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

Resolving the molecular details of proteome variation in the different tissues and organs of the human body will greatly increase our knowledge of human biology and disease. Here, we present a map of the human tissue proteome based on an integrated omics approach that involves quantitative transcriptomics at the tissue and organ level, combined with tissue microarray-based immunohistochemistry, to achieve spatial localization of proteins down to the single-cell level. Our tissue-based analysis detected more than 90% of the putative protein-coding genes. We used this approach to explore the human secretome, the membrane proteome, the druggable proteome, the cancer proteome, and the metabolic functions in 32 different tissues and organs. All the data are integrated in an interactive Web-based database that allows exploration of individual proteins, as well as navigation of global expression patterns, in all major tissues and organs in the human body.

Tissue-based map of the human proteome

The optical properties of metal nanoparticles have long been of interest in physical chemistry, starting with Faraday's investigations of colloidal gold in the middle 1800s. More recently, new lithographic techniques as well as improvements to classical wet chemistry methods have made it possible to synthesize noble metal nanoparticles with a wide range of sizes, shapes, and dielectric environments. In this feature article, we describe recent progress in the theory of nanoparticle optical properties, particularly methods for solving Maxwell's equations for light scattering from particles of arbitrary shape in a complex environment. Included is a description of the qualitative features of dipole and quadrupole plasmon resonances for spherical particles; a discussion of analytical and numerical methods for calculating extinction and scattering cross-sections, local fields, and other optical properties for nonspherical particles; and a survey of applications to problems of recent interest involving triangula...

/pdf/the-optical-properties-of-metal-nanoparticles-the-influence-16vrpkvhkg.pdf

The Optical Properties of Metal Nanoparticles: The Influence of Size, Shape, and Dielectric Environment

Fundamentals of Plasmonics.- Electromagnetics of Metals.- Surface Plasmon Polaritons at Metal / Insulator Interfaces.- Excitation of Surface Plasmon Polaritons at Planar Interfaces.- Imaging Surface Plasmon Polariton Propagation.- Localized Surface Plasmons.- Electromagnetic Surface Modes at Low Frequencies.- Applications.- Plasmon Waveguides.- Transmission of Radiation Through Apertures and Films.- Enhancement of Emissive Processes and Nonlinearities.- Spectroscopy and Sensing.- Metamaterials and Imaging with Surface Plasmon Polaritons.- Concluding Remarks.

/pdf/plasmonics-fundamentals-and-applications-4syb9877sr.pdf

Plasmonics: Fundamentals and Applications

CHARMM (Chemistry at HARvard Molecular Mechanics) is a highly versatile and widely used molecu- lar simulation program. It has been developed over the last three decades with a primary focus on molecules of bio- logical interest, including proteins, peptides, lipids, nucleic acids, carbohydrates, and small molecule ligands, as they occur in solution, crystals, and membrane environments. For the study of such systems, the program provides a large suite of computational tools that include numerous conformational and path sampling methods, free energy estima- tors, molecular minimization, dynamics, and analysis techniques, and model-building capabilities. The CHARMM program is applicable to problems involving a much broader class of many-particle systems. Calculations with CHARMM can be performed using a number of different energy functions and models, from mixed quantum mechanical-molecular mechanical force fields, to all-atom classical potential energy functions with explicit solvent and various boundary conditions, to implicit solvent and membrane models. The program has been ported to numer- ous platforms in both serial and parallel architectures. This article provides an overview of the program as it exists today with an emphasis on developments since the publication of the original CHARMM article in 1983.

/pdf/charmm-the-biomolecular-simulation-program-4kexem0xkx.pdf

CHARMM: the biomolecular simulation program.

Protein and messenger RNA (mRNA) copy numbers vary from cell to cell in isogenic bacterial populations. However, these molecules often exist in low copy numbers and are difficult to detect in single cells. We carried out quantitative system-wide analyses of protein and mRNA expression in individual cells with single-molecule sensitivity using a newly constructed yellow fluorescent protein fusion library for Escherichia coli. We found that almost all protein number distributions can be described by the gamma distribution with two fitting parameters which, at low expression levels, have clear physical interpretations as the transcription rate and protein burst size. At high expression levels, the distributions are dominated by extrinsic noise. We found that a single cell's protein and mRNA copy numbers for any given gene are uncorrelated.

/pdf/quantifying-e-coli-proteome-and-transcriptome-with-single-1xqg8lgkev.pdf

Quantifying E. coli proteome and transcriptome with single-molecule sensitivity in single cells.

Label-free chemical contrast is highly desirable in biomedical imaging. Spontaneous Raman microscopy provides specific vibrational signatures of chemical bonds, but is often hindered by low sensitivity. Here we report a three-dimensional multiphoton vibrational imaging technique based on stimulated Raman scattering (SRS). The sensitivity of SRS imaging is significantly greater than that of spontaneous Raman microscopy, which is achieved by implementing high-frequency (megahertz) phase-sensitive detection. SRS microscopy has a major advantage over previous coherent Raman techniques in that it offers background-free and readily interpretable chemical contrast. We show a variety of biomedical applications, such as differentiating distributions of omega-3 fatty acids and saturated lipids in living cells, imaging of brain and skin tissues based on intrinsic lipid contrast, and monitoring drug delivery through the epidermis.

/pdf/label-free-biomedical-imaging-with-high-sensitivity-by-41w9epjm6e.pdf

Label-free biomedical imaging with high sensitivity by stimulated raman scattering microscopy

A multiphoton microscopy based on coherent anti-Stokes Raman scattering is accomplished with near-infrared ultrashort laser pulses. We demonstrate vibrational imaging of chemical and biological samples with high sensitivity, high spatial resolution, noninvasiveness, and three-dimensional sectioning capability. {copyright} {ital 1999} {ital The American Physical Society}

Three-Dimensional Vibrational Imaging by Coherent Anti-Stokes Raman Scattering

Enzymatic turnovers of single cholesterol oxidase molecules were observed in real time by monitoring the emission from the enzyme's fluorescent active site, flavin adenine dinucleotide (FAD). Statistical analyses of single-molecule trajectories revealed a significant and slow fluctuation in the rate of cholesterol oxidation by FAD. The static disorder and dynamic disorder of reaction rates, which are essentially indistinguishable in ensemble-averaged experiments, were determined separately by the real-time single-molecule approach. A molecular memory phenomenon, in which an enzymatic turnover was not independent of its previous turnovers because of a slow fluctuation of protein conformation, was evidenced by spontaneous spectral fluctuation of FAD.

https://science.sciencemag.org/content/sci/282/5395/1877.full.pdf

Single-Molecule Enzymatic Dynamics

Confocal [1] and multiphoton [2] fluorescence microscopy have become powerful techniques for threedimensional imaging of chemical and biological samples, especially for live cells. This coincides with developments of various natural and artificial fluorescent probes for cellular constituents [3]. For chemical species or cellular components that either do not fluoresce or cannot tolerate labeling, infrared microscopy and spontaneous Raman microscopy can be used as contrast mechanisms based on vibrational properties. Conventional infrared microscopy is limited to low spatial resolution because of the long wavelength of light used. High resolution Raman microscopy of biological samples has been demonstrated with a confocal microscope [4]. However, the intrinsically weak Raman signal necessitates high laser powers (typically .10 mW) and is often overwhelmed by the fluorescence background of the sample. A multiphoton microscopy based on coherent anti-Stokes Raman scattering (CARS) [5] was put forward as an alternative way of providing vibrational contrast [6]. However, the sensitivity of CARS microscopy was limited by the nonresonant background signal, and high resolution three-dimensional sectioning was not achieved. In the study reported here, we demonstrate CARS microscopy in the chemically interesting vibrational spectral region around 3000 cm21 with high spatial resolution and three-dimensional sectioning capability. Most importantly, the use of near-infrared laser pulses generated by a Ti:sapphire laser s,855 nmd and an optical parametric oscillator/amplifier s,1.2 mmd allows a significant improvement in signal to background ratio in CARS detection. Unlike spontaneous Raman microscopy, the highly sensitive CARS microscopy requires only a moderate average power for excitation s,0.1 mWd, tolerable by most biological samples. CARS spectroscopy has been extensively used as a spectroscopic tool for chemical analyses in the condensed and gas phases [7]. In doing CARS spectroscopy, a pump laser and a Stokes laser beam, with center frequencies of np and nS , respectively, are spatially overlapped. The CARS signal at 2np 2 nS is generated in a direction determined by the phase-matching conditions. When the frequency difference np 2 nS coincides with the frequency of a molecular vibration of the sample, the CARS

/pdf/three-dimensional-vibrational-imaging-by-coherent-anti-4t6ahp4ekl.pdf

X. Sunney Xie

Papers

Quantifying E. coli proteome and transcriptome with single-molecule sensitivity in single cells.

Label-free biomedical imaging with high sensitivity by stimulated raman scattering microscopy

Three-Dimensional Vibrational Imaging by Coherent Anti-Stokes Raman Scattering

Single-Molecule Enzymatic Dynamics

Three-Dimensional Vibrational Imaging by Coherent Anti-Stokes Raman Scattering