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Register a new userPattern Formation in the Longevity-Related Expression of Heat Shock Protein-16.2 in Caenorhabditis elegans
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Aging in Caenorhabditis elegans is controlled, in part, by the insulin-like signaling and heat shock response pathways. Following thermal stress, expression levels of small heat shock protein 16.2 show a spatial patterning across the 20 intestinal cells that reside along the length of the worm. Here, we present a hypothesized mechanism that could lead to this patterned response and develop a mathematical model of this system to test our hypothesis. We propose that the patterned expression of heat shock protein is caused by a diffusion-driven instability within the pseudocoelom, or fluid-filled cavity, that borders the intestinal cells in C. elegans. This instability is due to the interactions between two classes of insulin like peptides that serve antagonistic roles. We examine output from the developed model and compare it to experimental data on heat shock protein expression. Furthermore, we use the model to gain insight on possible biological parameters in the system. The model presented is capable of producing patterns similar to what is observed experimentally and provides a first step in mathematically modeling aging-related mechanisms in C. elegans.
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Graph theoretical analyses of nervous systems usually omit the aspect of connection polarity, due to data insufficiency. The chemical synapse network of Caenorhabditis elegans is a well-reconstructed directed network, but the signs of its connections are yet to be elucidated. Here, we present the gene expression-based sign prediction of the ionotropic chemical synapse connectome of C. elegans (3,638 connections and 20,589 synapses total), incorporating available presynaptic neurotransmitter and postsynaptic receptor gene expression data for three major neurotransmitter systems. We made predictions for more than two-thirds of these chemical synapses and observed an excitatory-inhibitory (E:I) ratio close to 4:1 which was found similar to that observed in many real-world networks. Our open source tool (http://EleganSign.linkgroup.hu) is simple but efficient in predicting polarities by integrating neuronal connectome and gene expression data.
Gene expression is a noisy process and several mechanisms, both transcriptional and posttranscriptional, can stabilize protein levels in cells. Much work has focused on the role of miRNAs, showing in particular that miRNA-mediated regulation can buffer expression noise for lowly expressed genes. Here, using in silico simulations and mathematical modeling, we demonstrate that miRNAs can exert a much broader influence on protein levels by orchestrating competition-induced crosstalk between mRNAs. Most notably, we find that miRNA-mediated cross-talk (i) can stabilize protein levels across the full range of gene expression rates, and (ii) modifies the correlation pattern of co-regulated interacting proteins, changing the sign of correlations from negative to positive. The latter feature may constitute a potentially robust signature of the existence of RNA crosstalk induced by endogenous competition for miRNAs in standard cellular conditions.
Cell division timing is critical for cell fate specification and morphogenesis during embryogenesis. How division timings are regulated among cells during development is poorly understood. Here we focus on the comparison of asynchrony of division between sister cells (ADS) between wild-type and mutant individuals of Caenorhabditis elegans. Since the replicate number of mutant individuals of each mutated gene, usually one, is far smaller than that of wild-type, direct comparison of two distributions of ADS between wild-type and mutant type, such as Kolmogorov- Smirnov test, is not feasible. On the other hand, we find that sometimes ADS is correlated with the life span of corresponding mother cell in wild-type. Hence, we apply a semiparametric Bayesian quantile regression method to estimate the 95% confidence interval curve of ADS with respect to life span of mother cell of wild-type individuals. Then, mutant-type ADSs outside the corresponding confidence interval are selected out as abnormal one with a significance level of 0.05. Simulation study demonstrates the accuracy of our method and Gene Enrichment Analysis validates the results of real data sets.
Protein pattern formation is essential for the spatial organization of many intracellular processes like cell division, flagellum positioning, and chemotaxis. A prominent example of intracellular patterns are the oscillatory pole-to-pole oscillations of Min proteins in textit{E. coli} whose biological function is to ensure precise cell division. Cell polarization, a prerequisite for processes such as stem cell differentiation and cell polarity in yeast, is also mediated by a diffusion-reaction process. More generally, these functional modules of cells serve as model systems for self-organization, one of the core principles of life. Under which conditions spatio-temporal patterns emerge, and how these patterns are regulated by biochemical and geometrical factors are major aspects of current research. Here we review recent theoretical and experimental advances in the field of intracellular pattern formation, focusing on general design principles and fundamental physical mechanisms.
Molecular networks act as the backbone of cellular activities, providing an {excellent} opportunity to understand the developmental changes in an organism. While network data usually constitute only stationary network graphs, constructing multilayer PPI network may provide clues to the particular developmental role at each {stage of life} and may unravel the importance of these developmental changes. The developmental biology model of {Caenorhabditis elegans} {analyzed} here provides a ripe platform to understand the patterns of evolution during life stages of an organism. In the present study, the widely studied network properties exhibit overall similar statistics for all the PPI layers. Further, the analysis of the degree-degree correlation and spectral properties not only reveals crucial differences in each PPI layer but also indicates the presence of the varying complexity among them. The PPI layer of Nematode life stage exhibits various network properties different to rest of the PPI layers, indicating the specific role of cellular diversity and developmental transitions at this stage. The framework presented here provides a direction to explore and understand developmental changes occurring in different life stages of an organism.
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