抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction

中枢神経系疾患の治療は正常細胞（ニューロン）の機能維持を目的とするが，脳血管障害のように機能障害の原因が細胞の死滅に基づくことは多い．一方，脳腫瘍の治療においては薬物療法や放射線療法といった腫瘍細胞の死滅を目標とするものが大きな位置を占める．いずれの場合にも，細胞死の機序を理解することは各種病態や治療法の理解のうえで重要である．現在のところ最も研究の進んでいる細胞死の型はアポトーシスである．そのなかで重要な位置を占めるミトコンドリアにおける反応および抗アポトーシス因子について概要を紹介する．

Neuroscience 細胞死：最近の知見

■ Abstract Apoptosis is a genetically programmed, morphologically distinct form of cell death that can be triggered by a variety of physiological and pathological stimuli. Studies performed over the past 10 years have demonstrated that proteases play critical roles in initiation and execution of this process. The caspases, a family of cysteine-dependent aspartate-directed proteases, are prominent among the death proteases. Caspases are synthesized as relatively inactive zymogens that become activated by scaffold-mediated transactivation or by cleavage via upstream proteases in an intracellular cascade. Regulation of caspase activation and activity occurs at several different levels: ( a) Zymogen gene transcription is regulated; ( b) antiapoptotic members of the Bcl-2 family and other cellular polypeptides block proximity-induced activation of certain procaspases; and ( c) certain cellular inhibitor of apoptosis proteins (cIAPs) can bind to and inhibit active caspases. Once activated, caspases cleave a variety of intracellular polypeptides, including major structural elements of the cytoplasm and nucleus, components of the DNA repair machinery, and a number of protein kinases. Collectively, these scissions disrupt survival pathways and disassemble important architectural components of the cell, contributing to the stereotypic morphological and biochemical changes that characterize apoptotic cell death.

Mammalian caspases: structure ,a ctivation ,s ubstrates, and functions during apoptosis

基礎講座 電気泳動(Electrophoresis)

Purpose To study glial cell line-derived neurotrophic factor (GDNF) concentrations in aqueous humor (AH), lacrimal fluid (LF), and blood serum (BS) in patients with age-related cataract and primary open-angle glaucoma (POAG). Methods GDNF was studied in AH, LF, and BS in 47 patients with age-related cataract, and 30 patients with POAG combined with cataract (one eye in each person). AH was sampled during cataract surgery. Results GDNF concentration (pg/ml) in patients with POAG and cataract was lower than in cataract-only patients (p<0.001), both in AH (46.3±31.1 versus 88.9±46.9) and in LF (222±101 versus 344±134). The difference was not significant for the GDNF concentration in BS (194±56 versus 201±45). In the earlier (early and moderate) stages of POAG, compared to later (advanced and severe) stages, GDNF concentration was significantly lower in LF (176±99 versus 258±91; p = 0.027) and in BS (165±42 versus 217±55; p = 0.017), while GDNF concentration in AH showed an insignificant difference (40.0±25.7 versus 51.1±34.7). In patients with POAG, GDNF concentration in LF and BS was inversely correlated with the Humphrey visual field index: Pearson’s correlation coefficient r = −0.465 (p = 0.01) for LF and r = −0.399 (p = 0.029) for BS. When compared to the cataract group, patients in the earlier stages of POAG showed significantly lower GDNF concentrations in all studied biologic fluids. Conclusions Compared to patients with cataract only, GDNF levels are lower in the AH and LF of patients with POAG and cataract, especially at earlier stages of the disease (at these stages, the GDNF level in BS is also lower). At earlier stages of POAG, compared to later stages, GDNF content is lower in LF and BS. These data could serve as a reason for the therapeutic use of GDNF in patients with POAG.

Glial cell line-derived neurotrophic factor (GDNF) in patients with primary open-angle glaucoma and age-related cataract

Lipids play an important role in the function of membranes, for they determine their viscosity, the state of their receptors and ionic channels, and the activity of membrane-bound enzymes [9]. It has been shown that the lipid component of synaptosomes is a modulator of activity of the serotoninergic system [2]. Differences in the lipid composition of the brain have recently been demonstrated in mice selected on the basis of different brain weight and differing in their learning ability [1]. One of the most important processes leading to modification of the lipid component of membrane is free-radical lipid peroxidation (LPO), changes in the intensity of which accompany many changes in brain function [1, 2, 4, 8]. The aim of this investigation was to study the state of LPO and of the brain lipid composition during training.

Effect of bilateral avoidance conditioning on brain lipid composition in rats

Chronic Stress Induced by Keeping in Conditions of Nesting Material Deficiency in the Early Postnatal Period Affects Behavior and Stress Reactivity in Male Rats

Olfactory bulbectomy in rodents is widely used as a model of the symptoms of clinical depression and neurodegeneration, including cholinergic. Male C57BL/6 mice in the present study underwent olfactory bulbectomy. Formation of long-term nonassociative memory (habituation) and spatial memory were studied two and four weeks after surgery. The effect of bulbectomy on the state of neurons in the medial septal area was studied using immunohistochemical staining for choline acetyltransferase and NeuN at the end of the behavioral studies, i.e., four and seven weeks after surgery. Bulbectomy led to impaired habituation in terms of measures of motor activity in the open field test and impaired spatial learning, but not memory in a water maze at both time points. A decrease in the proportion of cholinergic cells in the medial septal area was seen at four but not seven weeks after surgery. There were no significant changes in the total number of neurons in this part of the brain. Thus, the occurrence of cognitive impairment after olfactory bulbectomy may be associated with the manifestations of transient cholinergic deficit at the early stages of the development of pathology.

Impaired Memory Formation and the Development of Transient Cholinergic Deficit in Mice after Olfactory Bulbectomy

It is well known that opiates, in particular morphine, are involved in a phenomenon of so-called pathological plasticity and can bring about considerable structural-functional changes in the CNS, which is an important mechanism of the formation of dependence. It has been found that realization of pharmacological effects during acute or chronic action of morphine may be related to changes in the activity of receptors, signal cascades mediated by secondary messengers, and shifts in the expression of some genes. Less is known about the relationship between the effects of morphine and functioning of intracellular proteolytic enzymes which are an important system of post-translational modification of proteins. On the basis of our results and data of literature, we hypothesized that a number of structural changes induced by morphine may be mediated by proteolytic enzymes from caspase family.

Natalia V. Gulyaeva

Papers

Glial cell line-derived neurotrophic factor (GDNF) in patients with primary open-angle glaucoma and age-related cataract

Effect of bilateral avoidance conditioning on brain lipid composition in rats

Chronic Stress Induced by Keeping in Conditions of Nesting Material Deficiency in the Early Postnatal Period Affects Behavior and Stress Reactivity in Male Rats

Impaired Memory Formation and the Development of Transient Cholinergic Deficit in Mice after Olfactory Bulbectomy

Involvement of brain intracellular proteolytic systems in the effects of opiates: Caspases