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

Signaling Recognition Events with Fluorescent Sensors and Switches.

In the last 10 years the field of molecular diagnostics has witnessed an explosion of interest in the use of nanomaterials in assays for gases, metal ions, and DNA and protein markers for many diseases. Intense research has been fueled by the need for practical, robust, and highly sensitive and selective detection agents that can address the deficiencies of conventional technologies. Chemists are playing an important role in designing and fabricating new materials for application in diagnostic assays. In certain cases assays based upon nanomaterials have offered significant advantages over conventional diagnostic systems with regard to assay sensitivity, selectivity, and practicality. Some of these new methods have recently been reviewed elsewhere with a focus on the materials themselves or as subclassifications in more generalized overviews of biological applications of nanomaterials.1-7 We intend to review some of the major advances and milestones in the field of detection systems based upon nanomaterials and their roles in biodiagnostic screening for nucleic acids, * To whom correspondence should be addressed. Phone: 847-4913907. Fax: 847-467-5123. E-mail: chadnano@northwestern.edu. Nathaniel L. Rosi earned his B.A. degree at Grinnell College (1999) and his Ph.D. degree from the University of Michigan (2003), where he studied the design, synthesis, and gas storage applications of metal−organic frameworks under the guidance of Professor Omar M. Yaghi. In 2003 he began postdoctoral studies as a member of Professor Mirkin’s group at Northwestern University. His current research focuses on the rational assembly of DNA-modified nanostructures into larger-scale materials.

/pdf/nanostructures-in-biodiagnostics-5553cs9yqw.pdf

Nanostructures in Biodiagnostics

Detection of chemical and biological agents plays a fundamental role in biomedical, forensic and environmental sciences1–4 as well as in anti bioterrorism applications.5–7 The development of highly sensitive, cost effective, miniature sensors is therefore in high demand which requires advanced technology coupled with fundamental knowledge in chemistry, biology and material sciences.8–13

In general, sensors feature two functional components: a recognition element to provide selective/specific binding with the target analytes and a transducer component for signaling the binding event. An efficient sensor relies heavily on these two essential components for the recognition process in terms of response time, signal to noise (S/N) ratio, selectivity and limits of detection (LOD).14,15 Therefore, designing sensors with higher efficacy depends on the development of novel materials to improve both the recognition and transduction processes. Nanomaterials feature unique physicochemical properties that can be of great utility in creating new recognition and transduction processes for chemical and biological sensors15–27 as well as improving the S/N ratio by miniaturization of the sensor elements.28

Gold nanoparticles (AuNPs) possess distinct physical and chemical attributes that make them excellent scaffolds for the fabrication of novel chemical and biological sensors (Figure 1).29–36 First, AuNPs can be synthesized in a straightforward manner and can be made highly stable. Second, they possess unique optoelectronic properties. Third, they provide high surface-to-volume ratio with excellent biocompatibility using appropriate ligands.30 Fourth, these properties of AuNPs can be readily tuned varying their size, shape and the surrounding chemical environment. For example, the binding event between recognition element and the analyte can alter physicochemical properties of transducer AuNPs, such as plasmon resonance absorption, conductivity, redox behavior, etc. that in turn can generate a detectable response signal. Finally, AuNPs offer a suitable platform for multi-functionalization with a wide range of organic or biological ligands for the selective binding and detection of small molecules and biological targets.30–32,36 Each of these attributes of AuNPs has allowed researchers to develop novel sensing strategies with improved sensitivity, stability and selectivity. In the last decade of research, the advent of AuNP as a sensory element provided us a broad spectrum of innovative approaches for the detection of metal ions, small molecules, proteins, nucleic acids, malignant cells, etc. in a rapid and efficient manner.37



Figure 1

Physical properties of AuNPs and schematic illustration of an AuNP-based detection system.



In this current review, we have highlighted the several synthetic routes and properties of AuNPs that make them excellent probes for different sensing strategies. Furthermore, we will discuss various sensing strategies and major advances in the last two decades of research utilizing AuNPs in the detection of variety of target analytes including metal ions, organic molecules, proteins, nucleic acids, and microorganisms.

/pdf/gold-nanoparticles-in-chemical-and-biological-sensing-5e2qojkdzn.pdf

Gold nanoparticles in chemical and biological sensing.

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.

The bimolecular quenching of the metal-to-ligand charge transfer (MLCT) excited state of Ru(phen)z(dppz)2+ (phen = 1,lO-phenanthroline, dppz = dipyrido[3,2-a:2’,3’-clphenazine) by proton transfer has been investigated in homogeneous acetonitrile solutions and in the presence of calf thymus DNA. In acetonitrile the monoexponential decay of the MLCT excited state emission of R~(phen)2(dppz)~+ is dynamically quenched by proton donors with pKa = 4.7-15.7. The emission lifetimes and quenching when the complex is bound to DNA have been measured for racemic mixtures, as well as Aand A-R~(phen)2(dppz)~+, and the values compared. In the presence of DNA the biexponential decay of the emission is quenched dynamically and three times slower than in acetonitrile when the quencher, in this case hydroquinone, is hydrophilic. Static quenching is observed in the presence of DNA when a hydrophobic proton donor, o-chlorophenol, is utilized. The static quenching with o-chlorophenol is shown to arise solely from the quenching of the long-lived component. These observations are explained in terms of two different modes of binding between the complex and DNA, as well as the different affinities for the aqueous medium of the quenchers.

Proton Transfer Quenching of the MLCT Excited State of Ru(phen)2dppz2+ in Homogeneous Solution and Bound to DNA

Transition metal complexes offer great potential as diagnostic and therapeutic agents, and a growing number of biological applications have been explored. To be effective, these complexes must reach their intended target inside the cell. Here we review the cellular accumulation of metal complexes, including their uptake, localization, and efflux. Metal complexes are taken up inside cells through various mechanisms, including passive diffusion and entry through organic and metal transporters. Emphasis is placed on the methods used to examine cellular accumulation, to identify the mechanism(s) of uptake, and to monitor possible efflux. Conjugation strategies that have been employed to improve the cellular uptake characteristics of metal complexes are also described.

/pdf/exploring-the-cellular-accumulation-of-metal-complexes-57w5yd9ro4.pdf

Exploring the cellular accumulation of metal complexes

Long-range photoinduced electron transfer has been systematically examined in a series of small DNA duplexes covalently modified with ethidium and Rh(phi)2bpy3+ through time-resolved and steady-state measurements of fluorescence quenching. Fast fluorescence quenching (k ≳ 1010 s-1) is observed for this donor/acceptor pair noncovalently bound to DNA, and transient absorption studies allow the assignment of this quenching to an electron-transfer mechanism. In the duplexes modified with tethered intercalators, intrahelix fluorescence quenching attributed to electron transfer occurs at distances up to 30 A. Over a donor/acceptor separation of ∼20 A, approximately 30% of the ethidium fluorescence is quenched, while at a separation of ∼30 A, approximately 10% quenching is observed. Time-resolved measurements indicate that this quenching is primarily static. Fluorescence polarization and melting studies indicate that the intercalators are rigidly bound, enhance helix stability, and the duplex populations are str...

Photoinduced electron transfer in ethidium-modified dna duplexes : dependence on distance and base stacking

MutY, like many DNA base excision repair enzymes, contains a [4Fe4S](2+) cluster of undetermined function Electrochemical studies of MutY bound to a DNA-modified gold electrode demonstrate that the [4Fe4S] cluster of MutY can be accessed in a DNA-mediated redox reaction Although not detectable without DNA, the redox potential of DNA-bound MutY is approximate to275 mV versus NHE, which is characteristic of HiPiP iron proteins Binding to DNA is thus associated with a change in [4Fe4S](3+/2+) potential, activating the cluster toward oxidation Given that DNA charge transport chemistry is exquisitely sensitive to perturbations in base pair structure, such as mismatches, we propose that this redox process of MutY bound to DNA exploits DNA charge transport and provides a DNA signaling mechanism to scan for mismatches and lesions in vivo

https://www.pnas.org/content/pnas/100/22/12543.full.pdf

DNA-mediated charge transport for DNA repair

The stack of base pairs within double helical DNA has been shown to mediate charge transport reactions. Charge transport through DNA can result in chemistry at a distance, yielding oxidative DNA damage at a site remote from the bound oxidant. Since DNA charge transport chemistry depends on coupling within the stacked base pair array, this chemistry is remarkably sensitive to sequence-dependent DNA structure and dynamics. Here, we discuss different features of DNA charge transport chemistry, including applications as well as possible biological consequences and opportunities.

Jacqueline K. Barton

Papers

Proton Transfer Quenching of the MLCT Excited State of Ru(phen)2dppz2+ in Homogeneous Solution and Bound to DNA

Exploring the cellular accumulation of metal complexes

Photoinduced electron transfer in ethidium-modified dna duplexes : dependence on distance and base stacking

DNA-mediated charge transport for DNA repair

Long-range DNA charge transport.