158 research outputs found

    Emergence of macroscopic simplicity from the Tumor Necrosis Factor-alpha signaling dynamics

    Get PDF
    The Tumor Necrosis Factor-α (TNF-α), a cytokine produced during the innate immune response to invading pathogens, is involved in numerous fundamental cellular processes. Here, to understand the temporal activation profiles of the TNF-α regulated signaling network, we developed a dynamic computational model based on the perturbation-response approach and the law of information (signaling flux) conservation. Our simulations show that the temporal average population response of the TNF-α stimulated transcription factors NF-κB and AP-1, and 3 groups of 180 downstream gene expressions follow first-order equations. Using the model, in contrast to a well-known previous study, our model suggests that the continuous activation of the third group of genes is not mainly due to the poor rate of mRNA decay process, rather, the law of signaling flux conservation stipulates the presence of secondary signaling, such as feedback mechanism or autocrine signaling, is crucial. Although the living system is perceived as sophisticated and complex, notably, our work reveals the presence of simple governing principles in cell population dynamics

    Genetic vehicle comprising majority of lowly expressed genes guides cell fate decision

    Get PDF
    Cells remarkably take a specific differentiation path among the multiple possibilities that can arise through the multi-dimensional regulation of genome activities. Such deterministic processes suggest the existence of cellular attractors. However, the origins and drivers of the attractors still remain elusive. Here we analyzed the temporal neutrophil differentiation microarray data for two different stimuli, dimethyl sulfoxide (DMSO) and all-trans-retinoic acid (atRA), and expressed their collective dynamics by temporal Pearson correlation and mutual information coordinates. We constructed ensemble of the genes which showed reduction of correlation fluctuations following the inverse square root law. Evaluating their temporal probability density distributions resulted in the emergence of distinct high density localizations from non-localized low density spread distributions, forming attractor cores for both atRA and DMSO. These attractor cores overlapped, pointing to the existence of a neutrophil cell fate attractor. Notably, we found the localizations of correlation distributions for the majority of lowly expressed genes (LEGs) ensembles overlapped with the whole genome attractor cores, while the remaining genomes' localizations did not overlap. Therefore, we postulate the existence of genetic vehicle, made up mainly of LEGs, for the guidance of cell fate

    Longitudinal Hierarchy Co3O4 Mesocrystals with High-dense Exposure Facets and Anisotropic Interfaces for Direct-Ethanol Fuel Cells

    Get PDF
    Novel electrodes are needed for direct ethanol fuel cells with improved quality. Hierarchical engineering can produce catalysts composed of mesocrystals with many exposed active planes and multi-diffused voids. Here we report a simple, one-pot, hydrothermal method for fabricating Co 3 O 4 /carbon/substrate electrodes that provides control over the catalyst mesocrystal morphology (i.e., corn tubercle pellets or banana clusters oriented along nanotube domains, or layered lamina or multiple cantilevered sheets). These morphologies afforded catalysts with a high density of exposed active facets, a diverse range of mesopores in the cage interior, a window architecture, and vertical alignment to the substrate, which improved efficiency in an ethanol electrooxidation reaction compared with a conventional platinum/carbon electrode. On the atomic scale, the longitudinally aligned architecture of the Co 3 O 4 mesocrystals resulted in exposed low- and high-index single and interface surfaces that had improved electron transport and diffusion compared with currently used electrodes

    Algivore or phototroph?: Plakobranchus ocellatus (Gastropoda) continuously acquires kleptoplasts and nutrition from multiple algal species in nature

    Get PDF
    The sea slug Plakobranchus ocellatus (Sacoglossa, Gastropoda) retains photosynthetically active chloroplasts from ingested algae (functional kleptoplasts) in the epithelial cells of its digestive gland for up to 10 months. While its feeding behavior has not been observed in natural habitats, two hypotheses have been proposed: 1) adult P. ocellatus uses kleptoplasts to obtain photosynthates and nutritionally behaves as a photoautotroph without replenishing the kleptoplasts; or 2) it behaves as a mixotroph (photoautotroph and herbivorous consumer) and replenishes kleptoplasts continually or periodically. To address the question of which hypothesis is more likely, we examined the source algae for kleptoplasts and temporal changes in kleptoplast composition and nutritional contribution. By characterizing the temporal diversity of P. ocellatus kleptoplasts using rbcL sequences, we found that P. ocellatus harvests kleptoplasts from at least 8 different siphonous green algal species, that kleptoplasts from more than one species are present in each individual sea slug, and that the kleptoplast composition differs temporally. These results suggest that wild P. ocellatus often feed on multiple species of siphonous algae from which they continually obtain fresh chloroplasts. By estimating the trophic position of wild and starved P. ocellatus using the stable nitrogen isotopic composition of amino acids, we showed that despite the abundance of kleptoplasts, their photosynthates do not contribute greatly to the nutrition of wild P. ocellatus, but that kleptoplast photosynthates form a significant source of nutrition for starved sea slugs. The herbivorous nature of wild P. ocellatus is consistent with insights from molecular analyses indicating that kleptoplasts are frequently replenished from ingested algae, leading to the conclusion that natural populations of P. ocellatus do not rely on photosynthesis but mainly on the digestion of ingested algae

    Longitudinal Hierarchy Co3O4 Mesocrystals with High-dense Exposure Facets and Anisotropic Interfaces for Direct-Ethanol Fuel Cells

    Get PDF
    Novel electrodes are needed for direct ethanol fuel cells with improved quality. Hierarchical engineering can produce catalysts composed of mesocrystals with many exposed active planes and multi-diffused voids. Here we report a simple, one-pot, hydrothermal method for fabricating Co 3 O 4 /carbon/substrate electrodes that provides control over the catalyst mesocrystal morphology (i.e., corn tubercle pellets or banana clusters oriented along nanotube domains, or layered lamina or multiple cantilevered sheets). These morphologies afforded catalysts with a high density of exposed active facets, a diverse range of mesopores in the cage interior, a window architecture, and vertical alignment to the substrate, which improved efficiency in an ethanol electrooxidation reaction compared with a conventional platinum/carbon electrode. On the atomic scale, the longitudinally aligned architecture of the Co 3 O 4 mesocrystals resulted in exposed low- and high-index single and interface surfaces that had improved electron transport and diffusion compared with currently used electrodes

    Collective Dynamics of Specific Gene Ensembles Crucial for Neutrophil Differentiation: The Existence of Genome Vehicles Revealed

    Get PDF
    Cell fate decision remarkably generates specific cell differentiation path among the multiple possibilities that can arise through the complex interplay of high-dimensional genome activities. The coordinated action of thousands of genes to switch cell fate decision has indicated the existence of stable attractors guiding the process. However, origins of the intracellular mechanisms that create “cellular attractor” still remain unknown. Here, we examined the collective behavior of genome-wide expressions for neutrophil differentiation through two different stimuli, dimethyl sulfoxide (DMSO) and all-trans-retinoic acid (atRA). To overcome the difficulties of dealing with single gene expression noises, we grouped genes into ensembles and analyzed their expression dynamics in correlation space defined by Pearson correlation and mutual information. The standard deviation of correlation distributions of gene ensembles reduces when the ensemble size is increased following the inverse square root law, for both ensembles chosen randomly from whole genome and ranked according to expression variances across time. Choosing the ensemble size of 200 genes, we show the two probability distributions of correlations of randomly selected genes for atRA and DMSO responses overlapped after 48 hours, defining the neutrophil attractor. Next, tracking the ranked ensembles' trajectories, we noticed that only certain, not all, fall into the attractor in a fractal-like manner. The removal of these genome elements from the whole genomes, for both atRA and DMSO responses, destroys the attractor providing evidence for the existence of specific genome elements (named “genome vehicle”) responsible for the neutrophil attractor. Notably, within the genome vehicles, genes with low or moderate expression changes, which are often considered noisy and insignificant, are essential components for the creation of the neutrophil attractor. Further investigations along with our findings might provide a comprehensive mechanistic view of cell fate decision

    Inter-rater reliability of the AFTD-pitting test among elderly patients in a long-term medical facility

    Get PDF
    BACKGROUND and AIM: The pitting test has been reported in various methods as a standard for evaluating chronic oedema, but a unified method has not been determined. This makes it difficult to accurately specify the prevalence of oedema. The present study aimed to evaluate inter-rater reliability of the AFTD-pitting test, which included 4 factors: Anatomical locations of oedema; Force required to pit; the amount of Time; and the Definition of oedema. The present study is the first stage of an international epidemiological study of chronic oedema.METHODS: This cross-sectional observational study was performed at a long-term care hospital in Ishikawa Prefecture, Japan. The inter-rater reliability of the pitting test for evaluating oedema using the AFTD-pitting test was tested for 34 locations on the body, with 10 seconds of pitting with a similar force to that of the reference rater and assessed using the modified Fukazawa method. One reference rater and four raters evaluated oedema in five patients. Then, the agreement rate and Cohen-s kappa coefficient were calculated.RESULTS: All protocols were completed by four raters for five bedridden patients. Agreement among the four raters was high, at >0.85, and the kappa coefficient showed almost perfect, moderate, and fair agreement for one (0.81), four (0.51-0.60) rater, respectively.CONCLUSION: The inter-rater reliability of four nurses who applied the AFTD-pitting test was high, and the kappa coefficient showed at least fair agreement. Therefore, the AFTD-pitting test is a useful method to assess whole-body chronic oedema
    corecore