High‐Performance Dopamine Sensors Based on Whole‐Graphene Solution‐Gated Transistors

Solution‐gated graphene transistors with graphene as both channel and gate electrodes are fabricated for the first time and used as dopamine sensors with the detection limit down to 1 nM, which is three orders of magnitude better than that of conventional electrochemical measurements. The sensing mechanism is attributed to the change of effective gate voltage applied on the transistors induced by the electro‐oxidation of dopamine at the graphene gate electrodes. The interference from glucose, uric acid, and ascorbic acid on the dopamine sensor is characterized. The selectivity of the dopamine sensor is dramatically improved by modifying the gate electrode with a thin Nafion film by solution process. This work paves the way for developing many other biosensors based on the solution‐gated graphene transistors by specifically functionalizing the gate electrodes. Because the devices are mainly made of graphene, they are potentially low cost and ideal for high‐density integration as multifunctional sensor arrays.     

多巴胺包覆纳米普鲁士蓝的制备及其对Sr2+的吸附性能研究

以水热法制备纳米普鲁士蓝,利用多巴胺盐酸将其包覆制备聚多巴胺纳米普鲁士蓝复合材料,研究其对溶液中Sr2+的吸附性能。考察溶液pH值、固液比、初始质量浓度、吸附时间等因素对复合材料吸附Sr2+的影响。在pH值为9.0、固液比0.4 mg/L、吸附时间60 min、初始质量浓度30 mg/L的条件下,Sr2+的吸附率和吸附容量分别达到70%和23.95 mg/L。结果表明,聚多巴胺包覆普鲁士蓝对Sr2+有较好的吸附效果,该复合材料对含锶放射性废水处理具有潜在的应用价值。研究结果可为核工业发展过程中产生的含锶放射性废水处理与环境修复提供一定的理论依据和技术支持。     

Toxic and Phenotypic Effects of AAV_Cre Used to Transduce Mesencephalic Dopaminergic Neurons

A popular approach to spatiotemporally target genes using the loxP/Cre recombination system is stereotaxic microinjection of adeno-associated virus (AAV) expressing Cre recombinase (AAV_Cre) in specific neuronal structures. Here, we report that AAV_Cre microinjection in the ventral tegmental area (VTA) of ErbB4 Cyt-1-floxed (ErbB4 Cyt-1^fl/fl) mice at titers commonly used in the literature (~10¹²–10¹³ GC/mL) can have neurotoxic effects on dopaminergic neurons and elicit behavioral abnormalities. However, these effects of AAV_Cre microinjection are independent of ErbB4 Cyt-1 recombination because they are also observed in microinjected wild-type (WT) controls. Mice microinjected with AAV_Cre (10¹²–10¹³ GC/mL) exhibit reductions of tyrosine hydroxylase (TH) and dopamine transporter (DAT) expression, loss of dopaminergic neurons, and they behaviorally become hyperactive, fail to habituate in the open field and exhibit sensorimotor gating deficits compared to controls microinjected with AAV_GFP. Importantly, these AAV_Cre non-specific effects are: (1) independent of serotype, (2) occur with vectors expressing either Cre or Cre-GFP fusion protein and (3) preventable by reducing viral titers by 1000-fold (10¹⁰ GC/mL), which retains sufficient recombination activity to target floxed genes. Our studies emphasize the importance of including AAV_Cre-injected WT controls in experiments because recombination-independent effects on gene expression, neurotoxicity and behaviors could be erroneously attributed to consequences of gene ablation.     

Mice Lacking Gpr179 with Complete Congenital Stationary Night Blindness Are a Good Model for Myopia

Mutations in GPR179 are one of the most common causes of autosomal recessive complete congenital stationary night blindness (cCSNB). This retinal disease is characterized in patients by impaired dim and night vision, associated with other ocular symptoms, including high myopia. cCSNB is caused by a complete loss of signal transmission from photoreceptors to ON-bipolar cells. In this study, we hypothesized that the lack of Gpr179 and the subsequent impaired ON-pathway could lead to myopic features in a mouse model of cCSNB. Using ultra performance liquid chromatography, we show that adult Gpr179^−/− mice have a significant decrease in both retinal dopamine and 3,4-dihydroxyphenylacetic acid, compared to Gpr179^+/+ mice. This alteration of the dopaminergic system is thought to be correlated with an increased susceptibility to lens-induced myopia but does not affect the natural refractive development. Altogether, our data added a novel myopia model, which could be used to identify therapeutic interventions.     

Reversible Photocontrol of Dopaminergic Transmission in Wild-Type Animals

Understanding the dopaminergic system is a priority in neurobiology and neuropharmacology. Dopamine receptors are involved in the modulation of fundamental physiological functions, and dysregulation of dopaminergic transmission is associated with major neurological disorders. However, the available tools to dissect the endogenous dopaminergic circuits have limited specificity, reversibility, resolution, or require genetic manipulation. Here, we introduce azodopa, a novel photoswitchable ligand that enables reversible spatiotemporal control of dopaminergic transmission. We demonstrate that azodopa activates D₁-like receptors in vitro in a light-dependent manner. Moreover, it enables reversibly photocontrolling zebrafish motility on a timescale of seconds and allows separating the retinal component of dopaminergic neurotransmission. Azodopa increases the overall neural activity in the cortex of anesthetized mice and displays illumination-dependent activity in individual cells. Azodopa is the first photoswitchable dopamine agonist with demonstrated efficacy in wild-type animals and opens the way to remotely controlling dopaminergic neurotransmission for fundamental and therapeutic purposes.     

脂肪酶固定化及其在食品领域中应用的研究进展

为构建新型固定化酶催化体系,以聚甲基丙烯酸缩水甘油酯为载体,利用贻贝仿生技术——多巴胺/聚乙烯亚胺共沉积进行修饰,采用扫描电镜（SEM）、能谱（EDS）、Zeta电位及红外光谱（FT-IR）表征所得材料,并研究其固定化近平滑假丝酵母CICC 33470所产脂肪酶的表征及酶学性质。最佳酶固定化条件为：固定化温度为30 ℃,固定化pH为7.0,固定化时间为5 h,初始酶活为337.76 U/mL,载体添加量为0.2 g。固定化酶最佳反应温度为50 ℃,最佳反应pH为8.0,最佳反应时间为10 min,最优条件下固定化酶酶活为484.42±5.97 U/g-载体。固定化酶的稳定性明显提高,重复使用8次后,固定化酶仍有39.22%的初始酶活。进一步将固定化酶用于催化乙酰丙酸与十二醇的酯化反应,转化率可达75.94%,充分证明聚甲基丙烯酸缩水甘油酯经修饰后是固定化脂肪酶的优良载体,为未来扩大脂肪酶的应用范围提供了基础数据。

     

手性拓扑电荷指数和构效关系研究

对拓扑电荷指数进行了扩展,得到了含电负性的手性拓扑电荷指数。将其与Julián-Qrtiz 等人对该指数的扩展结果相比较,结果表明,新的拓扑指数能够得到更好的QSAR 模型。进一步运用人工神经网络法构造了数学模型,该模型能够更好地预测手性化合物的活性。     

Cocaine craving, euphoria, and self-administration: A preliminary study of the effect of catecholamine precursor depletion.

The authors used the acute phenylalanine-tyrosine depletion (APTD) method to test the effect of transient catecholamine precursor depletion on cocaine craving, euphoria, and self-administration. Eight nondependent, nontreatment-seeking cocaine users self-administered 3 doses of cocaine (0.6, 1.5, 3.0 mg/kg, taken intranasally) following ingestion of (a) a nutritionally balanced amino acid mixture, (b) APTD, and (c) APTD followed by L-dopa/carbidopa (2 × 100 mg/25 mg). APTD decreased both cue and cocaine-induced drug craving but not euphoria or self-administration. APTD + L-dopa also decreased drug craving, possibly reflecting the ability of L-dopa to transiently decrease dopamine cell firing. Together, these preliminary results suggest that the craving elicited by cocaine and cocaine cues is related to changes in catecholamine neurotransmission. Euphoria and the self-administration of freely available drugs by regular users, in comparison, might be better accounted for by other mechanisms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

苯酰胺类D_2受体新配体的合成,~(125)I标记及生物分布研究

合成了苯酰胺类D2受体配体（S）－N－[(1-羟乙基－2－四氢吡咯烷基）甲基]－50氨基－2，3－二甲氧基苯甲胺胺（HEABZM），用红外光谱，核磁共振和质谱法进行了表征。以HEABZM为标记前体，制备了（S）－N－[1－羟乙基－2－四氢吡咯烷基）甲基]－5－氨基－4－^125I，3－二甲苯甲酰胺。标记率为79％，经萃取分离后，放化纯度在90％以上。小鼠休丙初步生物分布研究表明，该配合物在小鼠脑中有一定的区域分布，纹状体与小脑的比值略大于1。