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

Experimental introduction of RNA into cells can be used in certain biological systems to interfere with the function of an endogenous gene Such effects have been proposed to result from a simple antisense mechanism that depends on hybridization between the injected RNA and endogenous messenger RNA transcripts RNA interference has been used in the nematode Caenorhabditis elegans to manipulate gene expression Here we investigate the requirements for structure and delivery of the interfering RNA To our surprise, we found that double-stranded RNA was substantially more effective at producing interference than was either strand individually After injection into adult animals, purified single strands had at most a modest effect, whereas double-stranded mixtures caused potent and specific interference The effects of this interference were evident in both the injected animals and their progeny Only a few molecules of injected double-stranded RNA were required per affected cell, arguing against stochiometric interference with endogenous mRNA and suggesting that there could be a catalytic or amplification component in the interference process

Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans

Ligand: a versatile computerized approach for characterization of ligand-binding systems.

Cell signaling by receptor-tyrosine kinases

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.

The present invention relates to a modified arrestin which includes an arrestin molecule and a ubiquitin molecule. This modified arrestin has an increased affinity for a GPCR, and traffics with the GPCR into endosomes. The present invention further relates to a method of screening compounds and sample solutions for a GPCR agonist, antagonist, inverse agonist, or desensitization active compound. The modified arrestin is useful in the methods of the present invention.

Modified trafficking patterns for arrestin and g-protein-coupled receptors via arrestin-ubiquitin chimera

2001: An AAP (Association of American Physicians) odyssey.

A reconstitution assay for the guanine nucleotide regulatory protein of the adenylate cyclase system using turkey erythrocyte membranes as the acceptor preparation

Recent advances in the identification and isolation of cell-membrane hormone receptors are reviewed and critically evaluated. Three systems are examined in some detail: the isolated adrenergic, cholinergic, and insulin binding sites. A physiological receptor performs two important functions: specific binding of biologically active drugs and hormones, and activation of subsequent cellular processes such as adenyl cyclase or sodium ion permeability. In each of the three systems discussed, a binding site thought to represent the physiological receptor has been solubilized and partially purified. These binding sites appear to be macromolecules, generally proteins located within the plasma membranes of sensitive cells. They bind agonist and antagonist drugs rapidly and reversibly, with specificities and affinities generally parallel to those characterizing the interaction of these compounds with intact tissues in vivo. To date, only the binding characteristics of these isolated receptor sites have been studied, and little is known of their effector properties. Firm proof that the sites being studied are in fact identical with the physiological receptors will require their recombination with other cell-membrane constituents form intact systems in which addition of agonist drugs is followed not only by binding, but also by a characteristic biological response.

Robert J. Lefkowitz

Papers

Modified trafficking patterns for arrestin and g-protein-coupled receptors via arrestin-ubiquitin chimera

2001: An AAP (Association of American Physicians) odyssey.

A reconstitution assay for the guanine nucleotide regulatory protein of the adenylate cyclase system using turkey erythrocyte membranes as the acceptor preparation

Physiological receptors as physicochemical entities.

Techniques for the study of the biochemical basis of drug action