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.cell.com/cell/pdf/0092-8674(93)90509-O.pdf

Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programed cell death

Rapid progress in deciphering the biological mechanism of Alzheimer's disease (AD) has arisen from the application of molecular and cell biology to this complex disorder of the limbic and association cortices. In turn, new insights into fundamental aspects of protein biology have resulted from research on the disease. This beneficial interplay between basic and applied cell biology is well illustrated by advances in understanding the genotype-to-phenotype relationships of familial Alzheimer's disease. All four genes definitively linked to inherited forms of the disease to date have been shown to increase the production and/or deposition of amyloid β-protein in the brain. In particular, evidence that the presenilin proteins, mutations in which cause the most aggressive form of inherited AD, lead to altered intramembranous cleavage of the β-amyloid precursor protein by the protease called γ-secretase has spurred progress toward novel therapeutics. The finding that presenilin itself may be the long-sought γ-...

Alzheimer's Disease: Genes, Proteins, and Therapy

Normal tissue cells are generally not viable when suspended in a fluid and are therefore said to be anchorage dependent. Such cells must adhere to a solid, but a solid can be as rigid as glass or softer than a baby's skin. The behavior of some cells on soft materials is characteristic of important phenotypes; for example, cell growth on soft agar gels is used to identify cancer cells. However, an understanding of how tissue cells-including fibroblasts, myocytes, neurons, and other cell types-sense matrix stiffness is just emerging with quantitative studies of cells adhering to gels (or to other cells) with which elasticity can be tuned to approximate that of tissues. Key roles in molecular pathways are played by adhesion complexes and the actinmyosin cytoskeleton, whose contractile forces are transmitted through transcellular structures. The feedback of local matrix stiffness on cell state likely has important implications for development, differentiation, disease, and regeneration.

/pdf/tissue-cells-feel-and-respond-to-the-stiffness-of-their-6dx0rumap6.pdf

Tissue Cells Feel and Respond to the Stiffness of Their Substrate

This paper describes a procedure that makes it possible to design and fabricate (including sealing) microfluidic systems in an elastomeric materialpoly(dimethylsiloxane) (PDMS)in less than 24 h. A network of microfluidic channels (with width >20 μm) is designed in a CAD program. This design is converted into a transparency by a high-resolution printer; this transparency is used as a mask in photolithography to create a master in positive relief photoresist. PDMS cast against the master yields a polymeric replica containing a network of channels. The surface of this replica, and that of a flat slab of PDMS, are oxidized in an oxygen plasma. These oxidized surfaces seal tightly and irreversibly when brought into conformal contact. Oxidized PDMS also seals irreversibly to other materials used in microfluidic systems, such as glass, silicon, silicon oxide, and oxidized polystyrene; a number of substrates for devices are, therefore, practical options. Oxidation of the PDMS has the additional advantage that it ...

Rapid prototyping of microfluidic systems in poly(dimethylsiloxane)

Cytoskeletal proteins function as dynamic and complex components in many aspects of cell physiology and the maintenance of cell structure. However, very little is known about the coordinated system of these proteins. The knowledge of subcellular localization of proteins is crucial for understanding how proteins function within a cell. We present a framework for quantification of cytoskeletal protein localization from high-content microscopic images. Analyses of high content images of cells transfected by cytoskeleton genes involve individual cell segmentation, intensity transformation of subcellular compartments, protein segmentation based on correlation coefficients, and colocalization quantification of proteins in subcellular components. By quantifying the abundance of proteins in different compartments, we generate colocalization profiles that give insights into the functions of different cytoskeletal proteins.

/pdf/quantification-of-cytoskeletal-protein-localization-from-1399bcrqpg.pdf

Quantification of cytoskeletal protein localization from high-content images

PVDF (polyvinylidene difluoride) membranes have proven to be a useful support on which proteins or peptides can be immobilized during automated Edman degradation procedures (Matsudaira 1987). Several groups have reported that the initial and repetitive yields for samples electroblotted onto PVDF membranes (Baum et al 1987; Legendre and Matsudaira 1988; Moos et al 1988; Xu et al 1988; Yuen et al 1988) are much higher than samples blotted onto activated glass fiber filters (Vandekerchove et al 1985; Aebersold et al 1986). Since most of the measurements involved 100–500 pmole quantities of material, it would be valuable to evaluate the yields of < 100 pmole quantity of sample. In this study, I measured the initial and repetitive yields of 4–110 pmole quantities of 125I-s-lactoglobulin. The data suggests that both the repetitive and initial yields are independent of sample quantity and that sample loss during the sequencing cycles significantly affects the repetitive yields. Based on these results, it appears that sample detection is the major limit to routine sequence analysis of subpmole quantities of material.

Initial and Repetitive Yields from Proteins Blotted on PVDF Membranes

A two-dimensional finite-element flux-corrected transport algorithm developed for the solution of gas discharge problems is employed in the field of microfabricated electrophoretic devices used for DNA sequencing. This will assist in a comprehensive study of sample loading and injection in sample injectors in DNA electrophoresis and optimise system design. Results for the initial stages of loading and injection without pullback are introduced. Preliminary design optimisation investigates the adjustment of the pullback voltage for minimum DNA "leakage". The results demonstrate the capabilities of the numerical algorithm as a design and optimisation tool for DNA electrophoresis.

Paul Matsudaira

Papers

Quantification of cytoskeletal protein localization from high-content images

Initial and Repetitive Yields from Proteins Blotted on PVDF Membranes

Numerical modelling as a design optimisation tool for DNA electrophoresis

Intrahelical ion pairs in intermediate filaments.

Response to “Electron Microscopy of Biological Specimens in Liquid Water”