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Nonhuman Primates in Translational Research. 翻译研究中的非人灵长类动物。
IF 12 1区 农林科学 Q1 Agricultural and Biological Sciences Pub Date : 2022-02-15 DOI: 10.1146/annurev-animal-021419-083813
Alice F Tarantal, Stephen C Noctor, Dennis J Hartigan-O'Connor
Nonhuman primates are critically important animal models in which to study complex human diseases, understand biological functions, and address the safety of new diagnostics and therapies proposed for human use. They have genetic, physiologic, immunologic, and developmental similarities when compared to humans and therefore provide important preclinical models of human health and disease. This review highlights select research areas that demonstrate the importance of nonhuman primates in translational research. These include pregnancy and developmental disorders, infectious diseases, gene therapy, somatic cell genome editing, and applications of in vivo imaging. The power of the immune system and our increasing understanding of the role it plays in acute and chronic illnesses are being leveraged to produce new treatments for a range of medical conditions. Given the importance of the human immune system in health and disease, detailed study of the immune system of nonhuman primates is essential to advance preclinical translational research. The need for nonhuman primates continues to remain a high priority, which has been acutely evident during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) global pandemic. Nonhuman primates will continue to address key questions and provide predictive models to identify the safety and efficiency of new diagnostics and therapies for human use across the lifespan.
非人灵长类动物是研究复杂人类疾病、了解生物功能以及解决人类使用的新诊断和治疗安全性问题的重要动物模型。与人类相比,它们在基因、生理、免疫和发育方面具有相似性,因此提供了人类健康和疾病的重要临床前模型。这篇综述重点介绍了一些研究领域,这些领域证明了非人类灵长类动物在转化研究中的重要性。其中包括妊娠和发育障碍、传染病、基因治疗、体细胞基因组编辑以及体内成像的应用。免疫系统的力量以及我们对其在急性和慢性疾病中所起作用的日益了解,正被用来为一系列疾病提供新的治疗方法。鉴于人类免疫系统在健康和疾病中的重要性,对非人类灵长类动物免疫系统的详细研究对于推进临床前转化研究至关重要。对非人类灵长类动物的需求仍然是一个高度优先事项,这在严重急性呼吸综合征冠状病毒2型(严重急性呼吸系统综合征冠状病毒冠状病毒2型)全球大流行期间表现得非常明显。非人类灵长类动物将继续解决关键问题,并提供预测模型,以确定人类在整个生命周期内使用的新诊断和治疗的安全性和有效性。
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引用次数: 7
Genomics and the Evolutionary History of Equids. 基因组学和马科动物的进化史。
IF 12 1区 农林科学 Q1 Agricultural and Biological Sciences Pub Date : 2021-02-16 Epub Date: 2020-11-16 DOI: 10.1146/annurev-animal-061220-023118
Pablo Librado, Ludovic Orlando

The equid family contains only one single extant genus, Equus, including seven living species grouped into horses on the one hand and zebras and asses on the other. In contrast, the equine fossil record shows that an extraordinarily richer diversity existed in the past and provides multiple examples of a highly dynamic evolution punctuated by several waves of explosive radiations and extinctions, cross-continental migrations, and local adaptations. In recent years, genomic technologies have provided new analytical solutions that have enhanced our understanding of equine evolution, including the species radiation within Equus; the extinction dynamics of several lineages; and the domestication history of two individual species, the horse and the donkey. Here, we provide an overview of these recent developments and suggest areas for further research.

马科只有一个现存的属,马属,包括七个现存的物种,分别分为马和斑马和驴。相比之下,马的化石记录表明,过去存在着非常丰富的多样性,并提供了许多高度动态进化的例子,其中穿插着几波爆炸性的辐射和灭绝、跨大陆迁徙和局部适应。近年来,基因组技术提供了新的分析解决方案,增强了我们对马的进化的理解,包括马的物种辐射;几种世系的灭绝动态;以及马和驴这两个个体物种的驯化史。在这里,我们概述了这些最新的发展,并提出了进一步研究的领域。
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引用次数: 20
The Diversity of Primates: From Biomedicine to Conservation Genomics. 灵长类动物多样性:从生物医学到保护基因组学。
IF 12 1区 农林科学 Q1 Agricultural and Biological Sciences Pub Date : 2021-02-16 Epub Date: 2020-11-16 DOI: 10.1146/annurev-animal-061220-023138
Joseph D Orkin, Lukas F K Kuderna, Tomas Marques-Bonet

Until now, the field of primate genomics has focused on two major themes: understanding human evolution and advancing biomedical research. We propose that it is now time for a third theme to receive attention: conservation genomics. As a result of anthropogenic effects, the majority of primate species have become threatened with extinction. A more robust primate conservation genomics will allow for genetically informed population management. Thanks to a steady decline in the cost of sequencing, it has now become feasible to sequence whole primate genomes at the population level. Furthermore, technological advances in noninvasive genomic methods have made it possible to acquire genome-scale data from noninvasive biomaterials. Here, we review recent advances in the analysis of primate diversity, with a focus on genomic data sets across the radiation.

到目前为止,灵长类基因组学领域主要集中在两个主题上:理解人类进化和推进生物医学研究。我们建议现在应该关注第三个主题:保护基因组学。由于人类活动的影响,大多数灵长类物种面临灭绝的威胁。一个更强大的灵长类动物保护基因组学将允许基因知情的种群管理。由于测序成本的稳步下降,现在在种群水平上对整个灵长类基因组进行测序已经成为可能。此外,非侵入性基因组方法的技术进步使得从非侵入性生物材料中获取基因组规模数据成为可能。在这里,我们回顾了灵长类动物多样性分析的最新进展,重点是跨辐射的基因组数据集。
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引用次数: 8
Genetics and Evolution of Mammalian Coat Pigmentation. 哺乳动物皮毛色素沉着的遗传和进化。
IF 12 1区 农林科学 Q1 Agricultural and Biological Sciences Pub Date : 2021-02-16 Epub Date: 2020-11-18 DOI: 10.1146/annurev-animal-022114-110847
Eduardo Eizirik, Fernanda J Trindade

The diversity of mammalian coat colors, and their potential adaptive significance, have long fascinated scientists as well as the general public. The recent decades have seen substantial improvement in our understanding of their genetic bases and evolutionary relevance, revealing novel insights into the complex interplay of forces that influence these phenotypes. At the same time, many aspects remain poorly known, hampering a comprehensive understanding of these phenomena. Here we review the current state of this field and indicate topics that should be the focus of additional research. We devote particular attention to two aspects of mammalian pigmentation, melanism and pattern formation, highlighting recent advances and outstanding challenges, and proposing novel syntheses of available information. For both specific areas, and for pigmentation in general, we attempt to lay out recommendations for establishing novel model systems and integrated research programs that target the genetics and evolution of these phenotypes throughout the Mammalia.

哺乳动物皮毛颜色的多样性及其潜在的适应性意义,长期以来一直吸引着科学家和公众。近几十年来,我们对它们的遗传基础和进化相关性的理解有了实质性的提高,揭示了影响这些表型的力量的复杂相互作用的新见解。与此同时,许多方面仍然知之甚少,阻碍了对这些现象的全面理解。在这里,我们回顾了这一领域的现状,并指出了应该成为进一步研究重点的主题。我们特别关注哺乳动物色素沉着,黑化和模式形成的两个方面,突出了最近的进展和突出的挑战,并提出了新的综合现有信息。对于这两个特定的领域,以及一般的色素沉着,我们试图提出建议,建立新的模型系统和综合研究计划,目标是在哺乳动物中这些表型的遗传和进化。
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引用次数: 10
Insects: A Potential Source of Protein and Other Nutrients for Feed and Food. 昆虫:饲料和食物中蛋白质和其他营养物质的潜在来源。
IF 12 1区 农林科学 Q1 Agricultural and Biological Sciences Pub Date : 2021-02-16 Epub Date: 2020-11-23 DOI: 10.1146/annurev-animal-021419-083930
Kerensa J Hawkey, Carlos Lopez-Viso, John M Brameld, Tim Parr, Andrew M Salter

Sustainable production of healthy food for a growing global population, in the face of the uncertainties of climate change, represents a major challenge for the coming decade. Livestock provide food with high nutritional value but are frequently fed on human-edible crops and are associated with significant production of greenhouse gases. Recent years have seen increasing interest in the farming of insects as a sustainable source of human food, or as a replacement of ingredients such as soya or fishmeal in the feeds of terrestrial livestock or fish. This review provides an overview of insect physiology and growth regulation, considers the requirements for insect farming and mass production, and summarizes the nutritional value of the 10 most commonly studied insect species, before reviewing the literature on the use of insects as feed and food. We highlight the challenges required to develop a sustainable, safe, and affordable insect farming industry.

面对气候变化的不确定性,为不断增长的全球人口可持续生产健康食品是未来十年的一项重大挑战。牲畜提供高营养价值的食物,但往往以人类可食用的作物为食,并与大量温室气体的产生有关。近年来,人们对昆虫养殖越来越感兴趣,将其作为人类食物的可持续来源,或作为陆地牲畜或鱼类饲料中大豆或鱼粉等成分的替代品。本文综述了昆虫的生理和生长调控,考虑了昆虫养殖和大规模生产的要求,总结了10种最常研究的昆虫的营养价值,并对昆虫作为饲料和食物的文献进行了综述。我们强调了发展可持续、安全和负担得起的昆虫养殖业所面临的挑战。
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引用次数: 71
Physiological Genomics of Adaptation to High-Altitude Hypoxia. 适应高海拔缺氧的生理基因组学。
IF 12 1区 农林科学 Q1 Agricultural and Biological Sciences Pub Date : 2021-02-16 Epub Date: 2020-11-23 DOI: 10.1146/annurev-animal-072820-102736
Jay F Storz, Zachary A Cheviron

Population genomic studies of humans and other animals at high altitude have generated many hypotheses about the genes and pathways that may have contributed to hypoxia adaptation. Future advances require experimental tests of such hypotheses to identify causal mechanisms. Studies to date illustrate the challenge of moving from lists of candidate genes to the identification of phenotypic targets of selection, as it can be difficult to determine whether observed genotype-phenotype associations reflect causal effects or secondary consequences of changes in other traits that are linked via homeostatic regulation. Recent work on high-altitude models such as deer mice has revealed both plastic and evolved changes in respiratory, cardiovascular, and metabolic traits that contribute to aerobic performance capacity in hypoxia, and analyses of tissue-specific transcriptomes have identified changes in regulatory networks that mediate adaptive changes in physiological phenotype. Here we synthesize recent results and discuss lessons learned from studies of high-altitude adaptation that lie at the intersection of genomics and physiology.

对人类和其他高海拔地区动物的群体基因组研究已经产生了许多关于基因和途径的假说,这些基因和途径可能有助于对缺氧的适应。未来的进展需要对这些假设进行实验测试,以确定因果机制。迄今为止的研究表明,从候选基因列表到确定选择的表型目标是一项挑战,因为很难确定观察到的基因型与表型之间的关联是反映了因果效应,还是反映了其他性状变化的次要后果,而这些性状是通过稳态调节联系在一起的。最近对鹿小鼠等高海拔模型的研究揭示了呼吸、心血管和代谢特征的可塑性和进化性变化,这些特征有助于在缺氧条件下提高有氧运动能力;对组织特异性转录组的分析也发现了调控网络的变化,这些网络介导了生理表型的适应性变化。在此,我们总结了最近的研究成果,并讨论了在基因组学和生理学交叉领域的高海拔适应性研究中汲取的经验教训。
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引用次数: 0
Applications of Nanobodies. 纳米体的应用。
IF 12 1区 农林科学 Q1 Agricultural and Biological Sciences Pub Date : 2021-02-16 Epub Date: 2020-11-24 DOI: 10.1146/annurev-animal-021419-083831
Serge Muyldermans

Unique, functional, homodimeric heavy chain-only antibodies, devoid of light chains, are circulating in the blood of Camelidae. These antibodies recognize their cognate antigen via one single domain, known as VHH or Nanobody. This serendipitous discovery made three decades ago has stimulated a growing number of researchers to generate highly specific Nanobodies against a myriad of targets. The small size, strict monomeric state, robustness, and easy tailoring of these Nanobodies have inspired many groups to design innovative Nanobody-based multi-domain constructs to explore novel applications. As such, Nanobodies have been employed as an exquisite research tool in structural, cell, and developmental biology. Furthermore, Nanobodies have demonstrated their benefit for more sensitive diagnostic tests. Finally, several Nanobody-based constructs have been designed to develop new therapeutic products.

独特的,功能性的,同源二聚体的重链抗体,缺乏轻链,在Camelidae的血液中循环。这些抗体通过一个称为VHH或纳米体的单一结构域识别其同源抗原。三十年前的这一偶然发现刺激了越来越多的研究人员产生针对无数目标的高度特异性纳米体。这些纳米体的小尺寸、严格的单体状态、健壮性和易于裁剪的特点激发了许多团队设计创新的基于纳米体的多域结构来探索新的应用。因此,纳米体已被用作结构、细胞和发育生物学的精细研究工具。此外,纳米体已经证明了它们在更敏感的诊断测试中的益处。最后,一些基于纳米体的结构已经被设计用于开发新的治疗产品。
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引用次数: 107
Advances in Microbiome Research for Animal Health. 动物健康微生物组研究进展
IF 12 1区 农林科学 Q1 Agricultural and Biological Sciences Pub Date : 2021-02-16 Epub Date: 2020-12-14 DOI: 10.1146/annurev-animal-091020-075907
Raquel S Peixoto, Derek M Harkins, Karen E Nelson

Host-associated microbiomes contribute in many ways to the homeostasis of the metaorganism. The microbiome's contributions range from helping to provide nutrition and aiding growth, development, and behavior to protecting against pathogens and toxic compounds. Here we summarize the current knowledge of the diversity and importance of the microbiome to animals, using representative examples of wild and domesticated species. We demonstrate how the beneficial ecological roles of animal-associated microbiomes can be generally grouped into well-defined main categories and how microbe-based alternative treatments can be applied to mitigate problems for both economic and conservation purposes and to provide crucial knowledge about host-microbiota symbiotic interactions. We suggest a Customized Combination of Microbial-Based Therapies to promote animal health and contribute to the practice of sustainable husbandry. We also discuss the ecological connections and threats associated with animal biodiversity loss, microorganism extinction, and emerging diseases, such as the COVID-19 pandemic.

宿主相关微生物组在许多方面有助于元生物体的稳态。微生物组的贡献范围从帮助提供营养、帮助生长、发育和行为,到防止病原体和有毒化合物。在这里,我们总结了目前的知识的多样性和微生物组对动物的重要性,使用野生和驯化物种的代表性例子。我们展示了与动物相关的微生物群的有益生态作用如何被分为明确的主要类别,以及如何应用基于微生物的替代治疗来缓解经济和保护目的的问题,并提供关于宿主-微生物群共生相互作用的关键知识。我们建议采用定制的微生物疗法组合来促进动物健康,并为可持续畜牧业的实践做出贡献。我们还讨论了与动物生物多样性丧失、微生物灭绝和新发疾病(如COVID-19大流行)相关的生态联系和威胁。
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引用次数: 56
Genetic Engineering of Livestock: The Opportunity Cost of Regulatory Delay. 家畜基因工程:监管延迟的机会成本。
IF 12 1区 农林科学 Q1 Agricultural and Biological Sciences Pub Date : 2021-02-16 Epub Date: 2020-11-13 DOI: 10.1146/annurev-animal-061220-023052
Alison L Van Eenennaam, Felipe De Figueiredo Silva, Josephine F Trott, David Zilberman

Genetically engineered (GE) livestock were first reported in 1985, and yet only a single GE food animal, the fast-growing AquAdvantage salmon, has been commercialized. There are myriad interconnected reasons for the slow progress in this once-promising field, including technical issues, the structure of livestock industries, lack of public research funding and investment, regulatory obstacles, and concern about public opinion. This review focuses on GE livestock that have been produced and documents the difficulties that researchers and developers have encountered en route. Additionally, the costs associated with delayed commercialization of GE livestock were modeled using three case studies: GE mastitis-resistant dairy cattle, genome-edited porcine reproductive and respiratory syndrome virus-resistant pigs, and the AquAdvantage salmon. Delays of 5 or 10 years in the commercialization of GE livestock beyond the normative 10-year GE product evaluation period were associated with billions of dollars in opportunity costs and reduced global food security.

1985年首次报道了转基因牲畜,然而只有一种转基因食用动物,即快速生长的AquAdvantage鲑鱼被商业化。这一曾经充满希望的领域进展缓慢,有无数相互关联的原因,包括技术问题、畜牧业结构、缺乏公共研究资金和投资、监管障碍以及对公众舆论的担忧。这篇综述的重点是已经生产的转基因牲畜,并记录了研究人员和开发人员在这一过程中遇到的困难。此外,通过三个案例研究模拟了与转基因牲畜延迟商业化相关的成本:转基因乳牛抗乳腺炎,基因组编辑猪繁殖和呼吸综合征病毒抗性猪,以及AquAdvantage鲑鱼。转基因牲畜的商业化如果比标准的10年转基因产品评估期推迟5年或10年,就会造成数十亿美元的机会成本,并降低全球粮食安全。
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引用次数: 25
Endogenous Retroviruses Drive Resistance and Promotion of Exogenous Retroviral Homologs. 内源性逆转录病毒驱动抗性和促进外源性逆转录病毒同源物。
IF 12 1区 农林科学 Q1 Agricultural and Biological Sciences Pub Date : 2021-02-16 Epub Date: 2020-12-08 DOI: 10.1146/annurev-animal-050620-101416
Elliott S Chiu, Sue VandeWoude

Endogenous retroviruses (ERVs) serve as markers of ancient viral infections and provide invaluable insight into host and viral evolution. ERVs have been exapted to assist in performing basic biological functions, including placentation, immune modulation, and oncogenesis. A subset of ERVs share high nucleotide similarity to circulating horizontally transmitted exogenous retrovirus (XRV) progenitors. In these cases, ERV-XRV interactions have been documented and include (a) recombination to result in ERV-XRV chimeras, (b) ERV induction of immune self-tolerance to XRV antigens, (c) ERV antigen interference with XRV receptor binding, and (d) interactions resulting in both enhancement and restriction of XRV infections. Whereas the mechanisms governing recombination and immune self-tolerance have been partially determined, enhancement and restriction of XRV infection are virus specific and only partially understood. This review summarizes interactions between six unique ERV-XRV pairs, highlighting important ERV biological functions and potential evolutionary histories in vertebrate hosts.

内源性逆转录病毒(erv)作为古代病毒感染的标志物,为宿主和病毒进化提供了宝贵的见解。erv有望协助执行基本的生物学功能,包括胎盘、免疫调节和肿瘤发生。erv的一个子集与循环水平传播的外源性逆转录病毒(XRV)祖病毒具有高核苷酸相似性。在这些情况下,ERV-XRV相互作用已被记录,包括(a)重组导致ERV-XRV嵌合体,(b) ERV诱导对XRV抗原的免疫自身耐受性,(c) ERV抗原干扰XRV受体结合,以及(d)相互作用导致XRV感染的增强和限制。虽然重组和免疫自身耐受的机制已部分确定,但XRV感染的增强和限制是病毒特异性的,仅部分了解。本文综述了六种独特的ERV- xrv对之间的相互作用,重点介绍了ERV在脊椎动物宿主中的重要生物学功能和潜在的进化历史。
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引用次数: 16
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Annual Review of Animal Biosciences
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