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

A ubiquitous observation in cell biology is that the diffusive motion of macromolecules and organelles is anomalous, and a description simply based on the conventional diffusion equation with diffusion constants measured in dilute solution fails. This is commonly attributed to macromolecular crowding in the interior of cells and in cellular membranes, summarizing their densely packed and heterogeneous structures. The most familiar phenomenon is a sublinear, power-law increase of the mean-square displacement (MSD) as a function of the lag time, but there are other manifestations like strongly reduced and time-dependent diffusion coefficients, persistent correlations in time, non-Gaussian distributions of spatial displacements, heterogeneous diffusion and a fraction of immobile particles. After a general introduction to the statistical description of slow, anomalous transport, we summarize some widely used theoretical models: Gaussian models like fractional Brownian motion and Langevin equations for visco-elastic media, the continuous-time random walk model, and the Lorentz model describing obstructed transport in a heterogeneous environment. Particular emphasis is put on the spatio-temporal properties of the transport in terms of two-point correlation functions, dynamic scaling behaviour, and how the models are distinguished by their propagators even if the MSDs are identical. Then, we review the theory underlying commonly applied experimental techniques in the presence of anomalous transport like single-particle tracking, fluorescence correlation spectroscopy (FCS) and fluorescence recovery after photobleaching (FRAP). We report on the large body of recent experimental evidence for anomalous transport in crowded biological media: in cyto- and nucleoplasm as well as in cellular membranes, complemented by in vitro experiments where a variety of model systems mimic physiological crowding conditions. Finally, computer simulations are discussed which play an important role in testing the theoretical models and corroborating the experimental findings. The review is completed by a synthesis of the theoretical and experimental progress identifying open questions for future investigation.

https://iopscience.iop.org/article/10.1088/0034-4885/76/4/046602/pdf

Anomalous transport in the crowded world of biological cells.

The intracellular environment represents an extremely crowded milieu, with a limited amount of free water and an almost complete lack of unoccupied space. Obviously, slightly salted aqueous solutions containing low concentrations of a biomolecule of interest are too simplistic to mimic the “real life” situation, where the biomolecule of interest scrambles and wades through the tightly packed crowd. In laboratory practice, such macromolecular crowding is typically mimicked by concentrated solutions of various polymers that serve as model “crowding agents”. Studies under these conditions revealed that macromolecular crowding might affect protein structure, folding, shape, conformational stability, binding of small molecules, enzymatic activity, protein-protein interactions, protein-nucleic acid interactions, and pathological aggregation. The goal of this review is to systematically analyze currently available experimental data on the variety of effects of macromolecular crowding on a protein molecule. The review covers more than 320 papers and therefore represents one of the most comprehensive compendia of the current knowledge in this exciting area.

https://www.mdpi.com/1422-0067/15/12/23090/pdf

What Macromolecular Crowding Can Do to a Protein

Effects of molecular crowding on the structures, interactions, and functions of nucleic acids.

ConspectusOwing to their unique biological, physical, and chemical properties, fluoroalkylated organic substances have attracted significant attention from researchers in a variety of disciplines. Fluoroalkylated compounds are considered particularly important in pharmaceutical chemistry because of their superior lipophilicity, binding selectivity, metabolic stability, and bioavailability to those of their nonfluoroalkylated analogues. We have developed various methods for the synthesis of fluoroalkylated substances that rely on the use of visible-light photoredox catalysis, a powerful preparative tool owing to its environmental benignity and mechanistic versatility in promoting a large number of synthetically important reactions with high levels of selectivity.In this Account, we describe the results of our efforts, which have led to the development of visible-light photocatalytic methods for the introduction of a variety of fluoroalkyl groups (such as, −CF3, −CF2R, −CH2CF3, −C3F7, and −C4F9) and arylthi...

Controlled Fluoroalkylation Reactions by Visible-Light Photoredox Catalysis

The effect of salt on the dynamics of water molecules follows the Hofmeister series. For some “structure-making” salts, the self-diffusion coefficient of the water molecules, D, decreases with increasing salt concentration. For other “structure-breaking” salts, D increases with increasing salt concentration. In this work, the concentration and temperature dependence of the self-diffusion of water in electrolyte solutions is studied using molecular dynamics simulations and pulsed-field-gradient NMR experiments; temperature-dependent viscosities are also independently measured. Simulations of rigid, nonpolarizable models at room temperature show that none of the many models tested can reproduce the experimentally observed trend for the concentration dependence of D; that is, the models predict that D decreases with increasing salt concentration for both structure-breaking and structure-making salts. Predictions of polarizable models are not in agreement with experiment either. These results suggest that man...

Self-diffusion and viscosity in electrolyte solutions.

Effect of macromolecular crowding on reaction rates: a computational and theoretical study.

We investigate structural alterations of random-loop polymers due to changes in the crowding condition, as a model to study environmental effects on the structure of chromosome subcompartments. The polymer structure is changed in a nonmonotonic fashion with an increasing density of crowders: condensed at small volume fractions; decondensed at high crowding volume fractions. The nonmonotonic behavior is a manifestation of the nontrivial distance dependence of the depletion interactions. We also show that crowding-induced structural alterations affect the access of binding proteins to the surface of polymer segments and are distinguished from structural changes due to the increased number of specific polymer loops.

https://www.mccormick.northwestern.edu/biomedical/documents/backman/PhysRevLett-106-168102_Kim_CrowdingInducdStructAlt_Apr2011.pdf

Crowding-induced structural alterations of random-loop chromosome model.

A new procedure for calculating the nonlinear energy transfer and linear growth/damping rate of fully developed turbulence is derived. It avoids the unphysically large damping rates typically obtained using the predecessor method of Ritz [Ch. P. Ritz, E. J. Powers, and R. D. Bengtson, Phys. Fluids B 1, 153 (1989)]. It enforces stationarity of the turbulence to reduce the effects of noise and fluctuations not described by the basic governing equation, and includes the fourth‐order moment to avoid the closure approximation. The new procedure has been implemented and tested on simulated, fully developed two‐dimensional (2‐D) turbulence data from a 2‐D trapped‐particle fluid code, and has been shown to give excellent reconstructions of the input growth rate and nonlinear coupling coefficients with good noise rejection. However, in the experimentally important case where only a one‐dimensional (1‐D) averaged representation of the underlying 2‐D turbulence is available, this technique does not, in general, give acceptable results. A new 1‐D algorithm has thus been developed for analysis of 1‐D measurements of intrinsically 2‐D turbulence. This new 1‐D algorithm includes the nonresonant wave numbers in calculating the bispectra, and generally gives useful results when the width of the radial wave number spectrum is comparable to or less than that of the poloidal spectrum.

/pdf/technique-for-the-experimental-estimation-of-nonlinear-564vvvb3ed.pdf

Technique for the experimental estimation of nonlinear energy transfer in fully developed turbulence

https://www.cell.com/biophysj/pdf/S0006-3495(09)01751-2.pdf

Jun Soo Kim

Papers

Self-diffusion and viscosity in electrolyte solutions.

Effect of macromolecular crowding on reaction rates: a computational and theoretical study.

Crowding-induced structural alterations of random-loop chromosome model.

Technique for the experimental estimation of nonlinear energy transfer in fully developed turbulence

Crowding Effects on Association Reactions at Membranes