BACKGROUND & AIMS: :In 4 experiments, the authors investigated the reversal of spatial congruency effects when participants concurrently practiced incompatible mapping rules (J. G. Marble & R. W. Proctor, 2000). The authors observed an effect of an explicit spatially incompatible mapping rule on the way numerical information was associated with spatial responses. The authors also observed an effect of an incompatible numerical mapping rule (if smaller than 5, press right; if larger than 5, press left) on the Simon effect. This effect was observed only when both tasks used the same effectors. The results point to a shared spatial representation for explicit spatial information (locations) and implicit spatial information (numbers).

背景与目标： ：在4个实验中，作者研究了参与者同时练习不兼容的映射规则时空间一致性效果的逆转（J. G. Marble和R. W. Proctor，2000）。作者观察到明确的空间不兼容映射规则对数字信息与空间响应相关联的方式的影响。作者还观察到不兼容的数字映射规则（如果小于5，请按向右；如果大于5，请按向左）对西蒙效果的影响。仅当两个任务使用相同的效应器时，才观察到这种效果。结果指向用于显式空间信息（位置）和隐式空间信息（数字）的共享空间表示。

BACKGROUND & AIMS: :The hypoxic environment in tumor is reported to play an important role in pancreatic cancer progression. The interaction between stromal and cancer cells also contributes to the malignant behavior of pancreatic cancer. In the present study, we investigated whether hypoxic stimulation affects stromal as well as pancreatic cancer cells. Our findings demonstrated that hypoxia remarkably elevated the HIF-1alpha expression in both pancreatic cancer (PK8) and fibroblast cells (MRC5). Hypoxic stimulation accelerated the invasive activity of PK8 cells, and invasiveness was thus further accelerated when the hypoxic PK8 cells were cultured with conditioned medium prepared from hypoxic MRC5 cells (hypoxic conditioned medium). MMP-2, MMP-7, MT1-MMP and c-Met expressions were increased in PK8 cells under hypoxia. Hypoxic stimulation also increased the hepatocyte growth factor (HGF) secretion from MRC5 cells, which led to an elevation of c-Met phosphorylation in PK8 cells. Conversely, the elevated cancer invasion, MMP activity and c-Met phosphorylation of PK8 cells were reduced by the removal of HGF from hypoxic conditioned medium. In immunohistochemical study, the HIF-1alpha expression was observed in surrounding stromal as well as pancreatic cancer cells, thus indicating hypoxia exists in both of cancer and stromal cells. Moreover, the stromal HGF expression was found to significantly correlate with not only the stromal HIF-1alpha expression but also the c-Met expression in cancer cells. These results indicate that the hypoxic environment within stromal as well as cancer cells activates the HGF/c-Met system, thereby contributing to the aggressive invasive features of pancreatic cancer.

背景与目标： ：据报道肿瘤中的低氧环境在胰腺癌的进展中起重要作用。基质细胞与癌细胞之间的相互作用也有助于胰腺癌的恶性行为。在本研究中，我们调查了低氧刺激是否影响基质以及胰腺癌细胞。我们的研究结果表明，缺氧显着提高了胰腺癌（PK8）和成纤维细胞（MRC5）中HIF-1alpha的表达。低氧刺激加速了PK8细胞的侵袭活性，因此，当用由低氧MRC5细胞制备的条件培养基（低氧条件培养基）培养低氧PK8细胞时，侵袭性进一步加快。在缺氧条件下，PK8细胞中MMP-2，MMP-7，MT1-MMP和c-Met表达增加。缺氧刺激还增加了MRC5细胞的肝细胞生长因子（HGF）分泌，这导致PK8细胞中c-Met磷酸化的升高。相反，通过从低氧条件培养基中去除HGF，可以降低PK8细胞的癌浸润，MMP活性和c-Met磷酸化水平的升高。在免疫组织化学研究中，在周围的基质细胞和胰腺癌细胞中均观察到了HIF-1alpha的表达，因此表明在癌细胞和基质细胞中均存在缺氧。此外，发现基质HGF表达不仅与癌细胞中的基质HIF-1α表达而且与c-Met表达显着相关。这些结果表明基质以及癌细胞内的低氧环境激活了HGF / c-Met系统，从而促进了胰腺癌的侵袭性侵袭性特征。

BACKGROUND & AIMS: :A transcript (RNA I) from ColE1 inhibits initiation of replication of the plasmid DNA by binding to the precursor of the primer RNA (RNA II). The ability of RNA I to inhibit replication is altered by the presence of a plasmid-specified small protein, Rom. In vitro, RNA I binds to RNA II to form a very unstable complex, C*. Binding of a single molecule of Rom converts C* to a more stable complex, Cm*. Each of these complexes, C* or Cm*, transforms to a more stable complex, C** or Cm**, respectively. While formation of complex C* or Cm* is inferred from the inhibition of binding caused by a second RNA I species, that of complex C** or Cm** is detected by alteration of RNase sensitivity. Complex C* converts to complex Cm* very rapidly upon addition of Rom to the medium and complex Cm* converts to complex C* very rapidly by removal of Rom from the medium. On the other hand, complexes C** and Cm** do not rapidly interconvert, but can eventually transform to the same stable final product. Thus, Rom affects binding of RNA I to RNA II through conversion of a very unstable early intermediate to a more stable complex, creating a second pathway for their stable binding.

背景与目标： ：来自ColE1的转录本（RNA I）通过与引物RNA（RNA II）的前体结合，抑制质粒DNA复制的开始。质粒指定的小蛋白质Rom的存在改变了RNA I抑制复制的能力。在体外，RNA I与RNA II结合形成非常不稳定的复合物C *。 Rom单个分子的结合将C *转化为更稳定的复合物Cm *。这些复合物C *或Cm *分别转换为更稳定的复合物C **或Cm **。虽然可以通过抑制第二种RNA I物种的结合来推断复合物C *或Cm *的形成，但可以通过改变RNA酶的敏感性来检测复合物C **或Cm **的形成。在向培养基中添加Rom时，复合物C *非常迅速地转化为复合物Cm *，通过从培养基中去除Rom，复合物Cm *非常迅速地转化为复合物C *。另一方面，复合物C **和Cm **不会快速相互转换，但最终可以转换为相同的稳定最终产物。因此，Rom通过将非常不稳定的早期中间体转化为更稳定的复合物，从而影响RNA I与RNA II的结合，从而为它们的稳定结合创造了第二条途径。

BACKGROUND & AIMS: The amino-terminal segment of the membrane-anchored subunit of influenza hemagglutinin (HA) plays a crucial role in membrane fusion and, hence, has been termed the fusion peptide. We have studied the secondary structure, orientation, and effects on the bilayer structure of synthetic peptides corresponding to the wild-type and several fusogenic and nonfusogenic mutants with altered N-termini of the influenza HA fusion peptide by fluorescence, circular dichroism, and Fourier transform infrared spectroscopy. All peptides contained segments of alpha-helical and beta-strand conformation. In the wild-type fusion peptide, 40% of all residues were in alpha-secondary and 30% in beta-secondary structures. By comparison, the nonfusogenic peptides exhibited larger beta/alpha secondary structure ratios. The order parameters of the helices and the amide carbonyl groups of the beta-strands of the wild-type fusion peptide were measured separately, based on the infrared dichroism of the respective absorption bands. Order parameters in the range 0.1-0.7 were found for both segments of the wild-type peptide, which indicates that they are most likely aligned at oblique angles to the membrane normal. The nonfusogenic but not the fusogenic peptides induced splitting of the infrared absorption band at 1735 cm(-1), which is assigned to stretching vibrations of the lipid ester carbonyl bond. This splitting, which reports on an alteration of the hydrogen bonds formed between the lipid ester carbonyls and water and/or hydrogen-donating groups of the fusion peptides, correlated with the beta/alpha ratio of the peptides, suggesting that unpaired beta-strands may replace water molecules and hydrogen-bond to the lipid ester carbonyl groups. The profound structural changes induced by single amino acid replacements at the extreme N-terminus of the fusion peptide further suggest that tertiary or quaternary structural interactions may be important when fusion peptides bind to lipid bilayers.

背景与目标： 流感血凝素（HA）的膜锚定亚基的氨基末端片段在膜融合中起着至关重要的作用，因此被称为融合肽。我们已经通过荧光，圆二色性和傅里叶变换研究了对应于野生型和几个融合和非融合突变体的流感病毒HA融合肽的N末端改变的二级肽的二级结构，方向及其对双层肽结构的影响。红外光谱。所有肽都包含α-螺旋和β-链构象的区段。在野生型融合肽中，所有残基的40％在α-二级结构中，而30％在β-二级结构中。相比之下，非融合肽表现出较大的β/α二级结构比。基于各个吸收带的红外二色性，分别测量野生型融合肽的β链的螺旋和酰胺羰基的有序参数。对于野生型肽的两个片段，发现有序参数在0.1-0.7范围内，这表明它们最有可能以与膜法线倾斜的角度排列。非融合肽而非融合肽诱导了1735 cm（-1）处的红外吸收带的分裂，这被分配给了脂质酯羰基键的拉伸振动。该分裂报告了脂质酯羰基与融合肽的水和/或供氢基团之间形成的氢键的改变，与肽的β/α比率相关，表明未配对的β链可能取代水分子，并与脂质酯的羰基氢键合。融合肽极端N端由单个氨基酸置换引起的深刻结构变化进一步表明，当融合肽结合脂质双层时，三级或四级结构相互作用可能很重要。

BACKGROUND & AIMS: :Despite years of use as commercial herbicides, it is still unclear how dinitroanilines interact with tubulin, how they cause microtubule disassembly, and why they are selectively active against plant and protozoan tubulin. In this work, through a series of computational studies, a common binding site of oryzalin, trifluralin, and GB-II-5 on apicomplexan and kinetoplastid alpha-tubulin is proposed. Furthermore, to investigate how dinitroanilines affect tubulin dynamics, molecular dynamics simulations of Leishmania alpha-tubulin with and without a bound dinitroaniline are performed. The results obtained provide insight into the molecular mechanism by which these compounds interact with tubulin and function to prevent microtubule assembly. Finally, to aid in the design of effective parasitic microtubule inhibitors, several novel dinitroaniline analogues are evaluated. The location of the binding site and the relative binding affinities of the dinitroanilines all agree well with experimental data.

背景与目标： 尽管多年用作商业除草剂，但仍不清楚二硝基苯胺如何与微管蛋白相互作用，它们如何引起微管分解以及为什么它们对植物和原生动物微管蛋白具有选择性活性。在这项工作中，通过一系列的计算研究，提出了在稻草复合物和运动质体α-微管蛋白上，米杂列宁，三氟拉林和GB-II-5的共同结合位点。此外，为了研究二硝基苯胺如何影响微管蛋白动力学，进行了结合和不结合二硝基苯胺的利什曼原虫α-微管蛋白的分子动力学模拟。获得的结果提供了对这些化合物与微管蛋白相互作用并防止微管装配的分子机制的深入了解。最后，为帮助设计有效的寄生微管抑制剂，对几种新型的二硝基苯胺类似物进行了评估。二硝基苯胺的结合位点的位置和相对结合亲和力都与实验数据很好地吻合。

BACKGROUND & AIMS: :In order to investigate the mode of interaction between the N-quarternized cytosine base and the aromatic amino acid, the crystal structure of the 3-methyl-cytidine-5'-monophosphate:tryptamine complex was analyzed by X-ray diffraction. The complex crystals were stabilized by extensive hydrogen bond formations in which eight independent water molecules per complex pair participated. A prominent stacking interaction, characterized by a parallel alignment of both rings with a separation distance of ca. 3.4 A, was observed between the cytosine base and the indole ring. Combining the present results with X-ray crystallographic data on the adenine--and guanine--aromatic amino acid interactions, we summarize the structural characteristics observed in the stacking interaction of the N-quarternized nucleic acid base with the aromatic amino acid and discuss their biological implications, especially in connection with the significance of N-protonation of nucleic acid base for selective recognition by protein.

背景与目标： ：为了研究N-季铵化的胞嘧啶碱基与芳族氨基酸之间的相互作用方式，通过X射线衍射分析了3-甲基胞苷-5'-单磷酸酯：色胺的配合物的晶体结构。复杂的晶体通过广泛的氢键形成而稳定，其中每个复杂对有八个独立的水分子参与。突出的堆叠相互作用，其特征在于两个环的平行排列的间隔距离为ca。在胞嘧啶碱基和吲哚环之间观察到3.4A。将当前结果与腺嘌呤-鸟嘌呤-芳族氨基酸相互作用的X射线晶体学数据相结合，我们总结了在N-季铵化核酸碱基与芳族氨基酸的堆叠相互作用中观察到的结构特征，并讨论了它们的结构特征。生物学意义，特别是与核酸碱基的N质子化对于蛋白质选择性识别的意义有关。

BACKGROUND & AIMS: :Type 2 diabetes mellitus is the most common form of diabetes that occurs in both human and nonhuman primates. Although spontaneously diabetic nonhuman primates are used extensively in diabetic related research and are a proven valuable tool for the study of the natural history of diabetes, little is known about the key factors that can cause this metabolic disorder and the preventative measures that could be employed to minimize the consequences of diabetes. Using a model of developing and untreated diabetes, this study describes the effects of housing arrangement (socially group- versus individually single-housed), exercise, diet, age, and sex on fasting plasma glucose, key lipids associated with diabetes, and bodyweight in two large cohorts of nonhuman primates. Key findings include exercise/housing arrangement's contribution to significant differences in bodyweight, levels of fasting plasma glucose, total cholesterol, and high- and low-density lipoproteins. Age also had profound effects on glucose, triglyceride and high-density lipoproteins, particularly in single-caged animals. Moreover, females had higher fasting glucose, total cholesterol and triglyceride levels than male counterparts within the same housing situations. These factors may be critical to identifying preventive measures that could eventually be used to minimize obesity and diabetes in humans.

背景与目标： 2型糖尿病是人类和非人类灵长类动物中最常见的糖尿病形式。尽管自发性糖尿病非人类灵长类动物在糖尿病相关研究中被广泛使用，并且是研究糖尿病自然史的一种被证明有价值的工具，但对于引起这种代谢紊乱的关键因素以及可以采取的预防措施知之甚少尽量减少糖尿病的后果。本研究使用发展中的糖尿病和未经治疗的糖尿病模型，描述了住房安排（集体居住与个人独居），运动，饮食，年龄和性别对空腹血糖，糖尿病相关的主要脂质和体重的影响。两个大型的非人类灵长类动物。主要发现包括运动/住房安排对体重，空腹血糖水平，总胆固醇以及高密度和低密度脂蛋白的显着差异的贡献。年龄对葡萄糖，甘油三酸酯和高密度脂蛋白也有深远的影响，特别是在单笼动物中。此外，在相同的居住环境下，女性的空腹血糖，总胆固醇和甘油三酸酯水平高于男性。这些因素对于确定预防措施至关重要，这些预防措施最终可用于最大程度地减少人类的肥胖和糖尿病。

BACKGROUND & AIMS: :Trace eyeblink conditioning is used as a translational model of declarative memory but restricted to the temporal domain. Potential spatial aspects have never been experimentally addressed. We employed a spatiotemporal trace eyeblink conditioning paradigm in which a spatial dimension (application side of the unconditioned stimulus) was differentially coded by tone frequency of the conditioned stimulus and recorded conditioned reactions from both eyes. We found more and stronger conditioned reactions at the side predicted by the conditioned stimulus but only in aware participants. Thus, spatial effects are present in trace eyeblink conditioning and may be differentially conditioned depending on the awareness about the spatial relation between conditioned and unconditioned stimulus.

背景与目标： ：Trace眨眼条件用作声明性记忆的翻译模型，但仅限于时域。潜在的空间方面从未实验性地解决过。我们采用了时空迹线眨眼条件范式，其中空间维度（未条件刺激的应用侧）通过条件刺激的音调频率进行了差分编码，并记录了两只眼睛的条件反应。我们在条件刺激所预测的一侧发现了更多且更强的条件反应，但仅在有意识的参与者中。因此，空间效应存在于微量眨眼条件中，并且可以根据对条件刺激与非条件刺激之间的空间关系的了解而有区别地进行调节。

BACKGROUND & AIMS: :The central histone H3/H4 chaperone Asf1 comprises a highly conserved globular core and a divergent C-terminal tail. While the function and structure of the Asf1 core are well known, the function of the tail is less well understood. Here, we have explored the role of the yeast (yAsf1) and human (hAsf1a and hAsf1b) Asf1 tails in Saccharomyces cerevisiae. We show, using a photoreactive, unnatural amino acid, that Asf1 tail residue 210 cross-links to histone H3 in vivo and, further, that loss of C-terminal tail residues 211 to 279 weakens yAsf1-histone binding affinity in vitro nearly 200-fold. Via several yAsf1 C-terminal truncations and yeast-human chimeric proteins, we found that truncations at residue 210 increase transcriptional silencing and that the hAsf1a tail partially substitutes for full-length yAsf1 with respect to silencing but that full-length hAsf1b is a better overall substitute for full-length yAsf1. In addition, we show that the C-terminal tail of Asf1 is phosphorylated at T270 in yeast. Loss of this phosphorylation site does not prevent coimmunoprecipitation of yAsf1 and Rad53 from yeast extracts, whereas amino acid residue substitutions at the Asf1-histone H3/H4 interface do. Finally, we show that residue substitutions in yAsf1 near the CAF-1/HIRA interface also influence yAsf1's function in silencing.

背景与目标： ：中央组蛋白H3 / H4分子伴侣Asf1包含高度保守的球状核和发散的C末端尾巴。虽然Asf1核心的功能和结构是众所周知的，但尾部的功能却鲜为人知。在这里，我们探讨了酵母（yAsf1）和人（hAsf1a和hAsf1b）Asf1尾巴在酿酒酵母中的作用。我们显示，使用光反应性的非天然氨基酸，ASF1尾巴残基210在体内交联至组蛋白H3，此外，C末端尾巴残基211至279的损失削弱了yAsf1-histone结合亲和力，在体外接近200-折叠。通过几个yAsf1 C端截短和酵母-人类嵌合蛋白，我们发现残基210的截短增加了转录沉默，并且hAsf1a尾部在沉默方面部分替代了全长yAsf1，但全长hAsf1b总体上更好替代全长yAsf1。此外，我们显示出Asf1的C末端尾巴在酵母中的T270处被磷酸化。该磷酸化位点的丢失不能阻止酵母提取物中yAsf1和Rad53的共免疫沉淀，而Asf1-histone H3 / H4界面的氨基酸残基取代确实可以。最后，我们表明在CAF-1 / HIRA界面附近的yAsf1中的残基取代也会影响yAsf1的沉默功能。

BACKGROUND & AIMS: :Carbon nanotubes (CNT) possess excellent mechanical properties to play the role as reinforcement for imparting strength and toughness to brittle hydroxyapatite (HA) bioceramic coating. However, lack of processing technique to uniformly distribute multiwalled CNTs in HA coating and limited studies and sparse knowledge evincing toxicity of CNTs has kept researchers in dispute for long. In the current work, we have addressed these issues by (i) successfully distributing multiwalled CNT reinforcement in HA coating using plasma spraying to improve the fracture toughness (by 56%) and enhance crystallinity (by 27%), and (ii) culturing human osteoblast hFOB 1.19 cells onto CNT reinforced HA coating to elicit its biocompatibility with living cells. Unrestricted growth of human osteoblast hFOB 1.19 cells has been observed near CNT regions claiming assistance by CNT surfaces to promote cell growth and proliferation.

背景与目标： ：碳纳米管（CNT）具有出色的机械性能，可充当增强剂，为脆性羟基磷灰石（HA）生物陶瓷涂层赋予强度和韧性。然而，缺乏在HA涂层中均匀分布多壁CNT的加工技术，有限的研究以及有关CNTs毒性的稀疏知识一直困扰着研究人员。在当前的工作中，我们已通过以下方法解决了这些问题：（i）使用等离子喷涂成功地在HA涂层中分配多壁CNT增强材料，以提高断裂韧性（提高56％）和增强结晶度（提高27％），以及（ii）培养人将成骨细胞hFOB 1.19细胞涂在CNT增强的HA涂层上，以引发其与活细胞的生物相容性。在CNT区域附近观察到人类成骨细胞hFOB 1.19细胞的生长不受限制，声称其受CNT表面的辅助来促进细胞生长和增殖。

BACKGROUND & AIMS: :Brain and/or lung injury is the most frequent cause of admission to critical care units and patients in this setting frequently develop multiple organ dysfunction with high rates of morbidity and mortality. Mechanical ventilation is commonly used in the management of these critically ill patients and the consequent inflammatory response, together with other physiological factors, is also thought to be involved in distal organ dysfunction. This peripheral imbalance is based on a multiple-pathway cross-talk between the lungs and other organs, including the brain. Interestingly, acute respiratory distress syndrome survivors frequently present some cognitive deterioration at discharge. Such neurological dysfunction might be a secondary marker of injury and the neuroanatomical substrate for downstream impairment of other organs. Brain-lung interactions have received little attention in the literature, but recent evidence suggests that both the lungs and brain are promoters of inflammation through common mediators. This review addresses the current status of evidence regarding brain-lung interactions, their pathways and current interventions in critically ill patients receiving mechanical ventilation.

背景与目标： ：脑部和/或肺部损伤是重症监护病房最常见的病因，在这种情况下，患者经常发展为多器官功能障碍，发病率和死亡率较高。机械通气通常用于这些重症患者的治疗，随之而来的炎症反应以及其他生理因素也被认为与远端器官功能障碍有关。这种外围失衡是基于肺与其他器官（包括大脑）之间的多路径串扰。有趣的是，急性呼吸窘迫综合征幸存者经常在出院时表现出一些认知能力下降。这种神经功能障碍可能是损伤的次要标志，也是其他器官下游损伤的神经解剖学底物。脑-肺之间的相互作用在文献中很少受到关注，但是最近的证据表明，肺和脑都是通过常见的介质促进炎症的。这篇综述讨论了有关机械通气的危重患者脑-肺相互作用，其通路和当前干预措施的证据的现状。

BACKGROUND & AIMS: :Laminin 5/laminin 332 (LN332) is an adhesion substrate for epithelial cells. After secretion of LN332, a regulated cleavage occurs at the carboxy-terminus of its alpha3 subunit, which releases a tandem of two globular modules named LG4/5. We show that the presence of the LG4/5 domain in precursor LN332 decreases its integrin-mediated cell adhesion properties in comparison with mature LN332. Whereas cell adhesion to the recombinant LG4/5 fragment relies solely on the heparan sulfate proteoglycan (HSPG) receptor syndecan-1, we reveal that both syndecan-1 and the alpha3beta1 integrin bind to precursor LN332. We further demonstrate that syndecan-1 mediated cell adhesion to the LG4/5 fragment and pre-LN332 allows the formation of fascin-containing protrusions, depending on the GTPases Rac and Cdc42 activation. Reducing syndecan-1 expression in normal keratinocytes prevents cell protrusions on pre-LN332 with subsequent failure of the peripheral localization of the alpha3beta1 integrin. We finally show that cell migration on pre-LN332 requires syndecan-1. Therefore, the LG4/5 domain in precursor LN332 appears to trigger intracellular signaling events, which participate in keratinocyte motility.

背景与目标： ：层粘连蛋白5 /层粘连蛋白332（LN332）是上皮细胞的粘附底物。 LN332分泌后，在其alpha3亚基的羧基末端发生有规律的切割，释放出串联的两个球形模块LG4 / 5。我们显示，与成熟的LN332相比，前体LN332中LG4 / 5域的存在降低了其整合素介导的细胞粘附特性。虽然细胞对重组LG4 / 5片段的粘附仅依赖于硫酸乙酰肝素蛋白聚糖（HSPG）受体syndecan-1，但我们发现syndecan-1和alpha3beta1整联蛋白均与前体LN332结合。我们进一步证明了syndecan-1介导的细胞粘附到LG4 / 5片段和pre-LN332允许形成含有fascin的突起，具体取决于GTPa​​ses Rac和Cdc42的激活。减少正常角质形成细胞中syndecan-1的表达可以防止pre-LN332上的细胞突出，并随后导致alpha3beta1整联蛋白的外周定位失败。我们最终证明，前LN332上的细胞迁移需要syndecan-1。因此，前体LN332中的LG4 / 5结构域似乎触发了细胞内信号传导事件，该事件参与了角质形成细胞的运动。

BACKGROUND & AIMS: AIM:To determine whether concomitant iron affects the absorption of mycophenolate mofetil. METHODS:An open-label, single centre, randomized, crossover trial was conducted in 16 healthy males. Fasting subjects received mycophenolate mofetil alone (treatment A) or co-administered with iron (treatment B). RESULTS:The mycophenolic acid AUC(0,24 h) for treatments A and B were 42.5 +/- 10.5 and 44.7 +/- 12.4 microg ml(-1) h, respectively. anova modelling showed the relative bioavailability of mycophenolate mofetil to be similar for the two treatments (90% confidence interval 0.92, 1.19). CONCLUSIONS:There was no interaction between mycophenolate mofetil and iron supplements administered concomitantly to healthy fasting subjects.

背景与目标： 目的：确定伴随的铁是否影响霉酚酸酯的吸收。
方法：对16名健康男性进行了开放标签，单中心，随机，交叉试验。空腹受试者单独接受霉酚酸酯（治疗A）或与铁合用（治疗B）。
结果：处理A和B的霉酚酸AUC（0,24 h）分别为42.5 /-10.5和44.7 /-12.4 microg ml（-1）h。方差分析建模显示，两种处理的霉酚酸酯的相对生物利用度相似（90％置信区间为0.92、1.19）。
结论：麦考酚酸酯与健康禁食对象同时服用铁补充剂之间没有相互作用。

BACKGROUND & AIMS: :The mechanism underlying dopamine D1 receptor-mediated attenuation of glutamatergic synaptic input to nucleus accumbens (NAcc) neurons was investigated in slices of rat forebrain, using whole-cell patch-clamp recording. The depression by dopamine of EPSCs evoked by single-shock cortical stimulation was stimulus-dependent. Synaptic activation of NMDA-type glutamate receptors was critical for this effect, because dopamine-induced EPSC depressions were blocked by the competitive NMDA receptor antagonist D/L-2-amino-5-phosphonopentanoate (AP5). Application of NMDA also depressed the EPSC, and both this effect and the dopamine depressions were blocked by the A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), implicating adenosine release in the EPSC depression. A1 receptor agonists also depressed EPSCs by a presynaptic action, causing increased paired-pulse facilitation, but this was insensitive to AP5. Activation of D1 receptors enhanced both postsynaptic inward currents evoked by NMDA application and the isolated NMDA receptor-mediated component of synaptic transmission. The biochemical processes underlying the dopamine-induced EPSC depression did not involve either protein kinase A or the production of cAMP and its metabolites, because this effect was resistant to the protein kinase inhibitors H89 and H7 and the cAMP-specific phosphodiesterase inhibitor rolipram. We conclude that activation of postsynaptic D1 receptors enhances the synaptic activation of NMDA receptors in nucleus accumbens neurons, thereby promoting a transsynaptic feedback inhibition of glutamatergic synaptic transmission via release of adenosine. Unusually for D1 receptors, this phenomenon occurs independently of adenylyl cyclase stimulation. This process may contribute to the locomotor stimulant action of dopaminergic agents in the NAcc.

背景与目标： ：使用全细胞膜片钳记录技术，在大鼠前脑切片中研究了多巴胺D1受体介导的伏谷核（NAcc）神经元的谷氨酸能突触输入衰减的机制。单电刺激皮层刺激引起的EPSCs的多巴胺抑制与刺激有关。 NMDA型谷氨酸受体的突触激活对此效应至关重要，因为多巴胺诱导的EPSC抑郁症被竞争性NMDA受体拮抗剂D / L-2-氨基-5-膦基戊酸酯（AP5）阻止。 NMDA的应用也抑制了EPSC，这种作用和多巴胺抑制均被A1受体拮抗剂8-环戊基-1,3-二丙基黄嘌呤（DPCPX）阻断，这暗示了EPSC抑制中腺苷的释放。 A1受体激动剂还通过突触前作用抑制EPSC，导致成对脉冲促进作用增强，但这对AP5不敏感。 D1受体的激活增强了NMDA的应用诱发的突触后内向电流和突触传递的分离的NMDA受体介导的成分。多巴胺引起的EPSC抑郁症的生化过程既不涉及蛋白激酶A，也不涉及cAMP及其代谢产物的产生，因为这种作用对蛋白激酶抑制剂H89和H7以及cAMP特异性磷酸二酯酶抑制剂咯利普兰具有抵抗力。我们得出的结论是，突触后D1受体的激活增强伏伏核神经元中NMDA受体的突触激活，从而通过释放腺苷促进谷氨酸能突触传递的突触反馈抑制。对于D1受体，这种现象通常与腺苷酸环化酶的刺激无关地发生。该过程可能有助于NAcc中多巴胺能药物的运动刺激作用。

BACKGROUND & AIMS: :Several lines of evidence support the concept of two functionally distinct sites on antigen: the epitope, involved in interaction with the T cell receptor and the agretope, interacting with Ia. We investigated the Ia and T cell receptor interaction sites on the synthetic polypeptide antigen poly-18 [poly-EYK(EYA)5] using T cell hybridoma clones specific for this antigen in the context of I-Ad. Peptides with amino acid sequences related to poly-18 were synthesized. These were used to identify the critical residues in the minimum peptide sequence required for activation. Clone A.1.1 responds to the minimal peptide EYK(EYA)4 but not to (EYA)5. This identifies Lys3 as a critical amino acid for this hybridoma. Surprisingly, the substituted peptide EYAEAA(EYA)3 could activate A.1.1, indicating that an Ala at position 5 instead of a Tyr obviates the critical requirement for Lys3. This demonstrates that the function of critical residues may extend beyond contacting the T cell receptor or Ia, to include a third role: that of interacting with other amino acids of the T cell epitope, thus influencing the antigen's recognition by T cells.

背景与目标： ：有几条证据支持抗原上两个功能上不同的位点的概念：抗原决定簇，与T细胞受体相互作用，而抗原决定簇与Ia，相互作用。我们在I-Ad的背景下，使用对这种抗原具有特异性的T细胞杂交瘤克隆，研究了合成多肽抗原poly-18 [poly-EYK（EYA）5]上的Ia和T细胞受体相互作用位点。合成了具有与poly-18相关的氨基酸序列的肽。这些用于鉴定激活所需的最小肽序列中的关键残基。克隆A.1.1对最小肽EYK（EYA）4响应，但对（EYA）5没有响应。这将Lys3鉴定为该杂交瘤的关键氨基酸。出人意料的是，取代的肽EYAEAA（EYA）3可以激活A.1.1，表明位置5处的Ala而不是Tyr消除了Lys3的关键要求。这表明关键残基的功能可能超出接触T细胞受体或Ia的范围，包括第三种作用：与T细胞表位的其他氨基酸相互作用，从而影响抗原对T细胞的识别。