Boolean networks with robust and reliable trajectories

We construct and investigate Boolean networks that follow a given reliable trajectory in state space, which is insensitive to fluctuations in the updating schedule, and which is also robust against noise. Robustness is quantified as the probability that the dynamics return to the reliable trajectory after a perturbation of the state of a single node. In order to achieve high robustness, we navigate through the space of possible update functions by using an evolutionary algorithm. We constrain the networks to having the minimum number of connections required to obtain the reliable trajectory. Surprisingly, we find that robustness always reaches values close to 100 percent during the evolutionary optimization process. The set of update functions can be evolved such that it differs only slightly from that of networks that were not optimized with respect to robustness. The state space of the optimized networks is dominated by the basin of attraction of the reliable trajectory.Comment: 12 pages, 9 figure

a simple tool for the analysis of periodic cotyledon and leaf movement in Arabidopsis thaliana

Background The analysis of circadian leaf movement rhythms is a simple yet effective method to study effects of treatments or gene mutations on the circadian clock of plants. Currently, leaf movements are analysed using time lapse photography and subsequent bioinformatics analyses of leaf movements. Programs that are used for this purpose either are able to perform one function (i.e. leaf tip detection or rhythm analysis) or their function is limited to specific computational environments. We developed a leaf movement analysis tool—PALMA—that works in command line and combines image extraction with rhythm analysis using Fast Fourier transformation and non-linear least squares fitting. Results We validated PALMA in both simulated time series and in experiments using the known short period mutant sensitivity to red light reduced 1 (srr1-1). We compared PALMA with two established leaf movement analysis tools and found it to perform equally well. Finally, we tested the effect of reduced iron conditions on the leaf movement rhythms of wild type plants. Here, we found that PALMA successfully detected period lengthening under reduced iron conditions. Conclusions PALMA correctly estimated the period of both simulated and real-life leaf movement experiments. As a platform-independent console-program that unites both functions needed for the analysis of circadian leaf movements it is a valid alternative to existing leaf movement analysis tools

Editorial: Coupling in biological systems: Definitions, mechanisms, and implications

Peer Reviewe

BMP2 and TGF-β Cooperate Differently during Synovial-Derived Stem-Cell Chondrogenesis in a Dexamethasone-Dependent Manner

Recent studies highlighting mesenchymal stem cell (MSC) epigenetic memory suggest that a different differentiation medium may be required depending on the tissue of origin. As synovial-derived stem cells (SDSCs) attract interest we aimed to investigate the influence of TGF-β1, BMP-2 and dexamethasone on SDSC chondrogenesis in vitro. We demonstrate that dexamethasone-free medium led to enhanced chondrogenic differentiation at both the mRNA and matrix level. The greatest COL2A1/COL10A1 ratio was detected in cells exposed to a combination medium containing 10 ng/mL BMP-2 and 1 ng/mL TGF-β1 in the absence of dexamethasone, and this was reflected in the total amount of glycosaminoglycans produced. In summary, dexamethasone-free medium containing BMP-2 and TGF-β1 may be the most suitable when using SDSCs for cartilage tissue regeneration

Moran’s I quantifies spatio-temporal pattern formation in neural imaging data

Motivation: Neural activities of the brain occur through the formation of spatio-temporal patterns. In recent years, macroscopic neural imaging techniques have produced a large body of data on these patterned activities, yet a numerical measure of spatio-temporal coherence has often been reduced to the global order parameter, which does not uncover the degree of spatial correlation. Here, we propose to use the spatial autocorrelation measure Moran’s I, which can be applied to capture dynamic signatures of spatial organization. We demonstrate the application of this technique to collective cellular circadian clock activities measured in the small network of the suprachiasmatic nucleus (SCN) in the hypothalamus.Results: We found that Moran’s I is a practical quantitative measure of the degree of spatial coherence in neural imaging data. Initially developed with a geographical context in mind, Moran’s I accounts for the spatial organization of any interacting units. Moran’s I can be modified in accordance with the characteristic length scale of a neural activity pattern. It allows a quantification of statistical significance levels for the observed patterns. We describe the technique applied to synthetic datasets and various experimental imaging time-series from cultured SCN explants. It is demonstrated that major characteristics of the collective state can be described by Moran’s I and the traditional Kuramoto order parameter R in a complementary fashion

In Vitro Characterization of a Tissue Renin-Angiotensin System in Human Nucleus Pulposus Cells.

Low back pain is a clinically highly relevant musculoskeletal burden and is associated with inflammatory as well as degenerative processes of the intervertebral disc. However, the pathophysiology and cellular pathways contributing to this devastating condition are still poorly understood. Based on previous evidence, we hypothesize that tissue renin-angiotensin system (tRAS) components, including the SARS-CoV-2 entry receptor angiotensin-converting enzyme 2 (ACE2), are present in human nucleus pulposus (NP) cells and associated with inflammatory and degenerative processes. Experiments were performed with NP cells from four human donors. The existence of angiotensin II, angiotensin II type 1 receptor (AGTR1), AGTR2, MAS-receptor (MasR), and ACE2 in human NP cells was validated with immunofluorescent staining and gene expression analysis. Hereafter, the cell viability was assessed after adding agonists and antagonists of the target receptors as well as angiotensin II in different concentrations for up to 48 h of exposure. A TNF-α-induced inflammatory in vitro model was employed to assess the impact of angiotensin II addition and the stimulation or inhibition of the tRAS receptors on inflammation, tissue remodeling, expression of tRAS markers, and the release of nitric oxide (NO) into the medium. Furthermore, protein levels of IL-6, IL-8, IL-10, and intracellular as well as secreted angiotensin II were assessed after exposing the cells to the substances, and inducible nitric oxide synthase (iNOS) levels were evaluated by utilizing Western blot. The existence of tRAS receptors and angiotensin II were validated in human NP cells. The addition of angiotensin II only showed a mild impact on gene expression markers. However, there was a significant increase in NO secreted by the cells. The gene expression ratios of pro-inflammatory/anti-inflammatory cytokines IL-6/IL-10, IL-8/IL-10, and TNF-α/IL-10 were positively correlated with the AGTR1/AGTR2 and AGTR1/MAS1 ratios, respectively. The stimulation of the AGTR2 MAS-receptor and the inhibition of the AGTR1 receptor revealed beneficial effects on the gene expression of inflammatory and tissue remodeling markers. This finding was also present at the protein level. The current data showed that tRAS components are expressed in human NP cells and are associated with inflammatory and degenerative processes. Further characterization of the associated pathways is warranted. The findings indicate that tRAS modulation might be a novel therapeutic approach to intervertebral disc disease

Are circadian amplitudes and periods correlated? A new twist in the story [version 1; peer review: 2 approved]

Three parameters are important to characterize a circadian and in general any biological clock: period, phase and amplitude. While circadian periods have been shown to correlate with entrainment phases, and clock amplitude influences the phase response of an oscillator to pulse-like zeitgeber signals, the co-modulations of amplitude and periods, which we term twist, have not been studied in detail. In this paper we define two concepts: parametric twist refers to amplitude-period correlations arising in ensembles of self-sustained clocks in the absence of external inputs, and phase space twist refers to the co-modulation of an individual clock's amplitude and period in response to external zeitgebers. Our findings show that twist influences the interaction of oscillators with the environment, facilitating entrainment, fastening recovery to pulse-like perturbations or modifying the response of an individual clock to coupling. This theoretical framework might be applied to understand the emerging properties of other oscillating systems

The plant leaf movement analyzer (PALMA): a simple tool for the analysis of periodic cotyledon and leaf movement in Arabidopsis thaliana

Wagner L, Schmal C, Staiger D, Danisman S. The plant leaf movement analyzer (PALMA): a simple tool for the analysis of periodic cotyledon and leaf movement in Arabidopsis thaliana. Plant Methods. 2017;13(1): 2.Background The analysis of circadian leaf movement rhythms is a simple yet effective method to study effects of treatments or gene mutations on the circadian clock of plants. Currently, leaf movements are analysed using time lapse photography and subsequent bioinformatics analyses of leaf movements. Programs that are used for this purpose either are able to perform one function (i.e. leaf tip detection or rhythm analysis) or their function is limited to specific computational environments. We developed a leaf movement analysis tool—PALMA—that works in command line and combines image extraction with rhythm analysis using Fast Fourier transformation and non-linear least squares fitting. Results We validated PALMA in both simulated time series and in experiments using the known short period mutant sensitivity to red light reduced 1 (srr1-1). We compared PALMA with two established leaf movement analysis tools and found it to perform equally well. Finally, we tested the effect of reduced iron conditions on the leaf movement rhythms of wild type plants. Here, we found that PALMA successfully detected period lengthening under reduced iron conditions. Conclusions PALMA correctly estimated the period of both simulated and real-life leaf movement experiments. As a platform-independent console-program that unites both functions needed for the analysis of circadian leaf movements it is a valid alternative to existing leaf movement analysis tools