Identification of MarvelD3 as a tight junction-associated transmembrane protein of the occludin family

Background: Tight junctions are an intercellular adhesion complex of epithelial and endothelial cells, and form a paracellular barrier that restricts the diffusion of solutes on the basis of size and charge. Tight junctions are formed by multiprotein complexes containing cytosolic and transmembrane proteins. How these components work together to form functional tight junctions is still not well understood and will require a complete understanding of the molecular composition of the junction. Results: Here we identify a new transmembrane component of tight junctions: MarvelD3, a four-span transmembrane protein. Its predicted transmembrane helices form a Marvel (MAL and related proteins for vesicle traffic and membrane link) domain, a structural motif originally discovered in proteins involved in membrane apposition and fusion events, such as the tight junction proteins occludin and tricellulin. In mammals, MarvelD3 is expressed as two alternatively spliced isoforms. Both isoforms exhibit a broad tissue distribution and are expressed by different types of epithelial as well as endothelial cells. MarvelD3 co-localises with occludin at tight junctions in intestinal and corneal epithelial cells. RNA interference experiments in Caco-2 cells indicate that normal MarvelD3 expression is not required for the formation of functional tight junctions but depletion results in monolayers with increased transepithelial electrical resistance. Conclusions: Our data indicate that MarvelD3 is a third member of the tight junction-associated occludin family of transmembrane proteins. Similar to occludin, normal expression of MarvelD3 is not essential for the formation of functional tight junctions. However, MarvelD3 functions as a determinant of epithelial paracellular permeability properties

Plasma composition in a sigmoidal anemone active region

Using spectra obtained by the EIS instrument onboard Hinode, we present a detailed spatially resolved abundance map of an active region (AR)-coronal hole (CH) complex that covers an area of 359 arcsec x 485 arcsec. The abundance map provides first ionization potential (FIP) bias levels in various coronal structures within the large EIS field of view. Overall, FIP bias in the small, relatively young AR is 2-3. This modest FIP bias is a consequence of the AR age, its weak heating, and its partial reconnection with the surrounding CH. Plasma with a coronal composition is concentrated at AR loop footpoints, close to where fractionation is believed to take place in the chromosphere. In the AR, we found a moderate positive correlation of FIP bias with nonthermal velocity and magnetic flux density, both of which are also strongest at the AR loop footpoints. Pathways of slightly enhanced FIP bias are traced along some of the loops connecting opposite polarities within the AR. We interpret the traces of enhanced FIP bias along these loops to be the beginning of fractionated plasma mixing in the loops. Low FIP bias in a sigmoidal channel above the AR's main polarity inversion line where ongoing flux cancellation is taking place, provides new evidence of a bald patch magnetic topology of a sigmoid/flux rope configfiuration.Comment: For on-line animation, see http://www.mssl.ucl.ac.uk/~db2/fip_intensity.gif. Accepted by Ap

Selecting texture resolution using a task-specific visibility metric

In real-time rendering, the appearance of scenes is greatly affected by the quality and resolution of the textures used for image synthesis. At the same time, the size of textures determines the performance and the memory requirements of rendering. As a result, finding the optimal texture resolution is critical, but also a non-trivial task since the visibility of texture imperfections depends on underlying geometry, illumination, interactions between several texture maps, and viewing positions. Ideally, we would like to automate the task with a visibility metric, which could predict the optimal texture resolution. To maximize the performance of such a metric, it should be trained on a given task. This, however, requires sufficient user data which is often difficult to obtain. To address this problem, we develop a procedure for training an image visibility metric for a specific task while reducing the effort required to collect new data. The procedure involves generating a large dataset using an existing visibility metric followed by refining that dataset with the help of an efficient perceptual experiment. Then, such a refined dataset is used to retune the metric. This way, we augment sparse perceptual data to a large number of per-pixel annotated visibility maps which serve as the training data for application-specific visibility metrics. While our approach is general and can be potentially applied for different image distortions, we demonstrate an application in a game-engine where we optimize the resolution of various textures, such as albedo and normal maps

N-alkyl pyrrolidone ether podands as versatile alkali metal ion chelants

This work explores the coordination chemistry of a bis(pyrrolidone) ether ligand. Pyrrolidones are commercially important functional groups because of the high polarity and hence high hydrophilicity and surface affinity. An array of alkali metal ion complexes of a podand bearing two pendant pyrrolidone functionalities, namely 1-{2-[2-(2-oxo-pyrrolid-1-yl)-ethoxy]-ethyl}-pyrrolid-2-one (1) are reported. Reaction of this ligand with sodium hexafluorophosphate gives two discrete species of formulae [Na(1)2]PF6 (3) and [Na3(H2O)2(μ-1)2](PF6)3 (4), and a coordination polymer {[Na3(μ3-1)3(μ2-1)](PF6)3}n (5). The same reaction in methanol gives a 1 : 1 complex, namely [Na2(μ-1)2(MeOH)2](PF6)2 (6). Use of tetraphenyl borate as a less coordinating counter ion gives [Na2(1)2(H2O)4](BPh4)2 (7) and [Na2(1)4](BPh4)2 (8). Two potassium complexes have also been isolated, a monomer [K(1)2]PF6 (9) and a cyclic tetramer [K4(μ4-H2O)2(μ-1)4](PF6)4 (10). The structures illustrate the highly polar nature of the amide carbonyl moiety within bis(pyrrolidone) ethers with longer interactions to the ether oxygen atom. The zinc complex is also reported and {[ZnCl2(μ-1)]}n (11) exhibits bonding only to the carbonyl moieties. The ether oxygen atom is not necessary for Na+ complexation as exemplified by the structure of the sodium complex of the analogue 1,3-bis(pyrrolid-2-on-1-yl)- butane (2). Reaction of compound 1 with lithium salts results in isolation of the protonated ligand

School-based self-management intervention using theatre to improve asthma control in adolescents: a pilot cluster-randomised controlled trial.

BACKGROUND: Children with poorly controlled asthma have higher rates of unplanned healthcare use and school absences, as well as lower rates of medication adherence and knowledge. They also feel less comfortable using their medication at school, due to social fears and bullying. In this study, this was addressed through two school-based self-management interventions piloted to determine which one to use in a full trial. METHODS: We sought to assess the feasibility and acceptability of two school-based self-management intervention aimed at improving asthma control. Schools in London were randomised to (i) a theatre workshop for the whole year group aimed at raising awareness of asthma in schools, followed by self-management workshops for children (full intervention), (ii) theatre workshop alone (theatre only), or (iii) usual care (controls). Opt-out consent was obtained from parents. The study was a cluster randomised pilot trial, using London schools as the unit of allocation. Our primary aim was to assess the feasibility of delivering a self-management intervention in schools aimed at improving the asthma control test (ACT) score at 6 months. Secondary outcomes included acceptability of the school-based interventions, suitability of the theatre intervention and the full intervention with the self-management workshops, and generation of randomised data to inform future power calculations. Data were analysed by generalised mixed-effect models. RESULTS: The recruitment strategy for this trial was effective. Five schools were randomised to full intervention (189 children), four to theatre only (103 children), and six to controls (83 children). Asthma control test (ACT) score at baseline and 6 months was obtained from 178/358 participating children. Compared with the controls, there were no large differences found in ACT score with the full intervention; knowledge and perception of asthma improved though. GP and hospital visits increased in the full intervention group. Compared with controls, ACT score was unchanged in the theatre only group. CONCLUSION: The asthma self-management intervention trial in schools is feasible and acceptable. The full intervention consisting of both theatre and self-management workshop for asthmatics tended to be better suited to improve outcomes than the theatre intervention on its own. This full intervention should be the one carried forward into a main trial if funding for further research was sought. Further work is needed to understand why there was evidence that unscheduled visits to healthcare professionals increased with the full intervention. TRIAL REGISTRATION: The study was registered on the clinical trials database on 14th May 2018 (ID NCT03536416 )

Dataset and metrics for predicting local visible differences

A large number of imaging and computer graphics applications require localized information on the visibility of image distortions. Existing image quality metrics are not suitable for this task as they provide a single quality value per image. Existing visibility metrics produce visual difference maps, and are specifically designed for detecting just noticeable distortions but their predictions are often inaccurate. In this work, we argue that the key reason for this problem is the lack of large image collections with a good coverage of possible distortions that occur in different applications. To address the problem, we collect an extensive dataset of reference and distorted image pairs together with user markings indicating whether distortions are visible or not. We propose a statistical model that is designed for the meaningful interpretation of such data, which is affected by visual search and imprecision of manual marking. We use our dataset for training existing metrics and we demonstrate that their performance significantly improves. We show that our dataset with the proposed statistical model can be used to train a new CNN-based metric, which outperforms the existing solutions. We demonstrate the utility of such a metric in visually lossless JPEG compression, super-resolution and watermarking.</jats:p

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

Immersive competence and immersive literacy: Exploring how users learn about immersive experiences

While immersive experiences mediated through near-eye displays are still a relatively immature medium, there are millions of consumer devices in use. The level of awareness of the forms of the interface and media will vary enormously across the potential audience. Users might own personal devices or might encounter immersive systems in various venues. We introduce the term immersive competence to refer to the general practical knowledge and skills that users accumulate about how typical immersive interfaces work—the ways in which buttons are used, main locomotion techniques, etc. We then introduce the term immersive literacy to refer to awareness of how immersive interfaces are unique, when they might be appropriate, typical forms of media, etc. We sketch out how users develop competence and literacy with immersive media, and then highlight various open questions that are raised