Handsfield, N. Stott, T. Besier, D. Farina, D. Lloyd

This position paper proposes a modeling pipeline to develop clinically relevant neuromusculoskeletal models to understand and treat complex neurological disorders. Although applicable to a variety of neurological conditions, we provide direct pipeline applicative examples in the context of cerebral palsy (CP). This paper highlights technologies in: (1) patient‐specific segmental rigid body models developed from magnetic resonance imaging for use in inverse kinematics and inverse dynamics pipelines; (2) efficient population‐based approaches to derive skeletal models and muscle origins/insertions that are useful for population statistics and consistent creation of continuum models; (3) continuum muscle descriptions to account for complex muscle architecture including spatially varying material properties with muscle wrapping; (4) muscle and tendon properties specific to CP; and (5) neural‐based electromyography‐informed methods for muscle force prediction. This represents a novel modeling pipeline that couples for the first time electromyography extracted features of disrupted neuromuscular behavior with advanced numerical methods for modeling CP‐specific musculoskeletal morphology and function. The translation of such pipeline to the clinical level will provide a new class of biomarkers that objectively describe the neuromusculoskeletal determinants of pathological locomotion and complement current clinical assessment techniques, which often rely on subjective judgment. WIREs Syst Biol Med 2017, 9:e1368. doi: 10.1002/wsbm.1368

本立场文件提出了一个建模管道，以开发临床相关的神经肌肉骨骼模型，以了解和治疗复杂的神经系统疾病。虽然适用于各种神经系统疾病，但我们提供了脑瘫(CP)背景下的直接管道应用实例。本文重点介绍了以下技术:(1)从磁共振成像中开发的用于逆运动学和逆动力学管道的患者特定节段刚体模型;(2)有效的基于种群的方法来推导骨骼模型和肌肉起源/插入，这对种群统计和连续体模型的一致创建有用;(3)连续体肌肉描述，以解释复杂的肌肉结构，包括空间变化的肌肉包裹材料特性;(4) CP特有的肌肉和肌腱特性;(5)基于神经的肌电图预测肌肉力量的方法。这代表了一种新的建模管道，首次将肌电图提取的神经肌肉行为特征与先进的数值方法结合起来，用于模拟CP特异性肌肉骨骼形态和功能。将这种管道转化为临床水平将提供一类新的生物标志物，客观地描述病理运动的神经肌肉骨骼决定因素，并补充当前通常依赖主观判断的临床评估技术。中国生物医学工程学报，2017,32(1):444 - 444。doi: 10.1002 / wsbm.1368

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引用次数: 36

Systems biology of oxygen homeostasis 氧稳态的系统生物学

IF 7.9 Q1 Medicine

Wiley Interdisciplinary Reviews-Systems Biology and Medicine

Pub Date : 2017-02-21 DOI: 10.1002/wsbm.1382

Debangshu Samanta, N. Prabhakar, G. Semenza

Metazoan species maintain oxygen homeostasis through the activity of hypoxia‐inducible factors, which are transcriptional activators that regulate the expression of hundreds of genes to match O2 supply and demand. Here, we review the involvement of hypoxia‐inducible factors in the molecular physiology and pathophysiology of cellular O2 sensing, O2 delivery, O2 utilization, and systemic O2 sensing. WIREs Syst Biol Med 2017, 9:e1382. doi: 10.1002/wsbm.1382

后生动物物种通过缺氧诱导因子的活性维持氧气稳态，这些转录激活因子调节数百个基因的表达以匹配氧气供应和需求。在这里，我们回顾了缺氧诱导因子在细胞O2感知、O2传递、O2利用和全身O2感知的分子生理学和病理生理学中的作用。中国生物医学工程学报，2017,32(1):444 - 444。doi: 10.1002 / wsbm.1382

引用次数: 45

Physiological, metabolic and biotechnological features of extremely thermophilic microorganisms 极端嗜热微生物的生理、代谢和生物技术特征

IF 7.9 Q1 Medicine

Wiley Interdisciplinary Reviews-Systems Biology and Medicine

Pub Date : 2017-02-16 DOI: 10.1002/wsbm.1377

James A. Counts, Benjamin Zeldes, Laura L. Lee, Christopher T. Straub, M. Adams, R. M. Kelly

The current upper thermal limit for life as we know it is approximately 120°C. Microorganisms that grow optimally at temperatures of 75°C and above are usually referred to as ‘extreme thermophiles’ and include both bacteria and archaea. For over a century, there has been great scientific curiosity in the basic tenets that support life in thermal biotopes on earth and potentially on other solar bodies. Extreme thermophiles can be aerobes, anaerobes, autotrophs, heterotrophs, or chemolithotrophs, and are found in diverse environments including shallow marine fissures, deep sea hydrothermal vents, terrestrial hot springs—basically, anywhere there is hot water. Initial efforts to study extreme thermophiles faced challenges with their isolation from difficult to access locales, problems with their cultivation in laboratories, and lack of molecular tools. Fortunately, because of their relatively small genomes, many extreme thermophiles were among the first organisms to be sequenced, thereby opening up the application of systems biology‐based methods to probe their unique physiological, metabolic and biotechnological features. The bacterial genera Caldicellulosiruptor, Thermotoga and Thermus, and the archaea belonging to the orders Thermococcales and Sulfolobales, are among the most studied extreme thermophiles to date. The recent emergence of genetic tools for many of these organisms provides the opportunity to move beyond basic discovery and manipulation to biotechnologically relevant applications of metabolic engineering. WIREs Syst Biol Med 2017, 9:e1377. doi: 10.1002/wsbm.1377

据我们所知，目前生命的温度上限大约是120°C。在75°C及以上的温度下生长最佳的微生物通常被称为“极端嗜热菌”，包括细菌和古细菌。一个多世纪以来，人们一直对支持地球和其他太阳天体上热生物群落中生命的基本原理抱有极大的科学好奇心。极端嗜热菌可以是需氧菌、厌氧菌、自养菌、异养菌或化能养菌，它们存在于不同的环境中，包括浅海裂缝、深海热液喷口、陆地温泉——基本上，任何有热水的地方。研究极端嗜热菌的最初努力面临着挑战，包括它们与难以进入的地区隔离，在实验室培养存在问题，以及缺乏分子工具。幸运的是，由于它们相对较小的基因组，许多极端嗜热微生物是第一批被测序的生物，从而开辟了基于系统生物学的方法的应用，以探索它们独特的生理、代谢和生物技术特征。Caldicellulosiruptor细菌属，Thermotoga和Thermus细菌属，以及属于热球菌目和硫球菌目的古细菌，是迄今为止研究最多的极端嗜热菌。最近出现的许多这些生物的遗传工具提供了超越基本发现和操作的机会，以生物技术相关的代谢工程应用。中国生物医学工程学报，2017,39(9):1377。doi: 10.1002 / wsbm.1377

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引用次数: 29

Mathematical modeling of the female reproductive system: from oocyte to delivery. 女性生殖系统的数学建模:从卵母细胞到分娩。

IF 7.9 Q1 Medicine

Wiley Interdisciplinary Reviews-Systems Biology and Medicine

Pub Date : 2017-01-01 Epub Date: 2016-09-09 DOI: 10.1002/wsbm.1353

Alys R Clark, Jennifer A Kruger

From ovulation to delivery, and through the menstrual cycle, the female reproductive system undergoes many dynamic changes to provide an optimal environment for the embryo to implant, and to develop successfully. It is difficult ethically and practically to observe the system over the timescales involved in growth and development (often hours to days). Even in carefully monitored conditions clinicians and biologists can only see snapshots of the development process. Mathematical models are emerging as a key means to supplement our knowledge of the reproductive process, and to tease apart complexity in the reproductive system. These models have been used successfully to test existing hypotheses regarding the mechanisms of female infertility and pathological fetal development, and also to provide new experimentally testable hypotheses regarding the process of development. This new knowledge has allowed for improvements in assisted reproductive technologies and is moving toward translation to clinical practice via multiscale assessments of the dynamics of ovulation, development in pregnancy, and the timing and mechanics of delivery. WIREs Syst Biol Med 2017, 9:e1353. doi: 10.1002/wsbm.1353 For further resources related to this article, please visit the WIREs website.

从排卵到分娩，以及整个月经周期，女性生殖系统经历了许多动态变化，为胚胎植入和成功发育提供了最佳环境。在涉及生长和发展的时间尺度(通常是几小时到几天)上观察系统在伦理上和实践上都是困难的。即使在精心监测的条件下，临床医生和生物学家也只能看到发育过程的快照。数学模型正在成为补充我们对生殖过程知识的关键手段，并梳理出生殖系统的复杂性。这些模型已经成功地验证了关于女性不育和胎儿病理发育机制的现有假设，并提供了关于发育过程的新的实验可验证的假设。这一新的知识使辅助生殖技术得到了改进，并通过对排卵动力学、妊娠发育、分娩时间和机制的多尺度评估，正朝着临床实践的方向发展。中国生物医学工程学报，2017,29(4):553 - 553。doi: 10.1002 / wsbm.1353有关与本文相关的更多资源，请访问WIREs网站。

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引用次数: 6

Network dynamics: quantitative analysis of complex behavior in metabolism, organelles, and cells, from experiments to models and back. 网络动力学:代谢、细胞器和细胞中复杂行为的定量分析，从实验到模型再返回。

IF 7.9 Q1 Medicine

Wiley Interdisciplinary Reviews-Systems Biology and Medicine

Pub Date : 2017-01-01 Epub Date: 2016-09-07 DOI: 10.1002/wsbm.1352

Felix T Kurz, Jackelyn M Kembro, Ana G Flesia, Antonis A Armoundas, Sonia Cortassa, Miguel A Aon, David Lloyd

Advancing from two core traits of biological systems: multilevel network organization and nonlinearity, we review a host of novel and readily available techniques to explore and analyze their complex dynamic behavior within the framework of experimental-computational synergy. In the context of concrete biological examples, analytical methods such as wavelet, power spectra, and metabolomics-fluxomics analyses, are presented, discussed, and their strengths and limitations highlighted. Further shown is how time series from stationary and nonstationary biological variables and signals, such as membrane potential, high-throughput metabolomics, O₂ and CO₂ levels, bird locomotion, at the molecular, (sub)cellular, tissue, and whole organ and animal levels, can reveal important information on the properties of the underlying biological networks. Systems biology-inspired computational methods start to pave the way for addressing the integrated functional dynamics of metabolic, organelle and organ networks. As our capacity to unravel the control and regulatory properties of these networks and their dynamics under normal or pathological conditions broadens, so is our ability to address endogenous rhythms and clocks to improve health-span in human aging, and to manage complex metabolic disorders, neurodegeneration, and cancer. WIREs Syst Biol Med 2017, 9:e1352. doi: 10.1002/wsbm.1352 For further resources related to this article, please visit the WIREs website.

从生物系统的两个核心特征:多层次网络组织和非线性出发，我们回顾了许多新颖和现成的技术，以探索和分析实验-计算协同框架内的复杂动态行为。在具体的生物实例的背景下，分析方法，如小波，功率谱，代谢组学-通量组学分析，提出，讨论，并强调其优势和局限性。进一步展示了平稳和非平稳生物变量和信号的时间序列，如膜电位、高通量代谢组学、O2和CO2水平、鸟类运动，在分子、(亚)细胞、组织、整个器官和动物水平上，如何揭示潜在生物网络特性的重要信息。系统生物学启发的计算方法开始为解决代谢、细胞器和器官网络的综合功能动力学铺平道路。随着我们揭开这些网络的控制和调节特性及其在正常或病理条件下的动态的能力的扩大，我们解决内源性节律和时钟的能力也在扩大，以改善人类衰老的健康跨度，并管理复杂的代谢紊乱、神经变性和癌症。中国生物医学工程学报，2017,39(4):563 - 567。doi: 10.1002 / wsbm.1352有关与本文相关的更多资源，请访问WIREs网站。

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引用次数: 32

Regulatory elements in molecular networks 分子网络中的调控元件

IF 7.9 Q1 Medicine

Wiley Interdisciplinary Reviews-Systems Biology and Medicine

Pub Date : 2017-01-01 DOI: 10.1002/wsbm.1374

A. Doane, O. Elemento

Regulatory elements determine the connectivity of molecular networks and mediate a variety of regulatory processes ranging from DNA looping to transcriptional, posttranscriptional, and posttranslational regulation. This review highlights our current understanding of the different types of regulatory elements found in molecular networks with a focus on DNA regulatory elements. We highlight technical advances and current challenges for the mapping of regulatory elements at the genome‐wide scale, and describe new computational methods to uncover these elements via reconstructing regulatory networks from large genomic datasets. WIREs Syst Biol Med 2017, 9:e1374. doi: 10.1002/wsbm.1374

调控元件决定分子网络的连通性，并介导从DNA环到转录、转录后和翻译后调控的各种调控过程。这篇综述强调了我们目前对分子网络中发现的不同类型的调控元件的理解，重点是DNA调控元件。我们强调了在全基因组范围内绘制调控元件的技术进步和当前的挑战，并描述了通过从大型基因组数据集重建调控网络来发现这些元件的新计算方法。中国生物医学工程学报，2017,32(1):444 - 444。doi: 10.1002 / wsbm.1374

引用次数: 16

Behavioral epigenetics 行为实验胚胎学

IF 7.9 Q1 Medicine

Wiley Interdisciplinary Reviews-Systems Biology and Medicine

Pub Date : 2017-01-01 DOI: 10.1002/wsbm.1333

David Moore

Why do we grow up to have the traits we do? Most 20th century scientists answered this question by referring only to our genes and our environments. But recent discoveries in the emerging field of behavioral epigenetics have revealed factors at the interface between genes and environments that also play crucial roles in development. These factors affect how genes work; scientists now know that what matters as much as which genes you have (and what environments you encounter) is how your genes are affected by their contexts. The discovery that what our genes do depends in part on our experiences has shed light on how Nature and Nurture interact at the molecular level inside of our bodies. Data emerging from the world's behavioral epigenetics laboratories support the idea that a person's genes alone cannot determine if, for example, he or she will end up shy, suffering from cardiovascular disease, or extremely smart. Among the environmental factors that can influence genetic activity are parenting styles, diets, and social statuses. In addition to influencing how doctors treat diseases, discoveries about behavioral epigenetics are likely to alter how biologists think about evolution, because some epigenetic effects of experience appear to be transmissible from generation to generation. This domain of research will likely change how we think about the origins of human nature. WIREs Syst Biol Med 2017, 9:e1333. doi: 10.1002/wsbm.1333

为什么我们长大后会有这些特质?大多数20世纪的科学家只提到我们的基因和环境来回答这个问题。但是，最近在行为表观遗传学这一新兴领域的发现揭示了基因和环境之间的界面因素，这些因素在发育中也起着至关重要的作用。这些因素影响着基因的工作方式;科学家们现在知道，与你有什么基因(以及你遇到什么环境)同样重要的是，你的基因是如何受到环境的影响的。我们的基因在一定程度上取决于我们的经历，这一发现揭示了先天和后天是如何在我们体内的分子水平上相互作用的。来自全球行为表观遗传学实验室的数据支持这样一种观点，即一个人的基因本身并不能决定他或她最终是否会害羞、患有心血管疾病或非常聪明。影响基因活动的环境因素包括父母教养方式、饮食和社会地位。除了影响医生治疗疾病的方法外，行为表观遗传学的发现还可能改变生物学家对进化的看法，因为经验的一些表观遗传学效应似乎可以代代相传。这一研究领域可能会改变我们对人性起源的看法。中国生物医学工程学报，2017,33(4):533 - 533。doi: 10.1002 / wsbm.1333

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引用次数: 78

Modified mRNA as a therapeutic tool to induce cardiac regeneration in ischemic heart disease 修饰mRNA作为诱导缺血性心脏病心脏再生的治疗工具

IF 7.9 Q1 Medicine

Wiley Interdisciplinary Reviews-Systems Biology and Medicine

Pub Date : 2017-01-01 DOI: 10.1002/wsbm.1367

Y. Hadas, M. Katz, C. Bridges, L. Zangi

Ischemic heart disease (IHD) is a leading cause of morbidity and mortality in developed countries. Current pharmacological and interventional therapies provide significant improvement in the life quality of patient; however, they are mostly symptom‐oriented and not curative. A high disease and economic burden of IHD requires the search for new therapeutic strategies to significantly improve patients’ prognosis and quality of life. One of the main challenges during IHD is the massive loss of cardiomyocytes that possess minimal regenerative capacity. Recent understanding of the pathophysiological mechanisms underlying IHD, as well as new therapeutic approaches provide new hope for patients suffering from IHD. Synthetic modified mRNA (modRNA) is a new gene delivery vector that is increasingly used in in vivo applications. modRNA is a relatively stable, non‐immunogenic, highly‐expressed molecule that has been shown to mediate high and transient expression of proteins in different type of cells and tissues including cardiomyocytes. modRNA properties, together with its expression kinetics in the heart make it an attractive option for the treatment of IHD, especially after myocardial infarction. In this review we discuss the role of gene therapy in cardiac regeneration as an approach to treat IHD; traditional and innovative gene delivery methods; and focus specifically on modRNA structure, mode of delivery, and its use for the induction of endogenous regenerative capacity, mainly in the context of IHD. WIREs Syst Biol Med 2017, 9:e1367. doi: 10.1002/wsbm.1367

缺血性心脏病(IHD)是发达国家发病率和死亡率的主要原因。目前的药物和介入治疗显著改善了患者的生活质量;然而，它们大多是症状导向的，而不是治疗性的。IHD的高疾病和经济负担要求寻求新的治疗策略，以显着改善患者的预后和生活质量。IHD期间的主要挑战之一是具有最小再生能力的心肌细胞的大量损失。最近对IHD病理生理机制的认识以及新的治疗方法为IHD患者带来了新的希望。合成修饰mRNA (Synthetic modified mRNA, modRNA)是一种新型的基因传递载体，在体内的应用越来越广泛。modRNA是一种相对稳定、非免疫原性、高表达的分子，已被证明在包括心肌细胞在内的不同类型的细胞和组织中介导蛋白质的高表达和短暂表达。modRNA的特性及其在心脏中的表达动力学使其成为治疗IHD的一个有吸引力的选择，特别是在心肌梗死后。在这篇综述中，我们讨论了基因治疗在心脏再生中的作用，作为治疗IHD的一种方法;传统和创新的基因传递方法;并特别关注modRNA的结构、传递方式及其在诱导内源性再生能力方面的应用，主要是在IHD的背景下。中国生物医学工程学报，2017,32(1):444 - 444。doi: 10.1002 / wsbm.1367

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引用次数: 31