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Enduring Controversial Story in the Human Brain 人类大脑中经久不衰的争议故事
Pub Date : 2023-03-26 DOI: 10.26443/msurj.v18i1.194
Zhipeng Niu, Tanya Capolicchio
Adult hippocampal neurogenesis (AHN) is a well-studied phenomenon that involves the derivation of new neurons from neural progenitor cells in the dentate gyrus region of the hippocampus, an area responsible for cognitive functions such as learning and memory storage. Moreover, the hippocampus is known to be implicated in neurological conditions such as Alzheimer's disease. Although AHN has been extensively observed in animal models for twenty years, its existence and persistence in humans have been widely debated in academia, heavily based on post-mortem immunohistochemical markers. Using the search engines PubMed and Google Scholar for “Adult Human Neurogenesis,” 143 articles that were most relevant to the history of AHN discovery, detection in rodents, immunohistochemical studies on post-mortem human sections, and therapeutic development targeting AHN were reviewed. This review article highlights the current understanding of AHN in rodents and humans, its implications in neurodegenerative diseases and therapeutics, and the inconsistencies and methodological variabilities encountered in studying AHN in humans. Furthermore, the correlation between AHN and diseases such as mood disorders and Alzheimer's disease is still not well established, with conflicting findings reported. Standardization of transcriptomic methodologies and increased availability of post-mortem human brain samples are crucial in advancing AHN research. This review article attempts to discover the fascinating and controversial world of adult human neurogenesis and its potential implications in treating neurological disorders. Apart from the discussion on AHN existence, tackling devastating diseases with this supplemental knowledge can lead to therapeutic advancements which greatly rely on understanding not only the presence of AHN but the mechanisms mediating its availability.
成人海马神经发生(AHN)是一种被充分研究的现象,涉及海马齿状回区域的神经祖细胞衍生新的神经元,该区域负责认知功能,如学习和记忆储存。此外,海马体被认为与阿尔茨海默病等神经系统疾病有关。尽管AHN已经在动物模型中广泛观察了20年,但其在人类中的存在和持续性在学术界一直存在广泛的争论,主要基于死后免疫组织化学标记。通过PubMed和谷歌Scholar搜索“成人神经发生”,对143篇与AHN的发现史、啮齿动物的检测、人体解剖部分的免疫组织化学研究以及针对AHN的治疗开发最相关的文章进行了回顾。这篇综述文章强调了目前对啮齿动物和人类AHN的理解,其在神经退行性疾病和治疗中的意义,以及在研究人类AHN时遇到的不一致和方法上的差异。此外,AHN与情绪障碍和阿尔茨海默病等疾病之间的相关性仍未得到很好的确定,报道的结果相互矛盾。转录组学方法的标准化和增加死后人脑样本的可用性对于推进AHN研究至关重要。这篇综述文章试图发现成人神经发生的迷人和有争议的世界及其治疗神经系统疾病的潜在意义。除了对AHN存在的讨论之外,用这些补充知识来解决破坏性疾病可以导致治疗进步,这在很大程度上不仅依赖于对AHN存在的理解,而且依赖于对其可用性的机制的理解。
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引用次数: 0
At Once Friends and Foes 既是朋友又是敌人
Pub Date : 2023-03-26 DOI: 10.26443/msurj.v18i1.189
Mycobacterium tuberculosis (Mtb) is the causative agent of human tuberculosis (TB) disease. In chronic infections such as TB, consistent pro-inflammatory signalling promotes the generation of myeloid-derived suppressor cells (MDSCs). MDSCs are innate immune cells that are further divided into polymorphonuclear (PMN-MDSC) and monocytic (M-MDSC) subtypes on the basis of their morphology. These cells exert immunosuppressive effects on other immune cell types, thereby protecting the integrity of the lung tissue from damage caused by dysregulated Mtb. However, this comes at the expense of containing the Mtb infection. MDSCs’ unique double-edged role makes them an attractive target for host-directed TB therapeutics. This review aims to summarize current knowledge on the role of MDSCs in TB.
结核分枝杆菌(Mtb)是人类结核病的病原体。在结核病等慢性感染中,一致的促炎信号促进骨髓来源的抑制细胞(MDSCs)的产生。MDSCs是先天免疫细胞,根据其形态进一步分为多形核细胞(PMN-MDSC)和单核细胞(M-MDSC)亚型。这些细胞对其他免疫细胞类型发挥免疫抑制作用,从而保护肺组织的完整性免受Mtb失调引起的损伤。然而,这是以控制结核分枝杆菌感染为代价的。MDSCs独特的双刃剑作用使其成为宿主导向结核病治疗的有吸引力的靶点。本综述旨在总结目前关于MDSCs在结核病中作用的知识。
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引用次数: 0
Role of Iron in Epidermal Healing and Infection 铁在表皮愈合和感染中的作用
Pub Date : 2023-03-26 DOI: 10.26443/msurj.v18i1.188
Idia Boncheva
In recent years, the field of iron studies has expanded into sub-domains that investigate the regulation of this metal in various tissues including the heart, mucosal surfaces, tumours, and the skin. Iron homeostasis in the skin and the role of other non-hepatic cells in the regulation of iron are currently incompletely understood. This paper summarizes the role of iron in wound healing, highlights the importance of maintaining iron concentrations within an intermediate range to avoid toxicity or defects; and integrates the antimicrobial role, interactions, and regulation of various cell types. Notably, the autoregulation of hepcidin secretion by keratinocytes and recruited myeloid cells is described. Additionally, the potential therapeutic role of iron chelators in infection control and their mechanisms of action are explored. This paper aims to elucidate the relevance of local iron control in epidermal infections. Although some of the molecular details underlying this condition remain unclear, published data suggest that iron-regulating therapies are a promising treatment for the eradication of skin infections due to their wound-healing and immune-modulating potential. 
近年来,铁研究领域已经扩展到研究这种金属在包括心脏、粘膜表面、肿瘤和皮肤在内的各种组织中的调节的子领域。皮肤中的铁稳态和其他非肝细胞在铁调节中的作用目前还不完全清楚。本文总结了铁在伤口愈合中的作用,强调了将铁浓度维持在一个中等范围内以避免毒性或缺陷的重要性;并整合了各种细胞类型的抗菌作用,相互作用和调节。值得注意的是,角质形成细胞和募集的髓细胞分泌hepcidin的自我调节被描述。此外,还探讨了铁螯合剂在感染控制中的潜在治疗作用及其作用机制。本文旨在阐明局部铁控制与表皮感染的相关性。尽管这种情况的一些分子细节尚不清楚,但已发表的数据表明,铁调节疗法因其伤口愈合和免疫调节潜力而成为根除皮肤感染的一种有希望的治疗方法。
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引用次数: 0
Bacterial Interactions Affecting Chemotherapy Effectiveness 细菌相互作用影响化疗效果
Pub Date : 2023-03-22 DOI: 10.26443/msurj.v18i1.190
Jenni Chambers, T. A. Illingworth
Chemotherapy resistance is a recurring challenge in cancer treatment, with specific bacteria impairing the effectiveness of certain chemotherapies. This study reviews three bacteria and their impact on chemotherapy drugs: Mycoplasma  and gemcitabine, Fusobacterium nucleatum and oxaliplatin, bacterial β-glucuronase and irinotecan. Bacteria can have wide-ranging effects on cancer treatment; for instance, they may affect drug metabolism, alter toxin conversion, and encourage cancer growth. Whilst the presence of these bacteria was found to have a detrimental effect on the efficacy of chemotherapy treatment, we also consider wider interactions and interdependencies of the microbiota with drug treatments. Some cancer therapies depend on the delicate balance of the microbiome whilst simultaneously disrupting it by their very nature, particularly when antibiotics are introduced. Further research into the complex relationship between bacteria and the tumour micro-environment is needed. Treatments that focus on the immune-oncology microbiome axis or that explore genetic predisposition through the use of biomarkers could also support a more personalised approach.
化疗耐药是癌症治疗中反复出现的挑战,特定细菌会损害某些化疗的有效性。本研究综述了支原体和吉西他滨、核梭杆菌和奥沙利铂、细菌β-葡糖苷酶和伊立替康三种细菌及其对化疗药物的影响。细菌对癌症治疗有广泛的影响;例如,它们可能影响药物代谢,改变毒素转化,并促进癌症生长。虽然发现这些细菌的存在对化疗的疗效有不利影响,但我们也考虑了微生物群与药物治疗的更广泛的相互作用和相互依赖性。一些癌症治疗依赖于微生物群的微妙平衡,同时由于其本身的性质而破坏它,特别是在引入抗生素时。需要进一步研究细菌与肿瘤微环境之间的复杂关系。专注于免疫肿瘤学微生物组轴或通过使用生物标志物探索遗传易感性的治疗也可以支持更个性化的方法。
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引用次数: 0
Uncovering the Regulators of CRISPR-Cas Immunity 揭示CRISPR-Cas免疫的调控因子
Pub Date : 2023-03-22 DOI: 10.26443/msurj.v18i1.195
Idia Boncheva
The clustered regularly interspaced short palindromic repeats (CRISPR) system and the CRISPR-associated proteins (Cas) make up an adaptive immune mechanism used by many bacteria and archaea to protect themselves from invading genetic material. Despite the immense evolutionary advantage of the CRISPR-Cas system, it must be meticulously regulated as it has the potential to target endogenous genes and damage the host organism. Identifying the main regulators involved in this process and how they are influenced by distinct conditions are of great clinical interest, since this prokaryotic defense system can be exploited for genome editing and therapy development. This review aims to elucidate the regulation of the CRISPR system in bacterial communities—upon quorum sensing and alginate production in biofilms—and in stressed conditions—upon antibiotic treatment or induction of the Rcs response. Despite the intrinsic contradictions of the results gathered in this review, growth rate is identified as a potential unifying regulator of CRISPR immunity. Overall, the regulation of the CRISPR-Cas system is shown to be multi-dimensional and cross-sectional, to greatly vary amongst lineages, and to be highly sensitive to conditional changes.
聚集的规则间隔短回文重复序列(CRISPR)系统和CRISPR相关蛋白(Cas)构成了一种适应性免疫机制,许多细菌和古菌使用它来保护自己免受遗传物质的入侵。尽管CRISPR-Cas系统具有巨大的进化优势,但必须对其进行精心调控,因为它有可能靶向内源性基因并损害宿主生物。确定参与这一过程的主要调节因子以及它们如何受到不同条件的影响具有重大的临床意义,因为这种原核生物防御系统可以用于基因组编辑和治疗开发。这篇综述旨在阐明细菌群落中CRISPR系统对生物膜中群体感应和藻酸盐产生的调节,以及在应激条件下对抗生素治疗或诱导Rcs反应的调节。尽管本综述中收集的结果存在内在矛盾,但增长率被确定为CRISPR免疫的潜在统一调节因子。总的来说,CRISPR-Cas系统的调节是多维度和横断面的,在谱系之间差异很大,并且对条件变化高度敏感。
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引用次数: 0
Rho GTPase regulatory proteins contribute to podocyte morphology and function Rho-GTPase调节蛋白对足细胞形态和功能的影响
Pub Date : 2023-03-22 DOI: 10.26443/msurj.v18i1.193
Emily Foxman, S. Ibrahim, T. Takano
Podocytes are a critical cellular component of the glomerular filtration barrier, whose strict permselectivity prohibits the passage of large proteins and charged species into the urine. Phenotypic variability or injury of these highly specialized cells can lead to proteinuria and has been linked with altered activity of Rho GTPases, which are strongly associated with the actin cytoskeleton. Notable regulators of these intracellular molecular switches are called guanine nucleotide exchange factors (GEFs), GTPase-activating proteins (GAPs), and guanine nucleotide dissociation inhibitors (GDIs). In this study, the roles of several GEFs in podocyte morphology and activity were investigated, including ECT2, ARHGEF2, ARHGEF26, and ARHGEF40. Results from RhoA and Rac1 G-LISA Activation Assays indicated that the absence of ARHGEF40 impairs epidermal growth factor (EGF)-stimulated RhoA and Rac1 activation, whereas knockout of ARHGEF2 and ARHGEF26 may selectively diminish RhoA activation. Furthermore, filopodia formation was hindered for the ARHGEF40 knockout. There are a number of additional investigations underway to understand Rho GTPase regulatory proteins, including the elimination of new sets of GEFs and GAPs in vivo. It is hopeful that these studies can provide insights into potential novel therapeutic strategies for proteinuria.
足细胞是肾小球滤过屏障的关键细胞成分,其严格的过电选择性阻止大蛋白和带电物质进入尿液。这些高度特化细胞的表型变异或损伤可导致蛋白尿,并与Rho gtpase活性改变有关,Rho gtpase与肌动蛋白细胞骨架密切相关。这些细胞内分子开关的重要调节因子被称为鸟嘌呤核苷酸交换因子(GEFs), gtpase激活蛋白(GAPs)和鸟嘌呤核苷酸解离抑制剂(gdi)。在本研究中,我们研究了几种gef在足细胞形态和活性中的作用,包括ECT2、ARHGEF2、ARHGEF26和ARHGEF40。RhoA和Rac1 G-LISA激活实验结果表明,ARHGEF40的缺失会损害表皮生长因子(EGF)刺激的RhoA和Rac1的激活,而敲除ARHGEF2和ARHGEF26可能会选择性地降低RhoA的激活。此外,ARHGEF40基因敲除也阻碍了丝状足的形成。还有许多其他的研究正在进行中,以了解Rho GTPase调节蛋白,包括消除体内新的gef和gap。这些研究有望为蛋白尿的潜在新治疗策略提供见解。
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引用次数: 0
Description and Exploration of Mean-Gauss Surfaces 平均高斯曲面的描述与探索
Pub Date : 2023-03-21 DOI: 10.26443/msurj.v18i1.192
Alexander Naazeer
In this paper we explore solving the prescribed mean curvature equation for surfaces meeting a new relation given by (H_S) = λ(K_S), where H_S and K_S are the mean and Gaussian curvatures, respectively. We prove several existence theorems for various families of surfaces and state a conjecture for surfaces of revolution. To conclude, we state a weak existence theorem, and a strong conjecture concerning possible solutions. The intention is that by using differential geometry tools which would have likely been seen at the undergraduate level, the paper and its results are more accessible. My hope is that these new theorems find applications in the classification of surfaces in the future, or at the very least serves as an interesting curiosity.
本文探讨了满足(H_S)=λ(K_S)新关系的曲面的规定平均曲率方程的求解,其中H_S和K_S分别是平均曲率和高斯曲率。我们证明了各种曲面族的几个存在性定理,并给出了关于公转曲面的一个猜想。最后,我们给出了一个弱存在性定理和一个关于可能解的强猜想。其目的是通过使用微分几何工具,这可能在本科生水平上看到,论文及其结果更容易获得。我希望这些新定理将来能在曲面分类中得到应用,或者至少能成为一种有趣的好奇心。
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引用次数: 0
Review of Pumice Raft Formation Environments, Saturation, and Dispersal Mechanisms 浮冰筏形成环境、饱和和分散机制综述
Pub Date : 2023-03-20 DOI: 10.26443/msurj.v18i1.187
Nathalie R. Redick
Pumice rafting events are a common result of volcanic eruptions occurring near or beneath bodies of water. Such events are frequently associated with hazards such as tsunamis, and drift pumice is known to cause local economic disruptions, damage ships, impede naval traffic, devastate marine populations, and distribute potentially invasive species over long distances. However, our current understanding of the mechanisms that drive the formation and dispersal of drift pumice are extremely limited. This article reviews historical and characteristic pumice raft-forming eruptions, how interactions with water factor into macro- and micro-scale controls on pumice clast formation and dispersal, and current methods for detection and analysis to better track and mitigate hazards associated with explosive volcanic eruptions and pumice rafts.
浮石漂流事件是发生在水体附近或水下的火山爆发的常见结果。这类事件通常与海啸等灾害有关,众所周知,浮石漂移会造成当地经济中断,损坏船只,阻碍海上交通,摧毁海洋种群,并将潜在的入侵物种传播到很远的地方。然而,我们目前对浮石形成和扩散机制的理解非常有限。本文综述了历史和特征的浮石筏形成火山喷发,与水的相互作用如何在宏观和微观尺度上控制浮石碎屑的形成和扩散,以及目前的检测和分析方法,以更好地跟踪和减轻与爆炸性火山喷发和浮石筏相关的危害。
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引用次数: 1
Genome Annotation of Novel K1 Subcluster Mycobacteriophage Blizzard 新的K1亚簇食管分枝杆菌暴雪的基因组注释
Pub Date : 2022-04-08 DOI: 10.26443/msurj.v17i1.173
Morgane Brouillard-Galipeau, Bao-An Chau, Jamie Cyr, Rafael Intrevado, Sunu Kim, Cal Koger-Pease, E. Lapshina, A. Mircescu, Daniella Serrador, Michael Slattery, Benjamin Vonniessen, Michael Shamash, J. Chahal
The evolution of antimicrobial resistant pathogens constitutes a significant global public health threat. Combined with the lack of incentive for pharmaceutical companies to invest in developing new antibiotics, it is clear alternative treatments are needed. Bacteriophages present one possible avenue as they harness the diversity and specificity of a microorganism that has coevolved with bacteria. However, little is known about these bacterial viruses. The SEA-PHAGES program was designed to identify and characterize novel bacteriophages and their associated gene functions. Herein, we report the genome annotation of one such novel phage: Mycobacteriophage Blizzard (GenBank accession number MW712733). Blizzard’s gene content was functionally annotated using bioinformatic tools including DNA Master, Phamerator, and NCBI BLAST, to call start sites as well as predict gene function. Overall, 96 genes were identified, including a tRNA and a translational frameshift, using highly similar reference phages BEEST, Belladonna, and CREW. From the 96 genes identified, 46 were functionally annotated. The remaining 50 genes have unknown functions due to the lack of significant matches in the databases. Our results demonstrate a novel annotated phage, whose genome serves to expand the understanding of phage biology and potential implications as alternative treatment to antibiotics.
抗微生物药物耐药性病原体的演变构成了重大的全球公共卫生威胁。再加上制药公司投资开发新抗生素的动力不足,显然需要替代疗法。噬菌体提供了一种可能的途径,因为它们利用与细菌共同进化的微生物的多样性和特异性。然而,人们对这些细菌病毒知之甚少。SEA-PHAGES程序旨在鉴定和表征新型噬菌体及其相关基因功能。在此,我们报道了一种这样的新型噬菌体的基因组注释:Mycobacteriophage Blizzard (GenBank登录号MW712733)。使用DNA Master、Phamerator和NCBI BLAST等生物信息学工具对暴雪的基因内容进行功能注释,以调用起始位点并预测基因功能。总共鉴定了96个基因,包括一个tRNA和一个翻译移码,使用高度相似的参考噬菌体BEEST、颠茄和CREW。在鉴定的96个基因中,46个被功能注释。其余50个基因由于在数据库中缺乏显著匹配而功能未知。我们的研究结果展示了一种新的带注释的噬菌体,其基因组有助于扩大对噬菌体生物学的理解和作为抗生素替代治疗的潜在意义。
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引用次数: 0
An Analysis of Behaviour Change Techniques used in the Care for Child Development Parenting Program 行为改变技术在育儿计划中的应用分析
Pub Date : 2022-04-08 DOI: 10.26443/msurj.v17i1.180
Claire Wamboldt, Marilyn N. Ahun, F. Aboud
Care for Child Development (CCD) is one of several parenting programs implemented in low- and middle-income countries to improve child cognitive development outcomes by increasing responsive stimulation practices in caregivers of young children. Broadly, these programs have been demonstrated to be effective. However, there is markedly little high-quality evidence for the effectiveness of CCD. Despite this, CCD is promoted by UNICEF and the World Health Organisation as an evidence-based program and is implemented in many countries. We conducted a scoping review, including grey literature and a systematic search of published literature, to obtain an overview of the available evidence. We also performed an analysis of two quantitative outcomes, child cognitive development and caregiver behaviour, to investigate their correlation with behaviour change techniques used in CCD program implementation. We found no significant correlation between any behaviour change techniques and child cognitive development outcomes. There was a significant correlation between the techniques of performance and social support, as well as the total number of techniques used, and caregiver behaviour outcomes. This analysis was limited by the quality of reported data available about the program; of 27 total identified papers, only 14 reported quantitative data regarding either child cognitive development or caregiver behaviour change. Inconsistent reporting of this data required us to use a rating system to perform our analysis; we consequently lost specificity. Even those papers that did report quantitative data were subject to methodological flaws; the measures and study designs used did not always inspire confidence in their results. We concluded that CCD is not one single, well-defined program, and that there is an important distinction to be made between CCD-based and CCD-informed programs. The generic Care for Child Development Package (2012) is a framework that contains too many gaps to be easily adaptable. Not enough high-quality studies of this program are available to draw concrete conclusions concerning its effectiveness, in whole or in part.
儿童发展护理(CCD)是在低收入和中等收入国家实施的几个育儿项目之一,旨在通过增加幼儿照顾者的反应性刺激实践来改善儿童认知发展结果。总的来说,这些项目已被证明是有效的。然而,关于CCD有效性的高质量证据明显少之又少。尽管如此,联合国儿童基金会和世界卫生组织仍将《综合防治方案》作为一项循证方案加以推广,并在许多国家实施。我们进行了范围综述,包括灰色文献和已发表文献的系统检索,以获得现有证据的概述。我们还分析了两个定量结果,儿童认知发展和照顾者行为,以调查它们与CCD项目实施中使用的行为改变技术的相关性。我们发现任何行为改变技术和儿童认知发展结果之间没有显著的相关性。表现技巧和社会支持之间,以及使用的技巧总数和照顾者行为结果之间存在显著的相关性。这项分析受到有关该计划的报告数据质量的限制;在总共27篇论文中,只有14篇报告了关于儿童认知发展或照顾者行为改变的定量数据。不一致的数据报告要求我们使用评级系统进行分析;因此我们失去了特异性。即使那些报告了定量数据的论文也存在方法上的缺陷;所采用的测量方法和研究设计并不总是能激发人们对其结果的信心。我们的结论是,CCD不是一个单一的、定义明确的项目,在基于CCD的项目和基于CCD的项目之间有一个重要的区别。《关爱儿童发展一揽子计划》(2012年)是一个框架,其中存在太多差距,难以适应。目前还没有足够的高质量研究来得出关于该计划整体或部分有效性的具体结论。
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引用次数: 0
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McGill Science undergraduate research journal : MSURJ
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