关键词： alternative splicing   JASMONATE ZIM-domain (JAZ) protein   flavan-3-ols   jasmonic acid   MYC2 transcription factor   protein-protein interaction   Camellia sinensis  

摘要： Flavan-3-ols are abundant in the tea plant (Camellia sinensis) and confer tea with flavor and health benefits. We recently found that alternative splicing of genes is likely involved in the regulation of flavan-3-ol biosynthesis;however, the underlying regulatory mechanisms remain unknown. Here, we integrated metabolomics and transcriptomics to construct metabolite-gene networks in tea leaves, collected over five different months and from five spatial positions, and found positive correlations between endogenous jasmonic acid (JA), flavan-3-ols, and numerous transcripts. Transcriptome mining further identified CsJAZ1, which is negatively associated with flavan-3-ols formation and has three CsJAZ1 transcripts, one full-length (CsJAZ1-1), and two splice variants (CsJAZ1-2 and -3) that lacked 3 ' coding sequences, with CsJAZ1-3 also lacking the coding region for the Jas domain. Confocal microscopy showed that CsJAZ1-1 was localized to the nucleus, while CsJAZ1-2 and CsJAZ1-3 were present in both the nucleus and the cytosol. In the absence of JA, CsJAZ1-1 was bound to CsMYC2, a positive regulator of flavan-3-ol biosynthesis;CsJAZ1-2 functioned as an alternative enhancer of CsJAZ1-1 and an antagonist of CsJAZ1-1 in binding to CsMYC2;and CsJAZ1-3 did not interact with CsMYC2. In the presence of JA, CsJAZ1-3 interacted with CsJAZ1-1 and CsJAZ1-2 to form heterodimers that stabilized the CsJAZ1-1-CsMYC2 and CsJAZ1-2-CsMYC2 complexes, thereby repressing the transcription of four genes that act late in the flavan-3-ol biosynthetic pathway. These data indicate that the alternative splicing variants of CsJAZ1 coordinately regulate flavan-3-ol biosynthesis in the tea plant and improve our understanding of JA-mediated flavan-3-ol biosynthesis.

关键词： augmentative and alternative communication   communication   communication development   human rights   paediatric care   person-centred care   pictorial support   universal design  

摘要： Person-centred care, with its central focus on the patient in partnership with healthcare practitioners, is considered to be the contemporary gold standard of care. This type of care implies effective communication from and by both the patient and the healthcare practitioner. This is often problematic in the case of the paediatric population, because of the many communicative challenges that may arise due to the child's developmental level, illness and distress, linguistic competency and disabilities. The principle of universal design put forth in conventions and legislation means that the design of products and services should be usable by all people, to the greatest extent possible. Augmentative and alternative communication encompasses strategies, for example pictures and apps, that are typically used with people with communication disability. In this position paper, we argue for the universal use of augmentative and alternative communication to support person-centred communication and care for children, regardless of age or potential disability. Clinical examples are shared from three different paediatric care settings where pictorial supports were applied universally. Interviews were conducted with children and adolescents (with and without disabilities), parents and healthcare practitioners, and the principles of universal design were used as a framework to demonstrate how person-centred communication is supported in paediatric care.

关键词： adaptation   alternative splicing   evolution   gene regulation   iso-seq   RNA-seq  

摘要： Although alternative splicing is a ubiquitous co-transcriptional gene regulatory mechanism in plants, animals and fungi, its contribution to evolutionary transitions is understudied. Alternative splicing enables different mRNA isoforms to be generated from the same gene, expanding transcriptomic and thus proteomic diversity. While the role of gene expression variation in adaptive evolution is widely accepted, biologists still debate the functional impact of alternative isoforms on phenotype. In light of recent empirical research linking splice variation to ecological adaptations, we propose that alternative splicing is an important substrate for adaptive evolution and speciation, particularly at short timescales. In this article we synthesise what is known about the role of alternative splicing in adaptive evolution. We discuss the contribution of standing splice variation to phenotypic plasticity and how hybridisation can produce novel splice forms. Going forwards, we propose that alternative splicing be included as a standard analysis alongside gene expression analysis so we can better understand of how alternative splicing contributes to adaptive divergence at the micro- and macroevolutionary levels.

关键词： magnetic structure   Shubnikov group   neutron diffraction   isotropy subgroup   magCIF  

摘要： The antiferromagnetic structure of Tb14Ag51 with the propagation vector [1/3, 1/3, 0] and the parent space group P6/m is revisited using both magnetic symmetry and irreducible representation arguments. A new magnetic structure under the hexagonal Shubnikov magnetic space group P (6) over bar' which fits much better the experimental data is found. This new solution was obtained by constraining the spin arrangement to one of the three possible magnetic space groups of maximal symmetry that can be realized by a magnetic ordering transforming according to the four-dimensional physically irreducible representation that is known to be relevant in this magnetic phase. The refined model, parameterized under P (6) over bar', implicitly includes the presence of a third harmonic with the propagation vector at the gamma point [0, 0, 0], which has an important weight in the final result. The structure consists of 13 symmetry-independent Tb magnetic moments with the same size of 8.48 (2) mu(B), propagating cycloidally in the ab plane. The modulation has a substantial deviation from being purely sinusoidal due to the contribution of the mentioned third harmonic.

关键词： Finite elements   Multiscale mechanical problems   Geometrical and physical nonlinearity  

摘要： In this study, we present an alternative finite element to multiscale analysis. In this strategy, strain energy comes only from semi-discrete or lattice elements immersed in a continuum without stiffness, enabling mechanical analysis from molecular scales to macroscopic scales. Some characteristics of the proposed element are: (1) geometrically non-linear exact description that allows the presence of large displacements and large strain, (2) general mapping that allows curved and distorted elements generation with automatic immersions, (3) total compatibility with standard finite elements, and (4) huge degrees of freedom reduction with a small loss of continuum mobility. Throughout the text, the proposed strategy is presented in detail and applied in the determination of suitable meshes for any scale of analysis, which is an important information for future applications. To be direct, a Lennard-Jones-like (LJL) potential is chosen to build different crystalline-like structures that, when immersed in finite elements without stiffness, results in the desired continuous behavior. In this sense, some space of the paper is used to determine the energy constant of the LJL potential for these different "crystalline" structures at any scale. Taking advantage of the total compatibility of the proposed element with continuum elements, the multiscale strategy is straightforward applied. Selected examples are used to demonstrate the good behavior of the proposed element and its applicability. Future developments to enhance applications are commented at the conclusion section.

关键词： Adaptor protein   alternative translation start site   CpG DNA   macrophage   protein translation   Toll-like receptor  

摘要： Toll-like receptor (TLR) signaling relies on Toll/interleukin-1 receptor homology (TIR) domain-containing adaptor proteins that recruit downstream signaling molecules to generate tailored immune responses. In addition, the palmitoylated transmembrane adaptor protein family member Scimp acts as a non-TIR-containing adaptor protein in macrophages, scaffolding the Src family kinase Lyn to enable TLR phosphorylation and proinflammatory signaling responses. Here we report the existence of a smaller, naturally occurring translational variant of Scimp (Scimp TV1), which is generated through leaky scanning and translation at a downstream methionine. Scimp TV1 also scaffolds Lyn, but in contrast to full-length Scimp, it is basally rather than lipopolysaccharide (LPS)-inducibly phosphorylated. Macrophages from mice that selectively express Scimp TV1, but not full-length Scimp, have impaired sustained LPS-inducible cytokine responses. Furthermore, in granulocyte macrophage colony-stimulating factor-derived myeloid cells that express high levels of Scimp, selective overexpression of Scimp TV1 enhances CpG DNA-inducible cytokine production. Unlike full-length Scimp that localizes to the cell surface and filopodia, Scimp TV1 accumulates in intracellular compartments, particularly the Golgi. Moreover, this variant of Scimp is not inducibly phosphorylated in response to CpG DNA, suggesting that it may act via an indirect mechanism to enhance TLR9 responses. Our findings thus reveal the use of alternative translation start sites as a previously unrecognized mechanism for diversifying TLR responses in the innate immune system.

关键词： Immunology   Biomedicine   general  

关键词： MRSA   bacteremia   susceptibility testing   vancomycin   MIC  

摘要： Objectives: Variability in minimum inhibitory concentration (MIC) with automated susceptibility testing instruments may influence methicillin-resistant Staphylococcus aureus (MRSA) treatment. The purpose of this study was to evaluate the difference in vancomycin MIC values and the impact on vancomycin alternative therapy for MRSA bacteremia using the MicroScan and VITEK 2 automated systems. Methods: This was a retrospective multicenter cohort study of adult patients with MRSA bacteremia. Patients were stratified by susceptibility testing with MicroScan (May 2013-December 2016) or VITEK 2 (June 2017-February 2020). The primary outcome was vancomycin alternative therapy use. Secondary endpoints included MRSA MIC, 30-day mortality, 30-and 90-day readmission, and hospital length of stay (LOS). Results: A total of 193 patients were included for analysis: 89 in the MicroScan group and 104 in the VITEK 2 group. Vancomycin alternative therapy use was higher in the MicroScan group than the VITEK 2 group (56.2% vs 20.2%;p < 0.001). Median MIC value was 2 mg/L and 1 mg/L for MicroScan and VITEK 2, respectively ( p < 0.001). Median hospital LOS was shorter in the VITEK 2 period (16 vs 12 days;p = 0.02). Thirty-day mortality (10.1% vs 7.7%;p = 0.555) and 90-day readmission (34.8% vs 29.8%;p = 0.457) did not significantly differ between MicroScan and VITEK 2 groups. Conclusions: VITEK 2 use was associated with lower reported vancomycin MICs and less use of vancomycin alternative therapy. (c) 2022 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license ( http://***/licenses/by-nc-nd/4.0/ )

关键词： Alternative pathway   Complement system   Dendritic cells   Macrophages   Properdin   Viable   death cells  

摘要： Properdin, the only known positive regulator of the complement system, stabilizes the C3 convertase, thereby increasing its half-life. In contrast to most other complement factors, properdin is mainly produced extrahepatically by myeloid cells. Recent data suggest a role for properdin as a pattern recognition molecule. Here, we confirmed previous findings of properdin binding to different necrotic cells including Jurkat T cells. Binding can occur independent of C3, as demonstrated by HAP-1 C3 KO cells, excluding a role for endogenous C3. In view of the cellular source of properdin, interaction with myeloid cells was examined. Properdin bound to the surface of viable monocyte-derived pro- and anti-inflammatory macrophages, but not to DCs. Binding was demonstrated for purified properdin as well as fractionated P2, P3, and P4 properdin oligomers. Binding contributed to local complement activation as determined by C3 and C5b-9 deposition on the cell surfaces and seems a prerequisite for alternative pathway activation. Interaction of properdin with cell surfaces could be inhibited with the tick protein Salp20 and by different polysaccharides, depending on sulfation and chain length. These data identify properdin as a factor interacting with different cell surfaces, being either dead or alive, contributing to the local stimulation of complement activation.