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Differentiation of neural-type cells on multi-scale ordered collagen-silica bionanocomposites

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 Added by Carole Aime
 Publication date 2020
  fields Biology Physics
and research's language is English




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Cells respond to biophysical and biochemical signals. We developed a composite filament from collagen and silica particles modified to interact with collagen and/or present a laminin epitope (IKVAV) crucial for cell-matrix adhesion and signal transduction. This combines scaffolding and signaling and shows that local tuning of collagen organization enhances cell differentiation.

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The deluge of single-cell data obtained by sequencing, imaging and epigenetic markers has led to an increasingly detailed description of cell state. However, it remains challenging to identify how cells transition between different states, in part because data are typically limited to snapshots in time. A prerequisite for inferring cell state transitions from such snapshots is to distinguish whether transitions are coupled to cell divisions. To address this, we present two minimal branching process models of cell division and differentiation in a well-mixed population. These models describe dynamics where differentiation and division are coupled or uncoupled. For each model, we derive analytic expressions for each subpopulations mean and variance and for the likelihood, allowing exact Bayesian parameter inference and model selection in the idealised case of fully observed trajectories of differentiation and division events. In the case of snapshots, we present a sample path algorithm and use this to predict optimal temporal spacing of measurements for experimental design. We then apply this methodology to an textit{in vitro} dataset assaying the clonal growth of epiblast stem cells in culture conditions promoting self-renewal or differentiation. Here, the larger number of cell states necessitates approximate Bayesian computation. For both culture conditions, our inference supports the model where cell state transitions are coupled to division. For culture conditions promoting differentiation, our analysis indicates a possible shift in dynamics, with these processes becoming more coupled over time.
We present a method to estimate Gibbs distributions with textit{spatio-temporal} constraints on spike trains statistics. We apply this method to spike trains recorded from ganglion cells of the salamander retina, in response to natural movies. Our analysis, restricted to a few neurons, performs more accurately than pairwise synchronization models (Ising) or the 1-time step Markov models (cite{marre-boustani-etal:09}) to describe the statistics of spatio-temporal spike patterns and emphasizes the role of higher order spatio-temporal interactions.
204 - Lester Ingber 2012
Recent calculations further supports the premise that large-scale synchronous firings of neurons may affect molecular processes. The context is scalp electroencephalography (EEG) during short-term memory (STM) tasks. The mechanism considered is $mathbf{Pi} = mathbf{p} + q mathbf{A}$ (SI units) coupling, where $mathbf{p}$ is the momenta of free $mathrm{Ca}^{2+}$ waves $q$ the charge of $mathrm{Ca}^{2+}$ in units of the electron charge, and $mathbf{A}$ the magnetic vector potential of current $mathbf{I}$ from neuronal minicolumnar firings considered as wires, giving rise to EEG. Data has processed using multiple graphs to identify sections of data to which spline-Laplacian transformations are applied, to fit the statistical mechanics of neocortical interactions (SMNI) model to EEG data, sensitive to synaptic interactions subject to modification by $mathrm{Ca}^{2+}$ waves.
Place cells in the hippocampus are active when an animal visits a certain location (referred to as a place field) within an environment. Grid cells in the medial entorhinal cortex (MEC) respond at multiple locations, with firing fields that form a periodic and hexagonal tiling of the environment. The joint activity of grid and place cell populations, as a function of location, forms a neural code for space. An ensemble of codes is generated by varying grid and place cell population parameters. For each code in this ensemble, codewords are generated by stimulating a network with a discrete set of locations. In this manuscript, we develop an understanding of the relationships between coding theoretic properties of these combined populations and code construction parameters. These relationships are revisited by measuring the performances of biologically realizable algorithms implemented by networks of place and grid cell populations, as well as constraint neurons, which perform de-noising operations. Objectives of this work include the investigation of coding theoretic limitations of the mammalian neural code for location and how communication between grid and place cell networks may improve the accuracy of each populations representation. Simulations demonstrate that de-noising mechanisms analyzed here can significantly improve fidelity of this neural representation of space. Further, patterns observed in connectivity of each population of simulated cells suggest that inter-hippocampal-medial-entorhinal-cortical connectivity decreases downward along the dorsoventral axis.
Neural populations encode information about their stimulus in a collective fashion, by joint activity patterns of spiking and silence. A full account of this mapping from stimulus to neural activity is given by the conditional probability distribution over neural codewords given the sensory input. To be able to infer a model for this distribution from large-scale neural recordings, we introduce a stimulus-dependent maximum entropy (SDME) model---a minimal extension of the canonical linear-nonlinear model of a single neuron, to a pairwise-coupled neural population. The model is able to capture the single-cell response properties as well as the correlations in neural spiking due to shared stimulus and due to effective neuron-to-neuron connections. Here we show that in a population of 100 retinal ganglion cells in the salamander retina responding to temporal white-noise stimuli, dependencies between cells play an important encoding role. As a result, the SDME model gives a more accurate account of single cell responses and in particular outperforms uncoupled models in reproducing the distributions of codewords emitted in response to a stimulus. We show how the SDME model, in conjunction with static maximum entropy models of population vocabulary, can be used to estimate information-theoretic quantities like surprise and information transmission in a neural population.
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