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

Preface to the Princeton Landmarks in Biology Edition vii Preface xi Symbols Used xiii 1. The Importance of Islands 3 2. Area and Number of Speicies 8 3. Further Explanations of the Area-Diversity Pattern 19 4. The Strategy of Colonization 68 5. Invasibility and the Variable Niche 94 6. Stepping Stones and Biotic Exchange 123 7. Evolutionary Changes Following Colonization 145 8. Prospect 181 Glossary 185 References 193 Index 201

The Theory of Island Biogeography

5.1. Detection Formats 475 5.2. Food Quality and Safety Analysis 477 5.2.1. Pathogens 477 5.2.2. Toxins 479 5.2.3. Veterinary Drugs 479 5.2.4. Vitamins 480 5.2.5. Hormones 480 5.2.6. Diagnostic Antibodies 480 5.2.7. Allergens 481 5.2.8. Proteins 481 5.2.9. Chemical Contaminants 481 5.3. Medical Diagnostics 481 5.3.1. Cancer Markers 481 5.3.2. Antibodies against Viral Pathogens 482 5.3.3. Drugs and Drug-Induced Antibodies 483 5.3.4. Hormones 483 5.3.5. Allergy Markers 483 5.3.6. Heart Attack Markers 484 5.3.7. Other Molecular Biomarkers 484 5.4. Environmental Monitoring 484 5.4.1. Pesticides 484 5.4.2. 2,4,6-Trinitrotoluene (TNT) 485 5.4.3. Aromatic Hydrocarbons 485 5.4.4. Heavy Metals 485 5.4.5. Phenols 485 5.4.6. Polychlorinated Biphenyls 487 5.4.7. Dioxins 487 5.5. Summary 488 6. Conclusions 489 7. Abbreviations 489 8. Acknowledgment 489 9. References 489

Surface Plasmon Resonance Sensors for Detection of Chemical and Biological Species

I read this book the same weekend that the Packers took on the Rams, and the experience of the latter event, obviously, colored my judgment. Although I abhor anything that smacks of being a handbook (like, \"How to Earn a Merit Badge in Neurosurgery\") because too many volumes in biomedical science already evince a boyscout-like approach, I must confess that parts of this volume are fast, scholarly, and significant, with certain reservations. I like parts of this well-illustrated book because Dr. Sj6strand, without so stating, develops certain subjects on technique in relation to the acquisition of judgment and sophistication. And this is important! So, given that the author (like all of us) is somewhat deficient in some areas, and biased in others, the book is still valuable if the uninitiated reader swallows it in a general fashion, realizing full well that what will be required from the reader is a modulation to fit his vision, propreception, adaptation and response, and the kind of problem he is undertaking. A major deficiency of this book is revealed by comparison of its use of physics and of chemistry to provide understanding and background for the application of high resolution electron microscopy to problems in biology. Since the volume is keyed to high resolution electron microscopy, which is a sophisticated form of structural analysis, but really morphology in a modern guise, the physical and mechanical background of The instrument and its ancillary tools are simply and well presented. The potential use of chemical or cytochemical information as it relates to biological fine structure , however, is quite deficient. I wonder when even sophisticated morphol-ogists will consider fixation a reaction and not a technique; only then will the fundamentals become self-evident and predictable and this sine qua flon will become less mystical. Staining reactions (the most inadequate chapter) ought to be something more than a technique to selectively enhance contrast of morphological elements; it ought to give the structural addresses of some of the chemical residents of cell components. Is it pertinent that auto-radiography gets singled out for more complete coverage than other significant aspects of cytochemistry by a high resolution microscopist, when it has a built-in minimal error of 1,000 A in standard practice? I don't mean to blind-side (in strict football terminology) Dr. Sj6strand's efforts for what is \"routinely used in our laboratory\"; what is done is usually well done. It's just that …

Methods in Enzymology.

/pdf/functional-nucleic-acid-sensors-k8tlieshyr.pdf

Functional Nucleic Acid Sensors

Opioids are the primary drugs used in Western medicine for pain management and palliative care. Farming of opium poppies remains the sole source of these essential medicines, despite diverse market demands and uncertainty in crop yields due to weather, climate change, and pests. We engineered yeast to produce the selected opioid compounds thebaine and hydrocodone starting from sugar. All work was conducted in a laboratory that is permitted and secured for work with controlled substances. We combined enzyme discovery, enzyme engineering, and pathway and strain optimization to realize full opiate biosynthesis in yeast. The resulting opioid biosynthesis strains required the expression of 21 (thebaine) and 23 (hydrocodone) enzyme activities from plants, mammals, bacteria, and yeast itself. This is a proof of principle, and major hurdles remain before optimization and scale-up could be achieved. Open discussions of options for governing this technology are also needed in order to responsibly realize alternative supplies for these medically relevant compounds.

http://science.sciencemag.org/content/sci/349/6252/1095.full.pdf

Complete biosynthesis of opioids in yeast

The engineering of biological systems is anticipated to provide effective solutions to challenges that include energy and food production, environmental quality, and health and medicine. Our ability to transmit information to and from living systems, and to process and act on information inside cells, is critical to advancing the scale and complexity at which we can engineer, manipulate, and probe biological systems. We developed a general approach for assembling RNA devices that can execute higher-order cellular information processing operations from standard components. The engineered devices can function as logic gates (AND, NOR, NAND, or OR gates) and signal filters, and exhibit cooperativity. RNA devices process and transmit molecular inputs to targeted protein outputs, linking computation to gene expression and thus the potential to control cellular function.

/pdf/higher-order-cellular-information-processing-with-synthetic-2qyl0aes8e.pdf

Higher-Order Cellular Information Processing with Synthetic RNA Devices

Many applications of synthetic biology require the balanced expression of multiple genes. Although operons facilitate coordinated expression of multiple genes in prokaryotes and eukaryotes, coordinating the many post-transcriptional processes that determine the relative levels of gene expression in operons by a priori design remains a challenge. We describe a method for tuning the expression of multiple genes within operons by generating libraries of tunable intergenic regions (TIGRs), recombining various post-transcriptional control elements and screening for the desired relative expression levels. TIGRs can vary the relative expression of two reporter genes over a 100-fold range and balance expression of three genes in an operon that encodes a heterologous mevalonate biosynthetic pathway, resulting in a sevenfold increase in mevalonate production. This technology should be useful for optimizing the expression of multiple genes in synthetic operons, both in prokaryotes and eukaryotes.

Combinatorial engineering of intergenic regions in operons tunes expression of multiple genes

Recent studies have demonstrated the importance of noncoding RNA elements in regulating gene expression networks. We describe the design of a class of small trans-acting RNAs that directly regulate gene expression in a ligand-dependent manner. These allosteric riboregulators, which we call antiswitches, are made fully tunable and modular by rational design. They offer flexible control strategies by adopting active or inactive forms in response to ligand binding, depending on their design. They can be tailor-made to regulate the expression of target transcripts in response to different cellular effectors. Coupled with in vitro selection technologies for generating nucleic acid ligand-binding species, antiswitches present a platform for programming cellular behavior and genetic networks with respect to cellular state and environmental stimuli.

/pdf/programmable-ligand-controlled-riboregulators-of-eukaryotic-x3p7qf5xti.pdf

Programmable ligand-controlled riboregulators of eukaryotic gene expression.

Engineered biological systems hold promise in addressing pressing human needs in chemical processing, energy production, materials construction, and maintenance and enhancement of human health and the environment. However, significant advancements in our ability to engineer biological systems have been limited by the foundational tools available for reporting on, responding to, and controlling intracellular components in living systems. Portable and scalable platforms are needed for the reliable construction of such communication and control systems across diverse organisms. We report an extensible RNA-based framework for engineering ligand-controlled gene-regulatory systems, called ribozyme switches, that exhibits tunable regulation, design modularity, and target specificity. These switch platforms contain a sensor domain, comprised of an aptamer sequence, and an actuator domain, comprised of a hammerhead ribozyme sequence. We examined two modes of standardized information transmission between these domains and demonstrate a mechanism that allows for the reliable and modular assembly of functioning synthetic RNA switches and regulation of ribozyme activity in response to various effectors. In addition to demonstrating examples of small molecule-responsive, in vivo functional, allosteric hammerhead ribozymes, this work describes a general approach for the construction of portable and scalable gene-regulatory systems. We demonstrate the versatility of the platform in implementing application-specific control systems for small molecule-mediated regulation of cell growth and noninvasive in vivo sensing of metabolite production.

https://www.pnas.org/content/pnas/104/36/14283.full.pdf

Christina D. Smolke

Papers

Complete biosynthesis of opioids in yeast

Higher-Order Cellular Information Processing with Synthetic RNA Devices

Combinatorial engineering of intergenic regions in operons tunes expression of multiple genes

Programmable ligand-controlled riboregulators of eukaryotic gene expression.

A modular and extensible RNA-based gene-regulatory platform for engineering cellular function