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

Despite the concern that has been expressed about potential method biases, and the pervasiveness of research settings with the potential to produce them, there is disagreement about whether they really are a problem for researchers in the behavioral sciences. Therefore, the purpose of this review is to explore the current state of knowledge about method biases. First, we explore the meaning of the terms “method” and “method bias” and then we examine whether method biases influence all measures equally. Next, we review the evidence of the effects that method biases have on individual measures and on the covariation between different constructs. Following this, we evaluate the procedural and statistical remedies that have been used to control method biases and provide recommendations for minimizing method bias.

Sources of Method Bias in Social Science Research and Recommendations on How to Control It

I have developed "tennis elbow" from lugging this book around the past four weeks, but it is worth the pain, the effort, and the aspirin. It is also worth the (relatively speaking) bargain price. Including appendixes, this book contains 894 pages of text. The entire panorama of the neural sciences is surveyed and examined, and it is comprehensive in its scope, from genomes to social behaviors. The editors explicitly state that the book is designed as "an introductory text for students of biology, behavior, and medicine," but it is hard to imagine any audience, interested in any fragment of neuroscience at any level of sophistication, that would not enjoy this book. The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or

Principles of Neural Science

This paper presents a critical appraisal of resilience, a construct connoting the maintenance of positive adaptation by individuals despite experiences of significant adversity. As empirical research on resilience has burgeoned in recent years, criticisms have been levied at work in this area. These critiques have generally focused on ambiguities in definitions and central terminology; heterogeneity in risks experienced and competence achieved by individuals viewed as resilient; instability of the phenomenon of resilience; and concerns regarding the usefulness of resilience as a theoretical construct. We address each identified criticism in turn, proposing solutions for those we view as legitimate and clarifying misunderstandings surrounding those we believe to be less valid. We conclude that work on resilience possesses substantial potential for augmenting the understanding of processes affecting at-risk individuals. Realization of the potential embodied by this construct, however, will remain constrained without continued scientific attention to some of the serious conceptual and methodological pitfalls that have been noted by skeptics and proponents alike.

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The Construct of Resilience: A Critical Evaluation and Guidelines for Future Work

The secretion of glucocorticoids (GCs) is a classic endocrine response to stress. Despite that, it remains controversial as to what purpose GCs serve at such times. One view, stretching back to the time of Hans Selye, posits that GCs help mediate the ongoing or pending stress response, either via basal levels of GCs permitting other facets of the stress response to emerge efficaciously, and/or by stress levels of GCs actively stimulating the stress response. In contrast, a revisionist viewpoint posits that GCs suppress the stress response, preventing it from being pathologically overactivated. In this review, we consider recent findings regarding GC action and, based on them, generate criteria for determining whether a particular GC action permits, stimulates, or suppresses an ongoing stressresponse or, as an additional category, is preparative for a subsequent stressor. We apply these GC actions to the realms of cardiovascular function, fluid volume and hemorrhage, immunity and inflammation, metabolism, neurobiology, and reproductive physiology. We find that GC actions fall into markedly different categories, depending on the physiological endpoint in question, with evidence for mediating effects in some cases, and suppressive or preparative in others. We then attempt to assimilate these heterogeneous GC actions into a physiological whole. (Endocrine Reviews 21: 55‐ 89, 2000)

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How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions.

Chemical and physiological approaches to neuroendocrine mechanisms: attempts at integration.

In situ hybridization detection of estradiol-induced changes in ribosomal RNA levels in rat brain.

Fifteen years ago, one of us proposed the hypothesis that insulin resistance (IR) is a missing link between mood disorders and dementia.1, 2 See Figure 1. Recently, the field has exploded with the data supporting all components of the model, especially the connection between depressive disorders and IR.3, 4 Increasing number of studies also confirm a role of depressive disorders in accelerating onset of dementia.5, 6, 7 IR is a modifiable metabolic proinflammatory state underlying type 2 diabetes mellitus (T2DM), cardiovascular disease, vascular dementia and Alzheimer’s disease. Today both, mass media and specialty literature are replete with information on the topic and ‘stress’ is often cited as the cause. Yet, while ‘stress’ is invoked, the profound epigenetic effects of stressful and other daily experiences and the resulting health-related behaviors resulting from them need to be more clearly recognized and defined.

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Insulin resistance—a missing link no more

Publisher Summary The development of the neuroendocrine system involves not only the maturation of the individual components and their abilities to produce hormones but also the acquisition of the functional capacity of the brain and pituitary to be influenced by target gland hormones During development, target gland hormones may exert permanent organizational effects on the development of brain function, besides exerting their reversible activational actions on neuroendocrine function and behavior These multiple actions of target gland hormones are illustrated by the gonadal steroids This chapter examines the ontogeny of hypothalamo-hypophyseal-gonadal function in the laboratory rat in relation to the development of sexual behavior, neuroendocrine feedback systems, and the process of sexual differentiation During the development of the rat brain in late fetal and early postnatal life, two major events occur with respect to reproductive function—sexual maturation and sexual differentiation Sexual maturation is a result not only of neurological maturation, and of growth and maturation of the reproductive tract, gonads, pituitary, hypothalamic neurosecretory cells and hypothalamohypophyseal portal circulation, but also of acquisition of the competence of brain and pituitary to respond to the activating effects of gonadal steroids

Sexual Maturation and Differentiation: The Role of the Gonadal Steroids

Adrenal steroids can have prodigious effects on the structure, function, and survival of hippocampal neurons. In the rat hippocampus, the actions of adrenal steroids are mediated by two receptor types, the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR). Using in situ hybridization, we have examined the regulation of the messenger RNAs (mRNAs) encoding the glucocorticoid and mineralocorticoid receptors, by aldosterone, which acts selectively through MR, and by RU28362, which acts selectively through GR. Our results demonstrate that there is autoregulation of each receptor subtype, such that activation of GR regulates GR mRNA levels and MR activation regulates MR mRNA expression. In addition, there is evidence that aldosterone, acting through MR, can affect the expression of GR mRNA. The extent to which a specific agonist can produce a significant change in the expression of a particular steroid receptor mRNA varies between the different subfields of the hippocampus.

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Bruce S. McEwen

Papers

Chemical and physiological approaches to neuroendocrine mechanisms: attempts at integration.

In situ hybridization detection of estradiol-induced changes in ribosomal RNA levels in rat brain.

Insulin resistance—a missing link no more

Sexual Maturation and Differentiation: The Role of the Gonadal Steroids

Regulation of Glucocorticoid Receptor and Mineralocorticoid Receptor Messenger Ribonucleic Acids by Selective Agonists in the Rat Hippocampus