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

http://experimentationlab.berkeley.edu/sites/default/files/AFMImages/butt_AFM.pdf

Force measurements with the atomic force microscope: Technique, interpretation and applications

Contractile myocytes provide a test of the hypothesis that cells sense their mechanical as well as molecular microenvironment, altering expression, organization, and/or morphology accordingly. Here, myoblasts were cultured on collagen strips attached to glass or polymer gels of varied elasticity. Subsequent fusion into myotubes occurs independent of substrate flexibility. However, myosin/actin striations emerge later only on gels with stiffness typical of normal muscle (passive Young's modulus, E approximately 12 kPa). On glass and much softer or stiffer gels, including gels emulating stiff dystrophic muscle, cells do not striate. In addition, myotubes grown on top of a compliant bottom layer of glass-attached myotubes (but not softer fibroblasts) will striate, whereas the bottom cells will only assemble stress fibers and vinculin-rich adhesions. Unlike sarcomere formation, adhesion strength increases monotonically versus substrate stiffness with strongest adhesion on glass. These findings have major implications for in vivo introduction of stem cells into diseased or damaged striated muscle of altered mechanical composition.

/pdf/myotubes-differentiate-optimally-on-substrates-with-tissue-2s499cqco3.pdf

Myotubes differentiate optimally on substrates with tissue-like stiffness: pathological implications for soft or stiff microenvironments

Guided Lamb waves for identification of damage in composite structures: A review

Cell migration through 3D tissue depends on a physicochemical balance between cell deformability and physical tissue constraints. Migration rates are further governed by the capacity to degrade ECM by proteolytic enzymes, particularly matrix metalloproteinases (MMPs), and integrin- and actomyosin-mediated mechanocoupling. Yet, how these parameters cooperate when space is confined remains unclear. Using MMP-degradable collagen lattices or nondegradable substrates of varying porosity, we quantitatively identify the limits of cell migration by physical arrest. MMP-independent migration declined as linear function of pore size and with deformation of the nucleus, with arrest reached at 10% of the nuclear cross section (tumor cells, 7 µm2; T cells, 4 µm2; neutrophils, 2 µm2). Residual migration under space restriction strongly depended upon MMP-dependent ECM cleavage by enlarging matrix pore diameters, and integrin- and actomyosin-dependent force generation, which jointly propelled the nucleus. The limits of interstitial cell migration thus depend upon scaffold porosity and deformation of the nucleus, with pericellular collagenolysis and mechanocoupling as modulators.

/pdf/physical-limits-of-cell-migration-control-by-ecm-space-and-52gk5w0erg.pdf

Physical limits of cell migration: Control by ECM space and nuclear deformation and tuning by proteolysis and traction force

Summary Histone variants fine-tune transcription, replication, DNA damage repair, and faithful chromosome segregation. The histone H3 variant CENP-A/CENH3 seeds the kinetochore, creating the physical interface between centromeric chromatin and mitotic spindles. How kinetochore proteins modify CENP-A nucleosome dynamics and how these dynamics affect centromere chromatin is poorly understood. Using interdisciplinary analyses, we report that CENP-A nucleosomes are intrinsically more elastic than H3 nucleosomes, and that the kinetochore component CENP-C suppresses this innate elasticity. Shifting the balance between elastic and stiffer CENP-A states in vivo results in the suppression of centromeric chromatin plasticity, so that centromeric chromatin becomes less permissive to RNA polymerase 2, thereby diminishing new CENP-A loading, ensuing in mitotic defects. Restoring this balance rescues mitotic defects. Together, these data provide a link between innate structural properties possessed by histone variant nucleosomes, the adaptability of chromatin states in vivo, and the epigenetic plasticity of the underlying locus.

https://www.biorxiv.org/content/biorxiv/early/2019/03/14/392787.full.pdf

The accessibility of human centromeric chromatin is modulated by elastic CENP-A nucleosomes

Elephants and baleen whales are massive creatures that respond to exceptionally low frequency signals. Although we have many elephant and whale vocalization recordings, little is known about their hearing. Playback experiments suggest hearing in both proboscideans and mysticetes is tuned similarly to low or even infrasonic signals. This raises several interesting issues. First, they emit and perceive signals in two media, air and water, with radically different physical acoustic properties: 4.5‐fold differences in sound speed, three‐fold magnitude difference in acoustic impedance, and, for common percepts, whales must accommodate 60‐fold acoustic pressures. Also, a commonly held tenet is that upper hearing limit is inversely correlated with body mass, implying there should be virtually no whale‐elephant hearing overlap given body mass differences. This study analyzed how inner ears in these groups are structured and specialized for low‐frequency hearing. Computerized tomography and celloidin histology sections were analyzed in six baleen whale (n=15) and two elephant species (n=7). The data show mysticetes have a substantially greater hearing range than elephants but that coiling and apical cochlear structures are similar, suggesting common mechanical underpinnings for LF hearing, including cochlear radii consistent with the Whispering Gallery propagation effect. [Work supported by ONR, NIH, WHOI OLI, Seaver Foundation.]

Great ears: Functional comparisons of land and marine leviathan ears

Molecular Study of HIV-Tat Aggregation

Abstract Biomaterials with antimicrobial activity are gaining attention due to their biodegradability and efficacy in interacting with a wide range of microorganisms. A new cellulose nano-biomaterial, endospermic nanocellulose crystals (ENC) obtained from parenchymal tissue of ivory nut endosperm, has a natural capacity as a universal binder. This feature is enhanced when it is chemically functionalized, and can be exploited in the fight against microbes. We tested the ability of sulfated ENC in aqueous suspension to encapsulate viruses through a crosslinking reaction mediated by cations. 0.25% w/v ENC suspensions efficiently encapsulated spike (S) protein, preventing its interaction with ACE2 receptor. ENC was further able to encapsulate SARS-CoV-2 pseudoviruses and prevent infection of 293T-ACE2 cells. ENC also suppressed infection of MT-4 cells with HIV-1 LAI.04 . This antiviral activity of sulfated ENC is due to the irreversible interaction of ENC with viral particles mediated by crosslinking, as antiviral activity was less effective in the absence of cations. Additionally, ENC was used as a matrix to immobilize recombinant ACE2 receptors and anti-S IgG, creating molecular lures that efficiently inhibited SARS-CoV-2 infections in vitro . These results show that sulfated ENC from ivory nuts can be used as an efficient antiviral material. 

/pdf/sulfated-endospermic-nanocellulose-crystals-prevent-the-3md4sjeu.pdf

Emilios K. Dimitriadis

Papers

The accessibility of human centromeric chromatin is modulated by elastic CENP-A nucleosomes

Great ears: Functional comparisons of land and marine leviathan ears

Molecular Study of HIV-Tat Aggregation

Sulfated endospermic nanocellulose crystals prevent the transmission of SARS-CoV-2 and HIV-1

Periosteal stem cell microenvironment compositional and elasticity changes in the vicinity of bone fracture