Low energy visible light (LEVL) irradiation has beenshown to exert some beneficial effects on various cell cultures. For example, it increases the fertilizing capability of sperm cells, promotes cell proliferation, induces sprouting of neurons, and more. To learn about the mechanism of photobiostimulation, we studied the relationship between increased intracellular calcium ( Life on earth is entirely dependent upon the interaction of sunlight with cells especially in plant photosynthesis (1). Sunlight also has medical benefits, which have been exploited for over thousands of years in ancient Egypt, India, and China in treating skin diseases, psoriasis, vitiligo, and even cancer (2). Recent observations show that even low energy visible light (LEVL) 1 can serve as a medical tool. For example, LEVL increases the rate of wound healing (3), enhances the fertilizing capability of sperm cells (4), and increases the rate of healing bone defects (5). In vitro studies have found that LEVL increases proliferation of cells as fibroblasts (6), keratinocytes (7), and lymphocytes (8) and induces the respiratory burst in neutrophils (9). The mechanism of photobiostimulation by LEVL is still unclear. It has been suggested that reactive oxygen species (ROS), which can be produced by photosensitization of endogenous cell chromophores such as cytochromes (10) [Ca 2ϩ ] i followed by myosin phosphorylation and cell contractions (26). Growth factors and hormones were shown to stimulate ROS production, which were dependent on [Ca 2ϩ ] i rise (27). The relationship between ROS and [Ca 2ϩ ] i has been suggested to involve the redox-sensitive transcription factor N, which was found to change [Ca 2ϩ ] i homeostasis in response to changes in the redox state of thiol groups (28). The kinetics that characterize the [Ca 2ϩ ] i elevation have been shown to be an important parameter determining the kind of signal that will be evoked. Livingston et al. (29) showed that high concentrations of oxidants (Ͼ50 M) caused a sustained increase in [Ca 2ϩ ] i , whereas a transient increase in [Ca 2ϩ ] i was observed following administration of a low concentration of oxidants. More than a 4-fold increase in the [Ca 2ϩ ] i level was obtained in photodynamic treatment of mouse myeloma cells that had been enriched with exogenous photosensitizers before illumination, whereas only a slight increase in [Ca 2ϩ ] i was observed in irradiated cells without exogenous photosensitizers (30).Only a few works have dealt with calcium/ROS changes following LEVL irradiation. In this study, we have investigated * The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.§ The article describes research performed by Ronit Lavi as partial fulfillment of the requirements for her Ph.D. degree at Bar-Ilan University. To whom correspondence should be addressed. Tel.: 972-3-5317797; Fax: 972-3-...
A graded response to calcium is the defining feature of calcium-regulated exocytosis. That is, there exist calcium concentrations that elicit submaximal exocytotic responses in which only a fraction of the available population of secretory vesicles fuse. The role of calcium-dependent inactivation in defining the calcium sensitivity of sea urchin egg secretory vesicle exocytosis in vitro was examined. The cessation of fusion in the continued presence of calcium was not due to calcium-dependent inactivation. Rather, the calcium sensitivity of individual vesicles within a population of exocytotic vesicles is heterogeneous. Any specific calcium concentration above threshold triggered subpopulations of vesicles to fuse and the size of the subpopulations was dependent upon the magnitude of the calcium stimulus. The existence of multiple, stable subpopulations of vesicles is consistent with a fusion process that requires the action of an even greater number of calcium ions than the numbers suggested by models based on the assumption of a homogeneous vesicle population.
The fate of the persistent OP nerve agent O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate (VX) on granular activated carbons that are used for gas filtration was studied by means of 31P magic angle spinning (MAS) NMR spectroscopy. VX as vapor or liquid was adsorbed on carbon granules, and MAS NMR spectra were recorded periodically. The results show that at least 90% of the adsorbed VX decomposes within 20 days or less to the nontoxic ethyl methylphosphonic acid (EMPA) and bis(S-2-diisopropylaminoethane) {(DES)2}. Decomposition occurred irrespective of the phase from which VX was loaded, the presence of metal impregnation on the carbon surface, and the water content of the carbon. Theoretical and practical aspects of the degradation are discussed.
The ability of cells to coordinately migrate in groups is crucial to enable them to travel long distances during embryonic development, wound healing and tumorigenesis, but the fundamental mechanisms underlying intercellular coordination during collective cell migration remain elusive despite considerable research efforts. A novel analytical framework is introduced here to explicitly detect and quantify cell clusters that move coordinately in a monolayer. The analysis combines and associates vast amount of spatiotemporal data across multiple experiments into transparent quantitative measures to report the emergence of new modes of organized behavior during collective migration of tumor and epithelial cells in wound healing assays. First, we discovered the emergence of a wave of coordinated migration propagating backward from the wound front, which reflects formation of clusters of coordinately migrating cells that are generated further away from the wound edge and disintegrate close to the advancing front. This wave emerges in both normal and tumor cells, and is amplified by Met activation with hepatocyte growth factor/scatter factor. Second, Met activation was found to induce coinciding waves of cellular acceleration and stretching, which in turn trigger the emergence of a backward propagating wave of directional migration with about an hour phase lag. Assessments of the relations between the waves revealed that amplified coordinated migration is associated with the emergence of directional migration. Taken together, our data and simplified modeling-based assessments suggest that increased velocity leads to enhanced coordination: higher motility arises due to acceleration and stretching that seems to increase directionality by temporarily diminishing the velocity components orthogonal to the direction defined by the monolayer geometry. Spatial and temporal accumulation of directionality thus defines coordination. The findings offer new insight and suggest a basic cellular mechanism for long-term cell guidance and intercellular communication during collective cell migration.
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