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)

During the 5 s of the acrosome reaction of Limulus polyphemus sperm, a 60-μm-long bundle of scruin-decorated actin filaments straightens from a coiled conformation and extends from the cell. To identify the motive force for this movement, we examined the possible sources of chemical and mechanical energy and show that the coil releases ∼10−13 J of stored mechanical strain energy, whereas chemical energy derived from calcium binding is ∼10−15 J. These measurements indicate that the coiled actin bundle extends by a spring-based mechanism, which is distinctly different from the better known polymerization or myosin-driven processes, and that calcium initiates but does not power the reaction.

/pdf/stored-elastic-energy-powers-the-60-mm-extension-of-the-2oej1zim9o.pdf

Stored elastic energy powers the 60-μm extension of the Limulus polyphemus sperm actin bundle

Unsteady Motion, Finite Reynolds Numbers, and Wall Effect on Vorticella convallaria Contribute Contraction Force Greater than the Stokes Drag

satisfying experience in science occurs when information from several areas converge to give a big picture about an important problem. In three papers (Holtzman et al., 1994; Honts et al., 1994; McGough et al., 1994) in this issue of The Journal of Cell Biology, the disciplines of genetics and structural biology have revealed that two actin cross-linking proteins, fimbrin and alpha-actinin, bind to the same region on actin. Because both proteins belong to a superfamily of actin cross-linking proteins, we have some confidence that other members of the superfamily, including filamin, spectrin, dystrophin, and ABP-120, also bind the same region of actin. This information about binding sites is an important step toward understanding how actin illaments are organized by cross-linking proteins into bundles and supramolecular networks. This story is rooted in the classic biochemical studies of muscle proteins. Alpha-actinin was first purified from skeletal muscle (Maruyama and Ebashi, 1965) and characterized as a Z-line component; its rodlike shape was revealed by electron microscopy (see Meyer and Aebi, 1990). Later, spurred by cell biologists who demonstrated that cytoplasmic extracts of noumuscle cells could undergo reversible solgel transformations, a generation of biologists isolated and characterized a number of actin gelation and bundling proteins, including ABP-280 and filamin, speetrin, fascin, and ABP-120, from ameba (reviewed in Pollard and Cooper, 1986; Stossel et al., 1985; Weeds, 1982); alpha-actinin was rediscovered as a nonmuscle actin cross-linking protein (Burridge and Feramisco, 1981). During the late 1980's, eDNA sequencing showed that many of these gelation factors belonged to a superfamily that shares a common 27-kD NH2-terminal domain (Baron et al., 1987) that binds actin filaments. Fimbrin bundles actin filaments in intestinal brush border microvilli, and it is also located where actin bundles terminate at membrane adhesion plaques (Bretscher and Weber, 1980). The sequence databases (de Arruda et al., 1990) showed that fimbrin was also involved in cell transformation (Lin et al., 1994), and that it was a target of phosphorylation when leukocytes are activated by growth factors and mitogens (Zu et al., 1990). Hence, fimbrin is also called plastin and pp70. An important structural theme emerged from the sequences: cross-linking proteins in this superfamily are

/pdf/the-fimbrin-and-alpha-actinin-footprint-on-actin-2r296schmo.pdf

The fimbrin and alpha-actinin footprint on actin.

Differential stabilization of two hydrophobic cores in the transition state of the villin 14T folding reaction.

A method and apparatus for illuminating a subject with deep UV light and detecting 2-dimensional image information, e.g., a transmission image, fluorescence image, reflected light image, etc. The subject may be illuminated with a light pulse having a duration of 2 seconds or less and one or more components with a wavelength of between about 150 nm to about 300 nm. The light pulse may be arranged so as to minimize or eliminate any detrimental effect on the functioning of the subject, e.g., on a living cell. A concentration, mass, quantum yield, absorbance or other characteristics of one or more compounds in the subject may be determined based on one or more 2-dimensional images obtained of the subject. An illumination beam having left and right circularly polarized components may be generated, e.g., for circular dichroism analysis of a subject.

Paul Matsudaira

Papers

Stored elastic energy powers the 60-μm extension of the Limulus polyphemus sperm actin bundle

Unsteady Motion, Finite Reynolds Numbers, and Wall Effect on Vorticella convallaria Contribute Contraction Force Greater than the Stokes Drag

The fimbrin and alpha-actinin footprint on actin.

Differential stabilization of two hydrophobic cores in the transition state of the villin 14T folding reaction.

Method and apparatus for UV imaging