Law and the brain: introduction

Combining law and the brain as a matter for study requires the integration not just of two apparently remote fields of study but also of two profoundly different orientations towards research and study. We believe that, in spite of the difficulties, such a combination, perhaps even emerging in a new specialized discipline in the future, will not only enrich both fields but is the ineluctable consequence of the current assault on the secrets of the brain. The effort to bring the fields together is therefore a worthy task, and this issue is the first systematic effort to test this expectation.     

Estrogen-induced cell signalling in a cellular model of Alzheimer's disease

Alzheimer's disease (AD) is characterised by deposition of a 4 kDa amyloid-beta peptide (Abeta) into senile plaques of the affected brain. Abeta is a proteolytic product of the membrane protein, amyloid precursor protein (APP). An alternative cleavage pathway involves alpha-secretase activity and results in secretion of a 100 kDa non-amyloidogenic APP (sAPPalpha) and therefore a potential reduction in Abeta secretion. We have shown that estrogen induces alpha-cleavage and therefore results in the secretion of sAPPalpha. This secretion is signalled via MAP-kinase and PI-3 kinase signal-transduction pathways. These pathways also have the potential to inhibit the activation of glycogen synthase kinase 3beta (GSK), a protein involved in cell death. Therefore, the aim of this work was to further elucidate the estrogen-mediated signaling pathways involved in APP processing, with particular emphasis on GSK activity. By stimulating rat hypothalamic neuronal GT1-7 cells with estradiol, we found that estrogen decreases the activation state of GSK via the MAP kinase pathway. Moreover, the inhibition of GSK activity by LiCl causes enhanced sAPPalpha secretion in a pattern similar to that seen in response to estrogen, suggesting a pivotal role for this deactivation in APP processing. Further, inactivation of GSK by estrogen can be confirmed in an in vivo model. Elucidation of the signaling pathways involved in APP processing may help to understand the pathology of AD and may also prove beneficial in developing therapeutic strategies to combat AD.     

Truncation mutants of the tight junction protein ZO-1 disrupt corneal epithelial cell morphology

The tight junction is the most apical intercellular junction of epithelial cells and regulates transepithelial permeability through the paracellular pathway. To examine possible functions for the tight junction-associated protein ZO-1, C-terminally truncated mutants and a deletion mutant of ZO-1 were epitope tagged and stably expressed in corneal epithelial cell lines. Only full-length ZO-1 and one N-terminal truncation mutant targeted to cell borders; other mutants showed variable cytoplasmic distributions. None of the mutants initially disrupted the localization of endogenous ZO-1. However, long-term stable expression of two of the N-terminal mutants resulted in a dramatic change in cell shape and patterns of gene expression. An elongated fibroblast-like shape replaced characteristic epithelial cobblestone morphology. In addition, vimentin and smooth muscle actin expression were up-regulated, although variable cytokeratin expression remained, suggesting a partial transformation to a mesenchymal cell type. Concomitant with the morphological change, the expression of the integral membrane tight junction protein occludin was significantly down-regulated. The localizations of endogenous ZO-1 and another family member, ZO-2, were disrupted. These findings suggest that ZO-1 may participate in regulation of cellular differentiation.     

Carbon‐Coated Li3Nd3W2O12: A High Power and Low‐Voltage Insertion Anode with Exceptional Cycleability for Li‐Ion Batteries

The synthesis of carbon‐coated Li₃Nd₃W₂O₁₂ (C‐Li₃Nd₃W₂O₁₂), a low voltage insertion anode (0.3 V vs. Li) for a Li‐ion battery, is reported to exhibit extraordinary performance. The low voltage reversible insertion provides an increase in the energy density of Li‐ion power packs. For instance, C‐Li₃Nd₃W₂O₁₂ delivered an energy density of ≈390 Wh kg^?1 (based on cathode mass loading) when coupled with an LiMn₂O₄ cathode with an operating potential of 3.4 V. Furthermore, excellent cycling profiles are observed for C‐Li₃Nd₃W₂O₁₂ anodes both in half and full‐cell configurations. The full‐cell is capable of delivering very stable cycling profiles at high current rates (e.g., 2 C), which clearly suggests the high power capability of such garnet‐type anodes.     

小鼠淋巴细胞抗原CTLA-4的胞外肽段表达及纯化

目的: 真核细胞表达小鼠淋巴细胞抗原CTLA-4胞外段肽,研究表达肽段与抗原呈递细胞B7分子结合后减轻小鼠淋巴细胞刺激后的增殖抑制,从而启动T淋巴细胞进一步增殖。方法:从小鼠脾脏淋巴细胞获得总RNA,通过逆转录PCR扩增出CTLA-4全长基因,克隆并测序。依据胞外段序列和真核表达载体pcDNA3.1序列,合成引物扩增胞外片段,两者经内切核酸酶处理、连接构建重组表达pcDNA3.1载体,重组质粒经测序验证后,采用lipofectamine 2000转染入小鼠肝癌细胞Hepa1-6,经G418筛选获得稳定表达细胞株。结果:获得小鼠CTLA-4胞外段真核表达载体和小鼠肝癌细胞Hepa1-6稳定表达转染细胞株,制备了CTLA-4胞外肽段,经His标签抗体和小鼠CTLA-4抗体Western blot检测表达蛋白带均呈阳性。结论:获得CTLA-4胞外段肽,为进一步研究该肽的作用打下基础。