• 【“芯片上的人” 的发展: 实验室动物和人类物质的系统安全评估和效率评估的转化前沿替代方案?】 复制标题 收藏 收藏
    DOI:10.1177/026119291204000504 复制DOI
    作者列表:Marx U,Walles H,Hoffmann S,Lindner G,Horland R,Sonntag F,Klotzbach U,Sakharov D,Tonevitsky A,Lauster R
    BACKGROUND & AIMS: :Various factors, including the phylogenetic distance between laboratory animals and humans, the discrepancy between current in vitro systems and the human body, and the restrictions of in silico modelling, have generated the need for new solutions to the ever-increasing worldwide dilemma of substance testing. This review provides a historical sketch on the accentuation of this dilemma, and highlights fundamental limitations to the countermeasures taken so far. It describes the potential of recently-introduced microsystems to emulate human organs in 'organ-on-a-chip' devices. Finally, it focuses on an in-depth analysis of the first devices that aimed to mimic human systemic organ interactions in 'human-on-a-chip' systems. Their potential to replace acute systemic toxicity testing in animals, and their inability to provide alternatives to repeated dose long-term testing, are discussed. Inspired by the latest discoveries in human biology, tissue engineering and micro-systems technology, this review proposes a paradigm shift to overcome the apparent challenges. A roadmap is outlined to create a new homeostatic level of biology in 'human-on-a-chip' systems in order to, in the long run, replace systemic repeated dose safety evaluation and disease modelling in animals.
    背景与目标: : 各种因素,包括实验动物与人类之间的系统发育距离,当前的体外系统与人体之间的差异以及计算机模拟的限制,都需要新的解决方案来解决全球范围内不断增长的难题。物质测试。这篇评论提供了关于这一困境加剧的历史草图,并强调了迄今为止采取的对策的根本局限性。它描述了最近引入的微系统在 “芯片上的器官” 设备中模拟人体器官的潜力。最后,它着重于对旨在模仿 “芯片上的人” 系统中人体全身器官相互作用的第一批设备的深入分析。讨论了它们替代动物急性全身毒性测试的潜力,以及它们无法提供重复剂量长期测试的替代方法。受人类生物学,组织工程和微系统技术的最新发现的启发,这篇评论提出了一种范式转变,以克服明显的挑战。概述了在 “芯片上的人” 系统中创建新的生物稳态水平的路线图,以便从长远来看取代动物的系统重复剂量安全性评估和疾病建模。
  • 【泌乳素瘤的发生: 使用雌激素治疗动物的研究。】 复制标题 收藏 收藏
    DOI:10.1159/000094307 复制DOI
    作者列表:Sarkar DK
    BACKGROUND & AIMS: :Prolactin-secreting adenomas (prolactinomas) are the most prevalent form of pituitary tumors in humans. Our knowledge of the formation of these tumors is limited. Experimental work in animal has uncovered that estradiol exposure leads to prolactinoma formation via orchestrated events involving dopamine D2 receptors, transforming growth factor-beta(TGF-beta) isoforms and their receptors, as well as factors secondary to TGF-beta action. Additionally, these studies determined that TGF-beta and b-FGF interact to facilitate the communication between lactotropes and folliculo-stellate cells that is necessary for the mitogenic action of estradiol. The downstream signaling that governs lactotropic cell proliferation involves activation of the MAP kinase p44/42-dependent pathway.
    背景与目标: : 分泌催乳素的腺瘤 (催乳素瘤) 是人类最普遍的垂体肿瘤形式。我们对这些肿瘤形成的了解是有限的。动物的实验工作发现,雌二醇暴露通过涉及多巴胺D2受体,转化生长因子-β (TGF-β) 亚型及其受体以及TGF-β 作用继发的因子的精心安排的事件导致催乳素瘤的形成。此外,这些研究确定TGF-β 和b-FGF相互作用以促进乳酸和卵泡星状细胞之间的交流,这是雌二醇有丝分裂作用所必需的。控制促乳细胞增殖的下游信号传导涉及MAP激酶p44/42依赖性途径的激活。
  • 3 Climate change and animals in Saudi Arabia. 复制标题 收藏 收藏

    【沙特阿拉伯的气候变化和动物。】 复制标题 收藏 收藏
    DOI:10.1016/j.sjbs.2011.12.004 复制DOI
    作者列表:Williams JB,Shobrak M,Wilms TM,Arif IA,Khan HA
    BACKGROUND & AIMS: :Global warming is occurring at an alarming rate and predictions are that air temperature (T a) will continue to increase during this century. Increases in T a as a result of unabated production of greenhouse gases in our atmosphere pose a threat to the distribution and abundance of wildlife populations worldwide. Although all the animals worldwide will likely be affected by global warming, diurnal animals in the deserts will be particularly threatened in the future because T as are already high, and animals have limited access to water. It is expected that Saudi Arabia will experience a 3-5 °C in T a over the next century. For predicting the consequences of global warming for animals, it is important to understand how individual species will respond to higher air temperatures. We think that populations will not have sufficient time to make evolutionary adjustments to higher T a, and therefore they will be forced to alter their distribution patterns, or make phenotypic adjustments in their ability to cope with high T a. This report examines how increases in T a might affect body temperature (T b) in the animals of arid regions. We chose three taxonomic groups, mammals, birds, and reptiles (Arabian oryx, Arabian spiny-tailed lizard, vultures, and hoopoe larks) from Saudi Arabia, an area in which T a often reaches 45 °C during midday in summer. When T a exceeds T b, animals must resort to behavioral and physiological methods to control their T b; failure to do so results in death. The observations of this study show that in many cases T b is already close to the upper lethal limit of around 47° C in these species and therefore allowing their T b to increase as T a increases are not an option. We conclude that global warming will have a detrimental impact on a wide range of desert animals, but in reality we know little about the ability of most animals to cope with change in T a. The data presented should serve as base-line information on T b of animals in the Kingdom for future scientists in Saudi Arabia as they explore the impact of global warming on animal species.
    背景与目标: : 全球变暖正在以惊人的速度发生,据预测,本世纪气温 (T a) 将继续升高。由于大气中温室气体的不断增加,T a的增加对全世界野生动植物种群的分布和数量构成了威胁。尽管全球所有动物都可能受到全球变暖的影响,但由于T as已经很高,并且动物获得水的机会有限,因此将来沙漠中的昼夜动物将受到特别威胁。预计沙特阿拉伯在下个世纪将经历3-5 °C的温度。为了预测全球变暖对动物的影响,重要的是要了解单个物种如何应对较高的气温。我们认为,种群将没有足够的时间对较高的T a进行进化调整,因此他们将被迫改变其分布模式,或对其应对高T a的能力进行表型调整。本报告研究了T a的增加如何影响干旱地区动物的体温 (T b)。我们从沙特阿拉伯选择了三个分类学类别,即哺乳动物,鸟类和爬行动物 (阿拉伯羚羊,阿拉伯刺尾蜥蜴,秃鹫和云雀),该地区的夏季正午温度通常达到45 °C。当T a超过T b时,动物必须诉诸行为和生理方法来控制其T b; 否则会导致死亡。这项研究的观察结果表明,在许多情况下,这些物种的T b已经接近47 °c左右的致死上限,因此,随着T a的增加,允许其T b增加是不可行的。我们得出结论,全球变暖将对各种沙漠动物产生不利影响,但实际上,我们对大多数动物应对T a变化的能力知之甚少。所提供的数据应作为沙特阿拉伯未来科学家在探索全球变暖对动物物种的影响时,作为沙特阿拉伯动物T b的基线信息。
  • 【ASlive: 用于牲畜动物中替代剪接图谱的数据库。】 复制标题 收藏 收藏
    DOI:10.1186/s12864-020-6472-9 复制DOI
    作者列表:Liu J,Tan S,Huang S,Huang W
    BACKGROUND & AIMS: BACKGROUND:Alternative splicing is an important biological process whose precision must be tightly regulated during growth and development. Although there are species, disease (e.g. cancers), or study specific databases available in many organisms, no database exists in livestock animals specifically tailored for alternative splicing. DESCRIPTION:We present in this study the development and implementation of a database for alternative splicing atlas in livestock animals (ASlive.org). Using publicly available RNASeq data sets across many tissues, cell types, and biological conditions totaling 28.6 T bases, we built a database of alternative splicing events in five major livestock and poultry animal species (cattle, sheep, pigs, horses, and chickens). The database contains many types of information on alternative splicing events, including basic information such as genomic locations, genes, and event types, quantitative measurements of alternative splicing in the form of percent spliced in (PSI), overlap with known DNA variants, as well as orthologous events across different lineage groups. CONCLUSIONS:This database, the first of its kind in livestock animals, will provide a useful exploratory tool to assist functional annotation of animal genomes.
    背景与目标:
  • 【从澳大利亚动物和兽医中分离出的耐甲氧西林金黄色葡萄球菌的分子表征。】 复制标题 收藏 收藏
    DOI:10.1089/mdr.2017.0032 复制DOI
    作者列表:Worthing KA,Abraham S,Pang S,Coombs GW,Saputra S,Jordan D,Wong HS,Abraham RJ,Trott DJ,Norris JM
    BACKGROUND & AIMS: :This study aimed to determine the frequency and molecular epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) from Australian animals and whether animal-derived MRSA was similar to that from Australian veterinarians. A total of 1,080 clinical coagulase positive Staphylococcus isolates from Australian animals were collected during 2013. Sixteen (4%) of 360 S. aureus isolates were MRSA. Most MRSA came from companion animals, while none came from livestock. MRSA isolates were characterized using whole genome sequencing. ST22-IV (EMRSA-15) was the most common clone in dogs and cats. Clonal complex (CC) 8 was most common in horses. Most ST22-IV isolates were resistant to ciprofloxacin. Animal-derived MRSA genomes were interrogated for the presence of host-specific genetic markers (staphylokinase gene [scn], chemotaxis-inhibiting proteins gene [chp], staphylococcal complement inhibitor gene [sak], enterotoxin A gene [sea], and Von Willebrand Factor binding protein gene [vwb]). A subset of MRSA genomes previously collected from Australian veterinarians was also interrogated. There was no clear pattern in the distribution of host-specific markers among animal and veterinarian isolates. Animal- and veterinarian-derived MRSA were intermingled in the phylogenetic tree. The absence of MRSA in Australian livestock is in stark contrast with its presence in livestock from other countries. Possible explanations include Australia's geographic isolation, the absence of live animal importation into Australia, and most notably, the restrictions placed on the use of antimicrobials of critical importance in Australian livestock.
    背景与目标: : 这项研究旨在确定澳大利亚动物耐甲氧西林金黄色葡萄球菌 (MRSA) 的频率和分子流行病学,以及动物来源的MRSA是否与澳大利亚兽医相似。2013年共收集了来自澳大利亚动物的1,080株临床凝固酶阳性葡萄球菌。360株金黄色葡萄球菌中的16株 (4% 株) 为MRSA。大多数MRSA来自伴侣动物,而没有来自牲畜。使用全基因组测序对MRSA分离株进行鉴定。ST22-IV (EMRSA-15) 是狗和猫中最常见的克隆。克隆复合体 (CC) 8在马中最常见。大多数ST22-IV分离株对环丙沙星耐药。询问动物来源的MRSA基因组是否存在宿主特异性遗传标记 (葡萄球菌激酶基因 [scn],趋化性抑制蛋白基因 [chp],葡萄球菌补体抑制剂基因 [sak],肠毒素A基因 [sea] 和Von Willebrand因子结合蛋白基因 [vwb])。还询问了先前从澳大利亚兽医那里收集的MRSA基因组的子集。在动物和兽医分离株中,宿主特异性标记的分布没有明确的模式。动物和兽医来源的MRSA混合在系统发育树中。澳大利亚牲畜中没有MRSA与其他国家的牲畜中存在的MRSA形成鲜明对比。可能的解释包括澳大利亚的地理隔离,没有活体动物进口到澳大利亚,最值得注意的是,对在澳大利亚牲畜中使用至关重要的抗菌剂的限制。
  • 【非人类灵长类动物: 发育精神病理学的模型动物。】 复制标题 收藏 收藏
    DOI:10.1038/npp.2008.150 复制DOI
    作者列表:Nelson EE,Winslow JT
    BACKGROUND & AIMS: :Non-human primates have been used to model psychiatric disease for several decades. The success of this paradigm has issued from comparable cognitive skills, brain morphology, and social complexity in adult monkeys and humans. Recently, interest in biological psychiatry has focused on similar brain, social, and emotional developmental processes in monkeys. In part, this is related to evidence that early postnatal experiences in human development may have profound implications for subsequent mental health. Non-human primate studies of postnatal phenomenon have generally fallen into three basic categories: experiential manipulation (largely manipulations of rearing), pharmacological manipulation (eg drug-induced psychosis), and anatomical localization (defined by strategic surgical damage). Although these efforts have been very informative each of them has certain limitations. In this review we highlight general findings from the non-human primate postnatal developmental literature and their implications for primate models in psychiatry. We argue that primates are uniquely capable of uncovering interactions between genes, environmental challenges, and development resulting in altered risk for psychopathology.
    背景与目标: : 几十年来,非人类灵长类动物一直被用来模拟精神疾病。这种范例的成功源于成年猴子和人类可比的认知技能,大脑形态和社会复杂性。最近,人们对生物精神病学的兴趣集中在猴子类似的大脑,社交和情感发展过程上。在某种程度上,这与人类发展中的早期产后经历可能对随后的精神卫生产生深远影响的证据有关。出生后现象的非人类灵长类动物研究通常分为三个基本类别: 经验操作 (主要是饲养操作),药理操作 (例如药物引起的精神病) 和解剖定位 (由战略性手术损伤定义)。尽管这些努力提供了很多信息,但每个努力都有一定的局限性。在这篇综述中,我们重点介绍了非人类灵长类动物出生后发育文献的一般发现及其对精神病学灵长类动物模型的影响。我们认为灵长类动物具有独特的能力,能够揭示基因,环境挑战和发育之间的相互作用,从而导致心理病理学风险的改变。
  • 【开发标准测试,以检查实验动物血液的粘弹性,用于儿科机械支持装置评估。】 复制标题 收藏 收藏
    DOI:10.1097/01.mat.0000242248.66083.48 复制DOI
    作者列表:Marascalco PJ,Ritchie SP,Snyder TA,Kameneva MV
    BACKGROUND & AIMS: :We investigated the applicability of measuring the viscoelasticity of bovine, ovine, and porcine whole blood for the evaluation of sublethal damage to red blood cells (RBCs). An increase in blood viscosity and elasticity without changes in hematocrit and plasma viscosity would signify a decrease in RBC deformability. Blood viscoelasticity was assessed using a Vilastic Scientific viscoelastometer. Due to the natural absence of RBC aggregation and small RBC size in normal bovine and ovine blood, viscoelastic properties are less readily detected. However, we found that adjustment of blood hematocrit to a standard level of 40-50% allows for sensitive assessment of viscoelasticity in these blood types demonstrating a marked non-Newtonian behavior mostly related to RBC deformability. Porcine blood showed a pronounced non-Newtonian behavior at all tested hematocrit values, which makes it rheologically comparable to human blood. Both viscosity and elasticity were elevated after blood exposure to a uniform mechanical stress. RBCs rigidified by heat exposure demonstrated a loss of viscoelasticity dependence on shear rate. Measurements of blood viscoelasticity can be meaningful in bovine, ovine, and, especially, porcine blood, and can be used for evaluation of sublethal blood damage during in vitro and animal trials of heart-assist devices.
    背景与目标: : 我们研究了测量牛,羊和猪全血的粘弹性在评估对红细胞 (rbc) 的亚致死性损伤中的适用性。血液粘度和弹性的增加而血细胞比容和血浆粘度的变化将表明RBC变形性的降低。使用villastic科学粘弹性计评估血液粘弹性。由于正常牛和绵羊血液中天然不存在红细胞聚集和红细胞大小较小,因此不易检测到粘弹性。但是,我们发现将血液血细胞比容调整到40-50% 的标准水平可以对这些血型的粘弹性进行灵敏的评估,证明了明显的非牛顿行为,主要与RBC变形性有关。在所有测试的血细胞比容值下,猪血均显示出明显的非牛顿行为,这使其在流变上与人血相当。血液暴露于均匀的机械应力后,粘度和弹性均升高。通过暴露于热而硬化的rbc表现出对剪切速率的粘弹性依赖性丧失。在牛,羊,尤其是猪血中,血液粘弹性的测量可能是有意义的,并且可用于在心脏辅助设备的体外和动物试验中评估亚致死性血液损伤。
  • 【跳跃物种之间的细线: 动物中转座因子的水平转移催化基因组进化。】 复制标题 收藏 收藏
    DOI:10.1002/bies.201300072 复制DOI
    作者列表:Ivancevic AM,Walsh AM,Kortschak RD,Adelson DL
    BACKGROUND & AIMS: :Horizontal transfer (HT) is the transmission of genetic material between non-mating species, a phenomenon thought to occur rarely in multicellular eukaryotes. However, many transposable elements (TEs) are not only capable of HT, but have frequently jumped between widely divergent species. Here we review and integrate reported cases of HT in retrotransposons of the BovB family, and DNA transposons, over a broad range of animals spanning all continents. Our conclusions challenge the paradigm that HT in vertebrates is restricted to infective long terminal repeat (LTR) retrotransposons or retroviruses. This raises the possibility that other non-LTR retrotransposons, such as L1 or CR1 elements, believed to be only vertically transmitted, can horizontally transfer between species. Growing evidence indicates that the process of HT is much more general across different TEs and species than previously believed, and that it likely shapes eukaryotic genomes and catalyses genome evolution.
    背景与目标: : 水平转移 (HT) 是遗传物质在非交配物种之间的传递,这种现象被认为在多细胞真核生物中很少发生。然而,许多转座元素 (TEs) 不仅具有HT的能力,而且经常在广泛差异的物种之间跳跃。在这里,我们回顾并整合了BovB家族的逆转录转座子和DNA转座子中报告的HT病例,这些病例遍及所有大洲。我们的结论挑战了脊椎动物中HT仅限于感染性长末端重复序列 (LTR) 逆转录转座子或逆转录病毒的范例。这增加了其他非LTR反转录转座子 (例如L1或CR1元件) 被认为仅垂直传播的可能性,可以在物种之间水平转移。越来越多的证据表明,HT的过程在不同的TEs和物种之间比以前认为的更为普遍,并且它可能会塑造真核基因组并催化基因组进化。
  • 【健康实验动物外皮中毛癣菌和小孢子虫的腐生发生。(初步报告)。】 复制标题 收藏 收藏
    DOI:10.1007/BF00467084 复制DOI
    作者列表:Feuerman E,Alteras I,Hönig MD,Lehrer N
    BACKGROUND & AIMS: :A group of 199 healthy laboratory animals, comprising 63 guinea pigs; 58 white mice. 47 rats and 31 rabbits, was sampled for the presence of pathogenic dermatophytes. T. mentagrophytes, var. granulare, was isolated in 10% (5-guinea pigs, 6 mice, 6 rats and 2 rabbits) and M. gypseum was found in 7 animals (3 guinea pigs, 3 mice and one rat). No ringworm lesions were observed in the respective animals. This is the first report on such findings in Israel.
    背景与目标: : 一组199只健康的实验动物,包括63只豚鼠; 58只白鼠。对47只大鼠和31只兔子进行了采样,以寻找致病性皮肤癣菌的存在。在10% (5-豚鼠,6只小鼠,6只大鼠和2只兔子) 中分离出T. mentagrophytes,var.Granular,并在7只动物 (3只豚鼠,3只小鼠和一只大鼠) 中发现了gypsym。在各个动物中未观察到癣病变。这是以色列关于这种调查结果的第一份报告。
  • 【野生动物粪便样品中产生广谱 β-内酰胺酶的大肠杆菌分离株的克隆多样性。】 复制标题 收藏 收藏
    DOI:10.1093/femsle/fnx039 复制DOI
    作者列表:Cristóvão F,Alonso CA,Igrejas G,Sousa M,Silva V,Pereira JE,Lozano C,Cortés-Cortés G,Torres C,Poeta P
    BACKGROUND & AIMS: :The clonal diversity of extended-spectrum-β-lactamase (ESBL)-producing Escherichia coli isolates from nine different species of wild animals from distinct regions of Portugal and Spain and their content in replicon plasmids were analyzed. Among the initial 53 ESBL-producing E. coli isolates that were studied (from previous studies), 28 were selected, corresponding to different animal origins with distinct ESBL types and pulsed-field gel electrophoresis (PFGE) patterns. These 28 isolates produced different ESBLs ascribed to the following families: CTX-M, SHV and TEM. The isolates were classified into three phylogenetic groups: B1 (n = 11), A (n = 10) and D (n = 7). The seven E. coli of phylogroup D were then typed by multilocus sequence typing and ascribed to four distinct sequence types: ST117, ST115, ST2001 and ST69. The clonal diversity and relationship between isolates was studied by PFGE. Lastly, the plasmids were analyzed according to their incompatibility group using the PCR-based-replicon-typing scheme. A great diversity of replicon types was identified, with up to five per isolate. Most of the CTX-M-1 and SHV-12 producing E. coli isolates carried IncI1 or IncN replicons. The diversity of ESBL-producing E. coli isolates in wild animals, which can be disseminated in the environment, emphasizes the environmental and health problems that we face nowadays.
    背景与目标: : 分析了来自葡萄牙和西班牙不同地区的9种不同野生动物的产超广谱 β-内酰胺酶 (ESBL) 大肠杆菌的克隆多样性及其在复制子质粒中的含量。在最初研究的53种产生ESBL的大肠杆菌分离株中 (来自先前的研究),选择了28种,分别对应于具有不同ESBL类型和脉冲场凝胶电泳 (PFGE) 模式的不同动物来源。这28个分离株产生了不同的ESBLs,这些ESBLs归因于以下家族: ctx-m,SHV和TEM。分离株分为三个系统发育组: B1 (n = 11),A (n = 10) 和D (n = 7)。然后通过多基因座序列分型对系统组D的七个大肠杆菌进行分型,并归因于四种不同的序列类型: ST117,ST115,ST2001和st69。通过PFGE研究了分离株之间的克隆多样性和关系。最后,使用基于PCR的复制子分型方案根据其不相容性组分析质粒。鉴定出复制子类型的多样性,每个分离株最多5种。大多数产生大肠杆菌的CTX-M-1和SHV-12分离株都带有IncI1或IncN复制子。野生动物中产生ESBL的大肠杆菌分离物的多样性,可以在环境中传播,这强调了我们当今面临的环境和健康问题。
  • 【与动物实验室技术人员联系荨麻疹。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Agrup G,Sjöstedt L
    BACKGROUND & AIMS: :The occurrence of contact urticaria was studied in 101 laboratory technicians investigated for allergy to laboratory animals. Fourteen cases of contact urticaria caused by rat were found. Other animals causing contact urticarial reactions were mouse (7), guinea-pig (4), and cat (2). Hand eczema was not found in laboratory technicians with contact urticaria and IgE-antibodies to laboratory animals.
    背景与目标: : 在101实验室技术人员中研究了接触性荨麻疹的发生,调查了对实验动物的过敏。发现14例由大鼠引起的接触性荨麻疹。引起接触性荨麻疹反应的其他动物是小鼠 (7),豚鼠 (4) 和猫 (2)。在具有接触性荨麻疹和对实验动物的IgE抗体的实验室技术人员中未发现手湿疹。
  • 12 Modification of the Genome of Domestic Animals. 复制标题 收藏 收藏

    【家畜基因组的修饰。】 复制标题 收藏 收藏
    DOI:10.1080/10495398.2016.1261874 复制DOI
    作者列表:Lotti SN,Polkoff KM,Rubessa M,Wheeler MB
    BACKGROUND & AIMS: :In the past few years, new technologies have arisen that enable higher efficiency of gene editing. With the increase ease of using gene editing technologies, it is important to consider the best method for transferring new genetic material to livestock animals. Microinjection is a technique that has proven to be effective in mice but is less efficient in large livestock animals. Over the years, a variety of methods have been used for cloning as well as gene transfer including; nuclear transfer, sperm mediated gene transfer (SMGT), and liposome-mediated DNA transfer. This review looks at the different success rate of these methods and how they have evolved to become more efficient. As well as gene editing technologies, including Zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and the most recent clustered regulatory interspaced short palindromic repeats (CRISPRs). Through the advancements in gene-editing technologies, generating transgenic animals is now more accessible and affordable. The goals of producing transgenic animals are to 1) increase our understanding of biology and biomedical science; 2) increase our ability to produce more efficient animals; and 3) produce disease resistant animals. ZFNs, TALENs, and CRISPRs combined with gene transfer methods increase the possibility of achieving these goals.
    背景与目标: : 在过去的几年中,出现了新技术,可以提高基因编辑的效率。随着基因编辑技术的使用越来越容易,重要的是要考虑将新的遗传物质转移到牲畜的最佳方法。微量注射是一种技术,已被证明对小鼠有效,但对大型家畜动物效率较低。多年来,已使用多种方法进行克隆和基因转移,包括: 核转移,精子介导的基因转移 (SMGT) 和脂质体介导的DNA转移。这篇评论着眼于这些方法的不同成功率,以及它们是如何演变成更有效率的。以及基因编辑技术,包括锌指核酸酶 (ZFNs),转录激活因子样效应核酸酶 (TALENs) 和最新的簇调节间隔短回文重复序列 (CRISPRs)。通过基因编辑技术的进步,现在更容易获得和负担得起转基因动物。生产转基因动物的目标是: 1) 增进我们对生物学和生物医学科学的了解; 2) 提高我们生产更高效动物的能力; 3) 生产抗病动物。ZFNs,TALENs和CRISPRs结合基因转移方法增加了实现这些目标的可能性。
  • 【正常和糖尿病动物胰岛中胰岛素的糖基化。】 复制标题 收藏 收藏
    DOI:10.2337/diab.45.11.1489 复制DOI
    作者列表:Abdel-Wahab YH,O'Harte FP,Ratcliff H,McClenaghan NH,Barnett CR,Flatt PR
    BACKGROUND & AIMS: :The glycation of immunoreactive insulin (IRI) was assessed in extracts of pancreas and islets from control and hyperglycemic animal models. Glycated and nonglycated IRI were separated by affinity chromatography and quantified by radioimmunoassay. Hydrocortisone-treated Wistar rats (80 mg x kg-1 x day-1 and obese hyperglycemic (ob/ob) mice showed significant increases in plasma glucose (P < 0.001), percentage glycated hemoglobin (P < 0.001), plasma IRI (P < 0.01), and total pancreatic IRI content (P < 0.01), compared with their respective controls. These diabetic groups also demonstrated significant increases (P < 0.05) in the percentage of glycated pancreatic IRI above the controls. Streptozotocin-treated (200 mg/kg) Swiss TO mice exhibited significant increases in plasma glucose (P < 0.001), glycated hemoglobin (P < 0.001), and percentage glycated pancreatic IRI (P < 0.05), compared with untreated controls, despite a marked decrease in both plasma IRI (P < 0.001) and total pancreatic IRI content (P < 0.001). Significant elevations in the percentage of glycated IRI were also observed in islets isolated from obese hyperglycemic (ob/ob) mice (P < 0.001), compared with islets from lean controls, and when lean mouse islets were cultured in hyperglycemic media for 24 h (33.3 vs. 5.6 mmol/l D-glucose; P < 0.001). The contribution of glycated plus nonglycated insulin and proinsulin to the total IRI was estimated in lean and obese mouse pancreatic extracts following high-performance liquid chromatography separation. The contribution of proinsulin to the total IRI was approximately 10%. Proinsulin represented 27-28% of the total glycated IRI. These data indicate that the glycation of insulin and proinsulin occurs within the pancreatic islets and is elevated in both insulin-deficient and insulin-resistant diabetic animal models.
    背景与目标: : 在对照和高血糖动物模型的胰腺和胰岛提取物中评估了免疫反应性胰岛素 (IRI) 的糖基化。通过亲和色谱分离糖化和非糖化IRI,并通过放射免疫分析法进行定量。氢化可的松处理的Wistar大鼠 (80 mg × kg-1 × day-1) 和肥胖高血糖 (ob/ob) 小鼠的血浆葡萄糖 (P <0.001),糖化血红蛋白百分比 (P <0.001),血浆IRI (P <0.01),和胰腺IRI总含量 (P <0.01),与他们各自的对照组相比,这些糖尿病组的糖化胰腺IRI的百分比也显著增加 (P <0.05),高于对照组。链脲佐菌素治疗 (200 mg/kg) Swiss对小鼠的血浆葡萄糖显著增加 (P <0.001),与未治疗的对照组相比,糖化血红蛋白 (P < 0.001) 和糖化胰腺IRI百分比 (P <0.05),尽管血浆IRI (P < 0.001) 和总胰腺IRI含量 (P < 0.001) 均显著降低。与瘦肉对照组的胰岛相比,从肥胖高血糖 (ob/ob) 小鼠分离的胰岛 (P < 0.001) 中也观察到糖化IRI的百分比显著升高,当瘦鼠胰岛在高血糖培养基中培养24 h (33.3 vs. 5.6 mmol/l D-葡萄糖; P <0.001)。在高效液相色谱分离后,估计了瘦瘦和肥胖小鼠胰腺提取物中糖化加非糖化胰岛素和胰岛素原对总IRI的贡献。胰岛素原对总IRI的贡献约为10%。胰岛素原占总糖化IRI的27-28%。这些数据表明胰岛素和胰岛素原的糖基化发生在胰岛内,并且在胰岛素缺乏和胰岛素抵抗的糖尿病动物模型中均升高。
  • 【活的tularemia疫苗可保护实验动物免受致命的军团菌和李斯特菌感染。】 复制标题 收藏 收藏
    DOI:10.1111/j.1574-695X.1996.tb00239.x 复制DOI
    作者列表:Belyi YF,Tartakovskii IS,Mesheryakova IS,Petrosov VV,Prosorovskii SV
    BACKGROUND & AIMS: The efficacy of a live Francisella tularensis vaccine strain to cause nonspecific immunity toward experimental legionellosis and listeriosis was studied. Immunisation with tularemia vaccine protected over 80% and 17% of experimental animals against subsequent lethal challenge with Legionella pneumophila and Listeria monocytogenes, respectively. The protection was maximal during the first month following immunisation and declined thereafter. In order to delineate the immunostimulatory moieties of the Francisella microbe, several cell wall proteins have been purified and characterized. However, isolated cell wall components failed to induce protection.

    背景与目标: 研究了活的土拉弗朗西斯菌疫苗株对实验性军团菌病和李斯特菌病产生非特异性免疫的功效。用tularemia疫苗免疫分别保护了超过80% 和17% 的实验动物免受随后的嗜肺军团菌和单核细胞增生李斯特菌的致命攻击。在免疫后的第一个月,保护作用最大,此后下降。为了描述Francisella微生物的免疫刺激部分,已经纯化并鉴定了几种细胞壁蛋白。然而,孤立的细胞壁成分未能诱导保护。
  • 【有机磷杀虫剂杀nitrothion在储存的蚕豆中的行为及其对实验动物的生物学作用。】 复制标题 收藏 收藏
    DOI:10.1080/03601230701465718 复制DOI
    作者列表:Farghaly M,Mahdy F,Taha H,Fathy U
    BACKGROUND & AIMS: :Sound whole-seed faba beans were treated with (methyl-(14)C) fenitrothion [O, O-dimethyl-O-(3-methyl-4-nitrophenyl) phosphorothioate] at 5 and 10 mg insecticide/kg seeds, a dose normally used in practice. During the 30 weeks of storage period, the penetration and distribution of insecticide residues were studied. The amount of surface residues, internal residues and bound insecticide residues was estimated. Surface residues were found to decrease with the increase in time of storage, whereas internal residues showed a gradual increase with time apparently not dose dependent. Grain-bound residues increased with time and reached to its maximum (14-18%) after 24 weeks of storage. Chromatographic analysis of the internal extracts revealed the presence of the parent compound together with three main metabolites which were found in both free and conjugated form. Feeding mice for 90 days with a diet mixed with total internal fenitrothion residues in stored faba beans led to a reduction in body weight gain, and an appreciable decrease in cholinesterase activity of 32% for plasma and 15% for red blood cells (RBC(S)) after two months of experiment. Also, a significant decrease was showed in both total protein and albumin concentration at the end of feeding period (90 days). Liver and kidney function, as well as lipid profile of treated mice significantly increased at the end of feeding period. After a one-month recovery period, all the examined blood parameters returned to about the control values except blood urea and serum triglyceride.
    背景与目标: : 用 (甲基-(14)C) 杀nitro硫磷 [O,O-二甲基-O-(3-甲基-4-硝基苯基) 硫代磷酸酯] 以5和10 mg杀虫剂/kg种子处理全种子蚕豆,该剂量通常在实践中使用。在30周的储存期间,研究了杀虫剂残留物的渗透和分布。估算了表面残留物,内部残留物和结合的杀虫剂残留物的数量。发现表面残留物随储存时间的增加而减少,而内部残留物随时间逐渐增加,显然与剂量无关。谷物结合残留物随时间增加,并在储存24周后达到最大值 (14-18%)。内部提取物的色谱分析表明,存在母体化合物以及三种主要代谢物,它们均以游离和共轭形式存在。在两个月的实验后,用与储存的蚕豆中的总内部杀nitro离子残基混合的饮食喂养小鼠90天,导致体重增加减少,并且32% 对血浆和对红细胞 (RBC(S)) 的15% 胆碱酯酶活性明显降低。此外,在饲喂期结束时 (90天),总蛋白和白蛋白浓度均显着降低。在喂养期结束时,治疗小鼠的肝,肾功能以及脂质分布显着增加。经过一个月的恢复期后,除血尿素和血清甘油三酸酯外,所有检查的血液参数均恢复到约对照值。

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