BackgroundIn vertebrates, non-lens βγ-crystallins are widely expressed in various tissues, but their functions are unknown. The molecular mechanisms of trefoil factors, initiators of mucosal healing and being greatly involved in tumorigenesis, have remained elusive.Principal FindingsA naturally existing 72-kDa complex of non-lens βγ-crystallin (α-subunit) and trefoil factor (β-subunit), named βγ-CAT, was identified from frog Bombina maxima skin secretions. Its α-subunit and β-subunit (containing three trefoil factor domains), with a non-covalently linked form of αβ2, show significant sequence homology to ep37 proteins, a group of non-lens βγ-crystallins identified in newt Cynops pyrrhogaster and mammalian trefoil factors, respectively. βγ-CAT showed potent hemolytic activity on mammalian erythrocytes. The specific antiserum against each subunit was able to neutralize its hemolytic activity, indicating that the two subunits are functionally associated. βγ-CAT formed membrane pores with a functional diameter about 2.0 nm, leading to K+ efflux and colloid-osmotic hemolysis. High molecular weight SDS-stable oligomers (>240-kDa) were detected by antibodies against the α-subunit with Western blotting. Furthermore, βγ-CAT showed multiple cellular effects on human umbilical vein endothelial cells. Low dosages of βγ-CAT (25–50 pM) were able to stimulate cell migration and wound healing. At high concentrations, it induced cell detachment (EC50 10 nM) and apoptosis. βγ-CAT was rapidly endocytosed via intracellular vacuole formation. Under confocal microscope, some of the vacuoles were translocated to nucleus and partially fused with nuclear membrane. Bafilomycin A1 (a specific inhibitor of the vacuolar-type ATPase) and nocodazole (an agent of microtuble depolymerizing), while inhibited βγ-CAT induced vacuole formation, significantly inhibited βγ-CAT induced cell detachment, suggesting that βγ-CAT endocytosis is important for its activities.Conclusions/SignificanceThese findings illustrate novel cellular functions of non-lens βγ-cyrstallins and action mechanism via association with trefoil factors, serving as clues for investigating the possible occurrence of similar molecules and action mechanisms in mammals.

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Assuming the minimal requirements necessary to derive the Froissart bound, the number of subtractions for the fixed-momentum-transfer dispersion relation in the unphysical region 0

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Toll–IL-1R (TIR) family members play crucial roles in a variety of defense, inflammatory, injury, and stress responses. Although they have been widely investigated in mammals, little is known about TIRs in ancient vertebrates. In this study, we report a novel double Ig IL-1R related molecule (DIGIRR) from three model fish (Tetraodon nigroviridis, Gasterosteus aculeatus, and Takifugu rubripes), adding a previously unknown homolog to the TIR family. This DIGIRR molecule contains two Ig-like domains in the extracellular region, one Arg-Tyr–mutated TIR domain in the intracellular region, and a unique subcellular distribution within the Golgi apparatus. These characteristics distinguish DIGIRR from other known family members. In vitro injection of DIGIRR into zebrafish embryos dramatically inhibited LPS-induced and IL-1β–induced NF-κB activation. Moreover, in vivo knockdown of DIGIRR by small interfering RNA significantly promoted the expression of IL-1β–stimulated proinflammatory cytokines (IL-6 and IL-1β) in DIGIRR-silenced liver and kidney tissues and in leukocytes. These results strongly suggest that DIGIRR is an important negative regulator of LPS-mediated and IL-1β–mediated signaling pathways and inflammatory responses. The Arg-Tyr–mutated site disrupted the signal transduction ability of DIGIRR TIR. Evolutionally, we propose a hypothesis that DIGIRR and single Ig IL-1R related molecule (SIGIRR) might originate from a common ancient IL-1R–like molecule that lost one (in DIGIRR) or two (in SIGIRR) extracellular Ig-like domains and intracellular Ser and Arg-Tyr amino acids. DIGIRR might be an evolutionary “transitional molecule” between IL-1R and SIGIRR, representing a shift from a potent receptor to a negative regulator. These results help define the evolutionary history of TIR family members and their associated signaling pathways and mechanisms.

Aerosol-induced haze problem has become a serious environmental concern. Filtration is widely applied to remove aerosols from gas streams. Despite classical filtration theories, the nanoscale capture and evolution of aerosols is not yet clearly understood. Here we report an in situ investigation on the nanoscale capture and evolution of aerosols on polyimide nanofibers. We discovered different capture and evolution behaviors among three types of aerosols: wetting liquid droplets, nonwetting liquid droplets, and solid particles. The wetting droplets had small contact angles and could move, coalesce, and form axisymmetric conformations on polyimide nanofibers. In contrast, the nonwetting droplets had a large contact angle on polyimide nanofibers and formed nonaxisymmetric conformations. Different from the liquid droplets, the solid particles could not move along the nanofibers and formed dendritic structures. This study provides an important insight for obtaining a deep understanding of the nanoscale capture and evolution of aerosols and benefits future design and development of advanced filters.

The long-range biomechanical force propagating across large scale may reserve the capability to trigger coordinative responses within cell population such as during angiogenesis, epithelial tubulogenesis, and cancer metastasis. How cells communicate in a distant manner within the group for self-assembly remains largely unknown. Here we found that airway smooth muscle cells (ASMCs) rapidly self-assembled into well-constructed network on 3D Matrigel containing type I collagen (COL), which relied on long-range biomechanical force across the matrix to direct cell-cell distant interactions. Similar results happened by HUVEC cells to mimic angiogenesis. Interestingly, single ASMCs initiated multiple extended protrusions precisely pointing to neighboring cells in distance, depending on traction force sensing. Separate ASMCs sensed each other to move directionally on both non-fibrous Matrigel and more efficiently when containing fibrous COL, but lost mutual sensing on fixed gel or coated glass due to no longrange force transmission. Beads tracking assay demonstrated distant transmission of traction force, and finite element method modeling confirmed the consistency between maximum strain distribution on matrix and cell directional movements in experiments. Furthermore, ASMCs recruited COL from the hydrogel to build fibrous network to mechanically stabilize cell network.Our results revealed for the first time that cells can sense traction force transmitted through the matrix to initiate cell-cell distant mechanical communications, resulting in cell directional migration and coordinative self-assembly with active matrix remodeling. As an interesting phenomenon, cells sound able to 'make phone call' via long-range biomechanics, which implicates physiological importance such as for tissue pattern formation.

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