• 【Lgr5加入了胃体中胃干细胞标记的俱乐部。】 复制标题 收藏 收藏
    DOI:10.1038/ncb3567 复制DOI
    作者列表:Phesse TJ,Sansom OJ
    BACKGROUND & AIMS: :Several markers of gastric stem cells have been identified in recent years. Now a study demonstrates that Lgr5 marks a population of reserve stem cells located at the base of the corpus glands of the gastric epithelium, and that these cells can also act as a cell-of-origin for gastric tumorigenesis.
    背景与目标: : 近年来已鉴定出几种胃干细胞的标志物。现在,一项研究表明,Lgr5标志着位于胃上皮体腺体底部的储备干细胞种群,并且这些细胞也可以充当胃肿瘤发生的起源细胞。
  • 【古细菌Aeropyrum pernix中DNA复制起点的生化分析。】 复制标题 收藏 收藏
    DOI:10.1016/j.jmb.2006.07.076 复制DOI
    作者列表:Grainge I,Gaudier M,Schuwirth BS,Westcott SL,Sandall J,Atanassova N,Wigley DB
    BACKGROUND & AIMS: :We have characterised the interaction of the Aeropyrum pernix origin recognition complex proteins (ORC1 and ORC2) with DNA using DNase I footprinting. Each protein binds upstream of its respective gene. However, ORC1 protein alone interacts more tightly with an additional region containing multiple origin recognition box (ORB) sites that we show to be a replication origin. At this origin, there are four ORB elements disposed either side of an A+T-rich region. An ORC1 protein dimer binds at each of these ORB sites. Once all four ORB sites have bound ORC1 protein, there is a transition to a higher-order assembly with a defined alteration in topology and superhelicity. Furthermore, after this transition, the A+T-rich region becomes sensitive to digestion by DNase I and P1 nuclease, revealing that the transition promotes distortion of the DNA in this region, presumably as a prelude to loading of MCM helicase.
    背景与目标: : 我们使用DNase I足迹表征了Aeropyrum pernix起源识别复合物蛋白 (ORC1和ORC2) 与DNA的相互作用。每种蛋白质结合其各自基因的上游。然而,仅ORC1蛋白与包含多个起源识别框 (ORB) 位点的其他区域的相互作用更紧密,我们证明这是复制起源。在这个起源处,富含A T的区域的两侧都有四个ORB元素。ORC1蛋白二聚体在每个ORB位点结合。一旦所有四个ORB位点都结合了ORC1蛋白,就会过渡到具有定义的拓扑和超螺旋性变化的高阶组装。此外,在这种转变之后,富含A T的区域对DNase I和P1核酸酶的消化变得敏感,这表明该转变促进了该区域中DNA的扭曲,大概是MCM解旋酶加载的前奏。
  • 【天然釉质龋: 生化体积的比较组织学研究。】 复制标题 收藏 收藏
    DOI:10.1159/000345378 复制DOI
    作者列表:Barbosa de Sousa F,Dias Soares J,Sampaio Vianna S
    BACKGROUND & AIMS: :This study aimed to test the hypothesis that organic volume is the main variable for explaining the optical properties and predictive degree of diffusion of enamel histological points at zones of natural enamel caries (NEC; surface layer, SL, n = 30, and body of the lesion, BL, n = 58) and normal enamel (NE, n = 131). Molars with either NEC or NE were quantitatively analyzed regarding the mineral, organic and water volumes (considered as effective pore volume), opacity (predicted in 94% of cases by water volume in NEC), and water volume more easily available for diffusion, αd (squared water volume divided by the nonmineral volume; related to permeability). NEC presented lower mineral volumes and higher organic volumes, effective pore volume and opacity than NE. External origin of organic volume in NEC was evidenced by an organic gradient decreasing from the surface inward (R2 = -0.7), which was not detected in teeth with NE only; αd values of the SL and NE were similar and both were lower (p < 0.0001) than that of the BL. Comparing the SL from both NEC and artificial enamel caries (AEC; published data; n = 71), with similar mineral volumes, against developing enamel (published data), AEC showed more effective pore volume (3 times higher), higher αd and opacity than NEC mainly due to differences in organic volumes. Our results reasonably matched widely known features of NEC histological zones, and confirmed the organic volume as the main variable for explaining optical properties and αd (related to permeability).
    背景与目标: : 这项研究旨在检验以下假设: 有机体积是解释自然牙釉质龋 (NEC; 表面层,SL,n = 30) 和身体的光学特性和牙釉质组织学点扩散的预测程度的主要变量。病变,BL,n = 58) 和正常釉质 (NE,n = 131)。对具有NEC或NE的磨牙进行了定量分析,涉及矿物质,有机物和水的体积 (被认为是有效的孔隙体积),不透明度 (在94% 情况下由NEC中的水量预测) 以及更易于扩散的水量 α d (平方水体积除以非矿物质体积; 与渗透率相关)。NEC表现出比NE更低的矿物体积和更高的有机体积,有效孔体积和不透明度。NEC中有机体积的外部来源通过从表面向内减小的有机梯度 (R2 = -0.7) 来证明,这仅在具有NE的牙齿中没有检测到; SL和NE的 α d值相似,并且均低于BL (p <0.0001)。将具有相似矿物体积的NEC和人造牙釉质龋 (AEC; 已发布数据; n = 71) 的SL与正在开发的牙釉质 (已发布数据) 进行比较,AEC显示出更有效的孔体积 (高3倍),更高的 α d和不透明度比NEC主要是由于有机体积的差异。我们的结果合理地匹配了NEC组织学区域的众所周知的特征,并确认了有机体积是解释光学特性和 α d (与渗透率有关) 的主要变量。
  • 【纯种纯种耐碱耐金属漆酶的纯化,生化特性和染料脱色能力。】 复制标题 收藏 收藏
    DOI:10.1016/j.biortech.2012.10.085 复制DOI
    作者列表:Si J,Peng F,Cui B
    BACKGROUND & AIMS: :Extracellular laccase (Tplac) from Trametes pubescens was purified to homogeneity by a three-step method, which resulted in a high specific activity of 18.543 Umg(-1), 16.016-fold greater than that of crude enzyme at the same level. Tplac is a monomeric protein that has a molecular mass of 68 kDa. The enzyme demonstrated high activity toward 1.0mM ABTS at an optimum pH of 5.0 and temperature of 50 °C, and under these conditions, the catalytic efficiency (k(cat)/K(m)) is 8.34 s(-1) μM(-1). Tplac is highly stable and resistant under alkaline conditions, with pH values ranging from 7.0 to 10.0. Interestingly, above 88% of initial enzyme activity was maintained in the presence of metal ions at 25.0mM, leading to an increase in substrate affinity, which indicated that the laccase is highly metal-tolerant. These unusual properties demonstrated that the new fungal laccase Tplac has potentials for the specific industrial or environmental applications.
    背景与目标: : 通过三步法将来自Trametes pubescens的细胞外漆酶 (Tplac) 纯化至同质,这导致18.543 Umg(-1) 的高比活性,比相同水平的粗酶高16.016倍。Tplac是一种分子量为68 kDa的单体蛋白。该酶在5.0的最佳pH和50 °C的温度下表现出对1.0毫米ABTS的高活性,并且在这些条件下,催化效率 (k(cat)/K(m)) 为8.34 s(-1) μ m (-1)。Tplac在碱性条件下具有高度稳定和抗性,ph值范围从7.0到10.0。有趣的是,在25.0mm的金属离子存在下,初始酶活性保持88% 以上,导致底物亲和力增加,这表明漆酶具有高度的金属耐受性。这些不寻常的特性表明,新的真菌漆酶Tplac具有用于特定工业或环境应用的潜力。
  • 【褪黑素激素对松果体切除大鼠海马的影响: 免疫组织化学和生化研究。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Kus MA,Sarsilmaz M,Karaca O,Acar T,Gülcen B,Hismiogullari AA,Ogetürk M,Kus I
    BACKGROUND & AIMS: OBJECTIVE:The effects of melatonin on antioxidant status were examined in pinealectomized rats using enzymatic, histological and immunohistochemical techniques. The aim of this study is to investigate the effects of melatonin on hippocampal apoptosis. MATERIALS AND METHODS:Male Wistar rats (n=21) were divided into 3 groups: Group I and group II were designated as control (sham-pinealectomy) and pinealectomized rats, respectively. Rats in group III were pinealectomized and injected daily with melatonin (1 mg/kg) for 3 months beginning at day 7 after surgery. At the end of experimental period, all rats were killed by decapitation. The brains of the rats were removed and the hippocampus tissue was obtained from all brain specimens. The right hippocampal specimens of all rats were used for determination of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) levels. The left hippocampus tissue specimens of all animals were used for immunohistochemical and histological evaluation. RESULTS:The levels of SOD and GSH-Px were significantly decreased, and MDA levels were significantly increased in pinealectomized rats compared to the controls. In the histological and immunohistochemical evaluation of this group, increase of pyknotic cells, vacuolar degeneration and apoptosis were observed. However, increased SOD and GSH-Px enzyme activities, and decreased MDA levels were detected in the rats administered melatonin after pinealectomy. Furthermore, histological and apoptotic changes in hippocampus caused by pinealectomy were lost in the rats treated with melatonin. CONCLUSIONS:The results of our study revealed that pinealectomy-induced oxidative damage and morphological changes in the hippocampal tissue were suppressed by melatonin.
    背景与目标:
  • 【心肌肌钙蛋白I和T: 急性心肌梗死患者早期诊断、预后和准确分类的分子标志物。】 复制标题 收藏 收藏
    DOI:10.1007/s40291-012-0011-6 复制DOI
    作者列表:Tiwari RP,Jain A,Khan Z,Kohli V,Bharmal RN,Kartikeyan S,Bisen PS
    BACKGROUND & AIMS: :Acute myocardial infarction (AMI) is the leading cause of death worldwide, with early diagnosis still being difficult. Promising new cardiac biomarkers such as troponins and creatine kinase (CK) isoforms are being studied and integrated into clinical practice for early diagnosis of AMI. The cardiac-specific troponins I and T (cTnI and cTnT) have good sensitivity and specificity as indicators of myocardial necrosis and are superior to CK and its MB isoenzyme (CK-MB) in this regard. Besides being potential biologic markers, cardiac troponins also provide significant prognostic information. The introduction of novel high-sensitivity troponin assays has enabled more sensitive and timely diagnosis or exclusion of acute coronary syndromes. This review summarizes the available information on the potential of troponins and other cardiac markers in early diagnosis and prognosis of AMI, and provides perspectives on future diagnostic approaches to AMI.
    背景与目标: : 急性心肌梗死 (AMI) 是全球死亡的主要原因,早期诊断仍然很困难。正在研究有希望的新的心脏生物标志物,例如肌钙蛋白和肌酸激酶 (CK) 亚型,并将其整合到临床实践中,以早期诊断AMI。心脏特异性肌钙蛋白I和T (cTnI和cTnT) 作为心肌坏死的指标具有良好的敏感性和特异性,在这方面优于CK及其MB同工酶 (ck-mb)。除了作为潜在的生物学标志物外,心肌肌钙蛋白还提供了重要的预后信息。新型高灵敏度肌钙蛋白测定法的引入使急性冠状动脉综合征的诊断和排除更加敏感和及时。这篇综述总结了肌钙蛋白和其他心脏标志物在AMI早期诊断和预后中的潜力,并为AMI的未来诊断方法提供了展望。
  • 【I-125前列腺近距离放射疗法治疗的400例患者的生化无复发生存率: 吉尔福德经验。】 复制标题 收藏 收藏
    DOI:10.1038/pcan.2008.17 复制DOI
    作者列表:Nobes JP,Wells IG,Khaksar SJ,Money-Kyrle JF,Laing RW,Langley SE
    BACKGROUND & AIMS: :A total of 1200 patients had undergone I-125 prostate brachytherapy (BXT) in our centre. We present prospective outcome data for the first 400 treated patients. Data were analysed from a prospective database of 400 consecutive patients treated with permanent prostate BXT between March 1999 and December 2003. Patients were stratified into low (49%), intermediate (36%) and high (15%) risk as defined by the Memorial Sloan-Kettering Prognostic Index. Patients received 145 Gy BXT alone (41%), BXT with 3 months neoadjuvant androgen deprivation (NAAD) (39%), 45 Gy external beam radiotherapy (EBRT) with 110 Gy BXT (3%) or a combination of NAAD, 45 Gy EBRT and 110 Gy BXT (17%). Biochemical relapse-free survival (bRFS) and prostate-specific antigen (PSA) nadirs were analysed for treatment received in each risk group. Median follow-up was 54 months (range, 38-96 months) with a mean patient age of 63 years. Prostate cancer-specific survival was 99.5%. Twenty-eight patients (7%) experienced biochemical failure according to the 2006 Radiation Therapy Oncology Group-American Society for Therapeutic Radiology and Oncology (RTOG-ASTRO) Phoenix Consensus definition (PSA nadir plus >or=2 ng ml(-1)): nine low-, fourteen intermediate- and five high-risk patients. When stratified by treatment group for low-, intermediate- and high-risk groups, the 5-year actuarial bRFS was 98, 89 and 100% for BXT; 91, 87 and 88% for NAAD and BXT; 100, 80 and 100% for EBRT and BXT; and 100, 92 and 88% for NAAD, EBRT and BXT, respectively. Overall 4- and 5-year PSA
    背景与目标: : 我们中心共有1200例患者接受了I-125前列腺近距离放射疗法 (BXT)。我们提供了第400例接受治疗的患者的前瞻性结果数据。从1999年3月和2003年12月之间接受永久性前列腺BXT治疗的400连续患者的前瞻性数据库中分析了数据。根据纪念斯隆-凯特琳预后指数的定义,将患者分为低 (49%),中 (36%) 和高 (15%) 风险。患者单独接受145 Gy BXT (41%),BXT联合3个月新辅助雄激素剥夺 (NAAD) (39%),45 Gy外束放疗 (EBRT) 联合110 Gy BXT (3%) 或结合NAAD,45 Gy EBRT和110 Gy BXT (17%)。分析了每个风险组中接受的生化无复发生存率 (bRFS) 和前列腺特异性抗原 (PSA) nadirs。中位随访时间为54个月 (范围为38-96个月),患者平均年龄为63岁。99.5% 了前列腺癌特异性生存率。根据2006放射治疗肿瘤学小组-美国放射治疗与肿瘤学会 (rtog-astro) Phoenix共识定义 (PSA最低点加> 或 = 2 ng ml(-1)),28名患者 (7%) 经历了生化失败: 9低-,14名中危和5名高危患者。当按低,中和高风险组的治疗组进行分层时,BXT的5年精算brf为98、89和100%; NAAD和BXT为91、87和88%; EBRT和BXT为100、80和100%; 和100,NAAD、EBRT和BXT分别为92和88%。总体4年和5年PSA <或 = 0.5 ng ml(-1) 由83和86% 实现。这项前瞻性研究更新了我们的生化生存结果,并进一步证明了英国中心能够重现美国报告的BXT出色结果。
  • 【p53和Bcl-xL的表达作为晚期喉癌喉保存的预测标志物。】 复制标题 收藏 收藏
    DOI:10.1001/archotol.134.4.363 复制DOI
    作者列表:Kumar B,Cordell KG,D'Silva N,Prince ME,Adams ME,Fisher SG,Wolf GT,Carey TE,Bradford CR
    BACKGROUND & AIMS: OBJECTIVE:To assess tumor markers in advanced laryngeal cancer. DESIGN:Marker expression and clinical outcome. PATIENTS:Pretreatment tumor biopsy specimens were analyzed from patients enrolled in the Department of Veterans Affairs Laryngeal Cancer Study. MAIN OUTCOME MEASURES:Expression of p53 (OMIM TP53) and Bcl-xL (OMIM 600039) in pretreatment biopsy specimens was assessed for correlation with chemotherapy response, laryngeal preservation, and survival. RESULTS:Higher rates of larynx preservation were observed in patients whose tumors expressed p53 vs those that did not (80% [36 of 45 patients] vs 59% [24 of 41 patients], P =.03). Higher rates of larynx preservation were also observed in patients whose tumors expressed low levels of Bcl-xL vs high levels of Bcl-xL (90% [18 of 20 patients] vs 60% [30 of 50 patients], P =.02). Patients were categorized into 3 risk groups (low, intermediate, and high) based on their tumor p53 and Bcl-xL expression status. Patients whose tumors had the high-risk biomarker profile (low p53 expression and high Bcl-xL expression) were less likely to preserve their larynx than patients whose tumors had the intermediate-risk biomarker profile (high p53 expression and low or high Bcl-xL expression) or the low-risk biomarker profile (low p53 expression and low Bcl-xL expression). The larynx preservation rates were 100% (10 of 10 patients), 77% (26 of 34 patients), and 54% (7 of 13 patients) for the low-risk, intermediate-risk, and high-risk groups, respectively (P =.04, Fisher exact test). CONCLUSION:Tumor expression of p53 and Bcl-xL is a strong predictor of successful larynx preservation in patients treated with induction chemotherapy and followed by radiation therapy in responding tumors.
    背景与目标:
  • 【人类胆碱脱氢酶: 医学承诺和生化挑战。】 复制标题 收藏 收藏
    DOI:10.1016/j.abb.2013.07.018 复制DOI
    作者列表:Salvi F,Gadda G
    BACKGROUND & AIMS: :Human choline dehydrogenase (CHD) is located in the inner membrane of mitochondria primarily in liver and kidney and catalyzes the oxidation of choline to glycine betaine. Its physiological role is to regulate the concentrations of choline and glycine betaine in the blood and cells. Choline is important for regulation of gene expression, the biosynthesis of lipoproteins and membrane phospholipids and for the biosynthesis of the neurotransmitter acetylcholine; glycine betaine plays important roles as a primary intracellular osmoprotectant and as methyl donor for the biosynthesis of methionine from homocysteine, a required step for the synthesis of the ubiquitous methyl donor S-adenosyl methionine. Recently, CHD has generated considerable medical attention due to its association with various human pathologies, including male infertility, homocysteinuria, breast cancer and metabolic syndrome. Despite the renewed interest, the biochemical characterization of the enzyme has lagged behind due to difficulties in the obtainment of purified, active and stable enzyme. This review article summarizes the medical relevance and the physiological roles of human CHD, highlights the biochemical knowledge on the enzyme, and provides an analysis based on the comparison of the protein sequence with that of bacterial choline oxidase, for which structural and biochemical information is available.
    背景与目标: : 人胆碱脱氢酶 (CHD) 位于线粒体的内膜中,主要位于肝脏和肾脏中,并催化胆碱氧化为甘氨酸甜菜碱。它的生理作用是调节血液和细胞中胆碱和甘氨酸甜菜碱的浓度。胆碱对于调节基因表达,脂蛋白和膜磷脂的生物合成以及神经递质乙酰胆碱的生物合成很重要; 甘氨酸甜菜碱作为主要的细胞内渗透保护剂和甲基供体,从高半胱氨酸生物合成蛋氨酸,合成无处不在的甲基供体S-腺苷甲硫氨酸所需的步骤。最近,由于CHD与各种人类疾病有关,包括男性不育,同型半胱氨酸尿症,乳腺癌和代谢综合征,引起了广泛的医学关注。尽管重新引起了人们的兴趣,但由于难以获得纯化,活性和稳定的酶,该酶的生化特性仍然落后。本文综述了人类CHD的医学相关性和生理作用,重点介绍了该酶的生化知识,并根据蛋白质序列与细菌胆碱氧化酶的序列进行了比较,提供了结构和生化信息。
  • 【通过大量分离分析鉴定与抗病基因相关的标记: 一种使用分离种群检测特定基因组区域标记的快速方法。】 复制标题 收藏 收藏
    DOI:10.1073/pnas.88.21.9828 复制DOI
    作者列表:Michelmore RW,Paran I,Kesseli RV
    BACKGROUND & AIMS: :We developed bulked segregant analysis as a method for rapidly identifying markers linked to any specific gene or genomic region. Two bulked DNA samples are generated from a segregating population from a single cross. Each pool, or bulk, contains individuals that are identical for a particular trait or genomic region but arbitrary at all unlinked regions. The two bulks are therefore genetically dissimilar in the selected region but seemingly heterozygous at all other regions. The two bulks can be made for any genomic region and from any segregating population. The bulks are screened for differences using restriction fragment length polymorphism probes or random amplified polymorphic DNA primers. We have used bulked segregant analysis to identify three random amplified polymorphic DNA markers in lettuce linked to a gene for resistance to downy mildew. We showed that markers can be reliably identified in a 25-centimorgan window on either side of the targeted locus. Bulked segregant analysis has several advantages over the use of near-isogenic lines to identify markers in specific regions of the genome. Genetic walking will be possible by multiple rounds of bulked segregation analysis; each new pair of bulks will differ at a locus identified in the previous round of analysis. This approach will have widespread application both in those species where selfing is possible and in those that are obligatorily outbreeding.
    背景与目标: : 我们开发了大量的分离物分析,作为一种快速识别与任何特定基因或基因组区域相关的标记的方法。从单个杂交的分离种群中产生两个大量的DNA样本。每个池或整体包含对于特定性状或基因组区域相同但在所有未连接区域任意的个体。因此,这两个大块在选定区域在遗传上是不同的,但在所有其他区域似乎是杂合的。这两个大块可以用于任何基因组区域和任何分离的种群。使用限制性片段长度多态性探针或随机扩增的多态性DNA引物筛选大块的差异。我们已经使用大量的分离物分析来鉴定生菜中的三个随机扩增的多态性DNA标记,这些标记与抗霜霉病的基因相关。我们表明,可以在目标基因座两侧的25厘摩根窗口中可靠地识别出标记。与使用近等基因系鉴定基因组特定区域中的标记相比,大量分离物分析具有多个优势。通过多轮膨胀的分离分析,遗传行走是可能的; 每对新的大块在上一轮分析中确定的基因座上会有所不同。这种方法将在可能自交的物种和强制近交的物种中得到广泛应用。
  • 【人促甲状腺激素受体基因: 在甲状腺肿瘤中的表达及其与甲状腺分化和去分化标志物的相关性。】 复制标题 收藏 收藏
    DOI:10.1016/0303-7207(91)90018-n 复制DOI
    作者列表:Brabant G,Maenhaut C,Köhrle J,Scheumann G,Dralle H,Hoang-Vu C,Hesch RD,von zur Mühlen A,Vassart G,Dumont JE
    BACKGROUND & AIMS: :Human thyrotropin (TSH) receptor steady-state transcript levels were analyzed by Northern blot analysis in thyroids of patients with thyroid carcinoma, with hyperfunctioning adenoma and in normal controls. In control tissue and benign tumors expression levels of TSH receptor mRNA were high whereas in anaplastic carcinomas no normal TSH receptor mRNA was detected. In papillary and follicular tumors it varied from normal to markedly reduced levels. Thyroid peroxidase (TPO) and thyroglobulin (Tg) mRNA were strongly expressed in normal tissue and in hyperfunctioning adenomas but were completely lost in all anaplastic tumors. In papillary tumors expression of TPO and Tg mRNA varied from normal to a complete loss of expression of either TPO, Tg or both. Tg and TPO steady-state expression did not correlate to TSH receptor transcript levels. C-myc mRNA was highly expressed in anaplastic carcinomas, very variable in normal controls and in differentiated thyroid tumors and low in hyperfunctioning adenomas. In summary, TSH receptor mRNA is persistently expressed in all differentiated thyroid tissues and tumors but lost in undifferentiated carcinomas. Its persistence far along the transformation pathway further supports the concept that this gene which inserts the thyrocytes in the physiological regulatory network is almost constitutively expressed in this cell.
    背景与目标: : 通过Northern印迹分析在甲状腺癌,功能亢进性腺瘤患者和正常对照组的甲状腺中分析了人促甲状腺激素 (TSH) 受体稳态转录本水平。在对照组织和良性肿瘤中,TSH受体mRNA的表达水平很高,而在间变性癌中,未检测到正常的TSH受体mRNA。在乳头状和滤泡状肿瘤中,其水平从正常到明显降低不等。甲状腺过氧化物酶 (TPO) 和甲状腺球蛋白 (Tg) mRNA在正常组织和功能亢进的腺瘤中强烈表达,但在所有间变性肿瘤中完全消失。在乳头状肿瘤中,TPO和Tg mRNA的表达从正常到TPO,Tg或两者的完全丧失。Tg和TPO稳态表达与TSH受体转录水平无关。C-myc mRNA在间变性癌中高表达,在正常对照和分化的甲状腺肿瘤中非常可变,而在功能亢进的腺瘤中则低。总之,TSH受体mRNA在所有分化的甲状腺组织和肿瘤中持续表达,但在未分化的癌中丢失。它在转化途径上的持久存在进一步支持了这样的概念,即将甲状腺细胞插入生理调节网络中的基因几乎在该细胞中组成性表达。
  • 【兔网织红细胞裂解物中cap-poly(A) 协同作用的生化表征: eIF4G-PABP相互作用增加了eIF4E对加盖的mRNA 5 '-末端的功能亲和力。】 复制标题 收藏 收藏
    DOI:10.1093/nar/28.21.4068 复制DOI
    作者列表:Borman AM,Michel YM,Kean KM
    BACKGROUND & AIMS: :The 5' cap and 3' poly(A) tail of eukaryotic mRNAs cooperate to synergistically stimulate translation initiation in vivo. We recently described mammalian cytoplasmic extracts which, following ultracentrifugation to partially deplete them of ribosomes and associated initiation factors, reproduce cap-poly(A) synergy in vitro. Using these systems, we demonstrate that synergy requires interaction between the poly(A)-binding protein (PABP) and the eukaryotic initiation factor (eIF) 4F holoenzyme complex, which recognises the 5' cap. Here we further characterise the requirements and constraints of cap-poly(A) synergy in reticulocyte lysates by evaluating the effects of different parameters on synergy. The extent of extract depletion and the amounts of different initiation factors in depleted extracts were examined, as well as the effects of varying the concentrations of KCl, MgCl(2) and programming mRNA and of adding a cap analogue. The results presented demonstrate that maximal cap-poly(A) synergy requires: (i) limiting concentrations of ribosome-associated initiation factors; (ii) precise ratios of mRNA to translation machinery (low concentrations of ribosome-associated initiation factors and low, non-saturating mRNA concentrations); (iii) physiological concentrations of added KCl and MgCl(2). Additionally, we show that the eIF4G-PABP interaction on mRNAs which are capped and polyadenylated significantly increases the affinity of eIF4E for the 5' cap.
    背景与目标: : 真核mrna的5' 帽和3' 聚 (A) 尾协同刺激体内翻译起始。我们最近描述了哺乳动物的细胞质提取物,在超速离心以部分耗尽它们的核糖体和相关的起始因子后,它们在体外复制了cap-poly(A) 协同作用。使用这些系统,我们证明协同作用需要聚 (A) 结合蛋白 (PABP) 与真核起始因子 (eIF) 4F全酶复合物之间的相互作用,该复合物识别5' 帽。在这里,我们通过评估不同参数对协同作用的影响,进一步表征了网织红细胞裂解物中cap-poly(A) 协同作用的要求和约束。检查了提取物消耗的程度和消耗的提取物中不同起始因子的量,以及改变KCl,MgCl(2) 和编程mRNA的浓度以及添加cap类似物的影响。提出的结果表明,最大的cap-poly(A) 协同作用需要 :( i) 限制核糖体相关起始因子的浓度; (ii) mRNA与翻译机制的精确比率 (低浓度的核糖体相关起始因子和低的非饱和mRNA浓度); (iii) 添加的KCl和MgCl的生理浓度 (2)。此外,我们显示在被封端和多聚腺苷酸化的mrna上的eIF4G-PABP相互作用显着增加了eIF4E对5' 帽的亲和力。
  • 【肾病综合征的生物学标志物: 漫长的一步。】 复制标题 收藏 收藏
    DOI:10.3265/Nefrologia.pre2012.Jun.11396 复制DOI
    作者列表:Segarra-Medrano A,Carnicer-Cáceres C,Arbós-Via MA,Quiles-Pérez MT,Agraz-Pamplona I,Ostos-Roldán E
    BACKGROUND & AIMS: :One of the major challenges modern nephrology should face is the identification of biomarkers that are associated with histopathological patterns or defined pathogenic mechanisms that might aid in the non-invasive diagnosis of the causes of nephrotic syndrome, or in establishing prognosis sub-groups based on each type of disease, thus predicting response to treatment and/or recurrence. Advancements in the understanding of the pathogenesis of the different diseases that cause nephrotic syndrome, along with the progressive development and standardisation of plasma and urine proteomics techniques, have facilitated the identification of a growing number of molecules that might be useful for these objectives. Currently, the available information for many of the possible candidates identified to date, above all those discovered using proteomics, are still very preliminary. In this review, we summarise the available evidence for the different molecules that have been best assessed using clinical studies.
    背景与目标: : 现代肾脏病学应该面临的主要挑战之一是识别与组织病理学模式或确定的致病机制相关的生物标志物,这些标志物可能有助于非侵入性诊断肾病综合征的病因,或基于每种疾病建立预后亚组,从而预测对治疗和/或复发的反应。对引起肾病综合征的不同疾病的发病机理的理解的进步,以及血浆和尿液蛋白质组学技术的逐步发展和标准化,促进了对这些目标可能有用的分子的鉴定。目前,迄今为止确定的许多可能的候选者的可用信息,尤其是使用蛋白质组学发现的那些,仍然是非常初步的。在这篇综述中,我们总结了使用临床研究最佳评估的不同分子的可用证据。
  • 【Α-红霉素抑制DNA聚合酶 β 的生化模式。】 复制标题 收藏 收藏
    DOI:10.1016/s0304-4165(00)00119-7 复制DOI
    作者列表:Mizushina Y,Ueno T,Oda M,Yamaguchi T,Saneyoshi M,Sakaguchi K
    BACKGROUND & AIMS: :Quinone antibiotics, alpha- and beta-rubromycin, were originally found as inhibitors of retroviral reverse transcriptase. We investigated the effects of these agents on DNA metabolic enzymes including DNA and RNA polymerases as retroviral reverse transcriptase is a kind of the polymerase. As expected, we found that alpha- and beta-rubromycin strongly inhibited not only the retroviral reverse transcriptase activity, but the activities of the mammalian DNA polymerases, telomerase and terminal deoxynucleotidyl transferase in vitro. These agents should therefore be classified as DNA polymerase inhibitors. The Ki values of alpha-rubromycin against nucleotide substrate were 0.66 and 0.17 microM for DNA polymerase alpha and beta (pol. alpha and beta), respectively, and those of beta-rubromycin was 2.40 and 10.5 microM, respectively. Alpha-rubromycin strongly inhibited the pol. beta activity, and showed the strongest pol. beta inhibitory effect reported to date. At least on pol. beta, alpha-rubromycin was suggested to bind to the active region competing with the nucleotide substrate, and subsequently inhibit the catalytic activity. alpha-Rubromycin directly competed with the nucleotide substrate, and indirectly but simultaneously and non-competitively disturbed the template-DNA interaction with pol. beta.
    背景与目标: : 醌类抗生素,α-和 β-红霉素,最初被发现作为逆转录病毒逆转录酶的抑制剂。我们研究了这些药物对包括DNA和RNA聚合酶在内的DNA代谢酶的影响,因为逆转录病毒逆转录酶是一种聚合酶。正如预期的那样,我们发现 α-和 β-红霉素不仅在体外强烈抑制逆转录病毒逆转录酶活性,而且在体外抑制哺乳动物DNA聚合酶,端粒酶和末端脱氧核苷酸转移酶的活性。因此,这些药物应归类为DNA聚合酶抑制剂。对于DNA聚合酶 α 和 β (pol α 和 β),α-红霉素对核苷酸底物的Ki值分别为0.66和0.17微米,β-红霉素的Ki值分别为2.40和10.5微米。Α-红霉素强烈抑制pol。Β 活性,并显示出最强的pol。迄今报告的 β 抑制作用。至少在pol上。建议将 β,α-红霉素与与核苷酸底物竞争的活性区域结合,并随后抑制催化活性。Α-红霉素直接与核苷酸底物竞争,并间接但同时和非竞争性地干扰了模板-DNA与pol的相互作用。β。
  • 【衰老对大鼠脑中烟碱和毒蕈碱自身受体功能的影响: 与突触前胆碱能标志物和结合位点的关系。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Araujo DM,Lapchak PA,Meaney MJ,Collier B,Quirion R
    BACKGROUND & AIMS: :The main objective of the present work was to determine whether the regulation of ACh release by nicotinic and muscarinic autoreceptors is compromised in the aged rat brain. For this, the effects of the nicotinic agonist N-methylcarbamylcholine (MCC) and the muscarinic-M2 antagonist AF-DX 116 on ACh release from brain slices of young (3-month-old), adult (9-month-old), and aged (27-month-old) rats were tested. The ability of MCC to enhance spontaneous ACh release in hippocampal, cerebral cortical, and cerebellar slices was only modestly altered with age. In contrast, the sensitivity of muscarinic autoreceptors in the aged hippocampus and cerebral cortex, but not the striatum, to blockade by the muscarinic-M2 antagonist AF-DX 116 was severely attenuated. To assess whether the age-related changes in cholinergic autoreceptor function may be due to deficits in presynaptic cholinergic markers, we tested whether choline acetyltransferase (ChAT) activity, basal and evoked ACh release, and nicotinic and muscarinic binding sites are altered in the aged rats. ChAT activity in forebrain regions was decreased in the aged compared to the young and mature adult rats. Furthermore, the potassium-evoked, but not the spontaneous, release of ACh was markedly depressed in striatal, hippocampal, and cortical slices of aged rats. The densities of nicotinic and muscarinic-M2 binding sites, assessed using 3H-MCC and 3H-AF-DX 116 as selective ligands, respectively, were markedly reduced in homogenates of the striatum, hippocampus, cerebral cortex, and thalamus of aged rats. In contrast, muscarinic-M1 sites, selectively labeled with 3H-pirenzepine, were not affected. Therefore, it appears that age-related decrements in ChAT activity and in muscarinic-M2, but not nicotinic, binding sites in the rat brain are reflected in a decreased function of muscarinic-M2 autoreceptors. However, the positive correlation between loss of ChAT activity, decreased muscarinic-M2 binding sites, and impaired muscarinic autoreceptor function is clearly tissue dependent.
    背景与目标: : 当前工作的主要目的是确定在老年大鼠大脑中烟碱和毒蕈碱自身受体对ACh释放的调节是否受到损害。为此,烟碱激动剂N-甲基氨基甲酰胆碱 (MCC) 和muscarinic-M2拮抗剂af-dx 116对从年轻 (3个月大),成人 (9个月大) 的大脑切片中释放ACh的影响,并测试了年龄 (27个月大) 的大鼠。MCC增强海马,大脑皮层和小脑切片中自发性ACh释放的能力仅随年龄而略有变化。相反,老年海马和大脑皮层 (而不是纹状体) 中毒蕈碱自身受体对muscarinic-M2拮抗剂af-dx 116阻断的敏感性严重减弱。为了评估胆碱能自身受体功能的年龄相关变化是否可能是由于突触前胆碱能标志物的缺陷引起的,我们测试了胆碱乙酰转移酶 (ChAT) 活性,基础和诱发的ACh释放以及烟碱和毒蕈碱结合位点是否在老年大鼠中改变。与年轻和成年大鼠相比,老年人的前脑区域聊天活性降低。此外,在老年大鼠的纹状体,海马和皮质切片中,钾诱发的ACh释放 (而不是自发释放) 明显抑制。分别使用3H-MCC和3H-AF-DX 116作为选择性配体评估的烟碱和muscarinic-M2结合位点的密度在老年大鼠的纹状体,海马,大脑皮层和丘脑的匀浆中显着降低。相反,用3h-哌仑西平选择性标记的muscarinic-M1位点不受影响。因此,似乎与年龄相关的ChAT活动和muscarinic-M2 (而不是烟碱) 结合位点的衰老反映在muscarinic-M2自身受体的功能降低中。然而,ChAT活性丧失,muscarinic-M2结合位点降低和毒蕈碱自身受体功能受损之间的正相关显然是组织依赖性的。

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