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

Hypertension 66 (20.3%) 24 (24.2%) 30 (16.3%) NS Diabetes 20 (6.2%) 7 (7.1%) 10 (5.4%) NS Excess weight 78 (24%) 27 (27.3%) 44 (23.9%) NS Smokers 64 (19.7%) 17 (17.2%) 35 (19.0%) NS Age >50 years 137 (42.2%) 54 (54.5%) 67 (36.4%) <0.02 Kidney disease 7 (2.2%) 1 (1%) 5 (2.7%) NS Family history, DM 102 (31.4%) 28 (28.3%) 66 (35.9%) NS

Conflict of interest statement. None declared.

A progress report is presented on a selection of scientific, technological and commercial advances in the biomedical applications of magnetic nanoparticles since 2003. Particular attention is paid to (i) magnetic actuation for in vitro non-viral transfection and tissue engineering and in vivo drug delivery and gene therapy, (ii) recent clinical results for magnetic hyperthermia treatments of brain and prostate cancer via direct injection, and continuing efforts to develop new agents suitable for targeted hyperthermia following intravenous injection and (iii) developments in medical sensing technologies involving a new generation of magnetic resonance imaging contrast agents, and the invention of magnetic particle imaging as a new modality. Ongoing prospects are also discussed.

/pdf/progress-in-applications-of-magnetic-nanoparticles-in-1fdltiiz5p.pdf

Progress in applications of magnetic nanoparticles in biomedicine

Tissue engineering aims at developing functional substitutes for damaged tissues and organs. Before transplantation, cells are generally seeded on biomaterial scaffolds that recapitulate the extracellular matrix and provide cells with information that is important for tissue development. Here we review the nanocomposite nature of the extracellular matrix, describe the design considerations for different tissues and discuss the impact of nanostructures on the properties of scaffolds and their uses in monitoring the behaviour of engineered tissues. We also examine the different nanodevices used to trigger certain processes for tissue development, and offer our view on the principal challenges and prospects of applying nanotechnology in tissue engineering.

/pdf/nanotechnological-strategies-for-engineering-complex-tissues-39p00hx1z2.pdf

Nanotechnological strategies for engineering complex tissues.

Challenges Eun-Kyung Lim,†,‡,§ Taekhoon Kim, Soonmyung Paik, Seungjoo Haam, Yong-Min Huh,*,† and Kwangyeol Lee* Department of Chemistry, Korea University, Seoul 136-701, Korea †Department of Radiology, Yonsei University, Seoul 120-752, Korea Severance Biomedical Research Institute, Yonsei University College of Medicine, Seoul 120-749, Korea Division of Pathology, NSABP Foundation, Pittsburgh, Pennsylvania 15212, United States Department of Chemical and Biomolecular Engineering, Yonsei University, Seoul 120-749, Korea ‡BioNanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Korea Electronic Materials Laboratory, Samsung Advanced Institute of Technology, Mt. 14-1, Nongseo-Ri, Giheung-Eup, Yongin-Si, Gyeonggi-Do 449-712, Korea

Nanomaterials for theranostics: recent advances and future challenges.

Complex cell behaviours are triggered by chemical ligands that bind to membrane receptors and alter intracellular signal transduction. However, future biosensors, medical devices and other microtechnologies that incorporate living cells as system components will require actuation mechanisms that are much more rapid, robust, non-invasive and easily integrated with solid-state interfaces. Here we describe a magnetic nanotechnology that activates a biochemical signalling mechanism normally switched on by binding of multivalent chemical ligands. Superparamagnetic 30-nm beads, coated with monovalent ligands and bound to transmembrane receptors, magnetize when exposed to magnetic fields, and aggregate owing to bead-bead attraction in the plane of the membrane. Associated clustering of the bound receptors acts as a nanomagnetic cellular switch that directly transduces magnetic inputs into physiological cellular outputs, with rapid system responsiveness and non-invasive dynamic control. This technique may represent a new actuator mechanism for cell-based microtechnologies and man-machine interfaces.

http://www.medicinaycomplejidad.org/pdf/modelos/mannix2007natnanorec.pdf

Nanomagnetic actuation of receptor-mediated signal transduction.

The development of effective biological scaffold materials for tissue engineering and regenerative medicine applications hinges on the ability to present precise environmental cues to specific cell populations to guide their position and function. Natural extracellular matrices have an ordered nano-scale structure that can modulate cell behaviors critical for developmental control, including directional cell motility. Here we describe a method for fabricating fibrin gels with defined architecture on the nanometer scale in which magnetic forces are used to position thrombin-coated magnetic micro-beads in a defined 2-dimensional array and thereby guide the self-assembly of fibrin fibrils through catalytic cleavage of soluble fibrinogen substrate. Time-lapse and confocal microscopy confirmed that fibrin fibrils nucleate near the surface of the thrombin-coated beads and extend out in a radial direction to form these gels. When controlled magnetic fields were used to position the beads in hexagonal arrays, the fibrin nano-fibrils that polymerized from the beads oriented preferentially along the bead--bead axes in a geodesic (minimal path) pattern. These biocompatible scaffolds supported adhesion and spreading of human microvascular endothelial cells, which exhibited co-alignment of internal actin stress fibers with underlying fibrin nano-fibrils within some membrane extensions at the cell periphery. This magnetically-guided, biologically-inspired microfabrication system is unique in that large scaffolds may be formed with little starting material, and thus it may be useful for in vivo tissue engineering applications in the future.

http://www.medicinaycomplejidad.org/pdf/modelos/alsberg_tissueeng200.pdf

Magnetically-guided self-assembly of fibrin matrices with ordered nano-scale structure for tissue engineering.

A RecA-single-stranded DNA (RecA-ssDNA) filament searches a genome for sequence homology by rapidly binding and unbinding double-stranded DNA (dsDNA) until homology is found. We demonstrate that pulling on the opposite termini (3' and 5') of one of the two DNA strands in a dsDNA molecule stabilizes the normally unstable binding of that dsDNA to non-homologous RecA-ssDNA filaments, whereas pulling on the two 3', the two 5', or all four termini does not. We propose that the 'outgoing' strand in the dsDNA is extended by strong DNA-protein contacts, whereas the 'complementary' strand is extended by the tension on the base pairs that connect the 'complementary' strand to the 'outgoing' strand. The stress resulting from different levels of tension on its constitutive strands causes rapid dsDNA unbinding unless sufficient homology is present.

/pdf/reca-homology-search-is-promoted-by-mechanical-stress-along-3thkfgzj4m.pdf

RecA homology search is promoted by mechanical stress along the scanned duplex DNA

Systems and methods for the manipulation of particles within channels such as microfluidic channels are provided. In one set of embodiments, magnets are positioned around a channel. As a fluid containing magnetic and non-magnetic particles flows through the channel, the magnetic field created by the magnets can be used to transport the magnetic and/or non-magnetic particles to desired locations within the channel, which may useful in some cases for causing some separation of the particles. For example, the magnetic field may be used to transport magnetic or non-magnetic particles from a core fluid to a surrounding sheath fluid. In some cases, the magnetic field is used to transport non-magnetic particles to a small volume within the channel (e.g., a single-file row within the channel). The systems and methods described herein may find application in a variety of fields including, for example, continuous sorting of cells, removal of targeted cells from a stream of blood, or the arrangement of non-magnetic particles in channels for analysis.

Manipulation of particles in channels

RecA-family proteins mediate homologous recombination and recombinational DNA repair through homology search and strand exchange. Initially, the protein forms a filament with the incoming single-stranded DNA (ssDNA) bound in site I. The RecA–ssDNA filament then binds double-stranded DNA (dsDNA) in site II. Non-homologous dsDNA rapidly unbinds, whereas homologous dsDNA undergoes strand exchange yielding heteroduplex dsDNA in site I and the leftover outgoing strand in site II. We show that applying force to the ends of the complementary strand significantly retards strand exchange, whereas applying the same force to the outgoing strand does not. We also show that crystallographically determined binding site locations require an intermediate structure in addition to the initial and final structures. Furthermore, we demonstrate that the characteristic dsDNA extension rates due to strand exchange and free RecA binding are the same, suggesting that relocation of the complementary strand from its position in the intermediate structure to its position in the final structure limits both rates. Finally, we propose that homology recognition is governed by transitions to and from the intermediate structure, where the transitions depend on differential extension in the dsDNA. This differential extension drives strand exchange forward for homologs and increases the free energy penalty for strand exchange of nonhomologs.

/pdf/complementary-strand-relocation-may-play-vital-roles-in-reca-3olct18ih8.pdf

Efraim Feinstein

Papers

Nanomagnetic actuation of receptor-mediated signal transduction.

Magnetically-guided self-assembly of fibrin matrices with ordered nano-scale structure for tissue engineering.

RecA homology search is promoted by mechanical stress along the scanned duplex DNA

Manipulation of particles in channels

Complementary strand relocation may play vital roles in RecA-based homology recognition