Mechanisms of long-term dark adaptation

It has previously been suggested that long-term dark adaptation is controlled by bleaching signals that regulate the activity of an allosteric, positively cooperative protein (Stabell et al., 1986a, b). Recent biochemical evidence strongly supports this assumption, indicating that the primary regulator of the light-sensitive channels in the plasma membrane of the outer segments of the photoreceptors is a homo-oligomeric, allosteric, positively cooperative protein. In this report, we discuss the possibility that signals from bleached photopigments may control the dark-adaptation process through the allosteric protein of the plasma membrane. It is suggested that the concentrations of the bleached photopigment and of the allosteric effector are reciprocal quantities.     

Hippocampal PKA/CREB pathway is involved in the improvement of memory induced by spermidine in rats

Spermidine (SPD) is an endogenous polyamine that modulates N-methyl-D-aspartate (NMDA) receptor function, and has been reported to facilitate memory formation. In the current study we determined whether or not the PKA/CREB signaling pathway is involved in SPD-induced facilitation of memory of inhibitory avoidance task in adult rats. The post-training administration of the cAMP-dependent protein kinase (PKA) inhibitor, N-[2-bromocinnamylamino)ethyl]-5-isoquinoline sulfonamide [H-89, 0.5 ρmol intrahippocampal (ih)] or the antagonist of the NMDA receptor polyamine-binding site (arcaine, 0.02 nmol ih) with SPD (0.2 nmol ih) prevented memory improvement induced by SPD. Intrahippocampal administration of SPD (0.2 nmol) facilitated PKA and cAMP response element-binding protein (CREB) phosphorylation in the hippocampus 180 min, but not 30 min, after administration, and increased translocation of the catalytic subunit of PKA into the nucleus. Arcaine (0.02 nmol) and H-89 (0.5 ρmol) prevented the stimulatory effect of SPD on PKA and CREB phosphorylation. These results suggest that memory enhancement induced by the ih administration of SPD involves the PKA/CREB pathways in rats.     

兼职蛋白质及其哲学思考

在蛋白质组学天空中,新近提出的兼职蛋白质概念正越来越受到人们的关注。研究发现,某些蛋白质因其细胞定位、细胞类型、寡聚状态的不同及其配体、底物、辅因子和产物在细胞内浓度的变化而表现出不同的功能,从而对细胞和机体产生诸多有益作用,并使其发展出一系列完善机制以实现不同功能间的转换。兼职蛋白质概念的提出不仅改变了一个基因－－一种蛋白质－－一种功能的传统观念,也为大分子间相互作用、细胞复杂性及生物多样性研究     

Non-ligand activation of estrous behavior in rodents: cross-talk at the progesterone receptor

Estrous behavior in rodents is triggered by the binding of progesterone (P) to its intracellular receptor (PR). Non-steroidal agents (i.e., gonadotropin-releasing hormone, noradrenaline, dopamine and others), acting at the membrane, can facilitate estrous behavior in estrogen-primed rats. This action is mediated through the generation of second messengers (cyclic AMP, cyclic GMP, calcium) which, in turn, phosphorylate through diverse kinase systems (protein kinases A, G or C) either the PR or associated effector proteins linking the PR to the trans-activation machinery. P or its metabolites also activate cyclic AMP-signaling pathways by acting directly on the membrane or by modulating neurotransmitter release. Molecular processes resulting from second messenger signaling pathways and those from the progesterone-RP interaction synergize to elicit a full behavioral response.     

不同月龄小鼠行为训练与脑突触蛋白的相关性研究

不同年龄动物在各种行为实验中表现出学习记忆能力不同。一般地说,动物进入中年期以后,记忆保持力(retention)随年龄增长而下降。有关衰老性记忆障碍与脑内神经细胞变化的相关性已有大量观察记载,但中、幼年阶段的记忆力差异及其脑内突触机制     

Both exposure to a novel context and associative learning induce an upregulation of AKAP150 protein in mouse hippocampus

A-kinase anchoring protein 150 (AKAP150) is a multi-enzyme signaling complex that coordinates the action of PKA, PKC, and PP2B at neuronal membranes and synapses. We measured levels of AKAP150 protein in the hippocampus 6h after training mice in a contextual fear conditioning paradigm. In contextual fear conditioning mice learn to associate a context with a footshock presentation. Mice were divided in four experimental groups with different training protocols: naive, no footshock exposure, immediate footshock exposure, and footshock 3min after exposure to the context. We found that AKAP150 protein levels were increased upon exposing mice to the novel context independent of the training protocol. However, when the animals were habituated to the experimental context, only mice that learned to associate the context with the footshock showed an upregulation of AKAP150. We suggest that upregulated levels of AKAP150 contribute to processing the exposure to a novel context and associative learning.     

慢性应激对大鼠行为和免疫细胞热休克蛋白70表达的影响

目的：研究慢性不确定应激对大鼠急性整体热水浴后外周血和脾脏免疫细胞热休克蛋白70（Heat shock protein 70, HSP70）表达的影响。方法：随机将大鼠分成慢性应激组和控制组（每组14只）。通过4周的慢性不确定性应激诱发实验组大鼠明显的抑郁行为,此期间控制组大鼠正常饲养。随后给予大鼠42度整体热水浴刺激,维持直肠温度41度25min。热刺激后6h,采用流式细胞仪测定大鼠外周血和脾脏免疫细胞HSP70 水平。结果：与控制组大鼠相比,慢性应激大鼠在急性热刺激后HSP70合成明显减少。控制组大鼠的所有被检测的免疫细胞热应激后HSP70合成均明显增加。相反,慢性应激大鼠仅在外周血的单核细胞和粒细胞检测到HSP70合成增加,同时升高的水平明显低于控制组大鼠。结论：慢性应激降低大鼠免疫细胞HSP70的热诱导反应,提示HSP70保护性作用减弱可能参与了慢性应激损害免疫细胞功能的生物学过程     

替罗非班不同给药途径对DM合并急性STEMI患者PCI术后血小板α-颗粒膜蛋白及心肌灌注水平的影响

为探讨替罗非班不同给药途径对糖尿病（DM）合并急性ST段抬高型心肌梗死（STEMI）患者PCI术后血小板α-颗粒膜蛋白及心肌灌注水平的影响,对149例DM合并急性STEMI患者进行研究,测定并比较经静脉（A组）、冠脉给药途径（B组）和无替罗非班（C组）的患者术前及术中应用替罗非班后血小板α-颗粒膜蛋白GMP140浓度、造影结果、心肌酶及肌钙蛋白I水平峰值及峰值时间、心电图变化。结果显示A、B两组术中血小板α-颗粒膜蛋白浓度较术前明显降低（P〈0．05）,且B组较A组降低更明显（P〈0．05）,而C组未见明显变化（P〉0．05）,A、B两组术后即刻TIMI血流、2h sumSTR、心肌酶及肌钙蛋白Ⅰ峰值及峰值时间的变化均优于C组（P〈0．05）,且B组优于A组（P〈0．05）。因此,替罗非班可以降低血小板α-颗粒膜蛋白浓度和改善心肌灌注水平,与静脉途径给药相比,经冠脉给药更具有优势。     

P16、CyclinDl和CDK4在结直肠癌组织中表达及意义

细胞周期过程中癌基因的激活与抑癌基因的失活等是造成细胞恶性增殖、转化的重要因素。细胞周期G1／S期各调节因子的异常改变与细胞癌变关系尤为密切。P16、CyclinDl和CDK4均为重要的细胞周期调控蛋白,任何原因导致这些蛋白异常表达时,将引起细胞周期调节失控,导致肿瘤的发生和恶性演进。结直肠癌的发生发展同上述三者关系密切。本实验通过免疫组化方法进行检测结直肠癌组织中P16、CyclinDl和CDK4三者的表达及其与结直肠癌临床指标的关系,为揭示三者在结直肠癌发生发展中的作用提供一定的实验依据。     

Insomnia symptoms are associated with elevated C-reactive protein in young adults

Abstract

Objective: Insomnia is associated with elevated inflammation; however, studies have not investigated if this relationship is confounded with depression and neuroticism, which are associated with insomnia and inflammation. The current study examined the association of insomnia symptoms with C-reactive protein (CRP) and with interleukin-6 (IL-6), independently and after controlling for depressive symptoms and neuroticism. Design: Fifty-two young adults (mean age?=?25.2?±?3.9 years, 52% female) completed a baseline survey to assess psychological characteristics, followed by a plasma blood draw. Main outcome measures: Plasma CRP and IL-6. Results: When examined alone, insomnia symptoms were significantly associated with elevated CRP (β?=?0.52; R²?=?0.27), as was neuroticism (β?=?0.41, R²?=?0.17), but not depressive symptoms (β?=?0.21, R²?=?0.05). The association between insomnia symptoms and CRP remained significant when depressive symptoms and neuroticism were entered into the model simultaneously; this model did not explain more variance than the model with insomnia symptoms alone. No variables were associated with IL-6. Conclusions: Results suggest that insomnia symptoms are independently associated with elevated CRP in young adults, even after controlling for presumed overlapping psychological constructs. Findings highlight the potential importance of treating insomnia to reduce systemic inflammation.