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Drosophila telomere elongation. 果蝇端粒伸长。
Pub Date : 1997-01-01 DOI: 10.1002/9780470515433.ch5
H Biessmann, M F Walter, J M Mason

Drosophila melanogaster has an unusual telomere elongation mechanism. Instead of short repeats that are synthesized by telomerase, long retrotransposons, HeT-A and TART, transpose to the ends of chromosomes. This mechanism generates tandem arrays of these elements at the chromosome ends, in which all elements are oriented with their oligo(A) tails towards the centromere. Structural features of HeT-A and TART elements may provide clues as to their transposition mechanism. Drosophila telomere length polymorphism is mainly due to terminal retrotransposon arrays that differ between chromosome tips and that change with time. In addition, stable terminal chromosome deletions can be generated that do not contain terminal HeT-A and TART arrays, suggesting that, unlike the equivalent terminal repeats in yeast and humans, the presence and length of terminal arrays in Drosophila may not be critical for cell cycle progression.

黑腹果蝇具有不同寻常的端粒延伸机制。而不是由端粒酶合成的短重复序列,长反转录转座子,HeT-A和TART,转位到染色体的末端。这种机制在染色体末端产生这些元件的串联阵列,其中所有元件都以其寡核苷酸(A)尾部朝向着丝粒。HeT-A和TART元件的结构特征可能为其转位机制提供线索。果蝇端粒长度多态性主要是由于染色体末端的反转录转座子阵列不同,且随时间变化。此外,不包含末端HeT-A和TART阵列的稳定末端染色体缺失可以产生,这表明,与酵母和人类中的等效末端重复序列不同,果蝇中末端阵列的存在和长度可能对细胞周期进程并不重要。
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引用次数: 21
Spatial variability of soil moisture regimes at different scales: implications in the context of precision agriculture. 不同尺度土壤水分状况的空间变异性:在精准农业背景下的含义。
Pub Date : 1997-01-01 DOI: 10.1002/9780470515419.ch3
M Voltz

Precision agriculture is based on the concept of soil-specific management, which aims to adapt management within a field according to specific site conditions in order to maximize production and minimize environmental damage. This paper examines how the nature and sources of variation in soil moisture regimes affect our ability to simulate soil water behaviour within a field with adequate precision in order to advise optimal soil-specific management. Field examples of variation in soil moisture regimes are described to illustrate the difficulties involved. A discussion identifies three main points. First, it is recognized that the current modelling approaches to soil moisture regimes do not sufficiently account for local heterogeneities in soil and crop characteristics such as soil morphology and rooting patterns. Second, the estimation of within-field variation of soil hydraulic properties is difficult because of large short-range variation of the properties and general lack of observed data; one way to overcome this problem is to seek new measurement techniques or to find easy-to-measure auxiliary variables spatially correlated to the variables of interest. Last, as pollution impacts often become noticeable to society at scales larger than the scale of agricultural management, hydrological modelling can serve for linking both scales and advising agricultural practices that minimize undesirable pollution effects.

精准农业是基于土壤特定管理的概念,其目的是根据特定的场地条件调整田地内的管理,以最大限度地提高产量并减少对环境的破坏。本文研究了土壤水分制度变化的性质和来源如何影响我们在一个领域内以足够的精度模拟土壤水分行为的能力,以便为最佳的土壤特定管理提供建议。文中描述了土壤湿度变化的实地实例,以说明所涉及的困难。讨论确定了三个要点。首先,人们认识到,目前对土壤水分制度的建模方法没有充分考虑土壤和作物特征(如土壤形态和生根模式)的局部异质性。其次,由于土壤水力特性的短期变化较大,且观测数据普遍缺乏,因此难以估计土壤水力特性的场内变化;克服这一问题的一种方法是寻求新的测量技术或寻找与感兴趣的变量在空间上相关的易于测量的辅助变量。最后,由于污染对社会的影响往往在比农业管理规模更大的尺度上变得明显,水文模型可以将这两个尺度联系起来,并为尽量减少不良污染影响的农业做法提供建议。
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引用次数: 5
Modelling non-stationary spatial covariance structure from space-time monitoring data. 基于时空监测数据的非平稳空间协方差结构建模。
Pub Date : 1997-01-01 DOI: 10.1002/9780470515419.ch4
P Monestiez, W Meiring, P D Sampson, P Guttorp

Accurate interpolation of soil and climate variables at fine spatial scales is necessary for precise field management. Interpolation is needed to produce the input variables necessary for crop modelling. It is also important when deciding on regulations to limit environmental impacts from processes such as nitrate leaching. Non-stationarity may arise due to many factors, including differences in soil type, or heterogeneity in chemical concentrations. Many geostatistical methods make stationarity assumptions. Substantial improvements in interpolation or in the estimation of standard errors may be obtained by using non-stationary models of spatial covariances. This paper presents recent methodological developments for an approach to modelling non-stationary spatial covariance structure through deformations of the geographic coordinate system. This approach was first introduced by Sampson & Guttorp, although the estimation approach is updated in more recent papers. They compute a deformation of the geographic plane so that the spatial covariance structure can be considered stationary in terms of a new spatial coordinate system. This provides a non-stationary model for the spatial covariances between sampled locations and prediction locations. In this paper, we present a cross-validation procedure to avoid over-fitting of the sample dispersions. Results concerning the variability of the spatial covariance estimates are also presented. An example of the modelling of the spatial correlation field of rainfall at small regional scale is presented. Other directions in methodological development, including modelling temporally varying spatial correlation, and approaches to model temporal and spatial correlation are mentioned. Future directions for methodological development are indicated, including the modelling of multivariate processes and the use of external spatially dense covariables. Such covariates are frequently available in precision agriculture.

在精细空间尺度上对土壤和气候变量进行精确的插值是精确田间管理的必要条件。需要插值来产生作物建模所需的输入变量。在制定法规限制硝酸盐浸出等过程对环境的影响时,这一点也很重要。非平稳性可能由许多因素引起,包括土壤类型的差异或化学物质浓度的异质性。许多地质统计学方法都有平稳性假设。通过使用空间协方差的非平稳模型,可以获得插值或标准误差估计方面的实质性改进。本文介绍了通过地理坐标系的变形来模拟非平稳空间协方差结构的最新方法发展。这种方法最初是由Sampson & Guttorp提出的,尽管估计方法在最近的论文中有所更新。他们计算地理平面的变形,这样空间协方差结构就可以在新的空间坐标系中被认为是静止的。这为采样位置和预测位置之间的空间协方差提供了一个非平稳模型。在本文中,我们提出了一个交叉验证程序,以避免样本分散度的过度拟合。本文还给出了有关空间协方差估计的变异性的结果。给出了小区域尺度降水空间相关场的一个模拟实例。方法发展的其他方向,包括模拟时间变化的空间相关性,以及模拟时空相关性的方法。指出了方法学发展的未来方向,包括多变量过程的建模和外部空间密集协变量的使用。这些协变量在精准农业中经常可用。
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引用次数: 5
Variability and uncertainty in spatial, temporal and spatiotemporal crop-yield and related data. 空间、时间和时空作物产量及相关数据的变异性和不确定性。
Pub Date : 1997-01-01 DOI: 10.1002/9780470515419.ch9
A B McBratney, B M Whelan, T M Shatar

Application of the theories of precision agriculture to the practicalities of broad-acre farming relies on successful handling of the ramifications of uncertainty in information, i.e. information pertaining to the spatial and temporal variation of those factors which determine yield components and/or environmental losses. This paper discusses the uncertainty of yield and related variables as measured by their spatial and temporal variance. The magnitude of these two components gives a suggestion as to the appropriate scale of management. Simultaneous reporting on spatial and temporal variation is rare and the theory of these types of process is still in its infancy. Some brief theory is presented, followed by several examples from the Rothamsted classic experiments, yield-monitoring experiments in Australia, a long-term barley trial in Denmark, and a soil moisture monitoring network. It is clear that annual temporal variation is much larger than the spatial variation within single fields. This leads to the conclusion that if precision agriculture is to have a sound scientific basis and ultimately a practical outcome then the null hypothesis that still remains to be seriously researched is: 'given the large temporal variation in yields relative to the scale of a single field, then the optimal risk aversion strategy is uniform management.'

精准农业理论在大面积农业实践中的应用依赖于对信息不确定性后果的成功处理,即与决定产量组成部分和/或环境损失的那些因素的时空变化有关的信息。本文讨论了产量及其相关变量的时空变化的不确定性。这两个组成部分的大小为适当的管理规模提供了建议。同时报告空间和时间变化是罕见的,这些类型的过程的理论仍处于起步阶段。本文简要介绍了一些理论,然后列举了几个例子,包括洛桑研究所的经典实验、澳大利亚的产量监测实验、丹麦的长期大麦试验和土壤湿度监测网络。在单场范围内,年际变化明显大于空间变化。由此得出的结论是,如果精准农业要有坚实的科学基础,并最终取得实际成果,那么仍有待认真研究的零假设是:“考虑到相对于单个领域规模的产量的巨大时间变化,那么最佳的风险规避策略是统一管理。”
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引用次数: 31
Molecular evolution of multiply-antibiotic-resistant staphylococci. 多重耐药葡萄球菌的分子进化。
Pub Date : 1997-01-01 DOI: 10.1002/9780470515358.ch11
R A Skurray, N Firth

Methicillin-resistant Staphylococcus aureus (MRSA) is an intractable nosocomial pathogen. The chemotherapeutic intransigence of this organism stems from its predilection to antimicrobial resistance as a consequential response to selective pressures prevailing in the clinical environment. MRSA isolates are frequently resistant to all practicable antimicrobials except the glycopeptide, vancomycin. Although antimicrobial resistance sometimes arises via chromosomal mutation, the emergence of multiply-antibiotic-resistant staphylococci is primarily due to the acquisition of pre-existent resistance genes; such determinants can be encoded chromosomally or by plasmids and are often associated with transposons or insertion sequences. Clinical staphylococci commonly carry one or more plasmids, ranging from small replicons that are phenotypically cryptic or contain only a single resistance gene, to larger episomes that possess several such determinants and sometimes additionally encode systems that mediate their own conjugative transmission and the mobilization of other plasmids. The detection of closely related plasmids, elements and/or genes in other hosts, including coagulase-negative staphylococci and enterococci, attests to interspecific and intergeneric genetic exchange facilitated by mobile genetic elements and DNA transfer mechanisms. The extended genetic reservoir accessible to staphylococci afforded by such horizontal gene flux is fundamental to the acquisition, maintenance and dissemination of staphylococcal antimicrobial resistance in general, and multiresistance in particular.

耐甲氧西林金黄色葡萄球菌(MRSA)是一种难治性医院病原菌。这种生物的化疗不妥协源于其对抗微生物药物耐药性的偏好,作为对临床环境中普遍存在的选择压力的相应反应。MRSA分离株通常对除糖肽万古霉素以外的所有可行的抗菌素具有耐药性。虽然抗微生物药物耐药性有时是通过染色体突变产生的,但多重耐药葡萄球菌的出现主要是由于获得了预先存在的耐药基因;这些决定因子可以在染色体上或由质粒编码,并且通常与转座子或插入序列相关。临床葡萄球菌通常携带一个或多个质粒,从表型上隐型或只含有单一抗性基因的小复制子,到具有几个这样的决定因子的大复制子,有时还编码介导其自身结合传播和其他质粒动员的系统。在其他宿主中检测到密切相关的质粒、元件和/或基因,包括凝固酶阴性葡萄球菌和肠球菌,证明了移动遗传元件和DNA转移机制促进了种间和属间的遗传交换。这种水平基因通量为葡萄球菌提供了扩展的遗传库,对葡萄球菌抗微生物药物耐药性的获得、维持和传播至关重要,特别是多重耐药性。
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引用次数: 38
Repair and processing events at DNA ends. DNA末端的修复和加工过程。
Pub Date : 1997-01-01 DOI: 10.1002/9780470515433.ch13
T Lindahl, D E Barnes, A Klungland, V J Mackenney, P Schär

Cell nuclei contain several abundant enzymes that bind rapidly and avidly to exposed termini of DNA. The properties and physiological roles of such factors are described; they include poly (ADP-ribose) polymerase, DNA-dependent protein kinase, several DNA ligases and excision-repair enzymes. Telomeres normally seem shielded from these activities by telomere-binding proteins. If incomplete protection of telomeres occurred, the functions of the DNA end-specific enzymes would be relevant for processing of telomeres. This could include alternative pathways for telomere propagation in telomerase-negative cells.

细胞核中含有几种丰富的酶,它们能迅速地与暴露的DNA末端结合。介绍了这些因子的性质和生理作用;它们包括聚(adp -核糖)聚合酶、DNA依赖性蛋白激酶、几种DNA连接酶和切除修复酶。通常情况下,端粒似乎被端粒结合蛋白屏蔽了这些活动。如果端粒发生不完全保护,DNA末端特异性酶的功能将与端粒的加工有关。这可能包括端粒酶阴性细胞中端粒增殖的替代途径。
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引用次数: 5
Controversies in the cellular pharmacology of oligodeoxynucleotides. 寡脱氧核苷酸的细胞药理学争议。
Pub Date : 1997-01-01 DOI: 10.1002/9780470515396.ch7
C. Stein
Phosphodiester and phosphorothioate oligodeoxynucleotides are polyanions that cannot passively diffuse across cell membranes. Instead, the processes of adsorbtive endocytosis and pinocytosis probably account for the great majority of oligodeoxynucleotide internalization in most cell types. Oligodeoxynucleotides can adsorb to heparin-binding, cell surface proteins. An example of such a protein is the integrin Mac-1 (alpha M beta 2; CR3; CD11b/CD18), a receptor for fibrinogen which is found on neutrophils, macrophages and natural killer cells. Up-regulation of neutrophil cell surface Mac-1 expression by interleukin 8, arachidonic acid or tumour necrosis factor alpha leads to increased cell surface oligodeoxynucleotide binding and internalization. Binding and internalization can be blocked by both fibrinogen and by anti-Mac-1 monoclonal antibodies. Subsequent to internalization, oligodeoxynucleotides reside in subcellular vesicular structures, i.e. endosomes and lysosomes. However, in the absence of permeabilizing agents, these compartments may be sites of sequestration and the oligomers may be unavailable for antisense activity. At present, controversy surrounds the use of guanosine-rich phosphorothioate oligodeoxynucleotides as antisense agents. We examined the ability of the 24mer antisense rel A (p65) phosphorothioate oligodeoxynucleotide to inhibit nuclear translocation of NF kappa B in K-BALB murine fibroblasts. 7-Deaza-2'-deoxyguanosine substitution in the 5' guanosine quartet region demonstrated that inhibition of nuclear translocation could not be due to a Watson-Crick antisense effect. Rather, we favour the explanation that the parent molecule may be a sequence-specific, apatameric decoy.
磷酸二酯和硫代磷寡脱氧核苷酸是不能被动扩散穿过细胞膜的多阴离子。相反,在大多数细胞类型中,吸附内吞作用和胞饮作用的过程可能占了寡脱氧核苷酸内化的绝大部分。寡脱氧核苷酸可以吸附到肝素结合的细胞表面蛋白上。这种蛋白质的一个例子是整合素Mac-1 (α M β 2;CR3;CD11b/CD18),一种纤维蛋白原受体,存在于中性粒细胞、巨噬细胞和自然杀伤细胞中。白细胞介素8、花生四烯酸或肿瘤坏死因子α上调中性粒细胞表面Mac-1的表达,导致细胞表面寡脱氧核苷酸结合和内化增加。纤维蛋白原和抗mac -1单克隆抗体均可阻断其结合和内化。在内化之后,寡脱氧核苷酸驻留在亚细胞囊泡结构中,即核内体和溶酶体。然而,在缺乏渗透剂的情况下,这些隔室可能是隔离位点,低聚物可能无法进行反义活性。目前,围绕使用富鸟苷硫代寡脱氧核苷酸作为反义药物存在争议。我们检测了24mer反义rel A (p65)硫代寡脱氧核苷酸在K-BALB小鼠成纤维细胞中抑制NF κ B核易位的能力。5′鸟苷四重奏区7-Deaza-2′-脱氧鸟苷取代表明,核易位的抑制可能不是由于沃森-克里克反义效应。相反,我们倾向于这样一种解释,即母体分子可能是一个序列特异性的、非特异性的诱饵。
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引用次数: 0
Biological aspects of macrophage-stimulating protein (MSP) and its receptor. 巨噬细胞刺激蛋白(MSP)及其受体的生物学特性。
Pub Date : 1997-01-01 DOI: 10.1002/9780470515457.CH12
E. Leonard
Macrophage-stimulating protein (MSP; also known as HGF-like protein [HGFl]) is a 78 kDa plasma protein that is secreted by the liver into the circulation as single-chain, biologically inactive pro-MSP. The presence of conserved triple disulfide loops (kringles) places pro-MSP in a family of coagulation system serine protease zymogens that are activated by proteolytic cleavage. Although pro-MSP has lost enzymic activity, it has retained the activation mechanism, in that proteolytic cleavage at a single site yields biologically active disulfide-linked alpha beta-chain heterodimeric MSP. The MSP receptor is a transmembrane protein tyrosine kinase. MSP causes phosphorylation of the receptor cytoplasmic domain, association of phosphatidylinositol (PI)-3 kinase with the receptor, and phosphorylation of receptor-bound PI-3 kinase. Inhibition of PI-3 kinase by wortmannin prevents MSP action on cells. MSP stimulates motility of murine resident peritoneal macrophages. However, it does not act on exudate macrophages or blood monocytes, since these earlier maturational stages of the lineage do not express the receptor. MSP also stimulates keratinocyte cell lines, causing either chemotactic responses or increased cell numbers in culture. We suggest that pro-MSP diffuses into local tissue sites, where proteolytic cleavage to MSP results in stimulation of keratinocytes and macrophages. It possibly plays a role in tissue injury or wound healing.
巨噬细胞刺激蛋白;也称为hgf样蛋白[HGFl])是一种78 kDa的血浆蛋白,由肝脏以单链、无生物活性的前msp的形式分泌到循环中。保守的三二硫环(kringles)的存在将前msp置于凝血系统丝氨酸蛋白酶酶原家族中,该家族通过蛋白水解裂解激活。虽然pro-MSP失去了酶活性,但它保留了激活机制,在单位点的蛋白水解裂解产生具有生物活性的二硫连接α - β链异二聚体MSP。MSP受体是一种跨膜蛋白酪氨酸激酶。MSP引起受体细胞质域磷酸化,磷脂酰肌醇(PI)-3激酶与受体结合,以及受体结合的PI-3激酶磷酸化。wortmannin抑制PI-3激酶可阻止MSP对细胞的作用。MSP刺激小鼠腹腔巨噬细胞的运动。然而,它不作用于渗出巨噬细胞或血液单核细胞,因为这些谱系的早期成熟阶段不表达受体。MSP也刺激角化细胞细胞系,引起趋化反应或增加培养中的细胞数量。我们认为,前MSP扩散到局部组织部位,在那里,MSP的蛋白水解裂解导致角质形成细胞和巨噬细胞的刺激。它可能在组织损伤或伤口愈合中起作用。
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引用次数: 18
Oligonucleotide therapeutics for human leukaemia. 人类白血病的寡核苷酸疗法。
Pub Date : 1997-01-01 DOI: 10.1007/978-3-0348-8946-9_9
A. Gewirtz
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引用次数: 5
Differentiation and functions of T cell subsets. T细胞亚群的分化和功能。
Pub Date : 1997-01-01 DOI: 10.1002/9780470515280.ch10
T R Mosmann, L Li, H Hengartner, D Kagi, W Fu, S Sad

The Tc1 and Tc2 subsets of CD8+ T effector cells secrete different patterns of cytokines, but have similar functions, including perforin- and Fas-dependent cytotoxicity, and induction of delayed type hypersensitivity (DTH) reactions involving oedema and granulocytic infiltration. The characteristic cytokines of Tc1 (gamma-interferon) and Tc2 (interleukins 4 and 5) are expressed in vivo during the DTH reaction. Tc1 cells that are deficient in cytokine synthesis also induce similar levels of DTH, supporting the lack of correlation between CD8+ T cell cytokine patterns and DTH. CD8+ T cells often produce lower cytokine levels than CD4 cells because the CD8 cells kill their antigen-presenting cells before full stimulation can occur. This effect can be counteracted by increasing the frequency of stimulation, or using perforin-deficient T cells. A multiparameter analysis of cytokine effects on CD8+ T cell differentiation has been initiated, on the basis of the principle that normal immune responses involve complex cytokine mixtures. All combinations of seven cytokines were tested. In some combinations, the combined effect could not have been predicted from individual cytokine functions. Conditions were identified in which each of interleukins 4, 10 and 12 could have opposite effects on CD8+ T cell differentiation.

CD8+ T效应细胞的Tc1和Tc2亚群分泌不同模式的细胞因子,但具有相似的功能,包括穿孔素和fas依赖的细胞毒性,以及诱导迟发性超敏反应(DTH),包括水肿和粒细胞浸润。Tc1 (γ -干扰素)和Tc2(白细胞介素4和5)的特征性细胞因子在DTH反应中在体内表达。缺乏细胞因子合成的Tc1细胞也会诱导相似水平的DTH,支持CD8+ T细胞细胞因子模式与DTH之间缺乏相关性。CD8+ T细胞通常比CD4细胞产生更低的细胞因子水平,因为CD8细胞在完全刺激发生之前杀死了它们的抗原呈递细胞。这种影响可以通过增加刺激频率或使用穿孔素缺陷T细胞来抵消。基于正常免疫反应涉及复杂的细胞因子混合物的原理,细胞因子对CD8+ T细胞分化的多参数分析已经开始。检测7种细胞因子的所有组合。在某些组合中,不能从单个细胞因子的功能来预测联合效应。在这种情况下,白细胞介素4、10和12可能对CD8+ T细胞分化产生相反的影响。
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引用次数: 61
期刊
Ciba Foundation symposium
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