• 【新型BRD4-NUT融合亚型增加了坚果中线癌的致病复杂性。】 复制标题 收藏 收藏
    DOI:10.1038/onc.2012.487 复制DOI
    作者列表:Thompson-Wicking K,Francis RW,Stirnweiss A,Ferrari E,Welch MD,Baker E,Murch AR,Gout AM,Carter KW,Charles AK,Phillips MB,Kees UR,Beesley AH
    BACKGROUND & AIMS: :Nuclear protein in testis (NUT)-midline carcinoma (NMC) is a rare, aggressive disease typically presenting with a single t(15;19) translocation that results in the generation of a bromodomain-containing protein 4 (BRD4)-NUT fusion. PER-624 is a cell line generated from an NMC patient with an unusually complex karyotype that gave no initial indication of the involvement of the NUT locus. Analysis of PER-624 next-generation transcriptome sequencing (RNA-Seq) using the algorithm FusionFinder identified a novel transcript in which Exon 15 of BRD4 was fused to Exon 2 of NUT, therefore differing from all published NMC fusion transcripts. The three additional exons contained in the PER-624 fusion encode a series of polyproline repeats, with one predicted to form a helix. In the NMC cell line PER-403, we identified the 'standard' NMC fusion and two novel isoforms. Knockdown by small interfering RNA in either cell line resulted in decreased proliferation, increased cell size and expression of cytokeratins consistent with epithelial differentiation. These data demonstrate that the novel BRD4-NUT fusion in PER-624 encodes a functional protein that is central to the oncogenic mechanism in these cells. Genomic PCR indicated that in both PER-624 and PER-403, the translocation fuses an intron of BRD4 to a region upstream of the NUT coding sequence. Thus, the generation of BRD4-NUT fusion transcripts through post-translocation RNA-splicing appears to be a common feature of these carcinomas that has not previously been appreciated, with the mechanism facilitating the expression of alternative isoforms of the fusion. Finally, ectopic expression of wild-type NUT, a protein normally restricted to the testis, could be demonstrated in PER-403, indicating additional pathways for aberrant cell signaling in NMC. This study contributes to our understanding of the genetic diversity of NMC, an important step towards finding therapeutic targets for a disease that is refractory to current treatments.
    背景与目标: : 睾丸 (NUT) 中线癌 (NMC) 中的核蛋白是一种罕见的侵袭性疾病,通常表现为单个t(15;19) 易位,导致产生含溴结构域的蛋白4 (BRD4)-NUT融合。PER-624是由NMC患者产生的细胞系,其具有异常复杂的核型,没有给出涉及NUT基因座的初始指示。使用算法FusionFinder对每624下一代转录组测序 (RNA-Seq) 的分析鉴定了一种新的转录物,其中BRD4的外显子15与NUT的外显子2融合,因此不同于所有已发表的NMC融合转录物。每个624融合中包含的三个额外外显子编码一系列多脯氨酸重复序列,其中一个预测形成螺旋。在每403 NMC细胞系中,我们鉴定了 “标准” NMC融合和两种新的同工型。在任一细胞系中通过小干扰RNA敲低导致增殖减少,细胞大小增加和细胞角蛋白的表达与上皮分化一致。这些数据表明,PER-624中的新型BRD4-NUT融合体编码对这些细胞中的致癌机制至关重要的功能性蛋白质。基因组PCR表明,在PER-624和PER-403中,易位将BRD4的内含子融合到NUT编码序列上游的区域。因此,通过易位后RNA剪接产生BRD4-NUT融合转录物似乎是这些癌的共同特征,以前没有被认识到,其机制促进了融合的替代同工型的表达。最后,野生型NUT (一种通常限于睾丸的蛋白质) 的异位表达可以在PER-403中得到证实,这表明NMC中异常细胞信号传导的其他途径。这项研究有助于我们了解NMC的遗传多样性,这是为目前治疗方法难以治疗的疾病寻找治疗靶点的重要一步。
  • 【抗逆转录病毒方案复杂性指数。一种量化方案复杂性的新方法。】 复制标题 收藏 收藏
    DOI:10.1097/QAI.0b013e31811ed1f1 复制DOI
    作者列表:Martin S,Wolters PL,Calabrese SK,Toledo-Tamula MA,Wood LV,Roby G,Elliott-DeSorbo DK
    BACKGROUND & AIMS: BACKGROUND:Individuals with HIV disease often must adhere to complex medication regimens. To date, regimen complexity has not been examined in the literature using standardized procedures incorporating all important elements of antiretroviral (ARV) regimens. OBJECTIVE:This article presents a novel method of quantifying regimen complexity using objective criteria addressing the factors that may complicate adherence to ARV regimens. METHODS:Part 1 of this article describes the development of the Antiretroviral Regimen Complexity (ARC) Index scoring system. Based on input from pediatric and adult patients, caregivers of pediatric patients, and health care professionals, this comprehensive system includes the number of medications, dosing schedules, administration methods, special instructions, and required preparations associated with ARV regimens. Weights are applied for each of these factors to produce an overall score representing the regimen's level of complexity. Part 2 of this article presents reliability and validity data for the system. RESULTS:The ARC Index demonstrates excellent test-retest and interrater reliability as well as strong construct and discriminant validity. An on-line version of this system minimizes computation errors. CONCLUSIONS:Although modifications may be necessary for patients requiring nonstandard dosing instructions, preliminary evidence supports the utility of this measure as a reliable and valid indicator of the complexity of antiretroviral treatment regimens.
    背景与目标:
  • 【BCR激活的信号通路的复杂性。】 复制标题 收藏 收藏
    DOI:10.1016/s0952-7915(97)80074-x 复制DOI
    作者列表:DeFranco AL
    BACKGROUND & AIMS: :Cross-linking of the B cell antigen receptor (BCR) leads to the activation of three types of intracellular protein tyrosine kinases. These tyrosine kinases then phosphorylate signaling components to activate a variety of signaling reactions, including phosphatidylinositol 4,5-bisphosphate hydrolysis, Ras activation, and phosphatidylinositol 3-kinase activation. Each of these signaling reactions, and also the signaling molecules Vav and HS1, appears to be important for at least some of the many types of B cell responses to antigen. The complexity of BCR signaling reactions may be required to allow the B cell to respond in a number of distinct ways to antigen (proliferation, survival, apoptosis, maturational arrest, etc.) depending on the maturation state of the B cell, the location in the body, the physical nature of the antigen, and the possible presence of the antigen in complex with antibody or complement components.
    背景与目标: : b细胞抗原受体 (BCR) 的交联导致三种类型的细胞内蛋白酪氨酸激酶的激活。然后,这些酪氨酸激酶磷酸化信号传导成分以激活多种信号传导反应,包括磷脂酰肌醇4,5-二磷酸水解,Ras激活和磷脂酰肌醇3-激酶激活。这些信号反应中的每一个以及信号分子Vav和HS1似乎对于许多类型的b细胞对抗原的应答中的至少某些都很重要。可能需要BCR信号反应的复杂性,以使b细胞以多种不同的方式对抗原 (增殖,存活,凋亡,成熟停滞等) 做出反应,这取决于b细胞的成熟状态,在体内的位置,抗原的物理性质,以及可能存在的抗原与抗体或补体成分的复合物。
  • 【GISTogram: 日益增长的要点复杂性的图形呈现。】 复制标题 收藏 收藏
    DOI:10.1007/s00428-013-1467-4 复制DOI
    作者列表:Ricci R,Dei Tos AP,Rindi G
    BACKGROUND & AIMS: :Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. They have represented a paradigm of molecular-targeted therapies for solid tumors since the discovery of KIT mutations and KIT expression in GIST in 1998, which opened the way to the use of imatinib, a tyrosine kinase inhibitor able to inhibit the growth of cells expressing KIT-mutant isoforms. Since then, accumulating evidence revealed the rather heterogeneous nature of GIST, implying possible different diagnostic and therapeutic approaches for each specific case, leading to the development of drugs alternative to imatinib. In this brief commentary, we graphically represent the historical growing of genotype and phenotype evidence on GIST since 1998 in its increasing complexity by building up a graph, which we have called "GISTogram", that visually conveys most of GIST-characterizing features and the probability for each of them, either alone or in combination, to be observed in a single GIST case.
    背景与目标: 胃肠道间质瘤 (gist) 是胃肠道最常见的间叶性肿瘤。自从在GIST 1998年中发现KIT突变和KIT表达以来,它们代表了实体瘤分子靶向疗法的范例,这为使用伊马替尼开辟了道路,伊马替尼是一种酪氨酸激酶抑制剂,能够抑制表达KIT的细胞的生长-突变体同工型。从那时起,越来越多的证据揭示了GIST的异质性,这意味着每种特定病例可能采用不同的诊断和治疗方法,从而导致了替代伊马替尼的药物的开发。在这个简短的评论中,我们通过建立一个我们称为 “GISTogram” 的图形,以图形方式表示GIST 1998年的基因型和表型证据的历史增长,该图形在视觉上传达了大多数GIST特征特征以及每个特征的概率,无论是单独还是组合,在单一的要点情况下观察。
  • 【在培养皿中重现肿瘤复杂性: 研究肝癌细胞及其细胞外环境的类器官模型。】 复制标题 收藏 收藏
    DOI:10.3390/cancers11111706 复制DOI
    作者列表:van Tienderen GS,Groot Koerkamp B,IJzermans JNM,van der Laan LJW,Verstegen MMA
    BACKGROUND & AIMS: :Primary liver cancer, consisting predominantly of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), remains one of the most lethal malignancies worldwide. This high malignancy is related to the complex and dynamic interactions between tumour cells, stromal cells and the extracellular environment. Novel in vitro models that can recapitulate the tumour are essential in increasing our understanding of liver cancer. Herein, primary liver cancer-derived organoids have opened up new avenues due to their patient-specificity, self-organizing ability and potential recapitulation of many of the tumour properties. Organoids are solely of epithelial origin, but incorporation into co-culture models can enable the investigation of the cellular component of the tumour microenvironment. However, the extracellular component also plays a vital role in cancer progression and representation is lacking within current in vitro models. In this review, organoid technology is discussed in the context of liver cancer models through comparisons to other cell culture systems. In addition, the role of the tumour extracellular environment in primary liver cancer will be highlighted with an emphasis on its importance in in vitro modelling. Converging novel organoid-based models with models incorporating the native tumour microenvironment could lead to experimental models that can better recapitulate liver tumours in vivo.
    背景与目标: 原发性肝癌主要由肝细胞癌 (HCC) 和胆管癌 (CCA) 组成,仍然是全球最致命的恶性肿瘤之一。这种高度恶性与肿瘤细胞,基质细胞和细胞外环境之间复杂而动态的相互作用有关。可以概括肿瘤的新型体外模型对于增进我们对肝癌的了解至关重要。在这里,原发性肝癌衍生的类器官由于其患者特异性,自组织能力和对许多肿瘤特性的潜在概括而开辟了新的途径。类器官仅是上皮起源的,但是掺入共培养模型可以研究肿瘤微环境的细胞成分。然而,细胞外成分在癌症进展中也起着至关重要的作用,并且在当前的体外模型中缺乏代表性。在这篇综述中,通过与其他细胞培养系统的比较,在肝癌模型的背景下讨论了类器官技术。此外,将强调肿瘤细胞外环境在原发性肝癌中的作用,并强调其在体外建模中的重要性。将新的基于类器官的模型与结合了天然肿瘤微环境的模型融合在一起,可能会导致可以更好地在体内概括肝脏肿瘤的实验模型。
  • 【鸟枪对蜂蜜DNA的测序可以描述蜜蜂衍生的环境特征和蜜蜂的基因组复杂性。】 复制标题 收藏 收藏
    DOI:10.1038/s41598-020-66127-1 复制DOI
    作者列表:Bovo S,Utzeri VJ,Ribani A,Cabbri R,Fontanesi L
    BACKGROUND & AIMS: :Honey bees are large-scale monitoring tools due to their extensive environmental exploration. In their activities and from the hive ecosystem complex, they get in close contact with many organisms whose traces can be transferred into the honey, which can represent an interesting reservoir of environmental DNA (eDNA) signatures and information useful to analyse the honey bee hologenome complexity. In this study, we tested a deep shotgun sequencing approach of honey DNA coupled with a specifically adapted bioinformatic pipeline. This methodology was applied to a few honey samples pointing out DNA sequences from 191 organisms spanning different kingdoms or phyla (viruses, bacteria, plants, fungi, protozoans, arthropods, mammals). Bacteria included the largest number of species. These multi-kingdom signatures listed common hive and honey bee gut microorganisms, honey bee pathogens, parasites and pests, which resembled a complex interplay that might provide a general picture of the honey bee pathosphere. Based on the Apis mellifera filamentous virus genome diversity (the most abundant detected DNA source) we obtained information that could define the origin of the honey at the apiary level. Mining Apis mellifera sequences made it possible to identify the honey bee subspecies both at the mitochondrial and nuclear genome levels.
    背景与目标: : 蜜蜂由于其广泛的环境探索而成为大型监测工具。在他们的活动和蜂巢生态系统综合体中,他们与许多生物密切接触者,这些生物的痕迹可以转移到蜂蜜中,这可以代表一个有趣的环境DNA (eDNA) 特征库,以及有助于分析蜜蜂hologenome复杂性的信息。在这项研究中,我们测试了蜂蜜DNA的深度shot弹枪测序方法,并结合了专门适应的生物信息学管道。该方法应用于一些蜂蜜样品,指出来自跨越不同王国或门 (病毒、细菌、植物、真菌、原生动物、节肢动物、哺乳动物) 的191生物的DNA序列。细菌包括最多的物种。这些多王国的特征列出了常见的蜂巢和蜜蜂肠道微生物,蜜蜂病原体,寄生虫和害虫,它们类似于复杂的相互作用,可能提供了蜜蜂病态的一般情况。基于蜜蜂丝状病毒的基因组多样性 (检测到的最丰富的DNA来源),我们获得了可以在蜂场水平上定义蜂蜜起源的信息。挖掘Apis mellifera序列可以在线粒体和核基因组水平上鉴定蜜蜂亚种。
  • 【有和没有发育协调障碍的儿童步态复杂性和变异性的差异。】 复制标题 收藏 收藏
    DOI:10.1016/j.gaitpost.2008.08.005 复制DOI
    作者列表:Rosengren KS,Deconinck FJ,Diberardino LA 3rd,Polk JD,Spencer-Smith J,De Clercq D,Lenoir M
    BACKGROUND & AIMS: :We used elliptical Fourier analysis (EFA) to examine potential differences in the complexity and variability of gait of children with (N=10) and without (N=10) Developmental Coordination Disorder (DCD). Children with DCD generated movement patters with larger variability and complexity than typically developing (TD) children. In addition, children with DCD exhibited greater asymmetry in their movement patterns compared to TD children. Our results suggest that children with DCD have significantly greater difficulty producing consistent movement patterns both across their left and right legs and over repeated strides. EFA techniques show promise for distinguishing between different groups of individuals.
    背景与目标: : 我们使用椭圆傅立叶分析 (EFA) 来检查有 (N = 10) 和没有 (N = 10) 发育协调障碍 (DCD) 的儿童步态复杂性和变异性的潜在差异。与典型的发育 (TD) 儿童相比,患有DCD的儿童产生的运动模式具有更大的变异性和复杂性。此外,与TD儿童相比,DCD儿童的运动方式表现出更大的不对称性。我们的结果表明,患有DCD的儿童在左腿和右腿以及反复跨步时产生一致的运动模式的难度明显更大。全民教育技术显示出区分不同群体的希望。
  • 【跨景观的时空复杂性对生物控制的影响: 综述。】 复制标题 收藏 收藏
    DOI:10.1016/j.cois.2017.02.004 复制DOI
    作者列表:Cohen AL,Crowder DW
    BACKGROUND & AIMS: :Biological control is affected by the composition of landscapes surrounding agricultural fields. Natural enemy communities are typically more diverse, and effective at providing biological control services, in complex compared to simple landscapes. However, the use of simple metrics to characterize landscapes, such as the proportion of agricultural habitat, obscures the mechanisms by which landscapes affect biological control. Studies that evaluate the overall complexity of agricultural landscapes, and their temporal variability, allow for a greater mechanistic understanding of the impacts of landscape composition on biological control. From an applied perspective, decision support systems, which deliver real-time information about pest and natural enemy populations, are an effective tool for delivering recommendations to strengthen biological control across space and time.
    背景与目标: : 生物防治受农田周围景观组成的影响。与简单的景观相比,在复杂的环境中,天敌社区通常更加多样化,并且在提供生物防治服务方面有效。但是,使用简单的指标来表征景观,例如农业栖息地的比例,掩盖了景观影响生物控制的机制。评估农业景观的整体复杂性及其时间可变性的研究,可以更好地了解景观组成对生物控制的影响。从应用的角度来看,提供有关害虫和天敌种群的实时信息的决策支持系统是提供建议以加强时空生物控制的有效工具。
  • 【将方案复杂性与临床研究现场的资源管理和容量规划相协调。】 复制标题 收藏 收藏
    DOI:10.1007/s43441-020-00120-8 复制DOI
    作者列表:Morin DJ
    BACKGROUND & AIMS: BACKGROUND:Clinical research sites conduct trials with diverse complexities, timelines, and ever-changing workloads. Though the principal investigator (PI) is ultimately responsible for the content and conduct of trials, they rely heavily on site staff to successfully enroll and complete studies following good clinical practice (GCP) Guidelines. The mainstays of the site workforce are the clinical research coordinators (CRCs) to whom the trials are assigned. These CRCs work on many studies concurrently. Managing study assignments and workload is a difficult task that requires knowledge of the trial complexity, expected enrollment, and many other factors affecting performance. METHODS:Traditional methods for allocating workload to site staff quantitate trial complexity and estimate work hours by factoring in the number of trial participants. However, this does not account for the effects of associated workload or variability in staff attributes. It also neglects other factors that affect performance and assumes maximum enrollment and completion of the trial by all participants. This article introduces a novel approach that determines the effects of protocol complexity on CRC productivity without effort tracking. These metrics permit an assessment of how the CRC's performance is affected by the number of studies assigned. RESULTS:By understanding the effects of workload allocation on CRC productivity and capacity, the site manager can use an algorithmic approach toward improving performance. The process takes into account factors that are both within and outside the control of the site manager. CONCLUSION:Sites may benefit from analytics that measures how CRCs adapt to the effects of study complexity on cumulative workloads over time. Optimizing productivity also means conforming to GCP Guidelines and avoiding staff burnout. As studies become increasingly difficult, site managers need tools to manage complexity and balance workloads among staff.
    背景与目标:
  • 【经皮冠状动脉介入治疗中冠状动脉病变复杂性的影响: 大型多中心e-ultimmaster注册的一年结果。】 复制标题 收藏 收藏
    DOI:10.4244/EIJ-D-20-00361 复制DOI
    作者列表:Mohamed MO,Polad J,Hildick-Smith D,Bizeau O,Baisebenov RK,Roffi M,Íñiguez-Romo A,Chevalier B,von Birgelen C,Roguin A,Aminian A,Angioi M,Mamas MA
    BACKGROUND & AIMS: AIMS:The present study sought to examine the prevalence, clinical characteristics and one-year outcomes of patients undergoing percutaneous coronary intervention (PCI) to complex lesions (multivessel PCI, ≥3 stents, ≥3 lesions, bifurcation with ≥2 stents, total stent length >60 mm or chronic total occlusion [CTO]) in a prospective multicentre registry. METHODS AND RESULTS:Using the e-Ultimaster multicentre registry, a post hoc subgroup analysis was performed on 35,839 patients undergoing PCI, stratified by procedure complexity, and further by number and type of complex features. Overall, complex PCI patients (n=9,793, 27.3%) were older, more comorbid and were associated with an increased hazard ratio (HR) of the composite endpoint at one year (target lesion failure [TLF]: 1.41 [1.25; 1.59]), driven by an increased hazard of cardiac death (1.28 [1.05; 1.55]), target vessel myocardial infarction (1.48 [1.18; 1.86]) and clinically driven target lesion revascularisation. The hazard of complications increased with the rising number of complex features (3-6 vs 1-2 vs none) for all outcomes. All individual complex features were associated with an increased hazard of composite complications (except CTO) and definite/probable stent thrombosis. CONCLUSIONS:Overall, complex PCI is associated with an increased risk of mortality and complications at one year. The number and types of complex features have differing impacts on long-term outcomes.
    背景与目标:
  • 【景天酸代谢: 表达的可塑性,控制的复杂性。】 复制标题 收藏 收藏
    DOI:10.1071/FP02091 复制DOI
    作者列表:Holtum JAM
    BACKGROUND & AIMS: -2
    背景与目标: -2
  • 【人类概念学习中布尔复杂性的最小化。】 复制标题 收藏 收藏
    DOI:10.1038/35036586 复制DOI
    作者列表:Feldman J
    BACKGROUND & AIMS: :One of the unsolved problems in the field of human concept learning concerns the factors that determine the subjective difficulty of concepts: why are some concepts psychologically simple and easy to learn, while others seem difficult, complex or incoherent? This question was much studied in the 1960s but was never answered, and more recent characterizations of concepts as prototypes rather than logical rules leave it unsolved. Here I investigate this question in the domain of Boolean concepts (categories defined by logical rules). A series of experiments measured the subjective difficulty of a wide range of logical varieties of concepts (41 mathematically distinct types in six families--a far wider range than has been tested previously). The data reveal a surprisingly simple empirical 'law': the subjective difficulty of a concept is directly proportional to its Boolean complexity (the length of the shortest logically equivalent propositional formula)--that is, to its logical incompressibility.
    背景与目标: : 人类概念学习领域中尚未解决的问题之一涉及决定概念主观难度的因素: 为什么有些概念在心理上简单易学,而另一些则看起来困难、复杂或不连贯?20世纪60年代对这个问题进行了大量研究,但从未得到回答,并且最近将概念描述为原型而不是逻辑规则,这使它无法解决。在这里,我在布尔概念 (由逻辑规则定义的类别) 的领域中研究这个问题。一系列实验测量了各种逻辑概念的主观难度 (六个家族中有41种数学上不同的类型-比以前测试的范围要大得多)。数据揭示了一个令人惊讶的简单经验 “定律”: 概念的主观难度与其布尔复杂度 (最短的逻辑等价命题公式的长度) 成正比,即与其逻辑不可压缩性成正比。
  • 【骨髓造血干细胞生态位的细胞复杂性。】 复制标题 收藏 收藏
    DOI:10.1007/s00223-013-9805-8 复制DOI
    作者列表:Calvi LM,Link DC
    BACKGROUND & AIMS: :The skeleton serves as the principal site for hematopoiesis in adult terrestrial vertebrates. The function of the hematopoietic system is to maintain homeostatic levels of all circulating blood cells, including myeloid cells, lymphoid cells, red blood cells, and platelets. This action requires the daily production of more than 500 billion blood cells. The vast majority of these cells are synthesized in the bone marrow, where they arise from a limited number of hematopoietic stem cells (HSCs) that are multipotent and capable of extensive self-renewal. These attributes of HSCs are best demonstrated by marrow transplantation, where even a single HSC can repopulate the entire hematopoietic system. HSCs are therefore adult stem cells capable of multilineage repopulation, poised between cell fate choices which include quiescence, self-renewal, differentiation, and apoptosis. While HSC fate choices are in part determined by multiple stochastic fluctuations of cell autonomous processes, according to the niche hypothesis, signals from the microenvironment are also likely to determine stem cell fate. While it had long been postulated that signals within the bone marrow could provide regulation of hematopoietic cells, it is only in the past decade that advances in flow cytometry and genetic models have allowed for a deeper understanding of the microenvironmental regulation of HSCs. In this review, we will highlight the cellular regulatory components of the HSC niche.
    背景与目标: : 骨骼是成年陆生脊椎动物造血的主要部位。造血系统的功能是维持所有循环血细胞的稳态水平,包括髓样细胞,淋巴样细胞,红细胞和血小板。这一行动需要每天生产5000亿多个血细胞。这些细胞中的绝大多数是在骨髓中合成的,它们是由数量有限的造血干细胞 (hsc) 产生的,这些造血干细胞是多能的并且能够广泛的自我更新。骨髓移植可以最好地证明HSC的这些特性,即使单个HSC也可以重新填充整个造血系统。因此,hsc是能够多谱系再增殖的成体干细胞,在包括静止,自我更新,分化和凋亡在内的细胞命运选择之间保持平衡。尽管HSC命运的选择部分取决于细胞自主过程的多种随机波动,但根据利基假说,来自微环境的信号也可能决定干细胞命运。尽管长期以来一直假设骨髓中的信号可以提供造血细胞的调节,但直到过去十年,流式细胞术和遗传模型的进步才使人们对HSCs的微环境调节有了更深入的了解。在这篇综述中,我们将重点介绍HSC生态位的细胞调节成分。
  • 【任务复杂性对初次右全膝关节置换术前后制动响应时间的影响。】 复制标题 收藏 收藏
    DOI:10.1016/j.apmr.2007.10.025 复制DOI
    作者列表:Marques CJ,Cabri J,Barreiros J,Carita AI,Friesecke C,Loehr JF
    BACKGROUND & AIMS: OBJECTIVE:To study the effects of an increase in task complexity on brake response time (BRT) in patients undergoing total knee arthroplasty (TKA). DESIGN:A prospective repeated-measures design was used. The measurements took place 1 day before and 10 and 30 days after surgery. SETTING:Clinic. PARTICIPANTS:The data of patients (N=21) who were admitted for primary total arthroplasty of the right knee were pooled for analysis. INTERVENTIONS:On each measurement day patients performed 5 practice and 10 test trials for 2 tasks (1 simple, 1 complex) in a car simulator. Task complexity was increased by adding a second movement to the first task performed. MAIN OUTCOME MEASURES:BRT, reaction time (RT), and movement time were assessed. RESULTS:An increase in task complexity increased BRT, RT, and movement time at all measurement times. Right TKA increased BRT by increasing movement time. Thirty days after surgery BRT was no longer increased compared with preoperative values in both tasks. CONCLUSIONS:Task complexity consistently increased BRT and its components. The effects of task complexity remained constant throughout the 3 measurements. After right TKA, we suggest patients should be advised to wait 30 days after surgery before resuming driving.
    背景与目标:
  • 15 Complexity of minor histocompatibility loci. 复制标题 收藏 收藏

    【次要组织相容性基因座的复杂性。】 复制标题 收藏 收藏
    DOI:10.1016/0198-8859(85)90230-7 复制DOI
    作者列表:Click RE
    BACKGROUND & AIMS: :Allografts can be rejected as a result of major histocompatibility antigen disparity or as a result of differences at any of a number of minor histocompatibility antigens. In many cases, rejection due to multiple minor histoincompatibility is as difficult to control as that induced by major histoincompatibility. Although an understanding of the molecular, biochemical, and functional parameters of the major histocompatibility loci and their products is increasing at an exponential rate, little is known about these same facets of minor histocompatibility loci and their products. It is generally accepted that minor histocompatibility loci in the murine model have a degree of polymorphism similar to that of H-2K or H-2D. This conclusion was based on typing alleles by the classic F1-skin graft test. Based on these allelic assignments, numerous unexpected findings of CTL specificity were made. Therefore, a systematic analysis was made comparing CTL specificity, F1-complementation, and allograft rejection. Based on these three parameters, the data presented using strains of mice that were bred to, and therefore presumed to, differ only at H-3 indicate that the antigen disparity of these congenic strains and the parental B10 strain as defined by CTL specificity and skin graft rejection is much more complex than originally described. One especially interesting chromosomal region is H-3/beta 2-microglobulin in the fifth linkage group of chromosome 2. Using CTL, ten specificities are defined, three of which appear to be specific for beta 2-microglobulin-A, -B, and -C. These findings raise the question of whether any minor histocompatibility locus is polymorphic or is instead a composite of multiple minor H-loci which are masquerading as a single locus.
    背景与目标: : 同种异体移植物可以由于主要的组织相容性抗原差异或许多次要组织相容性抗原的差异而被排斥。在许多情况下,由于多个次要组织相容性引起的排斥与主要组织相容性引起的排斥一样难以控制。尽管对主要组织相容性基因座及其产物的分子,生化和功能参数的了解正在以指数速度增长,但对次要组织相容性基因座及其产物的这些相同方面知之甚少。人们普遍认为,鼠模型中的次要组织相容性基因座具有与H-2K或H-2D相似的多态性程度。该结论基于经典F1-skin移植试验对等位基因进行分型。基于这些等位基因分配,获得了许多意外的CTL特异性发现。因此,进行了比较CTL特异性,F1-complementation和同种异体移植排斥反应的系统分析。基于这三个参数,使用育成并且因此推测仅在H-3上有所不同的小鼠品系提供的数据表明,这些同系品系和亲本B10品系的抗原差异 (如由CTL特异性和皮肤移植物排斥定义) 比最初描述的要复杂得多。一个特别有趣的染色体区域是2号染色体第五连锁群中的H-3/β2-微球蛋白。使用CTL,定义了十种特异性,其中三种似乎对 β2-微球蛋白-a,-B和-C具有特异性。这些发现提出了一个问题,即任何次要组织相容性基因座是多态的,还是伪装成单个基因座的多个次要H基因座的复合物。

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