Pairs of endothelial cells on adhesive micropatterns rotate persistently, but pairs of fibroblasts do not; coherent rotation is present in normal mammary acini and kidney cells but absent in cancerous cells. Why? To answer this question, we develop a computational model of pairs of mammalian cells on adhesive micropatterns using a phase field method and study the conditions under which persistent rotational motion (PRM) emerges. Our model couples the shape of the cell, the cell's internal chemical polarity, and interactions between cells such as volume exclusion and adhesion. We show that PRM can emerge from this minimal model and that the cell-cell interface may be influenced by the nucleus. We study the effect of various cell polarity mechanisms on rotational motion, including contact inhibition of locomotion, neighbor alignment, and velocity alignment, where cells align their polarity to their velocity. These polarity mechanisms strongly regulate PRM: Small differences in polarity mechanisms can create significant differences in collective rotation. We argue that the existence or absence of rotation under confinement may lead to insight into the cell's methods for coordinating collective cell motility. C ollective cell migration is a crucial aspect of wound healing, growth and development of organs and tissues, and cancer invasion (1-3). Cells may move in cohesive groups ranging from small clusters of invading cancerous cells to ducts and branches during morphogenesis to monolayers of epithelial or endothelial cells. Two hallmarks of collective migration are strong cell-cell adhesion and multicellular polarity-an organization of the cellular orientation beyond the single-cell level (1). Cell-cell interactions can lead to collective behavior not evident in any single cell, including chemotaxis in clusters of cells that singly do not chemotax (4). Collective behavior may arise from cell-cell interactions altering the polarity of individual cells (5, 6). Many theories have been proposed for how this multicellular order appears, either in specific biological contexts (7-11) or in simpler, more generic models (12-16). Some authors argue that these dynamics are relatively universal and can be understood with minimal knowledge of the signaling pathways involved (2, 17).Collective rotation is commonly observed in collectively migrating cells, especially in confinement. Persistent rotations have been observed in the slime mold Dictyostelium discoideum (18), canine kidney epithelial cells on adhesive micropatterns (19), and small numbers of endothelial cells on micropatterns (20,21). Transient swirling patterns are also seen in epithelial monolayers (22). Recent work has also observed that the growth of spherical acini of human mammary epithelial cells in 3D matrix involves a coherent rotation persisting from a single cell to several cells; this rotation is not present in randomly motile cancerous cells (23). Similarly, cancerous cells on adhesive micropatterns do not develop coherent rotation (19). In a recent review ...
In this study, we investigated the utility of antimicrobial blue light therapy for multidrug-resistant Acinetobacter baumannii infection in a mouse burn model. A bioluminescent clinical isolate of multidrug-resistant A. baumannii was obtained. The susceptibility of A. baumannii to blue light (415 nm)-inactivation was compared in vitro to that of human keratinocytes. Repeated cycles of sublethal inactivation of bacterial by blue light were performed to investigate the potential resistance development of A. baumannii to blue light. A mouse model of third degree burn infected with A. baumannii was developed. A single exposure of blue light was initiated 30 minutes after bacterial inoculation to inactivate A. baumannii in mouse burns. It was found that the multidrug-resistant A. baumannii strain was significantly more susceptible than keratinocytes to blue light inactivation. Transmission electron microscopy revealed blue light-induced ultrastructural damage in A. baumannii cells. Fluorescence spectroscopy suggested that endogenous porphyrins exist in A. baumannii cells. Blue light at an exposure of 55.8 J/cm(2) significantly reduced the bacterial burden in mouse burns. No resistance development to blue light inactivation was observed in A. baumannii after 10 cycles of sublethal inactivation of bacteria. No significant DNA damage was detected in mouse skin by means of a skin TUNEL assay after a blue light exposure of 195 J/cm(2).
Nitrogen doped porous carbon nanopolyhedra (N-PCNPs) were prepared from direct carbonization of ZIF-8 nanopolyhedra. The N-PCNPs showed uniform morphology, narrow pore-size distribution centered at 3.7 nm, high surface area (2221 m 2 g À1 ) and good electrochemical properties and were used to modify a glassy carbon electrode to electrochemically detect ascorbic acid (AA), dopamine (DA) and uric acid (UA). Compared with the bare GC electrode and reduced graphene oxide modified glassy carbon (rGO/GC) electrode, the N-PCNPs modified GC electrode (N-PCNPs/GC) was found to perform better toward electrocatalytic oxidation of AA, DA and UA. For simultaneous sensing of three analytes, three well-separated voltammetry peaks were obtained using the N-PCNPs/GC electrode in differential pulse voltammetry measurements, and the corresponding peak separations between AA and DA, DA and UA were 228 mV, 124 mV respectively. The linear response ranges for the determination of AA, DA and UA were 80-2000 mM, 0.5-30 mM and 4-50 mM, respectively, and the detection limits (S/N ¼ 3) were 740 nM, 11 nM and 21 nM, respectively. Furthermore, the N-PCNPs/GC electrode showed good reproducibility and stability. The attractive features of N-PCNPs provided potential applications in the simultaneous determination of UA, AA and DA.
Fungal infections are a common cause of morbidity, mortality and cost in critical care populations. The increasing emergence of antimicrobial resistance necessitates the development of new therapeutic approaches for fungal infections. In the present study, we investigated the effectiveness of an innovative approach, antimicrobial blue light (aBL), for inactivation of Candida albicans in vitro and in infected mouse burns. A bioluminescent strain of C. albicans was used. The susceptibilities to aBL (415 nm) were compared between C. albicans and human keratinocytes. The potential development of aBL resistance by C. albicans was investigated via 10 serial passages of C. albicans on aBL exposure. For the animal study, a mouse model of thermal burn infected with the bioluminescent C. albicans strain was used. aBL was delivered to mouse burns approximately 12 h after fungal inoculation. Bioluminescence imaging was performed to monitor in real time the extent of infection in mice. The results obtained from the studies demonstrated that C. albicans was approximately 42-fold more susceptible to aBL than human keratinocytes. Serial passaging of C. albicans on aBL exposure implied a tendency of reduced aBL susceptibility of C. albicans with increasing numbers of passages; however, no statistically significant difference was observed in the post-aBL survival rate of C. albicans between the first and the last passage (P>0.05). A single exposure of 432 J/cm(2) aBL reduced the fungal burden in infected mouse burns by 1.75-log10 (P=0.015). Taken together, our findings suggest aBL is a potential therapeutic for C. albicans infections.
Background
Antimicrobial photodynamic inactivation with fullerenes bearing cationic charges may overcome resistant microbes.
Methods & results
We synthesized C60-fullerene (LC16) bearing decaquaternary chain and deca-tertiary-amino groups that facilitates electron-transfer reactions via the photoexcited fullerene. Addition of the harmless salt, potassium iodide (10 mM) potentiated the ultraviolet A (UVA) or white light-mediated killing of Gram-negative bacteria Acinetobacter baumannii, Gram-positive methicillin-resistant Staphylococcus aureus and fungal yeast Candida albicans by 1–2+ logs. Mouse model infected with bioluminescent Acinetobacter baumannii gave increased loss of bioluminescence when iodide (10 mM) was combined with LC16 and UVA/white light.
Conclusion
The mechanism may involve photoinduced electron reduction of 1(C60>)* or 3(C60>)* by iodide producing I· or I2 followed by subsequent intermolecular electron-transfer events of (C60>)−· to produce reactive radicals.
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