There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

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

计量经济分析 = Econometric analysis

Single-molecule force spectroscopy has emerged as a powerful tool to investigate the forces and motions associated with biological molecules and enzymatic activity. The most common force spectroscopy techniques are optical tweezers, magnetic tweezers and atomic force microscopy. Here we describe these techniques and illustrate them with examples highlighting current capabilities and limitations.

Single-molecule force spectroscopy: optical tweezers, magnetic tweezers and atomic force microscopy

At cell–cell adhesions, α-catenin contains a cryptic vinculin-binding site. Here, Yao et al. demonstrate, using magnetic tweezers, that physiologically relevant forces unfurl α-catenin to reveal the vinculin-binding site, and allow the reversible binding of vinculin to mechanically reinforce the adhesion.

/pdf/force-dependent-conformational-switch-of-a-catenin-controls-2kjdnn5a87.pdf

Force-dependent conformational switch of α-catenin controls vinculin binding.

Talin, a force-bearing cytoplasmic adapter essential for integrin-mediated cell adhesion, links the actin cytoskeleton to integrin-based cell–extracellular matrix adhesions at the plasma membrane. Its C-terminal rod domain, which contains 13 helical bundles, plays important roles in mechanosensing during cell adhesion and spreading. However, how the structural stability and transition kinetics of the 13 helical bundles of talin are utilized in the diverse talin-dependent mechanosensing processes remains poorly understood. Here we report the force-dependent unfolding and refolding kinetics of all talin rod domains. Using experimentally determined kinetics parameters, we determined the dynamics of force fluctuation during stretching of talin under physiologically relevant pulling speeds and experimentally measured extension fluctuation trajectories. Our results reveal that force-dependent stochastic unfolding and refolding of talin rod domains make talin a very effective force buffer that sets a physiological force range of only a few pNs in the talin-mediated force transmission pathway.

/pdf/the-mechanical-response-of-talin-tozrvdtwiw.pdf

The mechanical response of talin

National Research Foundation of Singapore through the Mechanobiology Institute at National University of Singapore; NIH [EB001480]

/pdf/mechanical-activation-of-vinculin-binding-to-talin-locks-2q6ds8yyg6.pdf

Mechanical activation of vinculin binding to talin locks talin in an unfolded conformation

The force-dependent interaction between talin and vinculin plays a crucial role in the initiation and growth of focal adhesions. Here we use magnetic tweezers to characterise the mechano-sensitive compact N-terminal region of the talin rod, and show that the three helical bundles R1–R3 in this region unfold in three distinct steps consistent with the domains unfolding independently. Mechanical stretching of talin R1–R3 enhances its binding to vinculin and vinculin binding inhibits talin refolding after force is released. Mutations that stabilize R3 identify it as the initial mechano-sensing domain in talin, unfolding at ∼5 pN, suggesting that 5 pN is the force threshold for vinculin binding and adhesion progression.

Mechanical activation of vinculin binding to talin locks talin in an unfolded

Recent experiments indicate that double-stranded DNA molecules of approximately 100 base pairs in length have a probability of cyclization which is up to 10(5) times larger than that expected based on the known bending modulus of the double-helix. We argue that for short molecules, the formation of a few base pairs of single-stranded DNA can provide a "flexible hinge" that facilitates loop formation. A detailed calculation shows that this mechanism explains the experimental data.

Jie Yan

Papers

Force-dependent conformational switch of α-catenin controls vinculin binding.

The mechanical response of talin

Mechanical activation of vinculin binding to talin locks talin in an unfolded conformation

Mechanical activation of vinculin binding to talin locks talin in an unfolded

Localized single-stranded bubble mechanism for cyclization of short double helix DNA.