Corrective feedback control of competing neural network with entire connections

Continuous persist activity of the competitive network is related to many functions, such as working memory, oculomotor integrator and decision making. Many competition models with mutual inhibition structures achieve activity maintenance via positive feedback, which requires meticulous fine tuning of the network parameters strictly. Negative derivative feedback, according to recent research, might represent a novel mechanism for sustaining neural activity that is more resistant to multiple neural perturbations than positive feedback. Many classic models with only mutual inhibition structure are not capable of providing negative derivative feedback because double-inhibition acts as a positive feedback loop, and lack of negative feedback loop that is indispensable for negative derivative feedback. Here in the proposal, we aim to derive a new competition network with negative derivative feedback. The network is made up of two symmetric pairs of EI populations that the four population are completely connected. We conclude that the negative derivative occurs in two circumstances, in which one the activity of the two sides is synchronous but push-pull-like in the other, as well as the switch of two conditions in mathematical analysis and numerical simulation.

Building an RNA-based Toggle Switch using Inhibitory RNA Aptamers

Synthetic RNA systems offer unique advantages such as faster response, increased specificity, and programmability compared to conventional protein-based networks. Here, we demonstrate an in-vitro RNA-based toggle switch using RNA aptamers ca- pable of inhibiting the transcriptional activity of T7 or SP6 RNA polymerases. The activities of both polymerases are monitored simultaneously by using Broccoli and Malachite green light-up aptamer systems. In our toggle switch, a T7 promoter drives the expression of SP6 inhibitory aptamers, and an SP6 promoter expresses T7 in- hibitory aptamers. We show that the two distinct states originating from the mutual inhibition of aptamers can be toggled by adding DNA sequences to sequester the RNA inhibitory aptamers. Finally, we assessed our RNA-based toggle switch in cell-like con- ditions by introducing controlled degradation of RNAs using a mix of RNases. Our results demonstrate that the RNA-based toggle switch could be used as a control ele- ment for nucleic acid networks in synthetic biology applications.

Mutual inhibition effect of sulfur compounds in the hydrodesulfurization of thiophene, 2-ethylthiophene and benzothiophene ternary mixture

The hydrodesulphurization of a model component and equimolar ternary mixture of thiophene, 2-ethylthiophene and benzothiophene over sulphided CoMo/γ-Al2O3 and CoMo/γ-Al2O3-Nb2O5 catalysts were investigated in a fixed bed flow reactor. The catalysts were prepared by incipient wetness impregnation method and characterized by textural characteristics, total acidity and chemical species present on the catalysts surface. The characterization results showed that both CoMo/γ-Al2O3-Nb2O5 and sulphided CoMo/γ-Al2O3 catalysts exhibit a mesoporous structure with cylindrical pores open at both ends, evidenced by the IV type adsorption–desorption isotherm with a H1 hysteresis loop and have an average pore diameter between 3 and 4 nm. The chemical species present on the catalysts surface evaluated by XPS indicated that Co2+ and Mo4+ species are present in the sulfide form on both catalysts surfaces. In addition, there are also found oxidic species arising from incomplete reduction and sulphidation. The presence of niobium oxide in the catalytic support had a positive effect in leading to higher specific surface area (170 m2/g) and total acidity (0.421 meq/g) compared with CoMo/γ-Al2O3 catalyst (140 m2/g and 0.283 meq/g) respectively. The evaluation results from the hydrodesulfurization showed that CoMo/γ-Al2O3-Nb2O5 catalyst had a higher activity in hydrodesulphurization process of thiophene, 2-ethylthiophene and benzothiophene. The CoMo/γ-Al2O3-Nb2O5 catalyst eliminated sulfur from the single component feed (corresponding to 2380 ppm S) and reduced below 10 ppm, for the feed consisting in the equimolar ternary mixture of thiophene, 2-ethylthiophene and benzothiophene (2380 ppm S). The reactivity of thiophen compounds was reduced due to competitive adsorption. It was observed that benzothiophene inhibits the transformation of thiophene and 2-ethylthiophene. A mutual inhibition effect between sulfur compounds was also observed when thiophene, 2-ethylthiophene and benzothiophene were combined and tested over the CoMo/γ-Al2O3 catalyst. The inhibition effect had a lower intensity by introducing Nb2O5 in the catalyst support.

How Dickkopf molecules and Wnt/beta-catenin interplay to self-organise the Hydra body axis

The antagonising interplay between canonical Wnt signalling and Dickkopf (Dkk) molecules has been identified in various processes involved in tissue organisation, such as stem cell differentiation and body-axis formation. Disruption of the interplay between these molecules is related to several diseases in humans. However, the detailed molecular mechanisms of the β-catenin/Wnt-Dkk interplay leading to robust formation of the body axis remain elusive. Although the β-catenin/Wnt signalling system has been shown in the pre-bilaterian model organism Hydra to interact with two ancestral Dkks (HyDkk1/2/4-A and -C) to self-organise and regenerate the body axis, the observed Dkk expression patterns do not match any current pattern-formation theory, such as the famous activator-inhibitor model. To explore the function of Dkk in Hydra patterning process, we propose a new mathematical model which accounts for the two Dkks in interplay with HyWnt3/β-catenin. Using a systematic numerical study, we demonstrate that the chosen set of interactions is sufficient to explain it de novo body-axis gradient formation in Hydra. The presented mutual inhibition model goes beyond the classical activator-inhibitor model and shows that a molecular mechanism based on mutual inhibition may replace the local activation/long-range inhibition loop. The new model is validated using a range of perturbation experiments. It resolves several contradictions between previous models and experimental data, and provides an explanation for the interplay between injury response and pattern formation.

Latent Pathogenic Fungi in the Medicinal Plant Houttuynia cordata Thunb. Are Modulated by Secondary Metabolites and Colonizing Microbiota Originating from Soil

Latent pathogenic fungi (LPFs) affect plant growth, but some of them may stably colonize plants. LPFs were isolated from healthy Houttuynia cordata rhizomes to reveal this mechanism and identified as Ilyonectria liriodendri, an unidentified fungal sp., and Penicillium citrinum. Sterile H. cordata seedlings were cultivated in sterile or non-sterile soils and inoculated with the LPFs, followed by the plants’ analysis. The in vitro antifungal activity of H. cordata rhizome crude extracts on LPF were determined. The effect of inoculation of sterile seedlings by LPFs on the concentrations of rhizome phenolics was evaluated. The rates of in vitro growth inhibition amongst LPFs were determined. The LPFs had a strong negative effect on H. cordata in sterile soil; microbiota in non-sterile soil eliminated such influence. There was an interactive inhibition among LPFs; the secondary metabolites also regulated their colonization in H. cordata rhizomes. LPFs changed the accumulation of phenolics in H. cordata. The results provide that colonization of LPFs in rhizomes was regulated by the colonizing microbiota of H. cordata, the secondary metabolites in the H. cordata rhizomes, and the mutual inhibition and competition between the different latent pathogens.

Mutually Antagonistic Protein Pairs of Cancer

Switch-like behavior of tumorigenesis could be governed by antagonistic gene and protein pairs with mutual inhibition. Unlike extensive analysis of gene expression, search for protein level antagonistic pairs has been limited. Here, potential cancer type specific antagonist protein pairs with mutual inhibition were obtained from large scale datasets. Cancer samples or cancer types were compared to retrieve potential protein pairs with contrasting differential expression patterns. Analysis of two different protein expression datasets showed that a few proteins participate in most of the mutually antagonistic relationships. Some proteins with highly antagonistic profile were identified, which could not be attained from a differential expression or a correlation based analysis. The antagonistic protein pairs are sparsely connected by molecular interactions. Glioma, melanoma, and cervical cancer, are more frequently associated with antagonistic proteins than most of the other cancer types. Integrative analysis of mutually antagonist protein pairs contributes to our understanding of systems level changes of cancer.

Contribution of the hybrid component to the structure and properties of ceramics based on metastable phases Al2O3

The paper presents results of the study of the effect of doping with yttrium oxide on ceramics of the composition (γ + θ) Al2O3 + nY2O3 (n = 0, 1, 2, 3 wt%), sintered at 1550°C for 2 h, from powders of the specified composition annealed at temperatures of 500 , 800, 1000°С. X-ray diffraction analysis established the formation in ceramics of yttrium aluminum garnet Y3Al5O12 (YAG) and a metastable phase of the same composition with a tetragonal lattice type in powders at temperatures above 1200°C. The effect of YAG on the physical and mechanical properties was established: high properties were demonstrated by ceramics of the composition α-Al2O3 + 2wt% Y2O3, obtained from a powder annealed at 1000°C. In addition, high physical and mechanical properties were observed in ceramics of the composition α-Al2O3 + 0wt% Y2O3, obtained from a powder annealed at 800°C. The effect of the so-called “mutual protection against crystallization” was discovered, which consists in the mutual inhibition of crystallization processes in powders of the Al2O3 – Y2O3 system.

Dissociable roles of cortical excitation-inhibition balance during patch-leaving versus value-guided decisions

In a dynamic world, it is essential to decide when to leave an exploited resource. Such patch-leaving decisions involve balancing the cost of moving against the gain expected from the alternative patch. This contrasts with value-guided decisions that typically involve maximizing reward by selecting the current best option. Patterns of neuronal activity pertaining to patch-leaving decisions have been reported in dorsal anterior cingulate cortex (dACC), whereas competition via mutual inhibition in ventromedial prefrontal cortex (vmPFC) is thought to underlie value-guided choice. Here, we show that the balance between cortical excitation and inhibition (E/I balance), measured by the ratio of GABA and glutamate concentrations, plays a dissociable role for the two kinds of decisions. Patch-leaving decision behaviour relates to E/I balance in dACC. In contrast, value-guided decision-making relates to E/I balance in vmPFC. These results support mechanistic accounts of value-guided choice and provide evidence for a role of dACC E/I balance in patch-leaving decisions.

Stress granules display bistable dynamics modulated by Cdk

Stress granules (SGs) are conserved biomolecular condensates that originate in response to many stress conditions. These membraneless organelles contain nontranslating mRNAs and a diverse subproteome, but our knowledge of their regulation and functional relevance is still incipient. Here, we describe a mutual-inhibition interplay between SGs and Cdc28, the budding yeast Cdk. Among Cdc28 interactors acting as negative modulators of Start, we have identified Whi8, an RNA-binding protein that localizes to SGs and recruits the mRNA of CLN3, the most upstream G1 cyclin, for efficient translation inhibition and Cdk inactivation under stress. However, Whi8 also contributes to recruiting Cdc28 to SGs, where it acts to promote their dissolution. As predicted by a mutual-inhibition framework, the SG constitutes a bistable system that is modulated by Cdk. Since mammalian cells display a homologous mechanism, we propose that the opposing functions of specific mRNA-binding proteins and Cdk’s subjugate SG dynamics to a conserved hysteretic switch.