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

https://www.seas.upenn.edu/%7Edischer/pdfs/Cell_on_Gel-CELLpaper.pdf

Matrix elasticity directs stem cell lineage specification.

Microarrays can measure the expression of thousands of genes to identify changes in expression between different biological states. Methods are needed to determine the significance of these changes while accounting for the enormous number of genes. We describe a method, Significance Analysis of Microarrays (SAM), that assigns a score to each gene on the basis of change in gene expression relative to the standard deviation of repeated measurements. For genes with scores greater than an adjustable threshold, SAM uses permutations of the repeated measurements to estimate the percentage of genes identified by chance, the false discovery rate (FDR). When the transcriptional response of human cells to ionizing radiation was measured by microarrays, SAM identified 34 genes that changed at least 1.5-fold with an estimated FDR of 12%, compared with FDRs of 60 and 84% by using conventional methods of analysis. Of the 34 genes, 19 were involved in cell cycle regulation and 3 in apoptosis. Surprisingly, four nucleotide excision repair genes were induced, suggesting that this repair pathway for UV-damaged DNA might play a previously unrecognized role in repairing DNA damaged by ionizing radiation.

/pdf/significance-analysis-of-microarrays-applied-to-the-ionizing-10j4beasgw.pdf

Significance analysis of microarrays applied to the ionizing radiation response

Although gold is the subject of one of the most ancient themes of investigation in science, its renaissance now leads to an exponentially increasing number of publications, especially in the context of emerging nanoscience and nanotechnology with nanoparticles and self-assembled monolayers (SAMs). We will limit the present review to gold nanoparticles (AuNPs), also called gold colloids. AuNPs are the most stable metal nanoparticles, and they present fascinating aspects such as their assembly of multiple types involving materials science, the behavior of the individual particles, size-related electronic, magnetic and optical properties (quantum size effect), and their applications to catalysis and biology. Their promises are in these fields as well as in the bottom-up approach of nanotechnology, and they will be key materials and building block in the 21st century. Whereas the extraction of gold started in the 5th millennium B.C. near Varna (Bulgaria) and reached 10 tons per year in Egypt around 1200-1300 B.C. when the marvelous statue of Touthankamon was constructed, it is probable that “soluble” gold appeared around the 5th or 4th century B.C. in Egypt and China. In antiquity, materials were used in an ecological sense for both aesthetic and curative purposes. Colloidal gold was used to make ruby glass 293 Chem. Rev. 2004, 104, 293−346

Gold nanoparticles: assembly, supramolecular chemistry, quantum-size-related properties, and applications toward biology, catalysis, and nanotechnology.

Semiconductor nanocrystals were prepared for use as fluorescent probes in biological staining and diagnostics. Compared with conventional fluorophores, the nanocrystals have a narrow, tunable, symmetric emission spectrum and are photochemically stable. The advantages of the broad, continuous excitation spectrum were demonstrated in a dual-emission, single-excitation labeling experiment on mouse fibroblasts. These nanocrystal probes are thus complementary and in some cases may be superior to existing fluorophores.

https://science.sciencemag.org/content/sci/281/5385/2013.full.pdf

Semiconductor Nanocrystals as Fluorescent Biological Labels

Highly localized chemical catalysis was carried out on the surface groups of a self-assembled monolayer with a scanning probe device. With the use of a platinum-coated atomic force microscope tip, the terminal azide groups of the monolayer were catalytically hydrogenated with high spatial resolution. The newly created amino groups were then covalently modified to generate new surface structures. By varying the nature of the catalyst and the chemical composition of the surface, it may be possible to synthesize molecular assemblies not readily produced by existing microfabrication techniques.

https://science.sciencemag.org/content/sci/268/5208/272.full.pdf

A strategy for the chemical synthesis of nanostructures.

Efforts toward expansion of the genetic alphabet: replication of DNA with three base pairs.

A general chemical strategy has been developed whereby antibody combining sites can be selectively derivatized with natural or synthetic molecules, such as catalytic groups, drugs, metals, or reporter molecules. Cleavable affinity labels were used to selectively introduce a thiol into the combining site of the immunoglobulin A MOPC 315. This thiol acted both as a nucleophile to accelerate ester thiolysis 60,000-fold and as a handle for selectively derivatizing the antibody with additional functional groups. For example, derivatization of the antibody with a fluorophore made possible a direct spectroscopic assay of antibody-ligand complexation. This chemistry should not only extend our ability to exploit antibody specificity in chemical catalysis, diagnostics, and therapeutics, but may also prove generally applicable to the functional modification of other proteins for which detailed structural information is unavailable.

https://science.sciencemag.org/content/sci/242/4881/1038.full.pdf

Introduction of nucleophiles and spectroscopic probes into antibody combining sites.

The three-dimensional structure of an antibody (39-A11) that catalyzes a Diels-Alder reaction has been determined. The structure suggests that the antibody catalyzes this pericyclic reaction through a combination of packing and hydrogen-bonding interactions that control the relative geometries of the bound substrates and electronic distribution in the dienophile. A single somatic mutation, serine-91 of the light chain to valine, is largely responsible for the increase in affinity and catalytic activity of the affinity-matured antibody. Structural and functional studies of the germ-line precursor suggest that 39-A11 and related antibodies derive from a family of germ-line genes that have been selected throughout evolution for the ability of the encoded proteins to form a polyspecific combining site. Germ line-encoded antibodies of this type, which can rapidly evolve into high-affinity receptors for a broad range of structures, may help to expand the binding potential associated with the structural diversity of the primary antibody repertoire.

https://science.sciencemag.org/content/sci/279/5358/1929.full.pdf

Immunological origins of binding and catalysis in a Diels-Alderase antibody.

We have generated a novel silver(I)-mediated unnatural DNA base pair consisting of two 2,6-bis(ethylthiomethyl)pyridine nucleobases SPy. This metallo-base pair has a remarkably high pairing stability and selectivity which rivals that of the natural base pairs dA:dT and dC:dG. UV-melting experiments revealed that the dSPy:dSPy self-pair can replace natural base pairs at multiple sites and still form stable DNA duplexes.

Peter G. Schultz

Papers

A strategy for the chemical synthesis of nanostructures.

Efforts toward expansion of the genetic alphabet: replication of DNA with three base pairs.

Introduction of nucleophiles and spectroscopic probes into antibody combining sites.

Immunological origins of binding and catalysis in a Diels-Alderase antibody.

A novel silver(i)-mediated DNA base pair.