The involvement of actin, calcium channels and exocytosis proteins in somato-dendritic oxytocin and vasopressin release

Hypothalamic magnocellular neurons release vasopressin and oxytocin not only from their axon terminals into the blood, but also from their somata and dendrites into the extracellular space of the brain, and this can be regulated independently. Differential release of neurotransmitters from different compartments of a single neuron requires subtle regulatory mechanisms. Somato-dendritic, but not axon terminal release can be modulated by changes in intracellular calcium concentration [(Ca(2+))] by release of calcium from intracellular stores, resulting in priming of dendritic pools for activity-dependent release. This review focuses on our current understanding of the mechanisms of priming and the roles of actin remodeling, voltage-operated calcium channels (VOCCs) and SNARE proteins in the regulation somato-dendritic and axon terminal peptide release

A C3(H20) recycling pathway is a component of the intracellular complement system

An intracellular complement system (ICS) has recently been described in immune and nonimmune human cells. This system can be activated in a convertase-independent manner from intracellular stores of the complement component C3. The source of these stores has not been rigorously investigated. In the present study, Western blotting identified a band corresponding to C3 in freshly isolated human peripheral blood cells that was absent in corresponding cell lines. One difference between native cells and cell lines was the time absent from a fluid-phase complement source; therefore, we hypothesized that loading C3 from plasma was a route of establishing intracellular C3 stores. We found that many types of human cells specifically internalized C3(H(2)O), the hydrolytic product of C3, and not native C3, from the extracellular milieu. Uptake was rapid, saturable, and sensitive to competition with unlabeled C3(H(2)O), indicating a specific mechanism of loading. Under steady-state conditions, approximately 80% of incorporated C3(H(2)O) was returned to the extracellular space. These studies identify an ICS recycling pathway for C3(H(2)O). The loaded C3(H(2)O) represents a source of C3a, and its uptake altered the cytokine profile of activated CD4(+) T cells. Importantly, these results indicate that the impact of soluble plasma factors should be considered when performing in vitro studies assessing cellular immune function

Asymptotic behavior of the solution of the space dependent variable order fractional diffusion equation: ultra-slow anomalous aggregation

We find for the first time the asymptotic representation of the solution to the space dependent variable order fractional diffusion and Fokker-Planck equations. We identify a new advection term that causes ultra-slow spatial aggregation of subdiffusive particles due to dominance over the standard advection and diffusion terms, in the long-time limit. This uncovers the anomalous mechanism by which non-uniform distributions can occur. We perform experiments on intracellular lysosomal distributions and Monte Carlo simulations and find excellent agreement between the asymptotic solution, particle histograms and experiments.Comment: 6 page

Time- and Space-Resolved Flow-Cytometry of Cell Organelles to Quantify Nanoparticle Uptake and Intracellular Trafficking by Cells

The design of targeted nanomedicines requires intracellular space- and time-resolved data of nanoparticle distribution following uptake. Current methods to study intracellular trafficking, such as dynamic colocalization by fluorescence microscopy in live cells, are usually low throughput and require extensive analysis of large datasets to quantify colocalization in several individual cells. Here a method based on flow cytometry to easily detect and characterize the organelles in which nanoparticles are internalized and trafficked over time is proposed. Conventional cell fractionation methods are combined with immunostaining and high-sensitivity organelle flow cytometry to get space-resolved data of nanoparticle intracellular distribution. By extracting the organelles at different times, time-resolved data of nanoparticle intracellular trafficking are obtained. The method is validated by determining how nanoparticle size affects the kinetics of arrival to the lysosomes. The results demonstrate that this method allows high-throughput analysis of nanoparticle uptake and intracellular trafficking by cells, therefore it can be used to determine how nanoparticle design affects their intracellular behavior

First-passage time of run-and-tumble particles

We solve the problem of first-passage time for run-and-tumble particles in one dimension. Exact expression is derived for the mean first-passage time in the general case, considering external force-fields and chemotactic-fields, giving rise to space dependent swim-speed and tumble rate. Agreement between theoretical formulae and numerical simulations is obtained in the analyzed case studies -- constant and sinusoidal force fields, constant gradient chemotactic field. Reported findings can be useful to get insights into very different phenomena involving active particles, such as bacterial motion in external fields, intracellular transport, cell migration, animal foraging

A new quantitative description of intracellular Ca2+ dynamics in the model of rat ventricular myocyte

The paper presents a new description of intracellular Ca2+ dynamics in the model of rat ventricular myocyte. The principal modifications based on the recently published data comprise: formulation of the function of peripheral dyads, incorporation of peripheral and tubular intracellular subspaces, reformulation of inactivation properties of surface of tubular ICa and description of the function of exogenous Ca2+ buffer in the intracellular space

Spatial chaos and complexity in the intracellular space of cancer and normal cells

BACKGROUND: One of the most challenging problems in biological image analysis is the quantification of the dynamical mechanism and complexity of the intracellular space. This paper investigates potential spatial chaos and complex behavior of the intracellular space of typical cancer and normal cell images whose structural details are revealed by the combination of scanning electron microscopy and focused ion beam systems. Such numerical quantifications have important implications for computer modeling and simulation of diseases. METHODS: Cancer cell lines derived from a human head and neck squamous cell carcinoma (SCC-61) and normal mouse embryonic fibroblast (MEF) cells produced by focused ion beam scanning electron microscopes were used in this study. Spatial distributions of the organelles of cancer and normal cells can be analyzed at both short range and long range of the bounded dynamical system of the image space, depending on the orientations of the spatial cell. A procedure was designed for calculating the largest Lyapunov exponent, which is an indicator of the potential chaotic behavior in intracellular images. Furthermore, the sample entropy and regularity dimension were applied to measure the complexity of the intracellular images. RESULTS: Positive values of the largest Lyapunov exponents (LLEs) of the intracellular space of the SCC-61 were obtained in different spatial orientations for both long-range and short-range models, suggesting the chaotic behavior of the cell. The MEF has smaller positive values of LLEs in the long range than those of the SCC-61, and zero vales of the LLEs in the short range analysis, suggesting a non-chaotic behavior. The intracellular space of the SCC-61 is found to be more complex than that of the MEF. The degree of complexity measured in the spatial distribution of the intracellular space in the diagonal direction was found to be approximately twice larger than the complexity measured in the horizontal and vertical directions. CONCLUSION: Initial findings are promising for characterizing different types of cells and therefore useful for studying cancer cells in the spatial domain using state-of-the-art imaging technology. The measures of the chaotic behavior and complexity of the spatial cell will help computational biologists gain insights into identifying associations between the oscillation patterns and spatial parameters of cells, and appropriate model for simulating cancer cell signaling networks for cancer treatment and new drug discovery