E alpha u and E beta u chain association: where lies the anomaly?

H-2u haplotype mice are unique among all E alpha+ strains because they do not provide in heterozygotes an E alpha chain that interacts with E betak,s,etc. sufficiently well to allow certain E-restricted immune responses. As a first step in understanding this peculiarity, we have sequenced E alpha u and E beta u cDNA and compared the derived amino acid sequences with those of previously analyzed alleles. Although no glaring structural abnormalities were found, we have identified some u-specific residues and suggest which are the most likely to provoke a pairing anomaly.     

载脂蛋白E

apo-E显示明显的多形性,其异构体部分来源于结构基因的变异,部分来源于翻译后的唾液酸糖化修饰。不同的异构体在受体结合活性上有明显的差别,其原因是由于在活性部位半胱氨酸对精氨酸的取代。apo-E与机体胆固醇代谢的关系极为密切。apo-E_2纯合子受体结合活性低下是Ⅲ型高脂血症形成的主要原因。apo-E_4可能与V型高脂血症的形成有关。     

E-learning: is there anything special about the "E"?

E-learning has been widely utilized in medical education and suggested by some proponents to represent a fundamental advance in educational methodology. We challenge this conclusion by examining e-learning in the context of broader learning theories, specifically as they relate to instructional design and methods. Core tenets of educational design are applied to e-learning in a unified model for instructional design, and examples of e-learning technologies are examined in the context of medical education, with reflections on research questions generated by these new modalities. Throughout, we argue that e-learning is a tool that, when designed appropriately, can be used to meet worthy educational goals.     

Prostaglandin E2 and T cells: friends or foes?

Our understanding of the key players involved in the differential regulation of T-cell responses during inflammation, infection and auto-immunity is fundamental for designing efficient therapeutic strategies against immune diseases. With respect to this, the inhibitory role of the lipid mediator prostaglandin E(2) (PGE(2)) in T-cell immunity has been documented since the 1970s. Studies that ensued investigating the underlying mechanisms substantiated the suppressive function of micromolar concentrations of PGE(2) in T-cell activation, proliferation, differentiation and migration. However, the past decade has seen a revolution in this perspective, since nanomolar concentrations of PGE(2) have been shown to potentiate Th1 and Th17 responses and aid in T-cell proliferation. The understanding of concentration-specific effects of PGE(2) in other cell types, the development of mice deficient in each subtype of the PGE(2) receptors (EP receptors) and the delineation of signalling pathways mediated by the EP receptors have enhanced our understanding of PGE(2) as an immune-stimulator. PGE(2) regulates a multitude of functions in T-cell activation and differentiation and these effects vary depending on the micro-environment of the cell, maturation and activation state of the cell, type of EP receptor involved, local concentration of PGE(2) and whether it is a homeostatic or inflammatory scenario. In this review, we compartmentalize the various aspects of this complex relationship of PGE(2) with T lymphocytes. Given the importance of this molecule in T-cell activation, we also address the possibility of using EP receptor antagonism as a potential therapeutic approach for some immune disorders.     

Syringomycin E channel: a lipidic pore stabilized by lipopeptide?

Highly reproducible ion channels of the lipopeptide antibiotic syringomycin E demonstrate unprecedented involvement of the host bilayer lipids. We find that in addition to a pronounced influence of lipid species on the open-channel ionic conductance, the membrane lipids play a crucial role in channel gating. The effective gating charge, which characterizes sensitivity of the conformational equilibrium of the syringomycin E channels to the transmembrane voltage, is modified by the lipid charge and lipid dipolar moment. We show that the type of host lipid determines not only the absolute value but also the sign of the gating charge. With negatively charged bilayers, the gating charge sign inverts with increased salt concentration or decreased pH. We also demonstrate that the replacement of lamellar lipid by nonlamellar with the negative spontaneous curvature inhibits channel formation. These observations suggest that the asymmetric channel directly incorporates lipids. The charges and dipoles resulting from the structural inclusion of lipids are important determinants of the overall energetics that underlies channel gating. We conclude that the syringomycin E channel may serve as a biophysical model to link studies of ion channels with those of lipidic pores in membrane fusion.     

Molecular interactions of ‘high risk’ human papillomaviruses E6 and E7 oncoproteins: implications for tumour progression

The aetiology of cervical cancer has been primarily attributed to human papillomaviruses (HPVs). These are characterized by the persistent expression of the two oncogenes, E6 and E7. Experimental studies show that E6 and E7 genes of the high risk HPVs deregulate key cell cycle controls. Recent work has uncovered new cellular partners for these proteins that throw light on many of the pathways and processes in which these viral proteins intervene. This review focuses on the regulation of host proteins by the viral oncoproteins and consequence of such interactions on cell survival, proliferation, differentiation and apoptosis.     

Microsomal prostaglandin E2 synthase: a safer target than cyclooxygenases?

Non-steroidal anti-inflammatory drugs (NSAIDs) are inhibitors of the cyclo-oxygenase (COX)-1 and -2 activities of prostaglandin G/H synthase-1 and -2, respectively. They have been extensively used in the treatment of prostaglandin E(2)-mediated chronic inflammatory diseases. Selective COX-2 inhibitors (coxibs), which were developed to provide an alternative with reduced gastrointestinal risk for the traditional NSAIDs, have been associated with an increased incidence of major adverse cardiovascular events. Could the targeting of microsomal prostaglandin E(2) synthase (mPGES-1) lead to novel anti-inflammatory drugs with possibly reduced risks of gastrointestinal and cardiovascular side effects?     

Parkin:一种作用极其广泛的E3泛素连接酶

Parkin，又名PARK2，自发现初始便与帕金森病(Parkinson’s disease, PD)密切相关。Parkin被认为是一种神经保护性基因。随着对其结构的深入了解，揭开了作为E3泛素连接酶的面纱。Parkin参与调控细胞周期、线粒体动态平衡和能量代谢等细胞进程，并与许多疾病息息相关，甚至在同一通路中发挥完全相反的作用，即细胞增殖和凋亡，表明这必是一个作用极其广泛且重要的基因。本文概述了Parkin的发现和结构及其自身抑制的特点，重点阐述其作为E3泛素连接酶参与的泛素化过程和进而引起的自噬、降解蛋白质、改变蛋白质亚细胞定位和蛋白质间互作等。这些或许都作为Parkin预防PD和抑制肿瘤的基础。在此基础上，总结了Parkin异常导致PD的两方面原因：蛋白质质量控制异常和线粒体功能障碍，并延展了Parkin异常致使线粒体功能障碍所引起的心血管及肾的疾病；Parkin与癌症的内在联系也从Parkin作为一种肿瘤抑制因子、调控细胞周期、细胞凋亡及转移、氧化应激及能量代谢等方面展开了介绍。并对其研究进行了展望，通过保持Parkin的活性状态或增强其表达，可能达到改善PD病人病情的目的。但Parkin抑制肿瘤生长的机制仍尚待破译，且要加强Parkin在介导PD与癌症风险间关系的潜在作用的研究。这些后续的深入研究为在相关疾病的诊断与治疗中作为靶标分子的应用奠定了基础。     

载脂蛋白E研究进展

载脂蛋白E在脂质代谢中发挥重要作用 ,三种亚型 (apoE2 ,apoE3和apoE4 )只有二个部位的氨基酸发生变化 ,呈现出不同的生理作用。apoE4与老年痴呆、心血管疾病的高发性相关 ,而且对各种脑外伤功能的恢复具有负面影响。apoE2则对老年痴呆具有防护作用 ,并与高脂蛋白血症有关。apoE3对机体正常生理功能的发挥起关键作用。体外及动物实验研究表明 ,血浆中的apoE多态性与人体的冠心病、高脂蛋白血症、动脉粥样硬化相关。而脑中的apoE是一种多功能分子 ,在淀粉样蛋白沉积与清除、稳定微管蛋白结构、细胞内信号传导等细胞过程中发挥重要作用 ,其多态性与老年痴呆相关。因此 ,从分子水平研究其结构与功能之间的构效关系 ,对探索相关疾病的发病机制、诊断及治疗具有重要意义。     

漫谈维生素E

维生素E(VE)是一种重要的脂溶性维生素,是6羟基苯骈二氢吡喃的衍生物。分子的C_2上具有甲基及烃键,烃键上又具有四个甲基;C_6上具有羟基,这个羟基极易被氧化,所以对氧极为敏感。下面简单介绍一下VE的生理功能。 1.保护生物膜 VE的抗氧化作用能使细     

载脂蛋白E研究进展

载脂蛋白E在脂质代谢中发挥重要作用,三种亚型（apoE2,apoE3和apoE4)只有二个部位的氨基酸发生变化,呈现出不同的生理作用。apoE4与老年痴呆、心血管疾病的高发性相关,而且对各种脑外伤功能的恢复具有负面影响。apoE2则对老年痴呆具有防护作用,并与高脂蛋白血症有关。apoE3对机体正常生理功能的发挥起关键作用。体外及动物实验研究表明,血浆中的apoE多态性与人体的冠心病、高脂蛋白血症、动脉粥样硬化相关。而脑中的apoE是一种多功能分子,在淀粉样蛋白沉积与清除、稳定微管蛋白结构、细胞内信号传导等细胞过程中发挥重要作用,其多态性与老年痴呆相关。因此,从分子水平研究其结构与功能之间的构效关系,对探索相关疾病的发病机制、诊断及治疗具有重要意义。     

Letter to the Editor: Resonance assignment of SlyD from E. coli

SlyD from Escherichia coli is a peptidyl–prolyl cis–trans isomerase involved in [Ni–Fe] hydrogenase metallocentre assembly in bacteria. We present here the backbone and side chain assignments for E. coli SlyD.