A speculative model of affective illness cyclicity based on patterns of drug tolerance observed in amygdala-kindled seizures

In this article, we discuss molecular mechanisms involved in the evolution of amygdala kindling and the episodic loss of response to pharmacological treatments during tolerance development. These phenomena allow us to consider how similar principles (in different neurochemical systems) could account for illness progression, cyclicity, and drug tolerance in affective disorders. We describe the phenomenon of amygdala-kindled seizures episodically breaking through effective daily pharmacotherapy with carbamazepine and valproate, suggesting that these observations could reflect the balance of pathological vs compensatory illness-induced changes in gene expression. Under certain circumstances, amygdala-kindled animals that were initially drug responsive can develop highly individualized patterns of seizure breakthroughs progressing toward a complete loss of drug efficacy. This initial drug efficacy may reflect the combination of drug-related exogenous neurochemical mechanisms and illness-induced endogenous compensatory mechanisms. However, we postulate that when seizures are inhibited, the endogenous illness-induced adaptations dissipate (the “time-off seizure” effect), leading to the re-emergence of seizures, a re-induction of a new, but diminished, set of endogenous compensatory mechanisms, and a temporary period of renewed drug efficacy. As this pattern repeats, an intermittent or cyclic response to the anticonvulsant treatment emerges, leading toward complete drug tolerance. We also postulate that the cyclic pattern accelerates over time because of both the failure of robust illness-induced endogenous adaptations to emerge and the progression in pathophysiological mechanisms (mediated by long-lasting changes in gene expression and their downstream consequences) as a result of repeated occurrences of seizures. In this seizure model, this pattern can be inhibited and drug responsivity can be temporarily reinstated by several manipulations, including lowering illness drive (decreasing the stimulation current.), increasing drug dosage, switching to a new drug that does not show crosstolerance to the original medication, or temporarily discontinuing treatment, allowing the illness to re-emerge in an unmedicated animal. Each of these variables is discussed in relation to the potential relevance to the emergence, progression, and suppression of individual patterns of episodic cyclicity in the recurrent affective disorders. A variety of clinical studies are outlined that specifically test the hypotheses derived from this formulation. Data from animal studies suggest that illness cyclicity can develop from the relative ratio between primary pathological processes and secondary endogenous adaptations (assisted by exogenous medications). If this proposition is verified, it further suggests that illness cyclicity is inherent to the neurobiological processes of episode emergence and amelioration, and one does not need to postulate a separate defect in the biological clock. The formulation predicts that early and aggressive long-term interventions may be optimal in order to prevent illness emergence and progression and its associated accumulating neurobiological, vulnerability factors.     

pH track of expanding bacterial populations

A method of pH distribution measurements in agar nutrient media containing expanding bacterial populations is described. It is based on measuring pH microsamples taken at different points of the media. The sample volume was 10 microliters. A pH sensitive field effect transistor was used as a measuring electrode. Acidification was found to occur in glucose media, while alkalization occurred in the media containing peptone.     

吉林蛟河针阔混交林树木生长的空间关联格局

以吉林蛟河21.12hm2(660m×320m)针阔混交林样地为对象,利用2009年和2014年森林生长观测数据,研究树木生长的空间自相关格局及其生境影响机制。在样地生境型划分结果的基础上,采用Ripley's L(r)函数分析不同生境型中树木种群空间分布特征;利用标记相关函数分析不同生境型中树木生长特征的空间关联格局。研究结果表明:(1)红松(生境型3:1—5m)、蒙古栎(生境型3:1—3m)、胡桃楸(生境型2:1—2m;生境型3:1—7m)、黄檗(生境型2:1—3m;生境型4:1—5m)、水曲柳(生境型3:1—2m;生境型4:1—2m)、瘤枝卫矛(生境型2:1—15m)在特定生境和空间尺度上呈随机分布,但空间格局仍以聚集性分布为主;其余10个物种则在全部0—30m尺度上呈聚集分布。(2)标记相关函数分析显示春榆、毛榛、色木槭、瘤枝卫矛和千金榆的径向生长至少在一个生境中表现出正相关格局;暴马丁香、胡桃楸、裂叶榆、瘤枝卫矛、水曲柳、紫椴、糠椴、毛榛、色木槭和白牛槭的径向生长至少在一个生境中表现出负相关格局;红松、黄檗、蒙古栎和簇毛槭的径向生长在全部尺度上均未检测到显著的空间关联格局。因此,不同树种径向生长的空间自相关特征不同,树种生长特征的空间关联格局具有明显的生境依赖性。     

土地整理项目区的景观格局及其生态效应

目前项目角度的土地整理生态效应评价较少,受到研究幅度的制约,而且已有研究中对景观格局优化目标和生态效应的系统分析较少.选择典型的土地整理项目作为研究案例,以GIS和景观指数为研究手段,结合景观格局优化目标建立相应的指标体系,对土地整理的生态效应进行评价.研究表明,土地整理项目的生态效应指标体系包括提升生物多样性、维持物质和能量流通、维持景观格局稳定、提升生活环境品质、提高生态服务价值等5个方面.研究区土地整理具有正效应和负效应,最大斑块面积提高、斑块密度减少、聚集度提高、廊道宽度和连通度提高、缓冲区宽度增加、植被覆盖增加、合理功能分区是土地整理的正效应,而景观多样性降低、分维数减少和生态服务价值降低是其负效应.因此,在土地整理规划和设计时应融入景观设计和生态保育思想.     

Characteristics of von Willebrand Factor multimer adhesion and its bio-inspired applications

The von Willebrand Factor (vWF) is a large multimeric protein that aids blood clotting. Hydrodynamic force triggers elongation of vWF; this regulates its activity by exposing binding sites for platelets and collagen. To investigate mechanisms of vWF multimer adhesion to relevant biological entities, a coarse grain molecular model is used to explore vWF interaction with collagen-coated surfaces. The vWF multimer model incorporates observed mechanical properties of vWF monomers in that the model A2 domain in each monomer is capable of significant elongation with sufficient applied force on the molecule. Brownian dynamics simulations have been performed to understand a single vWF multimer adhesion process in both free-draining and hydrodynamic interactions (HI) cases. Results show the configuration at the moment of adhesion is critical, as this dictates the configuration of vWF thereafter. The presence of the collagen-coated surface increases the stretching of vWF multimers and the elongation of model A2 domains. HI effect plays a hindering role in unfolding of vWF multimer and elongation of model A2 domains. The adhesion is impeded by HI, and results in hydrodynamic lift leading to vWF multimer migration away from the wall.     

Mitochondrial Dehydrogenases in Different Taxa of Tetrahymena: Effect of Insulin

Mitochondrial dehydrogenase activity was measured in seven taxa of Tetrahymena (T. pyriformis G1, T. hegewishi, T. malaccensis, T. pigmentosa, T. shapiro, T. thermophila CU-399, T. thermophila MS-1). Enzyme activity was different in the taxa investigated. Insulin reduced enzyme activity in six of the seven taxa studied. The duration of activity reduction was relatively long (5–10 min.) in most of the cases, and in T. hegewishi this lasted up to the end of the measurements (30 min.). There was no interrelation between the basic dehydrogenase activity of the taxon and the effect of insulin. There was also no correlation between the degree of relationship (of the taxa) and the dehydrogenase profile after insulin treatment.     

阿托品联合综合疗法治疗青少年屈光不正的疗效及安全性分析

目的:分析阿托品联合综合疗法治疗青少年屈光不正弱视的近期疗效及安全性。方法:以2017年2月至2017年5月于我院接受诊治的60例青少年屈光不正弱视患者(患眼102只)为研究对象,按接受诊治时间先后顺序分为对照组和观察组各30例。患眼分别为52和50只。观察治疗前后所有屈光不正弱视患者的视觉敏感度、图像诱发电位(P-VEP)、立体视功能的改善、治疗有效率和不良反应的发生情况。结果:治疗后,两组患眼对比度、波幅均较治疗前显著升高(P0.05),潜伏期低于治疗前(P0.05),且观察组各空间频率下的对比度、波幅均显著高于对照组(P0.05),潜伏期低于对照组(P0.05);观察组患眼的矫正幅度范围和矫正分开范围显著高于对照组,矫正近立体视锐角显著低于对照组(P0.05);观察组的治疗总有效率为92.00%,高于对照组的71.15%(P0.05);两组患者均未见明显的不良反应发生。结论:阿托品联合综合疗法对青少年屈光不正弱视的近期疗效较好,且安全性高。