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The role of cyclin F in Motor Neurone Disease 细胞周期蛋白F在运动神经元疾病中的作用
Q4 Multidisciplinary Pub Date : 2020-12-01 DOI: 10.5962/p.361941
Stephanie L. Rayner
of a thesis for a Doctorate of Philosophy submitted to Macquarie University, Sydney Mo Neurone Disease (MND) is characterised by the loss of motor neurons in the brain and spinal cord. Most patients with MND develop proteinaceous inclusions within affected neurons of the central nervous system, suggesting overall] dysregulation of protein degradation systems. Our team identified mutations in CCNF, the gene encoding cyclin F. Cyclin F is a substrate binding component of a multi-protein ubiquitin ligase (denoted SCFo«linF) | which mediates the ubiquitylation of substrates in order to influence the cell cycle. Overarching aims of this thesis concern the impact of CCNF mutations on the ubiquitin ligase activity of SCFeelin F and the downstream impact within cells. Addressing these aims involved using a series of biochemical assays (including in VItTO ubiquitylation assays, immunoprecipi-tations, proximity-ligation assays and mass spectrometry). Results demonstrate that an MND-linked mutation in cyclin F leads to defective ubiquitylation activity, ultimately leading to the accumulation of proteins tagged for degradation. Overall, the work provides insight into how the precise control of cyclin F ligase activity is dysregulated when cyclin F carries a disease-causing mutation. Furthermore, outcomes from this work provide novel links between cyclin F (a cell cycle regulator) and a devastating disease involving the degeneration of post-mitotic neurons.
悉尼莫神经元病(MND)的特征是大脑和脊髓中运动神经元的丧失。大多数MND患者在受影响的中枢神经系统神经元内出现蛋白质内含物,表明蛋白质降解系统总体失调。我们的团队发现了编码细胞周期蛋白F的CCNF基因的突变。细胞周期蛋白F是一种多蛋白泛素连接酶(表示为SCFo«linF)的底物结合成分,它介导底物的泛素化以影响细胞周期。本论文的主要目的是研究CCNF突变对SCFeelin F泛素连接酶活性的影响以及细胞内的下游影响。为了实现这些目标,需要使用一系列生物化学分析(包括VItTO泛素化分析、免疫沉淀、邻近连接分析和质谱分析)。结果表明,细胞周期蛋白F中MND连接的突变导致泛素化活性缺陷,最终导致标记降解的蛋白质积累。总的来说,这项工作深入了解了当细胞周期蛋白F携带致病突变时,细胞周期蛋白F连接酶活性的精确控制是如何失调的。此外,这项工作的结果提供了细胞周期蛋白F(一种细胞周期调节因子)与一种涉及有丝分裂后神经元变性的毁灭性疾病之间的新联系。
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引用次数: 0
Investigating undergraduate nurse responses to simulated interruptions during medication administration--a qualitative multi-method study 研究本科生护士在用药过程中对模拟中断的反应——一项多方法的定性研究
Q4 Multidisciplinary Pub Date : 2020-12-01 DOI: 10.5962/p.361932
C. Hayes
....................................................................................................................... xv Structure of the thesis ................................................................................................ xix List of definitions .......................................................................................................... xxi Chapter 1: Introduction .............................................................................................. 1 1.1 Background and significance ......................................................................... 1 1.2 Study aim ............................................................................................................. 6 1.3 Research questions ............................................................................................ 6 1.4 Chapter conclusion ........................................................................................... 6 Chapter 2: Literature review ....................................................................................... 7 2.
xv论文结构。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。xix定义列表。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。xxi第1章:引言。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。1.1背景和意义。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。1.2研究目的。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。6 1.3研究问题。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。6 1.4章节结论。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。6第2章:文献综述。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。7。
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引用次数: 0
The Chief Scientist is right, and why 首席科学家是对的,为什么
Q4 Multidisciplinary Pub Date : 2020-12-01 DOI: 10.5962/p.361925
P. Rez
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引用次数: 0
Black America Cares: The response of African Americans to the Nigerian Civil War, 1967-1970 美国黑人关心:非洲裔美国人对尼日利亚内战的反应,1967-1970
Q4 Multidisciplinary Pub Date : 2020-12-01 DOI: 10.5962/p.361930
J. Farquharson
Far from having only marginal significance and generating a ‘subdued’ response among African Americans, as some historians have argued, the Nigerian Civil War (1967-1970) collided at full velocity with the conflicting discourses and ideas by which black Americans sought to understand their place in the United States and the world in the late 1960s. Black liberal civil rights leaders leapt to offer their service as agents of direct diplomacy during the conflict, seeking to preserve Nigerian unity; grassroots activists from New York to Kansas organised food-drives, concerts and awareness campaigns in support of humanitarian aid for Biafran victims of starvation; while other pro-Biafran black activists warned of links between black ‘genocide’ in Biafra and the US alike. This thesis is the first to recover and analyse at length the extent, complexity and character of such African American responses to the Nigerian Civil War. Drawing on extensive use of private papers, activist literature, government records and especially the black press, it charts the way African Americans conceptualised, over time and in complex ways, their varied understandings of issues such as black internationalist solidarities, territorial sovereignty and political viability, humanitarian compassion and great power realpolitik, as well as colonial and neo-colonial influence in Africa. The thesis initially explores the longer twentieth century history of African American engagement with Nigeria by way of establishing context, before providing in-depth analysis of the key initiatives and events that comprised African American engagement with the civil war. Chapters move chronologically and thematically to discuss direct diplomatic efforts to broker peace, African American responses to alleged genocide in Biafra, the rise and fall of pro-Biafran political support, and the latter’s loss to what emerged as a stronger political bloc of those supporting Nigerian political unity. Situated methodologically and historiographically at the intersection of scholarship on black internationalism and the international history of the Nigerian Civil War, this thesis demonstrates the way the civil war not only provoked intense activism, but did so in ways that fundamentally connected with the central ideas, themes and concerns of the black freedom struggle in the United States.
正如一些历史学家所说,尼日利亚内战(1967年至1970年)非但没有微不足道的意义,也没有在非裔美国人中引起“温和”的反应,反而与20世纪60年代末美国黑人试图理解自己在美国和世界上的地位的相互冲突的话语和思想全速碰撞。黑人自由民权领袖在冲突期间迅速提供直接外交代理人的服务,寻求维护尼日利亚的团结;从纽约到堪萨斯州的草根活动家组织了食品运动、音乐会和提高认识运动,以支持对比亚弗兰饥饿受害者的人道主义援助;而其他支持比夫拉的黑人活动人士则警告说,比夫拉和美国的黑人“种族灭绝”之间存在联系。本文首次详细回顾和分析了非裔美国人对尼日利亚内战的反应的程度、复杂性和特点。它借鉴了私人报纸、活动家文献、政府记录,尤其是黑人媒体的广泛使用,描绘了非裔美国人随着时间的推移,以复杂的方式对黑人国际主义团结、领土主权和政治可行性、人道主义同情和大国现实政治等问题的不同理解进行概念化的方式,以及非洲的殖民主义和新殖民主义影响。本文通过建立背景,初步探讨了20世纪非裔美国人与尼日利亚接触的漫长历史,然后对非裔美国人参与内战的关键举措和事件进行了深入分析。各章按时间和主题展开,讨论斡旋和平的直接外交努力、非裔美国人对比亚夫拉种族灭绝指控的回应、支持比亚夫兰的政治支持的兴衰,以及后者输给了一个由支持尼日利亚政治团结的更强大的政治集团。本文在方法论和历史学上处于黑人国际主义学术与尼日利亚内战国际史的交叉点,展示了内战不仅引发了激烈的激进主义,而且从根本上与美国黑人自由斗争的核心思想、主题和关切相联系。
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引用次数: 0
Belief change without compactness 信念变化无紧凑性
Q4 Multidisciplinary Pub Date : 2020-12-01 DOI: 10.5962/p.361942
Jandson Santo Ribeiro Santo
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引用次数: 0
Richard Limon Stanton DistFRSN (1926-2020) 理查德·利蒙·斯坦顿(1926-2020)
Q4 Multidisciplinary Pub Date : 2020-12-01 DOI: 10.5962/p.361946
R. Marks
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引用次数: 0
The impact of anthropogenic stressors on coral reef carbonate sediment metabolism and dissolution 人为压力源对珊瑚礁碳酸盐沉积物代谢和溶解的影响
Q4 Multidisciplinary Pub Date : 2020-12-01 DOI: 10.5962/p.361938
C. Lantz
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引用次数: 0
Implementation of a harvest slot for Murray Cod: Initial impacts on the recreational harvest in a manmade reservoir and comparison to riverine fisheries Murray Cod捕捞时段的实施:对人造水库休闲捕捞的初步影响以及与河流渔业的比较
Q4 Multidisciplinary Pub Date : 2020-12-01 DOI: 10.5962/p.361916
A. Steffe, Jamin P. Forbes, R. Watts, L. Baumgartner, P. Brown, J. Thiem, N. Miles
Freshwater reservoirs support valuable commercial and recreational fisheries resources worldwide. Recreational fisheries in reservoirs are commonly managed using length-based harvest regulations, although empirical data is required to ensure these regulations are fit-for-purpose and that any changes do not result in negative population responses. Following a change from a 600 mm minimum legal length to a 550-750 mm harvest slot (HS) limit for both reservoir and river based recreational fisheries for Murray cod, Maccullochella peelii, we used a stratified random sampling design to assess the summer recreational fishery in Lake Mulwala, an important reservoir fishery. Specifically, we assessed the immediate effects of the HS on angler effort, catch and harvest in this fishery. Standardised parameters based on data from existing angler surveys were also used to investigate variability among fisheries for Murray cod. We found that (1) in Lake Mulwala, more than 50% of Murray cod harvested after the introduction of the HS were between 550 and 600 mm; (2) boat-based anglers almost exclusively targeted Murray cod and harvested more and larger fish than shore-based anglers; (3) the Murray cod population was severely truncated with high mandatory discard rates (93.7% for boat fisheries and 99.8% for shore fisheries) of fish below the lower HS limit; (4) standardised parameters varied among waterbodies, and comparatively higher effort, discard and harvest densities were observed in the reservoir fishery. The reliance on newly harvestable Murray cod in Lake Mulwala highlights the need for early and ongoing monitoring of regulatory changes across riverine and reservoir environments, encompassing both social and biological aspects of the fishery
淡水水库为世界各地宝贵的商业和休闲渔业资源提供了支持。水库中的休闲渔业通常使用基于长度的捕捞条例进行管理,尽管需要经验数据来确保这些条例符合目的,并且任何变化都不会导致负面的种群反应。在将墨累鳕鱼(Maccullochela peelii)的水库和河流休闲渔业的最小法定长度从600 mm改为550-750 mm的捕捞槽(HS)限制后,我们使用分层随机抽样设计来评估重要的水库渔业Mulwala湖的夏季休闲渔业。具体而言,我们评估了HS对该渔场垂钓者努力、捕捞和收获的直接影响。基于现有垂钓者调查数据的标准化参数也被用于调查墨累鳕鱼渔业的可变性。我们发现(1)在穆尔瓦拉湖,引入HS后收获的墨累鳕鱼中,50%以上在550至600毫米之间;(2) 船上垂钓者几乎完全以墨累鳕鱼为目标,比岸上垂钓者收获了更多更大的鱼;(3) 墨累鳕鱼种群严重减少,低于HS下限的鱼类强制丢弃率很高(船上渔业为93.7%,岸上渔业为99.8%);(4) 不同水体的标准化参数各不相同,在水库渔业中观察到相对较高的努力、丢弃和收获密度。对穆尔瓦拉湖新收获的墨累鳕鱼的依赖凸显了对河流和水库环境监管变化的早期和持续监测的必要性,包括渔业的社会和生物方面
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引用次数: 0
Institutional influences on education investment and pro-social behaviour 制度对教育投资和亲社会行为的影响
Q4 Multidisciplinary Pub Date : 2020-12-01 DOI: 10.5962/p.361929
Jing Chen
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引用次数: 0
Response to the 25 scientists 对25位科学家的回应
Q4 Multidisciplinary Pub Date : 2020-12-01 DOI: 10.5962/p.361921
A. Finkel
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引用次数: 0
期刊
Journal and Proceedings - Royal Society of New South Wales
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