9 research outputs found
Hydrogel scaffolds promote neural gene expression and structural reorganization in human astrocyte cultures
Hunter-gatherer foraging networks promote information transmission
Central-place foraging (CPF), where foragers return to a central location (or home), is a key feature of hunter–gatherer social organization. CPF could have significantly changed hunter–gatherers’ spatial use and mobility, altered social networks and increased opportunities for information-exchange. We evaluated whether CPF patterns facilitate information-transmission and considered the potential roles of environmental conditions, mobility strategies and population sizes. We built an agent-based model of CPF where agents moved according to a simple optimal foraging rule, and could encounter other agents as they moved across the environment. They either foraged close to their home within a given radius or moved the location of their home to new areas. We analysed the interaction networks arising under different conditions and found that, at intermediate levels of environmental heterogeneity and mobility, CPF increased global and local network efficiencies as well as the rate of contagion-based information-transmission. We also found that central-place mobility strategies can further improve information transmission in larger populations. Our findings suggest that the combination of foraging and movement strategies, as well as the environmental conditions that characterized early human societies, may have been a crucial precursor in our species’ unique capacity to innovate, accumulate and rely on complex culture
Querying Next Generation Sequencing Data for Insight into the Ion Channel Transcriptome (Channelome) of Cultured Human Astrocytes
Expression analysis of RNA sequencing data from human neural and glial cell lines depends on technical replication and normalization methods
Abstract Background The potential for astrocyte participation in central nervous system recovery is highlighted by in vitro experiments demonstrating their capacity to transdifferentiate into neurons. Understanding astrocyte plasticity could be advanced by comparing astrocytes with stem cells. RNA sequencing (RNA-seq) is ideal for comparing differences across cell types. However, this novel multi-stage process has the potential to introduce unwanted technical variation at several points in the experimental workflow. Quantitative understanding of the contribution of experimental parameters to technical variation would facilitate the design of robust RNA-Seq experiments. Results RNA-Seq was used to achieve biological and technical objectives. The biological aspect compared gene expression between normal human fetal-derived astrocytes and human neural stem cells cultured in identical conditions. When differential expression threshold criteria of |log 2 fold change|Â >Â 2 were applied to the data, no significant differences were observed. The technical component quantified variation arising from particular steps in the research pathway, and compared the ability of different normalization methods to reduce unwanted variance. To facilitate this objective, a liberal false discovery rate of 10% and a |log 2 fold change|Â >Â 0.5 were implemented for the differential expression threshold. Data were normalized with RPKM, TMM, and UQS methods using JMP Genomics. The contributions of key replicable experimental parameters (cell lot; library preparation; flow cell) to variance in the data were evaluated using principal variance component analysis. Our analysis showed that, although the variance for every parameter is strongly influenced by the normalization method, the largest contributor to technical variance was library preparation. The ability to detect differentially expressed genes was also affected by normalization; differences were only detected in non-normalized and TMM-normalized data. Conclusions The similarity in gene expression between astrocytes and neural stem cells supports the potential for astrocytic transdifferentiation into neurons, and emphasizes the need to evaluate the therapeutic potential of astrocytes for central nervous system damage. The choice of normalization method influences the contributions to experimental variance as well as the outcomes of differential expression analysis. However irrespective of normalization method, our findings illustrate that library preparation contributed the largest component of technical variance
Hydrogel scaffolds promote neural gene expression and structural reorganization in human astrocyte cultures
Biomaterial scaffolds have the potential to enhance neuronal development and regeneration. Understanding the genetic responses of astrocytes and neurons to biomaterials could facilitate the development of synthetic environments that enable the specification of neural tissue organization with engineered scaffolds. In this study, we used high throughput transcriptomic and imaging methods to determine the impact of a hydrogel, PuraMatrix™, on human glial cells in vitro. Parallel studies were undertaken with cells grown in a monolayer environment on tissue culture polystyrene. When the Normal Human Astrocyte (NHA) cell line is grown in a hydrogel matrix environment, the glial cells adopt a structural organization that resembles that of neuronal-glial cocultures, where neurons form clusters that are distinct from the surrounding glia. Statistical analysis of next generation RNA sequencing data uncovered a set of genes that are differentially expressed in the monolayer and matrix hydrogel environments. Functional analysis demonstrated that hydrogel-upregulated genes can be grouped into three broad categories: neuronal differentiation and/or neural plasticity, response to neural insult, and sensory perception. Our results demonstrate that hydrogel biomaterials have the potential to transform human glial cell identity, and may have applications in the repair of damaged brain tissue
Tissue and Species Differences in the Application of Quantum Dots as Probes for Biomolecular Targets in the Inner Ear and Kidney
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A Variational Synthesis of Evolutionary and Developmental Dynamics
This paper introduces a variational formulation of natural selection, paying special attention to the nature of 'things' and the way that different 'kinds' of 'things' are individuated from-and influence-each other. We use the Bayesian mechanics of particular partitions to understand how slow phylogenetic processes constrain-and are constrained by-fast, phenotypic processes. The main result is a formulation of adaptive fitness as a path integral of phenotypic fitness. Paths of least action, at the phenotypic and phylogenetic scales, can then be read as inference and learning processes, respectively. In this view, a phenotype actively infers the state of its econiche under a generative model, whose parameters are learned via natural (Bayesian model) selection. The ensuing variational synthesis features some unexpected aspects. Perhaps the most notable is that it is not possible to describe or model a population of conspecifics per se. Rather, it is necessary to consider populations of distinct natural kinds that influence each other. This paper is limited to a description of the mathematical apparatus and accompanying ideas. Subsequent work will use these methods for simulations and numerical analyses-and identify points of contact with related mathematical formulations of evolution