BACKGROUND & AIMS: Poly(1-vinyl-2-pyrrolidinone) (PVP) and copolymers of 1-vinyl-2-pyrrolidinone are insoluble in water when crosslinked but they can absorb very large amounts of water to become syringe-injectable hydrogels. Such gels have been investigated recently as potential substitutes for the vitreous humour in the eye. In this study, during the cytotoxic evaluation by sulforhodamine B colorimetric assay of variously crosslinked PVP gels, it was found that many of them showed protective/growth promoting effects on 3T3 mouse fibroblasts in static cultures, a phenomenon encountered previously only with aqueous solutions of a limited number of natural or synthetic polymers. Particularly, the gels crosslinked with diethylene glycol dimethacrylate (DEGDMA) induced a significant enhancement of cell proliferation, especially in serum-free cultures. No correlation between this effect and the essential gel properties (chemical composition, viscoelasticity and equilibrium water content) could be established. The study demonstrated that crosslinked PVP hydrogels showed a serum-like growth promoting effect on an anchorage-dependent cell line, which may be due to physical protection, inability of the insoluble gels to penetrate cell membranes, and their ability to mimic the extracellular matrix.

背景与目标： 聚 (1-乙烯基-2-吡咯烷酮) (PVP) 和1-乙烯基-2-吡咯烷酮的共聚物在交联时不溶于水，但它们可以吸收大量的水，成为可注射器注射的水凝胶。最近已经研究了这种凝胶作为眼睛玻璃体液的潜在替代品。在这项研究中，在通过sulforhodamine B比色法对各种交联的PVP凝胶进行细胞毒性评估期间，发现其中许多凝胶对静态培养中的3T3小鼠成纤维细胞表现出保护/促进生长的作用，这种现象以前仅在水溶液中遇到。有限数量的天然或合成聚合物。特别是，与二甘醇二甲基丙烯酸酯 (DEGDMA) 交联的凝胶可显着增强细胞增殖，尤其是在无血清培养物中。无法建立这种作用与基本凝胶特性 (化学成分，粘弹性和平衡水含量) 之间的相关性。研究表明，交联的PVP水凝胶对锚定依赖性细胞系表现出类似血清的生长促进作用，这可能是由于物理保护，不溶性凝胶无法穿透细胞膜以及它们模仿细胞外基质的能力。

BACKGROUND & AIMS: BACKGROUND:Several case reports have raised serious concerns about the safety of shoulder surgery in the beach-chair position, related to global cerebral hypoperfusion. We summarize our experiences with 15,014 cases of shoulder arthroscopy over an 11-year period. Our primary aim was to evaluate the incidence of intraoperative or immediate postoperative neurologic events and secondarily to relate other perioperative complications. METHODS:We searched our online deidentified departmental quality improvement and patient safety database for adverse outcomes associated with arthroscopic shoulder surgery performed in the beach-chair position for the 11-year period between April 2001 and November 2011, as well as our hospital-system database and a statewide database. This was compared with the total number of such cases, available from our department billing database. RESULTS:The total rate of adverse events was 0.37%. Neurologic abnormalities suggestive of acute cerebral ischemia or hemorrhage did not occur in the immediate perioperative period. One new neurologic deficit was reported, secondary to ischemic stroke, which occurred 24 hours after the surgery. The most frequent complications detected were unplanned return to care (0.067%), local anesthetic systemic toxicity (0.053%), and airway compromise requiring unplanned intubation (0.033%). Complications were infrequent and did not vary in incidence over the course of the study. CONCLUSIONS:This retrospective study suggests that intraoperative or immediate postoperative stroke is rare when surgery is conducted in beach-chair position in conjunction with regional anesthesia, propofol sedation, and spontaneous respiration via natural airway.

背景与目标：

BACKGROUND & AIMS: :Thrombosis is the main cause of failure of small-diameter synthetic vascular grafts when used for by-pass procedures. The development of bioresorbable vascular scaffolds with localized and sustained intra-luminal antithrombotic drug release could be considered a desirable improvement towards a valuable solution for this relevant clinical need. For this aim, we present the fabrication and characterization of aspirin-loaded electrospun poly(ε-caprolactone) tubular scaffolds as a vascular drug-delivery graft. Three different drug concentrations were considered (i.e., 1, 5 or 10 % w/w). Although a fibrous structure was clearly observed for all the collected scaffolds, aspirin content was directly implied in the final microstructure leading to a bimodal fiber diameter distribution and fused fibers at crossing-points (5 or 10 % w/w). Mechanical response highlighted a direct relationship for modulus and stress at break with the aspirin content, while the elongation at break was not remarkably different for the investigated cases. The temporal drug release was strongly dependent from the amount of loaded aspirin, reaching a steady state release after about 50 h. Finally, the adhesion assay confirmed the capability of the electrospun scaffolds to reduce platelet adhesion/aggregation onto aspirin loaded polymeric fibers. Aspirin-loaded electrospun tubular scaffold could represent a feasible candidate to develop a novel bioresorbable drug-releasing graft for small-diameter vessel replacements.

背景与目标： : 血栓形成是用于旁路手术时小直径合成血管移植物失败的主要原因。开发具有局部和持续的腔内抗血栓药物释放的生物可吸收血管支架可被认为是针对此相关临床需求的有价值解决方案的理想改进。为此，我们介绍了负载阿司匹林的电纺聚 (ε-己内酯) 管状支架作为血管药物递送移植物的制备和表征。考虑三种不同的药物浓度 (即1、5或10% w/w)。尽管对于所有收集的支架都清楚地观察到纤维结构，但在最终微结构中直接隐含阿司匹林含量，导致双峰纤维直径分布和在交叉点处的融合纤维 (5或10% w/w)。机械响应强调了模量和断裂应力与阿司匹林含量的直接关系，而断裂伸长率在所研究的情况下没有显着差异。暂时的药物释放强烈依赖于阿司匹林的载量，约50小时后达到稳定状态释放。最后，粘附试验证实了电纺支架减少血小板粘附/聚集在阿司匹林负载的聚合物纤维上的能力。阿司匹林负载的电纺管状支架可能是开发用于小直径血管置换的新型生物可吸收药物释放移植物的可行候选者。

BACKGROUND & AIMS: Inorganic arsenic is considered a human carcinogen based principally on epidemiological evidence. Unlike most initiating chemicals, arsenic is inactive or extremely weak in its ability to directly induce gene mutations. Arsenite has been shown, however, to enhance mutagenicity when present with other agents such as UV radiation. Synergistic potentiation of chromosomal damage has been shown with co-treatment with DNA-crosslinking agents. Arsenite at low concentrations is known to be highly selective in reacting with closely spaced (vicinal) dithiol groups in proteins. Poly(ADP-ribose) polymerase (PARP) is known to contain such vicinal dithiol groups. Stimulation of PARP is an immediate response of eukaryotic cells to DNA strand breaks and has been implicated in DNA repair. The effect of treatment with sodium arsenite on PARP activity was assessed as followsMolt-3 cells (a human T-cell lymphoma-derived cell line) in culture were treated for 24 h with concentrations of sodium arsenite ranging from 2.5 up to 25 microM. Speciation of inorganic arsenic and cell viability were determined. Cell cycle kinetics were measured by flow cytometry. Poly(ADP-ribose) synthesis was assayed using a palindromic decameric deoxynucleotide to stimulate enzyme activity. Results show that arsenite decreases PARP activity in a dose-dependent manner with an approximately 50% decrease in enzyme activity at 10 microM arsenite and 80% viability. The percent of cells in S-phase increases with increasing concentration of arsenite. These results provide further indication that arsenite may potentiate genetic damage through reaction with dithiols in DNA repair proteins such as PARP, perhaps resulting in interference with normal repair function.

背景与目标： 主要根据流行病学证据，无机砷被认为是人类致癌物。与大多数起始化学物质不同，砷在直接诱导基因突变的能力方面没有活性或极弱。然而，当与其他试剂 (例如紫外线辐射) 一起存在时，亚砷酸盐可以增强诱变性。与DNA交联剂共同处理已显示出染色体损伤的协同增强作用。众所周知，低浓度的亚砷酸盐在与蛋白质中紧密间隔的 (相邻) 二硫醇基团反应中具有很高的选择性。聚 (ADP-核糖) 聚合酶 (PARP) 已知包含此类邻二硫醇基团。刺激PARP是真核细胞对DNA链断裂的立即反应，并与DNA修复有关。用亚砷酸钠处理对PARP活性的影响进行评估，因为followsMolt-3培养物中的细胞 (人类T细胞淋巴瘤衍生的细胞系) 用2.5至25微米的亚砷酸钠浓度处理24小时。确定了无机砷的形态和细胞活力。通过流式细胞术测量细胞周期动力学。使用回文十聚脱氧核苷酸刺激酶活性测定聚 (ADP-核糖) 合成。结果表明，亚砷酸盐以剂量依赖性方式降低PARP活性，在10微米亚砷酸盐和80% 活力下酶活性降低约50%。S期细胞百分比随亚砷酸盐浓度的增加而增加。这些结果进一步表明，亚砷酸盐可能通过与DNA修复蛋白 (例如PARP) 中的二硫醇反应来增强遗传损伤，从而可能导致对正常修复功能的干扰。

BACKGROUND & AIMS: Using a melt-pressing technique, we produced a small solid cylinder containing cisplatin (CDDP) embedded in poly-d, l-lactic acid (CDDP-PLA). The in vitro release of CDDP from the polymer was examined in an immersion system. CDDP was released continuously for more than four weeks with no initial burst. Drug distribution for CDDP-PLA was compared with CDDP solution (CDDP-SOL) by subcutaneous administration into the back of rats. In the CDDP-PLA group, a high concentration of CDDP was maintained in the subcutaneous tissues near the implants for 20 days. However, in the CDDP-SOL group, the concentration of CDDP was low by 10 days after drug administration. CDDP-PLA may become a useful tool in locoregional chemotherapy as a solid type of drug delivery system with longlasting release.

背景与目标： 使用熔融压制技术，我们生产了一个小的固体圆柱体，其中包含嵌入聚d，l-乳酸 (CDDP-PLA) 中的顺铂 (CDDP)。在浸没系统中检查了CDDP从聚合物中的体外释放。CDDP连续发布超过四个星期，没有初始爆发。通过皮下给药到大鼠背部，将CDDP-PLA的药物分布与CDDP溶液 (CDDP-SOL) 进行比较。在cddp-pla组中，在植入物附近的皮下组织中维持高浓度的CDDP 20天。然而，在CDDP-SOL组中，给药后10天CDDP的浓度较低。Cddp-pla作为一种具有持久释放的固体药物输送系统，可能成为局部化疗的有用工具。

BACKGROUND & AIMS: :A biomimetic approach involving the self-assembly of mineral within the pores of three-dimensional porous polymer scaffolds is a promising strategy to integrate advantages of inorganic and organic phases into a single material for hard tissue engineering. Such a material enhances the ability of progenitor cells to differentiate down an osteoblast lineage in vitro and in vivo, compared with polymer scaffolds. The mechanisms regulating mineral formation in this one-step process, however, are poorly understood, especially the effects of ionic activity products (IP) of the mineralizing solution and incubation time. The aims of this study were to define the structure and composition of mineral formed within the pores of biodegradable polymer scaffolds as a function of IP and time. Three-dimensional poly(lactide-co-glycolide) scaffolds were fabricated by solvent casting/particulate leaching and incubated for 4-16 days in six variants of simulated body fluid whose IPs were varied by adjusting ionic concentrations. Scanning electron microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy demonstrated the formation of carbonated apatite with sub-micrometer sized crystals that grew into spherical globules extending out of the scaffold pore surfaces. As IP increased, more mineral grew on the scaffold pore surfaces, but the apatite became less crystalline and the Ca/P molar ratio decreased from 1.63 +/- 0.005 to 1.51 +/- 0.002. Since morphology, composition, and structure of mineral are factors that affect cell function, this study demonstrates that the IP of the mineralizing solution is an important modulator of material properties, potentially leading to enhanced control of cell function.

背景与目标： : 一种仿生方法，涉及矿物在三维多孔聚合物支架的孔中自组装，是一种将无机和有机相的优势整合到用于硬组织工程的单一材料中的有前途的策略。与聚合物支架相比，这种材料增强了祖细胞在体外和体内分化成骨细胞谱系的能力。然而，对这种一步过程中调节矿物形成的机制知之甚少，尤其是矿化溶液的离子活性产物 (IP) 和孵育时间的影响。这项研究的目的是定义在可生物降解的聚合物支架的孔中形成的矿物的结构和组成随IP和时间的变化。通过溶剂浇铸/颗粒浸出制备三维聚 (丙交酯-共-乙交酯) 支架，并在六种模拟体液变体中孵育4-16天，其IPs通过调节离子浓度而变化。扫描电子显微镜，x射线衍射和傅立叶变换红外光谱证明了碳酸磷灰石的形成，其亚微米尺寸的晶体长成球形小球，延伸出支架孔表面。随着IP的增加，更多的矿物在支架孔表面上生长，但是磷灰石变得不那么结晶，并且Ca/P摩尔比从1.63 +/- 0.005降低到1.51 +/- 0.002。由于矿物的形态，组成和结构是影响细胞功能的因素，因此这项研究表明，矿化溶液的IP是材料特性的重要调节剂，有可能导致对细胞功能的增强控制。

BACKGROUND & AIMS: An essential cellular factor for nuclear mRNA export called Mex67p which has homologous proteins in human and Caenorhabditis elegans was identified through its genetic interaction with nucleoporin Nup85p. In the thermosensitive mex67-5 mutant, poly(A)+ RNA accumulates in intranuclear foci shortly after shift to the restrictive temperature, but NLS-mediated nuclear protein import is not inhibited. In vivo, Mex67p tagged with green fluorescent protein (GFP) is found at the nuclear pores, but mutant mex67-5-GFP accumulates in the cytoplasm. Upon purification of poly(A)+ RNA derived from of UV-irradiated yeast cells, Mex67p, but not nucleoporins Nup85p and Nup57p, was crosslinked to mRNA. In a two-hybrid screen, a putative RNA-binding protein with RNP consensus motifs was found to interact with the Mex67p carboxy-terminal domain. Thus, Mex67p is likely to participate directly in the export of mRNA from the nucleus to the cytoplasm.

背景与目标： 通过与核孔蛋白Nup85p的遗传相互作用，鉴定了一种用于核mRNA输出的必需细胞因子Mex67p，该因子在人和秀丽隐杆线虫中具有同源蛋白。在热敏mex67-5突变体中，poly(A) RNA在转移到限制性温度后不久就在核内病灶中积累，但是NLS介导的核蛋白导入没有被抑制。在体内，在核孔处发现了用绿色荧光蛋白 (GFP) 标记的Mex67p，但是突变mex67-5-GFP在细胞质中积累。纯化源自紫外线照射的酵母细胞的poly(A) RNA后，Mex67p而不是核孔蛋白Nup85p和Nup57p与mRNA交联。在双杂交筛选中，发现具有RNP共有基序的推定RNA结合蛋白与Mex67p羧基末端结构域相互作用。因此，Mex67p可能直接参与mRNA从细胞核到细胞质的输出。

BACKGROUND & AIMS: In addition to its use for intravenous (I.V.) anesthesia, ketamine can provide pain relief in humans when administered spinally. To elucidate the mechanisms of intrathecal (I.T.) ketamine analgesia, we observed differences in the effects of I.V. and I.T. ketamine on intraspinal evoked potentials (ISEPs) in 28 dogs anesthetized with pentobarbital. Bipolar extradural electrodes were inserted at the cervical and lumbar regions of the spinal cord for recording descending ISEPs represented by the two negative deflections, Waves I and II. I.V. ketamine 2 and 10 mg/ kg did not affect the amplitude and latency of Wave I, whereas the large dose (10 mg/kg) significantly decreased the amplitude but not the latency of Wave II. I.T. ketamine 1 and 5 mg/kg caused significant dose-dependent decreases in both Wave I and II amplitudes and prolongations of both Wave I and II latencies. These I.T. effects on ISEPs are consistent with previous in vitro observations that ketamine blocks axonal conduction. We conclude that axonal conduction block may contribute to the analgesic mechanism of I.T. ketamine.

背景与目标： 除了用于静脉注射 (静脉注射) 麻醉外，氯胺酮还可以减轻脊柱注射时的疼痛。为了阐明鞘内 (I.T.) 氯胺酮镇痛的机制，我们观察了静脉注射和静脉注射氯胺酮对28只用戊巴比妥麻醉的狗的椎管内诱发电位 (ISEPs) 的影响。将双极硬膜外电极插入脊髓的颈椎和腰椎区域，以记录由两个负偏转波I和II表示的下降ISEPs。静脉内氯胺酮2和10 mg/kg不影响第I波的振幅和潜伏期，而大剂量 (10 mg/kg) 显着降低了振幅，但不影响第II波的潜伏期。I.T. 氯胺酮1和5 mg/kg引起I和II波振幅的显着剂量依赖性降低，以及I和II波潜伏期的延长。这些I.T. 对ISEPs的影响与先前的体外观察结果一致，即氯胺酮可阻断轴突传导。我们得出的结论是，轴突传导阻滞可能有助于i.T.氯胺酮的镇痛机制。

BACKGROUND & AIMS: :The time course of ethylene biosynthesis and perception was investigated in ripening peach fruit (Prunus persica) following treatments with the polyamines putrescine (Pu) and spermidine (Sd), and with aminoethoxyvinylglycine (AVG). Fruit treatments were performed in planta. Ethylene production was measured by gas chromatography, and polyamine content by high-performance liquid chromatography; expression analyses were performed by Northern blot or real-time polymerase chain reaction. Differential increases in the endogenous polyamine pool in the epicarp and mesocarp were induced by treatments; in both cases, ethylene production, fruit softening and abscission were greatly inhibited. The rise in 1-aminocyclopropane-1-carboxylate oxidase (PpACO1) mRNA was counteracted and delayed in polyamine-treated fruit, whereas transcript abundance of ethylene receptors PpETR1 (ethylene receptor 1) and PpERS1 (ethylene sensor 1) was enhanced at harvest. Transcript abundance of arginine decarboxylase (ADC) and S-adenosylmethionine decarboxylase (SAMDC) was transiently reduced in both the epicarp and mesocarp. AVG, here taken as a positive control, exerted highly comparable effects to those of Pu and Sd. Thus, in peach fruit, increasing the endogenous polyamine pool in the epicarp or in the mesocarp strongly interfered, both at a biochemical and at a biomolecular level, with the temporal evolution of the ripening syndrome.

背景与目标： : 在用多胺腐胺 (Pu) 和亚精胺 (Sd) 以及氨基乙氧基乙烯基甘氨酸 (AVG) 处理后，研究了成熟桃果实 (Prunus persica) 中乙烯生物合成和感知的时间过程。在植物中进行水果处理。通过气相色谱法测量乙烯产量，通过高效液相色谱法测量多胺含量; 通过Northern印迹或实时聚合酶链反应进行表达分析。处理可诱导外皮和中果皮中内源多胺库的差异增加; 在这两种情况下，乙烯的产生，果实的软化和脱落均受到极大抑制。在多胺处理的水果中，1-氨基环丙烷-1-羧酸氧化酶 (PpACO1) mRNA的上升被抵消并延迟，而乙烯受体PpETR1 (乙烯受体1) 和pper1 (乙烯传感器1) 的转录物丰度在收获时增强。精氨酸脱羧酶 (ADC) 和S-腺苷甲硫氨酸脱羧酶 (SAMDC) 的转录物丰度在表皮和中果皮中均瞬时降低。AVG作为阳性对照，与Pu和Sd具有高度可比的作用。因此，在桃子果实中，在生化和生物分子水平上，内源性多胺库的增加会强烈干扰成熟综合征的时间演变。

BACKGROUND & AIMS: :The intricate problems associated with the delivery and various unnecessary in vivo transitions of proteins and drugs needs to be tackled soon to be able to exploit the myriad of putative therapeutics created by the biotechnology boom. Nanomedicine is one of the most promising applications of nanotechnology in the field of medicine. It has been defined as the monitoring, repair, construction and control of human biological systems at the molecular level using engineered nanodevices and nanostructures. These nanostructured medicines will eventually turn the world of drug delivery upside down. PEGylation (i.e. the attachment of polyethylene glycol to proteins and drugs) is an upcoming methodology for drug development and it has the potential to revolutionise medicine by drastically improving the pharmacokinetic and pharmacodynamic properties of the administered drug. This article provides a total strategy for improving the therapeutic efficacy of various biotechnological products in drug delivery. This article also presents an extensive analysis of most of the PEGylated proteins, peptides and drugs, together with extensive clinical data. Nanomedicines and PEGylation, the latest offshoots of nanotechnology will definitely pave a way in the field of drug delivery where targeted delivery, formulation, in vivo stability and retention are the major challenges.

背景与目标： : 与蛋白质和药物的递送和各种不必要的体内转化相关的复杂问题需要尽快解决，以便能够利用生物技术繁荣带来的无数推定疗法。纳米医学是纳米技术在医学领域最有前途的应用之一。它被定义为使用工程纳米设备和纳米结构在分子水平上监视，修复，构建和控制人类生物系统。这些纳米结构的药物最终将颠覆药物输送的世界。聚乙二醇化 (即聚乙二醇与蛋白质和药物的结合) 是药物开发的一种即将到来的方法，它有可能通过大幅改善所给药药物的药代动力学和药效学特性来彻底改变药物。本文提供了提高各种生物技术产品在药物输送中的治疗效果的总体策略。本文还对大多数聚乙二醇化蛋白，肽和药物进行了广泛的分析，并提供了广泛的临床数据。纳米药物和聚乙二醇化是纳米技术的最新分支，无疑将在药物递送领域铺平道路，其中靶向递送，配方，体内稳定性和保留是主要挑战。

BACKGROUND & AIMS: :Our goal was to identify the role of poly(ADP-ribose) polymerase (PARP) in cerebrovascular dysfunction in Type 1 diabetes mellitus (T1D). In a first series of studies, rats were assigned to nondiabetic and diabetic (streptozotocin; 50 mg/kg IP) groups. Two to three months after injection of streptozotocin, we examine in vivo responses of pial arterioles to nitric oxide synthase (NOS)-dependent (adenosine diphosphate (ADP), acetylcholine and histamine) and -independent (nitroglycerin) agonists. After the initial examination of reactivity to the agonists, we treated pial arterioles acutely with an inhibitor of PARP (PJ-34; 1 microM), and then we again examined responses to the agonists. In a second series of studies, we examine superoxide production (lucigenin chemiluminescence) by parietal cortex tissue in nondiabetic and diabetic rats. We found that dilation of pial arterioles in response to ADP, acetylcholine and histamine, but not to nitroglycerin, was impaired in diabetic compared to nondiabetic rats. In addition, although PJ-34 did not alter responses in nondiabetic rats, PJ-34 alleviated T1D-induced impairment of NOS-dependent vasodilation. We also found that basal production of superoxide was increased in diabetic compared to nondiabetic rats and that PJ-34 decreased this basal production of superoxide. Our findings suggest that T1D impairs NOS-dependent reactivity of cerebral arterioles by a mechanism that appears to be related to the formation of superoxide via activation of PARP.

背景与目标： : 我们的目标是确定聚 (ADP-核糖) 聚合酶 (PARP) 在1型糖尿病 (T1D) 的脑血管功能障碍中的作用。在第一系列研究中，将大鼠分为非糖尿病组和糖尿病组 (链脲佐菌素; 50 mg/kg IP)。注射链脲佐菌素后两到三个月，我们检查了小动脉对一氧化氮合酶 (NOS) 依赖性 (二磷酸腺苷 (ADP)，乙酰胆碱和组胺) 和非依赖性 (硝酸甘油) 激动剂的体内反应。在初步检查对激动剂的反应性之后，我们用PARP抑制剂 (PJ-34; 1 microM) 急性治疗了小动脉，然后我们再次检查了对激动剂的反应。在第二系列研究中，我们检查了非糖尿病和糖尿病大鼠顶叶皮质组织产生的超氧化物 (荧光素化学发光)。我们发现，与非糖尿病大鼠相比，糖尿病大鼠对ADP，乙酰胆碱和组胺 (但对硝酸甘油) 的反应会减弱小动脉的扩张。此外，尽管PJ-34没有改变非糖尿病大鼠的反应，但PJ-34减轻了NOS依赖性血管舒张的T1D-induced损害。我们还发现，与非糖尿病大鼠相比，糖尿病大鼠中超氧化物的基础产量增加，PJ-34降低了超氧化物的基础产量。我们的发现表明，T1D通过一种机制损害了脑小动脉的NOS依赖性反应性，该机制似乎与通过PARP活化形成超氧化物有关。

BACKGROUND & AIMS: :Fractionation of rat L6 myoblast histone H4 mRNA into its three component subspecies revealed that one of the major subspecies (H4-1) contained poly(A). The unique poly(A)+ H4 mRNA makes up about 8% of the total polysomal H4 mRNA population detected. Unlike the poly(A)- histone mRNAs, whose levels are reduced by greater than 95% when myoblasts differentiate into myotubes, the poly(A)+ subspecies is reduced by only 70%. The poly(A)+ H4 mRNA from myotubes incubated with actinomycin D decays with a half-life of 37-42 min, which is similar to that obtained for the poly(A)- H4 mRNAs in myoblasts. Both the poly(A)+ and poly(A)- subspecies decay at an increased rate after inhibition of DNA synthesis. In myoblasts the poly(A)+ H4 mRNA exists almost exclusively in the polysomal compartment (greater than 95%) with little (less than 5%) in the free ribonucleoprotein (mRNA-protein or mRNP) complex compartment of the cell. Poly(A)- histone H4 mRNA subspecies, on the other hand, are distributed with approximately 80% in the polysomal compartment and 20% in the free mRNP complex compartment. The unique poly(A)+ H4 mRNA is unusual, not only in that it contains poly(A) but also in its behavior compared to poly(A)- H4 mRNAs during terminal differentiation.

背景与目标： : 将大鼠L6成肌细胞组蛋白H4 mRNA分离成其三个组成亚种，表明主要亚种 (H4-1) 之一含有poly(A)。独特的poly(A)+ h4mrna构成了检测到的总多体h4mrna群体的约8%。与当成肌细胞分化为肌管时其水平降低大于95% 的聚 (A)-组蛋白mrna不同，聚 (A) 亚种仅降低70%。与放线菌素d孵育的肌管中的poly(A) H4 mRNA衰变，半衰期为37-42分钟，这与在成肌细胞中获得的poly (a)- H4 mRNA相似。在抑制DNA合成后，poly(A) 和聚 (A) 亚种均以增加的速率衰减。在成肌细胞中，poly(A) h4mrna几乎仅存在于多体区室 (大于95%) 中，很少 (小于5%) 存在于细胞的游离核糖核蛋白 (mRNA-蛋白或mRNP) 复合区室中。另一方面，聚 (A)-组蛋白h4mrna亚种在多体区室中分布有大约80%，而在游离的mRNP复合物区室中20%。独特的poly(A) H4 mRNA是不寻常的，不仅因为它包含poly(A)，而且在末端分化过程中与poly(A)- H4 mRNA相比，其行为也是如此。

BACKGROUND & AIMS: :We studied the effects of AVG, ACC, and ethylene on the process of adventitious bud formation in vitro from bulb-scale explants of Lilium speciosum Thunb., cv. Rubrum nr. 10. AVG inhibited plantlet regeneration, especially at non-basal sites. The effects of AVG were counteracted by ACC and TIBA. Ethylene, applied in the first 3 or 7 days of the culture period in a concentration of 1 or 10 ppm, caused an increase in bud number per explant and suppressed the predominantly basipetal polarity of the regeneration sites. Ethylene increased the sensitivity of the tissue to exogenous auxin. A model is proposed showing the influence of ethylene, its biosynthetic pathway, and the other modifying factors on the regulation of plantlet induction in bulb-scale explants by auxin.

背景与目标： : 我们研究了AVG，ACC和乙烯对百合鳞茎鳞茎外植体体外不定芽形成过程的影响。Rubrum nr。10. AVG抑制了植株的再生，尤其是在非基础部位。ACC和TIBA抵消了AVG的影响。在培养的前3或7天以1或10 ppm的浓度施用乙烯，导致每个外植体的芽数增加，并抑制了再生位点的主要基本极性。乙烯增加了组织对外源生长素的敏感性。提出了一个模型，该模型显示了乙烯，其生物合成途径以及其他修饰因素对生长素对鳞茎规模外植体中小植株诱导的影响。

BACKGROUND & AIMS: :Members of the CCAAT/enhancer binding protein (C/EBP) family of transcription factors have been reported to be up-regulated in Alzheimer's disease. In the present study, we have investigated the effects of amyloid-beta (Abeta) peptides on C/EBPbeta and C/EBPdelta, previously shown to be induced by inflammatory stimuli in glial cells. Surprisingly, electrophoretic mobility shift assay showed that both Abeta(1-42) and Abeta(25-35) blocked C/EBP activation induced by the inflammatory cytokine interleukin-1beta (IL-1beta) or lipopolysaccharide (LPS) in mixed primary glial cell cultures from rat. Abeta also blocked IL-1beta- or LPS-induced C/EBP protein levels. The most prominent effects were observed on DNA binding activity and protein levels of C/EBPdelta. Our results demonstrate a dysregulation of C/EBP when glial cells are activated in the presence of Alzheimer Abeta peptides.

背景与目标： : 据报道，转录因子CCAAT/增强子结合蛋白 (C/EBP) 家族的成员在阿尔茨海默氏病中被上调。在本研究中，我们研究了淀粉样 β (Abeta) 肽对C/eppbeta和C/eppdelta的影响，这些蛋白先前被证明是由神经胶质细胞中的炎症刺激诱导的。令人惊讶的是，电泳迁移率变化测定表明，在来自大鼠的混合原代神经胶质细胞培养物中，Abeta(1-42) 和Abeta(25-35) 都阻断了由炎性细胞因子interleukin-1beta (IL-1beta) 或脂多糖 (LPS) 诱导的C/EBP激活。Abeta还阻断IL-1beta或LPS诱导的C/EBP蛋白水平。观察到对C/eppdelta的DNA结合活性和蛋白质水平最显着的影响。我们的结果表明，当存在阿尔茨海默氏病 β 肽时，神经胶质细胞被激活时，C/EBP失调。

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。