MarvelD3 regulates the c-Jun N-terminal kinase pathway during eye development in Xenopus.

Ocular morphogenesis requires several signalling pathways controlling the expression of transcription factors and cell-cycle regulators. However, despite a well-known mechanism, the dialogue between those signals and factors remains to be unveiled. Here, we identify a requirement for MarvelD3, a tight junction transmembrane protein, in eye morphogenesis in Xenopus MarvelD3 depletion led to an abnormally pigmented eye or even an eye-less phenotype, which was rescued by ectopic MarvelD3 expression. Altering MarvelD3 expression led to deregulated expression of cell-cycle regulators and transcription factors required for eye development. The eye phenotype was rescued by increased c-Jun terminal Kinase activation. Thus, MarvelD3 links tight junctions and modulation of the JNK pathway to eye morphogenesis

Anti-Stokes laser cooling in bulk Erbium-doped materials

We report the first observation of anti-Stokes laser-induced cooling in the Er^{3+}:KPb_{2}Cl_{5} crystal and in the Er^{3+}:CNBZn (CdF_{2}-CdCl_{2}-NaF-BaF_{2}-BaCl_{2}-ZnF_{2}) glass. The internal cooling efficiencies have been calculated by using photothermal deflection spectroscopy. Thermal scans acquired with an infrared thermal camera proved the bulk cooling capability of the studied samples. Implications of these results are discussed.Comment: 4 pages, 4 figures. The figures enclosed with this submission are low quality ones. Versions of this paper with high quality figures are available upon reques

The Tight Junction Associated Signalling Proteins ZO-1 and ZONAB Regulate Retinal Pigment Epithelium Homeostasis in Mice

Cell-cell adhesion regulates the development and function of epithelia by providing mechanical support and by guiding cell proliferation and differentiation. The tight junction (TJ) protein zonula occludens (ZO)-1 regulates cell proliferation and gene expression by inhibiting the activity of the Y-box transcription factor ZONAB in cultured epithelial cells. We investigated the role of this TJ-associated signalling pathway in the retinal pigment epithelium (RPE) in vivo by lentivirally-mediated overexpression of ZONAB, and knockdown of its cellular inhibitor ZO-1. Both overexpression of ZONAB or knockdown of ZO-1 resulted in increased RPE proliferation, and induced ultrastructural changes of an epithelial-mesenchymal transition (EMT)-like phenotype. Electron microscopy analysis revealed that transduced RPE monolayers were disorganised with increased pyknosis and monolayer breaks, correlating with increased expression of several EMT markers. Moreover, fluorescein angiography analysis demonstrated that the increased proliferation and EMT-like phenotype induced by overexpression of ZONAB or downregulation of ZO-1 resulted in RPE dysfunction. These findings demonstrate that ZO-1 and ZONAB are critical for differentiation and homeostasis of the RPE monolayer and may be involved in RPE disorders such as proliferative vitroretinopathy and atrophic age-related macular degeneration

Scale-free memory model for multiagent reinforcement learning. Mean field approximation and rock-paper-scissors dynamics

A continuous time model for multiagent systems governed by reinforcement learning with scale-free memory is developed. The agents are assumed to act independently of one another in optimizing their choice of possible actions via trial-and-error search. To gain awareness about the action value the agents accumulate in their memory the rewards obtained from taking a specific action at each moment of time. The contribution of the rewards in the past to the agent current perception of action value is described by an integral operator with a power-law kernel. Finally a fractional differential equation governing the system dynamics is obtained. The agents are considered to interact with one another implicitly via the reward of one agent depending on the choice of the other agents. The pairwise interaction model is adopted to describe this effect. As a specific example of systems with non-transitive interactions, a two agent and three agent systems of the rock-paper-scissors type are analyzed in detail, including the stability analysis and numerical simulation. Scale-free memory is demonstrated to cause complex dynamics of the systems at hand. In particular, it is shown that there can be simultaneously two modes of the system instability undergoing subcritical and supercritical bifurcation, with the latter one exhibiting anomalous oscillations with the amplitude and period growing with time. Besides, the instability onset via this supercritical mode may be regarded as "altruism self-organization". For the three agent system the instability dynamics is found to be rather irregular and can be composed of alternate fragments of oscillations different in their properties.Comment: 17 pages, 7 figur

Control of neural crest induction by MarvelD3-mediated attenuation of JNK signalling

Tight junctions are required for the formation of tissue barriers and function as suppressors of signalling mechanisms that control gene expression and cell behaviour; however, little is known about the physiological and developmental importance of such signalling functions. Here, we demonstrate that depletion of MarvelD3, a transmembrane protein of tight junctions, disrupts neural crest formation and, consequently, development of neural crest-derived tissues during Xenopus embryogenesis. Using embryos and explant cultures combined with a small molecule inhibitor or mutant mRNAs, we show that MarvelD3 is required to attenuate JNK signalling during neural crest induction and that inhibition of JNK pathway activation is sufficient to rescue the phenotype induced by MarvelD3 depletion. Direct JNK stimulation disrupts neural crest development, supporting the importance of negative regulation of JNK. Our data identify the junctional protein MarvelD3 as an essential regulator of early vertebrate development and neural crest induction and, thereby, link tight junctions to the control and timing of JNK signalling during early development

Bves Modulates Tight Junction Associated Signaling

Blood vessel epicardial substance (Bves) is a transmembrane adhesion protein that regulates tight junction (TJ) formation in a variety of epithelia. The role of TJs within epithelium extends beyond the mechanical properties. They have been shown to play a direct role in regulation of RhoA and ZONAB/DbpA, a y-box transcription factor. We hypothesize that Bves can modulate RhoA activation and ZONAB/DbpA activity through its regulatory effect on TJ formation. Immortalized human corneal epithelial (HCE) cells were stably transfected with Flag-tagged full length chicken Bves (w-Bves) or C-terminus truncated Bves (t-Bves). We found that stably transfected w-Bves and t-Bves were interacting with endogenous human Bves. However, interaction with t-Bves appeared to disrupt cell membrane localization of endogenous Bves and interaction with ZO-1. w-Bves cells exhibited increased TJ function reflected by increased trans-epithelial electrical resistance, while t-Bves cells lost TJ protein immunolocalization at cell-cell contacts and exhibited decreased trans-epithelial electrical resistance. In parental HCE and w-Bves cells ZONAB/DbpA and GEF-H1 were seen at cell borders in the same pattern as ZO-1. However, expression of t-Bves led to decreased membrane localization of both ZONAB/DbpA and GEF-H1. t-Bves cells had increased RhoA activity, as indicated by a significant 30% increase in FRET activity compared to parental HCE cells. ZONAB/DbpA transcriptional activity, assessed using a luciferase reporter probe, was increased in t-Bves cells. These studies demonstrate that Bves expression and localization can regulate RhoA and ZONAB/DbpA activity

Quality control of Bradyrhizobium inoculant strains: detection of nosZ and correlation of symbiotic efficiency with soybean leaf chlorophyll levels

Greenhouse gas emissions, such as N2O from excessive N-fertilizer use, are of concern. Symbiotic N2-fixation by pulses such as soybean might mitigate this issue, for which inoculants carrying locally adapted Bradyrhizobium strains are recommended. In the frame of this goal, enhancing the quality control of these inoculants is required on two key aspects: determining the presence of nosZ, for the strains being able to reduce N2O, and assessing N2-fixation potential. Previously it was demonstrated that, in soybean leaves, N-contents are well correlated with chlorophyll contents. However, no such correlations were made with either N obtained from N2-fixation or with nodules mass, which is an indicator of nodular activity. Here we aimed to leverage the correlation between N and chlorophyll levels to develop a simple and non-destructive laboratory method to be applied in quality control of inoculants, able to assess the N2-fixing capacity of rhizobial strains. To establish such correlations, we cultivated soybeans in vermiculite with N-free nutrient solution, and inoculated them with various Bradyrhizobium field isolates that displayed a range of symbiotic N2-fixing capacities. Subsequently, we measured chlorophyll with a portable chlorophyllometer, and correlated these measures with symbiotic parameters. Moreover, we tested for the presence of nosZ by PCR. We observed significant correlations between chlorophyll and shoot nitrogen obtained from N2-fixation and, in addition, we corroborated that chlorophyll contents were significantly correlated also with nodules mass. Two B. diazoefficiens strains stood out and possessed nosZ. In contrast, B. elkanii and B. japonicum isolates displayed lower chlorophyll and symbiotic performance, and lacked nosZ. Our findings highlight the potential of measuring chlorophyll contents and testing for the presence of nosZ as two straightforward techniques that may enhance laboratory tests for quality control, enabling selection of superior and safe locally isolated strains for soybean inoculants without increased production costs